CLINICAL PHARMACOLOGY

Case Scenario 1:
A 60 years old male suddenly developed drooping of eyelids and weakness of muscles
which was more pronounced in the evening. He was diagnosed to be suffering from
myasthenia gravis.
Question & Answer:
1. Enumerate the drugs used in this condition with rationale.
Neostigmine, Pyridostigmine –increases Ach concentration in NM junction.
Corticosteroids – decreases the production of NR antibodies,  synthesis of NR.
Azathioprine, Cyclosporine – immunosuppressant action.

2. Why Neostigmine is preferred rather than physostigmine?

Neostigmine produces more marked effect on skeletal muscles and less marked
muscarinic, CNS effects whereas physostigmine acts vice versa

3. What are the other modalities of treatment?

Plasmapheresis, Thymectomy.

4. What are the other uses of anticholinersterases?

Cobra bite, miotic, Alzheimer’s disease, post operative decurarization,
Post operative paralytic ileus & belladonna poisoning

5. Name the Diagnostic tests for Myasthenia gravis

Ameliorative test, Provocative test and demonstration of anti – Nicotinic Receptor
antibodies in plasma or muscle biopsy specimen.

6. Which is the more reliable test for myasthenia gravis?

Demonstration of anti – NR antibodies in plasma or muscle biopsy specimen

7. What is Myasthenic crisis?

It is characterized by acute weakness of respiratory muscles

8. What is the management for Myasthenic crisis?

Tracheal intubation and Mechanical Ventilation
Withhold anti – cholinesterases for 2-3 days and introduce methyl prednisolone pulse
therapy followed by gradual reintroduction of the anti-cholinesterases.

9. How will you differentiate between cholinergic crisis and Myasthenic crisis?
It can be differentiated by Edrophonium test. When 2mg of edrophonium is given iv, if
muscle strength improves it is Myasthenic crisis. If muscle strength worsens it is
cholinergic crisis.

10.What is the management of these two conditions?

Myasthenic crisis - ↑ dose of neos gmine.
Cholinergic crisis - ↓ dose of neos gmine.
Case scenario 2:
A young adult male comes with a history of frequent episodes of severe headache on the
right side with vomiting, increased sensitivity to light and sound. He was diagnosed to be
suffering from migraine.

Question & Answer:

1. What are the drugs used to treat this condition?
NSAIDs, anti-emetics, ergot alkaloids, triptans.

2. Give two limitations of ergot alkaloids.

Erratic oral absorption, vasospasm related complications, nausea and vomiting.

3. What is the mechanism of action of sumatriptan?

It is a selective 5HT1B /1D agonist and hence causes cerebral vasoconstriction.

4. Mention the different available formulations of Sumatriptan.

Sumatriptan is available as tablet (25 mg, 50 mg & 100 mg), intra-nasal spray and as vial
for subcutaneous injection.

5. What are the contraindications of sumatriptan?

CI – Patients with IHD, HT, Epilepsy, pregnancy, hepatic and renal impairment.

6. Can we combine ergot alkaloids with sumatriptan? Reason out

No, both ergot and sumatriptan cause vasoconstriction and hence dangerous additive
effect will be present.

7. What is the treatment for mild Migraine?

Simple analgesics / NSAIDS + antiemetics

8. Which patients are considered for prophylactic therapy?

Those patients suffering from severe migraine i.e 2-3 attacks per month lasting for 12-
48 hrs with accompanying symptoms.

9. What are the drugs used for prophylaxis of Migraine?

β blockers - Propanalol, Tricyclic Antidepressants- amitriptyline,
Calcium Channel Blockers- flunarizine, verapamil , Anti epileptic - Sodium valproate,
Gabapentin.

10. Among triptans, which is the most potent drug?

Rizatriptan
Case scenario 3:
An elderly man of 75 years comes with the complaints of tremor, inability to do routine
work. On examination the patient has mask like face and short shuffling gait and rigidity of
muscle.

Question & Answer:

1. What are the drugs used to treat this condition?
Levodopa, Dopamine Agonist - Bromocriptine, COMT inhibitors - Entacapone,
MAO –B inhibitors - Selegiline, Central anticholinergics - Benzhexol.

