Central Nervous System Pharmacology — MCQs

Central Nervous System Pharmacology Indian Medical PG Practice Questions and MCQs

Question 61: What is the side effect of phenytoin when its plasma concentration is above the therapeutic level?

A. Ataxia (Correct Answer)
B. Gum hypertrophy
C. Osteomalacia
D. Hirsutism

Explanation: Phenytoin is a commonly tested antiepileptic drug in NEET-PG due to its unique **non-linear (zero-order) kinetics** and a narrow therapeutic index (10–20 µg/mL). ### **Explanation of the Correct Answer** **Ataxia** is a **dose-dependent** (concentration-dependent) side effect. As plasma levels rise above the therapeutic range, phenytoin causes cerebellar-vestibular dysfunction. The progression typically follows a predictable pattern: * **>20 µg/mL:** Nystagmus (earliest sign) * **>30 µg/mL:** **Ataxia**, slurred speech, and diplopia * **>40 µg/mL:** Mental confusion, lethargy, and coma ### **Why Other Options are Incorrect** Options B, C, and D are all recognized side effects of phenytoin, but they are **non-dose-dependent** (chronic) side effects. They occur due to long-term use rather than acute toxicity: * **Gum Hypertrophy:** Occurs due to overgrowth of gingival collagen (stimulated by PDGF). * **Osteomalacia:** Phenytoin induces Cytochrome P450 enzymes, increasing the metabolism of Vitamin D, leading to hypocalcemia. * **Hirsutism:** Excessive hair growth is a common cosmetic side effect in chronic users. ### **High-Yield Clinical Pearls for NEET-PG** * **Mnemonic for Phenytoin Side Effects (HOT MALAI):** **H**irsutism, **O**steomalacia, **T**eratogenicity (Fetal Hydantoin Syndrome), **M**egaloblastic anemia (folate deficiency), **A**taxia, **L**ymphadenopathy, **A**rrhythmias (on rapid IV injection), **I**nsulin inhibition (hyperglycemia). * **Fetal Hydantoin Syndrome:** Characterized by cleft lip/palate and digital hypoplasia. * **Zero-order kinetics:** Small dose increases can lead to disproportionately large increases in plasma levels because metabolic enzymes (CYP2C9) become saturated.

Question 62: Schizophrenia can be treated with all the following medications EXCEPT:

A. Pemoline (Correct Answer)
B. Olanzapine
C. Sulpiride
D. Chlorpromazine

Explanation: **Explanation:** The treatment of Schizophrenia primarily involves blocking dopaminergic activity in the brain, whereas **Pemoline** (Option A) does the exact opposite. **Why Pemoline is the correct answer:** Pemoline is a central nervous system (CNS) stimulant that acts by increasing the release and inhibiting the reuptake of dopamine. It was historically used for ADHD and Narcolepsy. Because it increases dopaminergic activity, it can actually **exacerbate or induce psychotic symptoms** (the "Dopamine Hypothesis" of schizophrenia suggests that psychosis is linked to overactive dopamine in the mesolimbic pathway). Therefore, it is contraindicated in schizophrenia. **Why the other options are incorrect:** * **Olanzapine (Option B):** An atypical (second-generation) antipsychotic. it blocks both $D_2$ and $5-HT_{2A}$ receptors and is a first-line treatment for schizophrenia due to its lower risk of extrapyramidal side effects (EPS). * **Sulpiride (Option C):** A substituted benzamide that acts as a selective $D_2$ receptor antagonist. It is used effectively as an antipsychotic, particularly in Europe and Asia. * **Chlorpromazine (Option D):** A low-potency typical (first-generation) antipsychotic. It is the prototype drug of the phenothiazine class and works by blocking $D_2$ receptors. **High-Yield NEET-PG Pearls:** * **Dopamine Hypothesis:** Schizophrenia is associated with hyperdopaminergia in the mesolimbic pathway (positive symptoms) and hypodopaminergia in the mesocortical pathway (negative symptoms). * **Pemoline Alert:** It is rarely used today due to significant **hepatotoxicity** (requires regular LFT monitoring). * **Drug of Choice:** For treatment-resistant schizophrenia, the drug of choice is **Clozapine**, though it requires monitoring for agranulocytosis.

