NEET-PG 2015 - Pharmacology Practice Questions

Q: Which of the following is the most characteristic sexual side effect of SSRIs?

Delayed ejaculation. ***Delayed ejaculation*** - **Delayed ejaculation** is a common and characteristic sexual side effect of SSRIs due to their impact on serotonin pathways involved in sexual response. - This effect can lead to significant distress and non-adherence to treatment, and often requires dose adjustment or switching to an alternative antidepressant. *Erectile dysfunction* - While **erectile dysfunction** can occur with SSRIs, it is a less specific and less consistently reported sexual side effect compared to ejaculatory dysfunction. - Many factors, including underlying mood disorder and comorbidities, can contribute to erectile dysfunction, making it less characteristic of SSRI use alone. *Retrograde ejaculation* - **Retrograde ejaculation** is a condition where semen enters the bladder during orgasm, and while it can be a side effect of some medications (e.g., alpha-blockers), it is not a hallmark sexual side effect of SSRIs. - SSRIs primarily affect the process of emission and expulsion, leading more commonly to delayed or absent ejaculation rather than retrograde flow. *Anxiety* - **Anxiety** is generally a *primary symptom* of the conditions SSRIs are prescribed to treat, such as depression or anxiety disorders, not a sexual side effect of the medication itself. - Although SSRIs can initially cause or worsen anxiety in some patients before therapeutic effects are seen, this is a systemic side effect, not a sexual one.

Q: Most common renal sequela of lithium toxicity is?

Nephrogenic Diabetes Insipidus. ***Nephrogenic Diabetes Insipidus*** - **Lithium** interferes with the action of **ADH** on the renal tubules, specifically at the **collecting ducts**, leading to an inability to concentrate urine. - This results in **polyuria** (excessive urination) and **polydipsia** (excessive thirst), characteristic symptoms of **nephrogenic diabetes insipidus**. *Renal tubular acidosis* - While lithium can affect tubular function, **renal tubular acidosis** is less common than nephrogenic diabetes insipidus. - RTA involves impaired acid excretion or bicarbonate reabsorption, leading to **metabolic acidosis**. *Glycosuria* - **Glycosuria** (glucose in urine) is primarily associated with **diabetes mellitus** or other conditions affecting glucose reabsorption in the proximal tubule. - Lithium toxicity does not typically cause glycosuria. *MPGN* - **Membranoproliferative glomerulonephritis (MPGN)** is a type of glomerular injury characterized by specific changes in the glomerulus. - MPGN is not directly caused by **lithium toxicity**; lithium primarily affects tubular function rather than glomerular structure.

Q: Which drug is not administered as a transdermal patch?

Morphine. ***Morphine*** - **Morphine** is generally not administered transdermally due to its **poor lipid solubility** [1] and **large molecular size**, which limit its ability to penetrate the skin effectively. - While experimental patches have been developed, they are **not widely available** or commonly used in clinical practice for systemic delivery. *Fentanyl* - **Fentanyl** is a potent opioid that is commonly administered via a **transdermal patch** for chronic pain management [2]. - Its **high lipid solubility** and small molecular size allow it to be effectively absorbed through the skin, providing sustained analgesia. *Clonidine* - **Clonidine** is an alpha-2 adrenergic agonist available as a **transdermal patch** for the treatment of **hypertension**. - The patch provides a **continuous and steady release** of the drug, leading to consistent blood pressure control. *Diclofenac* - **Diclofenac** is a non-steroidal anti-inflammatory drug (NSAID) available in **transdermal patch** formulations for topical pain relief. - These patches are used for localized pain conditions like **osteoarthritis** and provide targeted drug delivery with reduced systemic side effects.

Q: Antidepressant drug used in nocturnal enuresis is:

Imipramine. ***Imipramine*** - **Imipramine**, a **tricyclic antidepressant (TCA)**, is frequently used off-label for **nocturnal enuresis** in children [1]. - Its mechanism of action in enuresis is thought to involve a combination of anticholinergic effects (which relax the bladder detrusor muscle) and central nervous system effects (which may increase bladder capacity and arousal from sleep) [1]. *Fluoxetine* - **Fluoxetine** is a **selective serotonin reuptake inhibitor (SSRI)** and is primarily used for depression, anxiety disorders, and OCD [2]. - It is not indicated for the treatment of nocturnal enuresis and does not have the same bladder-relaxing or arousal-modulating properties as imipramine in this context. *Trazodone* - **Trazodone** is a **serotonin antagonist and reuptake inhibitor (SARI)**, commonly prescribed for depression and insomnia due to its prominent sedative effects. - It is not used for nocturnal enuresis and its mechanism of action does not confer benefits for bladder control. *Sertraline* - **Sertraline** is another **selective serotonin reuptake inhibitor (SSRI)** used for a wide range of psychiatric conditions, including depression, anxiety, and panic disorder [2]. - Like fluoxetine, it is not an appropriate treatment for nocturnal enuresis and lacks the specific known effects beneficial for this condition.

Q: What is the primary mechanism of action of zonisamide?

