NEET-PG 2015 - Pharmacology Practice Questions

Q: What is the mechanism of action of ticagrelor?

Reversible inhibition of ADP action. ***Reversible inhibition of ADP action*** - **Ticagrelor** is a **P2Y12 receptor antagonist** that works by preventing ADP from binding to its receptor on platelets [2]. - This binding is **reversible**, meaning ticagrelor can dissociate from the receptor, allowing for some recovery of platelet function over time [2]. *Irreversible inhibition of ADP action* - **Clopidogrel** and **prasugrel** are examples of **irreversible P2Y12 inhibitors**, forming a permanent bond with the receptor [2]. - Irreversible inhibition leads to a longer duration of platelet inhibition, as new platelets must be generated for function to return [2]. *Reversible inhibition of GPIIb/IIIa* - **GPIIb/IIIa inhibitors** like **eptifibatide** and **tirofiban** block the final common pathway of platelet aggregation by preventing fibrinogen binding [1]. - While their action is reversible, they target a *different* mechanism than ticagrelor. *Irreversible inhibition of GPIIb/IIIa* - **Abciximab** is a GPIIb/IIIa inhibitor that binds **irreversibly** (or with very slow dissociation) to the receptor [1]. - Unlike reversible GPIIb/IIIa inhibitors, abciximab is a monoclonal antibody with a prolonged antiplatelet effect [1]. - This is still an incorrect answer as ticagrelor targets the P2Y12 receptor, not GPIIb/IIIa.

Q: How do thiazides cause hypercalcemia?

Decreased calcium excretion. ***Decreased calcium excretion*** - Thiazides inhibit the **Na-Cl co-transporter** in the **distal convoluted tubule**, leading to increased reabsorption of calcium [1], [2]. - This increased reabsorption of calcium is mediated by a low intracellular sodium concentration, which enhances the activity of the **Na+/Ca2+ exchanger** on the basolateral membrane [1]. *Increased parathyroid hormone secretion* - Thiazides **do not directly stimulate** parathyroid hormone (PTH) secretion; instead, they *decrease* calcium excretion, which would typically *lower* PTH levels through negative feedback. - Elevated PTH would lead to increased bone resorption and kidney calcium reabsorption, but this is not the **primary mechanism** for thiazide-induced hypercalcemia [2]. *Decreased calcitonin secretion* - **Calcitonin** is a hormone that *lowers* blood calcium levels, and its decrease would theoretically contribute to hypercalcemia. - However, thiazides have **no direct effect** on calcitonin secretion, making this an unlikely primary mechanism. *Increased calcium absorption* - While increased calcium absorption from the gut can contribute to hypercalcemia, thiazides do **not directly increase intestinal calcium absorption**. - Their primary action for influencing calcium levels is within the **kidney**, specifically on reabsorption, not absorption from the GI tract [1], [2].

Q: Which drug is not administered as a transdermal patch?

Morphine. ***Morphine*** - **Morphine** is generally not administered transdermally due to its **poor lipid solubility** [1] and **large molecular size**, which limit its ability to penetrate the skin effectively. - While experimental patches have been developed, they are **not widely available** or commonly used in clinical practice for systemic delivery. *Fentanyl* - **Fentanyl** is a potent opioid that is commonly administered via a **transdermal patch** for chronic pain management [2]. - Its **high lipid solubility** and small molecular size allow it to be effectively absorbed through the skin, providing sustained analgesia. *Clonidine* - **Clonidine** is an alpha-2 adrenergic agonist available as a **transdermal patch** for the treatment of **hypertension**. - The patch provides a **continuous and steady release** of the drug, leading to consistent blood pressure control. *Diclofenac* - **Diclofenac** is a non-steroidal anti-inflammatory drug (NSAID) available in **transdermal patch** formulations for topical pain relief. - These patches are used for localized pain conditions like **osteoarthritis** and provide targeted drug delivery with reduced systemic side effects.

