Central Nervous System Pharmacology Practice Questions

Q: The effect of thiopentone on the central nervous system is quickly terminated because of which of the following mechanisms?

Redistribution to other tissues. **Explanation:** The rapid termination of the anesthetic effect of **Thiopentone** (an ultra-short-acting barbiturate) is due to the phenomenon of **redistribution**, not metabolism. 1. **Why Option C is Correct:** Thiopentone is highly lipid-soluble. Upon intravenous injection, it rapidly crosses the blood-brain barrier and reaches peak concentrations in the brain (a highly perfused organ) within seconds, inducing anesthesia. However, as the drug continues to circulate, it moves down its concentration gradient from the brain back into the blood and is then **redistributed** to less perfused but larger-volume tissues, such as skeletal muscle and eventually adipose tissue. This drop in brain concentration leads to a quick recovery of consciousness (usually within 5–10 minutes), even though the drug is still present in the body. 2. **Why Other Options are Incorrect:** * **Options A & D:** Thiopentone is not metabolized in the CNS or systemic circulation. It undergoes slow hepatic metabolism (approx. 10–15% per hour). * **Option B:** While Thiopentone is metabolized by the liver, this process is far too slow to account for the rapid awakening seen after a single bolus dose. **High-Yield NEET-PG Pearls:** * **Context:** Redistribution is the characteristic mechanism for terminating the action of all highly lipid-soluble drugs given intravenously (e.g., Thiopentone, Propofol, Fentanyl). * **Cumulative Effect:** If Thiopentone is given via repeated doses or continuous infusion, the storage sites (muscle/fat) become saturated. At this point, the duration of action depends on metabolism rather than redistribution, leading to a prolonged recovery time (hangover effect). * **Context-Sensitive Half-life:** This is why Thiopentone has a long context-sensitive half-life compared to Propofol, making it unsuitable for maintaining anesthesia.

Q: Which of the following is a relatively cerebroselective anticholinesterase found to afford symptomatic improvement in Alzheimer's disease?

Donepezil. ### Explanation **Correct Option: A. Donepezil** Alzheimer’s disease is characterized by a cholinergic deficiency in the brain. **Donepezil** is a reversible, long-acting, and **relatively cerebroselective** (central-acting) acetylcholinesterase (AChE) inhibitor. Its high affinity for AChE in the brain compared to the periphery minimizes systemic side effects. By inhibiting the breakdown of acetylcholine in the synaptic cleft, it enhances cholinergic transmission, providing symptomatic improvement in cognitive function. Other drugs in this class include Rivastigmine and Galantamine. **Analysis of Incorrect Options:** * **B. Pyridostigmine:** This is a quaternary ammonium compound that does not cross the blood-brain barrier (BBB). It is used primarily for **Myasthenia Gravis** to act on the nicotinic receptors at the neuromuscular junction. * **C. Pyritinol:** Also known as Pyrithioxine, it is a semi-synthetic water-soluble analog of Vitamin B6. It is classified as a **nootropic** (cognitive enhancer) but is not an anticholinesterase and is not the first-line treatment for Alzheimer’s. * **D. Gemfibrozil:** This is a **fibrate** used as a hypolipidemic agent. It activates PPAR-α to lower triglyceride levels and has no role in the cholinergic system or Alzheimer’s management. **High-Yield Clinical Pearls for NEET-PG:** * **Rivastigmine:** A "pseudo-irreversible" inhibitor that inhibits both AChE and Butyrylcholinesterase (BuChE). It is available as a **transdermal patch** to reduce GI side effects. * **Galantamine:** Also acts as a **nicotinic receptor modulator**, enhancing the action of acetylcholine. * **Memantine:** An **NMDA receptor antagonist** often used in moderate-to-severe Alzheimer’s, frequently as an adjunct to Donepezil. * **Side Effects:** Common side effects of central AChE inhibitors include "SLUDGE" symptoms (diarrhea, nausea, bradycardia, and insomnia).

Q: Prolonged use of which of the following anticonvulsants can produce weight loss?