Question 63: What is the therapeutic indication of Donepezil?

A. Parkinsonism
B. Alzheimer's disease (Correct Answer)
C. Multiple sclerosis
D. Myasthenia gravis

Explanation: **Explanation:** **Correct Answer: B. Alzheimer's disease** **Mechanism and Rationale:** Donepezil is a **reversible, centrally-acting acetylcholinesterase (AChE) inhibitor**. In Alzheimer’s disease, there is a progressive loss of cholinergic neurons in the nucleus basalis of Meynert, leading to a deficiency of acetylcholine (ACh) in the cerebral cortex. Donepezil inhibits the enzyme responsible for breaking down ACh, thereby increasing its concentration at the synaptic cleft. This enhances cholinergic neurotransmission, which helps improve cognitive function and delay the progression of symptoms in mild to severe Alzheimer’s. **Analysis of Incorrect Options:** * **A. Parkinsonism:** This condition is characterized by a dopamine deficiency. Treatment involves dopamine agonists or levodopa. While some AChE inhibitors (like Rivastigmine) are used specifically for Parkinson’s Disease *Dementia*, Donepezil is not the primary treatment for motor Parkinsonism. * **C. Multiple Sclerosis:** This is an autoimmune demyelinating disorder of the CNS. Treatment focuses on disease-modifying therapies (e.g., Interferon-beta, Glatiramer) and steroids for acute relapses, not cholinergic enhancement. * **D. Myasthenia Gravis:** While this condition is treated with AChE inhibitors (like **Pyridostigmine**), these drugs must act **peripherally** at the neuromuscular junction. Donepezil is highly selective for the CNS and is not used for MG. **High-Yield Clinical Pearls for NEET-PG:** * **Other CNS AChE Inhibitors:** Rivastigmine (available as a transdermal patch) and Galantamine. * **Side Effects:** Primarily cholinergic (SLUDGE)—nausea, vomiting, diarrhea, and **bradycardia** (important to monitor in elderly patients). * **Metabolism:** Donepezil is metabolized by CYP450 (3A4 and 2D6), making it prone to drug interactions. * **Memantine:** Often used in combination with Donepezil; it is an NMDA receptor antagonist used for moderate-to-severe Alzheimer's.

Question 64: Vigabatrine is the drug of choice for which of the following conditions?

A. Febrile seizures
B. Myoclonic epilepsy
C. Infantile spasms (Correct Answer)
D. Partial seizures

Explanation: **Explanation:** **Infantile Spasms (West Syndrome)** is the correct answer. Vigabatrin is considered the drug of choice specifically for infantile spasms associated with **Tuberous Sclerosis**. Its mechanism of action involves the irreversible inhibition of **GABA transaminase**, the enzyme responsible for the degradation of GABA. This leads to increased levels of GABA (the primary inhibitory neurotransmitter) in the synaptic cleft, effectively suppressing the characteristic spasms. **Analysis of Incorrect Options:** * **A. Febrile Seizures:** The management of choice is usually reassurance or rectal diazepam (if prolonged). Long-term prophylaxis is generally avoided, but if necessary, phenobarbital or sodium valproate is used. * **B. Myoclonic Epilepsy:** Sodium Valproate is the drug of choice. Vigabatrin is actually contraindicated here as it can aggravate myoclonic and absence seizures. * **C. Partial Seizures:** While Vigabatrin is effective as an adjunctive therapy for refractory focal (partial) seizures, it is not the "drug of choice" due to its side effect profile. Carbamazepine or Levetiracetam are typically preferred. **High-Yield Clinical Pearls for NEET-PG:** * **Visual Field Defects:** The most significant adverse effect of Vigabatrin is **permanent bilateral concentric visual field constriction** (retinotoxicity), necessitating regular perimetry monitoring. * **West Syndrome Triad:** Infantile spasms, mental retardation, and a characteristic EEG pattern known as **Hypsarrhythmia**. * **Alternative Treatment:** For infantile spasms *not* caused by Tuberous Sclerosis, **ACTH** or oral prednisolone is often the first-line preference.

