Central Nervous System Pharmacology — MCQs

Central Nervous System Pharmacology Indian Medical PG Practice Questions and MCQs

Question 91: Arrange the following drugs in sequence of their use in status epilepticus: Phenytoin, Lorazepam, Phenobarbital, Propofol?

A. Phenytoin > Lorazepam > Phenobarbital > Propofol
B. Lorazepam > Phenytoin > Phenobarbital > Propofol (Correct Answer)
C. Lorazepam > Phenobarbital > Propofol > Phenytoin
D. Phenobarbital > Phenytoin > Propofol > Lorazepam

Explanation: **Explanation:** The management of **Status Epilepticus (SE)** follows a structured, time-dependent protocol designed to stop seizure activity rapidly and prevent neuronal damage. 1. **First-line (Stabilization/Initial Therapy):** **Benzodiazepines** are the drugs of choice due to their rapid onset. **Lorazepam (IV)** is preferred over Diazepam because it has a longer duration of action in the brain (less redistribution). 2. **Second-line (Urgent Therapy):** If seizures persist, a long-acting anticonvulsant is administered. **Phenytoin** (or Fosphenytoin) is the standard choice to provide sustained seizure control. 3. **Third-line (Refractory SE):** If seizures continue after the second-line agent, **Phenobarbital** is typically used. 4. **Fourth-line (Super-refractory SE):** For seizures failing all the above, general anesthetics like **Propofol**, Midazolam infusion, or Thiopental are used, often requiring intubation and ICU monitoring. **Analysis of Options:** * **Option B is correct** as it follows the standard clinical escalation: Benzodiazepine → Hydantoin → Barbiturate → General Anesthetic. * **Option A** is incorrect because Phenytoin takes 15-20 minutes to administer and act; it cannot be used before the rapid-acting Lorazepam. * **Option C & D** are incorrect because they delay the use of first-line Benzodiazepines or second-line Phenytoin, increasing the risk of permanent neurological injury. **High-Yield NEET-PG Pearls:** * **Drug of Choice (DOC):** IV Lorazepam (0.1 mg/kg). * **Fosphenytoin** is preferred over Phenytoin because it is water-soluble, causes less phlebitis ("Purple Glove Syndrome"), and can be infused faster. * **Definition Change:** SE is now clinically defined as continuous seizure activity for **>5 minutes** (previously 30 minutes) to encourage early intervention. * **Refractory SE:** Defined as failure of adequate doses of a Benzodiazepine and one antiepileptic drug.

Question 92: Which dopamine receptor exhibits an inhibitory action?

A. D5
B. Di
C. D2 (Correct Answer)
D. None

Explanation: **Explanation:** Dopamine receptors belong to the **G-protein coupled receptor (GPCR)** superfamily and are categorized into two main functional families based on their effect on the enzyme adenylyl cyclase. 1. **D2-like Family (D2, D3, D4):** These receptors are coupled to **Gi/o proteins**. Their activation **inhibits** the enzyme adenylyl cyclase, leading to a decrease in intracellular cyclic AMP (cAMP) levels. They also open potassium channels and close voltage-gated calcium channels, resulting in an overall inhibitory effect on the post-synaptic neuron. 2. **D1-like Family (D1, D5):** These receptors are coupled to **Gs proteins**. Their activation **stimulates** adenylyl cyclase, increasing cAMP levels and exerting an excitatory effect. **Analysis of Options:** * **Option C (D2):** Correct. As part of the D2-like family, it mediates inhibitory neurotransmission. It is the primary target for most antipsychotic drugs. * **Options A & B (D5 & D1):** Incorrect. Both belong to the D1-like family and are excitatory in nature (stimulate cAMP). * **Option D:** Incorrect, as D2 is a well-established inhibitory receptor. **High-Yield Clinical Pearls for NEET-PG:** * **Antipsychotics:** Most typical antipsychotics (e.g., Haloperidol) act by blocking **D2 receptors** in the mesolimbic pathway. * **Parkinson’s Disease:** Results from a loss of dopaminergic neurons in the substantia nigra. Treatment involves D2 agonists (e.g., Bromocriptine, Pramipexole). * **Location:** D1 and D2 are the most abundant dopamine receptors in the striatum. D4 receptors are specifically targeted by the atypical antipsychotic **Clozapine**.

