IJOPP Malaria

Indian Journal of Pharmacy Practice
ijopp
Vol.3(2), Apr-Jun, 2010
EDITOR-IN-CHIEF Dr. Shobha Rani R. Hiremath shobha24@yahoo.com
A P T I
ASSOCIATE EDITORS Dr. G. Parthasarathi partha18@airtelmail.in Dr. Pramil Tiwari ptiwari@niper.ac.in
ASSISTANT EDITORS Mr. Ramjan Shaik ramjanshaik@gmail.com Ms. Mahvash Iram mahvashiram@gmail.com
EDITORIAL OFFICE INDIAN JOURNAL OF PHARMACY PRACTICE

An Official Publication of Association of Pharmaceutical Teachers of India H.Q.: Al-Ameen College of Pharmacy, Opp. Lalbagh Main Gate, Hosur Road, Bangalore 560 027, INDIA Mobile: +91 9845399431 | +91 9845659585 | +91 9878488050 | +91 9972588878 +91 9916069842 | Ph: +91 80 22107467; Fax: +91 80 22225834 www.ijopp.org || ijopp@rediffmail.com
ijopp
Vol.3(2), Apr-Jun, 2010
EDITORIAL ADVISORY BOARD
Dr. Anil Kumar, Chattisgarh Dr. Atmaram P. Pawar, Pune Dr. Claire Anderson, Nottingham,UK. Dr. Dhanalakshmi Iyer, Mumbai Prof. Ganachari M S, Belgaum Dr. Geeta.S, Bangalore Dr. Hukkeri V.I, Ratnagiri (Dist) Dr. Krathish Bopanna, Bangalore Prof. Mahendra Setty C.R, Bangalore Dr. Miglani B D, New Delhi Dr. Mohanta G.P., Annamalai Nagar
Dr. Nagavi B.G, Ras Al-Khaimah, UAE Dr. Nalini Pais, Bangalore Dr. Rajendran S.D, Hyderabad Dr. Ramananda S.Nadig, Bangalore Dr. Revikumar K G, Cochin Dr. Sampada Patawardhan, Mumbai Dr. Sriram. S, Coimbatore Dr. Sreekant Murthy, Philadelphia, USA Dr. Sunitha C. Srinivas, Grahamstown, RSA Dr. Suresh B, Mysore Dr. Tipnis H.P, Mumbai
Disclaimer: The editor-in-chief does not claim any responsibility, liability for
statements made and opinions expressed by authors
ijopp
Vol.3(2), Apr-Jun, 2010
CONTENTS
Editorial
Review Articles
= Drug Interactions Citalopram Dilip KV, Mahesh NM, Raghunathaguptha A------------------------------------------------------------------------1-10
Research Articles
= of prescription pattern in terms of essentiality and rationality and assessment of Hospital Evaluation pharmacy services utilization in tertiary care teaching rural hospital. Shah AM, Dhanani JV, Shah RB, Agrawal A, Gajjar BMr--------------------------------------------------------11 -15
l of potential medication errors in a tertiary care hospital in Nepal. Pattern Kadir A, Subish P, Anil K, Ram B----------------------------------------------------------------------------------16-22
lof prescription practice for Antipsychotic drugs by Psychiatrists- A Survey Study Mukesh R, Mohanta GP, Lokesh U--------------------------------------------------------------------------------23-27
= A retrospective review on Malaria and Antimalarial drugs in Tripura, India A Survey Report Mallik S, Nilesh K, Rajesh G---------------------------------------------------------------------------------------28-33
l Comparative Study on the Sensitivity Pattern of Microorganisms Vidhya D, Sriram S, Manjula Devi A.S, Rajalingam B, Shivashankar S, Chitra B, Rajeswari R--------34-40
ijopp
Vol.3(2), Apr-Jun, 2010
Short Communication
= Counterfeiting of medicine is no more incurable now Sayed AHA-------------------------------------------------------------------------------------------------------------41-42
= Procurement Practices in Public Sector Medicines Mohanta GP, Veena R------------------------------------------------------------------------------------------------43-45
Case Report
= Lamotrigine Induced Erythema Multiforme: A Case Report Mahvash I, ShobhaRani R.H, MeghaBhat.Y----------------------------------------------------------------------46-49
= Induced Stevens Johnson Syndrome -A Case Report Ibuprofen Tapan S, Yogesh BS, Amit R-----------------------------------------------------------------------------------------50-53
Instructions to authors-----------------------------------------------------------------------------------------54-57
Editorial
Dear Readers, Seasons greetings to you all! Many thanks for your encouragement to ijopp in the form of contribution of articles and readership. We value your support. One of the key areas of Clinical Pharmacy is Pharmacovigilance and an important activity of a clinical pharmacist is ADR monitoring. Pharmacovigilance as we all know is the science relating to the detection, assessment, understanding and prevention of adverse effects of drugs. Pharmacovilance is currently of global improtance due to the reporting of several life threatening and fatal drug reactions, increased awareness of consumers regarding drug safety, withdrawal of few drugs in some countries leading to doubts regarding their safety in our country. In India, Central Drugs Standard Control Organization (CDSCO) launched a National Pharmacovigilance Programme in Nov 2004. It identified zonal, regional and peripheral centres across the nation to collect, document and report the ADRs. This was a welcome move towards monitoring drug safety. Centres involved were also actively participating in the programme. But unfortunately from the past two years due to certain reasons best known to them, National Pharmacovigilance Programme has come to a stand still. Our earnest hope is the revival of this programme with the participation of self motivated centres and involvement of more clinical pharmacists and Pharmacy Practice departments.
Dr. Shobha Rani R Hiremath Editor-in-Chief
Indian J. Pharm. Pract. 3(2), Apr-Jun, 2010
APTI
Citalopram Drug Interactions
Dilip Kumar V , Mahesh NM* , Raghunathaguptha A
1
ijopp
1 1 2
Department of Pharmacology, J.S.S. College of Pharmacy (Constituent College of J.S.S.
University, Mysore), S.S. Nagar, Mysore-570 015, Karnataka; 2Guptha's Clinic, Neuropsychiatry, Agrahara, Mysore-570004, Karnataka Address for Correspondence: mahesh_n_m@yahoo.com Abstract Citalopram is an antidepressant belonging to selective serotonin reuptake inhibitors. Citalopram produces its activity by inhibiting the reuptake of serotonin in the synaptic clefts. So, concomitant administration of drugs (opioids, Monoamino oxidase inhibitors) which are having affect on serotonin or other monoamine levels in the synaptic cleft may produce some adverse effects as a pharmacodynamic interaction. Citalopram is metabolized by CytochromeP450 (CYP) 2C19 and CYP2D6 to desmethylcitalopram and further by CYP3A4 to didesmethylcitalopram. Some drugs may either induce (carbamazepine and rifapicin) or inhibit (buspirone, tramodol, Tricyclic antidepressants) these enzymes and affecting the citalopram levels producing either therapeutic failure or serotonin toxicity. Similarly, citalopram mildly inhibits CYP2C19, CYP2D6 and CYP3A4 and thus affects the plasma levels of the drugs (imipramine, -blockers, trazodone) which are metabolized by the above enzymes. So, in this review we tried to summarize both the interactions of citalopram with other drugs and other drugs interaction with citalopram and their probable mechanisms which may be helpful for the psychiatrists or physicians to judge the appropriate therapy when the patient is to be co-administered with citalopram. Key words: Citalopram; Drug interactions; Pharmacodynamic; Pharmacokinetic. INTRODUCTION Citalopram is an antidepressant drug belonging to selective serotonin reuptake inhibitor (SSRI) class. Citalopram selectively inhibits serotonin (5HT) reuptake into the presynaptic neurons. This leads to elevated serotonin levels in the synaptic clefts. Serotonin acts on different types of serotonin receptors to produce antidepressant and other pharmacological effects. Citalopram is demethylated by CYP2C19 and CYP2D6 to N-desmethylcitalopram and N-desmethylcitalopram is further demetylated to di-desmethylcitalopram by 1 CYP3A4. Both of its metabolites are inactive. Some drugs which induce or inhibit these enzymes can also alter the plasma concentrations of citalopram by altering its liver metabolism. Citalopram is an inhibitor of CYP2D6 and also a weak inhibitor of CYP2C19 and CYP3A4. Hence, the plasma concentration of drugs which are substrates of these enzymes may be affected. And some drugs which have the potential to affect the synaptic levels of serotonin may affect the outcome of citalopram therapy. Thus, pharmacokinetic and
Indian Journal of Pharmacy Practice Received on 23/03/201 0 Accepted on 29/03/2010 APTI All rights reserved
pharmacodynamic drug interactions are likely to occur with citalopram. Citalopram is frequently prescribed to treat the depressive patients when compared to other SSRI class antidepressants such as fluoxetine, sertraline, fluoxamine and paroxetine. Fluoxetine, sertraline, fluoxamine and paroxetine can cause severe adverse drug interactions with other drugs when compared to citalopram.2 Hence, all the drug interactions identified with citalopram were reviewed to know its interaction potential especially when used to treat the depressive patients with or without co-morbidity. Interaction Potential of citalopram Citalopram has the potential to interact with many drugs through the pharmacodynamic and pharmacokinetic mechanisms. Its pharmacodynamic interaction is due to elevated levels of 5HT in the synaptic cleft. Such citalopram pharmacodynamic interaction was observed with non-steroidal antiinflammatory drugs (NSAIDs), antimigraine, anxiolytics, tricyclic antidepressants, monoamineoxidase inhibitors, beta blockers and opioids. Pharmacokinetically, citalopram inhibits different drug metabolising CYP450 isoenzymes. This mechanism increases the plasma levels of desipramine, trazadone,
aripiprazole, haloperidol, clozapine, reserpidone, metoprolol and perhexitine. Citalopram plasma levels can be decreased by carbamazepine and rifampicin, which induce CYP2C19, CYP3A4 and CYP2D6 3,4 enzymes. The interaction of many drugs with citalopram is individually explained with respect their effect on clinical outcome. Citalopram interactions with other drugs Non steroidal anti inflammatory drugs All selective serotonin reuptake inhibitors (SSRIs) (example, citalopram) increase the risk of upper gastrointestinal bleeding. This effect is potentiated by concurrent use of NSAIDs in depressive patients who are under treatment of SSRIs. The risk of upper gastrointestinal bleeding was found to be increased in the range of 5.2% to 12.2% when SSRIs and NSAIDs were administered together.5 SSRIs inhibits the serotonin transporter, which is responsible for the uptake of serotonin into platelets. Serotonin released from platelets in response to vascular injury promotes the vasoconstriction and changes the shape of the platelets leading to aggregation. SSRIs also inhibit the pulmonary endothelial metabolism of serotonin. It could thus be predicted that SSRIs would deplete platelet serotonin, leading to a reduced ability toform clots and a subsequent increase in the risk of bleeding.5,6 Anticoagulants Citalopram can increase the maximum prothrombin time when co-administered with oral anticoagulants (e.g., warfarin, acenocoumarol). Citalopram (40 mg/day) increased the normal maximum prothrombin time by 6.4% in a patient who was taking warfarin. It was considered as clinically insignificant as there was no evidence of bleeding.7 But, in another 63-year-old patient who was taking acenocoumarol (18 mg/week), citalopram (20 mg/day) addition resulted in the spontaneous gingival haemorrhage after 10 days. The haemorrhage, however, stopped five days after citalopram was withdrawn. This suggests the ability of citalopram including other SSRIs to increase the risk of bleeding by inhibiting serotonin levels and thus causing decreased platelet aggregation.8,9 Atypical antidepressants Citalopram can increase the plasma concentrations and pharmacodynamic aspect of trazodone. Citalopram increased the mean plasma concentrations of trazodone by 30% when compared to the trazodone monotherapy in depressive patients. This interaction is perhaps due to
inhibition of CYP3A4 metabolising enzymes responsible for the metabolism of trazodone. Increased trazodone plasma levels may result additive serotonergic effects like serotonin syndrome.10,11 Antiparkinsonian drugs Citalopram can decrease the bioavailability of selegiline. The bioavailability of selegiline was reduced by 30% in the presence of citalopram in a study involving 18 healthy subjects who were given citalopram 20 mg or a placebo daily for 10 days followed by four days with concurrent selegiline (10 mg/day). However, there was no change in the serum concentrations of the three main metabolites of selegiline and also vital signs or frequency of adverse events. The study concluded that there is no clinically relevant interaction between selegiline and 12 citalopram. Cardiovascular drugs Concurrent use of metoprolol and citalopram resulted in the twofold increase in the plasma levels of metoprolol. This may decrease its cardioselectivity. This interaction is due to inhibition of CYP2D6 and 2C19 isoenzymes by SSRIs. These metabolizing enzymes are involved in the metabolic clearance of beta-adrenergic blockers such as carvedilol, labetalol, metoprolol, nebivolol, propranolol and timolol.10,13 In another case study, citalopram raised perhexiline levels when concurrently administered in an elderly man.14 In vitro studies with human liver microsomes found that fluoxetine and paroxetine are potent inhibitors of metoprolol metabolism and fluvoxamine, sertraline and citalopram less potent. These results suggest the need for monitoring of the changes in the cardiovascular dynamics when SSRIs and cardiovascular drugs are concurrently administered.15 Anxiolytics Citalopram was found to have no effect on alprazolam plasma levels, although the time to maximum alprazolam concentration was delayed by 30 minutes. The prolongation of time of maximum plasma concentration of alprazolam (Tmax) is probably due to the effect of citalopram on the absorption of alprazolam. It is possible that citalopram may have a yet undiscovered effect on Pglycoproteins in the gut or some other effect on the gut wall to produce such effect.16 Antipsychotics Escitalopram and citalopram in 6 patients taking aripiprazole elevated the plasma levels of latter by 39% and 34% respectively than that was found in patients
taking aripiprazole alone.17 Aripiprazole is metabolized by CYP3A4 and CYP2D6 isoenzymes. In two individual studies in schizophrenics citalopram did not affect the plasma levels of clozapine.18,19 But in another study initiation of citalopram 20 mg/kg therapy in a schizophrenic patient who was regularly under clozapine treatment raised the plasma levels of clozapine. The patient reported sedation, hypersalivation and confusion. Total clozapine serum levels were found to be 1097 ng/ml. The total clozapine level dropped to 792 ng/ml when the citalopram dose was reduced to 20 mg daily and the symptoms resolved over the following 2 weeks.20 In a case study it was reported that a man with idiopathic priapism for 4 hours every 1-2 months experienced a prolonged bouts lasting for 6-8 hours when he was given resperidone. Then he experienced almost daily erections when he was given with citalopram with reduced resperidone dose which lasted for 12 hrs.21 Another study found that paroxetine, fluoxetine and sertraline increased olanzapine levels by about 32%, but citalopram had no 22 effect. SSRIs including citalopram inhibit CYP2D6 isoenzyme involved in the metabolism of the antipsychotics to cause such interactions. Tricyclic antidepressant The contradictory reports are available about the pharmacokinetic interaction outcome associated between tricyclic antidepressants and citalopram. In five patients who were taking amitriptyline, clomipramine or maprotiline, addition of citalopram (20 to 60 mg/day), did not change the plasma tricyclic antidepressant 23 levels. But, in a study in eight healthy volunteers citalopram caused 50% increase in the area under the curve of desipramine, a primary metabolite of imipramine. This was attributed to the strong ability of desmethylcitalopram to inhibit CYP2D6 enzymes involved in the hydroxylation of desipramine.24 Similarly, in another study, the levels of imipramine metabolites, desmethylclomipramine and 8-hydroxydesmethyl.25,26 clomipramine was found elevated. However, citalopram was successfully substituted for paroxetine in a case of tricyclic antidepressant toxicity during coadministration of desipramine and paroxetine.27 Chemotherapeutic agent Pharmacokinetic interaction was observed between the chemotherapeutic drugs and citalopram. A 74-year-old man who had been taking citalopram for two months developed rhabdomyolysis after undergoing initial treatment with irinotecan for gastrointestinal cancer. All
medications were discontinued. But, rhabdomyolysis was found exacerbated upon restarting citalopram to treat the depression. When citalopram was discontinued, he improved over the next five days. It was thought that the levels of citalopram might have increased because citalopram and irinotecan share at least one metabolic pathway through CYP3A4 enzymes. The cytochrome enzymes system may also have been compromised in the cancer patient.28 Other drugs interaction with citalopram Anti-migraine drugs Concurrent administration of triptan (e.g., Almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, zolmitriptan) and citalopram results in serotonin syndrome. Serotonin syndrome occurs due to excessive serotonergic effect. The symptoms include restlessness, hallucinations, loss of coordination, tachycardia, rapid changes in blood pressure, hyperthermia, over reactive reflexes, nausea, vomiting, and diarrhoea. Triptans are the agonists of 5HT1B/1D receptors. SSRIs cause the accumulation of serotonin at 29,30 the synaptic clefts. Combined use of these drugs results in serotonin syndrome due to additive serotonergic effect at the synaptic level. The clinicians should be aware of this drug interaction for better patient care.31 Appetite suppressant Serotonin syndrome may occur when appetite suppressants such as sibutramine, dexfenfluramine or fenfluramine are co-administered with citalopram. A 43year-old depressive woman taking citalopram 40 mg daily was given sibutramine 10 mg daily to treat obesity.Within a few hours of taking the first dose of sibutramine, symptoms of serotonin syndrome developed and continued for three days till she continued to take sibutramine. Sibutramine inhibits the reuptake of norepinephrine, dopamine, and 5HT. Dexfenfluramine and fenfluramine are nonspecific serotonin agonists that enhance the release of serotonin and also inhibit serotonin reuptake.32,33 The combination of these drugs may thus leads to excessive serotonergic effects.34 Anxiolytics On administration of buspirone and citalopram, serotonin syndrome and hyponatraemia were produced in an isolated case. Buspirone is metabolised by the same CYP3A4 isoenzymes responsible for the metabolism of citalopram. This may have caused increase in the plasma concentrations of citalopram leading excessive
serotonergic effect.35 There are no pharmacodynamic interactions noted in clinical studies in which citalopram was given with benzodiazepines36,37 But, alprazolam significantly elevated the plasma levels of citalopram by 38 13%. Hence, caution is required when these drugs are required to be administered. Monoamine Oxidase Inhibitors Serotonin syndrome was observed in a 34-year-old depressive patient when he was switched to citalopram 20 mg daily from moclobemide 100 mg administered 39 thrice a day for several months. Moclobemide and citalopram when taken in overdoses produces serotonin syndrome and may even lead to death.40,41,42 Limited animal data on the effects of combined use of SSRIs and monoamine oxidase inhibitors suggest that these drugs may act synergistically to elevate blood pressure and evoke behavioural excitation. In contrast these reports, citalopram does not appear to have any influence on the wet-dog shakes response induced by the combination of a monoamine oxidase inhibitor and L-tryptophan, which is 43 a precursor of 5HT. Selective Serotonin Reuptake Inhibitors The depressive patients, who did not respond to citalopram, have responded when another SSRI was coadministered. Fluvoxamine was (50 to100 mg/day) coadministered in seven depressive patients who failed to respond to citalopram (40 mg/day) for three weeks. All patients responded. It was found that plasma Scitalopram levels rose to two to threefolds due to stereoselective inhibition of the metabolism of Scitalopram by fluvoxamine. 44 In non-responding depressive patients, the interaction of SSRIs results in the beneficial outcome. Lithium Carbonate A study conducted in healthy individuals concluded that there was no pharmacokinetic change when citalopram and lithium carbonate were co-administered.45 But, the depressive patients who did not respond to citalopram alone have responded well in combination with 46 lithiumcarbonate without any signs of adverse effects. Even then the manufacturers cautioned the patients about excessive serotonin effects with the co-administration of 10,47 citalopram and lithium. Lithium may enhance the pharmacologic effects of citalopram through the hyperstimulation of the brainstem 5-HT1A and 5-HT2A receptors.48
Antiepileptic drugs Approximately 30% plasma levels of citalopram were reduced when it was given along with carbamazepine. Because, carbamazepine induces CYP3A4 isoenzyme involved in the metabolism (N-demethylation) of citalopram.49 In contrast, increase in the plasma levels of citalopram was observed when carbamazepine was replaced with oxcarbamazepine.50 Opioid analgesics The symptoms of serotonin syndrome and hallucinations were observed when the opioid analgesics were administered along with citalopram. A 70-year-old woman with mild recurrent depressive disorder who was taking citalopram 10 mg daily for three years showed the symptoms of serotonin syndrome when started taking tramadol 50 mg daily for pain relief following an operation. It was observed that CYP2D6 and CYP2C19 levels were lowered. 51 A 44 year old woman who was on citalopram treatment for 9 months developed the signs of serotonin syndrome after 24 hours of meperidine administration.52 A 65-year-old patient chronically treated with citalopram developed serotonin syndrome following initiation of fentanyl. It was concluded that development of serotonin syndrome is due to its property of inhibition of reuptake of serotonin causing overstimulation of the 5-HT1A and possibly the 5-HT2 receptors, resulting in manifestations of the serotonin syndrome.53 Visual hallucination occurred in a 90-yearold woman taking hydrocodone when her antidepressant was changed from citalopram 10 mg daily to escitalopram 10 mg daily.54 The seizures or myoclonus associated with citalopram treatment appeared to be decreased in the threshold when concurrently administered with dextropropoxyphene.55 In all the above cases, the symptoms of serotonin syndrome and hallucination have stopped on discontinuing the 54 administration of the opioids. Meperidine, fentanyl and other opioids are weak serotonin reuptake inhibitors. On co-administration of these drugs with citalopram may produce higher levels of serotonin in the synaptic cleft, which may result in the development of serotonin 53 syndrome and other adverse outcome. Antipsychotic Drugs Both pharmacokinetic and pharmacodynamic interactions were observed between the typical and atypical classes of antipsychotics and citalopram. Levomepromazine increased the initial steady-state
plasma levels of desmethylcitalopram, the primary metabolite of citalopram, between 10 and 20%. This pharmacokinetic interaction was due to potent inhibition of the CYP2D6 isoenzymes activity by levomepromazine. CytochromeP4502D6 isoenzymes are involved in metabolism of desmethylcitalopram.56 Urinary obstruction was observed in a 65 year old schizophrenic woman under treatment of aripiprazole when co administered with citalopram. The mechanism of urinary retention has been attributed to its cholinergic and central serotonergic effects. Aripiprazole is a partial agonist of dopamine D2 receptors and 5-HT1A serotonin receptors. It blocks 5-HT2 serotoninergic, 1-adrenergic and histamine-H1 receptors.57 The serotonin syndrome developed in a patient with bipolar affective disorder who was taking lithium carbonate and citalopram when olanzapine was added. The syndrome was due to serotonergic side effects of olanzapine together with serotonergic effects of citalopram. These symptoms resolved on cessation of 58 olanzapine administration. Similarly, serotonin syndrome was reported in a 42 year old woman who was taking citalopram along with quitapine. It was mentioned that serotonin syndrome was a consequence of increased brainstem and spinal cord 5-HT1A receptor modulation occurring with 5-HT2A receptor antagonism.59 These reports suggest that the psychiatrists are required to be alert about the adverse outcome associated with the combination of antipsychotics and citalopram. Tricyclic antidepressants In a study conducted in 18 patients who were taking citalopram and tricyclic antidepressants, the serum levels of citalopram was found increased by 44%.60 This interaction was related to the ability of tricyclic antidepressants to inhibit mildly CYP2C19 enzymes involved in the metabolism of citalopram.61 Chemotherapeutic agents In another case report, 85-year-old woman taking citalopram developed the symptoms of serotonin syndrome after linezolid was started. Symptoms were resolved over 72 hours upon discontinuing citalopram.62 Linezolid is a reversible non-selective inhibitor of monoamine oxidase. It has the potential to interact with 63 adrenergic and serotonergic agents. In 55-year-old man who was taking citalopram 40 to 60 mg daily reported a decrease in therapeutic efficacy (increased crying and panic attacks) after starting
rifampicin 600 mg twice daily. His condition improved when the rifampicin was stopped. Rifampicin is a potent inducer of the hepatic CYP450 enzymes system, particularly CYP3A4 isoenzymes involved in the metabolism of citalopram. Induction of the CYP enzymes may have decreased citalopram plasma levels to result in the therapeutic failure. 64 Concomitant administration of citalopram with fluconazole, an antifungal produces serotonin syndrome which may be of life threatening intensity. This interaction is concluded as the outcome of fluconazole's potent CYP3A4 isoenzyme inhibiting property.65 DISCUSSION All selective serotonin reuptake inhibiting antidepressants interact with many drugs. Of these antidepressants, interaction potential of citalopram is less.2 Nevertheless, citalopram was found to interact with many drugs. Reviewing of such drug interactions helps psychiatrists to take the precautionary steps while treating the patients with such interacting combinations. Citalopram increases serotonin levels in the brain to produce antidepressant effect.1 It is prescribed either alone or in combination with drugs of different therapeutic classes to treat the patients with depression with or without co-morbid illnesses. Citalopram acts by elevating serotonin levels in the synapse and it inhibits the cytochrome isoenzymes like CYP2C19, CYP2D6 and CYP3A4 involved in the metabolism of many drugs. This may leads to pharmacodynamic and pharmacokinetic drug interactions due to citalopram. In contrast, other drugs also potentially interact with citalopram by pharmacodynamic and pharmacokinetic mechanisms. These reports suggest that the citalopram behaves like a precipitant and/or index drug to result in drug-drug interactions. Pharmacokinetically, citalopram affects the plasma concentrations of other drugs. It has increased the plasma levels of atypical antipsychotics, trazodone and adrenergic receptor blockers to the different extent by inhibiting the CYP450 isoenzymes mentioned elsewhere. Citalopram elevated the plasma levels of aripiprazole up to 34% in six patients.16 And metoprolol plasma levels were increased by twofold.13 But, the patients from both the studies did not report any side effects. Citalopram (40mg daily), on co-administration with clozapine in schizophrenics reported sedation, hypersalivation and confusion with the clozapine serum levels of 1097 ng/ml. And the symptoms resolved when
the dose is reduced to 20mg daily with clozapine serum levels of 792 ng/ml. 19 In another case study, initiation of treatment with citalopram in a man who was regularly taking resperidone, resperidone plasma levels were elevated and resulted in idiopathic priapism.20 Similarly, citalopram increased the plasma concentrations of trazodone up to 30% in depressive patients and produced serotonin syndrome.11 These reports suggest the pharmacodynamic changes due to pharmacokinetic interaction with certain drugs. In contrast, the bioavailability of selegiline was decreased by 30% in presence of citalopram in a study involving 18 healthy subjects.12 In another study, citalopram delayed the time to maximum alprazolam concentration by 30 minutes perhaps by affecting its absorption.15 Nevertheless, there was no pharmacodynamic change or therapeutic failure observed in such patients. These drug interactions were considered as clinically insignificant. The drugs that alter the activity of CYP3A4, CYP2D6 and CYP2C19 enzymes involved in the metabolism of citalopram can thus alter the plasma levels of citalopram. Buspirone and alprazolam have increased the plasma concentrations of citalopram in depressive patients by inhibiting CYP3A4 isoenzyme. In an isolated case, buspirone and citalopram co-administration lead to serotonin syndrome and hyponatraemia.35,38 In another study, concomitant administration of citalopram with fluconazole produced serotonin syndrome of life threatening intensity. Because, fluconazole potently 65 inhibits CYP3A4 isoenzymes. In a patient citalopram 10 mg daily for three years showed the symptoms of serotonin syndrome when started taking tramadol 50 mg daily for pain relief following a surgical operation. Tramadol inhibits CYP2D6 and CYP2C19 enzymes. 5 1 Similarly, levomepromazine increased the initial steady-state plasma levels of desmethylcitalopram (10 to 20%), the primary metabolite of citalopram, by potently inhibiting CYP2D6 isoenzymes activity. The interaction was not considered as clinically significant.56 The serum levels of citalopram was found raised by 44% in eighteen patients who were taking combination of citalopram and tricyclic antidepressants (example imipramine).60 Imipramine reportedly inhibits CYP2C19 enzymes to a milder extent.61 Depressive patients who did not respond to citalopram (40 mg/day) alone responded when fluvoxamine (50 to100 mg/day) co-administered for
