Central Nervous System Pharmacology — MCQs

Central Nervous System Pharmacology Indian Medical PG Practice Questions and MCQs

Question 621: Which of the following statements about vigabatrin is true?

A. Blocks neuronal reuptake of GABA
B. Drug of choice in absence seizures
C. Life-threatening skin disorders may occur
D. Visual disturbances can occur (Correct Answer)

Explanation: **Vigabatrin** is a structural analog of GABA that acts as an **irreversible inhibitor of GABA transaminase (GABA-T)**, the enzyme responsible for the degradation of GABA. By inhibiting this enzyme, it significantly increases the concentration of GABA (an inhibitory neurotransmitter) in the synaptic cleft. ### Why the correct answer is right: **Option D: Visual disturbances can occur.** The most significant and characteristic adverse effect of vigabatrin is **permanent bilateral concentric visual field constriction** (peripheral vision loss), occurring in up to 30-50% of patients. This is due to retinal toxicity. Because of this risk, it is usually reserved for refractory cases, and regular ophthalmological monitoring (perimetry) is mandatory. ### Why the other options are wrong: * **Option A:** Vigabatrin inhibits the *metabolism* of GABA, not its reuptake. **Tiagabine** is the drug that blocks neuronal and glial reuptake of GABA by inhibiting the GAT-1 transporter. * **Option B:** Vigabatrin is not used for absence seizures; in fact, it may **exacerbate** absence and myoclonic seizures. It is primarily used for refractory focal seizures and is the **drug of choice for Infantile Spasms (West Syndrome)** associated with Tuberous Sclerosis. * **Option C:** Life-threatening skin disorders (like Stevens-Johnson Syndrome) are more commonly associated with **Lamotrigine, Phenytoin, or Carbamazepine**, rather than Vigabatrin. ### High-Yield NEET-PG Pearls: * **Mechanism:** Irreversible "Suicide" inhibition of GABA-T. * **DOC:** Infantile Spasms (West Syndrome) in Tuberous Sclerosis. * **Black Box Warning:** Permanent vision loss (Vigabatrin Risk Evaluation and Mitigation Strategy - REMS program). * **Mnemonic:** **Vi**gabratrin **G**ABA **T**ransaminase inhibitor → **Vi**sual field defects.

Question 622: Which of the following statements about selegiline is false?

A. It is a MAO-A inhibitor (Correct Answer)
B. It does not cause cheese reaction
C. It may be used in the on-off phenomenon
D. It is used in parkinsonism

Explanation: **Explanation:** **1. Why Option A is the Correct (False) Statement:** Selegiline is a **selective, irreversible inhibitor of MAO-B**, not MAO-A. In the brain, MAO-B is the primary enzyme responsible for the degradation of dopamine. By inhibiting MAO-B, selegiline increases the availability of dopamine in the striatum. MAO-A, conversely, primarily metabolizes norepinephrine and serotonin and is found predominantly in the gut and liver. **2. Analysis of Other Options:** * **Option B (It does not cause cheese reaction):** This is true. The "cheese reaction" (hypertensive crisis) occurs when dietary tyramine displaces norepinephrine. Since tyramine is primarily metabolized by MAO-A in the gut, selective MAO-B inhibitors like selegiline (at conventional doses) do not interfere with tyramine metabolism, thus avoiding this reaction. * **Option C (Used in on-off phenomenon):** This is true. Selegiline is used as an adjunct to Levodopa to smooth out motor fluctuations (end-of-dose wearing off and on-off phenomena) by prolonging the half-life of dopamine. * **Option D (Used in parkinsonism):** This is true. It is used both as monotherapy in early Parkinson’s disease (to delay the need for Levodopa) and as an adjunct in advanced stages. **High-Yield Clinical Pearls for NEET-PG:** * **Selectivity Loss:** At high doses (>10mg/day), selegiline loses its selectivity and can inhibit MAO-A, potentially causing the cheese reaction. * **Metabolism:** Selegiline is metabolized into **amphetamine and methamphetamine**, which may cause insomnia if taken late in the day. * **Rasagiline:** A newer, more potent MAO-B inhibitor that is not metabolized into amphetamine derivatives. * **Drug Interaction:** Avoid combining MAO inhibitors with SSRIs or Meperidine to prevent **Serotonin Syndrome**.

