FMGE 2023 - Pharmacology Practice Questions

Q: A 29-year-old male patient presents to the OPD with a 10-year history of coarse facial features and progressive enlargement of the hands and feet. Laboratory evaluation revealed elevated IGF-1 and non-suppressible growth hormone levels after the 75 g glucose challenge test. A diagnosis of acromegaly is made. Which of the following drugs is preferred for the management of this patient?

Lanreotide depot formulation. ***Lanreotide depot formulation***- This is a long-acting **somatostatin analog (SSA)** that binds to somatostatin receptors on the pituitary adenoma, effectively inhibiting the secretion of **growth hormone (GH)**.- SSAs, including lanreotide and **octreotide**, are considered the first-line medical therapy for acromegaly, especially when surgery fails or is contraindicated, as they control both GH and **IGF-1** levels.*Terlipressin*- *Terlipressin* is primarily used for the treatment of **bleeding esophageal varices** in patients with portal hypertension, as it acts as a **vasopressin analog** causing splanchnic vasoconstriction.- It has no therapeutic role in controlling sustained GH hypersecretion or managing the pituitary tumor responsible for **acromegaly**.*Ketoconazole*- *Ketoconazole* is primarily an **antifungal agent** but is occasionally used to inhibit **steroid biosynthesis** in conditions like **Cushing's syndrome** due to its effect on P450 enzymes.- It does not affect the production or secretion of **growth hormone** from the somatotropes and is therefore ineffective in treating **acromegaly**.*Leuprolide*- *Leuprolide* is a **Gonadotropin-Releasing Hormone (GnRH) agonist** used for conditions responsive to chemical castration, such as **prostate cancer** or **endometriosis**.- This agent targets the hypothalamic-pituitary-gonadal axis, having no clinical utility in directly suppressing the hypersecretion of **GH** in **acromegaly**.

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 male patient complained of imbalance, numbness of the foot, and muscle weakness. On history taking, he revealed that he has been taking multivitamin tablets more than the prescribed dose for 1 year. Which of the following is the most likely cause of the associated symptoms seen in this patient?

Vitamin B6 toxicity. ***Vitamin B6 toxicity*** - Chronic ingestion of high-dose **pyridoxine** (Vitamin B6) is a well-known cause of **sensory polyneuropathy**, which manifests as numbness (paresthesia) and gait imbalance (**ataxia**). - The toxicity primarily targets the sensory neurons of the **dorsal root ganglia**, leading to the observed sensory and motor deficits (muscle weakness). *Vitamin D toxicity* - This condition primarily causes **hypercalcemia**, leading to symptoms such as nausea, vomiting, confusion, and generalized weakness, often affecting renal function. - It is not typically associated with a chronic, distal, sensory-dominant **peripheral neuropathy** causing numbness and foot imbalance. *Vitamin C toxicity* - Vitamin C (ascorbic acid) is generally safe; high doses typically result in mild symptoms like gastrointestinal distress and an increased risk of developing **calcium oxalate kidney stones**. - It does **not** cause neurotoxic effects such as peripheral neuropathy or chronic ataxia. *Vitamin A toxicity* - Chronic hypervitaminosis A involves symptoms such as **hepatotoxicity**, dry skin/cheilitis, **bone and joint pain**, and pseudo-tumor cerebri (increased intracranial pressure). - While neurological symptoms like headache may occur due to increased pressure, clear-cut **sensory polyneuropathy and ataxia** are not characteristic features.

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: A female patient complains of swelling and pain in her great toe. Her uric acid level is found to be high. A drug that reduces uric acid levels is prescribed. Which of the following enzymes should the drug inhibit?

Xanthine oxidase. ***Xanthine oxidase*** - **Xanthine oxidase** catalyzes the conversion of hypoxanthine to xanthine and xanthine to uric acid in the purine degradation pathway - **Xanthine oxidase inhibitors** (allopurinol, febuxostat) are the mainstay drugs for chronic management of hyperuricemia and gout - By inhibiting this enzyme, these drugs reduce uric acid production, lowering serum uric acid levels and preventing crystal deposition in joints - The clinical presentation of **podagra** (acute pain and swelling of the great toe) with elevated uric acid is classic for **acute gouty arthritis** *Lysyl oxidase* - Involved in cross-linking collagen and elastin in connective tissue formation - Not related to purine metabolism or uric acid synthesis - Inhibition would affect collagen strength, not uric acid levels *Homogentisate oxidase* - Enzyme in the tyrosine degradation pathway - Deficiency causes alkaptonuria (accumulation of homogentisic acid) - Not involved in purine metabolism *Urease* - Bacterial enzyme that hydrolyzes urea to ammonia and carbon dioxide - Found in bacteria like *Helicobacter pylori* and *Proteus* species - Not involved in human uric acid synthesis or metabolism

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

A 29-year-old male patient presents to the OPD with a 10-year history of coarse facial features and progressive enlargement of the hands and feet. Laboratory evaluation revealed elevated IGF-1 and non-suppressible growth hormone levels after the 75 g glucose challenge test. A diagnosis of acromegaly is made. Which of the following drugs is preferred for the management of this patient?

Accepted Answer

Lanreotide depot formulation

Answer

Leuprolide

Answer

Ketoconazole

Answer

Terlipressin

Question 2

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 3

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 4

A male patient complained of imbalance, numbness of the foot, and muscle weakness. On history taking, he revealed that he has been taking multivitamin tablets more than the prescribed dose for 1 year. Which of the following is the most likely cause of the associated symptoms seen in this patient?

Accepted Answer

Vitamin B6 toxicity

Answer

Vitamin D toxicity

Answer

Vitamin C toxicity

Answer

Vitamin A toxicity

Question 5

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

Accepted Answer

Aliskiren

Answer

Losartan

Answer

Spironolactone

Answer

Captopril

Question 6

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 7

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 8

A female patient complains of swelling and pain in her great toe. Her uric acid level is found to be high. A drug that reduces uric acid levels is prescribed. Which of the following enzymes should the drug inhibit?

Accepted Answer

Xanthine oxidase

Answer

Lysyl oxidase

Answer

Homogentisate oxidase

Answer

Urease

Question 9

Which of the following drugs increases uric acid in urine?

Accepted Answer

Probenecid

Answer

Allopurinol

Answer

Colchicine

Answer

Febuxostat

Question 10

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