NEET-PG 2015 — Pharmacology

Q: Adverse effects of phenytoin include the following EXCEPT:

Hypercalcemia. ***Hypercalcemia*** - Phenytoin can actually lead to **hypocalcemia** due to its effect on vitamin D metabolism, increasing its degradation and leading to osteomalacia or rickets [1]. - Therefore, **hypercalcemia** is not an expected adverse effect of phenytoin use. *Lymphadenopathy* - **Generalized lymphadenopathy** is a known, though less common, adverse effect of phenytoin, sometimes mimicking lymphoma. - It's part of a broader hypersensitivity reaction that can occur with the drug. *Ataxia* - **Ataxia** is a common dose-dependent adverse effect of phenytoin, especially at higher therapeutic or toxic levels [1], [2]. - It manifests as impaired coordination and balance due to cerebellar dysfunction [1]. *Hirsutism* - **Hirsutism**, or excessive hair growth, is a well-known chronic side effect of phenytoin [1]. - This effect is more aesthetically concerning than medically dangerous and is particularly common in young women [1]. [Practice more Pharmacology PYQs on OnCourse]

Q: Drug not used in pulmonary hypertension is:

Alpha blocker. ***Alpha blocker*** - Alpha-blockers primarily cause **systemic vasodilation** [1] and are not indicated for the specific pulmonary vascular remodeling and vasoconstriction seen in pulmonary hypertension. [2] - Their use could lead to an undesirable drop in **systemic blood pressure** [3] without adequately addressing the pulmonary arterial pressure. *Calcium channel blocker* - **Calcium channel blockers** (namely **dihydropyridines** like nifedipine and amlodipine) are used in a small subset of pulmonary hypertension patients who are **vasoreactive** on acute testing. - They work by relaxing pulmonary arterial smooth muscle, reducing **pulmonary vascular resistance**. *Endothelin receptor antagonist* - **Endothelin receptor antagonists** (e.g., bosentan, ambrisentan) block the effects of **endothelin-1**, a potent vasoconstrictor and smooth muscle proliferator involved in pulmonary hypertension. - They improve hemodynamics, exercise capacity, and clinical outcomes by preventing **vasoconstriction** and **vascular remodeling**. *Prostacyclin* - **Prostacyclin analogs** (e.g., epoprostenol, treprostinil) are potent **vasodilators** and inhibitors of platelet aggregation. - They are highly effective in treating severe pulmonary hypertension by relaxing pulmonary arteries and preventing **thrombosis**. [Practice more Pharmacology PYQs on OnCourse]

Q: What is the cause of cough and angioedema in a patient receiving ACE inhibitors?

Bradykinin accumulation. ***Bradykinin accumulation*** - **ACE inhibitors** block the enzyme **angiotensin-converting enzyme (ACE)**, which is responsible for degrading **bradykinin**. - The resulting **accumulation of bradykinin** is a potent vasodilator and increases capillary permeability, leading to **cough** (5-20% of patients) and **angioedema** (0.1-0.7%). - This is the most **precise answer** as it specifies the mechanism: impaired degradation leading to accumulation. *Bradykinin (alone)* - While **bradykinin** is the mediator involved, this option is **less precise** than "bradykinin accumulation." - **Bradykinin** is naturally present in the body; the problem with ACE inhibitors is specifically the **accumulation** due to impaired degradation. - The correct answer requires understanding that it's the **excess levels**, not just the presence, that causes symptoms. *Increased renin levels* - **ACE inhibitors** block the conversion of **angiotensin I to angiotensin II**, leading to reduced negative feedback. - This causes **compensatory increase in renin secretion** from the juxtaglomerular apparatus. - However, increased renin is **not responsible** for cough or angioedema—these are bradykinin-mediated effects. *Increased angiotensin-II levels* - **ACE inhibitors** actually **decrease angiotensin-II levels**, which is their primary **antihypertensive mechanism**. - This option is **incorrect** as ACE inhibitors reduce (not increase) angiotensin-II. - The reduction in angiotensin-II does not cause cough or angioedema. [Practice more Pharmacology PYQs on OnCourse]

Q: What is the mechanism of action of ticagrelor?