three weeks. The plasma concentration of citalopram was increased by two to three folds due to selective inhibition of CYP3A4 and CYP2C19 enzymes by fluvoxamine.44 These reports suggest that the drugs that interact with citalopram by inhibiting CYP450 enzymes from mild to severe extent may produce excessive serotonergic reactions. These reactions may be life-threatening for many patients but, sometimes, beneficial to nonresponsive depressive patients. Hence, psychiatrists must be cautious and reduce the doses of index drug, if needed, while prescribing such interacting drug combinations. In contrast, the dose of citalopram is required to be increased in patients who are also prescribed with CYP450 enzymes inducers such as carbamazepine and rifampicin. Carbamazepine and rifampicin potently induces CYP3A4 isoenzyme involved in the metabolism (N-demethylation) of citalopram. Carbamazepine was found to decrease (30%) the plasma levels of citalopram.49 Less therapeutic efficacy (increased crying and panic attacks) of citalopram (40 to 60 mg daily) was observed in a 55-year-old depressive man when rifampicin (600 mg twice daily) was co-administered. The depressive condition improved when rifampicin administration was stopped.64 Pharmacodynamically, citalopram interacts potentially with many drugs from different therapeutic classes. Conversely, other drugs also interact with citalopram through the same mechanism. Serotonin reuptake inhibiting property of citalopram is responsible for such interactions. Citalopram including other SSRIs increase the risk of bleeding when administered with NSAIDS and oral anticoagulants by inhibiting serotonin levels and thus causing decreased platelet aggregation. 8 , 9 Meperidine, fentanyl and other opioids weakly inhibit serotonin reuptake. Serotonin syndrome, visual hallucinations and decrease in the threshold of the myoclonous were observed when the opioids were concurrently administered with citalopram.52, 53, 54, 55 Appetite suppressants like sibutramine, dexfenfluramine and fenfluramine have nonspecific serotonin agonistic activity that enhance the release of serotonin and also inhibit serotonin reuptake. These drugs produce serotonin syndrome when administered with 32,33,34 citalopram. Patients who did not respond to citalopram alone responded well with lithium carbonate combination.45,46 It was related to hyperstimulation of the 5-HT1A and 5-HT2A receptors by lithium in the
brainstem.48 Similarly, olanzapine and quitapine with citalopram produced serotonin syndrome as a consequence of increased brainstem and spinal cord 5HT1A receptor modulation occurring with 5-HT2A receptor antagonism.58,59 Fatal serotonergic effects were observed when citalopram was co-administered with monoamino oxidase inhibitor moclobemide and chemotherapeutic agent linezolid due to activation of 5-HT1A receptor.
40,41,42,62,63
These findings indicate that the outcome of pharmacodynamic interactions of citalopram is clinically significant. The consequences of excessive serotonergic effects may even produce death in the affected patients or prolonged hospital stay. Long hospital stay due to adverse interaction consequences may increase economic burden for the affected patients. To avoid such adverse consequences awareness about patient's conditions, adverse interactions including their management is required. In addition, withdrawal of an offending drug may be necessary to resolve exaggerated seroninergic symptoms. In spite of the adversities which are mentioned above, citalopram was found to be safest of its class. It was found to be safe in the treatment of hypertension as it is a weaker 15 inhibitor of CYP2C19. It was found to be a substitute for the treatment of paroxetine in tricyclic antidepressant toxicity.27 Citalopram did not affect the plasma levels of antipsychotic olanzapine which was found in case of fluoxetine, sertraline and paroxetine.22 Overall intensity of pharmacokinetic interactions of citalopram is minimum and which can be managed clinically. But, the pharmacodynamic interactions which were observed with drugs with serotonergic activity were found sometimes fatal. So, it is necessary that close monitoring of serotonin syndrome symptoms is required when these drugs are co administered and it is better to avoid this combination. Citalopram is producing some interaction on co administered with some drugs the outcome of which is its increased therapeutic efficacy. CONCLUSION Citalopram has the potential to interact with many drugs by pharmacokinetic and pharmacodynamic mechanisms. Many drugs similarly interact with citalopram. The nature of these interactions may vary from mild to severe. Close monitoring of these drug interactions consequences is required. This helps to avoid or manage the citalopram implicated interactions in the affected patients and thus reducing the cost associated with these
interactions and reducing the time of hospitalization. The interaction capacity of citalopram was less compared to other SSRIs in concurrent treatment with some antihypertensives, tricyclic antidepressants and antipsychotics. The interaction consequences of citalopram are some time manageable and even some times it gives an outcome which is beneficial. But pharmacodynamic interactions cannot be managed as the consequences of it were very severe which may even cause death. So close monitoring of the symptoms of pharmacodynamic interaction was required and even it will be better if these combinations with pharmacodynamic interactions is avoided. ACKNOLWLEDMENT The authors sincerely thank Dr. H.G. Shivakumar, Principal, J.S.S. College of Pharmacy, Mysore, for his support and encouragement. Our gratitude also goes to J.S.S. University, Mysore, for providing all the necessary facilities. REFERENCES 1. Karin H, Norio Y, Gunnel T, Jolanta W, Lars LG, Leif B. Metabolism of citalopram enantiomers in CYP2C19/CYP2D6 phenotyped panels of healthy Swedes. Br J Clin Pharmacol 2003;56:415-21. 2. Andre FJ, Connie S, Frank L. Citalopram. Human Psychopharmacology: Clinical and Experimental 2000;15(6):43951. 3. Olesen Ole V, Linnet Kristian. Studies on the Stereoselective Metabolism of Citalopram by Human Liver Microsomes and cDNA-Expressed Cytochrome P450 Enzymes. Pharmacology 1999;59:298-09. 4. Rochat, Amey B, Gillet M, Meyer M. Identification of three cytochrome P450 isozymes involved in Ndemethylation. Pharmacogenetics.1997;7(1):1-10. 5. Skop BP, Brown TM. Potential vascular and bleeding complications of treatment with selective serotonin reuptake inhibitors. Psychosomatics 1996;37:12-16. 6. Brunton Laurence L, Lazo John S, Parker Keith L. Goodman & Gilman's: The Pharmacological Basis Of Therapeutics. 11th ed. McGraw Hill; 2006. p.302. 7. Priskorn M, Sidhu JS, Larsen F, Davis JD, Khan AZ, Rolan PE. Investigation of multiple dose citalopram on the pharmacokinetics and pharmacodynamics of racemic warfarin. Br J Clin Pharmacol.1997;44:199202. 8. Borrs-Blasco J, Marco-Garbayo JL, Bosca-Sanleon
B, Navarro-Ruiz A. Probable interaction between citalopram and acenocoumarol. Ann Pharmacother. 2002;36:345. 9. Maurer-Spurej E, Pittendreigh C, Solomons K. The influence of selective serotonin reuptake inhibitors on human platelet serotonin. Thromb Haemost. 2004;91(1):119-128. 10.Celexa (Citalopram hydrobromide). Forest Pharmaceuticals, Inc. US Prescribing information, May 2007. 11. Prapotnik M, Waschgler R, Knig P, Moll W, Conca A. Therapeutic drug monitoring of trazodone: Are there pharmacokinetic interactions involving citalopram and fluoxetine? Int J Clin Pharmacol Ther.2004;42:1204. 12.Laine K, Anttila M, Heinonen E. Lack of adverse interactions between concomitantly administered selegiline and citalopram. Clin Neuropharmacol. 1997;20:41933. 13.Drug interactions between Celexa and metoprolol.. Drugs.com [online] 2010 Feb [cited 2010 Feb 28]; [3 screens]. Available from: URL:http://www.drugs. com/drug-interactions/celexa-with-metoprolol-679335-1615-0.html. 14. Karin Nyfort-Hansen. erhexiline toxicity related to citalopram use. Med J Aust 2002; 176 (11):560-61. 15.Belpaire FM, Wijnant P, Temmerman A, Rasmussen BB, Brsen K. The oxidative metabolism of metoprolol in human liver microsomes: inhibition by the selective serotonin reuptake inhibitors. Eur J Clin Pharmacol 1998;54:2614. 16.Hall J, Naranjo CA, Sproule BA, Herrmann N. Pharmacokinetic and pharmacodynamic evaluation of the inhibition of alprazolam by citalopram and fluoxetine. J Clin Psychopharmacol. 2003;23:34957. 17.Castberg I, Spigset O. Effects of comedication on the serum levels of aripiprazole: evidence from routine therapeutic drug monitoring service. Pharmacopsychiatry. 2007;40:10710. 18.Taylor D, Ellison Z, Ementon Shaw L, Wickham H, Murray R. Co-administration of citalopram and clozapine: effect on plasma clozapine levels. Int Clin Psychopharmacol. 1998;13:1921. 19.Avenoso A, Facciol G, Scordo MG. No effect of citalopram on plasma levels of clozapine, risperidone and their active metabolites in patients with chronic schizophrenia. Clin Drug Invest. 1998;16:3938.
20.Borba CP, Henderson DC. Citalopram and clozapine: potential drug interaction. J Clin Psychiatry. 2000;61:3012. 21.Freudenreich O. Exacerbation of idiopathic priapism with risperidone-citalopram combination. J Clin Psychiatry. 2002;63:24950. 22.Chiu C-C, Lu M-L, Huang M-C, Chen K-P. Heavy smoking, reduced olanzapine levels, and treatment effects. A case report. Ther Drug Monit 2004;26:57981. 23.Baettig D, Bondolfi G, Montaldi S, Amey M, Baumann P. Tricyclic antidepressant plasma levels after augmentation with citalopram: a case study. Eur J Clin Pharmacol. 1993;44:4035. 24.Gram LF, Hansen MG, Sindrup SH. Citalopram: interaction studies with levomepromazine, imipramine and lithium. Ther Drug Monit. 1993;15:1824. 25.Haffen E, Vandel P, Broly F. Citalopram: an interaction study with clomipramine in a patient heterozygous for CYP2D6 genotype. Pharmacopsychiatry 1999;32:2324. 26.Haffen E, Vandel P, Bonin B, Vandel S. Citalopram pharmacokinetic interaction with clomipramine. UDP-glucuronosyltransferase inhibition? A case report. Therapie. 1999;54:76870. 27.Ashton AK. Lack of desipramine toxicity with citalopram. J Clin Psychiatry 2000;61: 144. 28.Richards S, Umbreit JN, Fanucchi MP, Giblin J, Khuri F. Selective serotonin reuptake inhibitorinduced rhabdomyolysis associated with irinotecan. South Med J. 2003;96: 103133. 29.FDA ALERT [07/2006]: Potentially LifeThreatening Serotonin Syndrome with Combined Use of SSRIs or SNRIs and Triptan Medications. 30.Prod Info Axert(TM), 2001. 31.US Food and Drug Administration, 2006. 32.Prod Info Meridia(R), 1997. 33.Schenck CH, Mahowald MW. Potential hazard of serotonin syndrome associated with dexfenfluramine hydrochloride (Redux). J Am Med Assoc. 1996;276(15):1220-1. 34.Benazzi F. Organic hypomania secondary to sibutramine-citalopram interaction. J Clin Psychiatry. 2002;63:165. 35.Spigset O, Adielsson G. Combined serotonin syndrome and hyponatraemia caused by a
citaloprambuspirone interaction. Int Clin Psychopharmacol 1997;12:613. 36.Cipramil (Citalopram hydrobromide). Lundbeck Ltd. UK Summary of product characteristics, January 2007. 37.Celexa (Citalopram hydrobromide). Forest Pharmaceuticals, Inc. US Prescribing information, May 2007. 38.Leinonen E, Lepola U, Koponen H, Kinnunen I. The effect of age and concomitant treatment with other psychoactive drugs on serum concentrations of citalopram measured with a nonenantioselective method. Ther Drug Monit. 1996;18:11117. 39.Gum M, Clemente F, Segura A, Costa J. Sndrome serotoninrgico: moclobemida y citalopram. Med Clin (Barc). 1999;113:6778. 40.Neuvonen PJ, Pohjola-Sintonen S, Tacke U, Vuori E. Five fatal cases of serotonin syndrome after moclobemide-citalopram or moclobemideclomipramine overdoses. Lancet. 1993;342:1419. 41.Hjer J, Personne M, Skagius A-S, Hansson O. Serotoninergt syndrom: flera allvarliga fall med denna ofta frbisedda diagnos. Lakartidningen. 2002;99:20545, 205860. 42.Dams R, Benijts THP, Lambert WE. A fatal case of serotonin syndrome after combined moclobemide citalopram intoxication. J Anal Toxicol. 2001;25:14751. 43.Hiremagulur J, Keshavan Hrishi , Gurbani Nirmal K, Dandiya Prem C. Effect of citalopram (Lu 10-171) on tranylcypromine and tryptophan-induced wet-dog shakes in rats. Psychopharmacology.1980;70:209-12. 44.Bondolfi G, Chautems C, Rochat B, Bertschy G, Baumann P. Non-response to citalopram in depressive patients: pharmacokinetic and clinical consequences of a fluvoxamine augmentation. Psychopharmacology 1996;128:4215. 45.Gram LF, Hansen MG, Sindrup SH. Citalopram: interaction studies with levomepromazine, imipramine and lithium. Ther Drug Monit 1993;15:1824. 46.Baumann, Pierre, Nil R. A double-blind, placebocontrolled study of citalopram with and without lithium in the treatment of therapy-resistant depressive patients: a clinical, pharmacokinetic, and pharmacogenetic investigation. J Clin Psychopharmacol. 1996;16:30714. 47.Cipramil (Citalopram hydrobromide). Lundbeck Ltd. UK Summary of product characteristics, January
2007. 48.Drug interactions between Celexa and metoprolol. Drugs.com [online] 2010 Feb [cited 2010 Feb 28]; [3 s c r e e n s ] . Av a i l a b l e f r o m U R L : h t t p : / / www.drugs.com/drug-interactions/citalopram-withlithium-679-0-1477-0.html 49.Steinacher L, Vandel P, Zullino DF, Eap CB, Brawand-Amey M, Baumann P. Carbamazepine augmentation in depressive patients non-responding to citalopram: a pharmacokinetic and clinical pilot study. Eur Neuropsychopharmacol. 2002;12:25560. 50.Leinonen E, Lepola U, Koponen H. Substituting carbamazepine with oxcarbazepine increases citalopram levels. A report on two cases. Pharmacopsychiatry. 1996;29: 1568. 51.Mahlberg R, Kunz D, Sasse J, Kirchheiner J. Serotonin syndrome with tramadol and citalopram. Am J Psychiatry. 2004;161:1129. 52.Altman Evan M, Manos Gail H. Serotonin Syndrome Associated With Citalopram and Meperidine. Psychosomatics 2007;48(4):361-62. 53.Ailawadhi S, Sung KW, Carlson LA, Baer MR. Serotonin syndrome caused by interaction between citalopram and fentanyl. Journal of Clinical Pharmacy and Therapeutics 2007;32:199202. 54.Gnanadesigan N, Espinoza RT, Smith R, Israel M, R eu b en D B . In teractio n of s er o to n erg ic antidepressants and opioid analgesics: is serotonin syndrome going undetected? J Am Med Dir Assoc. 2005;6:2659. 55.Spigset O, Hedenmalm K, Dahl ML, Wiholm BE, Dahlqvist R. Seizures and myoclonus associated with antidepressant treatment: assessment of potential risk factors, including CYP2D6 and CYP2C19 polymorphisms, and treatment with CYP2D6 inhibitors. Acta Psychiatr Scand. 1997;96:37984. 56.Gram LF, Hansen MG, Sindrup SH. Citalopram: interaction studies with levomepromazine, imipramine and lithium. Ther Drug Monit.1993;15:1824. 57.Padala, Prasad R, Sadiq, Hasnain J, Padala, Kalpana. Urinary obstruction with citalopram and aripiprazole combination in an elderly patient. Journal of Clinical Psychopharmacology; December 2006;26 (6):66768. 58.Haslett CD, Kumar S. Can olanzapine be implicated in causing serotonin syndrome? Psychiatry.Clin Neurosci. 2002;56:5335.
59.Marlowe Karl, Schirgel Dorothea. Quetiapine and citalopram: aetiological significance in serotonin syndrome. NMJ;119:1237. 60.Leinonen E, Lepola U, Koponen H, Kinnunen I. The effect of age and concomitant treatment with other psychoactive drugs on serum concentrations of citalopram measured with a nonenantioselective method. Ther Drug Monit. 1996;18:11117. 61.Shin JG, Park JY, Kim MJ, Shon JH, Yoon YR, Cha IJ, et.al. Inhibitory effects of tricyclicantidepressants (TCAs) on human cytochrome P450 enzymes in vitro: mechanism of drug interaction between TCAs and phenytoin. Drug Metab Dispos 2002;30:110207. 62.Tahir N. Serotonin syndrome as a consequence of drug-resistant infections: an interaction between linezolid and citalopram. J Am Med Dir Assoc. 2004;5:11113. 63.Hendershot PE, Antal EJ, Welshman IR, Batts DH, Hopkins NK. Linezolid: pharmacokinetic and pharmacodynamic evaluation of co-administration with pseudoephedrine HCl, phenylpropanolamine HCl, and dextromethorphan HBr. Journal of Clinical Pharmacology 2001;41:56372. 64.Kukoyi O, Argo TR, Carnaham RM. Exacerbation of panic disorder with rifampin therapy in a patient receiving citalopram. Pharmacotherapy 2005;25:4357. 65.Levin Tomer T, Cortes-Ladino Alberto, Mark Weiss, M. Lia Palomba, Life-threatening serotonin toxicity due to a citalopram-fluconazole drug interaction: case reports and discussion. General Hospital Psychiatry 2008;30:37277.
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Evaluation of prescription pattern in terms of essentiality and rationality and assessment of Hospital pharmacy services utilization in tertiary care teaching rural hospital.
Shah AM *, Dhanani JV, Shah RB, Agrawal A, Gajjar BM
Department of Pharmacology, Pramukh Swami Medical College, Karamsad (Gujarat), PIN 388325 Address for Correspondence: dr_amit84@yahoo.co.in Abstract To evaluate the prescription pattern in terms of essentiality and rationality and assessment of Hospital pharmacy services utilization in tertiary care teaching rural hospital. A Prospective Observational Study was conducted. Total 100 patients attending various outpatient departments of Shree Krishna Hospital, a tertiary care teaching hospital were interviewed at their exit from the hospital and necessary information was gathered. Average time taken for interview with patient was 8.3 minutes with range of 7 to 10 minutes. All the prescriptions collected were analyzed for different parameters. Total 350 drugs were prescribed and average number of drugs per prescription was 3.5. Out of these 350 drugs, 60 (17.14%) were prescribed by generic name and the rest 290 (82.86%) were prescribed by brand name. Only 18 (5.14%) drugs were not prescribed from hospital formulary. 264 (75.43%) drugs were dispensed from the hospital pharmacy. On the basis of rationality score 53% prescriptions were rational, 30% semi rational and 17% irrational. Average rationality score was 20.56. In a hospital, where hospital formulary is based on WHO Essential medicine list, hundred percent utilization of hospital pharmacy services by doctors and patients would ensure rational prescribing for the benefit of the patients. Key words: prescription, out-patient, WHO, formulary INTRODUCTION Essential medicines are the drugs which satisfy health care need of majority of population and they should be available within the context of functioning health system at all time in adequate amount in appropriate dosage form with assured quality and adequate information with affordable price1. The WHO essential core list presents a list of minimum medicine needs for a basic health care system, listing the most efficacious, safe and cost-effective medicines for priority conditions. Priority conditions are selected on the basis of current and estimated future public health relevance, and potential for safe and cost-effective treatment2. The WHO essential complementary list presents essential medicines for priority diseases, for which specialized diagnostic or monitoring facilities, and/or specialist medical care, and/or specialist training are needed. In case of doubt medicines may also be listed as complementary on the basis of consistent higher costs or
Indian Journal of Pharmacy Practice Received on 20/03/2010 /0 Accepted on 24/03/2010 APTI All rights reserved /
less attractive cost-effectiveness in a variety of settings2. WHO Essential drug list helps in promotion of Rational Drug Therapy. Rational drug therapy means right drug to the right patient in a right manner (dose, duration, frequency and route of administration) at affordable cost1. Our hospital is a rural based tertiary care teaching hospital and the Hospital Formulary is based on WHO Essential drug list. Establishing the hospital formulary based on essential medicine list is not enough, assessing adherence of clinicians to the formulary is equally important. This study aims to check the compliance of doctors with hospital formulary, evaluation of utilization of hospital pharmacy services by doctors and patients, and evaluation of rationality of prescribing. METHODOLOGY A Prospective Observational Study was conducted in the Shree Krishna Hospital during the month of Jan-Feb 2009. The study was conducted under the aegis of Pharmacy Committee as a measure of audit. Permission from CEO was obtained prior to study. Ethics Committee approval was also taken. Written informed consent was taken from all participants after explaining detailed
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methodology to them. Total 100 patients attending various outpatient departments of Shree Krishna Hospital, a tertiary care teaching hospital were interviewed at their exit from the hospital and necessary information was gathered. Average time taken for interview with patient was 8.3 minutes with range of 7 to 10 minutes. All the prescriptions collected were analyzed for following parameters. ? of utilization of hospital pharmacy services by Extent doctors and patients. ? Reasons in cases of non-utilization of hospital pharmacy services. ? Prescription pattern in terms of essentiality and rationality. ? Whether medicines prescribed from Hospital Formulary. ? Whether medicines prescribed by generic or brand names. ? Appropriateness of drugs prescribed. For assessment of appropriateness of prescribing we have followed Phadke's criteria3. According to this criteria maximum 30 points score system was assigned as follows: ? drugs 20 points Main ? Complementary drugs 10 points Out of these total points, half the points for each of these two categories of the drugs were allocated for the correctness of the type of drug chosen for the condition and half for the correctness of the dose given, including route and frequency of administration and the duration of st nd therapy. So for the 1 choice 100% points, 2 choice 60% rd points & 3 choice 30% points were allocated. If more than two drugs were needed to be given in a condition, the points allocated were subdivided accordingly. Negative points were given for use of (a) irrational drug or irrational drug combination: -5; (b) unnecessary drug or injection: -5; (c) hazardous or banned drug: -10. These categories were defined as follows: (a) Irrational drug or irrational drug combination: a drug not recommended in the standard textbook of pharmacology or other established scientific literature. (b) Unnecessary drug or injection: a category of drug or formulation not recommended for that particular condition in the standard textbooks. (c) Hazardous or banned drug: drug listed under the heading 'Banned and bannable drugs' (Voluntary
Health Association of India, 1996, updated in 2003)4. Based on above mentioned criteria for analysis, net score was calculated and each prescription was graded accordingly as mentioned below: (a) 0 to 14 points- Irrational (b) 15 to 24 points- Semi rational (c) 25 to 30 points- Rational RESULTS Total 100 prescriptions from various outpatient departments were collected. In these prescriptions, total 350 drugs were prescribed. Average no. of drugs per prescription was 3.5. Department wise distribution of these prescriptions and average no. of drugs prescribed are shown in Table 1. Maximum number of drugs per prescription (4.58) was in medicine and ENT departments while lowest number per prescription (2) was in dental, ophthalmology and superspeciality clinics. Out of these 350 drugs only 60 (17.14%) were prescribed by generic name and rest 290 (82.86%) were prescribed by brand name. Out of 350 drugs prescribed, 332 (94.86%) drugs were prescribed from hospital formulary and only 18 (5.14%) drugs were not prescribed from hospital formulary. 264 (75.43%) drugs were dispensed from the hospital pharmacy and rest 86 (24.57%) were not dispensed from hospital pharmacy (figure 1). Total 38 patients had not taken some or all of the medicines prescribed, from the hospital pharmacy. We also tried to evaluate reasons for not purchasing drugs from hospital pharmacy, as shown in Table 2. On evaluating the prescriptions for appropriateness of prescribing 53% prescriptions were rational, 30% semi rational and 17% irrational (figure 2). Average rationality score was 20.56. DISCUSSION Rational prescribing is essential part of patient care. WHO has developed an essential drug list for promotion of rational drug therapy. Hospitals should have a formulary based on essential drug list. In our study we found that majority of prescriptions (94.86%) were from hospital formulary which is based on WHO essential drug list. In our study average no. of drugs per prescription was 3.5 which is almost similar to 3.52 reported by a similar study 5 done by Ansari et al . One of the studies conducted inTaiwan by Lai MS has reported average 4.3 drugs per 6 prescription. Inappropriate polypharmacy and potential
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Table.1: Department wise distribution of prescriptions co llected
Sl.No. 1 2 3 4 5 6 7 8 9 10 11 12
Name of department Medicine Surgery Skin Orthopedics ENT Obs & Gyn Paediatrics TB chest Psychiatry Dental Ophthalmology supersp eciality Total
No. of prescriptions 31 15 14 11 8 6 5 4 2 2 1 1 100
Total No. of drugs prescribed 143 43 64 26 37 13 12 17 7 4 2 2 350
No. of drugs per prescription 4.58 2.86 4.57 2.36 4.58 2.16 2.4 4.25 3.50 2 2 2 3.5
Table.2: Reaso ns for not purchasing drugs from hospital pharmacy (n=38)
Sl. No. 1 2 3 4 5 6 7
Reason Drugs not available in pharmacy store Drugs already present at home Long queue Cheaper d rugs/ brands available outside Free drugs availab le from drug bank/ samples/ other sources Advised b y doctor to take from outside ADR with brand available in hospital pharmacy
No. of patients (%) 1 4 (36.84%) 1 2 (31.57%) 7 (18.42%) 4 (10.52%) 3 (7.89%) 1 (2.63%) 1 (2.63%)
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Fig.2: Rationality score
drug therapeutic problems showed strong positive correlation with the number of drug per prescription7. The less no. of drugs per prescription carries less risk of adverse drug reactions and drug interactions. In our study 17.14% of drugs were prescribed by generic name and 82.86% by brand name. This suggests that there is a need for encouragement for prescribing medicines by generic name, particularly in a hospital attached to medical college. In this study 94.86% of drugs were prescribed from hospital formulary and only 18 (5.14%) drugs were not from hospital formulary. As our hospital formulary is based on WHO essential medicine list, it has direct impact on number of rational prescriptions. 86 drugs were not purchased from hospital pharmacy. Various reasons were given by patients for not purchasing drugs from the hospital pharmacy. Out of those, reasons like long queue, drugs out of stock and availability of cheaper brands outside are the issues which can be taken care of by the hospital authority for improving the compliance to hospital pharmacy. Steps can be taken for improvement like keeping enough stock and increasing pharmacy windows. In our study 53% of prescriptions were rational, which is
near to 59.2% reported in a study done by Ansari et al5. In our study 17% of prescriptions were irrational which is comparable to the nationwide multicentre study done by Krishnanangshu R et al which reported 4 to 26% of 8 prescriptions as irrational . This type of study is helpful in assessing adherence of doctors to the hospital formulary as well as compliance of both patients and doctors with the hospital pharmacy services. Further it is also helpful in finding out the issues responsible for noncompliance to the hospital pharmacy services. In conclusion, in a hospital, where hospital formulary is based on WHO Essential medicine list, hundred percent utilization of hospital pharmacy services by doctors and patients would ensure rational prescribing for the benefit of the patients. REFERENCES 1. Sharma HL, Sharma KK. Principles of pharmacology. 1st ed. Hyderabad: Paras medical publisher; 2007. p. 108-114 2. World Health Organization. WHO Model list of Essential Medicines. 15th list. (last cited 2008 Nov2). Available from URL: http://www.who.int/ medicines/publications/EML15.pdf 3. Phadke A. Drug supply and use: Towards rational
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policy in India. 1 ed. New Delhi: Sage publications; 1998. p. 85-100. 4. Community Development Medicinal Unit Documentation Centre. Banned and Bannable Drugs in India. 4th ed. (last cited 2008 dec 24). Available from URL: http://www.cdmubengal.org/other_info/ Banned Drugs India.pdf 5. Ansari KU, Singh S, Pandey RC. Evaluation of prescribing pattern for rational drug therapy. Ind J Pharmacol; 1998: 30: 408-410. 6. Lai MS, Chu CS, Lin SH, Lin MS. Prescribing pattern in primary health care in Taiwan. Int J Clin Pharmacol: 1995: 33: 437-441. 7. Muazu J , Ikunaiye NY , Abubakar A , Sadiq GU , Zarma SY and Umar YH. Assessment of Quality of Out-patient Prescriptions in the National Health Insurance Scheme Unit of a Tertiary Hospital in Nigeria. Res J Pharm Biol Chem Sci;2010: 1(1): 557561. 8. Krishnangshu R, Ghosh JM, Chandhri SB, Mandal A, Prasad S. Prescription audit analysis-A study of drug prescription practices in India. Calcutta: Voluntary Consumer Action Network (V-CAN), Consumer Utility &Trust Society, 1996.
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Pattern of potential medication errors in a tertiary care hospital in Nepal.

