FMGE 2023 - Pharmacology Practice Questions

Q: Which of the following is a first-line antitubercular drug prescribed in the initial 2 months of treatment?

Ethambutol. **Ethambutol** - **Ethambutol (E)** is a crucial component of the standard **four-drug regimen (RIPE)** used during the intensive initial phase (first 2 months) of active TB treatment. - Its primary function is to prevent emerging **rifampicin** or **isoniazid resistance**, although its main adverse effect is dose-related **optic neuritis**. *Streptomycin* - Streptomycin is an **aminoglycoside** and was historically used, but it is currently classified as a **second-line injectable agent** due to its toxicity and need for parenteral administration. - It is typically reserved for treating **multidrug-resistant TB (MDR-TB)** or in situations where oral first-line drugs cannot be used. *Linezolid* - Linezolid is an **oxazolidinone** antibiotic primarily reserved for treating highly resistant forms of TB, specifically **MDR-TB** or **XDR-TB**. - It is not included in the standard first-line regimen due to concerns regarding side effects like **myelosuppression** and **peripheral neuropathy**. *Levofloxacin* - Levofloxacin is a **fluoroquinolone** antibiotic, which is classified as a **second-line antitubercular agent**. - It is generally used in alternative regimens or for treating **drug-resistant TB** when standard first-line drugs are ineffective or contraindicated.

Q: What is the mechanism of action of dicumarol?

Inhibits vitamin K dependant Clotting factors. Inhibits vitamin K dependant Clotting factors- Dicumarol, a classic anticoagulant, acts as a **vitamin K antagonist** (VKA), preventing the utilization of vitamin K [1].- It inhibits the enzyme **vitamin K epoxide reductase**, which is essential for the activation (**gamma-carboxylation**) of factors II (prothrombin), VII, IX, and X [4]. *Activates antithrombin III.*- This mechanism is characteristic of **unfractionated heparin** and **low molecular weight heparins** (LMWH).- Heparin binds to **antithrombin III** (ATIII), greatly accelerating its ability to neutralize activated clotting factors, particularly Thrombin (IIa) and Factor Xa [2]. *Inhibits tissue plasminogen activator*- Dicumarol affects the synthesis of clotting factors and has no direct influence on the **fibrinolytic system** (clot breakdown).- Inhibition of **tissue plasminogen activator** (tPA) or plasmin is the role of anti-fibrinolytic drugs like **tranexamic acid**. *Inhibitor of factor Xa*- This is the specific mechanism utilized by the direct oral anticoagulants (DOACs), such as **rivaroxaban** and **apixaban** (referred to as 'xabans') [3].- While dicumarol ultimately reduces active **Factor X** levels, it acts indirectly by preventing its synthesis/activation, not by directly binding to and inhibiting the already formed Factor Xa.

Q: A patient with a history of hypertension is given the drug 'X'. Identify 'X'?

Aliskiren. ***Aliskiren*** - Aliskiren is a **direct renin inhibitor**. The diagram shows that drug 'X' directly inhibits the release or action of **renin** from the kidneys. - By inhibiting renin, it blocks the first and rate-limiting step of the **Renin-Angiotensin-Aldosterone System (RAAS)**, preventing the conversion of **angiotensinogen** to **angiotensin I**. *Captopril* - Captopril is an **Angiotensin-Converting Enzyme (ACE) inhibitor**. It acts later in the pathway to block the conversion of **angiotensin I** to **angiotensin II**. - This mechanism is different from drug 'X', which acts on **renin** at the beginning of the cascade. *Spironolactone* - Spironolactone is an **aldosterone antagonist** and a potassium-sparing diuretic. It acts at the end of the RAAS pathway. - It works by blocking **aldosterone receptors** in the distal tubules of the kidney, preventing sodium and water reabsorption, which is downstream from the action of renin. *Losartan* - Losartan is an **Angiotensin II Receptor Blocker (ARB)**. It prevents **angiotensin II** from binding to its receptors on blood vessels and the adrenal glands. - This action occurs much later in the pathway compared to the direct inhibition of **renin** shown by drug 'X'.

Q: Which statement best describes the relationship between drug potency and efficacy in dose-response curves?

Drug B is the most efficacious. ***Drug B is the most efficacious*** - **Efficacy** refers to the **maximum effect (Emax)** a drug can produce, represented by the plateau height of the dose-response curve on the y-axis - **Drug B's curve reaches the highest point**, indicating it produces the greatest maximal blocking effect (~100 units) - **This makes Drug B the most efficacious drug** among the three, as it can produce the largest therapeutic response regardless of how much drug is given - Efficacy order: Drug B > Drug C > Drug D *Drug C is the most potent* - **Potency** refers to the amount of drug needed to produce a given effect, measured by **EC50** (the concentration producing 50% of maximal effect) - **The lower the EC50, the more potent the drug** (curve shifted to the left) - **Drug B has the lowest EC50** (its curve is furthest to the left), making it the most potent drug, not Drug C - Drug C requires a higher concentration than Drug B to achieve 50% effect, so it is less potent - Potency order: Drug B > Drug C > Drug D *Drug C is as efficacious as drug D* - **Drug C has higher efficacy than Drug D** because its curve reaches a higher plateau on the y-axis - Drug C achieves a maximal blocking effect of approximately 100 units, while Drug D reaches only approximately 75 units - **Different efficacy values** mean they are not equally efficacious - A drug's efficacy is independent of the dose required and depends only on the maximum achievable effect *Drug D is more potent than drug C* - **Drug C is actually more potent than Drug D**, not the reverse - Drug C's dose-response curve is **shifted to the left** of Drug D's curve, indicating a lower EC50 - This means **Drug C requires a lower concentration** to achieve 50% of its maximal effect compared to Drug D - The leftward shift indicates greater potency for Drug C

Q: Which drug elicits the following response on blood pressure and heart rate, as shown in the image?

