Central Nervous System Pharmacology Practice Questions

Q: Which of the following agents blocks AMPA receptors?

All the above. **Explanation:** The correct answer is **D (All the above)**. This question tests the multi-modal mechanisms of action of various anti-epileptic drugs (AEDs). Glutamate is the primary excitatory neurotransmitter in the brain, acting on NMDA, AMPA, and Kainate receptors. Blocking the **AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid)** receptor reduces rapid excitatory neurotransmission, making it a key target for seizure control. * **Phenobarbitone:** While primarily known as a GABA-A receptor modulator (increasing the duration of chloride channel opening), it also inhibits excitatory transmission by blocking AMPA/Kainate receptors at higher therapeutic concentrations. * **Topiramate:** This is a "broad-spectrum" AED with multiple mechanisms: it blocks voltage-gated sodium channels, enhances GABA-A activity, inhibits carbonic anhydrase, and specifically antagonizes the **AMPA/Kainate** subtype of glutamate receptors. * **Lamotrigine:** Its primary action is blocking voltage-gated sodium channels to inhibit glutamate release. However, it also exerts inhibitory effects on postsynaptic AMPA receptors, contributing to its efficacy in both focal and generalized seizures. **Clinical Pearls for NEET-PG:** 1. **Perampanel** is the only "selective" non-competitive AMPA receptor antagonist (highly high-yield). 2. **Topiramate** is often associated with side effects like weight loss, nephrolithiasis (kidney stones), and "word-finding" difficulties (cognitive slowing). 3. **Lamotrigine** carries a Black Box Warning for Stevens-Johnson Syndrome (SJS); it must be titrated slowly. 4. **Phenobarbitone** remains the drug of choice for neonatal seizures in many traditional guidelines, though Levetiracetam is increasingly used.

Q: Which drug is contraindicated in absence seizures?

Tiagabine. Absence seizures are characterized by 3-Hz spike-and-wave discharges on EEG, resulting from oscillatory activity between the thalamus and cortex. **Tiagabine** is a selective GABA reuptake inhibitor (GAT-1 inhibitor) [1, 2, 3]. By increasing GABA concentrations in the synaptic cleft, it can paradoxically hyperpolarize thalamic neurons, leading to the activation of T-type calcium channels. This exacerbates the rhythmic discharges, potentially transforming absence seizures into **status epilepticus** or increasing their frequency [1, 2]. Other drugs that aggravate absence seizures include **Vigabatrin, Phenytoin, Carbamazepine, and Phenobarbital.** **Analysis of Incorrect Options:** * **A. Lamotrigine:** This is a broad-spectrum anticonvulsant effective against both focal and generalized seizures, including absence seizures (though usually second-line after Valproate or Ethosuximide). * **B. Clonazepam:** Benzodiazepines enhance GABA-A receptor activity. Clonazepam is effective in treating absence seizures, particularly in refractory cases, though sedation and tolerance limit its long-term use. * **D. Ethosuximide:** This is the **drug of choice** for pure absence seizures. It works by specifically inhibiting T-type $Ca^{2+}$ channels in thalamic neurons. **High-Yield Clinical Pearls for NEET-PG:** * **Drug of Choice (DOC) for Absence Seizures:** Ethosuximide (if only absence); Valproate (if absence is associated with GTCS). * **Drugs that worsen Absence/Myoclonic seizures:** "The Narrow Spectrum Drugs" – Phenytoin, Carbamazepine, Oxcarbazepine, Gabapentin, Tiagabine, and Vigabatrin. * **EEG Hallmark:** 3-Hz spike-and-wave pattern. * **Tiagabine Side Effect:** Can induce non-convulsive status epilepticus in patients without a history of epilepsy.

Q: Which monoclonal antibody is used in the management of Alzheimer's disease?