P2Y12 receptor antagonist. ***P2Y12 receptor antagonist*** - **Ticagrelor** is an **oral antiplatelet drug** that reversibly binds to the **P2Y12 ADP receptor** on platelet surfaces. - By blocking this receptor, it prevents **ADP-mediated platelet activation** and subsequent aggregation, reducing the risk of thrombotic events. *Cox inhibition* - **COX inhibitors** like **aspirin** prevent the synthesis of **thromboxane A2**, a powerful platelet aggregator. - This mechanism is characteristic of **NSAIDs** and **aspirin**, not ticagrelor. *GPIIB/IIIA inhibition* - **GPIIb/IIIa inhibitors** (e.g., abciximab, eptifibatide, tirofiban) directly block the final common pathway for platelet aggregation by preventing **fibrinogen binding** to the GPIIb/IIIa receptor. - While also an antiplatelet mechanism, this is distinct from ticagrelor's action on the P2Y12 receptor. *Inhibition of thromboxane synthase* - Inhibition of **thromboxane synthase** would reduce the production of **thromboxane A2**, similar to the effect of COX inhibition. - This is not the primary mechanism of action for ticagrelor; drugs like **dazoxiben** or **picotamide** act through this pathway. [Practice more Pharmacology PYQs on OnCourse]

Q: What was the first oral direct thrombin inhibitor to be developed and approved for clinical use?

Ximelagatran. ***Ximelagatran*** - **Ximelagatran** was the **first oral direct thrombin inhibitor** to be developed and approved for clinical use. - Despite its initial approval, it was later withdrawn due to concerns about **drug-induced liver injury**. *Indraparinux* - **Indraparinux** is a **synthetic heparin analog** and an **indirect Factor Xa inhibitor**, not a direct thrombin inhibitor. - It was developed as a long-acting anticoagulant but did not achieve widespread clinical adoption. *Dabigatran* - **Dabigatran** is currently a widely used **oral direct thrombin inhibitor**, but it was approved **after ximelagatran**. - It is often cited as the first of the modern non-vitamin K antagonist oral anticoagulants (**NOACs**) to be widely marketed, but not the very first to be developed and approved for clinical use. *Fondaparinux* - **Fondaparinux** is a synthetic **selective Factor Xa inhibitor**, structurally similar to the antithrombin-binding region of heparin. - It works indirectly by enhancing antithrombin's activity against Factor Xa, and is not a direct thrombin inhibitor. [Practice more Pharmacology PYQs on OnCourse]

137 Previous Year Questions with Answers & Explanations

137

Questions

Adverse effects of phenytoin include the following EXCEPT:

Drug not used in pulmonary hypertension is:

What is the cause of cough and angioedema in a patient receiving ACE inhibitors?

What is the mechanism of action of ticagrelor?

What was the first oral direct thrombin inhibitor to be developed and approved for clinical use?

Which of the following antidiabetic drugs is NOT an insulin secretagogue?

Which dopamine receptor is known for its inhibitory action in the central nervous system?

XDR-TB is defined as resistance to which of the following drug combinations?

Volume of distribution of a drug is 500 ml and target concentration of drug in blood is 5 g/L. 20% of administered drug is reached to systemic circulation. What will be the loading dose of that drug -

Q10

Regarding the concepts of efficacy and potency of a drug, which of the following statements is FALSE?

NEET-PG 2015 - Pharmacology NEET-PG Practice Questions and MCQs

Question 1: Adverse effects of phenytoin include the following EXCEPT:

A. Ataxia
B. Hirsutism
C. Hypercalcemia (Correct Answer)
D. Lymphadenopathy

Explanation: ***Hypercalcemia*** - Phenytoin can actually lead to **hypocalcemia** due to its effect on vitamin D metabolism, increasing its degradation and leading to osteomalacia or rickets [1]. - Therefore, **hypercalcemia** is not an expected adverse effect of phenytoin use. *Lymphadenopathy* - **Generalized lymphadenopathy** is a known, though less common, adverse effect of phenytoin, sometimes mimicking lymphoma. - It's part of a broader hypersensitivity reaction that can occur with the drug. *Ataxia* - **Ataxia** is a common dose-dependent adverse effect of phenytoin, especially at higher therapeutic or toxic levels [1], [2]. - It manifests as impaired coordination and balance due to cerebellar dysfunction [1]. *Hirsutism* - **Hirsutism**, or excessive hair growth, is a well-known chronic side effect of phenytoin [1]. - This effect is more aesthetically concerning than medically dangerous and is particularly common in young women [1].