Question 65: Akathisia is treated by which of the following medications, except?

A. Trihexyphenidyl
B. Propanolol
C. Haloperidol (Correct Answer)
D. Promethazine

Explanation: **Explanation:** **Akathisia** is a common and distressing Extrapyramidal Side Effect (EPS) characterized by subjective feelings of inner restlessness and an objective inability to sit still. It is most commonly caused by **Dopamine (D2) receptor antagonists**, such as typical antipsychotics. **Why Haloperidol is the correct answer:** Haloperidol is a high-potency typical antipsychotic and a potent D2 receptor blocker. It is a **primary cause** of akathisia, not a treatment for it. Administering haloperidol to a patient with akathisia would exacerbate the condition. **Analysis of other options:** * **Protolol (Beta-blockers):** Centrally acting lipophilic beta-blockers like Propranolol are considered the **first-line treatment** for akathisia. They help reduce the subjective feeling of restlessness. * **Trihexyphenidyl (Anticholinergics):** Centrally acting anticholinergics are effective in treating various EPS, including acute dystonia and parkinsonism. While less effective for akathisia than beta-blockers, they are still used as second-line agents. * **Promethazine:** This is an antihistamine with significant anticholinergic properties. It is frequently used in clinical practice to manage acute EPS. **High-Yield Clinical Pearls for NEET-PG:** 1. **Drug of Choice (DOC):** For Akathisia is **Propranolol**. 2. **Acute Dystonia:** The earliest EPS to appear (within hours); treated with intravenous/intramuscular anticholinergics (e.g., Benztropine, Promethazine). 3. **Tardive Dyskinesia:** Occurs after long-term use; characterized by choreoathetoid movements. Treatment involves switching to Clozapine or using VMAT-2 inhibitors (Valbenazine). 4. **Benzodiazepines:** Can also be used as an adjunct treatment for akathisia to reduce anxiety and motor restlessness.

Question 66: Which anti-convulsants are frequently used in the management of trigeminal neuralgia?

A. Phenytoin
B. Gabapentin
C. Baclofen
D. All of the above (Correct Answer)

Explanation: **Explanation:** Trigeminal neuralgia is characterized by sudden, severe, brief, stabbing, and recurrent episodes of pain in the distribution of one or more branches of the fifth cranial nerve. The primary pharmacological goal is to reduce the hyperexcitability of the trigeminal nerve and its nucleus. **Why "All of the Above" is correct:** While **Carbamazepine** remains the first-line drug of choice (DOC) for trigeminal neuralgia, several other agents are frequently used as alternatives or adjuncts: * **Phenytoin (Option A):** It was the first drug used for this condition. It works by blocking voltage-gated sodium channels, thereby stabilizing neuronal membranes and preventing repetitive firing. * **Gabapentin (Option B):** This is a structural analogue of GABA that binds to the $\alpha_2\delta$ subunit of voltage-gated calcium channels. It is highly effective, especially in patients who do not tolerate Carbamazepine or those with Multiple Sclerosis-associated neuralgia. * **Baclofen (Option C):** Although primarily a $GABA_B$ receptor agonist (skeletal muscle relaxant), it is frequently used in trigeminal neuralgia to enhance pre-synaptic inhibition. It is often used in combination with Carbamazepine or Phenytoin for a synergistic effect. **High-Yield Clinical Pearls for NEET-PG:** * **Drug of Choice:** Carbamazepine is the gold standard/first-line treatment. * **Second-line/Adjuncts:** Oxcarbazepine, Baclofen, Lamotrigine, and Gabapentin. * **Surgical Management:** If medical therapy fails, **Microvascular Decompression (Janetta procedure)** is the definitive surgical treatment. * **Mechanism Focus:** Most effective drugs for this condition work by inhibiting sodium channels or enhancing GABAergic inhibition to dampen paroxysmal neuronal discharges.