Topiramate. **Explanation:** **Topiramate** is a broad-spectrum antiepileptic drug known for its unique side effect profile. Unlike many anticonvulsants that cause weight gain, Topiramate is characteristically associated with **weight loss** and anorexia. This occurs due to its inhibitory effect on carbonic anhydrase enzymes and its influence on hypothalamic feeding centers, leading to reduced appetite and altered taste (dysgeusia). This property makes it a preferred choice for obese patients with epilepsy or migraine and has led to its FDA approval (in combination with phentermine) for chronic weight management. **Analysis of Incorrect Options:** * **Valproic acid:** This is a classic "weight gain" drug. It increases appetite and can lead to significant weight gain and metabolic syndrome, often making it a poor choice for patients with PCOS. * **Gabapentin:** Frequently associated with weight gain and peripheral edema. It is more commonly used for neuropathic pain than as a primary anticonvulsant. * **Oxcarbazepine:** Generally considered weight-neutral, though its most significant electrolyte abnormality is **hyponatremia** (more common than with carbamazepine). **NEET-PG High-Yield Pearls:** * **Topiramate Side Effects:** Remember the mnemonic "M-O-U-T-H": **M**etabolic acidosis (due to carbonic anhydrase inhibition), **O**cular effects (acute myopia/secondary angle-closure glaucoma), **U**rolithiasis (kidney stones), **T**eratogenicity (cleft lip/palate), and **H**ypohidrosis (reduced sweating/hyperthermia). * **Cognitive Dullings:** Topiramate is often nicknamed "Stupimax" because it can cause word-finding difficulties and cognitive slowing. * **Zonisamide** is another anticonvulsant that also causes weight loss and kidney stones.

Q: Fosphenytoin is different from phenytoin as:

All the above.. Fosphenytoin is a water-soluble phosphate ester **prodrug** of phenytoin, developed specifically to overcome the pharmaceutical limitations of parenteral phenytoin [1].1. **Why Option D is correct:** * **Option A (Less Intimal Damage):** Phenytoin is highly alkaline (pH ~12) and requires propylene glycol as a solvent, which causes severe local irritation, pain, and "Purple Glove Syndrome" (extensive limb ischemia). Fosphenytoin has a near-physiological pH (8.6–9.0) and is aqueous-based, making it significantly less damaging to the venous intima [1]. * **Option B (Compatibility with Glucose):** Phenytoin is highly insoluble and precipitates immediately if added to glucose solutions (it must only be used with Normal Saline). Fosphenytoin is highly water-soluble and remains stable in both **Dextrose (5%) and Normal Saline**, allowing for more flexible intravenous administration [1]. * **Option C (Prodrug Status):** Fosphenytoin is pharmacologically inactive until it is converted to phenytoin by **phosphatases** in the blood and liver (conversion half-life is ~8–15 minutes).**High-Yield Clinical Pearls for NEET-PG:** * **Dosing:** Fosphenytoin is prescribed in **Phenytoin Equivalents (PE)**. 1.5 mg of fosphenytoin = 1 mg of phenytoin.* **Infusion Rate:** It can be infused faster than phenytoin (up to **150 mg PE/min** vs. 50 mg/min for phenytoin), allowing for quicker achievement of therapeutic levels in Status Epilepticus.* **Monitoring:** While local complications are fewer, systemic side effects like **cardiac arrhythmias and hypotension** can still occur; ECG monitoring is mandatory during infusion.

Q: Which of the following is an exclusive 5-HT 1F receptor agonist approved by FDA for treatment of acute migraine attack?

Lasmiditan. **Explanation:** **Lasmiditan** is the correct answer. It is a first-in-class **selective 5-HT 1F receptor agonist** approved by the FDA for the acute treatment of migraine with or without aura. Unlike the "Triptans," which act on 5-HT 1B/1D receptors [1], Lasmiditan lacks vasoconstrictive properties because 5-HT 1F receptors are located on trigeminal nerve endings and not on blood vessels. This makes it a safer alternative for patients with cardiovascular contraindications. **Analysis of Incorrect Options:** * **A. Rimegepant:** This is a small-molecule **CGRP receptor antagonist** (Gepant). While used for acute migraine, its mechanism involves blocking the CGRP receptor rather than stimulating 5-HT receptors [3]. * **C. Eletriptan:** This is a standard **5-HT 1B/1D agonist** [1]. Its activation of 1B receptors causes cranial vasoconstriction, which is why triptans are contraindicated in patients with ischemic heart disease or uncontrolled hypertension [2]. * **D. Dosulepin:** This is a **Tricyclic Antidepressant (TCA)**. While TCAs (like Amitriptyline) are used for migraine *prophylaxis*, they are not used for acute attacks and do not act as selective 5-HT 1F agonists. **High-Yield Clinical Pearls for NEET-PG:** * **"Ditans" vs. "Triptans":** Ditans (Lasmiditan) = No vasoconstriction (Safe in CAD). Triptans = Vasoconstriction (Unsafe in CAD). * **Side Effect:** The most common side effect of Lasmiditan is **dizziness/somnolence**; patients are advised not to drive for 8 hours after taking a dose. * **Site of Action:** Lasmiditan acts centrally and peripherally to inhibit the release of neuropeptides and neurotransmitters involved in migraine pain signaling [3].

