Central Nervous System Pharmacology Practice Questions

Q: Which of the following antiepileptic agents acts on the GABAergic system to decrease the uptake of GABA into neurons and glial cells?

Tiagabine. ### Explanation **Correct Answer: D. Tiagabine** **Mechanism of Action:** Tiagabine is a selective inhibitor of the **GAT-1 (GABA Transporter-1)**. Under normal physiological conditions, GABA is cleared from the synaptic cleft into neurons and surrounding glial cells (astrocytes) via these transporters. By blocking GAT-1, Tiagabine prevents the reuptake of GABA, thereby increasing its concentration and prolonging its inhibitory action at the synaptic cleft. **Analysis of Incorrect Options:** * **A. Vigabatrin:** It acts on the GABAergic system but through a different mechanism. It is an irreversible inhibitor of **GABA-transaminase (GABA-T)**, the enzyme responsible for the degradation of GABA. This leads to increased intracellular levels of GABA. * **B. Progabide:** This is a **GABA receptor agonist** (acting on both GABA-A and GABA-B receptors) and a prodrug of GABA. It does not inhibit uptake. * **C. Gabapentin:** Despite its name, it does not act directly on GABA receptors or transporters. Its primary mechanism is the inhibition of **voltage-gated calcium channels (α2δ-1 subunit)**, which reduces the release of excitatory neurotransmitters like glutamate. **High-Yield NEET-PG Pearls:** * **Tiagabine:** Think "T" for **T**ransporter inhibitor. * **Vigabatrin:** Associated with a high-yield side effect: **Permanent bilateral visual field constriction** (requires periodic perimetry). It is the drug of choice for **Infantile Spasms** associated with Tuberous Sclerosis. * **GAT-1 vs. GABA-T:** Do not confuse reuptake (GAT-1/Tiagabine) with metabolism (GABA-T/Vigabatrin). * **Valproate:** Also affects GABA by inhibiting GABA-T and stimulating Glutamic Acid Decarboxylase (GAD), the enzyme that synthesizes GABA.

Q: All are adverse effects of phenytoin except?

Hypertension. **Explanation:** Phenytoin is a widely used hydantoin derivative for epilepsy, known for its narrow therapeutic index and a distinct profile of adverse effects. **Why Hypertension is the Correct Answer:** Phenytoin does **not** cause hypertension. In fact, when administered intravenously (especially if given too rapidly), phenytoin can cause **hypotension** and cardiac arrhythmias. This is primarily due to the solvent propylene glycol used in the formulation and the drug’s stabilizing effect on sodium channels in the myocardium. **Analysis of Incorrect Options:** * **Hypertrophy of Gums (Gingival Hyperplasia):** This is a classic side effect occurring in about 20% of patients. It is due to the overgrowth of gingival collagen fibers, stimulated by an increase in platelet-derived growth factor (PDGF). * **Hirsutism:** Phenytoin often causes excessive hair growth on the face and body, making it a less desirable choice for young female patients. * **Hypersensitivity:** Phenytoin can trigger various immune-mediated reactions, ranging from simple skin rashes to life-threatening conditions like **Stevens-Johnson Syndrome (SJS)** or **DRESS syndrome**, particularly in individuals with the HLA-B*1502 allele. **NEET-PG High-Yield Pearls:** To remember Phenytoin’s side effects, use the mnemonic **"PHENYTOIN"**: * **P**- P450 Inducer * **H**- Hypertrophy of gums / Hirsutism * **E**- Embryopathy (Fetal Hydantoin Syndrome: cleft lip/palate, microcephaly) * **N**- Neuropathy (Peripheral) * **Y**- Yields Vitamin D deficiency (Osteomalacia) * **T**- Teratogenicity * **O**- Osteomalacia * **I**- Interference with B12/Folate metabolism (Megaloblastic anemia) * **N**- Nystagmus (earliest sign of toxicity)

Q: Which of the following statements about phenytoin is FALSE?

