General Pharmacology Practice Questions

Q: Mechanism of action of sildenafil is:

Phosphodiesterase-5 inhibitor. **Explanation:** **Mechanism of Action (Correct Answer: C):** Sildenafil is a potent and selective inhibitor of **Phosphodiesterase-5 (PDE-5)**. Under normal physiological conditions, sexual stimulation leads to the release of Nitric Oxide (NO) in the corpus cavernosum. NO activates the enzyme guanylyl cyclase, which increases levels of **cyclic Guanosine Monophosphate (cGMP)**. cGMP causes smooth muscle relaxation and increased blood flow, resulting in an erection. PDE-5 is the enzyme responsible for the degradation of cGMP. By inhibiting PDE-5, sildenafil prevents the breakdown of cGMP, thereby enhancing the vasodilatory effect of NO and maintaining penile erection. **Analysis of Incorrect Options:** * **A. 5-alpha reductase inhibitor:** These drugs (e.g., **Finasteride**, Dutasteride) block the conversion of Testosterone to Dihydrotestosterone (DHT). They are used in Benign Prostatic Hyperplasia (BPH) and male pattern baldness. * **B. Antiandrogen:** These agents (e.g., **Flutamide**, Spironolactone) block androgen receptors or inhibit androgen synthesis. They are used in conditions like prostate cancer or hirsutism. * **D. Androgenic:** These are drugs that mimic male sex hormones (e.g., Methyltestosterone) used for replacement therapy in hypogonadism. **High-Yield Clinical Pearls for NEET-PG:** * **Contraindication:** Sildenafil must **never** be co-administered with **Nitrates** (e.g., Nitroglycerin) as it can cause life-threatening hypotension due to synergistic increases in cGMP. * **Other Uses:** Sildenafil is also FDA-approved for **Pulmonary Arterial Hypertension (PAH)**. * **Side Effects:** Common side effects include headache, flushing, and **blue-tinted vision (Cyanopsia)** due to weak inhibition of PDE-6 in the retina. * **Tadalafil vs. Sildenafil:** Tadalafil has a much longer half-life (~36 hours), often called the "weekend pill."

Q: Therapeutic index is a measure of:

Safety. **Explanation:** **Therapeutic Index (TI)** is a quantitative measurement of the relative **safety** of a drug. It represents the ratio between the dose that produces toxicity and the dose that produces the desired therapeutic effect. Mathematically, it is expressed as: **TI = TD₅₀ / ED₅₀** (or LD₅₀ / ED₅₀ in animal studies), where TD₅₀ is the toxic dose in 50% of the population and ED₅₀ is the effective dose in 50%. A higher TI indicates a wider margin of safety, meaning a large increase in dose is required to reach toxic levels. **Analysis of Incorrect Options:** * **B. Efficacy:** Refers to the maximum response (Emax) a drug can produce, regardless of dose. It is a measure of a drug's effectiveness, not safety. * **C. Potency:** Refers to the amount of drug (dose) required to produce an effect of a given intensity (usually measured by EC₅₀). A more potent drug requires a smaller dose but is not necessarily safer. * **D. Selectivity:** Refers to a drug’s ability to affect a particular receptor or target without affecting others. While related to side effects, it is not the formal definition of the Therapeutic Index. **High-Yield NEET-PG Pearls:** 1. **Narrow Therapeutic Index Drugs:** These require Therapeutic Drug Monitoring (TDM) because their therapeutic and toxic doses are very close. Examples: **W**arfarin, **A**minoglycosides/Anti-epileptics (Phenytoin, Lithium), **D**igoxin, **T**heophylline (**Mnemonic: W.A.D.T**). 2. **Therapeutic Window:** The range of dosages between the minimum effective concentration and the minimum toxic concentration. This is the "clinically safe" range. 3. **Certain Safety Factor:** A more rigorous measure of safety calculated as LD₁ / ED₉₉.

Q: Fexofenadine is a metabolic product of which of the following drugs?