Q: Disulfiram acts by blocking which enzyme?

Acetaldehyde dehydrogenase. ### Explanation **Mechanism of Action** The correct answer is **Acetaldehyde dehydrogenase (ALDH)**. Alcohol metabolism primarily follows a two-step oxidative pathway: 1. **Alcohol → Acetaldehyde:** Catalyzed by Alcohol Dehydrogenase (ADH). 2. **Acetaldehyde → Acetic Acid:** Catalyzed by Acetaldehyde Dehydrogenase (ALDH). Disulfiram irreversibly inhibits **ALDH**. When a patient on Disulfiram consumes alcohol, acetaldehyde cannot be converted to acetic acid, leading to its accumulation in the blood. This results in the **Disulfiram-Ethanol Reaction (DER)**, characterized by flushing, tachycardia, nausea, vomiting, and hypotension, which serves as an aversion therapy for chronic alcoholism. **Analysis of Incorrect Options** * **A. Alcohol dehydrogenase:** This enzyme is inhibited by **Fomepizole**, which is used in the treatment of Methanol and Ethylene glycol poisoning to prevent the formation of toxic metabolites (formaldehyde and oxalic acid). * **C. Pyruvate dehydrogenase:** This is a mitochondrial enzyme complex that converts pyruvate to Acetyl-CoA. It is inhibited by Arsenic and is not involved in ethanol metabolism. **High-Yield Clinical Pearls for NEET-PG** * **Disulfiram-like reaction:** Several other drugs can cause a similar reaction when taken with alcohol. Mnemonic: **"PM Cans"** (**P**rocarbazine, **M**etronidazole, **C**efoperazone/Cefotetan, **A**ntazoline, **N**itrofurantoin, **S**ulfonylureas like Chlorpropamide). * **Duration of Action:** Because Disulfiram is an irreversible inhibitor, its effects can last for **7–14 days** even after stopping the drug, as the body must synthesize new ALDH enzymes. * **Contraindication:** It should never be administered if the patient has consumed alcohol within the last 12 hours.

Q: Which of the following is NOT true about cocaine?

It is an amide local anesthetic.. **Explanation:** **1. Why Option A is the Correct Answer (The "NOT" True Statement):** Local anesthetics are classified into two groups: **Esters** and **Amides**. Cocaine is an **ester-linked** local anesthetic, not an amide. A simple mnemonic to distinguish them is that amide local anesthetics (like Lidocaine, Bupivacaine, Prilocaine) always contain the letter **"i"** twice in their name (e.g., L**i**doca**i**ne), whereas esters (Cocaine, Procaine, Tetracaine) contain it only once. **2. Analysis of Other Options:** * **Option B & D:** Cocaine is unique among local anesthetics because it is a potent **inhibitor of the presynaptic reuptake** of catecholamines (Norepinephrine and Dopamine). This leads to an accumulation of these neurotransmitters in the synaptic cleft, resulting in intense **sympathetic stimulation** (tachycardia, hypertension, and mydriasis). * **Option C:** While most esters are primarily metabolized by plasma pseudocholinesterase, Cocaine is unique as it undergoes significant metabolism by **liver carboxylesterases** in addition to plasma cholinesterase. **Clinical Pearls for NEET-PG:** * **Vasoconstriction:** Cocaine is the **only** local anesthetic that naturally causes vasoconstriction; all others (except ropivacaine/levobupivacaine at low doses) are vasodilators. * **Clinical Use:** Due to its vasoconstrictive and anesthetic properties, it is used topically in ENT surgeries (e.g., dacryocystorhinostomy) to reduce bleeding. * **Toxicity:** Overdose causes CNS stimulation followed by seizures and fatal cardiac arrhythmias. **Beta-blockers are contraindicated** in cocaine toxicity as they lead to unopposed alpha-adrenergic stimulation.

