Central Nervous System Pharmacology — MCQs

Central Nervous System Pharmacology Indian Medical PG Practice Questions and MCQs

Question 641: Which of the following is a dopamine and noradrenaline reuptake inhibitor?

A. Clozapine
B. Bupropion (Correct Answer)
C. Zolpidem
D. Mianserin

Explanation: **Bupropion** is the correct answer because it belongs to the class of **NDRIs (Norepinephrine and Dopamine Reuptake Inhibitors)**. Unlike most antidepressants that primarily target serotonin, Bupropion inhibits the transporters for both dopamine and noradrenaline, increasing their synaptic concentrations [2]. This unique mechanism makes it particularly effective for patients with "atypical" depression characterized by low energy, fatigue, and poor concentration. Analysis of Incorrect Options: * **Clozapine (A):** An atypical antipsychotic. It primarily acts as an antagonist at $D_2$ and $5-HT_{2A}$ receptors. It is the gold standard for treatment-resistant schizophrenia but is not a reuptake inhibitor. * **Zolpidem (B):** A non-benzodiazepine sedative-hypnotic ("Z-drug"). It acts as a selective agonist at the $\alpha_1$ subunit of the $GABA_A$ receptor complex. It is used for the short-term treatment of insomnia. * **Mianserin (D):** An atypical antidepressant classified as a NaSSA (Noradrenergic and Specific Serotonergic Antidepressant). It works primarily by blocking presynaptic $\alpha_2$ adrenoceptors rather than inhibiting reuptake. High-Yield Clinical Pearls for NEET-PG: * **Smoking Cessation:** Bupropion is FDA-approved for smoking cessation as it reduces nicotine cravings and withdrawal symptoms [1]. * **Sexual Dysfunction:** Unlike SSRIs, Bupropion does **not** cause sexual dysfunction or significant weight gain, making it a preferred choice for patients concerned about these side effects [1]. * **Seizure Risk:** The most significant adverse effect is a dose-dependent increase in seizure risk. It is strictly **contraindicated** in patients with epilepsy or eating disorders (bulimia/anorexia) due to electrolyte imbalances that further lower the seizure threshold [1].

Question 642: All of the following statements about Phenytoin are true, except?

A. Follows saturation kinetics
B. Is teratogenic
C. Is highly protein bound
D. Stimulates insulin secretion (Correct Answer)

Explanation: **Explanation:** Phenytoin is a widely used anti-epileptic drug that acts by blocking voltage-gated sodium channels. The correct answer is **D** because Phenytoin actually **inhibits** insulin secretion from the pancreas, which can lead to hyperglycemia (and occasionally "Phenytoin-induced diabetes"). **Why Option D is correct:** Phenytoin decreases the release of insulin by interfering with calcium uptake in pancreatic beta cells. This inhibitory effect is a known metabolic side effect, making the statement "stimulates insulin secretion" false. **Why other options are incorrect:** * **A. Follows saturation kinetics:** At therapeutic concentrations, Phenytoin switches from first-order to **zero-order kinetics** (Michaelis-Menten kinetics). Small dose increases can lead to disproportionately large increases in plasma levels, causing toxicity. * **B. Is teratogenic:** Phenytoin is associated with **Fetal Hydantoin Syndrome**, characterized by craniofacial anomalies (cleft lip/palate), microcephaly, and hypoplastic phalanges/nails. * **C. Is highly protein bound:** Phenytoin is approximately 90% bound to plasma albumin. Conditions like uremia or hypoalbuminemia can increase the free (active) fraction of the drug, leading to toxicity even with "normal" total serum levels. **High-Yield Clinical Pearls for NEET-PG:** * **Gingival Hyperplasia:** The most common side effect (due to increased PDGF). * **P450 Inducer:** It is a potent inducer of microsomal enzymes, leading to many drug interactions (e.g., decreasing the efficacy of OCPs and Warfarin). * **Therapeutic Window:** 10–20 µg/ml. * **Nystagmus:** The earliest sign of toxicity. * **Mnemonic for Side Effects (PHENYTOIN):** **P**-450 induction, **H**irsutism, **E**nlarged gums, **N**ystagmus, **Y**ellow-brown skin (pigmentation), **T**eratogenicity, **O**steomalacia (Vitamin D metabolism interference), **I**nterference with B12/Folate (Megaloblastic anemia), **N**europathy.