Terfenadine. ### Explanation **Correct Answer: D. Terfenadine** **Reasoning:** Fexofenadine is the **active acid metabolite** of Terfenadine. Originally, Terfenadine was a popular second-generation H1-antihistamine. However, it was discovered that Terfenadine is a prodrug that undergoes extensive first-pass metabolism in the liver via the **CYP3A4 enzyme** to become Fexofenadine. The medical significance of this conversion is critical for exams: Terfenadine itself is cardiotoxic; it blocks delayed rectifier K+ channels in the heart, leading to **QT interval prolongation** and a life-threatening polymorphic ventricular tachycardia known as **Torsades de Pointes**. This toxicity occurs if CYP3A4 is inhibited (e.g., by erythromycin or ketoconazole). Fexofenadine, however, provides the same antihistaminic benefits without the cardiotoxicity, leading to the withdrawal of Terfenadine from the market. **Analysis of Incorrect Options:** * **A. Loratadine:** It is a prodrug, but its active metabolite is **Desloratadine**. * **B. Astemizole:** Similar to Terfenadine, it was withdrawn due to Torsades de Pointes. Its active metabolite is **Norastemizole**. * **C. Cetirizine:** It is actually the active metabolite of **Hydroxyzine** (a first-generation antihistamine). Cetirizine itself is not a prodrug. **High-Yield Clinical Pearls for NEET-PG:** * **Active Metabolites:** Always remember the pairs: Terfenadine → Fexofenadine; Loratadine → Desloratadine; Hydroxyzine → Cetirizine. * **Safety Profile:** Fexofenadine is considered the least sedating second-generation antihistamine because it does not cross the blood-brain barrier. * **Drug Interactions:** Avoid taking Fexofenadine with fruit juices (like orange or grapefruit) as they inhibit OATP1A2, reducing the drug's absorption.

Q: Immune-mediated qualitative drug intolerance is called:

Hypersensitivity. **Explanation:** The correct answer is **Hypersensitivity (Option C)**. **1. Why Hypersensitivity is correct:** Hypersensitivity (or drug allergy) is defined as an **immune-mediated** reaction to a drug. It is a **qualitative** abnormality, meaning the reaction is different in nature from the drug's intended pharmacological action (e.g., a skin rash from Penicillin, rather than its antibacterial effect). These reactions occur only in sensitized individuals and are not dose-dependent in the traditional sense. **2. Analysis of Incorrect Options:** * **Supersensitivity (Option A):** This refers to an increased response to a drug due to a denervation or a reduction in the number of endogenous ligands (up-regulation of receptors). It is a physiological change in receptor sensitivity, not an immune response. * **Idiosyncrasy (Option B):** This is a genetically determined abnormal reactivity to a drug. While it is also a **qualitative** abnormality, it is **non-immunological**. A classic example is hemolysis in G6PD-deficient patients after taking Primaquine. * **Hyperacidity (Option D):** This is a clinical condition of excessive gastric acid secretion and is unrelated to drug intolerance mechanisms. **3. NEET-PG High-Yield Pearls:** * **Quantitative vs. Qualitative:** *Hyperreactivity* is a quantitative increase in response (same effect, lower dose), whereas *Hypersensitivity* and *Idiosyncrasy* are qualitative (different effect). * **Coombs & Gell Classification:** Hypersensitivity is divided into four types: Type I (IgE-mediated/Anaphylactic), Type II (Cytotoxic), Type III (Immune-complex), and Type IV (Delayed/Cell-mediated). * **Tachyphylaxis:** Rapidly developing tolerance after repeated doses (e.g., Ephedrine, Tyramine).

Q: Which of the following drugs inhibits de novo synthesis of purines?

