FMGE 2024 — Pharmacology
6 Previous Year Questions with Answers & Explanations
What is the mechanism of action of Ethosuximide?
What is the primary mechanism of action of methotrexate?
A patient having hypertension is on thiazides and is complaining of fatigue and hypokalemia. Which of the following drugs can prevent potassium loss?
A patient was given an antipsychotic drug, haloperidol, and the patient developed acute dystonia. Which is the next best step?
A group of people are travelling to the mountains, and a girl starts complaining of mountain sickness. What is the drug of choice?
Which of the following is an atypical antipsychotic with the least metabolic side effects?
FMGE 2024 - Pharmacology FMGE Practice Questions and MCQs
Question 1: What is the mechanism of action of Ethosuximide?
- A. Inhibits calcium channels in thalamic neurons (Correct Answer)
- B. Enhances GABAergic inhibition
- C. Blocks sodium channels
- D. Increases serotonin levels
Explanation: ***Inhibits calcium channels in thalamic neurons***- Ethosuximide selectively blocks **T-type calcium channels** (**transient type**) primarily found on **thalamic neurons**.- This blockade reduces the **low-threshold burst firing** responsible for the characteristic **3-Hz spike-and-wave discharge** seen in absence seizures.*Enhances GABAergic inhibition*- This mechanism is characteristic of **Benzodiazepines** and **Barbiturates**, which increase the frequency or duration of GABA-A channel opening.- While some broad-spectrum AEDs like **Valproate** also increase GABA levels, this is not the primary mechanism of action for Ethosuximide.*Blocks sodium channels*- Drugs that block neuronal sodium channels, such as **Phenytoin** and **Carbamazepine**, are effective against tonic-clonic and partial seizures.- This mechanism prevents the rapid, sustained firing of action potentials but is largely ineffective against the burst firing characteristic of absence seizures.*Increases serotonin levels*- This is the primary mechanism associated with **Selective Serotonin Reuptake Inhibitors (SSRIs)** and other antidepressants.- It is not relevant to the function of Ethosuximide, which is specific to modulating neuronal excitability through calcium channels.
Question 2: What is the primary mechanism of action of methotrexate?
- A. Inhibits RNA synthesis by blocking RNA polymerase
- B. Inhibits dihydrofolate reductase, leading to decreased DNA synthesis (Correct Answer)
- C. Interferes with microtubule formation during cell division
- D. Inhibits DNA synthesis by blocking thymidylate synthase
Explanation: ***Inhibits dihydrofolate reductase, leading to decreased DNA synthesis***- **Methotrexate (MTX)** is a **folate analog** that acts as a potent competitive inhibitor of the enzyme **dihydrofolate reductase (DHFR)**.- Inhibition of **DHFR** prevents the conversion of **dihydrofolate** to **tetrahydrofolate (THF)**, which is crucial for the synthesis of **purines** and **thymidylate**, halting DNA and RNA production.*Inhibits DNA synthesis by blocking thymidylate synthase*- This mechanism of action is primarily associated with the fluorinated pyrimidine analog **5-Fluorouracil (5-FU)**.- **5-FU** acts as a suicide substrate that irreversibly inhibits **thymidylate synthase**, not dihydrofolate reductase.*Inhibits RNA synthesis by blocking RNA polymerase*- While MTX affects nucleotide synthesis (building blocks for RNA), its primary and most impactful target is **DHFR**, affecting DNA synthesis prominently.- Direct blocking of **RNA polymerase** is the mechanism for drugs such as **Actinomycin D** (by DNA intercalation).*Interferes with microtubule formation during cell division*- This mechanism belongs to the class of **microtubule-targeting agents**, such as **vinca alkaloids** (**vincristine**) and **taxanes** (**paclitaxel**).- These agents disrupt the formation or disassembly of the **mitotic spindle**, leading to **mitotic arrest**, which is distinct from the mechanism of methotrexate.
Question 3: A patient having hypertension is on thiazides and is complaining of fatigue and hypokalemia. Which of the following drugs can prevent potassium loss?
- A. Acetazolamide
- B. Indapamide
- C. Furosemide
- D. Amiloride (Correct Answer)
Explanation: ***Amiloride***- Amiloride is a **potassium-sparing diuretic** that acts by blocking the **Epithelial Sodium Channel (ENaC)** in the collecting duct. [5]- By inhibiting Na+ reabsorption here, it decreases the electrical gradient that drives **potassium secretion**, effectively counteracting the hypokalemic effect of thiazides. [2]*Furosemide*- Furosemide is a **loop diuretic** that inhibits the Na-K-2Cl cotransporter in the thick ascending limb.- It is notorious for causing significant urinary **potassium loss** and would worsen the patient's **hypokalemia** and fatigue. [5]*Acetazolamide*- Acetazolamide is a **carbonic anhydrase inhibitor** that increases the delivery of Na+ and bicarbonate (HCO3-) to the collecting duct. [4]- The increased delivery of these ions promotes the secretion and loss of **potassium** in the urine, thus failing to prevent hypokalemia. [4]*Indapamide*- Indapamide is a **thiazide-like diuretic** that, similar to thiazides, inhibits the NaCl cotransporter in the distal convoluted tubule. [1]- Like other thiazides, Indapamide is a **potassium-wasting diuretic** and would exacerbate the existing **hypokalemia**. [3]
Question 4: A patient was given an antipsychotic drug, haloperidol, and the patient developed acute dystonia. Which is the next best step?
