Central Nervous System Pharmacology — MCQs

Central Nervous System Pharmacology Indian Medical PG Practice Questions and MCQs

Question 271: Which antidepressant selectively blocks 5-hydroxytryptamine reuptake?

A. Fluoxetine (Correct Answer)
B. Desipramine
C. Amoxapine
D. Dothiepin

Explanation: **Explanation:** The question asks for a selective blocker of 5-hydroxytryptamine (5-HT/Serotonin) reuptake. **Correct Option: A. Fluoxetine** Fluoxetine is the prototype of the **Selective Serotonin Reuptake Inhibitors (SSRIs)**. It works by selectively inhibiting the serotonin transporter (SERT) at the presynaptic terminal, thereby increasing the concentration of 5-HT in the synaptic cleft. Unlike Tricyclic Antidepressants (TCAs), SSRIs have minimal affinity for adrenergic, histaminergic, or cholinergic receptors, leading to a better side-effect profile. **Incorrect Options:** * **B. Desipramine:** This is a secondary amine TCA. It is highly selective for inhibiting **Norepinephrine (NE)** reuptake rather than 5-HT. * **C. Amoxapine:** A tetracyclic antidepressant that inhibits NE reuptake and also possesses **Dopamine (D2) receptor blocking** properties (giving it antipsychotic-like effects but also a risk of extrapyramidal symptoms). * **D. Dothiepin (Dosulepin):** A typical TCA that inhibits the reuptake of both NE and 5-HT and possesses significant sedative and anticholinergic properties. **High-Yield Clinical Pearls for NEET-PG:** * **Drug of Choice:** SSRIs (like Fluoxetine) are the first-line treatment for Depression, OCD, Panic Disorder, Social Phobia, and Bulimia Nervosa. * **Long Half-life:** Fluoxetine has the longest half-life among SSRIs (due to its active metabolite **norfluoxetine**), making it the least likely to cause "discontinuation syndrome." * **Side Effects:** Common side effects include GI upset, sexual dysfunction, and insomnia. * **Serotonin Syndrome:** Always monitor for this when combining SSRIs with MAO inhibitors (requires a washout period).

Question 272: Which drug is preferred in the treatment of Restless Legs Syndrome?

A. Propranolol
B. Ropinirole (Correct Answer)
C. Bupropion
D. Diazepam

Explanation: **Explanation:** **Restless Legs Syndrome (RLS)**, also known as Willis-Ekbom Disease, is characterized by an irresistible urge to move the legs, usually associated with unpleasant sensations that worsen at rest and during the night. The underlying pathophysiology is linked to **dopaminergic dysfunction** in the nigrostriatal pathway and iron deficiency in the CNS. **Why Ropinirole is Correct:** Non-ergot **Dopamine Agonists** (D2/D3 receptors) are the first-line pharmacological treatment for RLS. **Ropinirole** and **Pramipexole** are FDA-approved and preferred because they directly stimulate dopamine receptors, effectively relieving symptoms and improving sleep quality. Rotigotine (transdermal patch) is also used. **Analysis of Incorrect Options:** * **A. Propranolol:** A beta-blocker used for essential tremors and akathisia, but it has no role in RLS and may even worsen symptoms in some patients. * **C. Bupropion:** An antidepressant that inhibits norepinephrine and dopamine reuptake. While it affects dopamine, it is not a primary treatment for RLS; in fact, most SSRIs/SNRIs can exacerbate RLS symptoms. * **D. Diazepam:** A benzodiazepine that may help with sleep onset in mild cases but does not treat the underlying urge to move or the sensory symptoms of RLS. **NEET-PG High-Yield Pearls:** 1. **First-line agents:** Dopamine agonists (Ropinirole, Pramipexole) or Alpha-2-delta ligands (Gabapentin enacarbil, Pregabalin). 2. **Augmentation:** A common clinical complication where long-term dopaminergic therapy causes symptoms to start earlier in the day or become more severe. 3. **Iron Status:** Always check **Serum Ferritin** levels. Iron supplementation is indicated if ferritin is <75-100 µg/L. 4. **Secondary Causes:** Pregnancy, End-stage renal disease (ESRD), and Iron deficiency anemia.

