Central Nervous System Pharmacology Practice Questions

Q: Which of the following anti-epileptics is not given during pregnancy?

Valproate. ***Correct: Valproate*** - Valproate (Valproic Acid) is the anti-epileptic drug (AED) with the **highest teratogenic risk**, particularly causing **Neural Tube Defects (NTDs)** like spina bifida (1-2% risk), in a dose-dependent manner - It is **strictly contraindicated** during pregnancy (FDA Category X) due to increased risks of **major congenital malformations (10-20%)** and long-term neurodevelopmental consequences, including lower IQ and increased risk of **Autism Spectrum Disorder** in the child - This is the AED that should **NOT be given during pregnancy** *Incorrect: Lamotrigine* - Lamotrigine is generally considered one of the **safer AEDs** used in pregnancy, often a preferred alternative when monotherapy is necessary - While initial data suggested a small risk of oral clefts, current extensive evidence shows it has a **low overall risk** of major congenital malformations - Can be safely used during pregnancy when needed *Incorrect: Levetiracetam* - Levetiracetam (Keppra) is highly favored during pregnancy because it has one of the **lowest risks** of causing major congenital malformations among all AEDs - It is often recommended as the **drug of choice** for women who require AED continuation during gestation due to its favorable safety profile for both physical and neurodevelopmental outcomes *Incorrect: Carbamazepine* - Carbamazepine increases the risk of teratogenicity, classically associated with a risk of **NTDs** (~1%, lower than Valproate) and minor craniofacial defects like cleft lip/palate - Although generally reserved for situations where safer alternatives are ineffective, it **can still be used** when benefits outweigh risks - not absolutely contraindicated like valproate

Q: For benzodiazepines and barbiturates, which of the following is true?

Both have effect on GABA-A chloride channel. ***Both have effect on GABA-A chloride channel*** Both benzodiazepines and barbiturates act as **positive allosteric modulators** of the **GABA-A receptor**, a **ligand-gated chloride channel**, leading to increased frequency (BZDs) or duration (Barbiturates) of channel opening [1]. This enhancement of the inhibitory neurotransmitter GABA results in **CNS depression**, which is the basis for their anxiolytic, sedative, and hypnotic effects [1].***Flumazenil is the antidote for barbiturate*** **Flumazenil** is a competitive antagonist used specifically to reverse the effects of **benzodiazepines** by blocking their binding site on the GABA-A receptor [1]. There is **no specific pharmacological antidote** for barbiturate overdose; management involves supportive care like airway protection and respiratory support.***Cause additive sedation with alcohol*** Although both drugs cause severe **synergistic CNS depression** when combined with alcohol, this is a property shared by many CNS depressants, not unique to this pair, whereas their shared molecular target (D) is a fundamental defining characteristic. The combination of either BZDs or barbiturates with ethanol significantly **potentiates sedation** and increases the risk of respiratory depression and coma.***Thiopentone has short duration of action due to metabolism*** The ultra-short action of **thiopentone** following a single intravenous dose is primarily due to rapid **redistribution** out of the brain into highly perfused tissues (muscle and fat) since it is highly lipid-soluble [1, 2]. While it is eventually metabolized by the liver, **hepatic metabolism** is not the factor responsible for the swift onset and termination of its hypnotic effect [1].

Q: A woman diagnosed with migraine has a family history of coronary artery disease. What is the drug of choice for migraine prophylaxis?

Propranolol. ***Propranolol*** - **Propranolol** is a first-line drug for migraine prophylaxis, particularly favored in patients with co-existing conditions like hypertension, anxiety, or, as in this case, risk factors for **Coronary Artery Disease (CAD)**. - As a non-selective beta-blocker, it provides effective migraine prevention while potentially offering **cardioprotective benefits**, making it the safest and best choice here. *Topiramate* - **Topiramate** is also a first-line prophylactic agent, but it is often preferred when patients need to avoid weight gain or have co-existing seizure disorders. - It has no particular advantage over propranolol in lowering cardiac risk and is associated with common side effects such as cognitive impairment (**'fogginess'**) and **nephrolithiasis**. *Ergotamine* - **Ergotamine preparations** are severe vasoconstrictors and are used primarily for the **acute termination** of migraine attacks, not for long-term prophylaxis. - They are absolutely **contraindicated** in patients with established or high risk of **Coronary Artery Disease** (CAD) due to the risk of **myocardial infarction** and stroke. *Amitriptyline* - **Amitriptyline** (a TCA) is used for prophylaxis, especially in patients with co-existing **insomnia** or chronic **tension headaches**. - While effective, TCAs can have potential **cardiac side effects** (e.g., QTc prolongation, orthostatic hypotension) which makes **propranolol** a medically safer choice for patients with a family history of CAD.

