Central Nervous System Pharmacology Practice Questions

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]

Q: Which of the following is a 5-HT2A antagonist drug?

Ketanserin. **Explanation:** **Ketanserin** is a selective **5-HT2A receptor antagonist** that also possesses $\alpha_1$-adrenergic blocking properties. Its primary pharmacological action involves blocking 5-HT2A receptors on smooth muscles (causing vasodilation) and platelets (inhibiting aggregation). Clinically, it has been used as an antihypertensive agent and in the management of Raynaud’s phenomenon and carcinoid syndrome. **Analysis of Incorrect Options:** * **Clozapine (Option A):** While Clozapine is an atypical antipsychotic that has high affinity for 5-HT2A receptors, it is primarily classified as a **D2/5-HT2A antagonist**. However, in the context of pure pharmacological classification for competitive exams, Ketanserin is the "prototype" 5-HT2A antagonist. * **Cisapride (Option B):** This is a **5-HT4 agonist**. It was used as a prokinetic agent to increase lower esophageal sphincter tone and accelerate gastric emptying, though its use is now restricted due to the risk of QT prolongation (Torsades de Pointes). * **Sumatriptan (Option C):** This is a selective **5-HT1B/1D agonist**. It is the gold standard for the acute treatment of migraine, acting via vasoconstriction of cranial vessels and inhibition of neuropeptide release. **High-Yield Clinical Pearls for NEET-PG:** * **Ritanserin** is another specific 5-HT2A antagonist often mentioned alongside Ketanserin. * **Cyproheptadine** is a non-selective 5-HT2 antagonist (also blocks H1) used in **Serotonin Syndrome**. * **5-HT3 Antagonists** (e.g., Ondansetron) are the only 5-HT receptors that are **ionotropic** (ligand-gated ion channels); all others are G-protein coupled receptors (GPCRs).

Q: Which drug is used in absence seizures and has a narrow spectrum of antiepileptic activity?

Ethosuximide. **Explanation** **Ethosuximide** is the drug of choice for **absence seizures (petit mal)** in children. Its mechanism of action involves the selective inhibition of **T-type Ca²⁺ channels** in thalamic neurons, which are responsible for the characteristic 3-Hz spike-and-wave discharges seen on EEG in absence epilepsy. It is considered a **narrow-spectrum** agent because it is ineffective against generalized tonic-clonic seizures (GTCS) or focal seizures. **Analysis of Incorrect Options:** * **Sodium Valproate:** While it is also a drug of choice for absence seizures, it is a **broad-spectrum** antiepileptic. It is preferred over ethosuximide only if the patient has concomitant GTCS. * **Lamotrigine:** This is a broad-spectrum agent used for various seizures, including absence seizures (as an alternative). However, it is not the primary narrow-spectrum drug for this indication. * **Primidone:** A barbiturate derivative primarily used for focal and generalized tonic-clonic seizures. It is not used for absence seizures and can sometimes exacerbate them. **High-Yield NEET-PG Pearls:** * **Drug of Choice (DOC):** Ethosuximide is the DOC for pure absence seizures. If absence seizures coexist with GTCS, **Valproate** becomes the DOC. * **Side Effects of Ethosuximide:** Remember the mnemonic **EFGHIJ** – **E**thosuximide causes **F**atigue, **G**I distress, **H**eadache, **I**tching (Urticaria), and Stevens-**J**ohnson syndrome. * **EEG Finding:** Absence seizures are classically associated with **3-Hz spike-and-wave** patterns. * **Contraindication:** Avoid **Carbamazepine** and **Phenytoin** in absence seizures as they may worsen the condition.

Question 1

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

Accepted Answer

Memantine

Answer

Rivastigmine

Answer

Donepezil

Answer

Galantamine

Question 2

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 3

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 4

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 5

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

Accepted Answer

Duloxetine

Answer

Brofaromine

Answer

Citalopram

Answer

Nefazodone

Question 6

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

Accepted Answer

Osteomalacia

Answer

Weight gain

Answer

Alopecia

Answer

Liver damage

Question 7

What is the most common side effect of levodopa?

Accepted Answer

Nausea and vomiting

Answer

Diarrhoea

Answer

Tremor

Answer

Rash

Question 8

Which of the following is a 5-HT2A antagonist drug?

Accepted Answer

Ketanserin

Answer

Clozapine

Answer

Cisapride

Answer

Sumatriptan

Question 9

Which of the following local anesthetics is suitable for a patient with hypertension and heart disease?

Accepted Answer

Prilocaine and felypressin

Answer

Lignocaine without adrenaline

Answer

Prilocaine

Answer

Lignocaine with adrenaline 1:1000

Question 10

Which drug is used in absence seizures and has a narrow spectrum of antiepileptic activity?

Accepted Answer

Ethosuximide

Answer

Lamotrigine

Answer

Sodium valproate

Answer

Primidone

Central Nervous System Pharmacology — MCQs

Central Nervous System Pharmacology — MCQs

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