Central Nervous System Pharmacology — MCQs

Central Nervous System Pharmacology Indian Medical PG Practice Questions and MCQs

Question 181: Which of the following drugs is the first-line treatment for Tourette's syndrome?

A. Chlorpromazine
B. Haloperidol (Correct Answer)
C. Olanzapine
D. Risperidone

Explanation: **Explanation:** **Tourette’s Syndrome (TS)** is a neurodevelopmental disorder characterized by multiple motor and vocal tics. The pathophysiology is primarily linked to **dopaminergic overactivity** in the basal ganglia. Therefore, dopamine (D2) receptor antagonists are the mainstay of pharmacological treatment. **Why Haloperidol is correct:** **Haloperidol**, a high-potency typical antipsychotic, is the traditional **first-line drug** and the first FDA-approved medication for Tourette’s syndrome. It works by potently blocking D2 receptors, effectively reducing the frequency and severity of tics. While newer agents are often used in clinical practice to avoid side effects, Haloperidol remains the classic textbook answer and the gold standard for competitive exams like NEET-PG. **Why other options are incorrect:** * **Chlorpromazine:** A low-potency typical antipsychotic. While it blocks D2 receptors, its significant sedative and anticholinergic side effects make it less suitable for the long-term management of tics compared to Haloperidol. * **Olanzapine & Risperidone:** These are atypical antipsychotics. While **Risperidone** is frequently used "off-label" and is often preferred in modern clinical practice due to a lower risk of Extrapyramidal Symptoms (EPS), Haloperidol remains the established first-line reference in standard pharmacological hierarchy for TS. **High-Yield Clinical Pearls for NEET-PG:** * **Pimozide:** Another high-potency typical antipsychotic specifically indicated for TS when Haloperidol fails or causes intolerable side effects. * **Alpha-2 Agonists:** Drugs like **Clonidine** and **Guanfacine** are often preferred as initial therapy if the patient has comorbid ADHD. * **Side Effects:** When using Haloperidol, monitor for **Extrapyramidal Symptoms (EPS)** such as dystonia, akathisia, and tardive dyskinesia.

Question 182: 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?

A. Metoclopramide
B. Vitamin B complex (Correct Answer)
C. Chlorpromazine
D. Isoniazid

Explanation: **Explanation:** The correct answer is **Vitamin B complex**, specifically **Pyridoxine (Vitamin B6)**. **Mechanism of Interaction:** Levodopa is converted to dopamine by the enzyme **DOPA decarboxylase**. Pyridoxine acts as a vital cofactor for this enzyme. When Vitamin B6 is administered with plain levodopa, it accelerates the peripheral decarboxylation of levodopa into dopamine. Since dopamine cannot cross the blood-brain barrier (BBB), this reduces the amount of levodopa available to enter the CNS, thereby decreasing its therapeutic effect and increasing peripheral side effects (like nausea and tachycardia). **Why Carbidopa negates this:** Carbidopa is a **peripheral DOPA decarboxylase inhibitor**. It prevents the peripheral conversion of levodopa regardless of pyridoxine levels. Therefore, when the patient switched to the levodopa-carbidopa combination, the "pyridoxine effect" was blocked, and the therapeutic efficacy remained stable. **Analysis of Incorrect Options:** * **Metoclopramide (A):** A dopamine (D2) antagonist that crosses the BBB. It would worsen parkinsonism symptoms regardless of whether carbidopa is present. * **Chlorpromazine (C):** A typical antipsychotic and potent D2 blocker. Like metoclopramide, it antagonizes levodopa centrally and would not be "fixed" by adding carbidopa. * **Isoniazid (D):** While isoniazid can cause B6 deficiency, it does not directly accelerate the metabolism of levodopa in a way that carbidopa would specifically resolve. **High-Yield Clinical Pearls for NEET-PG:** * **The "Pyridoxine Effect":** Only occurs with levodopa monotherapy; it is clinically irrelevant in modern practice where levodopa is almost always combined with carbidopa or benserazide. * **Peripheral vs. Central:** Carbidopa does **not** cross the BBB; its sole purpose is to ensure levodopa reaches the brain. * **Dietary Note:** Patients on plain levodopa were historically advised to avoid B6-rich foods (like liver or fortified cereals), a restriction no longer necessary with combination therapy.

Question 183: Which drug should be avoided in a patient with non-ketotic hyperglycemia presenting with seizure?

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

Explanation: **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.

Question 184: What is the drug of choice for treating drug-induced parkinsonism caused by phenothiazines?

A. Levodopa
B. Benserazide
C. Benzhexol (Correct Answer)
D. Selegiline

Explanation: **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).

Question 185: All of the following drugs can cause neuroleptic malignant syndrome except?

