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Explain the questions

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aspirin AND platelet

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NSAID COX-2 inhibitors furosemide first pass metabolism oral contraceptive official pharmacology references

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1(c) Which one is not an example of an NSAID?

Options: Aceclofenac, Paracetamol, Diclofenac, Ranitine.
  • Aceclofenac and diclofenac are NSAIDs.
  • Paracetamol is mainly an analgesic and antipyretic. It has very weak anti-inflammatory action, so it is usually not classified as a conventional NSAID.
  • Ranitidine is an H2-receptor blocker used to reduce gastric acid. It is definitely not an NSAID.
Note: This MCQ is poorly framed because both paracetamol and ranitidine can be considered “not NSAIDs.” If the examiner expects one clearly unrelated drug, the intended answer is most likely (iv) Ranitine/ranitidine. Ranitidine has also been withdrawn or restricted in many countries because of NDMA impurity concerns.

1(d) Etoricoxib is a/an

Correct answer: (i) Selective COX-2 inhibitor
Etoricoxib is a selective cyclooxygenase-2 inhibitor, also called a coxib. It is an NSAID used for pain and inflammation, for example in osteoarthritis, rheumatoid arthritis, and acute gout.
  • It inhibits COX-2, reducing prostaglandin production and therefore pain and inflammation.
  • It is not an ACE inhibitor, antiemetic, or laxative.
  • COX-2 selective drugs tend to cause less gastric ulceration than nonselective NSAIDs, but can increase cardiovascular and blood-pressure risks in susceptible people.
Rheumatology, 2-Volume Set, p. 2022 edition section on NSAIDs identifies etoricoxib as a COX-2 selective inhibitor.

1(e) Furosemide is an example of

Correct answer: (i) High-ceiling diuretic
Furosemide is a loop diuretic, also called a high-ceiling diuretic because it can produce a powerful diuretic response.
  • It acts in the thick ascending limb of the loop of Henle.
  • It inhibits the Na⁺-K⁺-2Cl⁻ cotransporter.
  • It increases excretion of sodium, chloride, water, potassium, calcium, and magnesium.
  • Main uses: acute pulmonary edema, edema due to heart failure, liver disease or renal disease, and sometimes hypertension.
  • Important adverse effects: dehydration, hypotension, hypokalemia, metabolic alkalosis, hyperuricemia, and ototoxicity.
It is not an osmotic diuretic, potassium-sparing diuretic, or steroid.
Goodman & Gilman’s The Pharmacological Basis of Therapeutics, chapter on loop/high-ceiling diuretics.

2. Short notes: What to write

These are 3-mark short notes, so write definition, mechanism, main uses/importance, and one or two key adverse effects or precautions.

2(a) First-pass metabolism and its clinical importance

Definition:
First-pass metabolism, also called presystemic metabolism, is metabolism of a drug in the intestinal wall and liver before it reaches the systemic circulation after oral administration.
Pathway:
Oral drug → intestine → portal vein → liver → systemic circulation.
Effect:
It reduces the amount of unchanged active drug reaching the blood. Hence, it decreases oral bioavailability.
Examples:
Nitroglycerin, propranolol, lidocaine, morphine, and verapamil undergo significant first-pass metabolism.
Clinical importance:
  1. A larger oral dose may be required compared with IV dose.
  2. Some drugs are not useful orally because too little active drug reaches systemic circulation.
  3. Alternative routes can bypass it: sublingual, transdermal, rectal partly, inhalational, and parenteral routes.
  4. Example: nitroglycerin is given sublingually or transdermally because most oral nitroglycerin is metabolized during first pass.
  5. Liver disease or reduced hepatic blood flow can reduce first-pass metabolism, increasing drug availability and toxicity risk.
Lippincott Illustrated Reviews: Pharmacology, p. 41.

2(b) Aspirin as an antiplatelet drug

Mechanism:
  • Low-dose aspirin irreversibly acetylates and inhibits platelet COX-1.
  • This inhibits synthesis of thromboxane A2 (TXA2).
  • TXA2 normally causes platelet aggregation and vasoconstriction.
  • Platelets cannot synthesize new COX enzyme, so the effect persists for the platelet life span, about 7 to 10 days.
Uses:
  • Secondary prevention after myocardial infarction.
  • Unstable angina and acute coronary syndrome.
  • Prevention of ischemic stroke and transient ischemic attack.
  • After coronary stenting, usually combined with another antiplatelet drug for a specified period.
Usual antiplatelet dose:
Commonly low-dose aspirin, such as 75-150 mg once daily, depending on the clinical indication and local protocol.
Adverse effects:
  • Gastritis, peptic ulcer, and gastrointestinal bleeding.
  • Increased bleeding tendency.
  • Hypersensitivity or bronchospasm in aspirin-sensitive asthma.
  • Avoid routine use in children with viral illness because of Reye syndrome.
Quick Compendium of Clinical Pathology, section 5.6.2.1, Aspirin.

