Central Nervous System Pharmacology — MCQs

A 30-year-old female, married for one year, presents with hyperactivity for the past two weeks. A diagnosis of mania is made. She has had three prior episodes of mania in the last 5 years, and each time, she returns to her premorbid state after taking medication. Her urine pregnancy test is positive. Which is the preferred drug for the management of this patient?

Central Nervous System Pharmacology Indian Medical PG Practice Questions and MCQs

Question 191: What is the drug of choice for generalized tonic-clonic status epilepticus?

A. Ethosuxamide
B. Sodium valproate
C. Lamotrigene
D. Lorazepam (Correct Answer)

Explanation: **Explanation:** **Status Epilepticus (SE)** is a medical emergency defined as a continuous seizure lasting more than 5 minutes or recurrent seizures without recovery of consciousness between episodes. **Why Lorazepam is the Correct Answer:** Benzodiazepines are the first-line treatment for terminating active seizures due to their rapid onset of action and high affinity for GABA-A receptors, which enhances inhibitory neurotransmission. **Lorazepam** is the preferred drug of choice (DOC) over Diazepam because it is less lipid-soluble; it remains in the vascular compartment longer, providing a more sustained anticonvulsant effect (6–12 hours) compared to the rapid redistribution of Diazepam. **Analysis of Incorrect Options:** * **A. Ethosuximide:** This is the DOC for **Absence seizures** only. It works by blocking T-type calcium channels and has no role in managing status epilepticus or tonic-clonic seizures. * **B. Sodium Valproate:** While a broad-spectrum anticonvulsant used for maintenance therapy in GTCS, it is considered a second-line agent in SE (used if benzodiazepines fail). * **C. Lamotrigine:** This is used for long-term prophylaxis of various seizures and bipolar disorder. It is not available in a rapid-acting intravenous formulation suitable for emergency seizure termination. **High-Yield Clinical Pearls for NEET-PG:** * **Sequence of Management in SE:** 1. **1st Line:** Lorazepam (IV) or Midazolam (IM/Buccal if IV access is unavailable). 2. **2nd Line:** Phenytoin/Fosphenytoin, Levetiracetam, or Valproate. 3. **3rd Line (Refractory):** Phenobarbital, Propofol, or Thiopental (requires intubation). * **Drug of Choice for Febrile Seizures:** Diazepam (Rectal/IV). * **Drug of Choice for Absence Seizures:** Ethosuximide (Valproate if associated with GTCS).

Question 192: What is the antiepileptic of choice in post-diabetic peripheral neuropathy?

A. Pregabalin (Correct Answer)
B. Amitriptyline
C. Carbamazepine
D. Duloxetine

Explanation: ### Explanation **Correct Answer: A. Pregabalin** **Mechanism and Rationale:** Pregabalin (and its precursor Gabapentin) are structural analogs of GABA. However, they do not act on GABA receptors. Instead, they bind to the **$\alpha_2\delta$ subunit of voltage-gated calcium channels** in the CNS. This binding decreases the influx of calcium into nerve terminals, thereby reducing the release of excitatory neurotransmitters like glutamate, substance P, and norepinephrine. This modulation of "hyperexcited" neurons makes it the first-line antiepileptic drug (AED) for neuropathic pain, including Diabetic Peripheral Neuropathy (DPN). **Analysis of Incorrect Options:** * **B. Amitriptyline:** While this Tricyclic Antidepressant (TCA) is highly effective for neuropathic pain, it is **not an antiepileptic**. It works by inhibiting the reuptake of Serotonin and Norepinephrine. It is often avoided in elderly diabetics due to anticholinergic side effects and cardiotoxicity. * **C. Carbamazepine:** This is the drug of choice for **Trigeminal Neuralgia**, not diabetic neuropathy. Its primary mechanism is blocking use-dependent sodium channels. * **D. Duloxetine:** This is an SNRI (Serotonin-Norepinephrine Reuptake Inhibitor). While it is FDA-approved and a first-line treatment for DPN, it is **not classified as an antiepileptic drug**. **High-Yield Clinical Pearls for NEET-PG:** * **First-line for DPN:** Pregabalin, Duloxetine, or TCAs (Amitriptyline). * **Pregabalin vs. Gabapentin:** Pregabalin has superior bioavailability, faster onset of action, and more predictable pharmacokinetics. * **Drug of Choice (DOC) Summary:** * Trigeminal Neuralgia: **Carbamazepine** * Post-herpetic Neuralgia: **Gabapentin/Pregabalin** * Fibromyalgia: **Pregabalin** * Neuropathic pain with Depression: **Duloxetine** * **Side Effects of Pregabalin:** Dizziness, somnolence, and peripheral edema.