Q: Sodium thiopentone is regarded as an ultrashort-acting drug due to

Rapid redistribution. ***Rapid redistribution*** - The ultrashort action of **thiopentone** is primarily due to its rapid **redistribution** from the central compartment (brain) to peripheral tissues (muscle and fat). - This rapid drop in plasma and brain concentration leads to swift termination of the drug's hypnotic effect. *Metabolism* - While thiopentone is metabolized primarily by the **liver**, its metabolic clearance is relatively slow, contributing to its long elimination half-life rather than its quick onset/offset. *Excretion* - Thiopentone is only minimally excreted unchanged by the **kidneys**; renal excretion is not the reason for the ultrashort duration of action. *Short elimination half-life* - Thiopentone actually has a **long elimination half-life** (around 10–12 hours) because of its high lipid solubility, long protein binding, and slow systemic metabolism. - The duration of action is governed by redistribution, not by the elimination half-life.

Q: The application of the following product can lead to development of: (Recent NEET Pattern 2016-17)

Methemoglobinemia. ***Methemoglobinemia (Correct)*** - EMLA cream contains **lidocaine** and **prilocaine**, both of which are **amide-type local anesthetics** - Prilocaine, in particular, can cause methemoglobinemia due to its metabolite, **o-toluidine**, which oxidizes hemoglobin to methemoglobin - While methemoglobinemia is rare with proper use, it is a known and serious adverse effect, especially when applied to large areas, on broken skin, or in infants - This is the most specific adverse effect associated with prilocaine in EMLA cream *Seizures (Incorrect)* - Seizures are a known systemic toxicity of local anesthetics like lidocaine and prilocaine but are usually associated with **very high systemic concentrations**, often from accidental intravenous injection or excessive application over large areas - While possible with overdose, methemoglobinemia is a more specific and direct concern linked to prilocaine's metabolic pathway - CNS toxicity typically requires systemic absorption beyond what occurs with proper topical use *Depression (Incorrect)* - Depression is **not a direct or common adverse effect** of EMLA cream or its components - Systemic absorption of local anesthetics can cause central nervous system effects, but depression is generally not among them - CNS effects more commonly involve excitation (restlessness, tremors) or sedation depending on the dose *Hypertension (Incorrect)* - Local anesthetics generally cause **vasodilation** at therapeutic doses, potentially leading to **hypotension** rather than hypertension, especially with systemic absorption - Hypertension is not a characteristic side effect associated with the topical application of EMLA cream - The cardiovascular effects of local anesthetics, when present, typically involve decreased blood pressure and myocardial depression

Q: Which drug acts on the receptor X shown below in skeletal muscle?

Dantrolene. ***Correct: Dantrolene*** - **Dantrolene** acts directly on the **ryanodine receptor (RyR1)** shown as receptor X in the sarcoplasmic reticulum of skeletal muscle - It **blocks calcium release** from the sarcoplasmic reticulum by inhibiting the ryanodine receptor - **Mechanism**: Prevents excitation-contraction coupling by reducing intracellular calcium availability - **Clinical use**: Treatment of **malignant hyperthermia** and spasticity of central origin - This is the only drug among the options that directly targets the intracellular calcium release channel *Incorrect: Tubocurarine* - Acts on **nicotinic receptors at the neuromuscular junction** (postsynaptic membrane), not on intracellular receptors - Non-depolarizing neuromuscular blocker that prevents acetylcholine binding - Does not affect calcium release from sarcoplasmic reticulum *Incorrect: Baclofen* - Acts on **GABA-B receptors** in the spinal cord (presynaptic and postsynaptic) - Reduces muscle spasticity by inhibiting excitatory neurotransmitter release at spinal level - Does not directly act on skeletal muscle calcium channels or ryanodine receptors *Incorrect: Vecuronium* - Acts on **nicotinic receptors at the neuromuscular junction**, similar to tubocurarine - Non-depolarizing neuromuscular blocker used for muscle relaxation during anesthesia - Blocks neuromuscular transmission, not intracellular calcium release mechanisms

Q: A patient of hemiplegic stroke is having extreme stiffness of arm and truncal musculature. Which drug marked X will act on GABA-B receptors to reduce symptoms? (Recent NEET Pattern 2016-17)

