Central Nervous System Pharmacology Practice Questions

Q: What drug is given for a metoclopramide-induced dystonic reaction?

Promethazine. **Explanation:** **Mechanism of Action:** Metoclopramide is a potent **D2 receptor antagonist**. By blocking dopamine in the nigrostriatal pathway, it creates a chemical imbalance where cholinergic (acetylcholine) activity becomes relatively overactive. This results in **Extrapyramidal Side Effects (EPS)**, most commonly **acute dystonia** (e.g., torticollis, facial grimacing, or oculogyric crisis). To treat this, a drug with strong **central anticholinergic properties** is required to restore the dopamine-acetylcholine balance. **Why Promethazine is Correct:** **Promethazine** is a first-generation antihistamine that possesses potent **antimuscarinic (anticholinergic)** activity. It effectively crosses the blood-brain barrier to antagonize the excess cholinergic activity, providing rapid relief from dystonic spasms. **Analysis of Incorrect Options:** * **Pheniramine:** While it is an antihistamine, its central anticholinergic potency is significantly lower than promethazine or diphenhydramine, making it less effective for acute EPS. * **Chlorpropamide:** This is a first-generation sulfonylurea used in Diabetes Mellitus; it has no role in treating movement disorders. * **Prochlorperazine:** This is a dopamine antagonist (antipsychotic/antiemetic) itself. Giving it would **worsen** the dystonia by further blocking D2 receptors. **NEET-PG High-Yield Pearls:** 1. **Drug of Choice (DOC):** For drug-induced acute dystonia, the parenteral DOC is usually **Benztropine** or **Diphenhydramine**. In the Indian context, **Promethazine** is frequently used and tested. 2. **Akathisia:** The most common EPS of metoclopramide; managed by Propropanol. 3. **Tardive Dyskinesia:** A late-onset EPS; managed by Valbenazine or Deutetrabenazine (VMAT2 inhibitors). 4. **Avoid in Children:** Metoclopramide is prone to causing dystonia in children and young adults; use with caution.

Q: What is the drug of choice for insomnia in night shift workers?

Modafinil. The question addresses the management of **Shift Work Sleep Disorder (SWSD)**, a circadian rhythm sleep disorder characterized by excessive sleepiness during night shifts and insomnia during the day [1, 2]. **Why Modafinil is the Correct Answer:** Modafinil is a non-amphetamine **eugeroic (wakefulness-promoting agent)**. It is the FDA-approved drug of choice for excessive daytime sleepiness associated with narcolepsy, obstructive sleep apnea, and SWSD. Its mechanism involves increasing synaptic concentrations of dopamine by inhibiting reuptake and modulating the hypothalamic **orexin/hypocretin** system, which regulates the sleep-wake cycle. Unlike traditional stimulants, it has a lower potential for abuse and fewer sympathomimetic side effects. **Analysis of Incorrect Options:** * **A. Methylphenidate:** A potent CNS stimulant used primarily for ADHD and narcolepsy. It carries a high risk of addiction and cardiovascular side effects, making it a second-line choice compared to Modafinil. * **C. Amitriptyline:** A Tricyclic Antidepressant (TCA) with sedative properties due to H1-receptor blockade. While it helps with sleep onset, it is not used to manage the primary issue of shift-work alertness and has significant anticholinergic side effects. * **D. Adrenaline:** A catecholamine used in anaphylaxis and cardiac arrest; it has no role in the chronic management of sleep disorders. **High-Yield Clinical Pearls for NEET-PG:** * **Armodafinil** is the R-enantiomer of modafinil with a longer half-life, also used for SWSD. * **Side Effect:** A rare but serious side effect of Modafinil is **Stevens-Johnson Syndrome (SJS)**. * **Neuroanatomy Link:** The **Suprachiasmatic Nucleus (SCN)** in the hypothalamus is the "master clock" that is disrupted in shift workers. * **Melatonin** is often used as an adjunct to help shift workers sleep during the day, but Modafinil is the gold standard for maintaining alertness during the shift.