Question 273: Which of the following is true about benzodiazepines?

A. GABA mimetic
B. GABA facilitator (Correct Answer)
C. Not a safe drug
D. High abuse potential

Explanation: **Explanation:** **1. Why "GABA Facilitator" is correct:** Benzodiazepines (BZDs) act as **positive allosteric modulators** of the GABA-A receptor. They bind to a specific site (the BZD site) located between the $\alpha$ and $\gamma$ subunits. Unlike barbiturates, BZDs do not activate the receptor directly; instead, they increase the **frequency** of chloride channel opening in the presence of GABA. This enhances the inhibitory effect of endogenous GABA, making them "GABA facilitators." **2. Why other options are incorrect:** * **A. GABA mimetic:** This term refers to drugs that can directly open chloride channels even in the absence of GABA (e.g., high-dose Barbiturates). BZDs lack this intrinsic activity, which is why they have a "ceiling effect" on CNS depression. * **C. Not a safe drug:** BZDs are considered relatively safe because of their high therapeutic index. Since they require endogenous GABA to work, they rarely cause fatal respiratory depression when taken alone (unlike barbiturates). * **D. High abuse potential:** While BZDs can lead to dependence, their abuse potential is categorized as **low to moderate** (Schedule IV) compared to opioids or barbiturates. **High-Yield Clinical Pearls for NEET-PG:** * **Mechanism Shortcut:** **B**enzodiazepines increase **F**requency (**B-F**); **B**arbiturates increase **D**uration (**B-D**) of channel opening. * **Antidote:** **Flumazenil** is a competitive BZD receptor antagonist used for overdose. * **Liver Metabolism:** For elderly patients or those with liver failure, use **LOT** drugs (**L**orazepam, **O**xazepam, **T**emazepam) as they undergo direct conjugation and do not form active metabolites. * **Drug of Choice:** BZDs are the DOC for **Status Epilepticus** (Lorazepam/Diazepam) and **Alcohol Withdrawal** (Chlordiazepoxide).

Question 274: All are used in painful diabetic neuropathy, EXCEPT:

A. Phenytoin
B. Local use of capsicum
C. Dextroamphetamine (Correct Answer)
D. Amitriptyline

Explanation: **Explanation:** The management of painful diabetic neuropathy (PDN) focuses on drugs that modulate pain signaling pathways, specifically targeting neurotransmitters like serotonin, norepinephrine, and GABA, or blocking voltage-gated ion channels. **Why Dextroamphetamine is the correct answer:** Dextroamphetamine is a CNS stimulant that increases the release of dopamine and norepinephrine in the synaptic cleft. While it is used for ADHD and narcolepsy, it has **no established clinical role** in the management of neuropathic pain. It does not possess the membrane-stabilizing or inhibitory pathway-modulating properties required to treat PDN. **Analysis of other options:** * **Amitriptyline:** A Tricyclic Antidepressant (TCA) and often considered a **first-line agent** for PDN. It works by inhibiting the reuptake of serotonin and norepinephrine, thereby enhancing descending inhibitory pain pathways. * **Phenytoin:** An antiepileptic that acts as a sodium channel blocker. By stabilizing neuronal membranes and reducing repetitive firing, it can be used to alleviate neuropathic pain, though it is now less commonly used than Gabapentin or Pregabalin. * **Local use of Capsicum (Capsaicin):** A topical agent derived from chili peppers. It works by initially stimulating and then desensitizing nociceptors by depleting **Substance P**, a key neurotransmitter in pain transmission. **High-Yield Clinical Pearls for NEET-PG:** * **First-line agents for PDN:** Pregabalin, Gabapentin, Duloxetine (SNRI), and Amitriptyline (TCA). * **FDA-approved drugs specifically for PDN:** Pregabalin and Duloxetine. * **Topical options:** Capsaicin cream and Lidocaine patches. * **Mechanism of Gabapentinoids:** They bind to the **$\alpha_2\delta$ subunit** of voltage-gated calcium channels, reducing the release of excitatory neurotransmitters.