Baclofen. ***Baclofen*** - The image shows a drug 'X' acting on **GABA-B receptors** on both pre- and post-synaptic terminals, which is the mechanism of action for **baclofen**. - Baclofen is a centrally acting **muscle relaxant** often used to treat spasticity, stiffness, and muscle spasms, consistent with the symptoms in a patient with a hemiplegic stroke. *Diazepam* - Diazepam is a **benzodiazepine** that acts as an allosteric modulator primarily on **GABA-A receptors**, increasing the frequency of chloride channel opening. - While it has muscle relaxant properties, its primary mechanism is not via GABA-B receptors, and it has more pronounced sedative effects compared to baclofen. *Tizanidine* - Tizanidine is an **alpha-2 adrenergic agonist** that reduces spasticity by increasing presynaptic inhibition of motor neurons. - It does not primarily act on GABA-B receptors, distinguishing it from the drug depicted in the image. *Dantrolene* - Dantrolene acts directly on **skeletal muscle** by inhibiting calcium release from the sarcoplasmic reticulum, thereby uncoupling excitation-contraction. - It does not work on GABA receptors in the central nervous system; its effects are peripheral.

Q: A 6-year-old child has poor school performance. On scolding by teacher abnormal behavior is noted. EEG is performed. Which of the following drugs will cause worsening of the patient?

Carbamazepine. ***Carbamazepine*** - The EEG image shows **generalized spike-wave complexes at 3 Hz**, which are characteristic of **absence seizures** (also known as petit mal seizures). - **Carbamazepine** is known to **exacerbate absence seizures** and should be avoided in patients with this diagnosis. *Ethosuximide* - This is a **first-line drug** specifically for treating **absence seizures**. - It works by blocking **T-type calcium channels** in the thalamus, effectively reducing spike-wave discharges. *Valproate* - **Valproate** is a broad-spectrum anticonvulsant effective against various seizure types, including **absence seizures**, generalized tonic-clonic seizures, and myoclonic seizures. - It is an appropriate choice if ethosuximide is ineffective or if other seizure types coexist. *Clonazepam* - **Clonazepam** is a **benzodiazepine** that can be used as an add-on therapy for **absence seizures**, especially in refractory cases. - While it has sedative side effects, it does not typically worsen absence seizures; rather, it helps control them.

Question 1

Which of the following statements is not true regarding benzodiazepines and barbiturates?

Accepted Answer

Flumazenil can be used for severe alcohol withdrawal symptoms

Answer

Both can be used as a sedative hypnotic

Answer

With alcohol it causes CNS depression

Answer

Both act on GABA-A

Question 2

Which of the following anti-epileptics is not given during pregnancy?

Accepted Answer

Valproate

Answer

Lamotrigine

Answer

Carbamazepine

Answer

Levetiracetam

Question 3

For benzodiazepines and barbiturates, which of the following is true?

Accepted Answer

Both have effect on GABA-A chloride channel

Answer

Flumazenil is the antidote for barbiturate

Answer

Cause additive sedation with alcohol

Answer

Thiopentone has short duration of action due to metabolism

Question 4

Which of the following statements is incorrect?

Accepted Answer

Cannabis use can result in self-driven, repetitive behaviours

Answer

Alcohol in low dose causes brain stimulation and in higher doses, causes brain suppression

Answer

Opioids are very effective analgesics

Answer

Volatile inhalational agents (when abused) are mostly toxic to humans

Question 5

A woman diagnosed with migraine has a family history of coronary artery disease. What is the drug of choice for migraine prophylaxis?

Accepted Answer

Propranolol

Answer

Topiramate

Answer

Ergotamine

Answer

Amitriptyline

Question 6

Sodium thiopentone is regarded as an ultrashort-acting drug due to

Accepted Answer

Rapid redistribution

Answer

Short elimination half-life

Answer

Metabolism

Answer

Excretion

Question 7

The application of the following product can lead to development of: (Recent NEET Pattern 2016-17)

Accepted Answer

Methemoglobinemia

Answer

Seizures

Answer

Depression

Answer

Hypertension

Question 8

Which drug acts on the receptor X shown below in skeletal muscle?

Accepted Answer

Dantrolene

Answer

Tubocurarine

Answer

Baclofen

Answer

Vecuronium

Question 9

A patient of hemiplegic stroke is having extreme stiffness of arm and truncal musculature. Which drug marked X will act on GABA-B receptors to reduce symptoms? (Recent NEET Pattern 2016-17)

Accepted Answer

Baclofen

Answer

Dantrolene

Answer

Diazepam

Answer

Tizanidine

Question 10

A 6-year-old child has poor school performance. On scolding by teacher abnormal behavior is noted. EEG is performed. Which of the following drugs will cause worsening of the patient?

Accepted Answer

Carbamazepine

Answer

Ethosuximide

Answer

Valproate

Answer

Clonazepam

Central Nervous System Pharmacology — MCQs

Central Nervous System Pharmacology — MCQs

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