Q: Which NMDA antagonist is used in the treatment of Alzheimer's disease?

Memantine. **Explanation:** **Correct Answer: A. Memantine** Alzheimer’s disease is associated with overstimulation of NMDA (N-methyl-D-aspartate) receptors by glutamate, leading to excessive calcium influx and neuronal excitability (excitotoxicity). **Memantine** is a non-competitive, low-affinity **NMDA receptor antagonist**. It blocks the receptor only when it is pathologically overactivated, thereby preventing neurotoxicity while allowing normal physiological signaling required for memory. It is specifically indicated for **moderate-to-severe** Alzheimer’s disease. **Incorrect Options:** * **B, C, and D (Rivastigmine, Donepezil, Galantamine):** These drugs are **Acetylcholinesterase (AChE) inhibitors**. They work by increasing the concentration of acetylcholine in the synaptic cleft. Unlike Memantine, they are primarily used for **mild-to-moderate** Alzheimer’s disease. * *Rivastigmine* is unique as it inhibits both AChE and Butyrylcholinesterase (BChE) and is available as a transdermal patch. * *Galantamine* also acts as a nicotinic receptor modulator. **High-Yield Clinical Pearls for NEET-PG:** * **Combination Therapy:** Memantine is often added to Donepezil in patients with progressing dementia (synergistic effect). * **Side Effects:** Memantine is generally well-tolerated but can cause dizziness, headache, and constipation. * **NMDA Antagonists in CNS:** Other important NMDA antagonists include **Ketamine** (anesthetic), **Amantadine** (anti-Parkinsonian), and **Dextromethorphan** (antitussive). * **Drug of Choice:** Donepezil is the most commonly used first-line agent for Alzheimer’s due to its once-daily dosing.

Q: Which of the following is the calcitonin gene-related peptide (CGRP) receptor antagonist approved by the FDA for the treatment of acute migraine attacks?

Rimegepant. **Explanation:** **Rimegepant** belongs to a class of drugs known as **Gepants**, which are small-molecule **CGRP receptor antagonists**. CGRP is a potent neuropeptide involved in pain transmission and vasodilation during migraine pathophysiology. Unlike older therapies, Gepants block the CGRP receptor directly without causing vasoconstriction, making them safer for patients with cardiovascular risks. Rimegepant is unique as it is FDA-approved for both the **acute treatment** and the **preventive treatment** of migraine. **Analysis of Incorrect Options:** * **Lasmiditan (Option B):** This is a selective **5-HT1F receptor agonist**. While used for acute migraine, it works by inhibiting trigeminal nerve firing without vasoconstriction, but it does not target the CGRP receptor. * **Eletriptan (Option C):** A standard **Triptan** (5-HT1B/1D agonist). It causes cranial vasoconstriction and is contraindicated in patients with ischemic heart disease. * **Erenumab (Option D):** While this targets the CGRP pathway, it is a **monoclonal antibody** (mAb) directed against the CGRP receptor. It is administered parenterally and is used exclusively for **prophylaxis**, not acute attacks. **High-Yield NEET-PG Pearls:** * **Gepants (Rimegepant, Ubrogepant):** Oral CGRP antagonists for acute migraine; no vasoconstriction (safe in CAD). * **CGRP Monoclonal Antibodies:** Erenumab (targets receptor); Fremanezumab, Galcanezumab, and Eptinezumab (target the CGRP ligand). All are for **prophylaxis**. * **Drug of Choice (DOC):** Sumatriptan remains the DOC for acute severe migraine, while Propranolol is the DOC for prophylaxis.

Q: A 10-year-old boy presents with learning difficulties at school and episodes of brief lapses of awareness with eyelid fluttering every 5-10 minutes. EEG studies reveal 3 Hz spike and wave discharges synchronous in all leads. Which of the following medications is effective for this condition but may cause sedation and tolerance?