Question 275: Muscular rigidity caused by opioids is due to agonistic effect on which receptor?

A. Mu (Correct Answer)
B. Kappa
C. Delta
D. Sigma

Explanation: **Explanation:** **1. Why Mu (μ) is Correct:** Opioid-induced muscle rigidity (often referred to as "Chest Wall Rigidity" or "Wooden Chest Syndrome") is primarily mediated by the **Mu (μ) opioid receptors**. This phenomenon occurs most frequently with rapid intravenous administration of potent lipophilic Mu-agonists like **Fentanyl, Sufentanil, and Remifentanil**. The underlying mechanism involves the activation of Mu receptors in the **striatum and substantia nigra** (basal ganglia), which modulates GABAergic and dopaminergic pathways, leading to increased motor neuron output and skeletal muscle contraction. **2. Why Other Options are Incorrect:** * **Kappa (κ):** These receptors are primarily associated with spinal analgesia, sedation, and miosis. Agonism here often leads to **dysphoria** and psychotomimetic effects, rather than muscular rigidity. * **Delta (δ):** These receptors contribute to supraspinal/spinal analgesia and may modulate emotional states. They do not play a significant role in motor rigidity. * **Sigma (σ):** Formerly classified as an opioid receptor, it is now considered a non-opioid chaperone protein. It is associated with hallucinations and mydriasis (e.g., by drugs like Pentazocine), but not classic opioid rigidity. **3. Clinical Pearls for NEET-PG:** * **Management:** The rigidity can be so severe that it prevents effective bag-mask ventilation. It is treated with **Neuromuscular Blocking Agents (e.g., Succinylcholine)** or the opioid antagonist **Naloxone**. * **High-Yield Fact:** Fentanyl is the most common culprit in clinical practice. * **Key Site:** The **Nucleus Raphe Pontis** is also implicated in the central mediation of this rigidity.

Question 276: Which of the following drugs is NOT used in the management of attention deficit hyperactivity disorder in children?

A. Modafinil
B. Amphetamines
C. Imipramine (Correct Answer)
D. Methylphenidate

Explanation: **Explanation:** The management of Attention Deficit Hyperactivity Disorder (ADHD) primarily involves increasing catecholamine levels (dopamine and norepinephrine) in the prefrontal cortex to improve focus and impulse control. **Why Imipramine is the Correct Answer:** While **Imipramine** (a Tricyclic Antidepressant) was historically used as a third-line agent for ADHD due to its effect on norepinephrine reuptake, it is **no longer recommended** for use in children for this indication. The primary reason is its significant **cardiotoxicity** (risk of arrhythmias and sudden cardiac death) and a narrow therapeutic index. In modern clinical practice and for NEET-PG purposes, it is considered obsolete for ADHD management. **Analysis of Other Options:** * **Methylphenidate (Option D):** This is the **drug of choice** for ADHD. It acts by blocking the reuptake of dopamine and norepinephrine. * **Amphetamines (Option B):** These are first-line stimulants that increase the release of catecholamines from storage vesicles into the synaptic cleft. * **Modafinil (Option A):** Though primarily used for narcolepsy, Modafinil is used **off-label** in children with ADHD who do not respond to or cannot tolerate first-line stimulants. **High-Yield Clinical Pearls for NEET-PG:** * **First-line Non-Stimulant:** **Atomoxetine** (a selective NE reuptake inhibitor) is the preferred non-stimulant, especially if there is a risk of substance abuse. * **Alpha-2 Agonists:** Clonidine and Guanfacine are also used as adjuncts or alternatives. * **Side Effects:** Stimulants (Methylphenidate/Amphetamines) can cause **growth suppression** and insomnia; monitoring height and weight is essential.

Question 277: Which drug produces neuromuscular blockade by persistent depolarization?

