Central Nervous System Pharmacology Practice Questions

Q: What is the mechanism of action of local anesthetics?

Block sodium channels. ***Block sodium channels*** - Local anesthetics work by **reversibly binding** to the alpha subunit of **voltage-gated sodium channels** on the neuronal membrane. - This binding prevents the influx of sodium ions, thereby inhibiting the **depolarization** of the neuron and **propagation of action potentials**. *Block chloride channels* - **Chloride channels** are primarily involved in **hyperpolarization** or stabilization of the resting membrane potential, and their blockade is not the primary mechanism of local anesthesia. - Drugs like **benzodiazepines** modulate GABA-gated chloride channels for their anxiolytic and sedative effects. *Block calcium channels* - **Calcium channels** are important for neurotransmitter release and muscle contraction, but their blockade is not the way local anesthetics exert their effects. - **Calcium channel blockers** are used in cardiovascular medicine (e.g., diltiazem, verapamil) to reduce heart rate and blood pressure. *Block potassium channels* - **Potassium channels** are crucial for repolarization of the neuronal membrane and maintaining the resting potential. - While some toxins block potassium channels, it is not the principal mechanism by which **local anesthetics** achieve their nerve blocking effect.

Q: All of the following drugs are used for prophylaxis of migraine except;

Flutamide. ***Flutamide*** - **Flutamide** is an **antiandrogen** used in the treatment of prostate cancer, not for migraine prophylaxis. - Its mechanism of action involves blocking androgen receptors, which is irrelevant to migraine pathophysiology. *Flunarizine* - **Flunarizine** is a **calcium channel blocker** commonly used for migraine prophylaxis due to its vascular effects. - It helps stabilize neuronal membranes and reduce cerebral vasospasm, preventing migraine attacks. *Imipramine* - **Imipramine** is a **tricyclic antidepressant (TCA)** that can be used off-label for migraine prevention due to its neuromodulatory effects. - It works by affecting neurotransmitter levels, particularly serotonin and norepinephrine, which play a role in migraine pathways. *Propranolol* - **Propranolol** is a **beta-blocker** widely used for migraine prophylaxis, especially in patients with coexisting hypertension or anxiety. - Its mechanism involves modulating adrenergic activity and potentially stabilizing cortical excitability.

Q: Least teratogenic antiepileptic drug in pregnancy is:

Levetiracetam. ***Levetiracetam*** - **Levetiracetam** is generally considered one of the **safest antiepileptic drugs (AEDs)** during pregnancy, with a lower risk of major congenital malformations compared to other AEDs. - Studies have shown a **low incidence of neural tube defects** and other severe malformations when used as monotherapy. *Carbamazepine* - **Carbamazepine** is associated with an increased risk of **neural tube defects**, particularly **spina bifida**, during pregnancy. - It can also cause other malformations such as **facial dysmorphism** and developmental delays. *Valproate* - **Valproate** has the **highest teratogenic potential** among common AEDs, linked to a significantly increased risk of **neural tube defects**, **cardiac anomalies**, and **cognitive impairment (fetal valproate syndrome)**. - Due to its high risk, its use is generally **contraindicated in women of childbearing potential** unless no other effective alternative exists. *Phenytoin* - **Phenytoin** is associated with **fetal hydantoin syndrome**, characterized by specific facial features, **growth deficiency**, developmental delay, and increased risk of cleft lip/palate, and **cardiac defects**. - It is known for its **dose-dependent teratogenicity**, making careful monitoring crucial.

Q: All of the following are actions produced by mu receptors of morphine except:-

Hyperalgesia. ***Hyperalgesia*** - **Hyperalgesia** is not a primary physiological action of **μ-opioid receptor** activation; the fundamental role of these receptors is to produce **analgesia** by inhibiting pain transmission. - While **opioid-induced hyperalgesia** can occur with chronic use, it is a paradoxical compensatory response rather than a direct cellular action of the morphine-receptor complex. *Respiratory depression* - Activation of **μ-receptors** in the **brainstem** directly reduces the sensitivity of the respiratory center to **carbon dioxide**, leading to decreased respiratory rate. - This is one of the most clinically significant side effects and is the primary cause of death in **opioid overdose**. *Miosis* - Morphine stimulates the **Edinger-Westphal nucleus** via μ-receptors, resulting in excessive parasympathetic output to the eye. - This produces **pinpoint pupils**, a classic diagnostic sign of **opioid toxicity** that does not develop tolerance. *Decreased GI motility* - **μ-receptors** are highly expressed in the **myenteric plexus** of the gut, where their activation inhibits the release of acetylcholine and slows **peristalsis**. - This action results in **constipation**, which is a universal side effect of morphine therapy and typically requires prophylactic management.