Q: Which local anesthetic agent causes cutaneous vasoconstriction?

Ropivacaine. **Explanation:** The primary mechanism of most local anesthetics (LAs) involves the blockade of sodium channels, which typically results in **vasodilation** at clinical concentrations. This occurs due to the relaxation of vascular smooth muscle. However, **Ropivacaine** is a unique long-acting amide local anesthetic that possesses intrinsic **cutaneous vasoconstrictive** properties. **Why Ropivacaine is Correct:** Ropivacaine causes vasoconstriction at concentrations commonly used for clinical anesthesia (up to 1%). This intrinsic property reduces its own systemic absorption, prolongs the duration of action, and decreases the risk of systemic toxicity. It is chemically an S-enantiomer, which contributes to its lower cardiotoxicity compared to Bupivacaine. **Why the Other Options are Incorrect:** * **Lidocaine (Option A):** A prototype amide LA that causes significant vasodilation. It is often formulated with epinephrine to counteract this effect. * **Mepivacaine (Option C):** While it has less vasodilatory effect than lidocaine, it does not produce significant vasoconstriction like Ropivacaine. * **Procaine (Option D):** An ester-type LA known for being a potent vasodilator; it has a very short duration of action because it is rapidly cleared from the site of injection. **High-Yield Clinical Pearls for NEET-PG:** * **Exceptions to Vasodilation:** Only three local anesthetics cause significant vasoconstriction: **Cocaine** (most potent), **Ropivacaine**, and **Levobupivacaine**. * **Cocaine’s Mechanism:** Unlike Ropivacaine, Cocaine causes vasoconstriction by inhibiting the reuptake of norepinephrine at sympathetic nerve endings. * **Safety Profile:** Ropivacaine is preferred over Bupivacaine for epidural labor analgesia because it produces a "differential block" (greater sensory block with minimal motor block) and has a higher threshold for CNS and cardiac toxicity.

Q: A very potent and short-acting benzodiazepine was given to a patient for the purpose of causing hypnosis, but the drug caused psychiatric disturbances. Which of the following could be the hypnotic used?

Triazolam. **Explanation:** The correct answer is **Triazolam**. **1. Why Triazolam is correct:** Triazolam is an ultra-short-acting benzodiazepine (half-life: 2–3 hours) used primarily for the induction of sleep. Because of its high potency and rapid elimination, it is uniquely associated with a high incidence of **psychiatric disturbances**, including daytime anxiety, amnesia, confusion, and "rebound insomnia." More importantly, it can cause severe behavioral side effects such as agitation, hallucinations, and even paranoia (often referred to as the "Triazolam syndrome"). Due to these adverse psychiatric effects, its use has been restricted or banned in several countries. **2. Why other options are incorrect:** * **Flurazepam:** This is a long-acting benzodiazepine (half-life >50 hours due to active metabolites). Its primary side effect is "hangover" or excessive daytime sedation, rather than acute psychiatric disturbances. * **Nitrazepam:** An intermediate-acting benzodiazepine. While it can cause morning grogginess, it does not share the specific high-potency, short-acting profile linked to the psychiatric agitation seen with Triazolam. * **Temazepam:** An intermediate-acting drug (half-life 8–12 hours). It is metabolized by conjugation and is generally better tolerated in terms of behavioral side effects compared to Triazolam. **High-Yield Clinical Pearls for NEET-PG:** * **Shortest Acting BZD:** Midazolam (used for anesthesia) and Triazolam (used for hypnosis). * **Longest Acting BZD:** Flurazepam and Quazepam. * **BZDs safe in Liver Failure:** Remember the mnemonic **LOT** (Lorazepam, Oxazepam, Temazepam) as they undergo direct glucuronidation and have no active metabolites. * **Triazolam specific side effect:** Anterograde amnesia is more common with Triazolam than with most other oral BZDs.