Question 623: Which of the following drugs is an inverse agonist at H3 receptors used for the treatment of narcolepsy?

A. Dexmedetomidine
B. Pitolisant (Correct Answer)
C. Icatibant
D. Secukinumab

Explanation: Pitolisant is a first-in-class drug recently approved for the treatment of excessive daytime sleepiness (EDS) in adults with narcolepsy (with or without cataplexy). [1] 1. **Mechanism of Action:** Unlike H1 and H2 receptors which are postsynaptic, **H3 receptors** are primarily presynaptic autoreceptors located in the brain. [1] They normally inhibit the release of histamine. Pitolisant acts as a potent **selective H3-receptor antagonist/inverse agonist**. [1] By blocking these autoreceptors, it increases the synthesis and release of histamine in the brain, which promotes wakefulness and alertness (histamine is a major wake-promoting neurotransmitter). **Analysis of Incorrect Options:** * **A. Dexmedetomidine:** A highly selective **alpha-2 adrenergic agonist** used for sedation in intensive care settings and as an anesthetic adjunct. It causes sedation, not wakefulness. * **C. Icatibant:** A selective **bradykinin B2 receptor antagonist** used for the symptomatic treatment of acute attacks of hereditary angioedema (HAE). * **D. Secukinumab:** A human monoclonal antibody that binds to **Interleukin-17A (IL-17A)**, used in the treatment of psoriasis, ankylosing spondylitis, and psoriatic arthritis. **High-Yield Clinical Pearls for NEET-PG:** * **Narcolepsy Treatment Hierarchy:** Modafinil/Armodafinil (First-line), Pitolisant, Solriamfetol (DNRI), and Sodium Oxybate (for cataplexy). [2] * **Unique Feature:** Pitolisant is the only narcolepsy medication that is **not** classified as a controlled substance, as it lacks the typical abuse potential of stimulants. * **Metabolism:** It is metabolized by CYP2D6; dose adjustments are required in poor metabolizers or when given with drugs like paroxetine or fluoxetine.

Question 624: Which of the following drugs has spasmolytic activity and could also be used in the management of seizures caused by an overdose of a local anesthetic?

A. Baclofen
B. Dantrolene
C. Diazepam (Correct Answer)
D. Tizanidine

Explanation: **Explanation:** **Diazepam** is the correct answer because it possesses both potent **spasmolytic** properties and **anticonvulsant** activity. It acts as a positive allosteric modulator of the **GABA-A receptor**, increasing the frequency of chloride channel opening. This enhances postsynaptic inhibition in the spinal cord (reducing muscle tone) and the brain (raising the seizure threshold). In the event of **Local Anesthetic (LA) systemic toxicity**, CNS excitation (seizures) occurs due to the inhibition of cortical inhibitory pathways; Diazepam is a first-line agent to suppress these seizures. **Analysis of Incorrect Options:** * **Baclofen (A):** A GABA-B agonist that acts at the spinal level. While it is an effective spasmolytic for MS or spinal injury, it has no role in managing acute seizures and may even lower the seizure threshold in some patients. * **Dantrolene (B):** A direct-acting muscle relaxant that inhibits calcium release from the sarcoplasmic reticulum (RyR1 receptor). It is the drug of choice for **Malignant Hyperthermia** but lacks any central anticonvulsant activity. * **Tizanidine (D):** An alpha-2 adrenergic agonist. It reduces muscle spasticity by increasing presynaptic inhibition of motor neurons but does not possess anti-seizure properties. **Clinical Pearls for NEET-PG:** * **LA Toxicity Management:** The definitive treatment for Local Anesthetic Systemic Toxicity (LAST) is **Intravenous Lipid Emulsion (20% Lipid)**. Benzodiazepines like Diazepam or Midazolam are used specifically for seizure control. * **Mechanism Distinction:** Diazepam increases the *frequency* of GABA-A channel opening, whereas Barbiturates increase the *duration*. * **Drug of Choice:** Diazepam is also a drug of choice for **Status Epilepticus** (though Lorazepam is often preferred clinically due to a longer duration of action in the brain).

Question 625: All of the following statements are true regarding sumatriptan except?