2. Give two advantages of adding peripheral decarboxylase inhibitor to Levodopa.

Nausea, Vomiting, Cardiac Complications are minimized. Plasma t1/2 of Levodopa is
prolonged, on – off effect is minimised.

3. What are the problems accentuated by the addition of decarboxylase inhibitor?

Postural hypotension, Behavioural abnormalities & involuntary movements.

4. How do you treat drug induced Parkinsonism? What is the rationale?

Trihexyphenidyl, procyclidine, biperidin are the drug of choice for DIP.
Levodopa cannot be used in this condition as D2 receptors are already blocked by anti –
psychotic drugs, so central anticholinergics are given to reduce tremor and rigidity
produced by relative excess of cholinergic activity.

5. What is ON-OFF phenomenon?

Rapid and unpredictable fluctuations in motor control seen with prolonged therapy of
Levodopa

6. Name the drugs used to treat on-off phenomenon.

Bromocriptine, Ropinirole, Pramipexole.

7. Which drug is used in advanced cases of on-off phenomenon?

COMT inhibitor- Entacapone.

8. Can we prescribe Vitamin B complex supplementation with Levodopa? Reason out.

No, because pyridoxine enhance peripheral decarboxylation of Levodopa and abolishes
its therapeutic effect

9. Name the drugs given for mild Parkinsonism.

Anticholinergics, Selegiline.

10. Name the Glutamate antagonist used in Parkinsonism and its specific adverse effect.
Amantadine
Side effect – Livedo Reticularis (bluish discolouration) and ankle edema.
Case scenario 4:
A middle aged patient underwent herniorraphy under spinal anaesthesia with lignocaine.
The immediate post-operative period was uneventful. The next day patient complained of
headache.

Question & Answer:

1. How will you treat this condition?
Simple bed rest, analgesics and head down position while lying in bed.

2. What are the other complications of spinal anaesthesia?

Hypotension, meningitis, respiratory paralysis, cauda equina syndrome.

3. Name the drugs used to treat hypotension due to spinal anaesthesia.

IV fluids, mephentermine /methoxamine /Ephedrine.

4. What are the adverse effects of lignocaine?

Paresthesia, circum oral twitching, numbness, convulsions, bradycardia, hypotension &
cardio vascular collapse.

5. Name the local anaesthetic drug with high cardio toxicity.

Bupivacaine.

6. What is the mechanism of action of Local Anaesthesia?

Membrane stabilising effect – by blocking sodium channel.

7. Name any two routes by which Local Anaesthetics can be administered besides spinal.
Epidural Anaesthesia, plexus block, infiltration and surface anaesthesia.

8. What is EMLA?
EMLA is Eutectic Mixture of Local Anaesthesia (lidocaine & prilocaine). It is in the form
of a cream which is applied on the skin for IV cannulation and split skin graft.

9. What are the advantages of epidural anaesthesia?

Headache & neuronal complications are less because intrathecal space is not entered.

10. What is the other use of Lignocaine? Specify the route of administration
To treat ventricular arrhythmias in myocardial infarction, It is given by i.v route.
Case scenario 5:
A baby was brought with cleft lip and cleft palate. There was a history of drug intake by the
mother during pregnancy.

Question & Answer:

1. What are the likely drugs to cause this effect?
Phenytoin, anticancer drugs - Methotrexate.

2. What is teratogenicity?
It is the capability of a drug to cause foetal abnormalities when administered to the
mother.

3. Name the risk categories of drugs during pregnancy.

Group A , B, C ,D & X .

4. Which category is designated as the highest risk?

Group X

5. Name two drugs which come under Group X.

Estrogen, Isotretinoin, Ergometrine, Anti-canceer drugs.

6. Name the drugs which produce neural tube defect.

Sodium Valproate and Carbamazepine

7. How neural tube defect can be avoided?

By administration of folic acid prenatal and antenatal period.