Question 2: Drug not used in pulmonary hypertension is:

A. Endothelin receptor antagonist
B. Prostacyclin
C. Alpha blocker (Correct Answer)
D. Calcium channel blocker

Explanation: ***Alpha blocker*** - Alpha-blockers primarily cause **systemic vasodilation** [1] and are not indicated for the specific pulmonary vascular remodeling and vasoconstriction seen in pulmonary hypertension. [2] - Their use could lead to an undesirable drop in **systemic blood pressure** [3] without adequately addressing the pulmonary arterial pressure. *Calcium channel blocker* - **Calcium channel blockers** (namely **dihydropyridines** like nifedipine and amlodipine) are used in a small subset of pulmonary hypertension patients who are **vasoreactive** on acute testing. - They work by relaxing pulmonary arterial smooth muscle, reducing **pulmonary vascular resistance**. *Endothelin receptor antagonist* - **Endothelin receptor antagonists** (e.g., bosentan, ambrisentan) block the effects of **endothelin-1**, a potent vasoconstrictor and smooth muscle proliferator involved in pulmonary hypertension. - They improve hemodynamics, exercise capacity, and clinical outcomes by preventing **vasoconstriction** and **vascular remodeling**. *Prostacyclin* - **Prostacyclin analogs** (e.g., epoprostenol, treprostinil) are potent **vasodilators** and inhibitors of platelet aggregation. - They are highly effective in treating severe pulmonary hypertension by relaxing pulmonary arteries and preventing **thrombosis**.

Question 3: What is the cause of cough and angioedema in a patient receiving ACE inhibitors?

A. Bradykinin
B. Increased renin levels
C. Increased angiotensin-II levels
D. Bradykinin accumulation (Correct Answer)

Explanation: ***Bradykinin accumulation*** - **ACE inhibitors** block the enzyme **angiotensin-converting enzyme (ACE)**, which is responsible for degrading **bradykinin**. - The resulting **accumulation of bradykinin** is a potent vasodilator and increases capillary permeability, leading to **cough** (5-20% of patients) and **angioedema** (0.1-0.7%). - This is the most **precise answer** as it specifies the mechanism: impaired degradation leading to accumulation. *Bradykinin (alone)* - While **bradykinin** is the mediator involved, this option is **less precise** than "bradykinin accumulation." - **Bradykinin** is naturally present in the body; the problem with ACE inhibitors is specifically the **accumulation** due to impaired degradation. - The correct answer requires understanding that it's the **excess levels**, not just the presence, that causes symptoms. *Increased renin levels* - **ACE inhibitors** block the conversion of **angiotensin I to angiotensin II**, leading to reduced negative feedback. - This causes **compensatory increase in renin secretion** from the juxtaglomerular apparatus. - However, increased renin is **not responsible** for cough or angioedema—these are bradykinin-mediated effects. *Increased angiotensin-II levels* - **ACE inhibitors** actually **decrease angiotensin-II levels**, which is their primary **antihypertensive mechanism**. - This option is **incorrect** as ACE inhibitors reduce (not increase) angiotensin-II. - The reduction in angiotensin-II does not cause cough or angioedema.

Question 4: What is the mechanism of action of ticagrelor?

A. P2Y12 receptor antagonist (Correct Answer)
B. Cox inhibition
C. Inhibition of thromboxane synthase
D. GPIIb/IIIa inhibition

Explanation: ***P2Y12 receptor antagonist*** - **Ticagrelor** is an **oral antiplatelet drug** that reversibly binds to the **P2Y12 ADP receptor** on platelet surfaces. - By blocking this receptor, it prevents **ADP-mediated platelet activation** and subsequent aggregation, reducing the risk of thrombotic events. *Cox inhibition* - **COX inhibitors** like **aspirin** prevent the synthesis of **thromboxane A2**, a powerful platelet aggregator. - This mechanism is characteristic of **NSAIDs** and **aspirin**, not ticagrelor. *GPIIB/IIIA inhibition* - **GPIIb/IIIa inhibitors** (e.g., abciximab, eptifibatide, tirofiban) directly block the final common pathway for platelet aggregation by preventing **fibrinogen binding** to the GPIIb/IIIa receptor. - While also an antiplatelet mechanism, this is distinct from ticagrelor's action on the P2Y12 receptor. *Inhibition of thromboxane synthase* - Inhibition of **thromboxane synthase** would reduce the production of **thromboxane A2**, similar to the effect of COX inhibition. - This is not the primary mechanism of action for ticagrelor; drugs like **dazoxiben** or **picotamide** act through this pathway.

Question 5: What was the first oral direct thrombin inhibitor to be developed and approved for clinical use?

