Therapy

THERAPEUTICS
Dr. Sukant Sen

MD,PCR,PGDPHM Asst. Professor
An 18-year-old man is brought into the emergency department after being found on the street unresponsive. He is lethargic and does not answer questions. He has been given 1 ampule of Dextrose intravenously without result. On examination, his heart rate is 60 beats per minute, and respiratory rate is 8 per minute and shallow. His pupils are pinpoint and not reactive. There are multiple intravenous track marks on his arms bilaterally. The emergency physician concludes that the patient has had a drug overdose. What is the most likely diagnosis? What is the most appropriate medication to be given? After he is given the medication to reverse the overdose, what symptoms may he have?
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Summary: An 18-year-old unresponsive man presents with

pinpoint pupils, shallow respirations, and multiple intravenous track marks on his arms bilaterally.
Most likely diagnosis: Opioid overdose, likely heroin. Most appropriate medication to be given: Naloxone. After reversal of the overdose, what symptoms may he
have?Withdrawal symptoms may include lacrimation, rhinorrhea, sweating, dilated pupils, diarrhea, abdominal cramping, and tremor.
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A 22-year-old
woman is brought in the emergency department via ambulance because of a suicide attempt. Soon after a "night on the town," she called her boyfriend saying that she took a handful of sleeping tablets. On examination, she appears lethargic, but groans and moves all her extremities to painful stimuli. Her blood pressure is 110/70 mmHg, heart rate is 80 bpm, and oxygen saturation is 99 percent. Her pupils are of normal size and reactive to light. Her deep tendon reflexes are normal bilaterally. In the field, she was given an intravenous bolus of dextrose and an ampule of naloxone without response. Her boyfriend, with whom she had an argument, brings in the bottle of sleeping 4 medication which reads "lorazepam."
Summary: A 22-year-old
woman is brought to the
emergency department because of an suicide attempt overdose with lorazepam. She is hemodynamically stable, has no focal neurological deficits, but is lethargic.
Intravenous dextrose and naloxone have been given without response.

Danger
of an overdose with this class of medication:
Lorazepam is a benzodiazepine that belongs to a class of agents known as sedative-hypnotics that can depress the
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activity of the central nervous system (CNS).
Cellular mechanism of action of lorazepam: Binds to a

distinct benzodiazepine receptor site on the g-aminobutyric acid (GABA) receptor-chloride channel complex to allosterically increase the affinity and frequency of GABA interactions with
neuronal GABA-A receptors.
Pharmacological agent used to treat benzodiazepine overdose and its mechanism of action: Flumazenil is a
competitive antagonist at benzodiazepine receptors. It is used
clinically to reverse the symptoms of benzodiazepine overdose.

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A 35-year-old man is in the surgical holding area being evaluated prior to a scheduled hernia repair. He asks the anesthesiologist about the type of "anesthetic gas" to be used, because he recalls that his mother developed severe liver problems from general anesthesia for a hysterectomy performed 2 years previously. The patient asks whether nitrous oxide might be used, because he has heard that it was a safe agent. To allay the patient's anxiety, the anesthesiologist proposes spinal anesthetic for the surgery. What is the probable general anesthetic agent used for the patient's mother? What is the disadvantage of nitrous oxide as an inhalation anesthetic agent?
man is in the surgical holding area being evaluated prior to a scheduled hernia repair. The patients' mother developed severe liver problems from general anesthesia. The patient asks whether nitrous oxide might be used. Probable inhalation anesthetic agent used for the patient's mother: A halogenated agent, such as halothane. Disadvantage of nitrous oxide as an inhalation anesthetic agent: Lack of anesthetic potency requires large amounts to be used as a single agent, associated with postoperative nausea and vomiting.
A 28 yrs male is a known case of epilepsy. He is on antiepileptic drugs since last 2 years. Then he developed
pulmonary tuberculosis for which he is on RHZE (4drug) regimen since last 3 months. Now he developed seizure attack inspite of taking anti-epileptic drug?
1)
What is the cause his epileptic attack?
2) 3) 4)
Discuss if there is any drug interactions. How will you treat the patient? What precautions will you take during prescribing drugs?
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Following his third episode of gouty arthritis, a 50-year-old man sees you in the clinic. Each case was successfully treated acutely; however, your patient is interested in trying to prevent future episodes. He is on no medications regularly and has a normal physical examination today. Blood work reveals an elevated serum uric acid level and otherwise normal renal function and electrolytes. A 24-hour urine collection for uric acid reveals that he is underexcreting uric acid. Suspecting that this is the cause of his recurrent gout, you place him on probenecid. What is the mechanism of action of probenecid?
Which drugs could have their excretion inhibited by probenecid?