Norepinephrine. ***Norepinephrine*** - Norepinephrine is a potent agonist at **α1** and **β1** receptors with minimal **β2** activity. The strong **α1** stimulation causes intense vasoconstriction, leading to a marked increase in systolic, diastolic, and mean arterial pressure, as seen in the graph. - Although norepinephrine directly stimulates the heart via **β1** receptors, the significant rise in blood pressure activates the **baroreceptor reflex**. This reflex increases vagal tone, which overrides the direct chronotropic effect and results in a net decrease in heart rate (reflex bradycardia). *Isoproterenol* - Isoproterenol is a non-selective **β-agonist** (**β1** and **β2**) and lacks **α-agonist** effects. It would cause a significant increase in heart rate (**β1** effect). - Its potent **β2** receptor stimulation leads to vasodilation and a *decrease* in diastolic and mean arterial pressure, which is the opposite of the response shown. *Epinephrine* - Epinephrine stimulates **α1**, **β1**, and **β2** receptors. At typical doses, the direct **β1** effect increases the heart rate, and the **β2** effect partially counteracts **α1**-mediated vasoconstriction, leading to a smaller rise in diastolic pressure. - The pronounced reflex bradycardia and significant increase in both systolic and diastolic pressure are more characteristic of norepinephrine's lack of **β2** agonism. *Dopamine* - Dopamine's effects are dose-dependent. At pressor doses (high doses) that stimulate **α1** receptors to increase blood pressure, there is also significant **β1** receptor stimulation. - The concurrent **β1** stimulation typically causes tachycardia or prevents significant reflex bradycardia, which is inconsistent with the graph showing a decreased heart rate.

Q: Which of the following drugs increases uric acid in urine?

Probenecid. ***Probenecid***- This drug is a **uricosuric agent** that works by inhibiting the reabsorption of urate at the **proximal convoluted tubule** of the kidney.- By blocking reabsorption, **probenecid** promotes the excretion of uric acid into the urine, thereby reducing serum uric acid levels.*Colchicine*- *Colchicine* is primarily used for the management of **acute gout flares** and works by inhibiting neutrophil migration and subsequent inflammatory responses.- It does **not** significantly alter the renal handling of uric acid; therefore, it does not increase uric acid excretion in the urine.*Febuxostat*- *Febuxostat* is a **non-purine selective inhibitor of xanthine oxidase**, an enzyme required for uric acid synthesis.- Its mechanism is to **decrease the production** of uric acid by the body, thus lowering serum levels, rather than promoting its excretion in the urine.*Allopurinol*- *Allopurinol* is a **purine analog and a xanthine oxidase inhibitor** used for the prophylactic management of chronic gout.- Like Febuxostat, it acts to **decrease the synthesis** (production) of uric acid, contrasting with uricosuric agents which increase excretion.

Question 1

Which of the following is a first-line antitubercular drug prescribed in the initial 2 months of treatment?

Accepted Answer

Ethambutol

Answer

Streptomycin

Answer

Linezolid

Answer

Levofloxacin

Question 2

What is the mechanism of action of dicumarol?

Accepted Answer

Inhibits vitamin K dependant Clotting factors

Answer

Inhibitor of factor Xa

Answer

Activates antithrombin III.

Answer

Inhibits tissue plasminogen activator

Question 3

A patient with a history of hypertension is given the drug 'X'. Identify 'X'?

Accepted Answer

Aliskiren

Answer

Losartan

Answer

Spironolactone

Answer

Captopril

Question 4

Which statement best describes the relationship between drug potency and efficacy in dose-response curves?

Accepted Answer

Drug B is the most efficacious

Answer

Drug C is as efficacious as drug D

Answer

Drug D is more potent than drug C

Answer

Drug C is the most potent

Question 5

Which drug elicits the following response on blood pressure and heart rate, as shown in the image?

Accepted Answer

Norepinephrine

Answer

Epinephrine

Answer

Dopamine

Answer

Isoproterenol

Question 6

Which of the following drugs increases uric acid in urine?

Accepted Answer

Probenecid

Answer

Allopurinol

Answer

Colchicine

Answer

Febuxostat

Question 7

The most appropriate description of the vasomotor reversal of Dale is that

Accepted Answer

A patient pretreated with phentolamine develops severe hypotension on the administration of adrenaline

Answer

Repeated administration of ephedrine decreases its effect on blood pressure

Answer

An increase in pulse pressure is produced by the intravenous administration of isoprenaline

Answer

High dose of acetylcholine after alpha blockade produces vasomotor reversal

FMGE 2023 — Pharmacology