8. Name the three stages during pregnancy where drugs can produce teratogenicity.
Stage of fertilisation & implantation – Failure of pregnancy
Stage of organogenesis – Deformities occur
Stage of growth & development – Functional abnormalities

9. Name two antibiotics which have to be avoided in pregnancy.

Tetracycline, chloramphenicol

10. Name some drugs which have least/nil teratogenic effect?

Thyroxine , Paracetamol , Omeprazole, Heparin
Case scenario 6:
A girl aged 17 years came to the OPD with the history of tonic clonic seizures.
Investigations revealed that she has grand mal epilepsy.

Question & Answer:

1. What are the first line drugs to treat this condition?
Carbamazepine , Phenytoin.

2. Which drug is preferred in this patient? Rationale behind its use

Carbamazepine . Patient being a young girl, Phenytoin is not preferred as it causes gum
hypertrophy, hirsutism, acne & coarsening of facial features.

3. Which antiepileptic is to be cautiously used in paediatric patients?

Sodium valproate as it produces hepatic toxicity in children.

4. Give two new drugs which can be added in refractory cases.

Lamotrigine, Gabapentine, Topiramate.

5. Give two drugs used to treat post traumatic epilepsy.

Phenobarbitone ,Phenytoin , Valproate .

6. What are the other uses of carbamazepine?

Trigeminal neuralgia, Manic depressive psychosis.

7. Mention some of the adverse effects of Valproate.

Alopecia, curling of hair, ataxia, fulminant hepatitis.

8. What is the absolute contraindication for phenobarbitone?

Acute intermittent porphyria.

9. If the same patient develops petitmal epilepsy , what is the drug of choice?
Sodium valproate.

10. Name the drugs used to treat infantile spasm.

Corticosteroids give symptomatic relief
Valproate, Clonazepam - adjuvants
Case Scenario 7:
A patient came to ophthalmic OPD with the complaints of dimness of vision and headache.
On examination his intraocular tension was found to be 25 mm of Hg.

Question & Answer:

1. What are the major groups of drugs used in glaucoma? Give the mechanism of action of
each.
a. β blocker- ↓ secre on.
b. α2agonist - ↑ ou low
c. PG analogue-↑ ou low
d. Cholinergics- ↑ ou low
e. Carbonic anhydrase inhibitors-↓secre on

2. What are the first line drugs?

Latanoprost, β blockers.

3. Which beta blocker is preferred in patients with asthma?

Betaxalol as it is a selective β1 blocker with less broncho pulmonary, central &
metabolic side effects.

4. Mention two advantages of using beta blockers over miotics.

a. No diminution of vision in dim light.
b. No induced myopia, No headache, brow pain.
c. No fluctuations in i.o.t.
d. Convenient once / twice daily application

5. How can we minimize systemic side effects of ocular β blockers?

After instilling eye drops, apply mild pressure on the inner canthus for about 5 minutes
to prevent entry into nasolacrimal duct from which it is absorbed.

6. Name the drug used orally to reduce I.O.T.

Acetazolamide 0.25 g – 6 to 12th hourly ( HCO3 generation in ciliary epithelium)

7. Name the α2 agonist used in glaucoma?

Brimonidine, apraclonidine , dipivefrine

8. Name the PG analogues used in glaucoma?

Latanoprost ,Travoprost ,Bimatoprost

9. Why PG analogues are preferred as first choice drugs ?

PG analogues have good efficacy, once daily application and lack of systemic
complications

10. Name the drugs used in closed angle glaucoma

Osmotic agents like hypertonic mannitol ,acetazolamide and miotics are used to reduce
intra ocular tension vigorously before surgical therapy
Case Scenario 8:
A 42 yr old man with moderately severe coronary artery disease, with BMI of 32,
increased abdominal girth with controlled Hypertension came with Lipid Profile of
Cholesterol - 250 mg
Triglyceride - 100 mg
LDL - 260mg
VLDL - 70 mg
HDL - 32 mg

Question & Answer:

1. What is the drug of choice for the above condition?
STATINS are the drug of choice in hypercholesterolemia

2. What is its mechanism of action?

Statin acts by inhibiting HMG CoA reductase enzyme - a rate limiting step in cholesterol
synthesis. They increase the LDL receptor expression on Liver cells.