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man with recurrent gout is
prescribed probenecid.
Mechanism of action of probenecid:

Inhibits secretion of organic acids and decreases
reabsorption of uric acid, causing a net increase in secretion.
Other drugs whose secretion could be inhibited: Penicillin, indomethacin, and methotrexate.
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A 60-year-old man with hypertension and type II diabetes comes in to the office for a follow-up visit. Along with making appropriate diet and lifestyle changes, he is taking an angiotensin-converting enzyme (ACE) inhibitor-thiazide diuretic combination for his hypertension and metformin for his diabetes. His blood pressure and diabetes are under acceptable control. Routine blood work revealed normal electrolytes, renal function, and liver enzymes. He is noted to have elevated total cholesterol and low-density lipoprotein (LDL) levels, which have remained high in spite of his lifestyle changes. In an effort to reduce his risk of developing coronary artery disease, you start him on a 3-hydroxy-3-methylglutarylcoenzyme A (HMG-CoA) reductase inhibitor.
What is the mechanism of action of HMG-CoA reductase inhibitors? What effect do they have on total and LDL cholesterol levels? 12 What are the common adverse effects of HMG-CoA reductase inhibitors?
Summary: A 60-year-old man has hypertension, diabetes, and hyperlipidemia and is started on an HMG-CoA reductase inhibitor. Mechanism of action of HMG-CoA reductase inhibitors: Competitive inhibition of the rate limiting enzyme in cholesterol biosynthesis, results in compensatory increase in plasma cholesterol uptake in the liver mediated by an increase in the number of LDL receptors. Effect on total cholesterol: Up to 30 percent reduction. Effect on LDL cholesterol: Up to 50 percent reduction. Common adverse events: Elevated liver enzymes and hepatotoxicity, myalgia and myositis, irritability, sleep disturbance, anxiety.
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A 30 year old female patient suffering from acute respiratory infection was given an injection of benzyl penicillin and she immediately collapsed. On the examination, she had bronchospsam, sweating, pulse was very feeble and rapid and blood pressure was very low.
1) 2)
3)
4) 5)
What is your diagnosis in this case? How will you treat the patient? Explain the therapeutic status of adrenaline, dopamine, phenylephrine and promethazine in the treatment of this patients. What are the therapeutic uses of adrenaline? Explain how prazosin and propranolol antagonize 14 the action of adrenaline?
CASE 1
A 12-year-old girl presents to your clinic with a sore throat and fever. You diagnose her with pharyngitis caused by group A hemolytic streptococcus. She is given an IM injection of penicillin. Approximately 5 minutes later, she is found to be in respiratory distress and audibly wheezing. Her skin is mottled and cool, she is tachycardic (rapid heart rate), and her blood pressure has fallen to 70/20 mmHg. You immediately diagnose her as having an anaphylactic reaction to the penicillin and give a subcutaneous injection of epinephrine.
What effect will epinephrine have on this patient's vascular system? Which adrenoceptor primarily mediates the vascular response?
What effect will epinephrine have on her respiratory system? Which adrenoceptor primarily mediates the respiratory system response?
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ANSWERS TO CASE 1: Autonomic Sympathetic Nervous System Summary: A 12-year-old girl with "strep throat" is given an injection of penicillin and develops an acute anaphylactic reaction.
Effect of epinephrine on vascular system: Vasoconstriction. Adrenoceptor which primarily mediates the vascular response: Alpha-1 (1).
Effect of epinephrine on the pulmonary system: Bronchial muscle relaxation. Adrenoceptor which primarily mediates the pulmonary response: Beta-2 (2).
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A healthy 25-year-old man is undergoing a brief surgical procedure requiring general anesthesia. He underwent an unremarkable intubation and induction of anesthesia using IV succinylcholine and inhaled halothane. During the surgery the patient develops muscle rigidity and tachycardia, and his temperature rapidly rises.
What is the mechanism of action of succinylcholine? What reaction is occurring in the patient?
What drug should immediately be given to the patient, and what is its mechanism of action?
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ANSWERS TO CASE : Skeletal Muscle Relaxants
Summary: A 25-year-old man develops muscle rigidity, tachycardia, and high fever during surgery.
Mechanism of action of succinylcholine: Nicotinic receptor agonist at the motor endplate of the neuromuscular junction, which causes persistent stimulation and depolarization of muscle cells.
Reaction that is occurring: Malignant hyperthermia. Malignant hyperthermia is a rare autosomal dominant disorder characterized by tachycardia, muscle rigidity, and high body temperatures that occurs when the patient is exposed to inhaled anesthetics in combination with muscle relaxants, usually succinylcholine. Drug given for treatment and its mechanism of action: Dantrolene, which acts by interfering with calcium release from the sarcoplasmic reticulum.
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For a drug such as piroxicam with a 40-hour halflife and being dosed once daily (i.e., every 24 hours), steady state will be reached shortly following which DOSE (not which half-life)? (A) 1st dose (B) 3rd dose (C) 5th dose (D) 8th dose (E) 12th dose
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D. Approximately five half-lives are required for a drug to
reach steady-state concentrations. Since piroxicam has a halflife of 40 hours, it will require approximately 200 hours before
steady state is reached. If given every 24 hours, shortly after the 8th dose (192 hours at exactly the 8th dose) steady state will be reached.
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A patient of URTI was prescribed Erythromycin 250 mg TDS plus Terfenadine 25 mg BD plud Bromhexine & Dextromethorphan . A few days later he developed faintness with slow and irregular pulse. 1) What adverse reaction has taken place? 2) What is the mechanism of development of such reaction? 3) What will you do to prevent & treat such reaction? 4) Prescribe alternative treatment. 5) What other combination of drugs may cause such reactions.
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A 70 yrs old man has suffering from rheumatoid
arthritis. The symptoms have been well controlled on prednisolone 5 mg daily. He then
develops Tubersulosis and has been treated with