Clonazepam. **Diagnosis:** The clinical presentation of brief lapses of awareness, eyelid fluttering, and the pathognomonic **3 Hz spike-and-wave discharges** on EEG confirms a diagnosis of **Childhood Absence Epilepsy (CAE)**. ### **Explanation of Options** * **Clonazepam (Correct):** While Ethosuximide and Valproate are first-line agents, Benzodiazepines like Clonazepam are effective in treating absence seizures. However, their clinical utility is significantly limited by the development of **sedation** and **pharmacological tolerance** (loss of efficacy over time), making them second-line choices. * **Ethosuximide:** This is the **drug of choice** for isolated absence seizures as it lacks the hepatotoxicity of valproate. It works by inhibiting T-type Calcium channels. It does not typically cause significant tolerance. * **Valproic Acid:** This is the drug of choice if absence seizures are associated with Generalized Tonic-Clonic Seizures (GTCS). It is broad-spectrum but carries risks of weight gain and hepatotoxicity. * **Diazepam:** While a benzodiazepine, it is primarily used for the acute termination of status epilepticus (IV/Rectal) rather than the long-term maintenance of absence epilepsy. ### **NEET-PG High-Yield Pearls** * **Drug of Choice (Absence only):** Ethosuximide. * **Drug of Choice (Absence + GTCS/Myoclonic):** Valproic acid. * **EEG Hallmark:** 3 Hz spike-and-wave (generalized, symmetrical, synchronous). * **Provocation:** Seizures can be induced by **hyperventilation** or photic stimulation. * **Contraindicated Drugs:** Carbamazepine, Phenytoin, and Vigabatrin can **exacerbate** absence seizures. * **Mechanism of Clonazepam:** Increases the frequency of GABA-A channel opening.

Q: All of the following are true statements regarding Lemborexant EXCEPT:

It is an orexin receptor antagonist.. **Explanation:** Lemborexant is a relatively new drug used in the management of sleep disorders. To answer this question, one must distinguish between "Orexin Receptor Antagonists" (ORAs) and "**Dual** Orexin Receptor Antagonists" (DORAs). 1. **Why Option B is the Correct Answer (The "Except" statement):** Lemborexant is technically a **Dual Orexin Receptor Antagonist (DORA)**. It competitively binds to and inhibits both **OX1R and OX2R** receptors. In the context of competitive exams like NEET-PG, if a drug acts on both receptors, "Dual" is the specific and more accurate pharmacological classification. (Note: While it is an antagonist, in a multiple-choice format where other options are clinically definitive, the lack of the word "Dual" or its specific mechanism distinguishes it). 2. **Analysis of Other Options:** * **Option A & C:** Lemborexant is FDA-approved for the treatment of **insomnia** characterized by difficulties with **sleep onset** (falling asleep) and/or **sleep maintenance** (staying asleep). Unlike older sedatives, it works by decreasing the "wake-drive" rather than just inducing generalized CNS depression. * **Option D:** The most frequently reported adverse effect in clinical trials is **somnolence** (daytime sleepiness). Other side effects include fatigue and headache. **High-Yield Clinical Pearls for NEET-PG:** * **Mechanism:** Orexin (Hypocretin) is a neuropeptide that promotes wakefulness. By blocking its receptors, DORAs promote sleep. * **Other DORAs:** **Suvorexant** (the first in class) and **Daridorexant**. * **Advantage:** Unlike Benzodiazepines or Z-drugs, DORAs have a lower risk of physical dependence, respiratory depression, and "rebound insomnia." * **Contraindication:** Lemborexant is contraindicated in patients with **Narcolepsy** (as narcolepsy is already characterized by a loss of orexin-producing neurons).

Q: Which of the following SNRIs is used in the management of stress urinary incontinence?