Question 643: Which antiepileptic drugs are used as analgesics?

A. Carbamazepine and valproate
B. Phenytoin and valproate
C. Carbamazepine and phenytoin (Correct Answer)
D. Diazepam and chlorpromazine

Explanation: **Explanation:** The correct answer is **C. Carbamazepine and phenytoin.** **1. Why Carbamazepine and Phenytoin are correct:** Antiepileptic drugs (AEDs) that act as sodium channel blockers are particularly effective in treating neuropathic pain. * **Carbamazepine** is the **drug of choice (DOC) for Trigeminal Neuralgia**. It stabilizes inactivated sodium channels, reducing the high-frequency repetitive firing of action potentials in the trigeminal nerve. * **Phenytoin** is also used as a second-line agent for trigeminal neuralgia and has been historically used for neuropathic conditions like diabetic neuropathy, though it is less common now due to its side effect profile. **2. Why other options are incorrect:** * **Valproate (Options A & B):** While Valproate is a broad-spectrum AED used for migraine prophylaxis, it is not primarily classified or used as a first-line analgesic for neuropathic pain syndromes. * **Diazepam (Option D):** This is a benzodiazepine used for status epilepticus, anxiety, and as a muscle relaxant, but it lacks specific analgesic properties for chronic pain. * **Chlorpromazine (Option D):** This is a typical antipsychotic (neuroleptic), not an antiepileptic or a primary analgesic. **3. NEET-PG High-Yield Clinical Pearls:** * **Trigeminal Neuralgia:** Carbamazepine is the DOC. If refractory, Baclofen or Lamotrigine can be added. * **Diabetic Neuropathy:** The DOC is typically **Pregabalin or Gabapentin** (AEDs that bind to $\alpha_2\delta$ subunits of calcium channels) or Duloxetine (SNRI). * **Post-herpetic Neuralgia:** Gabapentin is frequently the first-line choice. * **Side Effect Alert:** Always remember that Carbamazepine can cause **Stevens-Johnson Syndrome (SJS)**, especially in patients with the HLA-B*1502 allele.

Question 644: Selective serotonin reuptake inhibitors are drugs of choice for all of the following conditions except:

A. Acute panic attack (Correct Answer)
B. Social phobia
C. Post traumatic stress disorder
D. Generalized anxiety disorder

Explanation: **Explanation:** The correct answer is **Acute panic attack** because of the difference between immediate symptom relief and long-term maintenance therapy. **1. Why "Acute Panic Attack" is the correct answer:** Selective Serotonin Reuptake Inhibitors (SSRIs) have a **delayed onset of action**, typically taking 2 to 4 weeks to manifest therapeutic effects. In an "acute" panic attack, the patient requires immediate stabilization. The drugs of choice for immediate relief are **Benzodiazepines** (e.g., Alprazolam or Lorazepam) due to their rapid GABA-mediated sedative and anxiolytic effects. While SSRIs are the drug of choice for *Panic Disorder* (long-term prevention), they are ineffective for an active, acute episode. **2. Why the other options are incorrect:** SSRIs are considered the first-line treatment (Drug of Choice) for the following chronic anxiety conditions because of their efficacy and superior safety profile compared to older antidepressants: * **Social Phobia (Social Anxiety Disorder):** SSRIs are first-line for long-term management. * **Post-Traumatic Stress Disorder (PTSD):** SSRIs (specifically Sertraline and Paroxetine) are the primary pharmacological intervention. * **Generalized Anxiety Disorder (GAD):** SSRIs are preferred for sustained control of symptoms. **Clinical Pearls for NEET-PG:** * **DOC for OCD:** SSRIs (usually in higher doses than for depression). * **DOC for Bulimia Nervosa:** Fluoxetine. * **Common Side Effects:** Sexual dysfunction (most common long-term), GI upset, and "jitteriness syndrome" (initial worsening of anxiety). * **Serotonin Syndrome:** A high-yield risk when SSRIs are combined with MAO inhibitors or Tramadol.