Bapineuzumab. Explanation: **Correct Option: C. Bapineuzumab** Alzheimer’s disease is characterized by the accumulation of **amyloid-beta (Aβ) plaques** in the brain [1]. Bapineuzumab is a humanized monoclonal antibody designed to bind to and clear these Aβ plaques. While its clinical trials showed limited efficacy in improving cognitive function, it remains the classic pharmacological example of immunotherapy targeting the amyloid cascade in Alzheimer’s pathology [2]. **Incorrect Options:** * **A. Abciximab:** This is a **Glycoprotein IIb/IIIa receptor antagonist**. It is used as an antiplatelet agent during percutaneous coronary intervention (PCI) to prevent ischemic complications. * **B. Ceolizumab (Certolizumab):** This is a **TNF-alpha inhibitor** (specifically a pegylated Fab' fragment). It is used in the management of autoimmune conditions like Crohn’s disease and Rheumatoid Arthritis. * **D. Vedolizumab:** This is an **integrin receptor antagonist** (α4β7 integrin). It is gut-selective and used primarily in the management of Inflammatory Bowel Disease (Ulcerative Colitis and Crohn’s). **High-Yield Clinical Pearls for NEET-PG:** * **Recent FDA Approvals:** While Bapineuzumab is a frequent exam option, stay updated on newer FDA-approved monoclonal antibodies for Alzheimer’s: **Aducanumab** and **Lecanemab**. * **Mechanism:** These drugs target the **Amyloid Hypothesis**, aiming to reduce the plaque burden that leads to neurodegeneration [1]. * **Side Effects:** A critical adverse effect to remember for these antibodies is **ARIA (Amyloid-Related Imaging Abnormalities)**, which includes brain edema or microhemorrhages.

Q: Which of the following conditions is a contraindication to the use of a local anesthetic agent?

Hypersensitivity to the drug. **Explanation:** **Correct Answer: D. Hypersensitivity to the drug** The only absolute contraindication among the choices is a known **hypersensitivity (allergy)** to the specific local anesthetic (LA) or its chemical class. Allergic reactions are more common with **Esters** (due to the metabolite para-aminobenzoic acid - PABA) than with **Amides**. Anaphylaxis, though rare, can be life-threatening, making hypersensitivity a definitive contraindication. **Analysis of Incorrect Options:** * **A. Parkinson’s Disease:** This is not a contraindication. While clinicians must be cautious with drug interactions (e.g., avoiding epinephrine in patients on COMT inhibitors to prevent hypertensive crises), LAs themselves do not worsen the pathology of Parkinson’s. * **B. Liver Damage:** This is a **relative contraindication/precaution**, not an absolute one. Amide LAs (like Lidocaine and Bupivacaine) are metabolized in the liver. In patients with hepatic failure, the half-life is prolonged, increasing the risk of **Systemic Toxicity (LAST)**. Dosage must be reduced, but the drugs are not strictly forbidden. * **C. Pregnancy (3rd Trimester):** LAs are frequently used for labor analgesia (Epidurals). While pregnancy increases sensitivity to LAs (requiring a dose reduction of ~30% due to engorged epidural veins and hormonal changes), it is not a contraindication. **High-Yield Clinical Pearls for NEET-PG:** * **Classification Trick:** Amides have two "i"s in their name (L**i**doca**i**ne, Bup**i**vaca**i**ne, Pr**i**loca**i**ne), while Esters have only one (Procaine, Benzocaine). * **Maximum Doses:** Lidocaine (4 mg/kg plain; 7 mg/kg with Adrenaline); Bupivacaine (2 mg/kg). * **Drug of Choice for LAST:** Intravenous **20% Lipid Emulsion** is the antidote for Local Anesthetic Systemic Toxicity. * **Prilocaine Side Effect:** Can cause **Methemoglobinemia** (treated with Methylene Blue).

Q: What is the drug of choice for myoclonic epilepsy in pregnancy?