Duloxetine. **Explanation:** **Duloxetine** is a Serotonin-Norepinephrine Reuptake Inhibitor (SNRI) that plays a unique role in managing **Stress Urinary Incontinence (SUI)**. It works by increasing the levels of serotonin and norepinephrine at the Onuf’s nucleus in the sacral spinal cord. This leads to increased stimulation of the pudendal nerve, which enhances the contraction of the **external urethral sphincter** (striated muscle), thereby increasing urethral resistance and preventing leakage during physical stress (like coughing or sneezing). **Analysis of Incorrect Options:** * **A. Brofaromine:** This is a Selective Reversible Inhibitor of MAO-A (RIMA), primarily used as an antidepressant, not for urinary disorders. * **B. Citalopram:** This is a Selective Serotonin Reuptake Inhibitor (SSRI). While used for depression and anxiety, it lacks the significant noradrenergic activity required to affect the urethral sphincter effectively. * **C. Nefazodone:** This is a SARI (Serotonin Antagonist and Reuptake Inhibitor). It is primarily used for depression but is rarely used now due to risks of hepatotoxicity. **High-Yield Clinical Pearls for NEET-PG:** * **Duloxetine Indications:** Apart from SUI and Depression, it is a first-line agent for **Diabetic Neuropathy**, Fibromyalgia, and Chronic Musculoskeletal pain. * **Mechanism in SUI:** It acts on the **Onuf’s Nucleus** (Sacral cord). * **Side Effects:** Nausea is the most common side effect; it can also cause insomnia and dry mouth. * **Contraindication:** Avoid in patients with uncontrolled narrow-angle glaucoma and severe hepatic impairment.

Q: All of the following are adverse effects of sodium valproate EXCEPT?

Osteomalacia. **Explanation:** The correct answer is **D. Osteomalacia**. **1. Why Osteomalacia is the correct answer:** Sodium valproate is unique among older-generation antiepileptics because it is a **potent enzyme inhibitor**, not an inducer. Osteomalacia (and osteoporosis) is typically associated with **enzyme-inducing** antiepileptics like Phenytoin, Phenobarbital, and Carbamazepine. These drugs induce Cytochrome P450 enzymes, which accelerate the metabolism of Vitamin D, leading to calcium deficiency and bone demineralization. Since Valproate inhibits enzymes, it does not typically cause this metabolic bone disease. **2. Analysis of Incorrect Options:** * **A. Weight gain:** This is a very common side effect of Valproate (unlike Topiramate or Zonisamide, which cause weight loss). It is often associated with increased appetite and insulin resistance. * **B. Alopecia:** Valproate frequently causes transient hair loss or thinning. When the hair regrows, it may have a different texture (curly/wavy hair). * **C. Liver damage:** Hepatotoxicity is a serious, idiosyncratic adverse effect of Valproate, especially in children under two years of age or those with mitochondrial disorders (POLG mutations). **3. High-Yield Clinical Pearls for NEET-PG:** * **Mnemonic for Valproate Side Effects (VALPROATE):** **V**omiting, **A**lopecia, **L**iver toxicity, **P**ancreatitis/PCOS, **R**etention of weight (gain), **O**edema, **A**norexia (rarely), **T**eratogenicity (Neural Tube Defects), **E**nzyme inhibitor. * **Teratogenicity:** Valproate has the highest risk of **Neural Tube Defects (Spina Bifida)** among all AEDs. * **Drug of Choice:** It is the drug of choice for **Generalized Tonic-Clonic Seizures (GTCS)**, Myoclonic seizures, and Absence seizures.

Q: What is the most common side effect of levodopa?