Sodium channels. ***Sodium channels (Correct Answer)*** - Zonisamide's primary mechanism involves **blocking voltage-sensitive sodium channels**, which stabilizes neuronal membranes and inhibits repetitive neuronal firing. - This action helps to prevent the propagation of **seizure activity** in the brain. *GABA receptors* - While zonisamide has some weak effects on GABA, it is not its **primary mechanism of action** for antiepileptic efficacy. - Drugs like **benzodiazepines** and **barbiturates** primarily act by enhancing GABAergic transmission. *T-type calcium channels* - Zonisamide also blocks T-type calcium channels, contributing to its broad-spectrum antiepileptic activity, but this is a **secondary mechanism** compared to its sodium channel blockade. - **Ethosuximide** is a classic example of a drug primarily acting on T-type calcium channels, especially for absence seizures. *Cl- channels* - Zonisamide does not primarily act on **chloride channels**; these are often modulated by GABA receptors. - Drugs that act directly on chloride channels are not typically used as **antiepileptics** in the same way.

Q: Buprenorphine is a partial agonist at which opioid receptor?

Mu. ***Mu*** - Buprenorphine primarily acts as a **partial agonist** at the **mu opioid receptor**, providing analgesic effects with a ceiling effect on respiratory depression. - Its partial agonism at the mu receptor contributes to its lower potential for respiratory depression and overdose compared to full mu agonists. *Kappa* - While buprenorphine has some antagonist activity at the kappa receptor, its primary therapeutic action is not at this receptor. - **Kappa receptor agonists** like pentazocine can produce dysphoria and psychotomimetic effects. *Delta* - The delta opioid receptor is involved in analgesia and emotional responses, but buprenorphine has very low affinity and activity at this receptor. - **Delta receptor agonists** are not widely used clinically due to limited efficacy and side effects. *ORL-1* - The ORL-1 (Opioid Receptor-like 1) receptor, also known as the nociceptin receptor, is distinct from classical opioid receptors. - Buprenorphine has **no significant activity** at the ORL-1 receptor, which primarily mediates pain, anxiety, and learning.

Q: Which diuretic is most likely to cause hyponatremia by impairing free water excretion?

Thiazide diuretics. ***Thiazide diuretics*** - **Thiazide diuretics** inhibit the **Na-Cl cotransporter in the distal convoluted tubule (DCT)**, impairing the kidney's ability to dilute urine and excrete free water - This impaired urinary dilution leads to **water retention relative to sodium**, resulting in **dilutional hyponatremia** - **Most common in elderly patients**, those on low-salt diets, or with pre-existing volume depletion - **Mechanism**: By blocking sodium reabsorption in the DCT (a key site for urinary dilution), thiazides prevent the generation of free water, leading to hyponatremia when water intake continues *Loop diuretics* - **Loop diuretics** inhibit the **Na-K-2Cl cotransporter in the thick ascending limb of Henle**, causing significant diuresis - They impair the medullary concentration gradient, **enhancing free water excretion** - **Less likely to cause hyponatremia** compared to thiazides because they promote rather than impair free water clearance - When hyponatremia occurs with loop diuretics, it's usually due to concurrent SIADH or excessive free water intake *Acetazolamide* - **Acetazolamide** is a **carbonic anhydrase inhibitor** acting primarily on the **proximal tubule** - Causes **bicarbonate and sodium excretion**, leading to mild diuresis - Main side effect is **metabolic acidosis** (type 2 RTA) - **Does not significantly impair free water excretion**, making hyponatremia uncommon *Amiloride* - **Amiloride** is a **potassium-sparing diuretic** that blocks **epithelial sodium channels (ENaC) in the collecting duct** - Weak diuretic effect, primarily used to prevent potassium loss - **Does not impair urinary dilution mechanisms**, so hyponatremia is rare - Main concern is **hyperkalemia**, especially with ACE inhibitors or in renal insufficiency

Q: Which of the following drugs is not used in the treatment of akathisia?

Haloperidol. ***Haloperidol*** - **Haloperidol** is a typical antipsychotic drug known to **cause** or worsen **akathisia**, rather than treat it. - Akathisia is an extrapyramidal symptom, and **first-generation antipsychotics** like haloperidol are frequent culprits due to their strong **D2 receptor blockade**. *Benzodiazepine* - **Benzodiazepines** like lorazepam or clonazepam are often used to treat akathisia due to their **sedative** and **anxiolytic** properties. - They act by enhancing **GABAergic transmission**, which can help calm the motor restlessness associated with akathisia. *Propranolol* - **Propranolol**, a **beta-blocker**, is a first-line treatment for akathisia, particularly effective for its objective motor symptoms. - It works by reducing **adrenergic activity**, which is thought to contribute to the motor restlessness. *Trihexyphenidyl* - **Trihexyphenidyl** is an **anticholinergic** agent primarily used to treat **parkinsonian-like extrapyramidal symptoms** (e.g., dystonia, pseudoparkinsonism). - While sometimes used for generalized EPS, it is **less effective** for the specific motor restlessness of akathisia compared to beta-blockers or benzodiazepines.