3. Name two drugs in that group. Answer  Atorvastatin & Rosuvastatin

4. What are adverse effects of statins?

Hepatotoxicity, myopathy, bowel upset, sleep disturbances, rise in serum
transaminases level.

5. When Statins should be taken?

Statins should be taken at bed time to obtain maximum effectiveness because HMG
CoA reductase enzyme activity is maximum at mid night. However, long acting statins
like atorvastatin & rosuvastatin can be given at any time.

6. Name the drugs which aggravate statins induced myopathy?

Nicotinic acid /gemfibrozil or CYP3A4 inhibitor – Ketoconazole /erythromycin
/cyclosporine /HIV protease inhibitor

7. What are the other hypolipidemic drugs?

Cholestyramine , Colestipol, Clofibrate , gemfibrozil & Nicotinic acid.

8. Name two drugs to treat hypertriglyceridaemia : Answer  Fibrates and nicotinic acid

9. What is the mechanism of action of fibrates?

The fibrates activate lipoprotein lipase that degrades VLDL. This effect is exerted
through (PPARa) Peroxisome Proliferator Activated Receptor a.

10. What is the mechanism of action of Ezetimibe?

Ezetimibe acts by inhibiting intestinal absorption of cholesterol & Phyto sterols and it
interferes with a specific CH transport Protein NPC1L 1 in intestinal mucosa reducing
absorption of both dietary & biliary cholesterol.
Case scenario 9:
A 45 yr old lady with lupus nephritis treated with long term systemic corticosteroids,
cyclophospamide & mycophenolate mofetil complaints of puffiness of face, headache,
weakness, polyuria & recurrent respiratory infection. On examination patient showed
features of drug induced cushing syndrome.

Question & Answer:

1. Which drug has induced the above condition?
Corticosteroids have induced Cushing syndrome.

2. Explain the reason for cushingoid feature.

Peripheral adipocytes are more sensitive to corticosteroid – facilitated lipolytic action of
Growth Hormone and Adrenaline, breakdown of fat predominates whereas truncal
adipocytes respond to raised insulin levels caused by glucocorticoid induced
hyperglycaemia and hence fat deposits over there.

3. What are the other adverse effects of steroids?

Peptic ulcer, osteoporosis, diabetes, hypertension, susceptibility to infections, foetal
abnormalities in pregnant women.

4. What are the adverse effects of topical steroids?

Fragile skin, Purple striae, easy bruising, telangiectasis, hypertrichosis , dermal atrophy,
glaucoma.

5. Name some Inhalational steroids?

Budesonide, Fluticasone, Flunisolide, Beclomethasone, ciclesonide & Betamethasone

6. Mention five other uses of steroids?

Severe allergic reactions, autoimmune diseases, Bronchial Asthma, Rheumatoid
arthritis, Ulcerative Colitis and Crohn’s disease.

7. Name some drugs which inhibit steroid synthesis

Metyrapone, aminoglutethimide, trilostane, Ketoconazole .

8. Mention two advantages of inhalational steroids.

Systemic effects are minimal.
Pituitary adrenal axis suppression is minimal.

9. What is the role of corticosteroid in anaphylaxis?

It is indicated only in severe /recurrent anaphylaxis & bronchospasm due to drug
hypersensitivity.

10.Name three mineralocorticoids.

Desoxy corticosterone acetate , Fludrocortisone , Aldosterone.
Case Scenario 10:
A 45 year old man presented with recurrent episodes of fever, respiratory tract infections
and diarrhoea. On examination patient had oral thrush. He was found to be positive for
HIV infection. He had CD4 count less than 400/cu.ml

Question & Answer:

1. What are the rationales of using ART in AIDS patient?
a. To prolong the lifespan.
b. To improve the quality of life.
c. To postpone the complications of AIDS.

2. Enumerate any four nucleoside reverse transcriptase inhibitors.

Zidovudine, Lamivudine, Didanosine, Abacavir and Stavudine.