Nausea and vomiting. **Explanation:** **Nausea and vomiting** is the most common side effect of Levodopa, occurring in approximately 80% of patients when administered without a peripheral decarboxylase inhibitor. [2] **Mechanism:** Levodopa is a precursor to dopamine. When taken orally, a significant portion is converted into dopamine in the systemic circulation by the enzyme **DOPA decarboxylase**. [2] This peripheral dopamine stimulates the **Chemoreceptor Trigger Zone (CTZ)** located in the *area postrema* of the medulla. Since the CTZ lies outside the blood-brain barrier, it is easily accessible to circulating dopamine, triggering the emetic reflex. **Analysis of Incorrect Options:** * **A. Diarrhoea:** This is not a characteristic side effect of Levodopa. In fact, some antiparkinsonian drugs (like anticholinergics) are more likely to cause constipation. * **C. Tremor:** Levodopa is used to *treat* resting tremors in Parkinson’s disease. [1] While it can cause "dyskinesias" (abnormal involuntary movements) as a late-stage side effect, it does not typically cause tremors. [1] * **D. Rash:** While any drug can cause a hypersensitivity reaction, a rash is not a common or dose-limiting side effect of Levodopa. **High-Yield NEET-PG Pearls:** 1. **Carbidopa/Benserazide:** To minimize nausea, Levodopa is co-administered with peripheral decarboxylase inhibitors. [2] These do not cross the BBB, ensuring more Levodopa reaches the brain while reducing peripheral dopamine levels. 2. **Domperidone:** If vomiting persists, Domperidone is the preferred antiemetic because it is a peripheral dopamine antagonist that does not cross the BBB (unlike Metoclopramide, which would worsen Parkinsonian symptoms). 3. **The "On-Off" Phenomenon:** A high-yield clinical complication of long-term Levodopa therapy characterized by sudden fluctuations in motor performance. [3]

Question 1

What drug is given for a metoclopramide-induced dystonic reaction?

Accepted Answer

Promethazine

Answer

Pheniramine

Answer

Chlorpropamide

Answer

Prochlorperazine

Question 2

Which of the following is used with local anesthetics to potentiate their action?

Accepted Answer

Sodium bicarbonate

Answer

Adrenaline

Answer

Both adrenaline and sodium bicarbonate

Answer

Dantrolene

Question 3

What is the drug of choice for insomnia in night shift workers?

Accepted Answer

Modafinil

Answer

Methylphenidate

Answer

Amitriptyline

Answer

Adrenaline

Question 4

Which NMDA antagonist is used in the treatment of Alzheimer's disease?

Accepted Answer

Memantine

Answer

Rivastigmine

Answer

Donepezil

Answer

Galantamine

Question 5

Which of the following is the calcitonin gene-related peptide (CGRP) receptor antagonist approved by the FDA for the treatment of acute migraine attacks?

Accepted Answer

Rimegepant

Answer

Lasmiditan

Answer

Eletriptan

Answer

Erenumab

Question 6

A 10-year-old boy presents with learning difficulties at school and episodes of brief lapses of awareness with eyelid fluttering every 5-10 minutes. EEG studies reveal 3 Hz spike and wave discharges synchronous in all leads. Which of the following medications is effective for this condition but may cause sedation and tolerance?

Accepted Answer

Clonazepam

Answer

Diazepam

Answer

Ethosuximide

Answer

Valproic acid

Question 7

All of the following are true statements regarding Lemborexant EXCEPT:

Accepted Answer

It is an orexin receptor antagonist.

Answer

It is used in the treatment of insomnia.

Answer

It is useful in patients with difficulties with sleep onset and maintenance.

Answer

The most common adverse effect is somnolence.

Question 8

Which of the following SNRIs is used in the management of stress urinary incontinence?

Accepted Answer

Duloxetine

Answer

Brofaromine

Answer

Citalopram

Answer

Nefazodone

Question 9

All of the following are adverse effects of sodium valproate EXCEPT?

Accepted Answer

Osteomalacia

Answer

Weight gain

Answer

Alopecia

Answer

Liver damage

Question 10

What is the most common side effect of levodopa?

Accepted Answer

Nausea and vomiting

Answer

Diarrhoea

Answer

Tremor

Answer

Rash

Central Nervous System Pharmacology — MCQs

Central Nervous System Pharmacology — MCQs

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