Q: Thymidine is responsible for resistance to which antibiotic ?

Sulfonamide. ***Sulfonamide*** - **Thymidine** can contribute to **sulfonamide resistance** because sulfonamides interfere with **folate metabolism** and the subsequent synthesis of purines and pyrimidines, including thymidine. - An excess of thymidine can bypass the metabolic block caused by sulfonamides, allowing bacteria to continue DNA synthesis and grow. *Erythromycin* - **Erythromycin** resistance is primarily mediated by **methylation of ribosomal RNA**, which prevents the antibiotic from binding to the 50S ribosomal subunit. - It does not directly involve thymidine or the folate synthesis pathway. *Tetracycline* - Resistance to **tetracyclines** is commonly due to **efflux pumps** that actively pump the drug out of the bacterial cell or **ribosomal protection proteins** that prevent tetracycline binding. - Thymidine production or metabolism is not a mechanism of tetracycline resistance. *Nitrofurantoin* - **Nitrofurantoin** resistance typically involves **mutations** in bacterial enzymes (like **nitrofuran reductase**) that are responsible for activating the drug into its active form. - These mutations prevent the drug from becoming bactericidal, and thymidine does not play a role in this mechanism.

Q: Which anti-cholinesterase drug is known for its central nervous system activity?

Physostigmine. ***Physostigmine*** - Unlike most other anti-cholinesterases, **physostigmine** is a **tertiary amine** and is relatively lipid-soluble, allowing it to cross the **blood-brain barrier**. [2] - Its ability to increase acetylcholine in the CNS makes it useful in treating anticholinergic toxicity (e.g., atropine overdose). [2] *Pyridostigmine* - **Pyridostigmine** is a **quaternary amine** and does not readily cross the blood-brain barrier, primarily acting peripherally. - It is mainly used in the long-term management of **myasthenia gravis**. *Edrophonium* - **Edrophonium** is a very short-acting **quaternary amine** that does not cross the blood-brain barrier. [1] - It is primarily used for the **diagnosis of myasthenia gravis** (Tensilon test) due to its rapid onset and short duration of action. [1] *Neostigmine* - **Neostigmine** is also a **quaternary amine** with poor lipid solubility, meaning it has minimal central nervous system activity. [2] - It is commonly used to reverse the effects of **non-depolarizing neuromuscular blockers** and in the treatment of **myasthenia gravis**.

Q: Which of the following is an action of muscarinic cholinergic receptors?

Decreased heart rate. ***Decreased heart rate*** - Activation of **muscarinic cholinergic receptors (M2 receptors)** in the heart leads to a decrease in heart rate and conduction velocity. - This effect is mediated by the **vagus nerve (parasympathetic nervous system)**, which releases acetylcholine to act on these receptors. - This is the **most characteristic and clinically significant cardiovascular effect** of muscarinic receptor activation, making it the expected answer. *Skeletal muscle contraction* - **Skeletal muscle contraction** is mediated by **nicotinic acetylcholine receptors (nAChRs)** at the **neuromuscular junction**, NOT muscarinic receptors. - Nicotinic receptors are **ligand-gated ion channels** that cause direct depolarization and muscle contraction when activated. - This is the only option that is **NOT a muscarinic receptor action**. *Acid secretion in stomach* - **Gastric acid secretion** IS mediated by **M3 muscarinic receptors** on parietal cells. - Acetylcholine from the vagus nerve directly stimulates parietal cells and also stimulates histamine release from enterochromaffin-like cells. - While this is a valid muscarinic action, in the context of distinguishing muscarinic effects, **cardiac effects** (decreased heart rate) are more emphasized as the classic teaching point. *Salivation and lacrimation* - **Salivation and lacrimation** ARE mediated by **M3 muscarinic receptors** in exocrine glands. - These are classic parasympathetic/muscarinic effects taught in physiology. - However, when distinguishing key muscarinic actions, **M2 receptor-mediated cardiac effects** are typically highlighted as the primary cardiovascular manifestation, while M3 effects on glands are secondary teaching points.