A. It has 99% oral bioavailability (Correct Answer)
B. It is contraindicated in coronary artery disease
C. It constricts cranial vessels
D. It is selective 5-HT 1B/1D receptor agonist

Explanation: **Explanation:** Sumatriptan is the prototype of the "Triptan" class, which revolutionized the management of acute migraine. **1. Why Option A is the Correct Answer (The False Statement):** Sumatriptan has a **low oral bioavailability (approximately 14-15%)**. This is primarily due to its poor absorption and significant first-pass metabolism by the enzyme Monoamine Oxidase-A (MAO-A). Because of this low bioavailability and slow onset when taken orally, other routes like subcutaneous (highest bioavailability ~97%), nasal spray, and rectal suppositories are often preferred for rapid relief. **2. Analysis of Other Options:** * **Option B (Contraindicated in CAD):** This is a **true** statement. Triptans cause vasoconstriction not only in cranial vessels but can also cause coronary vasospasm. Therefore, they are strictly contraindicated in patients with Ischemic Heart Disease (IHD), Prinzmetal angina, and uncontrolled hypertension. * **Option C (Constricts cranial vessels):** This is a **true** statement. Migraine involves the dilation of intracranial extracerebral blood vessels. Sumatriptan reverses this by acting on 1B receptors. * **Option D (Selective 5-HT 1B/1D agonist):** This is a **true** statement. Its mechanism involves: * **5-HT 1B:** Vasoconstriction of dilated cranial vessels. * **5-HT 1D:** Inhibition of pro-inflammatory neuropeptide release (Substance P, CGRP) from trigeminal nerve endings. **High-Yield Clinical Pearls for NEET-PG:** * **Drug of Choice:** Triptans are the DOC for **acute severe migraine** and **cluster headaches** (specifically SC Sumatriptan). * **Metabolism:** Sumatriptan is metabolized by **MAO-A**; it should not be used within 2 weeks of MAO inhibitors. * **Second Generation Triptans:** Rizatriptan, Zolmitriptan, and Eletriptan have better oral bioavailability and CNS penetration compared to Sumatriptan. * **Side Effect:** "Triptan sensations" (tightness in the chest and throat) are common but usually benign unless cardiac history is present.

Question 626: Which of the following drugs decreases the effect of levodopa?

A. Carbidopa
B. MAO inhibitors
C. Vitamin B complex (Correct Answer)
D. COMT inhibitors

Explanation: **Explanation:** The correct answer is **Vitamin B complex**, specifically **Vitamin B6 (Pyridoxine)**. **Mechanism of Interaction:** Levodopa is converted into dopamine by the enzyme **DOPA decarboxylase**. Pyridoxine (Vitamin B6) acts as a vital cofactor for this enzyme. When Vitamin B6 levels are high, 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 efficacy and increasing peripheral side effects (like nausea and arrhythmias). **Analysis of Incorrect Options:** * **A. Carbidopa:** This is a peripheral DOPA decarboxylase inhibitor. It is co-administered with levodopa specifically to **increase** its CNS bioavailability and prevent the very interaction caused by Vitamin B6. * **B. MAO inhibitors:** MAO-B inhibitors (e.g., Selegiline) prevent the breakdown of dopamine in the brain, thereby **potentiating** the effect of levodopa. (Note: Non-selective MAOIs are avoided due to the risk of hypertensive crisis). * **D. COMT inhibitors:** Drugs like Entacapone inhibit the COMT enzyme, preventing the peripheral degradation of levodopa to 3-O-methyldopa. This **increases** the half-life and brain delivery of levodopa. **High-Yield Clinical Pearls for NEET-PG:** * **The "Pyridoxine Reversal":** This interaction occurs only with plain Levodopa. If Levodopa is combined with **Carbidopa**, the inhibitory effect of Vitamin B6 is nullified because Carbidopa inhibits the enzyme that B6 would otherwise stimulate. * **Dietary Advice:** Patients on plain levodopa should avoid multi-vitamin supplements containing high doses of B6. * **Drug of Choice:** The combination of Levodopa + Carbidopa (Co-careldopa) is the gold standard for Parkinson’s disease.

Question 627: What is the most potent analgesic agent among the following?