Question 193: Which of the following agents blocks AMPA receptors?

A. Phenobarbitone
B. Topiramate
C. Lamotrigine
D. All the above (Correct Answer)

Explanation: **Explanation:** The correct answer is **D (All the above)**. This question tests the multi-modal mechanisms of action of various anti-epileptic drugs (AEDs). Glutamate is the primary excitatory neurotransmitter in the brain, acting on NMDA, AMPA, and Kainate receptors. Blocking the **AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid)** receptor reduces rapid excitatory neurotransmission, making it a key target for seizure control. * **Phenobarbitone:** While primarily known as a GABA-A receptor modulator (increasing the duration of chloride channel opening), it also inhibits excitatory transmission by blocking AMPA/Kainate receptors at higher therapeutic concentrations. * **Topiramate:** This is a "broad-spectrum" AED with multiple mechanisms: it blocks voltage-gated sodium channels, enhances GABA-A activity, inhibits carbonic anhydrase, and specifically antagonizes the **AMPA/Kainate** subtype of glutamate receptors. * **Lamotrigine:** Its primary action is blocking voltage-gated sodium channels to inhibit glutamate release. However, it also exerts inhibitory effects on postsynaptic AMPA receptors, contributing to its efficacy in both focal and generalized seizures. **Clinical Pearls for NEET-PG:** 1. **Perampanel** is the only "selective" non-competitive AMPA receptor antagonist (highly high-yield). 2. **Topiramate** is often associated with side effects like weight loss, nephrolithiasis (kidney stones), and "word-finding" difficulties (cognitive slowing). 3. **Lamotrigine** carries a Black Box Warning for Stevens-Johnson Syndrome (SJS); it must be titrated slowly. 4. **Phenobarbitone** remains the drug of choice for neonatal seizures in many traditional guidelines, though Levetiracetam is increasingly used.

Question 194: A patient undergoing surgery was given a muscle relaxant. It produced a marked fall in blood pressure and an increase in airway resistance, which were reversed with diphenhydramine. The muscle relaxant was most probably:

A. Atracurium
B. Diazepam
C. Tubocurarine (Correct Answer)
D. Vecuronium

Explanation: **Explanation:** The clinical presentation of **hypotension** (fall in blood pressure) and **bronchospasm** (increased airway resistance) following the administration of a muscle relaxant is a classic indicator of **histamine release**. The fact that these symptoms were reversed by **diphenhydramine** (an H1-receptor antagonist) confirms that histamine was the primary mediator. **1. Why Tubocurarine is correct:** **d-Tubocurarine**, a prototype non-depolarizing neuromuscular blocker, is notorious for causing significant histamine release from mast cells. Histamine causes peripheral vasodilation (leading to hypotension) and bronchial smooth muscle contraction (leading to bronchospasm). Additionally, tubocurarine has **ganglionic blocking** properties, which further contributes to the fall in blood pressure. **2. Why the other options are incorrect:** * **Atracurium:** While atracurium can cause histamine release, it is significantly less potent in this regard than tubocurarine. It is more commonly associated with its metabolite, **laudanosine**, which can lower the seizure threshold. * **Diazepam:** This is a benzodiazepine used for sedation and central muscle relaxation. It does not cause histamine release or significant airway resistance changes. * **Vecuronium:** This is an intermediate-acting steroid-based relaxant. It is preferred in cardiac surgeries because it is **hemodynamically stable** and lacks histamine-releasing or autonomic-blocking effects. **NEET-PG High-Yield Pearls:** * **Mivacurium** and **Atracurium** are other non-depolarizing blockers that can cause histamine release, but tubocurarine is the most potent inducer. * **Pancuronium** is known for causing **tachycardia** due to its vagolytic (atropine-like) action. * **Rocunorium** is the preferred agent for **Rapid Sequence Induction (RSI)** when Succinylcholine is contraindicated. * **Hoffman Elimination:** The spontaneous non-enzymatic degradation of Atracurium and Cisatracurium, making them safe in renal and hepatic failure.