Sodium valproate. **Explanation:** The drug of choice for **myoclonic epilepsy** (such as Juvenile Myoclonic Epilepsy) is **Sodium Valproate** [1]. It is a broad-spectrum antiepileptic that works by increasing GABA levels, blocking voltage-gated sodium channels, and inhibiting T-type calcium channels. While Valproate is generally avoided in pregnancy due to its high teratogenic potential (Neural Tube Defects) [2], it remains the **drug of choice for myoclonic seizures** because other agents are often ineffective or may even exacerbate this specific seizure type [1]. In clinical practice, if a patient is well-controlled on Valproate, the dose is minimized and supplemented with high-dose Folic Acid (5mg). **Why the other options are incorrect:** * **Carbamazepine:** It is the drug of choice for focal (partial) seizures [1] and trigeminal neuralgia. However, it is contraindicated in myoclonic seizures as it can **worsen** them. * **Phenobarbitone:** While used in neonatal seizures and status epilepticus, it is not the first-line agent for myoclonic epilepsy and is associated with significant sedation and cognitive side effects. * **Phenytoin:** Similar to Carbamazepine, Phenytoin is effective for generalized tonic-clonic and focal seizures [1] but can aggravate myoclonic and absence seizures. **High-Yield NEET-PG Pearls:** * **Teratogenicity:** Valproate is the most teratogenic AED (causes **Spina Bifida**) [2]. * **Safest in Pregnancy:** **Levetiracetam** and **Lamotrigine** are generally considered the safest AEDs during pregnancy. * **DOC for Absence Seizures:** Ethosuximide (Valproate is second line). * **DOC for Infantile Spasms:** Vigabatrin (in Tuberous Sclerosis) or ACTH.

Q: What is a specific inhibitor of alcohol dehydrogenase?

Fomepizole. **Explanation:** The metabolism of alcohols (Ethanol, Methanol, and Ethylene glycol) primarily occurs in the liver via two main enzymes: **Alcohol Dehydrogenase (ADH)** and **Aldehyde Dehydrogenase (ALDH)**. **1. Why Fomepizole is correct:** **Fomepizole** is a potent, competitive inhibitor of **Alcohol Dehydrogenase (ADH)**. By blocking this enzyme, it prevents the conversion of Methanol and Ethylene glycol into their toxic metabolites (Formaldehyde/Formic acid and Glycolic/Oxalic acid, respectively). It is the preferred antidote for Methanol and Ethylene glycol poisoning because it prevents metabolic acidosis and end-organ damage (like blindness or renal failure). **2. Why other options are incorrect:** * **Disulfiram:** It inhibits **Aldehyde Dehydrogenase (ALDH)**. This leads to the accumulation of Acetaldehyde if ethanol is consumed, causing the "Disulfiram-like reaction" (flushing, tachycardia, nausea). It is used in aversion therapy for chronic alcoholism. * **Methyl alcohol:** This is a substrate for ADH, not an inhibitor. It is metabolized into toxic formic acid. * **Zolpidem:** This is a non-benzodiazepine hypnotic (Z-drug) that acts on the $GABA_A$ receptor. It has no effect on alcohol-metabolizing enzymes. **High-Yield Clinical Pearls for NEET-PG:** * **Methanol Poisoning:** Characterized by "snowstorm vision" and optic disc hyperemia. * **Ethylene Glycol Poisoning:** Characterized by calcium oxalate crystals in urine (envelope-shaped) and acute tubular necrosis. * **Alternative Treatment:** If Fomepizole is unavailable, **Ethanol** can be used as an antidote because it has a higher affinity for ADH than methanol, acting as a competitive substrate. * **Cofactor:** Ethanol metabolism follows **zero-order kinetics** and requires $NAD^+$ as a cofactor.

Q: Which of the following drugs can cause toxic epidermal necrolysis as an adverse effect?