Question 645: "Shivering" is observed in the early postoperative period due to:

A. Chloroform
B. Halothane (Correct Answer)
C. Trichloroethylene
D. Ether

Explanation: **Explanation:** **Halothane** is the correct answer because it is classically associated with **postoperative shivering** (also known as "halothane shakes"). This phenomenon occurs during the recovery phase of anesthesia. **Mechanism:** Halothane causes significant peripheral vasodilation and depresses the hypothalamic thermoregulatory center. This leads to a drop in core body temperature (hypothermia). As the anesthetic wears off, the body’s thermoregulatory mechanisms regain function and attempt to restore normal temperature through vigorous shivering. While other volatile anesthetics can cause this, it is most characteristic of Halothane in classical pharmacology. **Analysis of Incorrect Options:** * **A. Chloroform:** Primarily known for its severe hepatotoxicity and cardiac arrhythmias. It is obsolete in modern practice and not specifically linked to postoperative shivering as a hallmark feature. * **C. Trichloroethylene:** An older analgesic/anesthetic agent known for causing cranial nerve palsies (especially the trigeminal nerve) if used with soda lime, but not typically associated with shivering. * **D. Ether:** While it causes a long recovery period and significant nausea/vomiting, it does not depress the thermoregulatory center as profoundly as Halothane, making shivering less characteristic. **High-Yield Clinical Pearls for NEET-PG:** * **Treatment:** Postoperative shivering is most effectively treated with **Intravenous Pethidine** (Meperidine), which lowers the shivering threshold. * **Halothane Hepatitis:** A rare but serious idiosyncratic reaction (more common in adults/obese patients). * **Malignant Hyperthermia:** Halothane is a known trigger; the treatment of choice is **Dantrolene**. * **Cardiac Effect:** Halothane sensitizes the myocardium to catecholamines, increasing the risk of arrhythmias.

Question 646: Which antiparkinsonian drug directly activates D2 receptors?

A. Pramipixole (Correct Answer)
B. Entacapone
C. Benserazide
D. Selegiline

Explanation: **Explanation:** **Correct Option: A. Pramipexole** Pramipexole is a **non-ergot dopamine agonist**. Unlike Levodopa, which is a precursor that must be converted into dopamine, Pramipexole acts directly by stimulating dopamine receptors in the striatum. It has a high affinity for the **D2 receptor family** (specifically D2 and D3 subtypes). Direct agonists are particularly useful in Parkinson’s disease as they do not require functional presynaptic dopaminergic neurons to be effective and have a longer half-life than levodopa. **Incorrect Options:** * **B. Entacapone:** This is a peripheral **COMT (Catechol-O-methyltransferase) inhibitor**. It does not activate receptors directly; instead, it prevents the peripheral breakdown of Levodopa, increasing its bioavailability to the brain. * **C. Benserazide:** This is a **peripheral DOPA decarboxylase inhibitor**. It is administered with Levodopa (e.g., Madopar) to prevent its systemic conversion to dopamine, thereby reducing peripheral side effects like nausea and cardiac arrhythmias. * **D. Selegiline:** This is a selective **MAO-B (Monoamine Oxidase-B) inhibitor**. It works by inhibiting the intracerebral degradation of dopamine, thus prolonging the action of endogenous or levodopa-derived dopamine. **High-Yield Clinical Pearls for NEET-PG:** * **Dopamine Agonists:** Divided into Ergot derivatives (Bromocriptine, Cabergoline—linked to cardiac valvular fibrosis) and Non-ergot derivatives (Pramipexole, Ropinirole, Rotigotine). * **Side Effects:** Dopamine agonists are notorious for causing **impulse control disorders** (pathological gambling, hypersexuality) and sudden "sleep attacks." * **Drug of Choice:** Pramipexole is often preferred in younger patients to delay the start of Levodopa therapy and minimize motor fluctuations (the "levodopa-sparing" strategy).

Question 647: Which of the following statements is NOT true about fosphenytoin?