Kadir A
1, 2, 3
, Subish P , Anil K , Ram B
1,2
1. Department of Hospital and Clinical Pharmacy, Manipal Teaching Hospital, Pokhara, Nepal; 2. Department of Pharmacology, Manipal College of Medical Sciences, Pokhara, Nepal; 3. Department of Social and Administrative Pharmacy, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand Address for Correspondence: alamkad2050@yahoo.com Abstract In the process of treating a patient, errors may occur at any stage of pharmacotherapy starting from the prescription writing, dispensing, administration and monitoring. The present study was conducted to identify the potential medication errors among the outpatients and to categorize them based on the onset, underlying cause, medication error index and severity of medication error. A cross-sectional study was conducted in Manipal Teaching Hospital, Pokhara, Nepal between July 2007 to October 2008. The prescriptions having medication error was photocopied and used as the data source. The encountered medication errors were classified based on their onset, underlying cause, medication error index and severity of medication errors. Altogether 66 medication errors were recorded in 59 prescriptions. Medication errors were noticed more in prescribed medication of male patients and with antird microbial class of drugs. All (100%; n=66) the errors had latent onset. More than 2/3 (68.18%; n=45) of errors had underlying cause as wrong dose. Similarly, more than 2/3rd (72.73%; n=48) of errors were found to be medication error index of 'Category B' which suggests an error occurred, but medication did not reach to the patients and the degree of severity of most of the medication errors (69.70%; n=46) were 'B' on severity scale means clinically significant error which can increase need for patient monitoring. Conclusively, the proper communication between pharmacists and prescribers prevented majority of potential errors which is appreciable and should be continued. Key words: Medication Error, Nepal, Outpatients, Pharmacovigilance. INTRODUCTION Rational pharmacotherapy involves the appropriate use of medications for the patients to their clinical needs, in doses that meet their own individual requirements, for an adequate period of time and at the lowest cost to them and their community (World Health Organization, 1987). A medication error is defined as any preventable event that may cause or lead to in appropriate use or patient harm while the medication is in the control of healthcare professional, patient or consumer (Institute of Medicine, 2000). Pharmacotherapy is a complex process which requires the involvement of wide variety of healthcare professional including doctor, pharmacist, nurses etc. It is evident that error in the pharmacotherapy is quite common and can occurs at the any stage of medication process like prescribing, dispensing, administration and monitoring (Gandhi et al., 2005, Runciman et al., 2003). Studies from Thailand and Georgia, and Colorado found
Indian Journal of Pharmacy Practice Received on 24/04/2010 /0 Accepted on 30/04/2010 APTI All rights reserved
that prescription error is the most common type of medication error and accounted for 20-40% of all medication error (Sangtawesin et al, 2003, Barker et al., 2002). A study from United States of America (USA) suggested that around 44000 to 98000 hospitalized patients die due to medication errors in USA every year and number of death due to medication error is increasing day by day. (Institute of Medicine, 2000 and Phillips et al., 1998). Similarly in Australia 2-4% of all hospital admissions and up to 30% for patients aging more than 75 years are due to medication related out of which 75% are potentially preventable (Runciman et al., 2003). Further, a study conducted in the neighboring country, India in 304 patients in public hospital found that 34% patients were having at least one medication error (Pote et al., 2007). Nepal is a developing country with poor healthcare status with a large number of drug use problem. Some of them are irrational prescribing and dispensing, polypharmacy,
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misuse of antibiotic, irrational drug promotion, adverse drug reaction, drug interaction etc (Blum, 2000). Moreover, status of hospital pharmacy is very poor and most of the hospital does not have their own hospital pharmacy. In addition, there is lack of drug information (DI) services in the most of hospital. Further more, there is lack of package insert in the pharmaceutical preparation manufactured by Nepalese pharmaceutical company which is supposed to be one of cheap source of DI in the developing country. This suggests the lack of vigilance to the medicine and high risk of medication errors. To improve the vigilance, pharmacovigilance program was recently started to monitor the drug related problem (Uppsala Report, 2007). Currently, there are five regional pharmacovigilance centers in the country. Drug Information and Pharmacovigilance Center in Manipal Teaching Hospital is one among them. The center is regional center for western region of Nepal. The center is located in Manipal Teaching Hospital which tertiary care teaching hospital in Western Nepal. The hospital also has a drugs and therapeutics committee (DTC). The committee has also taken several steps to ensure the safe use of medicines (Palaian and Mishra, 2005). In the past, there were several initiatives taken to minimize the medication error which include drug information services for healthcare providers, medication counseling to the patients, continue pharmacy education to the hospital pharmacists, triplet billing system, batch dispensing, telephonic queries to prescribers, envelope system for dispensing drugs, computer billing system, separation of inpatients from outpatients, dispensing only with prescription, dispensing by qualified pharmacists and arrangements of medicine in pharmacy (Dubey et al., 2006). After such initiative there is need to know the pattern of medication error in the hospital. Moreover, the study in this area is lacking in Nepal. The present study was conducted with the following objectives: 1. To identify the potential medication errors among the outpatient prescriptions 2. To categorize the identified medication errors based on their onset, underlying cause, medication error index and severity of the medication errors. Material and Methods Study type: Cross-sectional Study Study site: The study was conducted in the Outpatient Pharmacy of Manipal Teaching Hospital. Manipal Teaching Hospital is a tertiary care teaching hospital in
Western Nepal. It is 700 bedded multidisciplinary hospital having clinical departments such as Medicine, Surgery, Pediatric, Psychiatry, Orthopedic, Obstetrics and gynecology, Ophthalmology, Dermatology, Otorhinolaryngology and Dental. On an average 600 patients visit the hospital everyday. Outpatient pharmacy is one of the units of Hospital and Clinical Pharmacy Department situated at the ground floor of the hospital. Duration: The study was conducted during July 2007 to October 2008. Inclusion Criteria: Prescriptions having at least one medication error were included in this study. Source of data: Photocopy of the prescriptions was the sources of data. Operation modality: Pharmacists working in the outpatient pharmacy department whenever encountered the error in the prescription, he/she photocopied the prescription. Further the clarification with the prescriber was done before dispensing the prescription. After clarification the correction made by the prescriber was recorded in the backside of the photocopied prescription. The photocopied prescription is studied for the categorization of error in this study. Categorization of medication error was done based on published literatures (Jackson and Reines, 2003; Allan and Barker, 1990; Hartwig et al 1991 and Lustig, 2000). Result analysis: The data obtained from the prescription were entered in the Microsoft excel spread sheet and analyzed. Results: Altogether 59 prescriptions encountering medication error were photocopied. Demography: The demography of the patients whose prescription encountered potential medication error revealed that number patients were male (42.37%, n=25) as compared to female (28.81%, n=17), where as in 28.81% (n=17) sex was not mentioned. The Age distribution of patients encountering potential mediation error shows that more number of patients was in the age group 21-30 years (18.64%, n=11), followed by age group years 11-20 (13.56%, n=8), age group 41-50 years (10.17%, n=6), age group 31-40 years (8.47%, n=5), age group 61-70 years (6.78%, n=4), age group 0-10 years (3.39%, n=2), age group 51-60 years (1.69%, n=1) and age group >70 years (1.69%, n=1). However, in 35.59% (n=21) of prescription age of the patients were not mentioned. The department wise distribution of the prescription encountering potential medication error is given in Table 1.
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Table.1: Department distribution (n=59)
Dep artment
Medicine Surgery Orthopedics Pediatrics Obstetrics and gynecology Dermatology Ophthalmo logy Psychiatry Dental Otorhinolaryngology Unknown
No. of prescripti on
11 10 7 7 5 4 3 3 2 2 5
Percentage
18.64 16.95 11.86 11.86 8.47 6.78 5.08 5.08 3.39 3.39 8.47
Categorization of medication errors: Altogether 169 drugs were prescribed in 59 prescriptions encountering 66 medication errors. While classifying the medication error based on onset it was found that all the error
recorded (n=66) was latent. Categorization of medication error based on underlying cause: The classification of medication error based on underlying cause is shown in Table 2.
Table.2: Classification of medication error based on underlying cause (n=66)
Underlying cause W rong dose error W rong T ime error Extra dose error W rong dosage form error W rong dose preparation error W rong route of administration error Others
No. of Error 45 7 6 3 3 1 1
Percentage 68.18 10.61 9.09 4.55 4.55 1.52 1.52
Categorization of medication error based on medication error index: The classification based on medication error index is given in Figure 1.
Fig.1: Classification based on medication error index (n=66)
2% 3% 23%
Category A Category B Category C Category D
72%
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Categorization of medication error based o n severity: The classification based on severity is given in Figure 2. Fig.2: Classification based on Severity Index
9% 21%
A B C
70%
Classification of drugs involved in medication error: Similarly the classification of drugs which was involved in medication error is classified in Table 3.
Table.3: Class of drugs involved in medication erro r (n=66)
Class of drugs
Anti-microbial agents Gastrointestinal agents Drugs acting on central nervous system (CN S) Non-steroidal anti-inflammato ry drugs Anti-allergic drugs Corticosteroids Non-opiodal analgesics Anticancer drugs Drugs acting on cardiovascular system Drugs acting on resp iratory system Vitamins Others
Num ber of drugs