Question 93: Which of the following drugs are used in Generalized Tonic-Clonic Seizures (GTCS)?

A. Ethosuximide (Correct Answer)
B. Sodium valproate
C. Lamotrigine
D. Propofol

Explanation: **Explanation** The correct answer is **Ethosuximide**. **1. Why Ethosuximide is the Correct Answer:** Ethosuximide is the drug of choice for **Absence Seizures** (Petit Mal). Its mechanism of action involves the inhibition of **T-type Calcium channels** in thalamic neurons. While it is highly effective for absence seizures, it is notably **ineffective** against Generalized Tonic-Clonic Seizures (GTCS). In fact, if a patient has a combination of absence seizures and GTCS, ethosuximide alone may precipitate or worsen GTCS. **2. Analysis of Incorrect Options:** * **Sodium Valproate:** This is a broad-spectrum antiepileptic and is considered the **drug of choice for GTCS**, as well as myoclonic and atonic seizures. * **Lamotrigine:** Another broad-spectrum agent effective against GTCS. It acts by blocking voltage-gated sodium channels and inhibiting glutamate release. * **Propofol:** While used in the management of refractory **Status Epilepticus** (to induce anesthesia), it is not a standard maintenance therapy for GTCS. **3. High-Yield Clinical Pearls for NEET-PG:** * **Drug of Choice for GTCS:** Sodium Valproate (First line); Levetiracetam or Lamotrigine (Alternatives). * **Drug of Choice for Absence Seizures:** Ethosuximide (if only absence); Sodium Valproate (if absence + GTCS). * **Narrow-spectrum drugs to avoid in GTCS/Myoclonic seizures:** Carbamazepine, Phenytoin, and Vigabatrin (these can paradoxically worsen generalized seizures). * **Teratogenicity:** Valproate is associated with Neural Tube Defects (highest risk), while Lamotrigine is considered one of the safest in pregnancy.

Question 94: Which of the following drugs is a 5HT2c agonist approved for the treatment of obesity and can cause Serotonin Syndrome as an adverse effect?

A. Lorcaserin (Correct Answer)
B. Sibutramine
C. Modafinil
D. Rimonabant

Explanation: ### Explanation **Correct Option: A. Lorcaserin** Lorcaserin is a selective **5-HT2C receptor agonist** located in the hypothalamus. Activation of these receptors on pro-opiomelanocortin (POMC) neurons promotes satiety and reduces food intake. Because it increases serotonergic signaling, it carries a risk of **Serotonin Syndrome**, especially when co-administered with other serotonergic agents (like SSRIs or MAOIs). *Note: While Lorcaserin was FDA-approved for obesity, it was voluntarily withdrawn from the market in 2020 due to concerns regarding an increased risk of cancer.* **Incorrect Options:** * **B. Sibutramine:** This is a non-selective serotonin and norepinephrine reuptake inhibitor (SNRI). It was withdrawn globally due to increased risks of major adverse cardiovascular events (MI and stroke). * **C. Modafinil:** This is a wakefulness-promoting agent (eugeroic) used primarily for narcolepsy and shift-work sleep disorder. It acts by increasing synaptic dopamine and has no role in obesity management. * **D. Rimonabant:** This is a **CB1 cannabinoid receptor antagonist**. It was used for obesity but withdrawn due to severe psychiatric side effects, including depression and suicidal ideation. **High-Yield Clinical Pearls for NEET-PG:** * **Mechanism of Satiety:** 5-HT2C (Lorcaserin) and GLP-1 agonists (Liraglutide/Semaglutide) are key pathways for weight loss. * **Phentermine + Topiramate:** A common combination for obesity; Topiramate acts via GABA modulation and carbonic anhydrase inhibition. * **Orlistat:** A gastrointestinal lipase inhibitor; unique because it is not centrally acting but causes "steatorrhea" (oily stools). * **Qsymia:** Trade name for the Phentermine/Topiramate combination.