Q: The antiepileptic drug lacosamide acts by:

Inhibiting CRMP protein. **Explanation:** **Lacosamide** is a third-generation antiepileptic drug with a unique dual mechanism of action. Its primary mechanism is the **selective enhancement of slow inactivation of voltage-gated sodium channels**, which stabilizes hyperexcitable neuronal membranes. However, it also binds to **Collapsin Response Mediator Protein-2 (CRMP-2)**. CRMP-2 is a phosphoprotein involved in neuronal differentiation and axonal outgrowth; by modulating this protein, lacosamide is thought to exert neuroprotective effects and interfere with the process of epileptogenesis. **Analysis of Options:** * **Option A (Inhibiting synaptic vesicular protein):** This describes the mechanism of **Levetiracetam** and **Brivaracetam**, which bind to the **SV2A** protein to modulate neurotransmitter release. * **Option C (Inhibiting GABA metabolism):** This refers to drugs like **Vigabatrin** (inhibits GABA-transaminase) or **Tiagabine** (inhibits GABA reuptake via GAT-1). * **Option D (Inhibiting glutamate release):** While many drugs indirectly reduce glutamate (like Lamotrigine via sodium channel blockade), this is not the specific defining mechanism associated with Lacosamide’s interaction with CRMP-2. **High-Yield Clinical Pearls for NEET-PG:** * **Indications:** Approved for focal-onset (partial) seizures in patients aged 1 month and older. * **Pharmacokinetics:** It has excellent bioavailability (100%) and minimal drug-drug interactions, as it does not significantly induce or inhibit Cytochrome P450 enzymes. * **Adverse Effects:** A characteristic side effect is **PR interval prolongation** on ECG; therefore, it should be used with caution in patients with known conduction problems. * **Schedule:** It is a Schedule V controlled substance due to a low potential for abuse (euphoria).

Question 1

The effect of thiopentone on the central nervous system is quickly terminated because of which of the following mechanisms?

Accepted Answer

Redistribution to other tissues

Answer

Rapid metabolism within the central nervous system

Answer

Quick first-pass elimination by the liver

Answer

Rapid metabolism in systemic circulation

Question 2

Which of the following is a relatively cerebroselective anticholinesterase found to afford symptomatic improvement in Alzheimer's disease?

Accepted Answer

Donepezil

Answer

Pyridostigmine

Answer

Pyritinol

Answer

Gemfibrozil

Question 3

Prolonged use of which of the following anticonvulsants can produce weight loss?

Accepted Answer

Topiramate

Answer

Gabapentin

Answer

Oxcarbazepine

Answer

Valproic acid

Question 4

Fosphenytoin is different from phenytoin as:

Accepted Answer

All the above.

Answer

It is less damaging to the intima on intravenous administration.

Answer

It can be injected in a drip of glucose solution.

Answer

It is a prodrug of phenytoin.

Question 5

Which of the following is an exclusive 5-HT 1F receptor agonist approved by FDA for treatment of acute migraine attack?

Accepted Answer

Lasmiditan

Answer

Rimegepant

Answer

Eletriptan

Answer

Dosulepin

Question 6

Disulfiram acts by blocking which enzyme?

Accepted Answer

Acetaldehyde dehydrogenase

Answer

Alcohol dehydrogenase

Answer

Pyruvate dehydrogenase

Answer

All of the above

Question 7

Which of the following is NOT true about cocaine?

Accepted Answer

It is an amide local anesthetic.

Answer

It can produce sympathetic stimulation.

Answer

It is metabolized by the liver.

Answer

It blocks the presynaptic uptake of norepinephrine and dopamine.

Question 8

Which local anesthetic agent causes cutaneous vasoconstriction?

Accepted Answer

Ropivacaine

Answer

Lidocaine

Answer

Mepivacaine

Answer

Procaine

Question 9

A very potent and short-acting benzodiazepine was given to a patient for the purpose of causing hypnosis, but the drug caused psychiatric disturbances. Which of the following could be the hypnotic used?

Accepted Answer

Triazolam

Answer

Flurazepam

Answer

Nitrazepam

Answer

Temazepam

Question 10

The antiepileptic drug lacosamide acts by:

Accepted Answer

Inhibiting CRMP protein

Answer

Inhibiting synaptic vesicular protein

Answer

Inhibiting GABA metabolism

Answer

Inhibiting glutamate release

Central Nervous System Pharmacology — MCQs

Central Nervous System Pharmacology — MCQs

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