Lamotrigine. **Explanation:** **Lamotrigine** is a broad-spectrum antiepileptic drug (AED) that acts by blocking voltage-gated sodium channels and inhibiting glutamate release. Its most significant and life-threatening adverse effect is a severe hypersensitivity reaction manifesting as **Stevens-Johnson Syndrome (SJS)** or **Toxic Epidermal Necrolysis (TEN)**. The risk is highest during the first 8 weeks of treatment and is significantly increased if the drug is started at a high dose or escalated rapidly. **Analysis of Options:** * **Lamotrigine (Correct):** Known for causing severe skin rashes. To minimize this risk, clinicians follow a "low and slow" titration schedule. * **Felbamate:** Primarily associated with **aplastic anemia** and **severe hepatotoxicity**, which limits its clinical use. * **Gabapentin:** Generally well-tolerated; its main side effects are sedation, dizziness, and peripheral edema. It is not typically associated with life-threatening dermatological reactions. * **Vigabatrin:** Notorious for causing **permanent visual field defects** (concentric contraction) due to retinal toxicity, requiring regular perimetry monitoring. **High-Yield Clinical Pearls for NEET-PG:** * **Drug Interaction:** Valproate inhibits the metabolism of Lamotrigine, doubling its half-life and significantly increasing the risk of SJS/TEN. * **Other Drugs causing SJS/TEN:** Remember the mnemonic **SAPP**: **S**ulfonamides, **A**ntiepileptics (Phenytoin, Carbamazepine, Phenobarbital, Lamotrigine), **P**enicillins, and **P**iroxicam (NSAIDs). * **HLA Link:** HLA-B*1502 is strongly associated with SJS/TEN caused by Carbamazepine, particularly in Asian populations.

Question 1

Which of the following agents blocks AMPA receptors?

Accepted Answer

All the above

Answer

Phenobarbitone

Answer

Topiramate

Answer

Lamotrigine

Question 2

A patient undergoing surgery was given a muscle relaxant. It produced a marked fall in blood pressure and an increase in airway resistance, which were reversed with diphenhydramine. The muscle relaxant was most probably:

Accepted Answer

Tubocurarine

Answer

Atracurium

Answer

Diazepam

Answer

Vecuronium

Question 3

Which of the following statements is TRUE regarding dental local anesthetics containing 2% lignocaine with adrenaline 1:80,000?

Accepted Answer

Dental local anesthetics containing 2% lignocaine with adrenaline 1:80,000 may cause tachycardia.

Answer

Dental local anesthetics containing 2% lignocaine with adrenaline 1:80,000 are contraindicated in patients with heart disease in any dosage.

Answer

Dental local anesthetics containing 2% lignocaine with adrenaline 1:80,000 can produce allergic reactions, in which lignocaine is usually responsible.

Answer

Dental local anesthetics containing 2% lignocaine with adrenaline 1:80,000 or even prilocaine with felypressin should not be used in the pregnant patient because of the oxytocic effects of adrenaline or felypressin.

Question 4

Which drug is contraindicated in absence seizures?

Accepted Answer

Tiagabine

Answer

Lamotrigine

Answer

Clonazepam

Answer

Ethosuximide

Question 5

A patient developed nausea, vomiting, tingling, and numbness in the fingertips, which also turned blue, after taking a drug for an acute attack of migraine. Which of the following drugs is most likely implicated in causing these findings?

Accepted Answer

Dihydroergotamine

Answer

Sumatriptan

Answer

Aspirin

Answer

Butorphanol

Question 6

Which monoclonal antibody is used in the management of Alzheimer's disease?

Accepted Answer

Bapineuzumab

Answer

Abciximab

Answer

Ceolizumab

Answer

Vedolizumab

Question 7

Which of the following conditions is a contraindication to the use of a local anesthetic agent?

Accepted Answer

Hypersensitivity to the drug

Answer

Parkinson's disease

Answer

Liver damage

Answer

Pregnancy (3rd trimester)

Question 8

What is the drug of choice for myoclonic epilepsy in pregnancy?

Accepted Answer

Sodium valproate

Answer

Carbamazepine

Answer

Phenobarbitone

Answer

Phenytoin

Question 9

What is a specific inhibitor of alcohol dehydrogenase?

Accepted Answer

Fomepizole

Answer

Disulfiram

Answer

Methyl alcohol

Answer

Zolpidem

Question 10

Which of the following drugs can cause toxic epidermal necrolysis as an adverse effect?

Accepted Answer

Lamotrigine

Answer

Felbamate

Answer

Gabapentin

Answer

Vigabatrin

Central Nervous System Pharmacology — MCQs

Central Nervous System Pharmacology — MCQs

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