- A. Give Fluphenazine
- B. Give Benztropine (Correct Answer)
- C. Increase dose of haloperidol
- D. Change to clozapine
Explanation: ***Give Benztropine***- **Acute dystonia** is a severe extrapyramidal symptom (EPS) requiring rapid intervention, often treated intramuscularly or intravenously.- **Benztropine** (an anticholinergic agent) is the drug of choice for the immediate management of acute dystonia, working to restore the balance between dopamine and acetylcholine.*Change to clozapine*- While **clozapine** has a significantly lower risk of causing acute dystonia, it is not the initial treatment for an acute episode due to its slow titration requirements and side-effect profile.- Switching to clozapine is a long-term strategy for patients intolerant to other antipsychotics, not an acute rescue medication.*Give Fluphenazine*- **Fluphenazine** is a high-potency first-generation antipsychotic, similar to haloperidol, which also carries a high risk of EPS.- Administering another high-potency antipsychotic would perpetuate the excessive **dopaminergic blockade** responsible for the acute dystonia.*Increase dose of haloperidol*- **Acute dystonia** is a direct dose-related side effect of D2 receptor blockade by haloperidol in the nigrostriatal pathway.- Increasing the dose of **haloperidol** would worsen the underlying neurochemical imbalance, thereby intensifying the dystonic symptoms.
Question 5: A group of people are travelling to the mountains, and a girl starts complaining of mountain sickness. What is the drug of choice?
- A. Thiazide
- B. Acetazolamide (Correct Answer)
- C. Promethazine
- D. Dimenhydrinate
Explanation: ***Acetazolamide*** - This drug is the agent of choice for prophylaxis and treatment of **Acute Mountain Sickness (AMS)** due to its ability to accelerate **acclimatization**. - It functions as a **carbonic anhydrase inhibitor**, inducing a mild metabolic acidosis that stimulates the respiratory center, thereby increasing ventilation and improving blood oxygen saturation. *Promethazine* - This is an **antihistamine** (H1 blocker) often used for its potent **antiemetic** (nausea) and sedative effects. - While it may relieve nausea symptoms associated with AMS, it does not address the underlying physiological disturbances or enhance **acclimatization**. *Dimenhydrinate* - This medication is also an **antihistamine** typically employed to treat and prevent **motion sickness** and vertigo. - It lacks the crucial physiological mechanism (carbonic anhydrase inhibition) required to improve breathing efficiency and accelerate the body's response to **hypoxia**. *Thiazide* - This category of drugs, such as hydrochlorothiazide, are **diuretics** primarily used for hypertension and edema. - They do not possess the necessary respiratory stimulation properties of **Acetazolamide** and are therefore ineffective in treating or preventing mountain sickness.
Question 6: Which of the following is an atypical antipsychotic with the least metabolic side effects?
- A. Risperidone
- B. Ziprasidone (Correct Answer)
- C. Haloperidol
- D. Quetiapine
Explanation: ***Ziprasidone*** - Among the atypical (second-generation) antipsychotics, **Ziprasidone** has the lowest risk regarding adverse **metabolic side effects**, including **weight gain**, dyslipidemia, and insulin resistance. - Due to its minimal impact on metabolic parameters, it is a preferred choice for patients with pre-existing **cardiovascular risk factors** or obesity. *Haloperidol* - Haloperidol is a **first-generation (typical)** antipsychotic, which primarily risks **extrapyramidal symptoms (EPS)** and elevated prolactin, rather than being an atypical agent. - While its metabolic risk is generally lower than high-risk atypicals (e.g., Olanzapine), it is not the correct classification for answering a question focusing on *atypical* drugs. *Risperidone* - Risperidone is an atypical antipsychotic but carries a **moderate to high risk** of causing significant **weight gain** and **hyperprolactinemia**. - Its metabolic profile is considerably worse than that of Ziprasidone or Aripiprazole. *Quetiapine* - Quetiapine carries a substantial risk profile regarding metabolic adverse effects, specifically high rates of **sedation** and clinically significant **weight gain**. - It is frequently linked to the development of **dyslipidemia** and **Type 2 diabetes mellitus**.