Question 195: Which drug is contraindicated in absence seizures?

A. Lamotrigine
B. Clonazepam
C. Tiagabine (Correct Answer)
D. Ethosuximide

Explanation: Absence seizures are characterized by 3-Hz spike-and-wave discharges on EEG, resulting from oscillatory activity between the thalamus and cortex. **Tiagabine** is a selective GABA reuptake inhibitor (GAT-1 inhibitor) [1, 2, 3]. By increasing GABA concentrations in the synaptic cleft, it can paradoxically hyperpolarize thalamic neurons, leading to the activation of T-type calcium channels. This exacerbates the rhythmic discharges, potentially transforming absence seizures into **status epilepticus** or increasing their frequency [1, 2]. Other drugs that aggravate absence seizures include **Vigabatrin, Phenytoin, Carbamazepine, and Phenobarbital.** **Analysis of Incorrect Options:** * **A. Lamotrigine:** This is a broad-spectrum anticonvulsant effective against both focal and generalized seizures, including absence seizures (though usually second-line after Valproate or Ethosuximide). * **B. Clonazepam:** Benzodiazepines enhance GABA-A receptor activity. Clonazepam is effective in treating absence seizures, particularly in refractory cases, though sedation and tolerance limit its long-term use. * **D. Ethosuximide:** This is the **drug of choice** for pure absence seizures. It works by specifically inhibiting T-type $Ca^{2+}$ channels in thalamic neurons. **High-Yield Clinical Pearls for NEET-PG:** * **Drug of Choice (DOC) for Absence Seizures:** Ethosuximide (if only absence); Valproate (if absence is associated with GTCS). * **Drugs that worsen Absence/Myoclonic seizures:** "The Narrow Spectrum Drugs" – Phenytoin, Carbamazepine, Oxcarbazepine, Gabapentin, Tiagabine, and Vigabatrin. * **EEG Hallmark:** 3-Hz spike-and-wave pattern. * **Tiagabine Side Effect:** Can induce non-convulsive status epilepticus in patients without a history of epilepsy.

Question 196: Which monoclonal antibody is used in the management of Alzheimer's disease?

A. Abciximab
B. Ceolizumab
C. Bapineuzumab (Correct Answer)
D. Vedolizumab

Explanation: Explanation: **Correct Option: C. Bapineuzumab** Alzheimer’s disease is characterized by the accumulation of **amyloid-beta (Aβ) plaques** in the brain [1]. Bapineuzumab is a humanized monoclonal antibody designed to bind to and clear these Aβ plaques. While its clinical trials showed limited efficacy in improving cognitive function, it remains the classic pharmacological example of immunotherapy targeting the amyloid cascade in Alzheimer’s pathology [2]. **Incorrect Options:** * **A. Abciximab:** This is a **Glycoprotein IIb/IIIa receptor antagonist**. It is used as an antiplatelet agent during percutaneous coronary intervention (PCI) to prevent ischemic complications. * **B. Ceolizumab (Certolizumab):** This is a **TNF-alpha inhibitor** (specifically a pegylated Fab' fragment). It is used in the management of autoimmune conditions like Crohn’s disease and Rheumatoid Arthritis. * **D. Vedolizumab:** This is an **integrin receptor antagonist** (α4β7 integrin). It is gut-selective and used primarily in the management of Inflammatory Bowel Disease (Ulcerative Colitis and Crohn’s). **High-Yield Clinical Pearls for NEET-PG:** * **Recent FDA Approvals:** While Bapineuzumab is a frequent exam option, stay updated on newer FDA-approved monoclonal antibodies for Alzheimer’s: **Aducanumab** and **Lecanemab**. * **Mechanism:** These drugs target the **Amyloid Hypothesis**, aiming to reduce the plaque burden that leads to neurodegeneration [1]. * **Side Effects:** A critical adverse effect to remember for these antibodies is **ARIA (Amyloid-Related Imaging Abnormalities)**, which includes brain edema or microhemorrhages.