Q: Which of the following anti-epileptic drugs has the highest teratogenic potential?

Valproate. ***Correct: Valproate*** - **Valproate has the highest teratogenic potential** among all anti-epileptic drugs, with a **10-20% risk of major congenital malformations** - **Neural tube defects** (spina bifida) occur in **1-2% of exposed pregnancies**, which is 10-20 times higher than the general population - Other significant risks include **cardiac malformations, craniofacial abnormalities**, and **neurodevelopmental disorders** (autism spectrum disorder, reduced IQ) - **Fetal valproate syndrome** is a recognized clinical entity - Current guidelines strongly recommend **avoiding valproate in women of childbearing potential** unless no alternatives exist *Incorrect: Carbamazepine* - Has teratogenic risks but significantly **lower than valproate** (2-5% risk of major malformations) - Associated with **neural tube defects** (0.5-1% risk, lower than valproate) - Considered a safer alternative when valproate must be avoided *Incorrect: Phenytoin* - Causes **fetal hydantoin syndrome** with characteristic features: craniofacial anomalies, nail/digital hypoplasia, growth restriction, and developmental delay - Teratogenic risk is **moderate** (approximately 5-10% risk of major malformations) - Risk is significant but **lower than valproate** *Incorrect: Lamotrigine* - Considered **one of the safest anti-epileptic drugs** during pregnancy - Low teratogenic risk with **major malformation rate of 2-3%** (close to baseline population risk) - Slight increased risk of **oral clefts** at higher doses - **Preferred choice** for women of childbearing potential requiring anti-epileptic therapy

Q: Shortest acting local anaesthetic

Chloroprocaine. ***Chloroprocaine*** - **Chloroprocaine** is known for its rapid onset and very **short duration of action**, typically lasting 30-60 minutes, due to its **rapid hydrolysis** by plasma and liver esterases. - Its quick metabolism makes it suitable for short procedures where a brief blockade is desired, minimizing the risk of systemic toxicity. *Dibucaine* - **Dibucaine** is a local anesthetic with a **long duration of action**, typically 2 to 4 hours, which is much longer than chloroprocaine. - It is used topically and in spinal anesthesia, but its prolonged effect makes it unsuitable as the shortest-acting option. *Procaine* - **Procaine** is an ester-type local anesthetic with a relatively **short duration of action** (approximately 30-60 minutes), but it is generally longer than that of chloroprocaine. - It was one of the first synthetic local anesthetics and is less potent and shorter-acting than many modern agents. *Cocaine* - **Cocaine** has a moderate duration of action as a local anesthetic, typically lasting 60-90 minutes, which is longer than chloroprocaine. - While it is a potent local anesthetic and vasoconstrictor, its high abuse potential and systemic side effects limit its clinical use, mainly to topical application in otolaryngology.

Q: Exanthema is caused by which drug ?

Phenytoin. ***Phenytoin*** - **Phenytoin** is well-known to cause an exanthematous drug reaction, often presenting as a widespread, symmetrical rash that can be **maculopapular** - This adverse effect is part of a spectrum of dermatological reactions to phenytoin, which can range from mild rashes to severe cutaneous adverse reactions (SCARs) like **Stevens-Johnson syndrome (SJS)** or **toxic epidermal necrolysis (TEN)** - Phenytoin is one of the **most common drugs causing drug-induced exanthema** *Valproate* - While valproate can cause various side effects, **skin rashes and exanthema are uncommon** and not typically considered a characteristic adverse drug reaction - More common side effects of valproate include gastrointestinal disturbances, **tremor**, **weight gain**, and **hepatotoxicity** *NTG (Nitroglycerin)* - Nitroglycerin is primarily used for cardiovascular conditions and its common side effects are related to **vasodilation**, such as **headache**, dizziness, and flushing - **Exanthematous rashes are not a typical adverse effect** associated with nitroglycerin use *Digoxin* - Digoxin can cause various side effects, particularly **cardiac arrhythmias** and **gastrointestinal symptoms** - Although rare allergic reactions including skin rashes can occur, **exanthema is not a prominent or common adverse effect** of digoxin

Q: Ketamine belongs to which of the following group of drugs ?