3. What is the mechanism of action of NRTI.

They inhibit viral reverse transcriptase enzyme (RNA dependant DNA polymerase) after
getting activated in the body.

4. Write the drugs used to prevent vertical transmission.

Zidovudine, Nevirapine.

5. What is the dose related toxicity of zidovudine ?

Bone marrow depression.

6. Mention the drug used to treat the above toxicity by zidovudine.

Erythropoietin

7. What are the different combinations in HAART?

2 NRTI and 1NNRTI.
2NRTI and 1 PI
1NRTI, 1NNRTI and 1PI for advanced cases.

8. What are the drug combinations to be avoided?

Zidovudine and stavudine – Pharmacodynamic antagonism.
Stavudine and didanosine – lactic acidosis.
Lamivudine and didanosine – Clinically not additive.

9. Name the fusion inhibitor used in HIV therapy?

Enfuvirtide

10. The fusion inhibitor is not given orally, why?

It is a peptide and hence it is degraded by peptidases in the gut.
Case Scenario 11:
A 32 year old woman underwent segmental mastectomy for breast tumour of 3cm
diameter with two lymphnode involvement. She was started on 5FU, Adriamycin,
Cyclophosphamide & Vincristine (FACV), six cycles one month apart. She also received
Tamoxifen.

Question & Answer:

1. Write the mechanism of action of 5FU?
The metabolite of 5FU – 5DUMP forms covalent bond with thymidilate synthase & N-
methylene tetrahydrofolate. This inhibits synthesis of thymine & produces thymine
deficient death of cells.

2. Which drug produces haemorrhagic cystitis?

Cyclophosphomide.

3. Name the rescue for this complication.

MESNA- Mercapto Ethane Sulfonate Na (Sodium)

4. Which drug produces cardiotoxicity?

Doxorubicin

5. Name the rescue for cardiotoxicity.

Dexrazoxane - inhibits free radical formation &protects heart.

6. Mention two criteria for using tamoxifen?

Tumor cells should be HR positive
Post menopausal women

7. What is the purpose of giving tamoxifen?

To prevent spread of cancer to contralateral side.

8. Which drug is given for tamoxifen resistant cases ?

Fulvestrant

9. What are the adverse effects of Vincristine?

Nephrotoxicity, Peripheral neuropathy.

10. Name two drugs used for cancer chemotherapy induced vomiting.
5HT3 ANTAGONIST - Ondansetron, Granisetron,
CANNABINOIDS - Dronabinol.
Case Scenario 12:
A 25 year old married woman with a history of two months amenorrhoea came with the
complaints of vomiting and giddiness. Urine gravindex test was positive.

Question & Answer:

1. What is the drug of choice for this patient?
Doxylamine with Pyridoxine.

2. What is the mechanism of action of Domperidone?

It blocks the D2 receptor at Chemoreceptor Trigger Zone and Nucleus Tractus Solitarius.

3. Enumerate four prokinetic agents?

Metoclopromide, Cisapride, Mosapride, Tegaserod.

4. What is the drug of choice for radiotherapy induced vomiting?

Ondensetron, Granisetron, Metoclopramide, corticosteroids

5. What are the types of drugs used for motion sickness? Give one example for each.
a. Anticholinergic - Hyoscine
b. Antihistaminics - Cinnarazine

6. Enumerate the drugs used as broad spectrum antiemetics used in resistant cases?
Prochlorperazine, Chloropromazine and Haloperidol

7. What are the clinical uses of metoclopramide?

Used as anti emetic and as a prokinetic in gastro esophageal reflux disease

8. Why Metaclopramide is preferred over domperidone in levodopa induced vomiting ?

Only Metaclopramide has central D 2 blocking actions & domperidone crosses brain
poorly

9. What are all the contraindications for emesis in a poisoned patient?

CNS stimulant poisoning
Corrosive poisoning,
Kerosene poisoning,
Unconscious patient,
Morphine poisoning

10. Name the NK1 receptor antagonist used as anti emetic in chemotherapy induced
vomiting ?
Aprepitant