27 14 7 5 4 2 2 1 1 1 1 1
Percentage
40.91 21.21 10.61 7.58 6.06 3.03 3.03 1.52 1.52 1.52 1.52 1.52
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Table.3 : Site of Infection Diagnosed
Sl. No.
SITE OF INFECTION
% OF CASES
n=482
Gastro-intestinal
26.86
Respiratory
22.39
Others
50.74
The prescriptions were also evaluated for their rationality and irrationality. Based on the number of antibiotics prescribed in each prescription 71.64% prescriptions were found to be rational, the remaining of 28.36% prescriptions were found irrational with two or three
antibiotics prescribed in each prescription. When prescriptions were evaluated based on the drug interaction 58.21% prescriptions were found to be rational and 41.79% prescriptions were irrational, the data have been represented in Table-4.
Table.4: Rationality and Irratio nality of Prescriptions
RATIONAL Sl. No. PATTERN (%) 1 Number of antibiotics p rescribed 71.64
IRRATIONAL (%) 28.36
Drug interaction
58.21
41.79
DISCUSSION The inappropriate utilization of antibiotics, especially in infants and children, forced many researchers to evaluate the consumption of this class of antimicrobial agent in order to control the risk and its misuse. Studying the antimicrobial prescribing pattern in an Indian tertiary hospital has showed that two antimicrobials per prescription was maximum in pediatrics, while one antimicrobial was maximum in surgery, urology and internal medicine departments. Amikacin, ciprofloxacin, cefotaxime and cloxacillin were the most preferred drugs10. The result of present study demonstrates that antibiotics are frequently used in infants and children. In
contradict to the previous observation it was found that the most widely used antibiotics belong to class of quinolones and penicillins (Pn). Norfloxacin, ciprofloxacin, ofloxacin and amoxicillin are found to be most frequently used antibiotics in pediatrics. Resistance against quinolones such as norfloxacin, ciprofloxacin, etc. develops quite slowly and hence they are widely used11.Amoxicillin is active against all organisms sensitive to Pn G, in addition it inhibits many gram negative bacilli, its oral absorption is better and is not interfered by food along with this higher and more sustained blood levels are produced12. Amoxicillin with
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Steps taken to prevent the medication errors: Majority of times (89.39%, n=59) after encountering mediation error pharmacists clarified the errors with the prescribers. Whereas in few instances (7.58%, n=5) action taken after encountering the medication error are not recorded. However, in one instances (1.52%, n=1) the drugs were wrongly dispensed by the pharmacists and in one instances (1.52%, n=1) correction was done after few doses. Example of potential medication error: Some of the potential medication errors are described in Table 4.
Table.4: Exam ple of potential medication error
Name of drugs
Secnidazole Cloxacillin
Medication errors
Tab Secnidazole was prescribed as 2 gm two tab HS single dose which after clarification with prescriber it was dispensed as Tab Secnidazole 1 gm two tab HS. Cap Cloxacillin was prescribed as 500 mg three times daily for 7 days which after clarification with prescriber, it was dispensed as Cap Cloxacillin 500 mg four times daily for 7 days Tab. Azithromycin was prescribed as 500 mg four times daily for 7 day which after clarification with prescriber, it was dispensed as Tab. Azithromycin 500 mg once daily for 7 days Tab. Tramadol was prescribed as 500 mg whenever necessary which after clarification with prescriber it was modified as Tab Tramadol 50 mg whenever necessary. Tab. Ranitidine was prescribed as 4 0 mg daily 7 day which after consultation with prescriber it was modified as Tab. Ranitidine 150 mg twice daily for 7 days.
Azithromycin Tramadol Ranitidine
DISCUSSION Altogether 66 medication errors were identified in 59 prescriptions. The study found that all the medication error has latent onset. In most of the cases (68.18%) underlying cause for medication error was found to be wrong dose. Similarly, most of the medication errors were found to be medication error index of 'Category B' which suggests an error occurred, but medication did not reach to the patients. The degree of severity of most of the medication error was found to be 'B' on severity scale means clinically significant error which can increase need for patient monitoring. Medication error was found more with anti-microbial class of drugs. There are several underlying cause involved in medication error which include wrong dosing interval, wrong dose, wrong route, wrong drug, wrong dosage form etc. We found that most promising underlying cause for medication error was wrong dose (68.18%) followed by wrong time (10.61%) and extra doses (9.09%). Similarly in a study conducted in 36 healthcare facilities in Georgia and Colorado found most frequent types of error were wrong time (43%), omission (30%), wrong dose (17%) (Barker et al., 2002). Whereas in another study conducted in India found most common types were drug interaction (68%) followed by incorrect interval (12.1%) and incorrect dose [over and under dose] (9.6%)
(Pote et al., 2007). This suggests that wrong dose and wrong timing are the common underlying cause involved in medication error. We found that medication error was more with the antimicrobial class of drugs (40.91%) followed by GI agents (21.21%), CNS agents (10.61%). This is because antimicrobial are the class of drugs used commonly in different specialties. A study conducted in India by Pote S et al. also found anti-microbial class of drugs were more involved in medication error (Pote et al., 2007) and Similar result was found in study conducted in Israel where anti-infective class of drugs were involved in 38.7% of medication error (Lustig A, 2000). It suggests that anti-microbial class of drugs need special focus. A study suggests that more than 75% of potential medication errors can be prevented (Runciman et al., 2003). In our study we found that more than two-third of medication error (72.73%) were found to be medication error index of 'Category B' means an error occurred, but medication did not reach to the patients which is very good from the patients point of views followed by 22.73% of 'Category A' in medication error index which suggest circumstances or events that have the capacity to cause error. Similarly in a study conducted in Thailand, 76.71% of medication errors were prevented
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(Sangtawesin et al, 2003). This suggests that reporting medication error is not a fault finding process rather it is a preventing of its incidence. Hence, reporting of medication error should be encouraged. More than 2/3 of the Medication error found clinically significant error which can increase need for patient monitoring. Similarly a study conducted in Israel found that 11%, 16%, 34% and 80% of clinically significant error occurs per day in Internal Medicine, Intensive Care, Surgery and Hemato Oncology Departments respectively (Lustig A, 2000). Several strategies have been recommended to prevent the medication errors in the health care setting. Some of them are computerized physician order, clinical pharmacist monitoring order, improved communication between healthcare practitioners etc. In this study majority of time (89.39%) pharmacists clarify their doubt with the prescribers to prevent the medication errors. Hence, it is evidence that proper communication between healthcare professionals can prevent the majority of potential errors. CONCLUSION Medication error in the healthcare setting is a common phenomenon. Medication error is more common with anti-microbial class of drugs and the most common underlying cause behind medication error is wrong dose. Most of the errors are clinically significant and it can be prevented by working together in a healthcare team. We experienced that most of the medication error was mainly due to poor prescription writing. Since, we prevent most of the potential medication errors through proper communication with prescriber which is highly appreciable. But the matter should be discussed in DTC meeting to minimize the risks. ACKNOWLEDGEMENT Authors acknowledge Mr. Pradip Ojha, Hospital Pharmacist, Manipal Teaching Hospital for his help during data collection. REFERENCES 1. Allan EL, Barker KN. Fundamentals of medication error research. Am. J. Hosp. Pharm 1990;47: 555-71. 2. Barker KN, Flynn EA, Pepper GA, Bates DW, Mikeal RL. Medication errors observed in 36 health care facilities. Arch. Intern. Med 2002;162:1897-903. 3. Blum NL. Drug Information Development-a case study Nepal. Rational Pharmaceutical Management Project. United States Pharmacopeia 2000. 4. Dubey AK, Palaian S, Shankar PR, Mishra P, Prabhu M. Introduction to medication errors and the error
rd
prevention initiatives in a teaching hospital in Western Nepal. Pak. J. Pharm. Sci 2006;19(3):24451. 5. Gandhi TK, Weingart SN, Seger AC, Borus J, Poon EG. Outpatient prescribing errors and the impact of computerized prescribing. J. Gen. Intern. Med 2005;20:837-41. 6. H a r t w i g S C , D e n e r S D , S c h n e i d e r P J . Severityindexed, incident report-based medication error-reporting program. Am. J. Hosp. Pharm 1991;48:2611-6. 7. Institute of Medicine, committee on quality healthcare in America. To err is human: building a safer health system. Kohn LT, Corrigan JM, Donaldson MS, editors. In: Report of the institute of medicine 2000. Washington DC: National academy press; 2000. 8. Jackson MA, Reines WG. A systematic approach to preventing medication errors. US Pharm 2003;28(6):69-76. 9. Lustig A. Medication error prevention by pharmacists- an Israeli solution. Pharm World Sci 2000;22(1): 21-5. 10. Phillips DP, Christenfeld N, Glynn LM. Increase in US medication-error deaths between 1983 and 1993. The Lancet 1998;351:643-44. 11. Palaian S, Mishra P. Role of drug and therapeutics committee towards drug safety: experiences from w e s t e r n N e p a l . K a t h m a n d u . U n i v. M e d 2005;3(9):79-80. 12. Pote S, Tiwari P, D'cruz S. Medication prescribing errors in a public teaching hospital in India: a prospective study. Pharm. Pract 2007;5(1):17-21. 13. Runciman WB, Roughead EE, Semple SJ, Adams RJ. Adverse drug events and medication errors in Australia. Int. J. Qual. Health Care 2003;15(I):i49i59. 14. Sangtawesin V, Kanjanapattanakul W, Srisan P, Nawasiri W, Ingchareonsunthorn P. Medication errors at Queen Sirikit National Institute of Child Health. J. Med. Assoc.Thai 2003;86(Suppl 3): S5705. 15. Uppsala Reports 2007. Nepal joins the programme. 36: 5-6. Available from: URL:<www.whoumc.org/graphics/10205.pdf 16. World Health Organization. The rational use of drugs: report of the conference of experts1987. Nairobi, 1985 Nov 25
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APTI
ijopp
Study of prescription practice for Antipsychotic drugs by Psychiatrists- A Survey

Mukesh Ratnaparakhi* Guru Prasad Mohanta , Lokesh Upadayay
1 2 3
1. Marathwada Mitra Mandal's College of Pharmacy, Thergaon, Pune- 411033, India; 2. Annamalai University, Annamalai Nagar - 608 002, India; 3. CARISM, Sastra University, Tanjavur -613 402, India. Address for Correspondence: mukeshparkhi@yahoo.co.in Abstract This study was revealed with prescribing patterns of antipsychotic and monitoring practices of psychiatrists in Pune region. We were surveyed 100 psychiatrists in Pune region out of that 50 gave a positive response. This survey includes the study of antipsychotic types prescribed its frequency, the age of the patients and the diagnosis of patients for whom they prescribed these medications. We were prepared a questionnaires format and were distributed to various psychiatrists in the form of hard copy within the Pune region. Questionnaires formats were collected after fulfillment by psychiatrics in the form of hard copy. In that 88 % of psychiatrics prescribed ATAs, most commonly risperidone (67 %). Patients diagnosis was include psychotic, mood, anxiety, externalizing, and pervasive developmental disorders. Symptoms persist in patients were aggression, low frustration tolerance, and affect dysregulation was also common. Percent of all prescriptions were for years. Most clinicians monitored patients, but there were wide variations in the type and frequency of tests performed. Our study reveals that there exists considerable variation in patterns of prescribing psychotropic medications and a significant increase in the number of patients suffering from psychiatric illnesses seeking treatment. Prescribing patterns vary due to differences in diagnosis, the discomfort that some psychiatrists feel toward prescribing, differing levels of awareness and recognition due to cultural variances, the perceived negative stigma of mental illness, and insufficient education regarding the etiology and management of psychiatric disorders. Key words: Anti-psychotic drugs, prescribing pattern, mental illness INTRODUCTION In the last 2 decades, the treatment of psychosis has been 13 revolutionized by the widespread adoption of ATAs. These agents, presently available in India include risperidone, olanzapine, quetiapine, and clozapine, have fewer propensities to cause extrapyramidal side effects and carry a significantly lower risk of tardive dyskinesia than do typical agents.4 For adults, monitoring guidelines and established indications for the use of these medications exist, but not for children, with some exceptions. Some data exist to support the use of clozapine to treat refractory schizophrenia in patients aged under 18 years5 and to reduce aggression in this 6 7 population ; the review by Kranzler and colleagues cites it as the drug of choice for this indication. Olanzapine has been reported to provide good response in early-onset schizophrenia. The adoption of ATA's as first-line drugs
Indian Journal of Pharmacy Practice Received on 28/03/2010 / Accepted on 31/03/2010 APTI All rights reserved /
is primarily based on a similar practice for treating adults. The more acceptable side effect profile and the safety of ATAs have broadened the indications for their use. ATAs are being used increasingly to treat various nonpsychotic disorders, not only in adults but also in children and adolescents.814 As is often the case, controlled trials are rare and are characterized by small sample sizes, diagnostically heterogeneous samples, retrospective designs, short follow-up, and the lack of control groups.1518 Some data support short-term, sustained efficacy in reducing aggression,1924 tics,25 and mania.26,27 Other uses for ATAs, for example, as adjunctive treatment for anxiety and depression, are only supported by data for adults. Unfortunately, these medications are not without their shortcomings. Most studies of adults and children find weight gain to be a side effect of 2831 ATAs. Although this is to some extent a class effect, weight gain is generally more common and greater with 31 olanzapine and clozapine. Prior to treatment, adults
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with psychosis have a higher risk of glucose intolerance than do control subjects without psychosis; these medications increase that risk.32,33 Medications such as olanzapine and clozapine, which cause more weight gain in adults, are generally more likely to disturb glucose metabolism, but this change has been found with use of all these medications in adult populations to differing extents. Finally, undesirable effects on lipid metabolism 3335 have also been identified in adults. Weight gain with ATA use is by no means universal or inevitable. Awareness of this side effect, warning patients about it, and early intervention with diet and exercise have been advised.36 The use of ATAs in treating psychotic disorder has been increasing exponentially, raising concerns as to the appropriateness of this practice.37, Evidence-based guidelines on frequency and type of monitoring do not exist. To better appreciate current practices, we surveyed psychiatric to quantify their prescribing of this class of medications, the disorders and symptoms being treated, and the type and frequency of monitoring being used currently. With respect to this in present study we had surveyed the psychiatrists to study the use of atypical antipsychotic, their patient compliance to different formulations. METHOD We surveyed child and adolescent psychiatrists, developmental pediatricians after obtaining approval from their professional organizations. Questionnaire We developed a questionnaire asking whether the physicians prescribed these medications, for which indications, and in which age groups. Questionnaires format were given to various psychiatrics in the form of
hard copy within the Pune region. Questionnaires were collected from the psychiatrics after their fulfillment as a hard copy. Analysis Student t test was used to compare differences in categorical outcome variables. Instat software was used for analysis. RESULT The survey of antipsychotic agent prescribing by psychiatrists was conducted in a 100 psychiatrists out of them 50 gave a positive response. The survey was conducted on questionnaire basis. Questionnaire formats was given to psychiatrics and collected in the form of hard copy. The survey was conducted from August to January on a weekly basis. Some of the questions were found to be ineligible due to misinterpretation. Respondents were asked, which dosage forms you generally preferred. The most commonly used dosage forms are injectables, depot injections, oral dosage forms, liquid preparations out of which 34% were injectables, 58% of oral dosage forms, 2% of liquid preparations and 6% of depot injections were generally preferred by psychiatrists. The various types of psychiatric patients were visited to hospital as, Neurosis, depression, mood disorders, anxiety, bipolar disorders, and schizophrenia. Out of which 61% of the patients suffered from schizophrenia 9% of the patients suffered from depression, 1 % of the patients suffered from neurosis, 13 % from anxiety and 7% from mood disorders. Regarding long acting dosage form only 10% of psychiatrist prefers long acting preparations and in contrast to that 80% of the psychiatrists think that mouth dissolving tablet is the best option for psychotic patients
Fig.1: Percentage of Prescribers by Age of Patients
Percentage of Prescribers by Age of Patients