Q: What is the half-life of nicotine in blood?

2 hours. ***2 hours*** - Nicotine has a **relatively short half-life** in the blood, typically around 2 hours, contributing to frequent dosing in tobacco users. - This rapid elimination means that nicotine concentrations decrease significantly within a few hours after the last dose, leading to **withdrawal symptoms** or cravings. *15 minutes* - A 15-minute half-life would imply an **extremely rapid clearance**, which is not characteristic of nicotine. - Such quick elimination would make it very difficult to maintain consistent drug levels and would lead to immediate, intense withdrawal. *5 hours* - While longer than the actual half-life, 5 hours is still within the realm of substances requiring **multiple daily doses**. - However, it would mean nicotine levels would remain elevated for a longer period than observed, potentially delaying withdrawal. *24 hours* - A 24-hour half-life would mean nicotine would accumulate significantly in the body with daily use, leading to **prolonged effects** and a much slower decline in concentrations after cessation. - This half-life is typical for drugs designed for **once-daily dosing**, which is not the case for nicotine.

Q: Quinine primarily acts on which stage of the Plasmodium life cycle?

Erythrocytic. ***Correct: Erythrocytic*** - Quinine primarily acts as a **blood schizonticide**, targeting the asexual erythrocytic stages of the *Plasmodium* parasite. - Its mechanism involves interfering with the parasite's ability to detoxify **heme**, leading to accumulation of toxic byproducts and parasite death within **red blood cells**. - This is why quinine is effective in treating **acute malaria attacks** during the symptomatic phase of the disease. *Incorrect: Exoerythrocytic* - The **exoerythrocytic stage** occurs in the liver, where sporozoites develop into merozoites. - Quinine has **minimal or no activity** against these liver stages, meaning it does not prevent initial infection or relapse from hepatic dormant forms (hypnozoites). - Drugs like **primaquine** target this stage. *Incorrect: Pre-erythrocytic* - The **pre-erythrocytic stage** is another term for the exoerythrocytic or liver stage of the parasite life cycle, occurring before the parasite enters red blood cells. - Medications that target this stage are known as **causal prophylactics**, which quinine is not. - Quinine has **no significant activity** at this stage. *Incorrect: None of the options* - This option is incorrect as quinine specifically targets the **erythrocytic stage**, making that option the correct answer. - Quinine's effectiveness in treating malaria stems from its action during the **symptomatic phase** of the disease, which corresponds to the erythrocytic cycle in red blood cells.

Q: Which diuretic is most likely to cause hyponatremia by impairing free water excretion?

Thiazide diuretics. ***Thiazide diuretics*** - **Thiazide diuretics** inhibit the **Na-Cl cotransporter in the distal convoluted tubule (DCT)**, impairing the kidney's ability to dilute urine and excrete free water - This impaired urinary dilution leads to **water retention relative to sodium**, resulting in **dilutional hyponatremia** - **Most common in elderly patients**, those on low-salt diets, or with pre-existing volume depletion - **Mechanism**: By blocking sodium reabsorption in the DCT (a key site for urinary dilution), thiazides prevent the generation of free water, leading to hyponatremia when water intake continues *Loop diuretics* - **Loop diuretics** inhibit the **Na-K-2Cl cotransporter in the thick ascending limb of Henle**, causing significant diuresis - They impair the medullary concentration gradient, **enhancing free water excretion** - **Less likely to cause hyponatremia** compared to thiazides because they promote rather than impair free water clearance - When hyponatremia occurs with loop diuretics, it's usually due to concurrent SIADH or excessive free water intake *Acetazolamide* - **Acetazolamide** is a **carbonic anhydrase inhibitor** acting primarily on the **proximal tubule** - Causes **bicarbonate and sodium excretion**, leading to mild diuresis - Main side effect is **metabolic acidosis** (type 2 RTA) - **Does not significantly impair free water excretion**, making hyponatremia uncommon *Amiloride* - **Amiloride** is a **potassium-sparing diuretic** that blocks **epithelial sodium channels (ENaC) in the collecting duct** - Weak diuretic effect, primarily used to prevent potassium loss - **Does not impair urinary dilution mechanisms**, so hyponatremia is rare - Main concern is **hyperkalemia**, especially with ACE inhibitors or in renal insufficiency

Q: At which receptor is the primary action of antipsychotic medications required?