A. Nitrous oxide (Correct Answer)
B. Nitric oxide
C. Carbon dioxide
D. Oxygen

Explanation: **Explanation:** **Nitrous oxide ($N_2O$)**, also known as "laughing gas," is a colorless, odorless gas used extensively in anesthesia. Among the options provided, it is the only agent with significant **analgesic (pain-relieving)** properties. Its analgesic effect is primarily mediated through the release of endogenous opioid peptides (endorphins) and the inhibition of NMDA receptors in the central nervous system. While $N_2O$ is a weak general anesthetic (High MAC value of 104%), it is a **potent analgesic**; even a 20% concentration can provide pain relief equivalent to a therapeutic dose of morphine. **Analysis of Incorrect Options:** * **Nitric oxide (NO):** This is a potent endogenous vasodilator and cell-signaling molecule. In clinical practice, inhaled NO is used to treat pulmonary hypertension, but it possesses no analgesic or anesthetic properties. * **Carbon dioxide ($CO_2$):** This is a metabolic byproduct. While it acts as a respiratory stimulant, it does not have analgesic properties. In fact, high levels (hypercapnia) lead to respiratory acidosis and distress. * **Oxygen ($O_2$):** Essential for life and aerobic metabolism, oxygen is used to prevent hypoxia during anesthesia but has no inherent analgesic effect. **High-Yield Clinical Pearls for NEET-PG:** * **Second Gas Effect:** $N_2O$ is rapidly absorbed, increasing the concentration of a concurrently administered volatile anesthetic (e.g., Halothane) in the alveoli. * **Diffusion Hypoxia:** Occurs during recovery if $N_2O$ is discontinued abruptly without supplemental $O_2$; $N_2O$ rushes out of the blood into the alveoli, diluting $O_2$. * **Contraindication:** $N_2O$ should be avoided in patients with **pneumothorax, intestinal obstruction, or middle ear surgery**, as it expands into closed, air-filled spaces. * **Vitamin $B_{12}$ Deficiency:** Chronic exposure can lead to megaloblastic anemia by inactivating methionine synthase.

Question 628: Valproic acid causes all of the following EXCEPT?

A. It is an enzyme inducer
B. It causes obesity
C. It causes hirsutism (Correct Answer)
D. It causes neural tube defects

Explanation: **Explanation:** Valproic acid (Sodium Valproate) is a broad-spectrum anti-epileptic drug with a unique side-effect profile. The correct answer is **C (Hirsutism)** because Valproic acid actually causes **alopecia** (hair loss), which is often transient and results in curly regrowth. Hirsutism is a classic side effect of **Phenytoin**, not Valproate. **Analysis of Options:** * **Option A (Enzyme Inducer):** This is a false statement regarding Valproate, but in the context of "Valproate causes all EXCEPT," it is a tricky distractor. Valproate is actually a potent **Microsomal Enzyme Inhibitor**. However, in many NEET-PG MCQ formats, the focus is on its clinical adverse effects. * **Option B (Obesity):** Valproate is notorious for causing significant **weight gain** and increased appetite, leading to obesity. This is a common reason for non-compliance, especially in young patients. * **Option D (Neural Tube Defects):** Valproate is highly teratogenic. It interferes with folate metabolism, leading to a 10-fold increase in the risk of **Spina Bifida** (Neural Tube Defects). **High-Yield Clinical Pearls for NEET-PG:** * **Mnemonic for Valproate Side Effects (VALPROATE):** **V**omit, **A**lopecia, **L**iver toxicity (Hepatotoxicity—most serious in children <2 years), **P**ancreatitis, **R**etention of fat (Obesity), **O**edema, **A**norexia, **T**eratogenicity (NTD), **E**nzyme Inhibitor. * **Drug of Choice:** Valproate is the DOC for Generalized Tonic-Clonic Seizures (GTCS), Myoclonic seizures, and Absence seizures. * **Polycystic Ovarian Syndrome (PCOS):** Valproate is associated with an increased risk of PCOS in young women due to weight gain and hormonal shifts.

Question 629: The active agent of cannabis chemically resembles which endogenous compound?