2(c) Oral contraceptive pill

Definition:
Oral contraceptive pills are hormonal tablets used to prevent pregnancy.
Types:
  1. Combined oral contraceptive pills (COCs): estrogen plus progestin.
  2. Progestin-only pills: contain only progestin.
Examples:
Ethinyl estradiol with levonorgestrel, norethisterone, desogestrel, or drospirenone.
Mechanism of action:
  1. Suppress FSH and LH release, thereby preventing ovulation.
  2. Progestin thickens cervical mucus, making sperm entry difficult.
  3. Produces endometrial changes that reduce implantation likelihood.
  4. Alters tubal motility.
Benefits/uses besides contraception:
  • Regularizes menstrual cycles.
  • Reduces dysmenorrhea and menorrhagia.
  • Helps acne and symptoms of polycystic ovarian syndrome.
  • Reduces risk of ovarian and endometrial cancer.
Adverse effects:
  • Nausea, breast tenderness, headache, and breakthrough bleeding.
  • May raise blood pressure.
  • Combined pills can increase the risk of venous thromboembolism.
Important contraindications for combined pills:
  • Pregnancy.
  • History of thromboembolism or stroke.
  • Migraine with aura.
  • Severe hypertension.
  • Active liver disease.
  • Smoker aged over 35 years.
  • Current breast cancer.
Drug interaction:
Enzyme-inducing drugs such as phenytoin, carbamazepine, phenobarbital, and rifampicin can reduce pill effectiveness. Use an additional contraceptive method.
Goldman-Cecil Medicine, Oral Contraceptives section, p. 2576.
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Answer the questions

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organophosphate poisoning AND atropine

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asthma AND glucocorticoids

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proton pump inhibitors AND sucralfate

Searching the Web

WHO organophosphorus poisoning atropine pralidoxime management guidance

3. Organophosphorus poisoning

The farmer has organophosphorus insecticide poisoning, producing a cholinergic crisis due to acetylcholinesterase inhibition.

(a) Name three organophosphorus compounds

  1. Parathion
  2. Malathion
  3. Chlorpyrifos
Other examples: diazinon, dichlorvos, monocrotophos.

(b) Drugs used in treatment

  1. Atropine - main antidote for muscarinic manifestations.
  2. Pralidoxime (2-PAM) - reactivates acetylcholinesterase if given early, before enzyme “aging.”
  3. Diazepam - for seizures, agitation, and may help control central nervous system manifestations.
Supportive treatment is equally important:
  • Remove contaminated clothing and wash skin.
  • Maintain airway, suction secretions, give oxygen.
  • Intubation and ventilatory support if respiratory failure occurs.
  • IV fluids and monitoring.

(c) Role of atropine in organophosphorus poisoning

  • Organophosphates inhibit acetylcholinesterase, causing accumulation of acetylcholine.
  • Atropine competitively blocks muscarinic receptors. It reverses muscarinic features such as:
    • Excess salivation and lacrimation
    • Bronchorrhea and bronchospasm
    • Bradycardia
    • Sweating
    • Vomiting, diarrhoea, abdominal cramps
    • Miosis
Important point: Atropine does not reverse nicotinic manifestations such as muscle fasciculations, weakness, or paralysis. These improve with pralidoxime and respiratory support.
Atropine is given repeatedly and titrated until chest secretions are dry and air entry improves. Pupil size alone is not a reliable end point.

4. Bronchodilators, glucocorticoids in asthma, and beta-blockers

(a) Name three bronchodilators

  1. Salbutamol - short-acting beta-2 agonist
  2. Ipratropium bromide - antimuscarinic bronchodilator
  3. Theophylline - methylxanthine bronchodilator
Other acceptable examples: terbutaline, formoterol, salmeterol, tiotropium.

(b) Mechanism of glucocorticoids in bronchial asthma

Examples: beclomethasone, budesonide, fluticasone, prednisolone, hydrocortisone.
Glucocorticoids are mainly anti-inflammatory drugs, not immediate bronchodilators.
They:
  1. Bind to intracellular glucocorticoid receptors and alter gene transcription.
  2. Decrease inflammatory cytokines, eosinophils, mast cells, and airway edema.
  3. Inhibit phospholipase A2 via lipocortin formation, reducing prostaglandins and leukotrienes.
  4. Reduce mucus secretion and airway hyperresponsiveness.
  5. Increase beta-2 receptor responsiveness, improving the effect of beta-2 agonists.
  6. Reduce frequency and severity of asthma exacerbations.
Key point: Inhaled corticosteroids are used for long-term asthma control. Systemic steroids are used in severe acute attacks.

(c) Why are non-selective beta-blockers contraindicated in bronchial asthma?

Non-selective beta-blockers, such as propranolol, block both beta-1 and beta-2 receptors.
  • Blockade of bronchial beta-2 receptors causes bronchoconstriction/bronchospasm.
  • They may precipitate a severe asthma attack.
  • They also reduce the bronchodilator response to salbutamol and other beta-2 agonists.
Therefore, non-selective beta-blockers are contraindicated in bronchial asthma. Even beta-1 selective blockers should be used cautiously in an asthmatic patient.

5. Proton pump inhibitors and sucralfate

(a) Name three proton pump inhibitors

  1. Omeprazole
  2. Pantoprazole
  3. Esomeprazole
Other examples: lansoprazole, rabeprazole, dexlansoprazole.

(b) Mechanism of action of PPIs

PPIs are prodrugs that are activated in the acidic secretory canaliculi of gastric parietal cells.
They:
  1. Irreversibly inhibit the H⁺/K⁺ ATPase proton pump in parietal cells.
  2. Block the final step of gastric acid secretion.
  3. Suppress both basal and meal-stimulated gastric acid secretion.
  4. Produce marked and prolonged reduction of gastric acidity until new proton pumps are synthesized.
They are commonly used in peptic ulcer disease, GERD, Zollinger-Ellison syndrome, and prevention of NSAID-induced ulcers.

(c) Why should antacids not be given with sucralfate?

Sucralfate needs an acidic gastric environment to polymerize and form a protective viscous barrier over an ulcer.
Antacids increase gastric pH. Therefore, if given together, they:
  • Reduce the activation and polymerization of sucralfate.
  • Decrease formation of the protective ulcer coating.
  • Reduce the therapeutic effect of sucralfate.
Hence, antacids should be avoided with sucralfate or separated by at least 30 minutes.
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