Question 197: A patient developed nausea, vomiting, tingling, and numbness in the fingertips, which also turned blue, after taking a drug for an acute attack of migraine. Which of the following drugs is most likely implicated in causing these findings?

A. Dihydroergotamine (Correct Answer)
B. Sumatriptan
C. Aspirin
D. Butorphanol

Explanation: ### **Explanation** **Correct Option: A. Dihydroergotamine** The patient is presenting with **Ergotism** (St. Anthony’s Fire). Dihydroergotamine (DHE) and Ergotamine are non-selective 5-HT$_{1}$ receptor agonists used for acute migraine. Their primary side effect profile stems from **potent, long-lasting peripheral vasoconstriction** mediated by alpha-adrenergic and serotonergic receptors. * **Mechanism of Symptoms:** Vasoconstriction leads to reduced peripheral blood flow, causing tingling, numbness, and cyanosis (fingertips turning blue). If severe, this can progress to gangrene. Nausea and vomiting are common due to the stimulation of the Chemoreceptor Trigger Zone (CTZ). --- ### **Why Other Options are Incorrect:** * **B. Sumatriptan:** While Triptans are selective 5-HT$_{1B/1D}$ agonists that cause vasoconstriction, their action is primarily limited to **cranial vessels**. While they can cause chest tightness (coronary vasospasm), they rarely cause the severe peripheral ischemia and cyanosis characteristic of ergot alkaloids. * **C. Aspirin:** An NSAID used for mild-to-moderate migraine. Common side effects include gastric irritation, peptic ulcers, and anti-platelet effects, but it does not cause peripheral vasoconstriction or cyanosis. * **D. Butorphanol:** An opioid agonist-antagonist used as a nasal spray for migraine. It causes sedation, dizziness, and potential dependence, but not peripheral ischemia. --- ### **High-Yield Clinical Pearls for NEET-PG:** * **Ergotism Management:** The drug of choice for reversing ergot-induced peripheral ischemia is **Sodium Nitroprusside** (a potent vasodilator). * **Contraindications:** Ergot alkaloids are strictly contraindicated in patients with Peripheral Vascular Disease (PVD), Coronary Artery Disease (CAD), hypertension, pregnancy, and renal/hepatic impairment. * **Drug Interaction:** Concurrent use of **CYP3A4 inhibitors** (e.g., Erythromycin, Ritonavir) can precipitate ergot toxicity by slowing its metabolism.

Question 198: What is the drug of choice for myoclonic epilepsy in pregnancy?

A. Carbamazepine
B. Sodium valproate (Correct Answer)
C. Phenobarbitone
D. Phenytoin

Explanation: **Explanation:** The drug of choice for **myoclonic epilepsy** (such as Juvenile Myoclonic Epilepsy) is **Sodium Valproate** [1]. It is a broad-spectrum antiepileptic that works by increasing GABA levels, blocking voltage-gated sodium channels, and inhibiting T-type calcium channels. While Valproate is generally avoided in pregnancy due to its high teratogenic potential (Neural Tube Defects) [2], it remains the **drug of choice for myoclonic seizures** because other agents are often ineffective or may even exacerbate this specific seizure type [1]. In clinical practice, if a patient is well-controlled on Valproate, the dose is minimized and supplemented with high-dose Folic Acid (5mg). **Why the other options are incorrect:** * **Carbamazepine:** It is the drug of choice for focal (partial) seizures [1] and trigeminal neuralgia. However, it is contraindicated in myoclonic seizures as it can **worsen** them. * **Phenobarbitone:** While used in neonatal seizures and status epilepticus, it is not the first-line agent for myoclonic epilepsy and is associated with significant sedation and cognitive side effects. * **Phenytoin:** Similar to Carbamazepine, Phenytoin is effective for generalized tonic-clonic and focal seizures [1] but can aggravate myoclonic and absence seizures. **High-Yield NEET-PG Pearls:** * **Teratogenicity:** Valproate is the most teratogenic AED (causes **Spina Bifida**) [2]. * **Safest in Pregnancy:** **Levetiracetam** and **Lamotrigine** are generally considered the safest AEDs during pregnancy. * **DOC for Absence Seizures:** Ethosuximide (Valproate is second line). * **DOC for Infantile Spasms:** Vigabatrin (in Tuberous Sclerosis) or ACTH.