A. Endorphin
B. Endomorphins
C. Anandamide (Correct Answer)
D. Enkephalin

Explanation: ### Explanation The active agent of cannabis is **$\Delta^9$-tetrahydrocannabinol ($\Delta^9$-THC)**. It exerts its effects by binding to G-protein coupled receptors, specifically **CB1** (primarily in the CNS) and **CB2** (primarily in the immune system). **Why Anandamide is Correct:** Anandamide (N-arachidonoylethanolamine) is the primary **endogenous cannabinoid** (endocannabinoid). Chemically, both THC and Anandamide are lipid-based molecules that act as agonists at cannabinoid receptors. Anandamide is synthesized "on-demand" from membrane phospholipids and acts as a retrograde neurotransmitter, inhibiting the release of other neurotransmitters like GABA and glutamate. **Why the Other Options are Incorrect:** * **Options A, B, and D (Endorphins, Endomorphins, and Enkephalins):** These are all **endogenous opioid peptides**. While they are part of the body's natural reward and pain-modulation system, they act on **mu ($\mu$), kappa ($\kappa$), and delta ($\delta$) opioid receptors**. They are chemically peptides (chains of amino acids), whereas cannabis derivatives are terpenophenolic compounds. **High-Yield Clinical Pearls for NEET-PG:** * **Receptor Distribution:** CB1 receptors are highly concentrated in the **basal ganglia, hippocampus, and cerebellum** (explaining effects on motor control and memory). They are notably absent in the brainstem cardiorespiratory centers, which is why cannabis overdose is rarely fatal. * **Other Endocannabinoids:** Besides Anandamide, **2-Arachidonylglycerol (2-AG)** is the other major endogenous ligand. * **Therapeutic Uses:** Synthetic THC analogs like **Dronabinol** and **Nabilone** are used for chemotherapy-induced nausea and as appetite stimulants in AIDS-related wasting. * **Rimonabant:** A CB1 receptor antagonist previously used for obesity but withdrawn due to severe psychiatric side effects (depression/suicide).

Question 630: Which of the following drugs is commonly used for migraine prophylaxis?

A. Propranolol (Correct Answer)
B. Valproate
C. Topiramate
D. Ethosuxamide

Explanation: **Explanation:** Migraine prophylaxis is indicated when attacks are frequent (more than 2-3 per month), severe, or unresponsive to acute treatment. **Correct Answer: A. Propranolol** Beta-blockers, specifically **Propranolol**, are considered the **first-line agents** for migraine prophylaxis. The underlying mechanism involves stabilizing the vascular tone by preventing vasodilation, inhibiting central β1 receptors, and modulating serotonergic transmission in the cortical spreading depression pathway. It is particularly preferred in patients with co-existing hypertension or performance anxiety. **Analysis of Incorrect Options:** * **B. Valproate & C. Topiramate:** While both are indeed used for migraine prophylaxis (Antiepileptics), the question asks for the drug "commonly used" or the traditional first-line choice. In standard pharmacological hierarchy for NEET-PG, Propranolol remains the classic primary answer unless contraindications (like asthma) are mentioned. Note: Topiramate is often preferred if weight loss is desired, while Valproate is avoided in women of childbearing age. * **D. Ethosuximide:** This drug is the drug of choice for **Absence Seizures** (Petit mal). It works by blocking T-type calcium channels in the thalamus and has no clinical role in migraine management. **High-Yield Clinical Pearls for NEET-PG:** * **DOC for Acute Migraine:** Sumatriptan (5-HT 1B/1D agonist). * **DOC for Prophylaxis:** Propranolol (Beta-blocker). * **Contraindications for Propranolol:** Bronchial asthma, Heart block, and Peripheral Vascular Disease (Raynaud’s). * **Newer Agents:** CGRP antagonists (e.g., Erenumab) are used for refractory cases. * **Amitriptyline** (TCA) is the preferred prophylactic agent if the patient also suffers from tension-type headaches or depression.

Practice by Chapter

General Anesthetics

Practice Questions

Local Anesthetics

Practice Questions

Sedative-Hypnotics

Practice Questions

Antiepileptic Drugs

Practice Questions

Antiparkinsonian Drugs

Practice Questions

Opioid Analgesics

Practice Questions

Drugs of Abuse and Addiction

Practice Questions

Psychostimulants

Practice Questions

Hallucinogens

Practice Questions

CNS Stimulants and Cognitive Enhancers

Practice Questions

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