Question 95: A 70-year-old man with a known history of Parkinson's disease is to receive prophylaxis against Influenza A virus. He is given a drug that is useful for Parkinson's disease and also for prophylaxis against influenza. Which mechanism of action is most likely for the prescribed drug?

A. Prevents viral entry and penetration into the host cell
B. Prevents viral uncoating (Correct Answer)
C. Inhibits viral replication
D. Prevents the assembly of newly synthesized virus particles

Explanation: The drug described is **Amantadine**. It is a unique pharmacological agent that bridges neurology and virology, making it a classic high-yield topic for NEET-PG. [1] **1. Why the Correct Answer is Right:** Amantadine (and its derivative Rimantadine) acts as an antiviral by targeting the **M2 proton channel** of the Influenza A virus. By blocking this channel, the drug prevents the acidification of the viral interior, which is a necessary step for the virus to shed its protein coat and release its RNA into the host cell cytoplasm. Thus, it **prevents viral uncoating**. In Parkinson’s disease, Amantadine works by increasing dopamine release, inhibiting dopamine reuptake, and acting as a weak NMDA receptor antagonist. [2] **2. Why the Other Options are Incorrect:** * **Option A:** Drugs like **Enfuvirtide** (for HIV) or **Maraviroc** prevent entry/penetration. Amantadine acts after the virus has already entered the cell via endocytosis. * **Option C:** This is the mechanism for drugs like **Acyclovir** (DNA polymerase inhibitor) or **Ribavirin** (RNA polymerase inhibitor). Amantadine does not interfere with the synthesis of viral nucleic acids. * **Option D:** **Protease inhibitors** (e.g., Ritonavir) prevent the processing of viral proteins and assembly. **Oseltamivir** (Neuraminidase inhibitor) prevents the release of progeny virions, not the assembly itself. [3] **Clinical Pearls for NEET-PG:** * **Spectrum:** Amantadine is active *only* against Influenza A; it is ineffective against Influenza B (which lacks M2 channels). * **Side Effects:** A characteristic side effect is **Livedo Reticularis** (a purplish, lace-like skin rash) and ankle edema. * **Resistance:** Most current seasonal Influenza A strains (H1N1, H3N2) have developed high resistance to Amantadine, limiting its clinical use as an antiviral today.

Question 96: What is the byproduct of GABA metabolism?

A. Glutamate
B. Aspartate
C. Glycine
D. Succinate (Correct Answer)

Explanation: The metabolism of GABA (Gamma-Aminobutyric Acid), the primary inhibitory neurotransmitter in the CNS [1], occurs via a pathway known as the **GABA Shunt**. This process is essential for maintaining the balance of neurotransmitters and providing energy to neurons. 1. **Mechanism of GABA Metabolism:** * GABA is first converted into **Succinic Semialdehyde** by the enzyme **GABA-Transaminase (GABA-T)**. * Succinic semialdehyde is then oxidized by **Succinic Semialdehyde Dehydrogenase (SSADH)** to form **Succinate** (Succinic acid). * Succinate enters the **Kreb’s Cycle (TCA cycle)**, where it is utilized for ATP production. This direct link between neurotransmitter degradation and energy metabolism is why Succinate is the definitive byproduct. **Analysis of Incorrect Options:** * **A. Glutamate:** This is the immediate *precursor* of GABA, formed via the decarboxylation of glutamate by the enzyme GAD (Glutamic Acid Decarboxylase) [2]. * **B. Aspartate:** This is an excitatory neurotransmitter but is not a direct byproduct of the GABA metabolic pathway. * **C. Glycine:** This is a separate inhibitory neurotransmitter primarily active in the spinal cord and brainstem [1]; it is not involved in GABA degradation. **High-Yield Clinical Pearls for NEET-PG:** * **Vigabatrin:** A key pharmacological agent that acts as an **irreversible inhibitor of GABA-Transaminase**. By blocking the conversion of GABA to Succinic semialdehyde, it increases GABA levels in the brain, making it effective for infantile spasms and refractory epilepsy. * **Vitamin B6 (Pyridoxine):** GAD requires Vitamin B6 as a cofactor. Deficiency can lead to decreased GABA levels and seizures. * **GABA Shunt:** It bypasses the alpha-ketoglutarate to succinate step of the TCA cycle.

