Following analgesic inhibits COX-3 enzyme (A)Aspirin (B) Paracetamol (C)Celecoxib (D)Indomethacin
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COX-3 enzyme inhibitor paracetamol acetaminophen mechanism
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Answer: (B) Paracetamol
Paracetamol (acetaminophen) is the analgesic classically associated with COX-3 inhibition.
Explanation
| Drug | Primary COX target | Clinical note |
|---|---|---|
| Aspirin | COX-1 (irreversible) > COX-2 | Non-selective; antiplatelet at low doses |
| Paracetamol | COX-3 (proposed) | Analgesic + antipyretic; negligible anti-inflammatory effect |
| Celecoxib | Selective COX-2 | NSAID used in arthritis; spares COX-1 |
| Indomethacin | COX-1 and COX-2 (non-selective) | Potent anti-inflammatory NSAID |
Key facts about COX-3
- COX-3 (also called COX-1b or COX-1 variant) is a splice variant of COX-1, predominantly expressed in the CNS (cerebral cortex) and heart.
- Paracetamol selectively inhibits this central isoform, which explains its analgesic and antipyretic effects without significant peripheral anti-inflammatory activity (since COX-3 is mostly central, not peripheral).
- This also accounts for why paracetamol does NOT inhibit platelet aggregation or cause gastric irritation - it does not significantly inhibit peripheral COX-1 or COX-2.
- The COX-3 hypothesis was first proposed by Chandrasekharan et al. (2002), and while the exact mechanism is still debated, COX-3 inhibition remains the most cited pharmacological explanation for paracetamol's action in exam contexts.
Why the other options are wrong
- Aspirin - irreversibly acetylates and inhibits COX-1 (and COX-2 at higher doses), not COX-3.
- Celecoxib - selective COX-2 inhibitor, used to reduce GI side effects compared to non-selective NSAIDs.
- Indomethacin - one of the most potent non-selective COX-1/COX-2 inhibitors; used for gout and closing patent ductus arteriosus.
The correct answer is (B) Paracetamol.
15 In the treatment of hypertension the beta adrenergic blockers have the following advantage: (A)They Have Minimal Effect On Work Capacity, Sleep Quality And Libido (B) Used Alone, They Have High Ceiling Antihypertensive Efficacy (C)They Do Not Cause Postural Hypotension (D) They Can Be Used In Combination With Any Other Antihypertensive Drug
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beta adrenergic blockers hypertension advantages no postural hypotension pharmacology
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Answer: (C) They Do Not Cause Postural Hypotension
This is a well-established advantage of beta-blockers over other antihypertensive drug classes, particularly alpha-blockers and vasodilators.
Analysis of Each Option
(A) They Have Minimal Effect On Work Capacity, Sleep Quality And Libido - INCORRECT
Beta-blockers are actually known to cause several side effects:
- Reduced exercise tolerance / work capacity - by blocking beta-2 receptors in skeletal muscle vasculature and reducing cardiac output during exertion
- Sleep disturbances / nightmares - especially lipophilic ones like propranolol that cross the blood-brain barrier
- Sexual dysfunction / reduced libido - a recognised and clinically significant side effect
- These adverse effects are reasons why beta-blockers are often poorly tolerated
(B) Used Alone, They Have High Ceiling Antihypertensive Efficacy - INCORRECT
Beta-blockers actually have a low ceiling effect as antihypertensives when used as monotherapy. Beyond a certain dose, further increases do not produce proportionally greater BP reduction. They are more effective when combined with other agents (e.g., a diuretic). This is in contrast to drugs like ACE inhibitors and ARBs.
(C) They Do Not Cause Postural Hypotension - CORRECT
This is the key advantage. Beta-blockers lower blood pressure primarily by:
- Reducing heart rate and cardiac output
- Decreasing renin release (beta-1 blockade on juxtaglomerular cells)
Because they do NOT block alpha-1 receptors (which mediate peripheral vascular resistance), they do not impair the normal sympathetic venoconstriction response to standing. Therefore, they do not cause postural (orthostatic) hypotension - unlike:
- Alpha-blockers (e.g., prazosin)
- Vasodilators (e.g., hydralazine)
- Centrally acting agents (e.g., methyldopa)
This makes beta-blockers particularly safe for elderly patients who are at risk of falls from postural hypotension.
(D) They Can Be Used In Combination With Any Other Antihypertensive Drug - INCORRECT
Beta-blockers have important contraindicated combinations:
- Verapamil or diltiazem (non-dihydropyridine calcium channel blockers) - combining these with beta-blockers can cause severe bradycardia, heart block, or cardiac arrest, as both depress SA/AV nodal conduction
- They also must be used cautiously with other drugs that depress cardiac conduction
So they definitely cannot be used with "any" other antihypertensive drug.
Summary Table
| Option | Statement | Verdict |
|---|---|---|
| A | Minimal effect on work capacity, sleep, libido | False - beta-blockers worsen all three |
| B | High ceiling antihypertensive efficacy alone | False - low ceiling effect |
| C | Do not cause postural hypotension | TRUE - correct answer |
| D | Can combine with any antihypertensive | False - contraindicated with verapamil/diltiazem |
The correct answer is (C).
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