40% 35% 30% 25% 20% 15% 10% 5% 0% 20-30 30-40 40-50 50-60 Age in years
P recentage
24
Table.1: Percentage of prescribers by medication
Medication Risperido ne Olanzapine Quetiapine Clozapine
Percentage 67 23 24 0.5
Table.2: Percentage of prescribers by indication
Indication Schizophrenia Bipolar mood disorder Depression Tourette syndrome Eating disorder Obsessivecompulsive disorder Posttraumatic stress disorder Other anxiety disorders Pervasive developmental disorder Mental retardation Attention-deficit hyperactivity disorder Oppositional defiant disorder Conduct disorder Impulsivity Poor frustration tolerance Affective dysregulation Insomnia
as a drug delivery medium. 30 % of patients have age more than 50 year. 79% the psychiatrists answered that they use tranquilizers before giving antipsychotic agents while 21% answered that they are not used tranquilizers before giving antipsychotic agents. The most commonly used methods for reducing catatonia in patients were ECT, Anti-psychotic agents and exercise show that 60% use of ECT, 25% use of antipsychotic agents, 14% use of benzodiazepines and 1% exercise helped in reducing catatonia as reported by the psychiatrists. 79% the psychiatrists answered that they use tranquilizers before giving antipsychotic agents while 21% answered that they are not used tranquilizers before giving anti-psychotic agents. The drug abuse was found to be 30% and drug dependence 70% as reported by the psychiatrists. DISCUSSION These data suggest a high rate of prescribing ATAs for various indications and symptoms. A significant
Percentage 79 80 28 72 24 53 33 29 88 48 51 51 59 65 73 83 33
proportion of these prescriptions are given to children aged under the age of 9 years. These medications are currently being used off-label without clear guidelines for indications, dosing, and monitoring. Subjects report that they monitor patients extensively and frequently, but the practices are not uniform. This situation may be due to lack of data and guidelines. A 43.9% rate of AIMS testing is impressive; however, this means that 56.1% of patients under the age of 18 years who are being prescribed this medication are not being monitored in this way. Further, there are significant discrepancies in the timing of follow-up (3 months, 6 months, or 12 months.) Although these survey results do not establish the total number of patients being treated with ATAs, they do establish that the prescribing of ATAs by psychiatrics in Pune India is ubiquitous. There is an urgent need for more data regarding safety. reports suggests that most of the doctors found long acting preparations and oral dosage forms more compatible as
25
compared to injectables and liquid dosage forms. CONCLUSION This study reveals that there has been a significant increase in the number of patients suffering from psychiatric illnesses seeking treatment, which has precipitated an increase in the number of prescriptions written by psychiatrists for antipsychotic agents. However, there exists considerable variation in patterns of prescribing psychotropic medications, as well as a general lack of concordance between diagnosis and psychotropic medications prescribed in the medical field as a whole. Prescribing patterns vary due to differences in diagnosis, the discomfort that some psychiatrists feel toward prescribing, differing levels of awareness and recognition due to cultural variances, the perceived negative stigma of mental illness, and insufficient education regarding the etiology and management of psychiatric disorders. These variations are particularly evident in the prescribing trends of primary care physicians with antipsychotic medications. In order to have a positive impact on patient populations, it is important for psychiatrist to make use of various newly introduced medications to manage the spectrum of these disorders that are so frequently appearing in their practices. ACKNOWLEDGEMENT The authors are thankful to Dr. M. J. Patil Principal Marathwada Mitra Mandals College of Pharmacy for providing the necessary support. REFERENCES 1. Lambert M, Conus P, Lambert T. Pharmacotherapy of first-episode psychosis. Expert Opin Pharmacother. 2003;4(5):71750. 2. Pappadopulos E, Macintyre Ii JC, Crismon ML. Treatment recommendations for the use of antipsychotics for aggressive youth (TRAAY) Part II. J Am Acad Child Adolesc Psychiatry. 2003;42(2):14561. 3. Curran S, Harris L, Macdonald A. Antipsychotics in clinical practice: guidelines for safe and effective use. Hum Psychopharmacol. 2002;17(2):7582. 4. Varghese Sunny T. Antipsychotic drug prescription in postgraduate psychiatry training programs in India: Time to reflect. Ind J Psychiatry 2007;49(3):225. 5. Lalonde P. Evaluating antipsychotic medications: predictors of clinical effectiveness. Report of an expert review panel on efficacy and effectiveness.
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2001;11(3):28588. 18. Nguyen M, Murphy T. Olanzepine and hypertriglyceridemia. J Am Acad Child Adolesc Psychiatry. 2001;40(2):133. 19. Martin A, L'Ecuyer S. Triglyceride, cholesterol and weight changes among risperidone-treated youths. A retrospective study. Eur Child Adolesc Psychiatry. 2002;11(3):12933. 20. Reyes M, Olah R, Csaba K. Long-term safety and efficacy of risperidone in children with disruptive behaviour disorders. Results of a 2-year extension s t u d y. E u r C h i l d A d o l e s c P s y c h i a t r y. 2006;15(2):97104. 21. Aman MG. Management of hyperactivity and other acting-out problems in patients with autism spectrum disorder. Semin Pediatr Neurol. 2004;11(3):22528. 22. Findling RL, McNamara NK, Branicky LA. A double-blind pilot study of risperidone in the treatment of conduct disorder. J Am Acad Child Adolesc Psychiatry. 2000;39(4):50916. 23. Shea S, Turgay A, Carroll A. Risperidone in the treatment of disruptive behavioral symptoms in children with autistic and other pervasive developmental disorders. Pediatrics. 2004;114(5):63441. 24. Troost PW, Lahuis BE, Steenhuis MP. Long-term effects of risperidone in children with autism spectrum disorders: a placebo discontinuation study. J A m A c a d C h i l d A d o l e s c P s y c h i a t r y. 2005;44(11):113744. 25. McCracken JT, McGough J, Shah B. Risperidone in children with autism and serious behavioral problems. N Engl J Med. 2002;347(5):31421. 26. Scahill L, Leckman JF, Schultz RT. A placebocontrolled trial of risperidone in Tourette's syndrome. Neurology. 2003;60(7):113035. 27. Delbello MP, Schwiers ML, Rosenberg HL. A double-blind, randomized, placebo-controlled study of quetiapine as adjunctive treatment for adolescent mania. J Am Acad Child Adolesc Psychiatry. 2002;41(10):121623.
28. Delbello MP, Kowatch RA, Adler CM, et al. A double-blind randomized study comparing quetiapine and divalproex for adolescent mania. J A m A c a d C h i l d A d o l e s c P s y c h i a t r y. 2006;45(3):30513. 29. Addington J, Mansley C, Addington D. Weight gain in first-episode psychosis. Can J Psychiatry. 2003;48(4):27276. 30. Allison DB, Casey DE. Anti-psychotic-induced weight gain: a review of the literature. J Clin Psychiatry. 2001;62(Suppl 17):2231. 31. Theisen FM, Linden A, Geller F. Prevalence of obesity in adolescent and young adult patients with and without schizophrenia and in relationship to antipsychotic medication. J Psychiatr Res. 2001;35(6):33945. 32. Survey of Atypical Antipsychotic Prescribing by Canadian Child Psychiatrists and Developmental Pediatricians for Patients Aged Under 18 Years The Canadian Journal of Psychiatry 2007 June;52(6):367. 33. Wirshing DA, Wirshing WC, Kysar L. Novel antipsychotics: comparison of weight gain liabilities. J Clin Psychiatry. 1999;60(6):35863. 34. Meyer JM. A retrospective comparison of weight, lipid, and glucose changes between risperidone- and olanzapine-treated inpatients: metabolic outcomes after 1 year. J Clin Psychiatry. 2002;63(5):42533. 35. Lund BC, Perry PJ, Brooks JM. Clozapine use in patients with schizophrenia and the risk of diabetes, hyperlipidemia, and hypertension: a claims-based approach. Arch Gen Psychiatry. 2001;58(12): 117276. 36. Meyer JM. Novel antipsychotics and severe hyperlipidemia. J Clin Psychopharmacol. 2001;21(4):36974. 37. Koro CE, Fedder DO, L'Italien GJ. An assessment of the independent effects of olanzapine and risperidone exposure on the risk of hyperlipidemia in schizophrenic patients. Arch Gen Psychiatry. 2002;59(11):102126.
27
APTI
Mallik Santanu* , Kumar Nilesh , Gautam Rajesh
1 2
ijopp
1 1 1
A retrospective review on Malaria and Antimalarial drugs in Tripura, India A Survey Report
Department of Pharmacy, Lovely Professional University, Phagwara, Punjab-144402 Regional Institute of Pharmaceutical Science and Technology, Abhoynagar, Agartala, Tripura-799105 Address for Correspondence: santanu.mallik@gmail.com
Abstract This study reveals the status of disease malaria in Indian hilly areas with respect to availability of drugs and to identify the common causative parasites of malaria. The work was carried out in urban and rural areas of Tripura. In both cases 500 indoor patients' bed tickets were surveyed to find out the causative parasite, recovery period, antimalarial drug used and again to compare the facilities, diagnostic procedure and clinical status. In this study it was observed that the clinical pharmacy strategies were not well maintained in hospitals of both the areas but the disease was well handled in semi rural areas. The self medication, magic remedies /mantras are still in practice among rural peoples .In this survey it was observed that; in primary cases of malaria, patient recovered within 5-7 days; whereas in severe cases it took 25-30 days, if proper medication is provided. But 25% of patients come to hospital only when disease is in chronic situation. In both the places two types of parasites were mainly found Plasmodium falciparum & Plasmodium vivax .In acute cases of malaria, chloroquine group of drugs were widely prescribed and in normal cases the proguanil group was the choice of drug by the physicians. Key words: Malaria, Anti-malarial drugs, Malaria parasite, Plasmodium INTRODUCTION Malaria is one of the most common infectious diseases and an enormous public health problem. Malaria has infected humans for over 50,000 years, and has been a human pathogen for the entire history of the species1. Each year, there are approximately 350500 million 2 cases of malaria , killing between one and three million people, the majority of whom are young children in SubSaharan Africa3.There are sixty three species of mosquitoes still today reported worldwide. Among them, four species are very active in India, namely, Plasmodium falciparum (pf), Plasmodium vivax (pv), Plasmodium ovale(po) and Plasmodium culex (pc). The parasites multiply within red blood cells, causing symptoms that include anemia (light-headedness, shortness of breath, tachycardia, etc.), as well as other general symptoms such as fever, chills, nausea, flu-like illness, and, in severe cases, coma, and death. Malaria transmission can be reduced by preventing mosquito bites with mosquito nets and insect repellents, or by mosquito control measures such as spraying insecticides inside houses and draining standing water where mosquitoes lay their eggs4.
Ninety percent of malaria-related deaths occur in SubSaharan Africa. Malaria is commonly associated with poverty, but is also a cause of poverty5. As per WHO latest estimation, there are 300-500 million cases globally and 1.5- 2.7 million deaths occur due to malaria each year, 90% of which are in Africa. In India, The National Malaria Eradication Programme (NMEP) was started in 1958 and achieved near complete disappearance of 6 disease in 1960s . In 1995, NMEP has reported 2.3 million proven cases out of which 0.8 million were by Plasmodium falciparum and there were 1012 deaths. However, the actual incidence of malaria in India is estimated to be between 15-35 million cases per year7. For diagnosis of malarial parasites, direct microscopy of peripheral smear is widely used. Other processes involved dip stick/ Quantitative Buffy coat technique (QBC).To study the epidemiological distribution of falciparum with its positive rate, Hbgm% label is used as a parameter8. Based on direct microscopy of peripheral blood smear, 7,490 patients having history of fever were registered in outpatient department of Agartala Government Medical college hospital (G. B. Pant hospital) during March 2003 - 2005. Blood was collected aseptically in EDTA vial, smear was prepared of all 7,490 registered cases and leishman stain was done.
28
Hemoglobin estimations were done by acid hematin method for all 36 positive cases in the department of clinical microbiology. Out of 7,490 smears 36 were positive. Among the 36 positive patients, males were more than females with 66.66% and 33.33% respectively. Smear showed Plasmodium falciparm positive rate in 86.11%, others vivax in 8.33% and gametocyte in 5.55%. Hemoglobin pattern was markedly decreased below 8% in 66.66% and below 10% and above 8% in 36.11% cases only. Mostly were treated at home and 9 detailed drug history was not known . In Tripura Anopheles dirus & minimus, Culex species were also seen. In order to improve detection of hemoparasites, QBC Assay was introduced in Tripura in private laboratory since July, 2000. During these 5 year period, total no of 6449 blood samples were examined by QBC Assay. Samples were received from patients with pyrexia of acute onset as well as PUO patients. QBC capillaries processed as per standard protocol. Giemsa stain was done in thin smear for confirmation of species. Out of 6449 samples, 1349 (21%) were positive for malaria. Among them, 1072 (79%) P.falciparum 197 (15%) P.vivax, 80 (6%) mixed infection. Surprisingly, in 4 patients Microfilaria was detected where clinical suspision was for malaria though not in indigenous people. This was first time in Tripura Microfilaria could be detected from day time samples because of using sensitive diagnostic tool. Incidence of malaria in Tripura is quite high, P.falciparum is the predominant species9, 10. A number of anti malarial drugs are prescribed by the doctors globally, like Chloroquine, Quinine and mefloquine, Primaquine, Antifols and Quinghaosu (Artemisinine) MATERIALS AND METHODS Study site The study was conducted in five different hospitals, situated in three different locations, one is Agartala Govt, Medical College and G.B.P. Hospital, Indira Gandhi Memorial Hospital, B.R. Ambedkar Teaching Hospital, Agartala; Tripura Sundari Hospital, Udaipur; Santir Bazar Public Health Center, Santir Bazar, South Tripura were selected. Study Period The study was carried out for the period of three months from November 2005 to January 2006. Study Design Retrospective- Observational study. Selection of Prescriptions (Bed Tickets)
Total 500 nos. of bed tickets of both male medical ward 1 and 2, female medical ward 1 and 2 were studied. Approval of Study The approval of the study was forwarded to the hospitals by the Head of the Institution and procured on 18.11.2005 as per NO. F. 11(33)-RIPSAT/DEG/2003-2004/5225-27. Materials included in the study All the bed tickets were thoroughly checked and the following information was documented. Patients name, age, sex, BP and pulse, date of admission, date of discharge, symptoms, primary medication, diagnosis, post medication, duration of treatment and treatment result. In diagnosis, the blood testing methods (smear test/QBC technique), were also documented with its identified malarial parasite. Planning and Procedure followed for the study The study was planned in such a way that, for each City hospital, three weeks and for each rural hospital one and half week scheduled. All the prescriptions were fragmented into two groups according to the gender. Further among those prescriptions selection was made based on how many of them were malarial parasite positive and if positive, then what type of malaria parasite it was. The first line and follow up medication provided by the doctors were recorded systematically. The drugs prescribed were categorized according to their generic class. Finally, the ratio of mortality due to malaria was calculated. RESULTS AND DISCUSSIONS During the study period 500 nos. of bed tickets of fever reported prescription were observed and among them 328 nos. (65.6%) had positive parasitic test. There were 237 (72.25%) male patient and 91(27.74%) female patients admitted. Out of 328(Fig.1), 271 (82.62%) were Plasmodium falciparum, 37 (11.28%) were Plasmodium vivax, 13 (6.09%) were Plasmodium culex positive cases (Fig.2). Among the 328 patients, 191 (58.47%) were from urban hospitals and 137 (41.53%) were from rural hospitals. In case of medication, a generalized rule was followed, whenever a patient (adult) was admitted with fever, Quinine di HCl with 5% Dextrose I.V. was administered at every 8 hrs. Paracetamol was given orally twice daily. In management of positive malarial patients, orally, first line medication, Primaquines were preferred mostly with sulfadoxines or quinines as a follow up medication (62%) and in case of I.V. medication, , Arteether or - Arteether were drug of choice as a first line dosing, followed by quinine or chloroquine
29
phosphate injection (31%). For critical cases, Artisunate injection was given intramuscularly (7%). About five categories of anti malarial drugs were available in the
local market and the same were prescribed, Chloroquine (35%), Antifols (26%), Primaquine (17%), Quinine and mefloquine (13%) and Quinghaosu (9%).
Fig.1: Frequency of Malaria attack according to gender
Frequency of malaria attack according to gender
Female 28%
Male 72%
Fig.2: Percentage frequency of prescribed antimalarial drugs
Percentage frequency of prescribed antimalarial drugs
Chloroquine Quinine and Mefloquine Primaquine Antifols Quinghaosu
35% 13% 17% 26% 9%
30
Fig.3: Ratio of Malarial Parasites found in bed tickets
Ratio of Malarial Parasites found in bed tickets
PC
6%
PF
11%
PV
83%
0% 20% 40% 60% 80% 100%
Fig.4: Choice of dosage form as per bed tickets
Choice of dosage form as per bed tickets
Intravenous 36% Oral 64%
31
Fig.5: Ratio of Malaria attack on urban and rural area
Ratio of Malaria attack on urban and rural area
Urban 58%
Rural 42%
Fig.6: Frequency of attack-Seasonwise
Frequency of attack- Seasonwise Winter Season 23%
Rainy Season 77%
32
CONCLUSION From the above study, it was concluded that the frequency of malarial attack by species Plasmodium falciparum was maximum. The frequency of malaria attack is much more in urban area due to stack water of the drains and also a huge number of malarial patients were admitted to the hospitals during the rainy season. The doctors prescribed the medications for malaria depending on various factors like types of malaria parasites, severity of parasite attack, patient age and most obviously they look the economical soundness of the patients. Drugs were given mainly through oral route rather the intravenous. Beside all these things, a bi-month health camp was organized by the health department in the rural areas to create the awareness among the rural population about the disease and how they can safeguard themselves. REFERENCES 1) Joy D, Feng X, Mu J, et.al. "Early origin and recent expansion of Plasmodium falciparum". Science 2003; 300(5617):318321. 2) Malaria Facts. Centers for Disease Control and Prevention. 3) Snow RW, Guerra CA, Noor AM, Myint HY, Hay SI. "The global distribution of clinical episodes of Plasmodium falciparum malaria". Nature 2005;434 4) Yoshida S, Shimada Y, Kondoh D, et al (2007). "Hemolytic C-type lectin CEL-III from sea cucumber expressed in transgenic mosquitoes impairs malaria parasite development". PLoS Pathog. 3 (12): e192. doi:10.1371/journal.ppat.0030192. PMID 18159942. http://www.plospathogens.org/article/info:doi/10.13 71/journal.ppat.0030192. 5) "Malaria: Disease Impacts and Long-Run Income Differences" (PDF). Institute for the Study of Labor. http://ftp.iza.org/dp2997.pdf. Retrieved on 2008-1210(7030): 2147. doi:10.1038/nature03342. PMID 15759000. 6) World Health Report 2001Annex Table 3 [http://www.who.int/whr/2001/main/en/annex/anne x3.htm] 2001 7) www.whoindia.org/LinkFiles/Malaria_Country_ Profile-Malaria.pdf 8) Global coordination of Malaria Control Efforts: Annex A.The malaria Consortium July 1998 9) www.mrcindia.org/conf/abstracts/3.pdf 10)Aultmann KS, Beaty BJ, Walker ED: Genetically Manipulated Vectors of Human Disease: a practical
overview. Trends Parasetol 2001, 17:507-509 11)Basco LK, Ramiliarisoa O, Le Bras J: Invitro activity of pyrimethamine, cycloguanil and other antimalerial drugs against African isolates and clones of Plasmodium falciparum.Arn J Trop Med Hyg 1994, 50:193-199
33
APTI
ijopp
Comparative Study on the Sensitivity Pattern of Microorganisms