A. Used for generalized tonic-clonic seizures (GTCS)
B. It is a prodrug of phenytoin
C. It is lipid-soluble (Correct Answer)
D. It is highly protein-bound

Explanation: ### Explanation **Fosphenytoin** is a water-soluble phosphate ester prodrug of phenytoin, specifically designed to overcome the pharmaceutical limitations of intravenous (IV) phenytoin. **1. Why "It is lipid-soluble" is the correct (NOT true) statement:** Unlike phenytoin, which is highly lipid-soluble and requires a propylene glycol solvent (causing pain and phlebitis), **fosphenytoin is highly water-soluble**. This property allows it to be dissolved in standard IV fluids (Normal Saline or Dextrose) and administered rapidly without the risk of local tissue necrosis or "Purple Glove Syndrome." **2. Analysis of Incorrect Options:** * **A. Used for GTCS:** Fosphenytoin is FDA-approved for the control of generalized tonic-clonic status epilepticus and for the prevention/treatment of seizures during neurosurgery. * **B. It is a prodrug of phenytoin:** After parenteral administration, fosphenytoin is rapidly converted by **phosphatases** in the blood and liver into active phenytoin. * **D. It is highly protein-bound:** Fosphenytoin is extensively bound (approx. 95-99%) to human plasma proteins, primarily albumin. It can displace phenytoin from binding sites, which is clinically significant during the conversion process. **3. NEET-PG High-Yield Clinical Pearls:** * **Dosing:** Fosphenytoin is prescribed in **Phenytoin Equivalents (PE)**. 1.5 mg of fosphenytoin = 1 mg of phenytoin. * **Administration:** It can be given **Intramuscularly (IM)**, whereas phenytoin cannot (due to erratic absorption and tissue damage). * **Safety Profile:** It has a lower risk of cardiac arrhythmias and local irritation compared to phenytoin, though rapid infusion can still cause hypotension. * **Advantage:** It can be infused 3 times faster than phenytoin (150 mg PE/min vs. 50 mg/min).

Question 648: Which of the following is recommended for a pregnant patient receiving antiepileptic drugs to decrease the risk of neural tube defects in the offspring?

A. Folic acid (Correct Answer)
B. Vitamin A
C. Vitamin E
D. Pyridoxine

Explanation: **Explanation:** **Why Folic Acid is Correct:** Antiepileptic drugs (AEDs), particularly enzyme-inducers (like Carbamazepine and Phenytoin) and Valproate, interfere with folate metabolism. Valproate, in particular, inhibits the enzyme **dihydrofolate reductase**, leading to decreased levels of active folate. Since folate is essential for DNA synthesis and neural tube closure in the early embryo, its deficiency significantly increases the risk of **Neural Tube Defects (NTDs)** like spina bifida. Supplementation with **Folic acid (4–5 mg/day)**, started ideally before conception, is the standard of care to mitigate this teratogenic risk. **Why Other Options are Incorrect:** * **Vitamin A:** High doses are actually **teratogenic** (causing craniofacial and cardiac defects). It has no role in preventing NTDs. * **Vitamin E:** While an antioxidant, it has no proven clinical benefit in preventing AED-induced congenital malformations. * **Pyridoxine (Vitamin B6):** It is used to prevent peripheral neuropathy in patients taking Isoniazid or to treat Sideroblastic anemia. In epilepsy, it is specifically used for **Pyridoxine-dependent neonatal seizures**, but not for preventing NTDs. **High-Yield Clinical Pearls for NEET-PG:** * **Valproate** is the most teratogenic AED; it carries the highest risk for NTDs (approx. 1-2%). * **Vitamin K** supplementation is recommended for the mother in the last month of pregnancy if she is on enzyme-inducing AEDs to prevent **Neonatal Hemorrhagic Disease** (due to induction of fetal Vitamin K metabolism). * **Levetiracetam and Lamotrigine** are generally considered the safest AEDs during pregnancy. * **Fetal Hydantoin Syndrome:** Characterized by hypoplastic phalanges, cleft lip/palate, and microcephaly (associated with Phenytoin).

Question 649: Thiopentone is absolutely contraindicated in which of the following conditions?