Mycophenolate. **Explanation:** **Correct Answer: C. Mycophenolate** Mycophenolate mofetil (MMF) is a potent, reversible inhibitor of the enzyme **Inosine Monophosphate Dehydrogenase (IMPDH)**. This enzyme is the rate-limiting step in the **de novo synthesis of guanosine nucleotides (purines)**. While most cells can use the "salvage pathway" to produce purines, T and B lymphocytes are uniquely dependent on the de novo pathway for proliferation. By inhibiting this synthesis, Mycophenolate exerts a selective cytostatic effect on lymphocytes, making it a cornerstone in transplant medicine and autoimmune therapy. **Analysis of Incorrect Options:** * **A & B (Cyclosporine and Tacrolimus):** These are **Calcineurin Inhibitors**. They work by binding to intracellular proteins (Cyclophilin and FKBP-12, respectively) to inhibit calcineurin, thereby preventing the dephosphorylation of NFAT (Nuclear Factor of Activated T-cells). This inhibits the transcription of **Interleukin-2 (IL-2)**, rather than affecting purine synthesis. * **D (Infliximab):** This is a chimeric monoclonal antibody that acts as a **TNF-α (Tumor Necrosis Factor) inhibitor**. It neutralizes the biological activity of TNF-α by binding to its soluble and transmembrane forms, used primarily in Crohn’s disease and Rheumatoid Arthritis. **High-Yield NEET-PG Pearls:** * **Selectivity:** Mycophenolate is preferred over Azathioprine in many regimens because of its higher lymphocyte selectivity and lower incidence of bone marrow suppression. * **Side Effects:** The most common dose-limiting side effects of Mycophenolate are **GI distress** (nausea, diarrhea) and hematological (leukopenia). * **Teratogenicity:** It is associated with "Mycophenolate embryopathy" (ear and facial malformations), making it contraindicated in pregnancy. * **Drug Interaction:** Unlike Azathioprine, Mycophenolate metabolism is **not** affected by Allopurinol.

Question 1

Mechanism of action of sildenafil is:

Accepted Answer

Phosphodiesterase-5 inhibitor

Answer

5 alpha reductase inhibitor

Answer

Antiandrogen

Answer

Androgenic

Question 2

Which of the following routes of administration results in 100 percent bioavailability of a drug?

Accepted Answer

Intravenous

Answer

Subcutaneous

Answer

Intramuscular

Answer

Intradermal

Question 3

Therapeutic index is a measure of:

Accepted Answer

Safety

Answer

Efficacy

Answer

Potency

Answer

Selectivity

Question 4

Maximum response a drug can produce regardless of its dose is known as:

Accepted Answer

Efficacy

Answer

Potency

Answer

Intrinsic activity

Answer

Agonist

Question 5

What does the therapeutic window of a medication refer to?

Accepted Answer

The optimum dosage in which a drug's main effects are obtained with minimal side effects

Answer

An inventory of treatments recommended for a particular disorder

Answer

A holistic treatment approach, involving but not limited to a cycle of psychopharmacology

Answer

A recommended dosage and treatment plan

Question 6

Fexofenadine is a metabolic product of which of the following drugs?

Accepted Answer

Terfenadine

Answer

Loratadine

Answer

Astemizole

Answer

Cetirizine

Question 7

Which of the following statements about the phases of clinical trials for a drug is FALSE?

Accepted Answer

The maximum number of drug failures occurs in Phase III.

Answer

Phase I involves healthy volunteers.

Answer

Efficacy of the drug can be determined in Phase II.

Answer

Post-marketing surveillance is conducted in Phase IV.

Question 8

Immune-mediated qualitative drug intolerance is called:

Accepted Answer

Hypersensitivity

Answer

Supersensitivity

Answer

Idiosyncrasy

Answer

Hyperacidity

Question 9

Intake of which of the following medications is associated with an increased incidence of dry socket?

Accepted Answer

Oral contraceptives

Answer

Antihypertensives

Answer

Antiepileptics

Answer

Oral hypoglycemics

Question 10

Which of the following drugs inhibits de novo synthesis of purines?

Accepted Answer

Mycophenolate

Answer

Cyclosporine

Answer

Tacrolimus

Answer

Infliximab

General Pharmacology — MCQs

General Pharmacology — MCQs

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