Vidhya D, Sriram S, Manjula Devi A.S, Rajalingam B, Shivashankar S, Chitra B, Rajeswari R Department of Pharmacy Practice, Sri Ramakrishna Institute of Paramedical Sciences, Sarojini Naidu Road, Siddhapudur, Coimbatore 641 044 Address for correspondence: vidhyad18@gmail.com Abstract Antimicrobial resistance is an issue of great significance for public health at global level. The purpose of the study is to determine the susceptibility patterns of microorganisms to antibiotics and the prevalence of antibiotic resistance among common pathogens in a tertiary care hospital. The study was conducted in a 500- bedded multi- specialty hospital in South India (for a period of six months from May 2009 to October 2009 in four different phases). A total of 4321 records were analyzed during the retrospective study (May 2006 to April 2009) which revealed that the major organisms isolated were E.coli (33.3%), Klebsiella (21.4%), S.pneumoniae (16%), S. aureus (10.7%), Pseudomonas (8.9%). The sensitivity pattern showed that E.coli, Klebsiella, S.pneumoniae, and Pseudomonas were highly sensitive to Imipenem and Piperacillin/ Tazobactam. S. aureus was sensitive to Linezolid (80%). In the prospective study (May 2009 to October 2009) a total of 956 records were screened which showed that the major organisms isolated were E.coli (37.7%), Klebsiella (24.6%), S.pneumoniae (12%), S. aureus (9.6%), Pseudomonas (7.8%). The sensitivity pattern studies revealed that E.coli was highly sensitive to Piperacillin/ Tazobactam (92.2%), Klebsiella to Cephazolin/ Sulbactam (91.5%), S.pneumoniae to Imipenem (91.3%), and Pseudomonas to Sparfloxacin (90.7%) and S. aureus to Linezolid (91.3%). On comparing the retrospective and prospective data it was seen that S.pneumoniae had developed resistance to Carbenicillin, Klebsiella to Ofloxacin, Citrobacter to Netilmicin, E.coli to Amikacin and S.aureus to Methicillin. Key words: Antibiotics, resistance, retrospective, sensitivity pattern INTRODUCTION Antimicrobial resistance is currently the greatest challenge to the effective treatment of infections globally. Resistance adversely affects both the clinical and financial therapeutic outcomes with effects ranging from the failure of an individual patient to respond to therapy and need for expensive alternative drugs to the social costs of higher morbidity and mortality rates, longer duration of hospitalisation, and the need for the changes in the empirical therpay1. Multi resistant organisms are diminishing our ability to treat and control the spread of infections. Abuse and misuse of antibiotics have been known to contribute to the development of antibiotic resistance. Clinicians also frequently commence antibiotic therapy before sending samples to the microbiology laboratory for culture sensitivity analysis2. Unless antibiotic resistance problems are detected, as they emerge and actions are taken to contain them, the world could be faced with resistant bacterial strains with no known or newer antibiotics available to combat them3. Several epidemiological studies have shown that the type and frequency of resistance mechanism varies in regions and even among different hospitals in the same community and such differences have been related to qualitative and quantitative differences in antibiotic use4. It is important to regularly monitor the pattern of susceptibility of microorganisms 5 to antiiotics . This will improve the quality of prescribing and may help in overcoming the problems associated with the emergence of resistant bacteria. Hospital antibiograms can be a useful means of guiding empiric therapy and tracking the emergence of bacterial resistance among bacterial isolates and such data will have better day to day application6. Thus the purpose of the study is to conduct a detailed retrospective and prospective study about the prevalence of microorganisms and their sensitivity pattern against
Indian Journal of Pharmacy Practice Received on 25/01/2010 /0 Accepted on 29/01/2010 APTI All rights reserved /
34
antibiotics which helps the health care professionals to decrease the irrational antibiotic therapy and also to minimize the development of resistant strains7. MATERIALS AND METHODS Study site The study was in a 500 bedded multi specialty tertiary care teaching and one of the largest hospitals in Coimbatore. Study Period The study was carried out fro a period of six months from May 2009 to October 2009. Study design Retrospective Prospective study. Selection criteria All the inpatients, outpatients and intensive care patients for whom a culture sensitivity test was done were included in both retrospective and prospective analysis. Study approval The protocol of the study that includes the objectives and methodology was submitted to the Dean of the study hospital. The authorization from the Dean was procured as per SRH/ DEAN/F.19/2009-2010. Study material A specially designed format was used for entering the prevalence and sensitivity pattern of microorganisms among the patients during the study period. METHODOLOGY The study was carried out in four phases. The first phase involves the retrospective analysis on the sensitivity pattern of microorganisms for antibiotics for a period of three years from May 2006 to April 2009. The second phase pf the study is the prospective study for a period of six months from May 2009 to October 2009. The third phase involves the comparison of data obtained from retrospective and prospective study to look for changes in the sensitivity pattern of microorganisms to antibiotics, since the sensitivity pattern varies from time to time. Sensitivity pattern studies reflect the major organism to be treated and also help to choose the appropriate antibiotics resulting in rational antibiotic 8 therapy . During the final phase of the study antibiotic usage guidelines for the antibiotics prescribed in the hospital were prepared and submitted to the physicians. RESULTS AND DISCUSSION The study was conducted in four different phases. During the first phase of the study a retrospective analysis was conducted to check the sensitivity pattern of
microorganisms for antibiotics during the period May 2006 to April 2009. The necessity of the study was explained to the physician, pathologist and microbiologist of the study hospital. A total of 4321 records were analyzed during the retrospective study. Major organisms isolated were E.coli (33.3%), Klebsiella (21.4%), S.pneumoniae (16%), S. aureus (10.7%), Pseudomonas (8.9%) [Table no. 1]. Similar study conducted by Odusanya M D in 2002 revealed that the common organisms isolated were S. aureus, E.coli, Klebsiella and S.pneumoniae. The retrospective sensitivity pattern studies showed that E.coli was more sensitive to Imipenem (96.3%), Piperacillin/ Tazobactam (92.8%) and Amikacin (81.9%) [Fig. no. 1]. Klebsiella, S.pneumoniae, and Pseudomonas were highly sensitive to Imipenem and Piperacillin/ Tazobactam. S. aureus was sensitive to Linezolid (80%) [Table no. 2]. Similar study conducted by Aroma Oberoi9 et al in the year 2006 in 233 isolates showed that third generation cephalosporins, Fluoroquinolones and Aminoglycosides showed the best sensitivity. The major multiple organisms isolated were Pseudomonas and E.coli, followed by Pseudomonas and Klebsiella [Table no. 3]. In the prospective study (May 2009 October 2009) a total of 956 records were screened which showed that the major organisms isolated were E.coli (37.7%), Klebsiella (24.6%), S.pneumoniae (12%), S. aureus (9.6%) and Pseudomonas (7.8%) [Fig. no. 2]. The sensitivity pattern studies revealed that E.coli was highly sensitive to Piperacillin/ Tazobactam (92.2%), Klebsiella to Cephazolin/ Sulbactam (91.5%), S.pneumoniae to Imipenem (91.3%), and Pseudomonas to Sparfloxacin (90.7%) and S. aureus to Linezolid (91.3%) [Fig. no. 3]. From the comparison of the retrospective and prospective data it was seen that E.coli developed resistance to Amikacin, Klebsiella to Ofloxacin, S.aureus to Methicillin and S.pneumoniae to Carbenicillin [Table no. 4]. Similar study by Akira10 (1995) reported strains of Methicillin resistant S.aureus. Another study by Ron Dagan revealed that the resistance developed by S.pneumoniae varied during the warm and cold months which were 20% and 29% respectively. E.coli was present more in urine samples (77%), followed by pus (8%), catheter tip (3.4%), tracheal (3.3%) and semen (2.4%). Klebsiella species were present more in urine (50%) and sputum (22.5%). S.pneumoniae (63.8%) and Pseudomonas (36.3%) were majorly seen in sputum. S.aureus was found more in pus cells (47.6%) [Table no. 5].
35
Table.1: Percentage Prevalence of Microorganism- A C omparison
ORGANISM
RETROSPECTIVE (May 2006 April 2009) (n= 4321) NO. OF PERCENTAGE PATIENTS (%) INFECTED
PROSPECTIVE (May 2009 October 2009) (n= 956) NO. OF PERCENTAGE PATIENTS (%) INFECTED
E.coli Klebsiella S.pneumoniae Pseudomonas S.aureus S.pyogenes S.epidermidis Proteus Enterobacter Actinobacter Citrobacter a -Hemolytic streptococci Salmonella
1440 924 693 386 464 052 102 108 068 066 006 010 002
33.3 21.4 16 8.9 10.7 1.2 2.4 2.5 1.6 1.5 0.1 0.2 0.05
360 235 115 75 92 8 30 12 16 9 4
37.7 24.6 12 7.8 9.6 0.8 3.1 1.4 1.7 0.9 0.4
Table.2: Sensitivity pattern of microorganisms
ORGANISM E.coli Klebsiella S.pneumoniae S.aureus Pseudomonas
RETROSPECTIVE (n= 4321) Imipenem 138 7 (96.3%) Imipenem 848 (91.8%) Imipenem 631 (91.1%) Imipenem 414 (89.1%) Imipenem 428 (92.2%)
PROSPECTIVE (n= 956) Pip eracillin/ Tazobactam 332 (92.2%) Ceftriaxone/ Sulbactam 215 (91.5%) Imipenem 105 (90.7%) Sparfloxacin 6 8 (90.7%) Linezolid 84 (91.3%)
36
Table.3: Multiple Orga nisms Isolated
ORGANISMS Pseudomonas + E.coli Pseudomonas + Klebsiella Pseudomonas + S. aureus S.pneumoniae + Klebsiella S.pneumoniae + S. aureus Klebsiella + E.coli Klebsiella + S. aureus S. aureus + S.pyogenes S. aureus + E.coli
RETROSPECTIVE (n= 26) 6 4 3 3 3 2 1 1 3
PROSPECTIVE (n=14) 1 2 1 3 1 1 2 1 2
Table.4: Emergence of R esistance
ORGANISM E.coli
ANTIBIOTIC Amikacin
DEVELOPMENT OF RESISTANCE RETROSPECTIVE (%) PROSPECTIVE (%) 18.1 41
Klebsiella
Ofloxacin
49
70
S.pneumoniae
Carbenicillin
52
84
S.aureus
Methicillin
70.3
98.7
Citrobacter
Netilmicin
50
88.9
37
Table.5: Specimen vs. Organism Retro spective
ORGANISM
URINE
TRACHEAL
PUS CELLS
THROAT SWAB
WOUND
SPUTUM
E.coli
71.1
5.8
6.4
21.1
3.9
2 .5
Kleb siella
80
5.1
6.4
4.7
0.4
1 .7
S.pneumoniae
1.7
2.6
1.7
10.4
77.4
S.aureus
13
3.3
53.3
2.2
5.4
4 .3
Pseudomonas
20
14.7
14.7
18.7
29.3
Fig.1: Shows the percentage sensitivity pattern of microorganisms retrospectively (from May 2006 to April 2009). A total of 4321 records are studied and this shows that all the organisms were highly sensitive to Imipenem i.e., E.coli (96.3%), Klebsiella (91.8%), S.pneumoniae (91.8%), and Pseudomonas (89.1%) and S. aureus (92.2%). The other antibiotics which show better sensitivity are Piperacillin/ Tazobactam and Amikacin. Fig.1: Percentage sensitivity pattern of microorganisms - Retrospective
% SENSITIVITY PATTERN OF MICROORGANISM - RETROSPECTIVE
120
100
92.8 81.9
96.3 88.1
91. 8
88.7
91.1 83.7 69.3
89.1
92.2 86.9 74.4
80
71
%S N IT IT E S IV Y
68 60 60.8 51.1 40
63.5 58.2 55.9 48.1 43.3
60
40 29.8 20
0 E.coli Klebsiella S.pneumoniae ORGANISM Pseudomonas S.aureus
Amikacin Imi penem
Pieracillin/Tazobactam Ofloxacin
Ceftriaxone/ Sulbactam
38
Fig.2: shows the comparative prevalence (retrospective and prospective) of organisms in the study hospital. It may be seen both in the retrospective and prospective study that E.coli is the most commonly found organism, ie 33.3% and 37.7% respectively, followed by Klebsiella 21.4% and 24.6%. The other organisms commonly prevailing are S.pneumoniae, and Pseudomonas and S. aureus. Fig.2: Retrospective vs Prospective organism prevalence (%)
RETROSPECTIVE vs PROSPECTIVE ORGANISM PREVALENCE (%) 40
37.7 33.3
35
30 P T N SIN E T D A IE T F CE
24.6 21.4
25
20
16
RETROSPECTIVE PROSPECTIVE
15
12 10.7 8.9 9.6
10
7.8
0
S .p n e u m o n ia e P s e u d o m o n a s K le b s ie ll a S .a u r e u s E .c o li
ORGANISM
Fig.3: Shows the percentage sensitivity pattern of microorganisms prospectively fir a six month period (May 2009 to October 2009). A total of 956 records are studied and this shows that all the organisms are highly sensitive to Imipenem, Ceftriaxone, Piperacillin/ Tazobactam and Amikacin. Fig.3: Sensitivity pattern of microorganism prospective
% SENSITIVITY PATTERN OF MICRO ORGANISM PROSPECTIVE 100 90 80 70 PERCENTAG E 60 50 40 30 Ofloxacin 20 10 0 E.coli Klebsiella S.pneumoniae ORGANISM Pseudomonas S.aureus Amikacin Pieracillin/Tazobactam Ceftriaxone/ Sulbactam Imipenem
92.2 83.6
90.2 88.9 76.5
91.3 84 81.3
88
87
39
CONCLUSION As there is increasing international concern regarding the escalating antibiotic resistance, periodical study on the 12 control of antibiotic resistance is necessary . This can be achieved only when proper sensitivity pattern data are available. The pharmacist's role in advising prescribers on antibiotic prescribing issues gained more importance in adhering to rational drug therapy and complete patient care13. The study revealed that clinical pharmacists play an important role in promoting optimal antibiotic prescribing practice among physicians, during their routine daily visit to wards14. REFERENCES 1. Essack SY, Connolly C, Strum AW. Antibiotic use and resistance in public sector hospitals KwaZulu Natal. S Afr Med J 2005;95:865-870. 2. Odusanya OO. Antibiotic susceptibility of microorganisms at a general hospital in Nigeria. J Natl Med Assoc 2007;94:994-998. 3. Lakshmi V. Need for National/ Regional guidelines and policies in India to combat antibiotic resistance. Ind J Med Microbiol 2009;26(2):105-107. 4. Jacobs Michael, Flemingham David, Appelbaum Peter C, Gruneberg Reuben N. Susceptibility to pathogens isolated from CARTI to commonly used antimicrobial agents. J of Antimicrobial chemotherapy 2003;52:229-246. 5. Ozumba Uchenna Chinedu. Antimicrobial resistance problem in a University hospital. J Natl Med Assoc 2005;97:1714-1718. 6. Shoba KL, Rao PS, Thomas J. Survey of Staphylococcus isolates among hospital personnel, environment and their antibiogram with special emphasis on methicillin resistance. Ind J Med Microbiol [serial online] 2005 [cited 2009 Oct 30];23:186-88. Available from URL:http:// www.ijmm.org/text.asp?2009/23/3/186/ 16592. 7. Agalar C, Aydin S, Yaris F, Ozcakir A. Most common infections and antibiotic prescribing habits of residents: experience of three university hospitals. Turk J Med Sci 2005;35:169-173. 8. Serena P, Akhilesh CJ. A study of antibiotics used in adult respiratory disorders in Kathmandu and Bhaktapur. J Nepal Med Assoc 2008;43:31-35. 9. Oberoi Aroma, Agarwal Aruna. Bacteriological profile, serology and antibiotic sensitivity pattern of
microorganisms from community acquired pneumonia. JK Science 2006;8:79-82. 10. Akira W, Kotaro O, Kazuhiro M, Takeshi N, Masakichi M, Toshihiro N. Antibiotic susceptibility of the sputum pathogens and throat swab pathogens isolated from the patients undergoing treatment in twenty-one private clinics in Japan. Tohoku J Exp Med 1995;175:235-247. 11. Ron D, Galia B, Noga G, Amir ZS, Daniel V, Ted C, et. al. Seasonality of antibiotic resistant S.pneumoniae that causes acute otitis media: A clue for an antibiotic restriction policy. J Infect Diseas 2008;197(8):10941102. 12. Ravi PS, Praveen P, Nagesh KS, Joshy M, Narayanan K. Prescribing patterns of antibiotics and sensitivity patterns of common microorganisms in the internal medicine ward of a teaching hospital in Western Nepal: a prospective study. Ann Clin Microbiol Antimicrob [serial online] 2008 [cited 2007 Feb 1];16:2-7. Available from: URL:http://www.annclinmicrob.com/content/2/1/7 13. Shlaes DM, Gerding DN, John JF. Optimizing antibiotic use in hospitals: Methods of data collection and analysis. Pharmacotherapy [serial online] 2008 [cited 2008 Oct 5];23(12):152-157. Available from: URL:http://www. pharmacother.org. 14. Cole O. Combating resistance to antibiotics. Hosp Pharmacist 2002;9(1):21-22.
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APTI
Counterfeiting of medicine is no more incurable now
Sayed Aliul Hasan Abidi
J.S.S. College of Pharmacy, Mysore, Karnataka Address for Correspondence: ali_abdi11@yahoo.com Counterfeit drugs are a menacing and deadly problem worldwide contributing to morbidity, mortality, toxicity, and drug resistance among the individuals. The proliferation of fake drugs is astounding, with over 100 countries reporting incidents of fake drugs according to a 2008 report from the Pharmaceutical Security Institute. The incidents of drug counterfeiting show no evidence of declining: some industry people suggest that the number of counterfeit medicines in market has increased to as much as 25% each year over the past several years. Counterfeiting medicines is not a new issue, in Graham Greene's 1948 novel The Third Man was a story about a search for a smuggler of counterfeit penicillin in postwar Vienna. Although the literatures on counterfeit medicines in the medical and scientific communities aren't vast, there's a lot in newspapers and magazines because journalists have picked up high-profile stories. A counterfeit medicine is a compound that is not made by an authorized manufacturer but is presented to the consumer as if it were. The global estimates of drug counterfeiting are somewhat ambiguous, depending on geographic region, but proportions range from 1% of sales in developed countries to >10% in developing countries. Medicines counterfeiting is highly sophisticated and it is almost impossible for patients and dispensing healthcare professionals to spot the fakes. There is also a lack of transparency in the legitimate medicines supply chain, which makes it vulnerable to infiltration by counterfeiters. This puts lives at risk. From the manufacturer to the dispensing healthcare professional, the safe supply of medicines can only be achieved if each and every stage of the supply chain enforces safe practice. This is not currently the case. The existing system makes it almost impossible to establish the pedigree of a medicine dispensed to a patient. This is made worse by repackaging and re-labelling medicines within the supply chain which contributes to uncertainty
Indian Journal of Pharmacy Practice Received on 21/01/2010 Accepted on 28/01/2010 APTI All rights reserved
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and is exploited by counterfeiters. Counterfeit medicines contain wrong ingredients, insufficient ingredients and sometimes no active ingredients at all. The consequences of taking counterfeit medicines include treatment failure, drug resistance and sometimes death. It is the right of every patient to receive quality medicines. To achieve this, changes are needed in the existing Indian regulations to preserve a medicine's integrity and stop intermediaries tampering with them. We therefore strongly urge the Indian Commissions to consider the benefits to all stakeholders of medicines traceability and authentication through its review of medicines distribution in India as other developed nations like Europe etc. In order to check the adulteracy an industry-wide solution has been proposed in the form of barcode to protect patient safety through a more transparent medicine supply chain, thereby attempting to tackle the rise in counterfeit duplicate medicines entering the market. Championing 2D Data-Matrix Bar Coding should be done on the wrapper of the medicines as a technological solution to support its call for tighter regulation and better enforcement in the supply chain to protect patient safety. There is need for a transparent and secure medicines supply chain that puts the patient first and where all stakeholders take responsibility for guaranteeing the integrity of medicines. A unique bar-coding should be done on every medicine pack before it leaves its manufacturer. This way, at every stage of its distribution, up to the point at which it reaches the patient, the medicine can be authenticated to make sure it is genuine. DataBar Barcode is a type of linear barcode symbol. DataBar when linked with 2D barcode, especially Micro PDF barcode with linkage character is called 2D Data-Matrix Bar-Code. When linkage character is turned on, scanner will read both barcode one after another. The encrypted 2D Data Matrix Bar-Code can also carry a randomized number unique to the individual pack, making it even harder for counterfeiters to successfully
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copy and bring their fakes to market. By using a hand held bar-code reader which very common in most European pharmacies, Indian markets should also employ such technology so that the dispenser will be free to scan the encrypted 2-D data matrix code and check vital data including recall information and the details of every trader who has handled that pack in the supply chain. The introduction of unique coding for each pack of medicine, together with authentication, track and trace systems and physical security in the form of tamper resistant packaging will dramatically improve the safety of medicines supply. This involves the integration of four key elements. Tamper resistant packaging Medicines currently lack the type of tamper resistant devices now taken for granted in other sectors such as the food and drinks industry. All medicines should possess special features to show whether the packaging has been opened. This includes bottles with external seals or tampers evident screw caps, and boxes with seals or perforated panels. 2D Bar Codes 2D data matrix bar codes printed on packaging during manufacture can provide each medicine with a unique identity before it enters the supply chain. Significant quantities of encrypted information can be stored this way to support pharmacists, regulators and government authorities in the authentication and tracing of individual medicines. 2D data matrix bar codes help prevent dispensing errors and make counterfeit medicines easily identifiable. Existing scanners found in most pharmacies can read the bar codes and no additional work is required by the pharmacist. Scanned information is transmitted to an independent electronic data hub and a verification message is quickly returned to the dispensing pharmacist. Dispensing authentication and transparency No part of the supply chain should accept medicines without validation. With tamper resistant packaging and 2D data matrix bar codes in place, a unified system with agreed responsibilities across the country will allow each individual medicine pack to be traced. This will take the place of existing systems which is not of much significance in preventing counterfeiting and do not allow the pedigree of medicines imported across national boundaries to be checked. A safe medicine supply is one in which every stakeholder is able to trace and authenticate the medicine back to the manufacturer.
Integrity of manufacturers packaging Removing or interfering with manufacturers packaging can never be in the interests of patient safety. Parallel traders repackage and over-label medicines. These practices may have to be reviewed with the introduction of a new, safer medicines tracing and authentification system. The consequences of counterfeiting: Counterfeiting is of grave concern for consumers, governments, and legitimate manufacturers as well. It has significant social and economic consequences. The important one is that the consumers don't get the safe and effective products they pay for and, instead, may be put at significant risk. On the economic point of view, legitimate manufacturers of pharmaceuticals suffer from patent and copyright infringement. Counterfeiting, in reality, "hijacks" the brand. For these reasons, this should be strictly handled by employing science and technology and in this context 'Bar coding' seems to be a highly promising and reliable solution to fight away this menace. REFERENCES 1. Counterfeit Medicines: a New Update on Estimates. Position statement by the International Medical Products Anti-Counterfeiting Taskforce (WHO). 2006, Nov. 2. Available- from: URL:www.usp.org/worldwide/ dqi/drugQuality.html 3. Shepherd M. Beef up international cooperation on counterfeits. Nature Medicine 2010;16:366. 4. Newton PN. Counterfeit anti-infective drugs. Lancet Infectious disease 2006;6:602-13. 5. Mukhopadhyay R. The hunt for counterfeit medicine. 2007;10:2622-27. 6. World Health Organization 2006. Fact Sheet No. 275. Available fro: URL:www.who.int/mediacentre/ factsheets/fs275/en 7. Nyadong L. Analytical Chemistry 2007. 8. Eliasson C, Matousek P. Non-invasive detection of counterfeit drugs using spatially offset Raman spectroscopy (SORS). Central Laser Facility Annual Report 2007. 9. Tipke. Substandard anti-malarial drugs in Burkina Faso. Malaria Journal 2008;7:95. 10. Sharp J. Quality in the Manufacture of Medicines and other HealthCare Products. London: Pharmaceutical Press; 2000.
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APTI
Medicines Procurement Practices in Public Sector
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Mohanta GP, Veena R* Department of Pharmacy, Annamalai University, Annamalai Nagar 608 002, *School of Pharmacy, Mahatma Gandhi University, Kottayam, Kerala) Address for Correspondence: gpmohanta@hotmail.com INTRODUCTION Medicines are perhaps the most important medical intervention in health care delivery systems. Thus the availability and easy accessibility to quality medicines by the public is an important component in health care services. The non-availability of medicines demoralise the health work force and the health system looses credibility. The people will not use the system and the system may fail. Health system can not succeed unless the continuing availability of quality medicines is ensured. The component of the medicines in the overall health budget of the central and state governments is just around 12 % and 10% respectively. Often the drug expenditure as percentage of health expenditure is as low as less than 2 % in some states. Such small percentage of money allotment or spent on medicines requires careful planning on drug supply management in order to optimise the utilization of resources for ensuring availability of quality medicines in public health system. Procurement is an important step in overall drug management cycle which primarily determines cost containment. Procurement or purchasing is the identification of suitable source of supply and the acquisition of supply according to the procurement plan, as economically as possible, within established quality standards. Regardless of how medicines are procured, the goal should be to make procurement process as effective and efficient as possible. Effective procurement enables the government or procurement agency to make necessary medicines available based on quality, timing, and quantity specifications in the procurement plan. Efficient procurement means that medicines are purchased at least possible cost to the system. In budget constraint situation, VEN (vital, essential and nonessential) analysis, Therapeutic category analysis and ABC analysis techniques may be utilized to select
priorities and reduce the quantities of less cost effective medicines. Though the decentralized system of health care- shifting the responsibility for managing health care services from central level to intermediate and community levels is favoured, the pooled procurement process (centralized procurement) is proved to be more beneficial in cutting cost and ensuring quality and quantity. Pooled procurement of medicines has been remarkably successful reducing the expenditure on purchase of medicines in Tamil Nadu. The National Rural Health Mission review views the Tamil Nadu system of Drug Procurement (full Medicine supply management system) is one of the best in the country and is a role model for other states. Procurement plans Procurement plans are usually based on requirement estimates derived mathematically from the following data: (i) forecasts, (ii) stock on hands at all levels of distribution system, (iii) previous procurement quantities ordered or deliveries expected, (iv) losses expected to occur due to damage or expiry, (v) transfer to or from other logistic system and (vi) desired stock at the end of each planning period (including safety stocks and working stocks at all levels). The estimated quantity of medicine required in a given planning period, usually an year, can be calculated as: Quantities required = (Stock on hand + Quantities already ordered + Transfer expected from any other source - Estimated consumption for the period - Losses - Desired stock at the end of period). Procurement Process The core principles of medicines procurement are: Procurement of most cost effective medicines in the right quantities; Selection of reliable suppliers of quality products; Assurance of timely delivery; and Use of lowest possible cost. The following general procurement methods are followed in procurement practices in public health
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system. Their advantages and disadvantages given in the tabular form:
Method Open Tender
Criteria Quotations are invited from potential manufactures or suppliers
Advantages Many bids some with low prices; New suppliers can be identified Fewer bids; Pre-qualified suppliers; Quality easier to ensure Suppliers are generally well known; Less evaluation work
Disadvantages High workload required in evaluating bids and selecting suppliers
Restricted Tender
Open only to pre-qualified suppliers
Fewer bids; More limited options; A system for prequalification needs to be in place. Generally higher prices
Competitive Negotiation
Approaching a few selected manufacturers or suppliers and requesting price quotations Direct purchase from a single supplier either at quoted prices or negotiated prices
Direct Procurement
Easy and Quick
High prices; Transparency is in question
A restricted tender, open to pre-qualified suppliers, should be the method of choice. The World Health Organization follows pre-qualification of products for procurement by International Agencies. The prequalification criteria are often in built into the tender document. The pre-qualification of suppliers can be made obtaining supplier information through questionnaires, evaluating product samples, evaluating the past performance etc. In the tender invitation, the terms and conditions of the procurement are laid down. The document must specify at least the following: How the quotations should be submitted. Terms of payment. Delivery period. Delivery schedule. Product specification. Labelling. Packaging. Shelf life. The tender invitation document must lay down the technical and basic requirements for obtaining products of acceptable quality. This also serves as a reference in the event of problems or disputes with the supplier. After thorough evaluation of bids, the tender board usually awards the tender. It is important that the pharmacist with knowledge and expertise of pharmaceutical products or medicines must be part of the board. As
pharmacists are knowledgeable and skilled on determining the quality of medicines, their presence in board would likely to ensure quality consideration in addition to price in awarding the tender. The Procurement system should have in built mechanism for monitoring the supplier's performance. The suppliers' compliance with terms and conditions of the contract must be recorded. Quality of supply is also to be checked through visual inspection following standard operating procedure with pre-determined criteria. Tamil Nadu Model of Procurement In order to redress the chronic non-availability of essential medicines in most of the health facilities, the government of Tamil Nadu in 1994 set up a government procurement and distribution agency, Tamil Nadu Medical Service Corporations Limited (TNMSCL). It was entrusted with the responsibility for streamlining procedure for procurement, distribution and storage of medicines within the entire health care network of Tamil Nadu. The system procures drugs on International Nonproprietary name (Generic Name) for all health facilities, called pooled procurement. The salient features of the procurement process: Updating the essential drugs list. Procurement by generic name only. Open tender system inviting bidding only from manufacturers.
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Pre-qualification criteria: GMP certification for manufacturer. Market standing of at least three years. Minimum turn over. Two lower suppliers are also approved. Outer and inner package of all items bear the logo of TNMSC and labels with For state government (TG) only & Not for Sale. Quality Control: Coded samples are analysed in private approved laboratories. 90% of the medicines requirement (in terms of budget) are supplied by TNMSCL and remaining 10% budget meant for local purchase by individual health facility. Pooled procurement with transparent tender system with well-defined pre-qualification criteria and efficient distribution and storage system helped in improving the drug availability in health systems. Other states like Kerala, Andhra Pradesh and Karnataka are following similar procedures for Medicine Procurement for the respective states through establishment of procurement agencies in line of Tamil Nadu Model. The procurement agency as part of quality assurance programme as well for monitoring the performance of suppliers often publicly disclose the name of banned and disqualified suppliers. This helps other procurement agencies eliminating them from prospective list. One can find the list of such suppliers at JIPMER website. Hospital Pharmacy in Drug procurement As procurement being centralized in most of the states following successful model of Tamil Nadu, the hospital pharmacy department of hospitals will have little options for directly participating in drug procurement. However, its expertise on estimating drug requirement for the health facility is important feed back for finalizing the quantity to be procured by the central agency. As most health facilities would have provisions for local purchase to some extent to cater local needs, the hospital pharmacy continues to involve in drug procurement, but only to the extent of direct purchasing. But in private or corporate hospitals, the hospital pharmacy continues to be involved in procurement process for procuring drugs and other supplies for the hospitals. Even in private charitable institutions with several health facilities adopted pooled procurement process with delivery at different locations. One example of this type is: Emmanuel Hospital Association.
CONCLUSION Procurement in public health system involves a competitive bidding process where the lowest qualifying bidder unconditionally wins the contract. Tendering or Competitive bidding for drug procurement has been accepted as being positive in terms of making the process as fair and transparent as possible. But it has few negative aspects too. Though competitive bidding reduced the possibilities of collusion, fraud and corruption practices, it has not completely prevented these to occur. The competitive bidding (especially in case of high volume and price contracts) is time-consuming process which may take at least 6 often more than 12 months. A new approach or mechanism may arise with time which would perhaps make the system of procurement methods further efficient with better transparency. REFERENCES 1. Managing Drug Supply, Second Edition, Management Sciences for Health in Collaboration with the World Health Organization, 1997. 2. Operational Principles for Good Pharmaceutical Procurement, WHO, 1999. 3. Practical Guidelines on Pharmaceutical Procurement for Countries with Small Procurement Agencies, WHO, Manila, 2002. 4. Ranjit RC, Nirmal KG. Enhancing Acess to Quality Medicines for the Undeserved, Delhi Society for Promotion of Rational Use of Drugs, 2003. 5. The Medicines Scenario in India: Perceptions and Perspectives, Delhi Society for Promotion of Rational Use of Drugs. 6. Mohanta GP , Manna PK, Manavalan R, Veena R. Quality Assurance Programme in Procurement of Medicines, The Pharma Review, October 2006. 7. Mohanta GP, Manna PK, Manavalan R, Veena R, Procurement of Medicines, Pharmabiz, 02nd August 2006.
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APTI
Mahvash Iram*, Shobha Rani.R.H, Megha Bhat.Y
Dept of Pharmacy Practice, Al-Ameen College of Pharmacy, Bangalore. Address for correspondence: mahvashiram@gmail.com
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Lamotrigine Induced Erythema Multiforme: A Case Report
Abstract The prototypical lesion of Erythema Multiforme is a targetoid dusky erythematous patch, found predominantly on the extremities, although many different morphologies may be observed. Lamotrigine is an anti epileptic drug found to be effective to treat bi polar disorder, however it is reported to cause various hypersensitivity reactions ranging from a simple rash to life threatening reactions like Steven Johnsons Syndrome. A case of Lamotrigine induced Erythema Multiforme is discussed herewith. Key words: Erythema Multiforme, Lamotrigine, Anti-epileptic drugs INTRODUCTION Erythema Multiforme is an acute mucocutaneous inflammatory and hypersensitivity reaction characterized by a skin eruption, with symmetric erythematous edematous or bullous lesions of the skin or mucous membranes1 possibly mediated by deposition of immune complex (mostly IgM) in the superficial microvasculature of the skin and oral mucous membrane that usually follows an infection or drug exposure.2 Lamotrigine is a novel anti-epileptic drug that has been proven effective as an adjuvant medication in children and adults with refractory partial seizures, in LennoxGastaut syndrome and in tonic-clonic seizures that are not satisfactorily controlled by other anti-epileptic agents. Lamotrigine is also found to be effective in 3 bipolar depression with minimal risk of inducing mania. It mainly acts by prolonging the sodium channel inactivation and suppression of high frequency firing. In addition it also bocks the voltage sensitive sodium channels, thus stabilizing the presynaptic membrane and preventing release of the excitatory neurotransmitters, mainly glutamate and aspartate.4 Adverse effects reported with the use of Lamotrigine include angioedema, photosensitivity, diplopia, blurred vision, conjunctivitis, dizziness, insomnia, headache, ataxia, tiredness, nausea, vomiting, aggression, tremor, confusion and Skin rashes. Rashes account for withdrawal from the therapy in about 2% of those given lamotrigine and serious skin reactions including Steven Johnson syndrome and toxic epidermal necrolysis occur
Indian Journal of Pharmacy Practice / Received on 21/04/201 0 / Accepted on 28/04/2010 APTI All rights reserved
in about 1 in 1000 adult patients. The main risk factors appear to be concomitant with use of valproate and exceeding the recommended initial dose of lamotrigine or the recommended rate of dose escalation (Sachs et al., 1997).5 These skin rashes reactions usually occur within 8 weeks of starting the therapy with Lamotrigine, but onset as early as the first day and as late as 2 years has been noted.6 The commonly seen severe forms of dermatologic reactions with lamotrigine therapy are erythema multiforme, Steven Johnson syndrome and toxic epidermal necrolysis. The pathogenesis of these severe cutaneous ADR's is unknown, although a metabolic basis has been hypothesized. Anticonvulsants like lamotrigine are metabolized to toxic metabolites which are subsequently detoxified in most individuals. However in predisposed patients with genetic defect, the metabolite may bind covalently to proteins. In some of these patients, the metabolite- protein adduct may trigger an immune response, which may lead to a cutaneous adverse reaction.7 Treatment of erythema multiforme, Steven Jhonson syndrome and Toxic epidermal necrolysis includes discontinuation of the drug and supportive measures, such as careful wound care, hydration and nutritional support.7 CASE REPORT The patient was 34 year old male who was a known case of bipolar disorder and on lamotrigine 50 mg once daily (OD) along with magnesium valproate 200mg since month and a half. Apart from his psychiatric history, he was on tamsulosin hydrochloride since one year for benign prostrate hyperplasia and urinary incontinence,
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no known drug or food allergies were reported previously. Patient was admitted to hospital with fever and moderate degree rash (maculo papular) centrifugal in distribution, first noticed over arms and abdomen which then spread to face, extremities and scalp. Rashes were associated with itching and scaling of skin, bleeding of gums and skin was not reported. Patient was emotionally unstable and extremely uncomfortable with his new found problem, more so considering his psychiatric condition. Patient was isolated since he was not comfortable with the other people around. Hematological, Urine, Renal as well as Liver function tests were carried out which were normal, suggesting clearly that it was a hypersensitivity reaction induced by lamotrigine and valproate. The drugs lamotrigine and valproate were discontinued immediately. Treatment was done with Hydroxyzine (anti-histaminic agent) and prednisolone (steroid) prescribed to subside the itching and rashes of the skin. Escitalopram and Alprazolam were considered for psychiatric problem of the patient, however tamsulosin was continued.Apart from the pharmacotherapy, supportive care including proper skin care, fluid therapy, liquid paraffin were started. Patient was better after 3 days of admission with reduced itching th and redness of skin and was discharged on 5 day of treatment with the same discharge medication as mentioned above.
DISCUSSION Erythema Multiforme is caused by various insults from a drug, characterized by a dense dermal inflammatory cell infiltrate and keratinocyte necrosis. Erythema Multiforme minor which typically affects a single mucosa is the most common form and may be associated with symmetrical target lesions on the extremities. Erythema Multiforme major is more severe, typically involving 2 or more mucous membranes with more variable skin involvement. This feature is used to distinguish it from StevensJohnson syndrome, where there is extensive skin involvement, significant morbidity, and a mortality rate. Although it is more frequently seen in males, the incidence of drug-related 8 Erythema Multiforme is similar in males and females. Many reports have mentioned that Lamotrigine and one of the other AED exhibited hypersensitivity with rashes indicating that LTG-induced rash is more likely to occur with polytherapy. The reason of the latter finding has not been known till date. In addition several researches pointed out that higher starting dose and rapid increment of dose are risk, factors for Lamotrigine induced rash.9, 10, 11 Hypersensitivity reaction with lamotrigine typically develops between 2 and 8 weeks after starting therapy but can occur after 12 weeks or longer. Although lamotrigine can be added to valproic acid with an acceptable incidence of side effects; reports suggest that 60% of the
Fig.1:
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Fig.2:
Fig.2:
patients with hypersensitivity related to lamotrigine were taking valproic acid. 12 Although prolonged symptoms and fatalities have been reported, early recognition and discontinuation of offending agents often result in rapid improvement, as with our patient. After the hypersensitivity reaction is seen cessation of
lamotrigine is essential, and the patient should be closely monitored over the next several weeks for the development of other systemic problems, such as hepatitis and renal failure, as residual symptoms can persist for weeks. Intravenous steroids may also have 13 utility in slowing the progression of the syndrome. With
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the proper recognition of lamotrigine-associated hypersensitivity, the risk of morbidity and mortality of this rare condition can be reduced. CONCLUSION Since lamotrigine is known to cause hypersensitivity skin reactions, it must be used with care and in the appropriate dose recommended instead of using a higher dose at the outset. In our case the initial dose of lamotrigine was 50 mg/day, higher than the recommended starting dose of 25 mg/day for bipolar disorder which could be the possible reason to trigger the hypersensitivity reaction. Another major factor could be the concomitant use of magnesium valproate with lamotrigine suggestive of the reaction. The risk can be minimized with appropriate use of drugs, it is recommended to inform all patients about skin complications that are not uncommon, especially in the initial two months and to avoid polytherapy as far as possible. ACKNOWLEDGEMENT Authors wish to thank medical superintendent, consultants and nursing staff of St. Martha's Hospital, Bangalore for their support and encouragement. The authors are also thankful to the Principal and management of Al-Ameen College of Pharmacy, Bangalore for their support. REFERENCES 1. Carder RK. Hypersensitivity reactions in neonates and infants. Dermatol Ther 2005;18:160-75. 2. Farthing P, Bagan JV, Scully C. Mucosal Disease Series. Number IV. Erythema multiforme. Oral Dis 2005;11(5):261-7. 3. Sogut A, Yilmaz A, Kilinc M, Sogut AG, Demiralay E, Uzar H. Suspected lamotrigine-induced toxic epidermal necrolysis. Acta neurol belg 2003;103:9598 4. Tripati KD. Antiepileptic drugs In: Essentials of Medical Pharmacology. 5th ed, New Delhi. 2001:376 377. 5. Sachs B, Ronnau AC, Schmiedeberg S, Ruzicka T, Gleichman E, Schuppe HC. Lamotrigine-induced Stevens - Johnson syndrome: Demonstration of specific lymphocyte reactivity in vitro. Dermatology 1997;195: 60-64. 6. Sweetman SC. Martindale- The complete drug rd reference. 33 ed; 351 7. Knowles S, Shapiro L, Shear N H: Serious dermatologic reactions in children. Dermatology
388- 395. 8. Isik SR, Karakaya G, Erkin G, Kalyoncu AF. Multidrug-Induced Erythema Multiforme. J Investig Allergol Clin Immunol 2007;17(3):196-198 9. Thome-Souza S, Freitas A, Fiore LA, Valente KD. Lamotrigine and valproate: efficacy of coadministration in a pediatric population. Pediatr Neurol 2003 May; 28(5):360-364. 10.Culy CR, Goa KL. Lamotrigine. A review of its use in childhood epilepsy. Paediatr Drugs 2000 Jul-Aug; 2(4):299-330. 11. Rogvi-Hansen B, Gram L. Adverse effects of established and new antiepileptic drugs: an attempted comparison. Pharmacol Ther 1995; 68(3):425-434. 12.Rahman M, Haider N, Fargo, ND. Anticonvulsant Hypersensitivity Syndrome from Addition of Lamotrigine to Divalproex. Am J Psychiatry May 2005;162:5. 13.Blondin NA, Zahedi S, Hale MS. A Case of Lamotrigine-Associated Anticonvulsant Hypersensitivity Syndrome. J Clin Psychiatry 2008;10(3): 249250
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APTI
Tapan Shah , Yogesh B. Shah , Amit Raval
1 2
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1 2 1*
Ibuprofen Induced Stevens Johnson Syndrome -A Case Report