Does not require drug dosage monitoring. Phenytoin is a high-yield topic in NEET-PG due to its complex pharmacokinetics and distinct side-effect profile. **Explanation for the Correct Option:** Option D is the false statement because Phenytoin **requires frequent Therapeutic Drug Monitoring (TDM)**. This is primarily due to its **zero-order (non-linear/saturation) kinetics** at therapeutic concentrations. Small increases in dose can lead to disproportionately large increases in plasma levels, rapidly reaching toxic ranges. Additionally, it has a **narrow therapeutic index** (10–20 µg/mL), making monitoring essential for safety and efficacy. **Analysis of Incorrect Options:** * **A. Causes hirsutism:** This is a well-known side effect. Phenytoin causes an overgrowth of body hair (hirsutism) and **gingival hyperplasia** (due to increased expression of platelet-derived growth factor). * **B. Has teratogenic effects:** Phenytoin is a known teratogen. It causes **Fetal Hydantoin Syndrome**, characterized by craniofacial anomalies (cleft lip/palate), microcephaly, and hypoplastic phalanges/nails. * **C. Has a narrow therapeutic index:** This is true. The margin between the effective dose and the toxic dose is very small, necessitating the TDM mentioned above. **High-Yield Clinical Pearls for NEET-PG:** * **Mechanism:** Blocks voltage-gated sodium channels in the inactive state. * **Metabolism:** It is a potent **CYP450 inducer**, leading to numerous drug interactions (e.g., decreasing the efficacy of oral contraceptives and warfarin). * **Adverse Effects Mnemonic (P-H-E-N-Y-T-O-I-N):** **P**-450 induction, **H**irsutism, **E**nlarged gums, **N**ystagmus (earliest sign of toxicity), **Y**ellow-brown skin, **T**eratogenicity, **O**steomalacia (Vitamin D interference), **I**nterference with B12/Folate (Megaloblastic anemia), **N**europathy. * **Zero-order kinetics** is also followed by Aspirin (at high doses), Warfarin, and Ethanol.

Q: Morphine withdrawal is characterized by all of the following symptoms except:

Miosis. **Explanation:** The correct answer is **A. Miosis**. **1. Why Miosis is the correct answer:** Morphine withdrawal symptoms are generally the **physiological opposite** of the drug’s acute effects. Acute opioid use causes miosis (pinpoint pupils) due to stimulation of the Edinger-Westphal nucleus. Conversely, **mydriasis (pupillary dilation)** is a hallmark sign of opioid withdrawal. Therefore, miosis is not a feature of withdrawal; it is a feature of acute intoxication. **2. Analysis of incorrect options:** * **B. Muscle aches and body pain:** Opioids are potent analgesics. During withdrawal, the pain threshold drops significantly, leading to characteristic myalgia, bone pain, and abdominal cramps. * **C & D. Yawning and Rhinorrhoea:** These are "wet" symptoms caused by autonomic hyperactivity. Early signs of morphine withdrawal include the "flu-like" triad of **yawning, rhinorrhoea, and lacrimation**, along with diaphoresis (sweating). **3. NEET-PG High-Yield Pearls:** * **The "Rule of Opposites":** If the drug causes constipation, withdrawal causes diarrhea. If the drug causes sedation, withdrawal causes insomnia and agitation. * **Piloerection:** The appearance of "gooseflesh" (cold turkey) is a highly specific sign of severe opioid withdrawal. * **Miosis Exception:** While most opioids cause miosis, **Meperidine (Pethidine)** is an exception; it can cause mydriasis due to its atropine-like (anticholinergic) action. * **Management:** Clonidine (α2 agonist) is used to reduce autonomic hyperactivity, while Methadone or Buprenorphine are used for detoxification and maintenance.

Q: Droperidol is used as:

All of the above. **Explanation:** Droperidol is a butyrophenone derivative, chemically related to Haloperidol. Its pharmacological profile allows it to be used across multiple clinical scenarios: 1. **Antipsychotic:** Like other butyrophenones, Droperidol is a potent central **D2 receptor antagonist**. While primarily used in anesthesia today, it was originally developed as an antipsychotic medication. 2. **Antiemetic:** It acts on the Chemoreceptor Trigger Zone (CTZ) in the area postrema of the medulla. It is highly effective in preventing and treating **Postoperative Nausea and Vomiting (PONV)**, even in sub-therapeutic doses. 3. **Neurolept Analgesia:** This is a state of quiescence, altered consciousness, and indifference to surroundings. It is achieved by combining a neuroleptic (Droperidol) with a potent opioid analgesic (Fentanyl). The fixed-dose combination (50:1 ratio) is known as **Innovar**. If nitrous oxide is added to this combination, it becomes **Neurolept Anesthesia**. **Why "All of the above" is correct:** Since Droperidol possesses sedative/antipsychotic properties, potent antiemetic effects, and is a core component of neurolept analgesia, all three individual options are clinically accurate descriptions of its use. **High-Yield Clinical Pearls for NEET-PG:** * **Black Box Warning:** The FDA issued a warning for Droperidol regarding **QT interval prolongation** and potential Torsades de Pointes. ECG monitoring is recommended. * **Side Effects:** Can cause extrapyramidal symptoms (dystonia) due to dopamine blockade. * **Contraindication:** Avoid in patients with Parkinson’s disease. * **Innovar Composition:** 2.5 mg Droperidol + 0.05 mg Fentanyl per mL.

Q: Which drug should be avoided in a patient with non-ketotic hyperglycemia presenting with seizure?