Q: Where is the benzodiazepine binding site located on GABA receptors?

γ-subunit. ***γ-subunit*** - The **benzodiazepine binding site** is located at the interface between the **α and γ subunits** of the GABA-A receptor, with the **γ-subunit (especially γ2) being essential** for benzodiazepine sensitivity. - The presence of the **γ2 subunit** is **mandatory** for benzodiazepine binding - receptors lacking this subunit are **insensitive to benzodiazepines**. - Benzodiazepines bind to this site and act as **positive allosteric modulators**, increasing the frequency of **chloride channel opening** in response to GABA. - This is the **standard answer** for NEET-PG and medical PG examinations in India. *α-subunit* - The **α-subunit** contributes to forming the benzodiazepine binding pocket at the α-γ interface. - Different **α-subunit isoforms** (α1, α2, α3, α5) determine the pharmacological profile and tissue distribution of benzodiazepine effects. - However, the **α-subunit alone** cannot bind benzodiazepines without the γ-subunit. *β-subunit* - The **β-subunit** contains the primary binding site for **GABA** itself. - It does not participate in benzodiazepine binding but is crucial for the receptor's overall function and GABAergic signaling. *δ-subunit* - The **δ-subunit** replaces the γ-subunit in certain GABA-A receptor subtypes that mediate **tonic inhibition**. - Receptors containing **δ-subunits** are **insensitive to benzodiazepines** but sensitive to neurosteroids and certain general anesthetics. - This is a key distinguishing feature between phasic (γ-containing) and tonic (δ-containing) GABA-A receptors.

Q: How do thiazides cause hypercalcemia?

Decreased calcium excretion. ***Decreased calcium excretion*** - Thiazides inhibit the **Na-Cl co-transporter** in the **distal convoluted tubule**, leading to increased reabsorption of calcium [1], [2]. - This increased reabsorption of calcium is mediated by a low intracellular sodium concentration, which enhances the activity of the **Na+/Ca2+ exchanger** on the basolateral membrane [1]. *Increased parathyroid hormone secretion* - Thiazides **do not directly stimulate** parathyroid hormone (PTH) secretion; instead, they *decrease* calcium excretion, which would typically *lower* PTH levels through negative feedback. - Elevated PTH would lead to increased bone resorption and kidney calcium reabsorption, but this is not the **primary mechanism** for thiazide-induced hypercalcemia [2]. *Decreased calcitonin secretion* - **Calcitonin** is a hormone that *lowers* blood calcium levels, and its decrease would theoretically contribute to hypercalcemia. - However, thiazides have **no direct effect** on calcitonin secretion, making this an unlikely primary mechanism. *Increased calcium absorption* - While increased calcium absorption from the gut can contribute to hypercalcemia, thiazides do **not directly increase intestinal calcium absorption**. - Their primary action for influencing calcium levels is within the **kidney**, specifically on reabsorption, not absorption from the GI tract [1], [2].

Question 1

Which of the following is the most characteristic sexual side effect of SSRIs?

Accepted Answer

Delayed ejaculation

Answer

Retrograde ejaculation

Answer

Erectile dysfunction

Answer

Anxiety

Question 2

Most common renal sequela of lithium toxicity is?

Accepted Answer

Nephrogenic Diabetes Insipidus

Answer

Renal tubular acidosis

Answer

Glycosuria

Answer

MPGN

Question 3

Which drug is not administered as a transdermal patch?

Accepted Answer

Morphine

Answer

Fentanyl

Answer

Clonidine

Answer

Diclofenac

Question 4

Antidepressant drug used in nocturnal enuresis is:

Accepted Answer

Imipramine

Answer

Fluoxetine

Answer

Trazodone

Answer

Sertraline

Question 5

What is the primary mechanism of action of zonisamide?

Accepted Answer

Sodium channels

Answer

GABA receptors

Answer

Cl- channels

Answer

T-type calcium channels

Question 6

Buprenorphine is a partial agonist at which opioid receptor?

Accepted Answer

Mu

Answer

Kappa

Answer

Delta

Answer

ORL-1

Question 7

Which diuretic is most likely to cause hyponatremia by impairing free water excretion?

Accepted Answer

Thiazide diuretics

Answer

Loop diuretics

Answer

Acetazolamide

Answer

Amiloride

Question 8

Which of the following drugs is not used in the treatment of akathisia?

Accepted Answer

Haloperidol

Answer

Benzodiazepine

Answer

Propranolol

Answer

Trihexyphenidyl

Question 9

Where is the benzodiazepine binding site located on GABA receptors?

Accepted Answer

γ-subunit

Answer

β-subunit

Answer

δ-subunit

Answer

α-subunit

Question 10

How do thiazides cause hypercalcemia?

Accepted Answer

Decreased calcium excretion

Answer

Increased parathyroid hormone secretion

Answer

Decreased calcitonin secretion

Answer

Increased calcium absorption

NEET-PG 2015 — Pharmacology