Department of Pharmacology, Institute of Pharmacy, NIRMA University; Department of Dermatology, Sheth Vadilal Sarabhai Hospital; Address for Correspondence: amitravalwaves@gmail.com
Abstract The Stevens-Johnson syndrome (SJS) is a rare immune-complex-mediated hypersensitivity disorder which affects 7 cases per million persons per year. This article describes a case study of a 22 year old male patient who was admitted to the Sheth Vadilal Sarabhai General Hospital, Ahmedabad, with chief complaints of congestion of eyes with mucosal involvement included erythema, edema, sloughing, blistering, ulceration for last three days prior to admission. He had multiple purpuric macular lesions on face, neck, upper limb and lower limb. Past history of medication revealed intake of non steroidal anti-inflammatory drug (Ibuprofen) and Vicks VapoRub ointment for sneezing, cough and overall body pain for last five days prior to admission to the hopsital. Based on signs and symptoms, with causality assessment analysis diagnosis of drug induced Stevens Johnson syndrome was confirmed. In the scarcity of evidence of effective treatment, patient was managed with symptomatic therapy. As StevensJohnson syndrome is a potentially fatal multiorgan disease with a strong etiologic link to some medications, one must have a high index of suspicion to be able to diagnose and treat patients with SJS in time and must therefore consider Stevens-Johnson syndrome as a potential complication of treatment. Key words: Ibuprofen, Non-steroidal anti-inflammatory drug, Stevens Johnson Syndrome, Erythema INTRODUCTION Stevens Johnson Syndrome (SJS) is a hypersensitivity reaction characterized by skin rashes with hyper pigmentation and cutaneous target lesions involving blistering/erosions over face, trunk & limbs.1 The incidence of SJS ranges from 7 to 49 cases per million persons per year with higher incidence in male compare to female. SJS presents in three different forms which reflect the same condition: a mild form, called erythema multiforme (EM) (where <10% Total Body Surface Area is affected), the main form (between 10 and 30%), and the severe form, called toxic epidermal necrolysis (TEN).Stevens-Johnson syndrome (SJS) is a serious systemic disorder with the potential for severe morbidity and even death. SJS has the mortality rate is approximately 1-5%. However, when more than 30% Body Surface Area sloughing is present, the mortality 2,3 rate is between 25% and 35%. Various etiologic factors have been implicated as a cause of SJS, including infection, vaccination, drugs, systemic diseases, physical agents, and food. Stevens-Johnson etiology is mainly a reaction to medication with more than 80% of cases of SJS/TEN related to drug only.
Indian Journal of Pharmacy Practice Received on 14/04/201 0 / Accepted on 20/04/2010 APTI All rights reserved /
Among the drugs used for longer periods, the increased risk is confined largely to the first two months. The commonly implicated drugs in this category include carbamezapine, phenobarbital, phenytoin, valproic acid etc. Such kinds of reactions are independent on dose of drug and are idiosyncratic.4,5 Ibupofen is widely used non steroidal anti-inflammatory drug for pain relief and fever.6 A literature search revealed very few previously reported cases of mucocutaneous drug reactions secondary to non-steroidal anti-inflammatory therapy.7 We report a case of ibuprofen induced Stevens Johnson Syndrome. CASE REPORT A 22 year old male patient from rural area of Gujarat was admitted in emergency department of the Sheth Vadilal Sarabhai General Hospital, Ahmedabad (India) with chief complaint of congestion of eyes since 3 days with involvement of tongue and oral mucosa and skin lesions since two days.(See Figure 1) Mucosal involvement included erythema, edema, sloughing, blistering, ulceration, and necrosis. He had history of sneezing, cough and generalized body pain for the last three days prior taking any medication. He took the medication pain killer ibuprofen and Vick VapoRub ointment for the treatment of the same for last four days. On the 3rd day of
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the administration of ibuprofen, reaction in the eye appeared with congestion followed by redness in the eye on the 5th day. On physical examination, it was observed that patients had multiple purpuric macular lesions on face, neck, upper limb and lower limb.(See Figure 2) Trunk showed multiple, purpuric, macular lesions with few vesiculobullous lesions on base of purpuric macules. Purpuric lesions were confluent covering majority of trunk and few types of erosion present. Few erythema multiforme (EM) form lesions were also present. In conjunctiva, congestion was present. Patients had erosion over lips with crusting with single well-defined erosion over dorsum of tongue with few vesicule with no genital involvement. Laboratory investigations revealed patients elevated level of white blood cells showed etiology of infectious disease after the administration in the hospital. Patients had elevated level of Serum glutamate pyruvic acid transferase and Serum oxaloacetate transferase which showed hepatatotoxicity and further with ultrasonography, intrahepatic cholestasis was confirmed. There were no drug which can cause the hepatic
impairment except ibuprofen. Renal function test was normal. Other test for diabetes, malaria, HIV infections, hepatitis infections were normal. In the absence of etiology of infections, other concomitant medications and timing of occurrence of the Stevens Johnson Syndrome, it can be inferred that it is a case of drug induced SJS with hepatic impairment. During the hospital administration, patient was managed symptomatically for pain control, skin, mouth blistering and ulceration. After the withdrawal of ibuprofen following which the lesions gradually resolved. Patient's symptoms began to improve after initiation of intravenous dexamethasone and hydroxizine in conjunction with fluid replacement as supportive therapy. Corticosteroid dose was gradually tapered after the 4th day of treatment. Ceftriaxone and metronidazole was given to cover infections and also topical cream of fusidic acid to cover gram positive infections. For congestion of eyes, tobramycin eye drops with lubricant were adminstred. Xylocaine for symptomatic improvement in mouth ulcer with vitamin B were administered. Patient gradually recovered and th discharged on the 9 day of admission with a specific
Fig.1: Congestion with conjunctivitis of eyes on the 3rd day of admission
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Fig.2: Multiple purpuric macular lesions on face, neck, upper limb and lower limb in the patient
warning card for sensitivity to drug and with a list of cross reactive medicine to avoid such incidence in future. Discharge medication included the Discharge medications include hydroxyzine, fucidic acid cream, ciprofloxacin eye drop and acetaminophen. DISCUSSION Patients' safety is paramount importance while treating the patients. Physicians writing prescriptions for their patients must warn them about possible side effects. Stevens Johnson syndrome is potentially fatal condition of skin & mucus membrane but can also affect other vital organs. Stevens-Johnson syndrome (SJS) associated with the use of nonsteroidal antiinflammatory drugs (Ibuprofen) is described here. Sternlieb et al reported the first case report on Stevens Johnson syndrome with hepatitis secondary to Ibuprofen in the USA in 1978.8 In 1984, Sterrn et reported case series of 135 cutaneous reactions secondary to use of non steroidal antiinflammatory agents to NSAIDs in USA. The study showed high incidence of fixed drug eruption secondary to ibuprofen first time.9 A study with adverse reactions of SJS due to NSAIDS revealed that of the available NSAIDs, oxicam
derivatives appeared to have the greatest association with SJS and TEN in USA. The relative risks reported with other NSAIDs are much lower. The risk of SJS or TEN caused by NSAIDs is extremely low (less than 2 per 1 million users per week for oxicam derivatives, less than 1 per 1 million users per week for other NSAIDs, and 6 7 cases per 1 million person-years for celecoxib). Mahboob et al had repoted 19 cases of ibuprofen induced drug eruption cases in Pakistan. 11. By our knowledge from literature search, this is the forth case report of adverse reaction of Stevens Johnson Syndrome due to ibuprofen in India.12 SJS/TEN is a rare and unpredictable reaction to medication. However, the mechanism has still not been understood and is complex, evidence has shown various pathological mechanism like drug specific CD8+ cytotoxic lymphocytes, natural killer cell activation, cytokines including perforin/granzyme, Fas-L and Tumour Necrosis Factor (TNF) alpha.13 Cytokines play a role in the immunopathological and molecular mechanisms of drug-induced hypersensitivity reactions (HSR). A study of ibuprofen-induced SJS showed that in the patient with SJS, high lymphocyte level,and high
52
cytokine secretion in the patient's sera with the high level of tumor necrosis factor alpha (TNF-alpha) as high as in patients found to have TEN.14 Finally, the presented case reinforce that StevensJohnson syndrome is a potentially fatal multiorgan disease with a strong etiologic link to some medications. One must have a high index of suspicion to be able to diagnose and treat patients with SJS in time and must therefore consider Stevens-Johnson syndrome as a potential complication of treatment, especially when use of medication is questionable. Affected patients and their first-degree relatives should be instructed to avoid any identified drugs or chemicals that may be responsible. This is critical for the subsequent survival of these patients. Intensive treatment must also be done together with specialist physicians, where available. Treatment with steroid agents may be helpful, but this option remains controversial. CONSENT Written informed consent was obtained from the patient for publication of this case report. A copy of the written consent is available for review from the journal's Editorin-Chief. REFERENCES 1. Castana O., Rempelos G., Anagiotos G., Apostolopoulou C., Dimitrouli A., Alexakis D. Stevens Johnson Syndrome: A case report. Annals of Burns and Fire Disasters 2009; 22(3): 147-151. 2. French LE. Toxic epidermal necrolysis and Stevens Johnson syndrome: our current understanding. Allergol Int. 2006;55(1):9-16. 3. Bastuji-Garin S, Fouchard N, Bertocchi M, et al. SCORTEN: a severity-of-illness score for toxic epidermal necrolysis. J Invest Dermatol. 2000;115(2):149-53. 4. Stevens Johnson Syndrome. [http://www. skinassn.org/causes-of-stevens-johnsonsyndrome.html]
5. Roujeau JC, Kelly JP, Naldi L, Rzany B, Stern RS, Anderson T, et al. Medication use and the risk of Stevens-Johnson syndrome or toxic epidermal necrolysis. N Engl J Med. 1995 .14;333(24):1600-7. 6. I b u p r o f e n D r u g Information[www.nlm.nih.gov/medlineplus/druginf o/med /a682159 .htm] 7. Ward KE, Archambault R, Mersfelder TL. Severe adverse skin reactions to nonsteroidal antiinflammatory drugs:A review of the literature. Am J Health Syst Pharm 2010.1;67(3):206-13. 8. Sternlieb P, Robinson RM. Stevens-Johnson syndrome plus toxic hepatitis due to ibuprofen. N Y State J Med. 1978;78(8):1239-43 9. Stern RS, Bigby M. An expanded profile of cutaneous reactions to nonsteroidal anti-inflammatory drugs. Reports to a specialty-based system for spontaneous reporting of adverse reactions to drugs. JAMA. 1984 21;252(11):1433-7. 10. Nirken MH. Stevens-Johnson syndrome and toxic e p i d e r m a l n e c r o l y s i s i n adults.[http://uptodateonline.com/patients/content/t opic.do?topicKey=~KMM0KgcQUwSCr8z]. 11. Mahboob A, Haroon TS. Drugs causing fixed eruptions: a study of 450 cases. Int J Dermatol. 1998 Nov;37(11):833-8 12. Patel R, Marfatia Y. Clinical study of cutaneous drig eruptions in 200 patients. Indian Journal of Dermatol Venereol Leprol 2008; 74:80 13. Stevens Johnson Syndrome & Toxic Epidermal Necrolysis[http://dermnetnz.org/reactions/sjsten.html] 14. Neuman M, Nicar M. Apoptosis in ibuprofeninduced Stevens-Johnson syndrome. Transl Res. 2007 May;149(5):254-9.)
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INSTRUCTIONS TO AUTHORS -2010 INDIAN JOURNAL OF PHARMACY PRACTICE (ijopp)