D2 dopaminergic. ***D2 dopaminergic*** - The **antipsychotic effects** of typical (first-generation) antipsychotics are primarily mediated through **D2 receptor blockade** [1]. - Blocking D2 receptors in the **mesolimbic pathway** helps reduce positive symptoms of psychosis like hallucinations and delusions [2]. *M, muscarinic* - **Muscarinic receptor blockade** is a common adverse effect of some antipsychotics, leading to anticholinergic side effects such as **dry mouth** and **blurred vision**, rather than their primary therapeutic action. - This action does not directly contribute to the antipsychotic effect. *D1 dopaminergic* - While D1 receptors are involved in dopamine signaling, they are **not the primary target** for the antipsychotic action of most drugs [1]. - Some atypical antipsychotics may affect D1 receptors, but it's secondary to their D2 antagonism and serotonin modulation. *5HT4 serotonergic* - **Serotonin receptors (5HT)**, particularly 5HT2A, are important targets for atypical (second-generation) antipsychotics. - However, 5HT4 receptors are **not a primary target** for the antipsychotic effects, and 5HT2A blockade modulates dopamine release, which is still connected to the D2 hypothesis.

Question 1

What is the mechanism of action of ticagrelor?

Accepted Answer

Reversible inhibition of ADP action

Answer

Irreversible inhibition of ADP action

Answer

Reversible inhibition of GPIIb/IIIa

Answer

Irreversible inhibition of GPIIb/IIIa

Question 2

How do thiazides cause hypercalcemia?

Accepted Answer

Decreased calcium excretion

Answer

Increased parathyroid hormone secretion

Answer

Decreased calcitonin secretion

Answer

Increased calcium absorption

Question 3

Which drug is not administered as a transdermal patch?

Accepted Answer

Morphine

Answer

Fentanyl

Answer

Clonidine

Answer

Diclofenac

Question 4

Thymidine is responsible for resistance to which antibiotic ?

Accepted Answer

Sulfonamide

Answer

Erythromycin

Answer

Tetracycline

Answer

Nitrofurantoin

Question 5

Which anti-cholinesterase drug is known for its central nervous system activity?

Accepted Answer

Physostigmine

Answer

Edrophonium

Answer

Pyridostigmine

Answer

Neostigmine

Question 6

Which of the following is an action of muscarinic cholinergic receptors?

Accepted Answer

Decreased heart rate

Answer

Skeletal muscle contraction

Answer

Acid secretion in stomach

Answer

Salivation and lacrimation

Question 7

What is the half-life of nicotine in blood?

Accepted Answer

2 hours

Answer

15 minutes

Answer

5 hours

Answer

24 hours

Question 8

Quinine primarily acts on which stage of the Plasmodium life cycle?

Accepted Answer

Erythrocytic

Answer

Exoerythrocytic

Answer

Pre-erythrocytic

Answer

None of the options

Question 9

Which diuretic is most likely to cause hyponatremia by impairing free water excretion?

Accepted Answer

Thiazide diuretics

Answer

Loop diuretics

Answer

Acetazolamide

Answer

Amiloride

Question 10

At which receptor is the primary action of antipsychotic medications required?

Accepted Answer

D2 dopaminergic

Answer

M, muscarinic

Answer

5HT4 serotonergic

Answer

D1 dopaminergic

NEET-PG 2015 — Pharmacology