A. Amantadine (Correct Answer)
B. Domperidone
C. Haloperidol
D. Metoclopramide

Explanation: ### Explanation **Neuroleptic Malignant Syndrome (NMS)** is a life-threatening idiosyncratic reaction characterized by the "tetrad" of muscle rigidity, fever (hyperpyrexia), autonomic instability, and altered mental status. The underlying pathophysiology is a **severe deficiency of dopamine** in the central nervous system. #### Why Amantadine is the Correct Answer: Amantadine is a **dopaminergic drug** (it increases dopamine release and inhibits reuptake). Because NMS is caused by dopamine depletion, Amantadine is actually used in the *treatment* of NMS, not as a cause. However, it is crucial to note that the **sudden withdrawal** of Amantadine (or Levodopa) in Parkinson’s patients can precipitate NMS. #### Why the Other Options are Incorrect: NMS is typically triggered by drugs that **block Dopamine (D2) receptors**: * **Haloperidol:** A high-potency typical antipsychotic and the most common cause of NMS. * **Metoclopramide:** A prokinetic and antiemetic that blocks central D2 receptors; it is a well-documented non-antipsychotic cause of NMS. * **Domperidone:** Although it primarily acts peripherally, it is a D2 receptor antagonist. While much rarer than Metoclopramide due to poor blood-brain barrier penetration, it is pharmacologically capable of contributing to dopamine blockade. #### NEET-PG High-Yield Pearls: * **Drug of Choice for NMS:** **Dantrolene** (muscle relaxant) or **Bromocriptine** (D2 agonist). * **Key Lab Finding:** Significantly elevated **Creatine Phosphokinase (CPK)** due to rhabdomyolysis. * **Differential Diagnosis:** Unlike Serotonin Syndrome, NMS presents with "lead-pipe" rigidity and bradyreflexia (Serotonin syndrome features hyperreflexia and myoclonus). * **Mnemonic for NMS Features:** **FEVER** (Fever, Encephalopathy, Vitals unstable, Elevated enzymes, Rigidity).

Question 186: All of the following are peripherally acting muscle relaxants except?

A. Dantrolene
B. Pancuronium
C. Succinylcholine
D. Baclofen (Correct Answer)

Explanation: Skeletal muscle relaxants are broadly classified into two categories based on their site of action: **Peripherally acting** (acting at the neuromuscular junction or on the muscle fiber itself) and **Centrally acting** (acting on the spinal cord or brain) [3]. **Why Baclofen is the Correct Answer:** **Baclofen** is a **centrally acting** muscle relaxant [3]. It is a **GABA-B receptor agonist** that works primarily at the spinal cord level [3]. By activating these receptors, it induces hyperpolarization, leading to pre-synaptic inhibition of excitatory neurotransmitters (like glutamate) [3]. It is clinically used to treat spasticity associated with multiple sclerosis or spinal cord injuries [3]. **Analysis of Incorrect Options:** * **Pancuronium:** A peripherally acting **Non-depolarizing Neuromuscular Blocker**. It competes with acetylcholine for nicotinic receptors ($N_m$) at the motor endplate. * **Succinylcholine:** A peripherally acting **Depolarizing Neuromuscular Blocker** [1]. It acts as an agonist at $N_m$ receptors, causing persistent depolarization and subsequent paralysis [1]. * **Dantrolene:** A peripherally acting relaxant that acts directly on the muscle fiber [2]. It inhibits the **Ryanodine receptors (RyR1)** on the sarcoplasmic reticulum, preventing the release of calcium required for contraction [3]. **High-Yield NEET-PG Pearls:** * **Dantrolene** is the drug of choice for **Malignant Hyperthermia** and Neuroleptic Malignant Syndrome. * **Succinylcholine** is known for causing post-operative muscle pain and hyperkalemia (avoid in burn/trauma patients) [1]. * **Tizanidine** is another centrally acting relaxant that acts as an **$\alpha_2$ adrenergic agonist** [3]. * **Mephenesin** is the prototype for centrally acting muscle relaxants [4].

Question 187: Which among the following may be used as a sedative-hypnotic?

A. Zolmitriptan
B. Zileuton
C. Zolpidem (Correct Answer)
D. Zalcitabine

Explanation: **Explanation:** **Correct Answer: C. Zolpidem** **Mechanism and Use:** Zolpidem is a non-benzodiazepine sedative-hypnotic belonging to the "Z-drug" class (which also includes Zaleplon and Eszopiclone) [2]. Unlike benzodiazepines, which bind non-selectively to various $GABA_A$ receptor subtypes, Zolpidem acts as a selective agonist at the **$\alpha_1$ subunit** of the $GABA_A$ receptor (BZ1 site) [1]. This selectivity results in potent sedative and hypnotic effects with minimal anticonvulsant, muscle relaxant, or anxiolytic properties [1]. It is preferred for the short-term management of insomnia because it preserves sleep architecture (minimal effect on REM sleep) [2] and has a lower risk of tolerance and dependence compared to traditional benzodiazepines [1]. **Analysis of Incorrect Options:** * **A. Zolmitriptan:** A selective 5-HT$_{1B/1D}$ receptor agonist used in the acute treatment of **migraine** attacks. It works by causing cranial vasoconstriction and inhibiting neuropeptide release. * **B. Zileuton:** A 5-lipoxygenase (5-LOX) inhibitor used in the maintenance treatment of **asthma**. It prevents the synthesis of leukotrienes (LTB4, LTC4, LTD4, and LTE4). * **D. Zalcitabine:** A nucleoside reverse transcriptase inhibitor (NRTI) formerly used in the treatment of **HIV/AIDS**. **High-Yield Clinical Pearls for NEET-PG:** * **Antidote:** Like benzodiazepines, the effects of Zolpidem can be reversed by **Flumazenil** [1]. * **Side Effects:** A unique and frequently tested side effect of Z-drugs is **complex sleep behaviors** (e.g., sleep-walking, sleep-driving). * **Pharmacokinetics:** Zolpidem has a short half-life (~2 hours), making it ideal for sleep induction without significant "hangover" effects the next morning.