A. Indraparinux
B. Fondaparinux
C. Dabigatran
D. Ximelagatran (Correct Answer)

Explanation: ***Ximelagatran*** - **Ximelagatran** was the **first oral direct thrombin inhibitor** to be developed and approved for clinical use. - Despite its initial approval, it was later withdrawn due to concerns about **drug-induced liver injury**. *Indraparinux* - **Indraparinux** is a **synthetic heparin analog** and an **indirect Factor Xa inhibitor**, not a direct thrombin inhibitor. - It was developed as a long-acting anticoagulant but did not achieve widespread clinical adoption. *Dabigatran* - **Dabigatran** is currently a widely used **oral direct thrombin inhibitor**, but it was approved **after ximelagatran**. - It is often cited as the first of the modern non-vitamin K antagonist oral anticoagulants (**NOACs**) to be widely marketed, but not the very first to be developed and approved for clinical use. *Fondaparinux* - **Fondaparinux** is a synthetic **selective Factor Xa inhibitor**, structurally similar to the antithrombin-binding region of heparin. - It works indirectly by enhancing antithrombin's activity against Factor Xa, and is not a direct thrombin inhibitor.

Question 6: Which of the following antidiabetic drugs is NOT an insulin secretagogue?

A. Glinides
B. Exenatide
C. Pramlintide (Correct Answer)
D. Sulfonylureas

Explanation: ***Pramlintide*** - **Pramlintide** is an **amylin analog** which delays gastric emptying, suppresses glucagon secretion, and promotes satiety, thereby reducing postprandial glucose. It is **not an insulin secretagogue**. - Its mechanism of action is distinct from drugs that directly stimulate insulin release from pancreatic beta cells. - **This is the correct answer** as pramlintide has no role in enhancing insulin secretion. *Exenatide* - **Exenatide** is a **glucagon-like peptide-1 (GLP-1) receptor agonist** that enhances **glucose-dependent** insulin secretion. - Unlike traditional insulin secretagogues (sulfonylureas and glinides), GLP-1 agonists work through the **incretin effect** and only stimulate insulin release when glucose levels are elevated. - In strict pharmacological classification, GLP-1 agonists are **incretin mimetics**, not traditional insulin secretagogues, as they do not cause insulin release independent of glucose levels. - However, they do enhance insulin secretion in a physiological manner. *Glinides* - **Glinides**, such as repaglinide and nateglinide, are **insulin secretagogues** that stimulate rapid and short-lived insulin release from pancreatic beta cells. - They bind to the **sulfonylurea receptor** on beta cells, leading to membrane depolarization and insulin exocytosis. - Unlike GLP-1 agonists, glinides can cause insulin release **regardless of glucose levels**. *Sulfonylureas* - **Sulfonylureas**, such as glyburide and glipizide, are **insulin secretagogues** that stimulate insulin secretion by binding to the sulfonylurea receptor on pancreatic beta cells. - This binding leads to **closure of ATP-sensitive potassium channels**, membrane depolarization, and subsequent insulin release, regardless of blood glucose levels. - This glucose-independent action increases the risk of hypoglycemia compared to incretin-based therapies.

Question 7: Which dopamine receptor is known for its inhibitory action in the central nervous system?

A. Dopamine Receptor D5
B. No inhibitory dopamine receptor present
C. Dopamine Receptor D2 (Correct Answer)
D. Dopamine Receptor D1

Explanation: ***Dopamine Receptor D2*** - The **D2 receptor** is a member of the D2-like family (D2, D3, D4), which are **G-protein coupled receptors** that inhibit adenylyl cyclase activity. - Its activation typically leads to a **decrease in neuronal excitability** and neurotransmitter release, providing an inhibitory effect in the CNS. *Dopamine Receptor D5* - The **D5 receptor** belongs to the D1-like family (D1, D5), which are **G-protein coupled receptors** that stimulate adenylyl cyclase activity. - Activation of D5 receptors typically leads to **excitatory effects** rather than inhibitory ones in the CNS. *No inhibitory dopamine receptor present* - This statement is incorrect as specific dopamine receptor subtypes, particularly the **D2-like family**, are well-established to exert inhibitory actions in the CNS. - These inhibitory effects are crucial for various physiological processes, including motor control and reward pathways. *Dopamine Receptor D1* - The **D1 receptor** is part of the D1-like family (D1, D5) and is known for its **excitatory effects** in the CNS. - Activation of D1 receptors leads to an **increase in intracellular cAMP** and generally enhances neuronal activity.

Question 8: XDR-TB is defined as resistance to which of the following drug combinations?