Question 97: Which of the following drugs is used in the treatment of Alzheimer's disease?

A. Neostigmine
B. Rivastigmine (Correct Answer)
C. Trihexyphenidyl
D. Benztropine

Explanation: **Explanation:** **Alzheimer’s Disease (AD)** is characterized by a deficiency of cholinergic transmission in the brain. The primary therapeutic strategy involves increasing acetylcholine levels in the synaptic cleft using **Centrally Acting Reversible Acetylcholinesterase Inhibitors.** **Why Rivastigmine is Correct:** **Rivastigmine** is a carbamate derivative that inhibits both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Unlike many other drugs in its class, it is "pseudo-irreversible" and has a high affinity for the G1 isoform of AChE found predominantly in the brain. It is FDA-approved for mild-to-moderate Alzheimer’s and is uniquely available as a **transdermal patch**, which reduces gastrointestinal side effects. **Analysis of Incorrect Options:** * **A. Neostigmine:** While it is an AChE inhibitor, it is a **quaternary ammonium compound**. This means it is highly polar, does not cross the blood-brain barrier (BBB), and therefore cannot treat CNS disorders like Alzheimer’s. It is used for Myasthenia Gravis and reversing neuromuscular blockade. * **C & D. Trihexyphenidyl and Benztropine:** These are **central anticholinergics**. Since Alzheimer’s is a disease of "too little" acetylcholine, blocking acetylcholine receptors would worsen cognitive decline and memory loss. These drugs are instead used to treat Drug-Induced Parkinsonism (EPS). **High-Yield Clinical Pearls for NEET-PG:** * **Other AD Drugs:** Donepezil (long half-life), Galantamine, and **Memantine** (an NMDA receptor antagonist used in moderate-to-severe cases). * **Side Effects:** Think "Cholinergic excess"—Diarrhea, Urination, Miosis, Bradycardia, Emesis, Lacrimation, Salivation (DUMBELS). * **Newer Monoclonal Antibodies:** Aducanumab and Lecanemab (target Amyloid-beta plaques).

Question 98: What is the drug of choice for the management of dystonia?

A. Trihexyphenidyl (Correct Answer)
B. Propranolol
C. Vitamin E
D. Clonazepam

Explanation: **Explanation:** **1. Why Trihexyphenidyl is correct:** Dystonia is a movement disorder characterized by sustained or repetitive muscle contractions, often resulting from an imbalance between dopamine and acetylcholine in the basal ganglia (specifically, a relative excess of cholinergic activity). **Trihexyphenidyl** is a centrally acting **antimuscarinic (anticholinergic)** agent. By blocking muscarinic receptors in the striatum, it restores the dopaminergic-cholinergic balance. It is considered the drug of choice for various forms of dystonia, including drug-induced acute dystonic reactions (e.g., from antipsychotics) and idiopathic torsion dystonia. **2. Why the other options are incorrect:** * **Propranolol:** This is a non-selective beta-blocker and is the drug of choice for **Essential Tremors** and akathisia, not dystonia. * **Vitamin E:** High-dose Vitamin E has been studied for the prevention or management of **Tardive Dyskinesia**, but it has no established role in treating acute or primary dystonia. * **Clonazepam:** While benzodiazepines can be used as adjunctive therapy for generalized dystonia due to their GABAergic muscle-relaxant effects, they are not the primary drug of choice. **3. Clinical Pearls for NEET-PG:** * **Acute Dystonia:** For emergency management of drug-induced dystonia (e.g., oculogyric crisis), parenteral (IV/IM) **Promethazine** or **Benztropine** is often used. * **Focal Dystonia:** For localized conditions like blepharospasm or cervical dystonia (torticollis), **Botulinum toxin** is the preferred treatment. * **Side Effects:** Remember the "anti-SLUDGE" profile of Trihexyphenidyl: dry mouth, blurred vision (cycloplegia), urinary retention, and constipation. It should be avoided in elderly patients due to the risk of confusion and glaucoma.