Question 188: Parkinsonism is induced by all drugs except?

A. Reserpine
B. Metoclopramide
C. Chlorpromazine
D. Amantadine (Correct Answer)

Explanation: **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 189: Which of the following is NOT true about d-Tubocurarine (d-TC)?

A. Excreted unchanged by the kidney.
B. Causes hypotension by ganglion blocking action. (Correct Answer)
C. Has vagolytic action.
D. Effects last for 2-3 hours.

Explanation: **Explanation:** d-Tubocurarine (d-TC) is the prototype of non-depolarizing (competitive) neuromuscular blockers. Understanding its side-effect profile is crucial for NEET-PG. **Why Option B is the correct answer (The "NOT true" statement):** While d-TC does cause hypotension, the primary mechanism is **histamine release** from mast cells, not significant ganglion blockade. Although d-TC has some weak ganglion-blocking properties, the profound drop in blood pressure and associated bronchospasm are clinically attributed to histamine. In modern practice, newer agents like Vecuronium are preferred because they lack this histamine-releasing property. **Analysis of other options:** * **Option A:** d-TC is highly polar and is primarily excreted **unchanged in the urine** (approx. 70%). This makes it contraindicated in patients with renal failure. * **Option C:** d-TC possesses **vagolytic action** (antimuscarinic effect at the heart), which can contribute to tachycardia, though this effect is more pronounced with Gallamine. * **Option D:** d-TC is a **long-acting** muscle relaxant. Its effects typically last for **2-3 hours**, making it unsuitable for short procedures like intubation. **High-Yield NEET-PG Pearls:** 1. **Hofmann Elimination:** Remember that *Atracurium* and *Cisatracurium* undergo spontaneous degradation (Hofmann elimination) and are the drugs of choice in liver/kidney failure. 2. **Reversal:** The blockade of d-TC is reversed by Acetylcholinesterase inhibitors like **Neostigmine**. 3. **Order of Paralysis:** Small, rapid muscles (eyes, fingers) are paralyzed first; the **diaphragm** is the last to be paralyzed and the first to recover.

Question 190: Which of the following is NOT a characteristic feature of a non-depolarizing neuromuscular blockade?

A. Potentiated by magnesium
B. Potentiated by neostigmine (Correct Answer)
C. Relatively slow onset
D. In partial paralysis, nerve stimulation shows fade

Explanation: ### Explanation **Correct Answer: B. Potentiated by neostigmine** **Why it is correct:** Non-depolarizing neuromuscular blockers (NDNMBs) like **atracurium** and **vecuronium** act as competitive antagonists at the nicotinic acetylcholine receptors ($N_m$) at the neuromuscular junction [2]. **Neostigmine** is an acetylcholinesterase inhibitor that prevents the breakdown of acetylcholine (ACh). This increases the concentration of ACh at the synapse, which then competes with and displaces the NDNMB from the receptor. Therefore, neostigmine **reverses** (antagonizes) the blockade rather than potentiating it [1], [2]. **Analysis of Incorrect Options:** * **A. Potentiated by magnesium:** Magnesium inhibits the pre-synaptic release of acetylcholine and reduces the sensitivity of the post-junctional membrane. Thus, hypermagnesemia potentiates the effects of NDNMBs. * **C. Relatively slow onset:** Compared to depolarizing blockers like Succinylcholine (which acts within 30–60 seconds), NDNMBs generally have a slower onset of action (typically 2–5 minutes). * **D. Nerve stimulation shows fade:** In partial non-depolarizing blockade, repetitive nerve stimulation (like Train-of-Four) shows "fade" [2]. This occurs because NDNMBs also block pre-junctional nicotinic receptors, which normally facilitate the mobilization of ACh vesicles to meet the demand of rapid stimulation. **High-Yield Clinical Pearls for NEET-PG:** * **Reversal Agent:** Neostigmine is co-administered with **Glycopyrrolate** (or Atropine) to prevent bradycardia and excessive secretions caused by muscarinic stimulation [1]. * **Sugammadex:** A novel reversal agent specifically for **Rocuronium** and Vecuronium; it works by chelation (encapsulation) rather than enzyme inhibition. * **Hoffman Elimination:** A spontaneous non-enzymatic degradation (temperature and pH-dependent) unique to **Atracurium** and **Cisatracurium**, making them safe in renal or hepatic failure [2]. * **Drug Interactions:** Aminoglycosides, Tetracyclines, and Volatile anesthetics also potentiate NDNMBs.

Practice by Chapter

General Anesthetics

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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

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Psychostimulants

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Hallucinogens

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CNS Stimulants and Cognitive Enhancers

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