Question 67: 'Diffusion hypoxia' is likely to occur only after use of nitrous oxide because it?

A. Is a respiratory depressant
B. Has low blood solubility and is used in high concentration (Correct Answer)
C. Is a very potent anaesthetic
D. Interferes with diffusion of oxygen into the tissues

Explanation: **Explanation:** **Diffusion Hypoxia (Fink Effect)** occurs during the recovery phase of anesthesia. The correct answer is **Option B** due to two specific properties of Nitrous Oxide ($N_2O$): 1. **Low Blood Solubility:** $N_2O$ is relatively insoluble in blood (Blood:Gas partition coefficient = 0.47). This allows it to leave the blood and enter the alveoli very rapidly once the mask is removed. 2. **High Concentration:** Unlike potent volatile anesthetics used in 1-5% concentrations, $N_2O$ is administered in high concentrations (up to 70%). When $N_2O$ administration is stopped, a massive volume of the gas rushes out of the blood into the alveoli. This "flooding" of the alveoli **dilutes the partial pressure of Oxygen ($PAO_2$)**, leading to a transient drop in oxygen saturation. This is prevented by administering 100% pure oxygen for a few minutes during the recovery phase. **Why other options are incorrect:** * **Option A:** $N_2O$ is actually a very weak respiratory depressant compared to other inhalational agents. Diffusion hypoxia is a physical gas-exchange phenomenon, not a result of depressed drive. * **Option C:** $N_2O$ is a **low-potency** anesthetic (MAC > 100%). Its low potency is exactly why it must be used in high concentrations, which contributes to diffusion hypoxia. * **Option D:** $N_2O$ does not interfere with the internal respiration or the diffusion of oxygen at the tissue/cellular level; it affects the concentration of oxygen within the lung alveoli. **High-Yield Pearls for NEET-PG:** * **Second Gas Effect:** The same properties (low solubility/high concentration) allow $N_2O$ to speed up the induction of a co-administered volatile anesthetic (e.g., Halothane). * **Contraindication:** $N_2O$ should be avoided in patients with pneumothorax, intestinal obstruction, or middle ear surgery because it diffuses into air-filled cavities faster than nitrogen can leave, increasing the volume/pressure of the cavity.

Question 68: Which of the following drugs is considered relatively safe for epileptic patients during pregnancy?

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

Explanation: **Explanation:** Managing epilepsy during pregnancy requires balancing maternal seizure control against the risk of teratogenicity. While almost all older anti-epileptic drugs (AEDs) carry some risk, **Phenobarbitone** is considered relatively safer compared to the other options listed, particularly Valproate. **1. Why Phenobarbitone is the correct answer:** Phenobarbitone has been used for decades. While it is associated with a risk of congenital malformations (specifically cardiac defects and orofacial clefts) and neonatal hemorrhage (due to Vitamin K deficiency), its **teratogenic potential is lower** than that of Valproate or Phenytoin. In many clinical guidelines, if a patient is already well-controlled on Phenobarbitone, it is often continued at the lowest effective dose. **2. Why the other options are incorrect:** * **Valproate (Option C):** This is the **most teratogenic** AED. It is strongly associated with **Neural Tube Defects (NTDs)** like spina bifida, as well as cognitive impairment in the offspring. It is generally contraindicated in pregnancy unless no other drug works. * **Phenytoin (Option D):** Associated with **Fetal Hydantoin Syndrome**, characterized by craniofacial dysmorphism, hypoplastic phalanges/nails, and growth retardation. * **Carbamazepine (Option A):** Also associated with NTDs and craniofacial defects, though the risk is slightly lower than Valproate. **High-Yield Clinical Pearls for NEET-PG:** * **Drug of Choice (DOC):** Currently, **Levetiracetam** and **Lamotrigine** are considered the safest first-line AEDs in pregnancy. * **Folic Acid:** All pregnant women on AEDs should receive high-dose folic acid (5 mg/day) to reduce the risk of NTDs. * **Neonatal Care:** Infants born to mothers on enzyme-inducing AEDs (Phenobarbitone, Phenytoin) should receive **Vitamin K** at birth to prevent hemorrhagic disease of the newborn.