Phenytoin. **Explanation:** **Phenytoin** is the correct answer because it is uniquely contraindicated in seizures associated with **Non-Ketotic Hyperglycemic (NKH)** states. 1. **Mechanism of Contraindication:** Phenytoin inhibits the release of insulin from pancreatic beta cells (by stabilizing membranes and reducing calcium influx). In a patient already suffering from severe hyperglycemia, Phenytoin can further elevate blood glucose levels, exacerbating the underlying metabolic derangement. Furthermore, clinical studies have shown that Phenytoin is often ineffective in controlling seizures caused by NKH; the definitive treatment is aggressive hydration and insulin therapy, not anticonvulsants. 2. **Analysis of Incorrect Options:** * **Carbamazepine (A):** While it acts on sodium channels like Phenytoin, it does not significantly interfere with insulin secretion or glucose metabolism. * **Valproate (B):** Valproate is a broad-spectrum AED. While it can cause weight gain and metabolic syndrome over long-term use, it does not acutely worsen hyperglycemia in an emergency NKH setting. * **Clobazam (D):** As a benzodiazepine, it is used for acute seizure control and has no adverse effect on glycemic control. **Clinical Pearls for NEET-PG:** * **Drug of Choice for NKH Seizures:** Fluid resuscitation (Normal Saline) and Insulin. * **Phenytoin Side Effects (High Yield):** Remember the mnemonic **HOT MALAI** (Hirsutism, Osteomalacia, Teratogenicity, Megaloblastic anemia, Ataxia, Lymphadenopathy, **Insulin inhibition**, and Gum Hyperplasia). * **Zero-order Kinetics:** Phenytoin follows capacity-limited elimination, making its plasma levels highly sensitive to small dose changes.

Q: What is the drug of choice for treating drug-induced parkinsonism caused by phenothiazines?

Benzhexol. **Explanation:** The correct answer is **Benzhexol** (also known as Trihexyphenidyl). **Mechanism and Rationale:** Drug-induced parkinsonism (DIP) is a common extrapyramidal side effect of antipsychotics like phenothiazines. These drugs work by blocking **D2 receptors** in the nigrostriatal pathway. In the striatum, there is a functional balance between **Dopamine (inhibitory)** and **Acetylcholine (excitatory)**. When phenothiazines block dopamine receptors, it leads to a relative cholinergic overactivity. To treat this, we use **centrally acting anticholinergics** like Benzhexol, Benztropine, or Procyclidine. They restore the balance by reducing cholinergic tone. **Why other options are incorrect:** * **Levodopa (A) & Benserazide (B):** These are used for idiopathic Parkinson’s disease. In DIP, dopamine receptors are already blocked by the offending drug; therefore, increasing dopamine levels with Levodopa is ineffective and can worsen the underlying psychosis. * **Selegiline (D):** This is a MAO-B inhibitor used as an adjuvant in idiopathic Parkinson’s. It does not address the acute cholinergic-dopaminergic imbalance caused by receptor blockade. **High-Yield Clinical Pearls for NEET-PG:** * **Drug of Choice (DOC):** For drug-induced parkinsonism and acute muscular dystonia, the DOC is a central anticholinergic (Benzhexol/Benztropine) or an antihistamine with strong anticholinergic properties (Promethazine). * **Avoid Levodopa:** Never use Levodopa in DIP as it can precipitate or worsen psychosis. * **Tardive Dyskinesia:** Unlike other extrapyramidal symptoms, anticholinergics **worsen** tardive dyskinesia. The DOC for tardive dyskinesia is Valbenazine or Deutetrabenazine (VMAT2 inhibitors).

Q: In a child with infantile spasms and visual defects, which highly effective drug is generally avoided?

Vigabatrin. **Explanation:** **Vigabatrin** is a structural analog of GABA that irreversibly inhibits GABA-transaminase. While it is highly effective for infantile spasms (West Syndrome)—and is the first-line treatment for cases associated with Tuberous Sclerosis—it is notorious for causing **permanent peripheral visual field constriction** (retinal toxicity) in up to 30-50% of patients. In a child who already has pre-existing visual defects, adding a drug with a high risk of permanent visual loss is contraindicated or generally avoided to prevent further morbidity. **Analysis of Incorrect Options:** * **A. Lamotrigine:** This is an anticonvulsant used for various seizure types (like Lennox-Gastaut syndrome) but is not a primary treatment for infantile spasms and does not carry a specific risk of permanent visual field loss. * **B. Topiramate:** While it can cause ocular side effects like acute myopia or secondary angle-closure glaucoma, it is not the "highly effective" drug typically associated with the specific management dilemma of infantile spasms and chronic visual field defects. * **C. ACTH:** Adrenocorticotropic hormone is the overall first-line treatment for idiopathic infantile spasms. It has significant systemic side effects (hypertension, immunosuppression, Cushingoid features) but does not cause visual field defects. **Clinical Pearls for NEET-PG:** * **West Syndrome Triad:** Infantile spasms, Hypsarrhythmia on EEG, and Mental retardation. * **Drug of Choice (DOC):** ACTH is the DOC for most cases; **Vigabatrin** is the DOC specifically if **Tuberous Sclerosis** is the underlying cause. * **Monitoring:** Patients on Vigabatrin require baseline and periodic ophthalmologic screening (e.g., perimetry or electroretinogram).