Question 99: What is the primary action of both fenfluramine and phentermine?

A. To produce central nervous system stimulation
B. To suppress appetite (Correct Answer)
C. To treat narcolepsy
D. To treat attention deficit disorders in children

Explanation: The correct answer is **B. To suppress appetite**. Fenfluramine and phentermine are classified as **anorexiants** (appetite suppressants) used in the short-term management of obesity [1]. **Mechanism of Action:** * **Fenfluramine:** Primarily acts by increasing the release and inhibiting the reuptake of **serotonin (5-HT)** in the hypothalamus, which enhances satiety [1]. * **Phentermine:** Acts as a sympathomimetic amine, increasing the release of **norepinephrine** (and to a lesser extent, dopamine) in the hypothalamus, which stimulates the "fight or flight" response and reduces hunger [1]. **Analysis of Incorrect Options:** * **Option A:** While phentermine is a sympathomimetic that can cause CNS stimulation, fenfluramine is unique because it often causes **sedation** rather than stimulation. Therefore, "CNS stimulation" is not a shared primary action. * **Options C & D:** These are clinical indications for other CNS stimulants like **Modafinil** (Narcolepsy) and **Methylphenidate** or **Amphetamines** (ADHD). Fenfluramine and phentermine are not used for these conditions [1]. **High-Yield Clinical Pearls for NEET-PG:** * **Fen-Phen Combination:** Historically used together but withdrawn because fenfluramine was linked to **valvular heart disease** and **pulmonary hypertension** due to overstimulation of 5-HT2B receptors. * **Current Status:** Fenfluramine has been repurposed at low doses for the treatment of seizures in **Dravet syndrome**. * **Phentermine:** Remains one of the most commonly prescribed short-term anti-obesity drugs; it is often combined with **Topiramate** (Qsymia) for synergistic weight loss.

Question 100: Flumazenil is:

A. A diazepam inverse agonist
B. A diazepam antagonist (Correct Answer)
C. An opioid antagonist
D. An opioid inverse agonist

Explanation: ### Explanation **1. Why Option B is Correct:** Flumazenil is a specific **competitive antagonist** at the benzodiazepine (BDZ) binding site on the $\text{GABA}_A$ receptor. It binds with high affinity but possesses no intrinsic activity. By occupying the receptor, it prevents benzodiazepines (like Diazepam) from exerting their inhibitory effects. It is primarily used to reverse benzodiazepine-induced sedation and in the management of BDZ overdose. **2. Why the Other Options are Incorrect:** * **Option A (Inverse Agonist):** An inverse agonist (e.g., **Beta-carbolines**) binds to the same receptor but produces the *opposite* physiological effect of an agonist. While Diazepam is anxiolytic and anticonvulsant, an inverse agonist would be anxiogenic and pro-convulsant. Flumazenil neutralizes both agonists and inverse agonists. * **Options C & D (Opioid Antagonist/Inverse Agonist):** These terms refer to drugs like **Naloxone** or **Naltrexone**, which act on $\mu, \kappa,$ and $\delta$ opioid receptors. Flumazenil has no affinity for opioid receptors and cannot reverse respiratory depression caused by opioids. **3. High-Yield Clinical Pearls for NEET-PG:** * **Mechanism:** Competitive antagonism at the $\text{GABA}_A$ receptor complex. * **Half-life:** It has a very short half-life (~1 hour). Because many benzodiazepines (like Diazepam) have longer half-lives, **re-sedation** can occur, necessitating repeated doses or an infusion. * **Contraindication/Risk:** Use with caution in patients with long-term BDZ dependence or TCA overdose, as it can precipitate **acute withdrawal seizures**. * **Route:** Administered intravenously (IV) only.

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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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