Question 69: Which of the following dopamine agonists used in the treatment of Parkinsonism is available as a transdermal patch but not an oral formulation?

A. Apomorphine
B. Ropinirole
C. Rotigotine (Correct Answer)
D. Pramipexole

Explanation: **Explanation:** **Rotigotine** is a non-ergoline dopamine agonist that is uniquely formulated as a **transdermal patch** for the treatment of Parkinson’s disease and Restless Legs Syndrome. It is not available in an oral formulation because it undergoes extensive first-pass metabolism in the liver, leading to poor oral bioavailability. The transdermal delivery system provides continuous drug delivery over 24 hours, ensuring stable plasma levels and reducing "off" periods. **Analysis of Incorrect Options:** * **Apomorphine (Option A):** This is a potent dopamine agonist used for "rescue" therapy during severe "off" episodes. It is administered via **subcutaneous injection** or continuous infusion, not as a patch. It also has poor oral bioavailability. * **Ropinirole (Option B) & Pramipexole (Option D):** These are non-ergoline dopamine agonists commonly used as first-line agents. Both are primarily administered as **oral formulations** (available in immediate and extended-release tablets). **High-Yield NEET-PG Pearls:** * **Rotigotine:** Think "Rotigotine = Rotates on the skin" (Patch). It acts on D1, D2, and D3 receptors. * **Pramipexole:** Has antioxidant properties and is excreted unchanged in the urine (requires dose adjustment in renal failure). * **Ropinirole:** Metabolized by CYP1A2; smoking can induce this enzyme and decrease drug levels. * **Ergot vs. Non-Ergot:** Rotigotine, Ropinirole, and Pramipexole are non-ergot derivatives, meaning they do not carry the risk of cardiac valvular fibrosis associated with older drugs like Bromocriptine or Pergolide.

Question 70: Sumatriptan is used in which of the following conditions?

A. Glaucoma
B. Migraine (Correct Answer)
C. Hypertension
D. Opioid withdrawal

Explanation: **Explanation:** **Sumatriptan** is the prototype of the 'Triptan' class of drugs, which are the first-line agents for the **abortive (acute) treatment of moderate-to-severe migraine attacks.** **1. Why Migraine is Correct:** Sumatriptan acts as a selective **5-HT$_{1B/1D}$ receptor agonist**. Its therapeutic effect in migraine is mediated through three mechanisms: * **Vasoconstriction:** Stimulation of 5-HT$_{1B}$ receptors on intracranial blood vessels causes vasoconstriction of dilated meningeal vessels. * **Neuropeptide Inhibition:** Stimulation of 5-HT$_{1D}$ receptors on trigeminal nerve terminals inhibits the release of pro-inflammatory neuropeptides (like CGRP and Substance P). * **Central Inhibition:** It reduces pain transmission in the trigeminal nucleus caudalis. **2. Why Other Options are Incorrect:** * **Glaucoma:** Sumatriptan has no role here. Drugs like Timolol (beta-blocker) or Latanoprost (PG analog) are used. * **Hypertension:** Sumatriptan is actually **contraindicated** in patients with uncontrolled hypertension or ischemic heart disease because it can cause coronary vasospasm. * **Opioid Withdrawal:** This is managed with Methadone, Buprenorphine, or Clonidine. **High-Yield Clinical Pearls for NEET-PG:** * **Route of Administration:** Sumatriptan has low oral bioavailability (approx. 15%). Subcutaneous administration is the fastest and most effective route. * **Adverse Effects:** "Triptan sensations" (chest tightness, tingling, and warmth) are common. * **Contraindications:** Ischemic heart disease (Prinzmetal angina, MI), peripheral vascular disease, and concurrent use of MAO inhibitors. * **Drug of Choice:** While Triptans are for acute attacks, **Propranolol** is the drug of choice for migraine prophylaxis.

Practice by Chapter

General Anesthetics

Practice Questions

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

Practice Questions

Psychostimulants

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Hallucinogens

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CNS Stimulants and Cognitive Enhancers

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