A. INH plus rifampicin
B. Fluoroquinolones plus INH plus amikacin
C. Fluoroquinolones plus rifampicin plus kanamycin
D. Fluoroquinolones plus INH plus rifampicin plus amikacin (Correct Answer)

Explanation: **Fluoroquinolones plus INH plus rifampicin plus amikacin** - **Extensively drug-resistant tuberculosis (XDR-TB)** is defined by resistance to the most effective anti-TB drugs: **isoniazid (INH)**, **rifampicin**, any **fluoroquinolone**, and at least one of the three injectable second-line drugs (**amikacin**, **kanamycin**, or **capreomycin**). - This combination signifies a substantial therapeutic challenge due to limited treatment options and a high risk of treatment failure. *INH plus rifampicin* - Resistance to **INH** and **rifampicin** defines **multidrug-resistant tuberculosis (MDR-TB)**, which is a precursor to XDR-TB but not XDR-TB itself. - While serious, MDR-TB is not as extensively resistant as XDR-TB, as it doesn't include resistance to fluoroquinolones and second-line injectables. *Fluoroquinolones plus INH plus amikacin* - This combination is incomplete for the definition of XDR-TB because it omits **rifampicin** from the core definition. - XDR-TB specifically requires resistance to both **INH** and **rifampicin** (defining MDR-TB), in addition to resistance to a fluoroquinolone and one of the injectable second-line drugs. *Fluoroquinolones plus rifampicin plus kanamycin* - This combination is also incomplete for the definition of XDR-TB as it omits **isoniazid (INH)**, which is one of the two most crucial first-line drugs that characterize MDR-TB. - XDR-TB builds upon MDR-TB's resistance to both INH and rifampicin.

Question 9: Volume of distribution of a drug is 500 ml and target concentration of drug in blood is 5 g/L. 20% of administered drug is reached to systemic circulation. What will be the loading dose of that drug -

A. 1 gm
B. 5 gm
C. 25 gm
D. 12.5 gm (Correct Answer)

Explanation: ***12.5 gm*** - The formula for loading dose (LD) is: LD = (Target Concentration × Volume of Distribution) / Bioavailability. - Given: Target Concentration = 5 g/L, Volume of Distribution = 500 mL = 0.5 L, Bioavailability = 20% = 0.2. - So, LD = (5 g/L × 0.5 L) / 0.2 = 2.5 g / 0.2 = **12.5 g**. *1 gm* - This value would be obtained if the target concentration was 2 g/L with 100% bioavailability, or if the calculation incorrectly handled the volume or bioavailability factor. - It does not account for the specified **bioavailability of 20%** or the given target concentration and volume of distribution. *5 gm* - This result would be obtained if the bioavailability was assumed to be 50% (LD = 2.5 g / 0.5 = 5 g), or if the volume of distribution was incorrectly used in the calculation. - This option does not correctly factor in the **20% bioavailability** of the administered drug. *25 gm* - This value would result from mistakes such as dividing by bioavailability of 10% instead of 20% (LD = 2.5 g / 0.1 = 25 g), or by multiplying bioavailability instead of dividing by it. - This answer significantly **overestimates** the required dose, which could lead to drug toxicity.

Question 10: Regarding the concepts of efficacy and potency of a drug, which of the following statements is FALSE?

A. ED50 of the drug corresponds to efficacy (Correct Answer)
B. Drugs that produce a similar pharmacological effect can have different levels of efficacy
C. In a clinical setup, efficacy is more important than potency
D. In the log dose response curve, the height of the curve corresponds with efficacy

Explanation: ***ED50 of the drug corresponds to efficacy*** - **ED50** (median effective dose) is the dose at which 50% of individuals exhibit the specified effect; it quantifies **potency**, not efficacy. - **Efficacy** refers to the maximum effect a drug can produce, while potency refers to the amount of drug needed to produce an effect. *In a clinical setup, efficacy is more important than potency* - **Efficacy** determines the maximal therapeutic benefit a drug can achieve for a patient, making it crucial for clinical outcomes. - While **potency** influences the dose required, a highly potent drug that is not very efficacious may not be clinically useful. *Drugs that produce a similar pharmacological effect can have different levels of efficacy* - Two drugs might act on the same receptor but elicit different maximal responses, indicating varying **efficacy**. - For example, a **partial agonist** and **full agonist** interacting with the same receptor will have different efficacies. *In the log dose response curve, the height of the curve corresponds with efficacy* - The **maximal response** or plateau of the dose-response curve represents the **efficacy** of a drug. - A higher plateau on the curve indicates a drug with greater intrinsic activity achieving a larger effect.