Question 199: All of the following are true about opioids except?

A. Naloxone is short acting
B. Naltrexone is used to lower craving in alcoholics
C. Nalmefene can be used for opioid poisoning
D. Nalmefene is shorter acting than naloxone (Correct Answer)

Explanation: ### Explanation This question tests your knowledge of opioid antagonists, specifically their pharmacokinetics and clinical applications. **1. Why Option D is the Correct (False) Statement:** The statement is incorrect because **Nalmefene is actually longer-acting than Naloxone.** While Naloxone has a very short half-life (about 1 hour), Nalmefene has a significantly longer half-life (about 8–10 hours). This makes Nalmefene advantageous in treating overdoses of long-acting opioids (like Methadone) as it reduces the risk of "re-narcotization" (where the antagonist wears off before the agonist, leading to respiratory depression relapse). **2. Analysis of Other Options:** * **A. Naloxone is short acting:** This is **true**. Due to its short duration of action (30–90 minutes), patients treated for opioid overdose must be monitored closely, as repeated doses or a continuous infusion may be required. * **B. Naltrexone is used to lower craving in alcoholics:** This is **true**. Naltrexone blocks the $\mu$-opioid receptors involved in the reward pathway, thereby reducing the "high" associated with alcohol consumption and decreasing cravings. * **C. Nalmefene can be used for opioid poisoning:** This is **true**. Like naloxone, it is a pure opioid antagonist and is FDA-approved for the reversal of opioid effects. **3. Clinical Pearls for NEET-PG:** * **Naloxone:** Drug of choice for acute opioid poisoning. Administered IV/IM/Intranasal (not oral due to high first-pass metabolism). * **Naltrexone:** Used for **maintenance** in opioid detoxified patients and for **alcohol dependence**. It is orally effective. * **Methylnaltrexone/Alvimopan:** Peripheral opioid antagonists used to treat opioid-induced constipation without reversing analgesia (they do not cross the BBB). * **Naloxegol:** A pegylated derivative of naloxone used for opioid-induced constipation.

Question 200: A 30-year-old female, married for one year, presents with hyperactivity for the past two weeks. A diagnosis of mania is made. She has had three prior episodes of mania in the last 5 years, and each time, she returns to her premorbid state after taking medication. Her urine pregnancy test is positive. Which is the preferred drug for the management of this patient?

A. Promethazine
B. Haloperidol (Correct Answer)
C. Clonazepam
D. Lithium

Explanation: **Explanation:** The patient is a pregnant female presenting with an acute episode of mania. The management of bipolar disorder during pregnancy requires a careful balance between maternal stability and fetal safety. **Why Haloperidol is the Correct Answer:** **Haloperidol** is a high-potency typical antipsychotic and is considered the **first-line treatment for acute mania in pregnancy**. It has a long-standing safety record with no proven association with major congenital malformations (unlike mood stabilizers). It effectively controls hyperactivity and psychotic symptoms while posing the least risk to the developing fetus, especially during the first trimester. **Analysis of Incorrect Options:** * **Lithium (Option D):** While Lithium is the gold standard for maintenance in bipolar disorder, it is highly **teratogenic** during the first trimester. It is associated with **Ebstein’s anomaly** (tricuspid valve displacement). Given the positive pregnancy test, it is avoided in the acute phase. * **Promethazine (Option A):** This is an antihistamine with sedative properties. While safe in pregnancy (often used for hyperemesis gravidarum), it has no primary efficacy in treating the core symptoms of mania. * **Clonazepam (Option C):** Benzodiazepines can be used as adjuncts for sleep or agitation, but they are not primary antimanic agents. There are also concerns regarding "floppy infant syndrome" and potential cleft palate risks if used chronically in early pregnancy. **High-Yield Clinical Pearls for NEET-PG:** * **Drug of Choice (DOC) for Mania in Pregnancy:** Haloperidol. * **Teratogenicity of Valproate:** Highest risk among mood stabilizers; causes **Neural Tube Defects** (Meningomyelocele). * **Teratogenicity of Carbamazepine:** Also causes Neural Tube Defects. * **Lithium Monitoring:** If used later in pregnancy, doses must be adjusted due to increased GFR and renal clearance; it must be stopped shortly before delivery to prevent neonatal lithium toxicity.

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