Indian Journal of Pharmacy Practice (ijopp) is official journal of Association of Pharmaceutical Teachers of India (APTI). Indian Journal of Pharmacy Practice, a quarterly publication is devoted to publishing reviews and research articles in the area of Pharmacy Practice. Articles in the areas of clinical pharmacy, hospital pharmacy, community pharmacy, pharmaceutical care, pharmacovigilance, pharmacoeconomics, clinical research, clinical pharmacokinetics and other related issues can be sent for publication in ijopp. All manuscripts should be submitted in triplicate along with 'Authorship Responsibility Undertaking', signed by all the authors of the paper to, The Editor, Indian Journal of Pharmacy Practice, Association of Pharmaceutical Teachers of India, H.Q.: Al-Ameen College of Pharmacy, Hosur Road, Opp. Lalbagh Main Gate, Bangalore- 560 027. Authors should retain a copy of all materials submitted to the journal; the editor cannot accept responsibility for loss or damage to submitted materials. Manuscripts will be subjected to peer review process to determine their suitability for publication, provided they fulfilled the requirements of the journal. After the review, manuscript will be returned for revision along with reviewer's and /or editor's comments. One original copy of the final revised manuscript should be submitted for publication within one month after receiving the comments. It is also desirable to submit the final revised manuscript on a CD prepared in MS word version 6.0/95 or a higher version. Submission of a manuscript to ijopp for publication implies that the same work has not been either published or under consideration for publication in another journal. Author/s publishing results from in-vivo experiments involving animal or humans should state whether due permission for conduct of these experiments was obtained from the relevant authorities /Ethics committee/Institutional Review Board. Manuscript preparation: Manuscripts should be concisely typewritten in double space in A4 sized sheets, only on one side with a 2 cm margin on all sides. The manuscript shall be prepared in Times New Roman font using a font size of 12. Title shall be in a font size 14. All section titles in the manuscript shall be in font size 12, bold face capitals. Subtitles in each section shall be in font size 12, bold face lower case followed by a colon. The pages shall be numbered consecutively with arabic numbers, beginning with title page, ending with the (last) page of figure legends. The length of an Review/ Science Education article should not exceed 25 manuscript pages to include figures, tables and references. No abbreviations or acronyms shall be used in the Title or Abstract acronyms, except for measurements. All the references, figures (Fig.) and tables (Table) in the text shall be numbered consecutively as they first appear. No sentence shall start with a numeral. Abbreviations like & and etc shall be avoided in the paper. There shall not be any decorative borders anywhere in the text including the title page. The entire MS Word document with graphs and illustrations pasted in it shall not exceed 2 MB. Manuscripts must conform to the Uniform Requirements for Manuscripts Submitted to Biomedical Journals http://www.icmje.org/. The Content of the manuscript shall be organized in the following sequence and shall start on separate pages: title page (including author's name, affiliations and address for correspondence), abstract (including atleast 4 key words), text (consisting of introduction, materials and methods, results, discussion, conclusion and acknowledgements), references, figure legends, tables and figures. Titles should be short, specific, and clear. Beginning with the first page of text, each page should be consecutively numbered. For the Review Articles, the author(s) is absolutely free to design the paper. The Abstract section is needed for review articles too. The article should not exceed 15 manuscript pages including figures, tables and references. References, figures, and legends shall follow the general guidelines described below. For all other Articles, the following format shall be strictly followed. Title Page. The following information should appear: title of article (A running title or short title of not more than 50 characters), authors' name, and last name. The author to whom all correspondence be addressed should be denoted by an asterisk mark. Full mailing address with pin-code numbers, phone and fax numbers, and functional e-mail address should be provided of the author for correspondence. Names of the authors should appear as initials followed by surnames for men and one given-name followed by surname for women. Full names may be given in some instances to avoid confusion. Names should not be prefixed or suffixed by titles or degrees.
54
Abstract: The abstract is limited to 250 words, and should describe the essential aspects of the investigation. In the first sentence, the background for the work should be stated; in the second sentence the specific purpose or hypothesis shall be provided; followed sequentially by summary of methods, results and conclusion. No references should be cited. Introduction: A brief background information on what has been done in the past in this area and the importance of the proposed investigation shall be given. Introduction shall end with a statement of the purpose or hypothesis of the study. Material and Methods: This section may be divided into sub-sections if it facilitates better reading of the paper. The research design, subjects, material used, and statistical methods should be included. Results and discussion shall not be drawn into this section. In human experimentation, ethical guidelines shall be acknowledged. Results: This section may be divided into subsections if it facilitates better reading of the paper. All results based on methods must be included. Tables, graphic material and figures shall be included as they facilitate understanding of the results. Discussion: Shall start with limited background information and then proceed with the discussion of the results of the investigation in light of what has been published in the past, the limitations of the study, and potential directions for future research. The figures and graphs shall be cited at appropriate places. Conclusion: Here, the major findings of the study and their usefulness shall be summarized. This paragraph should address the hypothesis or purpose stated earlier in the paper. Acknowledgments. Acknowledgments should appear on a separate page. Tables. Each table should be given on a separate page. Each table should have a short, descriptive title and numbered in the order cited in the text. Abbreviations should be defined as footnotes in italics at the bottom of each table. Tables should not duplicate data given in the text or figures. Only MS word table format should be used for preparing tables. Tables should show lines separating columns with those separating rows. Units of measurement should be abbreviated and placed below the column headings. Column headings or captions should not be in bold face. It is essential that all tables have legends, which explain the contents of the table. Tables should not be very large that they run more than one A4 sized page. If the tables are wide which may not
fit in portrait form of A4 size paper, then, it can be prepared in the landscape form. Authors will be asked to revise tables not conforming to this standard before the review process is initiated. Tables should be numbered as Table No.1 Title., Table No.2 Title. Etc. Tables inserted in word document should be in tight wrapping style with alignment as center. Figures, Photographs and Images: Graphs and bar graphs should preferably be prepared using Microsoft Excel and submitted as Excel graph pasted in Word. These graphs and illustrations should be drawn to approximately twice the printed size to obtain satisfactory reproduction. Specification of Legends/values in Graphs Font Arial, size- 10 pt, Italics- None] Diagrams made with Indian ink on white drawing paper, cellophane sheet or tracing paper with hand written captions or titles will not be accepted. Photographs should be submitted only on photo-glossy paper. Photographs should bear the names of the authors and the title of the paper on the back, lightly in pencil. Alternatively photographs can also be submitted as 'jpeg/TIFF with the resolution of 600 dpi or more' images. Figure and Table titles and legends should be typed on a separate page with numerals corresponding to the illustrations. Keys to symbols, abbreviations, arrows, numbers or letters used in the illustrations should not be written on the illustration itself but should be clearly explained in the legend. The complete sets of original figures must be submitted. Legends should be in the present tense (e.g., 'Illustration shows ...'). Subjects' names must not appear on the figures. Labels should contrast well with the background. Images should be uniform in size and magnification. Illustrations should be free of all identifying information relative to the subject and institution. Written permission for use of all previously published illustrations must be included with submission, and the source should be referenced in the legends. Written permission from any person recognizable in a photo is required. Legends must be double spaced, and figures are numbered in the order cited in the text. Color prints shall be submitted only if color is essential in understanding the material presented. Label all pertinent findings. The quality of the printed figure directly reflects the quality of the submitted figure. Figures not conforming to acceptable standards will be returned for revision. Figures should be numbered as Fig.1, Fig.2 etc. ; Figures inserted in word document should be in square wrapping style with horizontal alignment as center.
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Resolution: Drawings made with Adobe Illustrator and CorelDraw (IBM/DOS) generally give good results. Drawings made in WordPerfect or Word generally have too low a resolution; only if made at a much higher resolution (1016 dpi) can they be used. Files of scanned line drawings are acceptable if done at a minimum of 1016 dpi. For scanned halftone figures a resolution of 300 dpi is sufficient. Scanned figures cannot be enlarged, but only reduced. Figures/Images should be submitted as photographic quality scanned prints, and if possible attach an electronic version (TIFF/ JPEG). Chemical terminology - The chemical nomenclature used must be in accordance with that used in the chemical abstracts. Symbols and abbreviations - Unless specified otherwise, all temperatures are understood to be in degrees centigrade and need not be followed by the letter 'C'. Abbreviations should be those well known in scientific literature. In vitro, in vivo, in situ, ex vivo, ad libitum, et al. and so on are two words each and should be written in italics. None of the above is a hyphenated word. All foreign language (other than English) names and words shall be in italics as a general rule. General Guidelines for units and symbols - The use of the International System of Units (SI) is recommended. For meter (m), gram (g), kilogram (kg), second (s), minute (m), hour (h), mole (mol), liter (l), milliliter (ml), microliter (l). No pluralization of symbols is followed. There shall be one character spacing between number and symbol. A zero has to be used before a decimal. Decimal numbers shall be used instead of fractions. Biological nomenclature - Names of plants, animals and bacteria should be in italics. Enzyme nomenclature - The trivial names recommended by the IUPAC-IUB Commission should be used. When the enzyme is the main subject of a paper, its code number and systematic name should be stated at its first citation in the paper. Spelling - These should be as in the Concise Oxford Dictionary of Current English. PAGE LAYOUT GUIDELINES Indian Journal of Pharmacy Practice ___________________________________________
Page size Margins Page numbers Indent Footer / Headers Title Text Tables Letter Portrait 8.5 X 11.0 All Margins, 1 Numbered as per the assigned page /Absolutely no break or Missed sections None, Absolutely, No Tab None 14pt Times New Roman, bold, centered followed by a single blank line. 12pt Times New Roman, full justification1.5 line spacing between paragraph. No indentation At the end of context with rows and columns active; tables should have individual rows and columns for each value expressed. All text should be fully justified.
Please put all primary section titles in UPPER CASE letters (Example INTRODUCTION, MATERIALS AND METHODS, RESULTS, DISCUSSION, ACKNOW-LEDGEMENT, REFERENCES) and subheading in both Upper and Lower Case letters (Italics). Do not number your subtitles (for example, 1.0 Introduction; 2.0 Background; 2.1.1 are not acceptable). Do not use the tab key to indent blocks of text such as paragraphs of quotes or lists because the page layout program overrides your left margin with its own, and the tabs end up in mid-sentence. References Literature citations in the text must be indicated by Arabic numerals in superscript. Each reference separately in the order it appears in the text. The references should be cited at the end of the manuscript in the order of their appearance in the text. In case of formal acceptance of any article for publication, such articles can be cited in the reference as in press, listing all author's involved. References should strictly adhere to Vancouver style of citing references. Format: Author(s) of article (surname initials). Title of article. Journal title abbreviated Year of publication; volume number (issue number):page numbers. Standard journal article (If more than six authors, the first three shall be listed followed by et al.) You CH, Lee KY, Chey WY, Menguy R. Electrogastrographic study of patients with unexplained nausea, bloating and vomiting. Gastroenterology 1980;79:311-4. Books and other monographs Format:Author(s) of book (surname initials). Title of book. Edition. Place of publication: Publisher; Year of publication. Personal author(s) Eisen HN. Immunology: an introduction to molecular and cellular principles of the immune response. 5th ed. New York: Harper and Row; 1974. Editor, compiler, as author Dausser J, Colombani J, editors. Histocompatibility testing 1972. Copenhagen: Munksgaard; 1973. Organisation as author and publisher Institute of Medicine (US). Looking at the future of the Medicaid program. Washington: The Institute; 1992. Conference proceedings Kimura J, Shibasaki H, editors. Recent advances in clinical neurophysiology. Proceedings of the 10th International Congress of EMG and Clinical Neurophysiology; 1995 Oct 15-19; Kyoto, Japan. Amsterdam: Elsevier; 1996. Dissertation Kaplan SJ. Post-hospital home health care: the elderly's access and utilization [dissertation]. St. Louis (MO): Washington Univ.; 1995. 56
Patent Larsen CE, Trip R, Johnson CR, inventors; Novoste Corporation, assignee. Methods for procedures related to the electrophysiology of the heart. US patent 5529 067. 1995 Jun 25. Chapter or article in a book Format: Author(s) of chapter (surname initials). Title of chapter. In: Editor(s) name, editors. Title of book. Place of publication: Publisher; Year of publication. page numbers. Electronic journal article Morse SS. Factors in the emergence of infectious diseases. Emerg Infec Dis [serial online] 1995Jan-Mar [cited 1996 Jun 5];1(1):[24 screens]. Available from: URL: http://www.cdc.gov/ ncidod/EID/eid.htm World Wide Web Format: Author/editor (surname initials). Title [online]. Year [cited year month day]. Available from: URL: World Wide Web page McCook A. Pre-diabetic Condition Linked to Memory Loss [online]. 2003 [cited 2003 Feb 7]. Available from: URL: http:// www.nlm.nih.gov/medlineplus/news/fullstory_11531 .html Abbreviations for Journals For More information on medline indexed journals : Download list of medline journals: ftp://ftp.ncbi.nih.gov/pubmed/J_Medline.zip American Journal of Pharmacy- (Amer J Pharm) Analytical Chemistry- (Anal Chem) British Journal of Pharmacology and Chemotherapy(Brit J Pharmacol) Canadian Journal of Pharmaceutical Sciences- (Can J Pharm Sci) Clinical Pharmacokinetics- (Clin Pharmacokinet) Drug Development and Industrial Pharmacy- (Drug
Develop Ind Pharm) Helvitica Chimica Acta- (Helv Chim Acta) Indian Journal of Medical Sciences- (Indian J Med Sci) Indian Journal of Pharmaceutical Sciences- (Indian J Pharm Sci) Journal of the American Chemical Society, The- (J Amer Chem Soc) Journal of Biological Chemistry- (J Biol Chem) Journal of Organic Chemistry, The- (J Org Chem) Journal of Pharmacology and Experimental Therapeutics- (J Pharmacol Exp Ther) New England Journal of Medicine- (N Engl J Med) Pharmaceutical Journal, The (Pharm J) PharmacologicalResearch Communications(Pharmacol Res Commun) AUTHOR's CHECKLIST FOR SENDING PROOFS TO EDITORIAL OFFICE In order to maintain quality and consistency in Indian Journal of Pharmacy Practice, we ask you to perform the following items prior to submitting your final proof for publication: ? Include the original, hard copy of Author's Transfer of Copyright signed by each author ? Thoroughly check the article for typographic errors, format errors, grammatical errors, in particular: spelling of names, affiliations, any symbols, equations in the context, etc. ? Provide graphs and figures in excel format, Pictures are required as high resolution images (300 dpi). ? Provide laser printed hard copies of all figures and graphics in black and white or scanned copies can also be sent to ijopp@rediffmail.com ? Submit a proof corrected with RED INK ONLY.
Send the Corrected Proof, Copyright Transfer Form, with covering letter in a single envelope to the Following Address Authors are required to send their contributions or manuscripts through post or courier services. Dr. Shobha Rani R Hiremath Editor, Indian Journal of Pharmacy Practice (ijopp). C/o. Association of Pharmaceutical Teachers of India (APTI), H.Q: Al-Ameen College of Pharmacy, Opp. Lalbagh Main gate, Hosur Road, Bangalore 560 027, Karnataka, INDIA. All enquiries can be made through e-mail: ijopp@rediffmail.com
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Indian Journal of Pharmacy Practice

EDITOR-IN-CHIEF Dr. Shobha Rani R. Hiremath shobha24@yahoo.com

ASSOCIATE EDITORS Dr. G. Parthasarathi partha18@airtelmail.in Dr. Pramil Tiwari ptiwari@niper.ac.in

EDITORIAL OFFICE INDIAN JOURNAL OF PHARMACY PRACTICE

Indian Journal of Pharmacy Practice

EDITORIAL ADVISORY BOARD

Indian Journal of Pharmacy Practice

Indian Journal of Pharmacy Practice

= Procurement Practices in Public Sector Medicines Mohanta GP, Veena R------------------------------------------------------------------------------------------------43-45

Dr. Shobha Rani R Hiremath Editor-in-Chief

Indian J. Pharm. Pract. 3(2), Apr-Jun, 2010

Department of Pharmacology, J.S.S. College of Pharmacy (Constituent College of J.S.S.

Indian J. Pharm. Pract. 3(2), Apr-Jun, 2010

Indian J. Pharm. Pract. 3(2), Apr-Jun, 2010

Indian J. Pharm. Pract. 3(2), Apr-Jun, 2010

Indian J. Pharm. Pract. 3(2), Apr-Jun, 2010

Indian J. Pharm. Pract. 3(2), Apr-Jun, 2010

Indian J. Pharm. Pract. 3(2), Apr-Jun, 2010

Indian J. Pharm. Pract. 3(2), Apr-Jun, 2010

Indian J. Pharm. Pract. 3(2), Apr-Jun, 2010

Indian J. Pharm. Pract. 3(2), Apr-Jun, 2010

Indian J. Pharm. Pract. 3(2), Apr-Jun, 2010

Indian J. Pharm. Pract. 3(2), Apr-Jun, 2010

Indian J. Pharm. Pract. 3(2), Apr-Jun, 2010

Table.1: Department wise distribution of prescriptions co llected

No. of prescriptions 31 15 14 11 8 6 5 4 2 2 1 1 100

Total No. of drugs prescribed 143 43 64 26 37 13 12 17 7 4 2 2 350

Indian J. Pharm. Pract. 3(2), Apr-Jun, 2010

Fig.2: Rationality score

Indian J. Pharm. Pract. 3(2), Apr-Jun, 2010

Indian J. Pharm. Pract. 3(2), Apr-Jun, 2010

Pattern of potential medication errors in a tertiary care hospital in Nepal.

, Subish P , Anil K , Ram B

Indian J. Pharm. Pract. 3(2), Apr-Jun, 2010

Indian J. Pharm. Pract. 3(2), Apr-Jun, 2010

Table.1: Department distribution (n=59)

Table.2: Classification of medication error based on underlying cause (n=66)

Percentage 68.18 10.61 9.09 4.55 4.55 1.52 1.52

Category A Category B Category C Category D

Indian J. Pharm. Pract. 3(2), Apr-Jun, 2010

Table.3: Class of drugs involved in medication erro r (n=66)

Num ber of drugs

Indian J. Pharm. Pract. 3(2), Apr-Jun, 2010

Table.3 : Site of Infection Diagnosed

Table.4: Rationality and Irratio nality of Prescriptions

RATIONAL Sl. No. PATTERN (%) 1 Number of antibiotics p rescribed 71.64

IRRATIONAL (%) 28.36

Indian J. Pharm. Pract. 3(2), Apr-Jun, 2010

Azithromycin Tramadol Ranitidine

Indian J. Pharm. Pract. 3(2), Apr-Jun, 2010

Indian J. Pharm. Pract. 3(2), Apr-Jun, 2010

Study of prescription practice for Antipsychotic drugs by Psychiatrists- A Survey

Indian J. Pharm. Pract. 3(2), Apr-Jun, 2010

Fig.1: Percentage of Prescribers by Age of Patients

Percentage of Prescribers by Age of Patients

Indian J. Pharm. Pract. 3(2), Apr-Jun, 2010

Table.1: Percentage of prescribers by medication

Medication Risperido ne Olanzapine Quetiapine Clozapine

Table.2: Percentage of prescribers by indication

Indian J. Pharm. Pract. 3(2), Apr-Jun, 2010

Indian J. Pharm. Pract. 3(2), Apr-Jun, 2010

Indian J. Pharm. Pract. 3(2), Apr-Jun, 2010