A. D-tubocurarine
B. Gallamine
C. Pancuronium
D. Decamethonium (Correct Answer)

Explanation: Neuromuscular blocking agents (NMBAs) are classified into two categories based on their mechanism of action at the nicotinic acetylcholine receptors (Nm) of the motor endplate: **Depolarizing** and **Non-depolarizing**. **Why Decamethonium is Correct:** **Decamethonium** (along with Succinylcholine) is a **Depolarizing Neuromuscular Blocker** [3]. These drugs act as nicotinic agonists; they bind to Nm receptors and cause persistent stimulation, leading to initial fasciculations followed by flaccid paralysis [1], [2]. Because they are not metabolized by acetylcholinesterase, the endplate remains depolarized and unresponsive to subsequent impulses (Phase I block) [1]. **Why the other options are Incorrect:** * **A, B, and C (D-tubocurarine, Gallamine, Pancuronium):** These are all **Non-depolarizing (Competitive) Blockers** [3]. They act as competitive antagonists at the Nm receptor. They prevent acetylcholine from binding but do not cause depolarization themselves [3]. **High-Yield NEET-PG Pearls:** * **Succinylcholine (Suxamethonium):** The only depolarizing blocker currently used in clinical practice (Decamethonium is largely of historical/experimental interest) [2]. * **Dual Block (Phase II Block):** With prolonged exposure or high doses, depolarizing blockers can lead to a state where the membrane repolarizes but remains insensitive to ACh, resembling a non-depolarizing block [4]. * **Metabolism:** Succinylcholine is rapidly hydrolyzed by **Pseudocholinesterase** (Butyrylcholinesterase). Patients with atypical pseudocholinesterase experience prolonged apnea. * **Key Side Effects of Depolarizing Blockers:** Hyperkalemia (critical in burn/trauma patients), muscle soreness, and triggering of Malignant Hyperthermia.

Question 278: Dantrolene acts on which receptor?

A. Ryanodine receptor (Correct Answer)
B. Cannabinoid receptor
C. Both of the above
D. None of the above

Explanation: **Explanation:** **1. Why Ryanodine Receptor (RyR1) is correct:** Dantrolene is a peripherally acting skeletal muscle relaxant [1]. Its primary mechanism of action is the blockade of the **Ryanodine Receptor (RyR1)** channels located on the **Sarcoplasmic Reticulum (SR)** of skeletal muscle fibers. By inhibiting these receptors, dantrolene prevents the release of calcium from the SR into the cytosol. Since calcium is essential for the interaction between actin and myosin, its reduction leads to decreased muscle contraction (excitation-contraction uncoupling) [1]. **2. Why other options are incorrect:** * **Cannabinoid receptors (CB1/CB2):** These are G-protein coupled receptors involved in appetite, pain-sensation, and mood. Drugs like Dronabinol act here, but they have no direct role in the mechanism of dantrolene. * **Options C and D:** These are incorrect as the action is specific to the Ryanodine receptor. **3. High-Yield Clinical Pearls for NEET-PG:** * **Drug of Choice (DOC):** Dantrolene is the life-saving drug of choice for **Malignant Hyperthermia** (often triggered by Succinylcholine or Halothane) and **Neuroleptic Malignant Syndrome (NMS)**. * **Specificity:** It acts specifically on RyR1 (skeletal muscle) rather than RyR2 (cardiac muscle), which is why it does not cause significant cardiotoxicity at therapeutic doses. * **Adverse Effect:** The most serious side effect of chronic dantrolene use (e.g., for spasticity) is **hepatotoxicity**; therefore, Liver Function Tests (LFTs) should be monitored. * **Other uses:** It is also used to treat spasticity associated with Upper Motor Neuron lesions (e.g., Stroke, Cerebral Palsy, Multiple Sclerosis) [1].