Phencyclidine. ***Phencyclidine***- **Ketamine** is structurally related to **phencyclidine (PCP)**, sharing a similar mechanism of action as an **NMDA receptor antagonist** [2]. Ketamine is also categorized as a general anesthetic [1].- Both drugs primarily induce a state of **dissociative anesthesia**, characterized by a trance-like state without loss of consciousness [2].*Phenols*- **Phenols** are a class of organic compounds typically used as antiseptics and disinfectants, such as carbolic acid.- They do not possess anesthetic properties or a similar chemical structure to ketamine.*Barbiturate*- **Barbiturates** are central nervous system depressants that produce a wide range of effects, including sedation, hypnosis, and anesthesia [3].- They act primarily by enhancing the activity of **GABA-A receptors**, a different mechanism than ketamine.*Benzodiazepine*- **Benzodiazepines** are a class of psychoactive drugs primarily used for treating anxiety, insomnia, and seizures.- They also act by enhancing **GABA-A receptor** activity, leading to central nervous system depression, unlike ketamine's dissociative effects.

Q: A recently approved drug for treatment of the 'off phenomenon' in Parkinsonism:

Safinamide. ***Safinamide*** - **Safinamide** is a recently approved drug that acts as a **reversible monoamine oxidase B (MAO-B) inhibitor** and also modulates **glutamate release**. - It is specifically indicated as an adjunct therapy for Parkinson's disease patients experiencing motor fluctuations ("off" time) treated with levodopa. *Ziconotide* - **Ziconotide** is a synthetic **conopeptide** that selectively blocks N-type calcium channels. - It is used for the management of severe chronic pain in patients for whom intrathecal therapy is warranted, not for Parkinsonism. *Evenamide* - **Evenamide** is an investigational drug, currently in clinical trials, primarily developed as an adjunctive treatment for **schizophrenia**. - It works as a **glutamate modulator** but is not approved for Parkinson's disease. *Lacosamide* - **Lacosamide** is an anti-epileptic drug that selectively enhances **slow inactivation of voltage-gated sodium channels**. - It is used for the treatment of **partial-onset seizures** and has no indication for Parkinson's disease.

Question 1

Which of the following is true regarding nicotine substitution therapy?

Accepted Answer

There should be a 15-minute gap between nicotine gum and coffee/soda/acidic food as they decrease its absorption

Answer

Preferably given by gastrointestinal route.

Answer

Varenicline comes with a black box warning of cardiovascular death

Answer

Nicotine chewing gum is better for constant use as it gives 25% higher blood level than lozenges

Question 2

What is the mechanism of action of local anesthetics?

Accepted Answer

Block sodium channels

Answer

Block chloride channels

Answer

Block calcium channels

Answer

Block potassium channels

Question 3

All of the following drugs are used for prophylaxis of migraine except;

Accepted Answer

Flutamide

Answer

Flunarizine

Answer

Imipramine

Answer

Propranolol

Question 4

Least teratogenic antiepileptic drug in pregnancy is:

Accepted Answer

Levetiracetam

Answer

Carbamazepine

Answer

Valproate

Answer

Phenytoin

Question 5

All of the following are actions produced by mu receptors of morphine except:-

Accepted Answer

Hyperalgesia

Answer

Respiratory depression

Answer

Miosis

Answer

Decreased GI motility

Question 6

Which of the following anti-epileptic drugs has the highest teratogenic potential?

Accepted Answer

Valproate

Answer

Carbamazepine

Answer

Phenytoin

Answer

Lamotrigine

Question 7

Shortest acting local anaesthetic

Accepted Answer

Chloroprocaine

Answer

Dibucaine

Answer

Procaine

Answer

Cocaine

Question 8

Exanthema is caused by which drug ?

Accepted Answer

Phenytoin

Answer

Valproate

Answer

NTG

Answer

Digoxin

Question 9

Ketamine belongs to which of the following group of drugs ?

Accepted Answer

Phencyclidine

Answer

Phenols

Answer

Barbiturate

Answer

Benzodiazepine

Question 10

A recently approved drug for treatment of the 'off phenomenon' in Parkinsonism:

Accepted Answer

Safinamide

Answer

Ziconotide

Answer

Evenamide

Answer

Lacosamide

Central Nervous System Pharmacology — MCQs

Central Nervous System Pharmacology — MCQs

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