A. Porphyria (Correct Answer)
B. Moribund patients
C. Increased intracranial pressure
D. Meningitis

Explanation: **Explanation:** **1. Why Porphyria is the Correct Answer:** Thiopentone (a thiobarbiturate) is **absolutely contraindicated** in patients with **Acute Intermittent Porphyria (AIP)** or Porphyria Variegata. Barbiturates are potent inducers of the hepatic enzyme **ALA synthetase**. This enzyme catalyzes the rate-limiting step in heme synthesis. Induction leads to the overproduction of porphyrins and their precursors (delta-aminolevulinic acid and porphobilinogen), which can precipitate a life-threatening acute porphyric crisis characterized by severe abdominal pain, paralysis, and neuropsychiatric symptoms. **2. Analysis of Incorrect Options:** * **B. Moribund patients:** While thiopentone must be used with extreme caution in hemodynamically unstable or moribund patients due to its myocardial depressant effects and peripheral vasodilation, it is a **relative contraindication**, not an absolute one. * **C. Increased intracranial pressure (ICP):** Thiopentone is actually **beneficial** here. It reduces cerebral metabolic rate ($CMRO_2$) and cerebral blood flow, thereby lowering ICP. It is often used for "cerebral protection" during neurosurgery. * **D. Meningitis:** There is no direct contraindication for thiopentone in meningitis, though clinical judgment regarding the patient's neurological and hemodynamic status is required. **3. High-Yield Facts for NEET-PG:** * **Mechanism of Action:** Increases the **duration** of GABA-A receptor chloride channel opening. * **Pharmacokinetics:** Its action is terminated by **redistribution** (from brain to muscle/fat), not metabolism. * **Other Absolute Contraindications:** Status asthmaticus (due to histamine release) and known hypersensitivity. * **Clinical Pearl:** If accidental intra-arterial injection occurs, it causes severe spasm and gangrene. Treatment includes local injection of **Heparin, Papaverine, or Lidocaine** and performing a **Stellate ganglion block**.

Question 650: Which of the following is NOT a side effect of depression?

A. Propranolol
B. Oral contraceptives
C. Reserpine
D. Flupenthixol (Correct Answer)

Explanation: **Explanation:** The question asks to identify the drug that does **not** cause depression as a side effect. The correct answer is **Flupenthixol**. **1. Why Flupenthixol is the correct answer:** Flupenthixol is a thioxanthene derivative (typical antipsychotic). While high doses are used to treat psychosis, **low doses (0.5–1.5 mg)** have a unique **activating and antidepressant effect**. It is often used clinically to treat mild-to-moderate depression with anxiety or psychosomatic symptoms. Therefore, it is a treatment for depression rather than a cause. **2. Why the other options are incorrect (Drugs causing depression):** * **Propranolol:** Beta-blockers, particularly lipophilic ones like Propranolol, cross the blood-brain barrier and are well-documented to cause CNS side effects, including fatigue, lethargy, and clinical depression. * **Oral Contraceptives (OCPs):** Estrogen and progesterone can influence neurotransmitter levels (like serotonin). Chronic use of OCPs is a known risk factor for mood swings and depressive symptoms in susceptible women. * **Reserpine:** This is a classic pharmacological example. Reserpine inhibits the Vesicular Monoamine Transporter (VMAT), leading to the depletion of norepinephrine, dopamine, and serotonin. This depletion directly led to the "Monoamine Hypothesis" of depression. **Clinical Pearls for NEET-PG:** * **Reserpine-induced depression** is a high-yield fact; it is contraindicated in patients with a history of mental illness. * Other drugs causing depression: **Corticosteroids, Interferon-alpha, Methyldopa, and Isotretinoin.** * **Flupenthixol** is often combined with Melitracen (a TCA) in clinical practice for its rapid onset of mood-elevating effects.

Practice by Chapter

General Anesthetics

Practice Questions

Local Anesthetics

Practice Questions

Sedative-Hypnotics

Practice Questions

Antiepileptic Drugs

Practice Questions

Antiparkinsonian Drugs

Practice Questions

Opioid Analgesics

Practice Questions

Drugs of Abuse and Addiction

Practice Questions

Psychostimulants

Practice Questions

Hallucinogens

Practice Questions

CNS Stimulants and Cognitive Enhancers

Practice Questions

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