Question 279: Morphine can be administered by all of the following routes except:

A. Intramuscular
B. Transdermal
C. Epidural
D. Subarachnoid (Correct Answer)

Explanation: **Explanation:** The correct answer is **Subarachnoid (Option D)**. However, it is important to clarify a common pharmacological distinction: while Morphine is frequently administered via the **intrathecal** route (which is technically the subarachnoid space), in the context of standard medical examinations like NEET-PG, this question often tests the distinction between drugs suitable for **Transdermal patches**. *Note: There appears to be a discrepancy in the provided key. In standard clinical practice, Morphine is indeed given via the subarachnoid/intrathecal route. However, Morphine is **NOT** administered via the **Transdermal** route (Option B) because it is relatively hydrophilic and lacks the potency required for effective skin penetration.* **Analysis of Routes:** 1. **Intramuscular (A):** A standard route for acute pain management; morphine has good systemic absorption here. 2. **Transdermal (B):** **Incorrect for Morphine.** Only highly lipid-soluble and potent opioids like **Fentanyl** and **Buprenorphine** are available as transdermal patches. Morphine’s high hydrophilicity makes it unsuitable for this route. 3. **Epidural (C):** Commonly used for regional analgesia (e.g., post-operative or labor pain). 4. **Subarachnoid (D):** Also known as intrathecal administration. Morphine is used here for long-lasting spinal anesthesia due to its low lipid solubility, which allows it to remain in the CSF longer. **High-Yield Clinical Pearls for NEET-PG:** * **Lipid Solubility:** Fentanyl is highly lipid-soluble (rapid onset, short duration); Morphine is water-soluble (slow onset, long duration in CSF). * **Metabolism:** Morphine is metabolized to **Morphine-6-glucuronide** (active analgesic) and **Morphine-3-glucuronide** (neuroexcitatory/seizures). * **Contraindication:** Avoid Morphine in head injuries (increases intracranial pressure) and bronchial asthma (histamine release). * **Drug of Choice:** Morphine remains the gold standard for **Myocardial Infarction** pain and **Acute Left Ventricular Failure** (cardiac asthma).

Question 280: What is the mechanism of action of Levetiracetam?

A. Blocking SV2A protein (Correct Answer)
B. Inhibiting reuptake of GABA
C. Inhibiting GABA transaminase enzyme
D. Calcium channel blocker

Explanation: **Explanation:** **Mechanism of Action (Correct Answer: A)** Levetiracetam is a unique antiepileptic drug (AED) that does not act through traditional ion channel or GABAergic pathways. Its primary mechanism involves binding to the **Synaptic Vesicle Protein 2A (SV2A)**. This protein is located on the membranes of presynaptic vesicles and is involved in vesicle docking and fusion. By binding to SV2A, Levetiracetam modulates the release of neurotransmitters (specifically reducing the release of excitatory glutamate), thereby stabilizing neuronal excitability. **Analysis of Incorrect Options:** * **Option B (Inhibiting reuptake of GABA):** This is the mechanism of **Tiagabine**, which inhibits the GAT-1 transporter, increasing GABA concentration in the synaptic cleft. * **Option C (Inhibiting GABA transaminase):** This is the mechanism of **Vigabatrin**, which prevents the breakdown of GABA, leading to increased inhibitory levels. * **Option D (Calcium channel blocker):** This describes drugs like **Ethosuximide** (T-type Ca²⁺ channels) or **Gabapentin/Pregabalin** (α2δ subunit of N-type Ca²⁺ channels). **High-Yield Clinical Pearls for NEET-PG:** * **Pharmacokinetics:** It has near 100% bioavailability, minimal protein binding, and is excreted unchanged in urine (no CYP450 involvement), making it ideal for patients on multiple medications. * **Side Effects:** The most characteristic side effect is **behavioral changes** (irritability, aggression, or "Levy-rage"). * **Clinical Use:** It is a broad-spectrum AED used for focal-onset seizures, myoclonic seizures (JME), and generalized tonic-clonic seizures. * **Brivaracetam:** A newer analog with a higher affinity for SV2A than Levetiracetam.

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General Anesthetics

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Local Anesthetics

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Sedative-Hypnotics

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Antiepileptic Drugs

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Antiparkinsonian Drugs

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Opioid Analgesics

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Drugs of Abuse and Addiction

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Psychostimulants

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Hallucinogens

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CNS Stimulants and Cognitive Enhancers

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