rifampicin and other antitubercular drugs. The signs and symptoms of rhematoid arthritis flare up after 3 weeks. How do you explain it.
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lepromatous patient during the course of
therapy with dapsone suddenly develops fever, exacerbation of the lesions and
appearance of erythematous nodules. What may be the case and what will be the management of the case?
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patient of hypertension and angina was prescribed propranolol 40 mg tds. Within a week his B.P. was controlled but intensity and incidence of anginal attack was increased. 1) What is the cause of increased anginal attack? 2) What measures will you take to check such attacks & control hypertension in such patient? 3) Is there a single drug which can serve both purpose in such patients?
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A young married female was taking oral contraceptive pills(E&P) and she developed pulmonary tuberculosis for which she was prescribed ATT. A few months back she developed ammenorrhea , nausea, vomiting and weight gain. 1) Explain why she develops such symptoms? 2) Describe the mechanism of drug interaction if any taking place? 3) What corrective measure will you take? 4) What precaution should have been taken?
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THERAPEUTICS

Dr. Sukant Sen

Summary: An 18-year-old unresponsive man presents with

woman is brought to the

Intravenous dextrose and naloxone have been given without response.

of an overdose with this class of medication:

activity of the central nervous system (CNS).

Cellular mechanism of action of lorazepam: Binds to a

neuronal GABA-A receptors.

clinically to reverse the symptoms of benzodiazepine overdose.

What is the cause his epileptic attack?

Which drugs could have their excretion inhibited by probenecid?

man with recurrent gout is

Mechanism of action of probenecid:

Inhibits secretion of organic acids and decreases

reabsorption of uric acid, causing a net increase in secretion.

ANSWERS TO CASE : Skeletal Muscle Relaxants

D. Approximately five half-lives are required for a drug to

A 70 yrs old man has suffering from rheumatoid

develops Tubersulosis and has been treated with

lepromatous patient during the course of

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