Q: Parkinsonism is induced by all drugs except?

Amantadine. **Explanation:** The pathophysiology of Parkinsonism involves a deficiency of dopamine in the nigrostriatal pathway. Therefore, any drug that reduces dopamine levels or blocks dopamine receptors can induce **Drug-Induced Parkinsonism (DIP)**. **Why Amantadine is the Correct Answer:** Amantadine is an **anti-parkinsonian drug**, not a cause of it. Its mechanism involves increasing dopamine release from presynaptic terminals, inhibiting dopamine reuptake, and acting as an NMDA receptor antagonist. It is clinically used to treat early Parkinson’s disease and to reduce levodopa-induced dyskinesias. **Analysis of Incorrect Options (Drugs that cause Parkinsonism):** * **Reserpine:** It is a vesicular monoamine transporter (VMAT) inhibitor. It depletes presynaptic stores of dopamine, leading to a functional deficiency. * **Metoclopramide:** A potent central **D2 receptor antagonist** used as an antiemetic. It crosses the blood-brain barrier and is a common cause of extrapyramidal symptoms (EPS) in clinical practice. * **Chlorpromazine:** A typical (first-generation) antipsychotic that works by blocking D2 receptors in the mesolimbic and nigrostriatal pathways. Nigrostriatal blockade directly results in Parkinsonian symptoms (tremor, rigidity, bradykinesia). **High-Yield Clinical Pearls for NEET-PG:** * **Most common cause of DIP:** Antipsychotics (Haloperidol, Chlorpromazine). * **Other causative agents:** Valproate, Flunarizine (calcium channel blocker used for migraine), and Tetrabenazine. * **Treatment of choice for DIP:** Centrally acting anticholinergics like **Trihexyphenidyl (Benzhexol)** or **Benztropine**. Levodopa is usually ineffective because the receptors are blocked. * **Amantadine Side Effect:** Look for **Livedo Reticularis** (purplish lace-like skin discoloration) and ankle edema in exam vignettes.

Question 1

Which of the following antiepileptic agents acts on the GABAergic system to decrease the uptake of GABA into neurons and glial cells?

Accepted Answer

Tiagabine

Answer

Vigabatrin

Answer

Progabide

Answer

Gabapentin

Question 2

All are adverse effects of phenytoin except?

Accepted Answer

Hypertension

Answer

Hypertrophy of gums

Answer

Hirsutism

Answer

Hypersensitivity

Question 3

Which of the following statements about phenytoin is FALSE?

Accepted Answer

Does not require drug dosage monitoring

Answer

Causes hirsutism

Answer

Has teratogenic effects

Answer

Has a narrow therapeutic index

Question 4

Morphine withdrawal is characterized by all of the following symptoms except:

Accepted Answer

Miosis

Answer

Muscle aches and body pain

Answer

Yawning

Answer

Rhinorrhoea

Question 5

A patient with Parkinsonism experienced a decreased therapeutic effect of levodopa when a specific drug was co-administered. However, no such interaction was observed when the patient switched to a levodopa-carbidopa combination. What is the likely identity of the drug prescribed by the physician?

Accepted Answer

Vitamin B complex

Answer

Metoclopramide

Answer

Chlorpromazine

Answer

Isoniazid

Question 6

Droperidol is used as:

Accepted Answer

All of the above

Answer

Antipsychotic

Answer

Antiemetic

Answer

Neurolept analgesia

Question 7

Which drug should be avoided in a patient with non-ketotic hyperglycemia presenting with seizure?

Accepted Answer

Phenytoin

Answer

Carbamazepine

Answer

Valproate

Answer

Clobazam

Question 8

What is the drug of choice for treating drug-induced parkinsonism caused by phenothiazines?

Accepted Answer

Benzhexol

Answer

Levodopa

Answer

Benserazide

Answer

Selegiline

Question 9

In a child with infantile spasms and visual defects, which highly effective drug is generally avoided?

Accepted Answer

Vigabatrin

Answer

Lamotrigine

Answer

Topiramate

Answer

ACTH

Question 10

Parkinsonism is induced by all drugs except?

Accepted Answer

Amantadine

Answer

Reserpine

Answer

Metoclopramide

Answer

Chlorpromazine

Central Nervous System Pharmacology — MCQs

Central Nervous System Pharmacology — MCQs

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