FMGE 2017 — Pharmacology

Q: Empirical drug of choice for treatment of meningococcal meningitis is:-

Ceftriaxone. ***Ceftriaxone*** - As a **third-generation cephalosporin**, **Ceftriaxone** provides excellent coverage against common bacterial causes of meningitis, including *Neisseria meningitidis*. - It achieves high concentrations in the **cerebrospinal fluid (CSF)**, making it highly effective for CNS infections. *Cefotetan* - **Cefotetan** is a **second-generation cephalosporin** that has limited CSF penetration and less reliable coverage against common meningitis pathogens. - While it has activity against some gram-negative bacteria, it is not considered a first-line agent for empirical treatment of meningitis. *Cefoxitin* - **Cefoxitin** is also a **second-generation cephalosporin** with limited ability to cross the blood-brain barrier, making it unsuitable for treating meningitis. - Its spectrum of activity is more focused on anaerobic bacteria and some gram-negative organisms, not typically the main culprits in meningitis. *Gentamicin* - **Gentamicin** is an **aminoglycoside antibiotic** that has poor penetration into the CSF and is less effective as a monotherapy for meningitis. - It is often used in combination with other antibiotics, but not as an empirical monotherapy for suspected meningococcal meningitis. [Practice more Pharmacology PYQs on OnCourse]

Q: Which of the following aminoglycosides is most cochleotoxic:-

Gentamycin. ***Gentamycin*** - **Gentamycin** is known to be the most **cochleotoxic** aminoglycoside, causing irreversible damage to the hair cells in the cochlea [1]. - This toxicity can lead to **permanent hearing loss** and **tinnitus** due to its selective accumulation in inner ear fluids [2]. *Streptomycin* - While streptomycin can cause ototoxicity, its primary adverse effect is vestibulo-toxicity, affecting **balance** more than hearing [2]. - It mainly targets the hair cells of the semicircular canals and otolithic organs, leading to **vertigo** and ataxia [3]. *Amikacin* - Amikacin is also an ototoxic aminoglycoside but is generally considered **less cochleotoxic** than gentamycin. - Its ototoxic effects are comparable to gentamicin, but it is often reserved for infections resistant to other aminoglycosides. *Minocycline* - Minocycline is a **tetracycline antibiotic**, not an aminoglycoside, and is not associated with significant ototoxicity. - Its side effects typically include photosensitivity, gastrointestinal upset, and **vestibular dysfunction** (dizziness, vertigo) in some patients, distinct from cochlear damage. [Practice more Pharmacology PYQs on OnCourse]

Q: Zileuton is:-

5-Lipoxygenase inhibitor. ***5-Lipoxygenase inhibitor*** - **Zileuton** specifically inhibits **5-lipoxygenase**, an enzyme crucial for the synthesis of **leukotrienes**. - By blocking this enzyme, zileuton reduces the production of **pro-inflammatory leukotrienes**, which are involved in the pathophysiology of **asthma**. *Phospholipase inhibitor* - **Phospholipase A2 inhibitors** like **corticosteroids** act upstream by preventing the release of **arachidonic acid**, a precursor to both prostaglandins and leukotrienes. - Zileuton's action is more specific to the **leukotriene pathway**, occurring after arachidonic acid is already formed. *Cyclooxygenase inhibitor* - **Cyclooxygenase (COX) inhibitors** (like NSAIDs) block the synthesis of **prostaglandins** and **thromboxanes** from arachidonic acid. - Zileuton does not affect the COX pathway but rather targets the **lipoxygenase pathway**. *Leukotriene receptor antagonist* - **Leukotriene receptor antagonists** (e.g., Montelukast, Zafirlukast) block the binding of leukotrienes to their receptors, preventing their downstream effects. - While both target the **leukotriene pathway**, zileuton works by **inhibiting their production**, not their receptor binding. [Practice more Pharmacology PYQs on OnCourse]

Q: Which among the following is an iron chelator?

Desferrioxamine. ***Desferrioxamine*** - **Desferrioxamine** is a specific iron chelator used to treat **acute iron poisoning** and chronic iron overload, such as in patients with **thalassemia** requiring frequent transfusions. - It works by binding to free iron in the bloodstream and promoting its **excretion via urine**. *BAL* - **BAL (dimercaprol)** is primarily used as a chelating agent for **heavy metal poisoning**, particularly **arsenic, mercury, and lead** [1], [2]. - While it can chelate some metals, its affinity and primary use are not for iron. *EDTA* - **EDTA (ethylenediaminetetraacetic acid)** is a chelator often used for **lead poisoning** [1], [2] and hypercalcemia. - It has a high affinity for various divalent and trivalent metal ions [2], but it is not the primary or most specific iron chelator. *Penicillamine* - **Penicillamine** is a chelating agent primarily used for the treatment of **copper overload** in **Wilson's disease**. - It is also used in the treatment of severe **rheumatoid arthritis** and **cystinuria**, but not typically for iron chelation. [Practice more Pharmacology PYQs on OnCourse]

Q: Which of these is the best for management of methanol poisoning?

Fomepizole. ***Fomepizole*** - **Fomepizole** is a competitive inhibitor of **alcohol dehydrogenase**, the enzyme responsible for metabolizing methanol into toxic metabolites like formic acid. - By inhibiting this enzyme, it prevents the formation of these toxic metabolites, thereby reducing organ damage and metabolic acidosis in methanol poisoning. *Naltrexone* - **Naltrexone** is an **opioid receptor antagonist** used in the treatment of alcohol and opioid dependence. - It does not have any direct action on the metabolism of methanol or its toxic byproducts. *Disulfiram* - **Disulfiram** inhibits **aldehyde dehydrogenase**, leading to an unpleasant reaction when alcohol is consumed (flushing, nausea, vomiting). - It is used for alcohol cessation and has no role in the management of methanol poisoning. *Acamprosate* - **Acamprosate** is a medication used to reduce alcohol cravings in individuals recovering from alcohol dependence, possibly by modulating **glutamate neurotransmission**. - It does not directly affect the metabolism of methanol or mitigate its toxic effects. [Practice more Pharmacology PYQs on OnCourse]

16 Previous Year Questions with Answers & Explanations

Questions

All Subjects Anatomy (10)Biochemistry (4)Community Medicine (2)Dental (1)Dermatology (1)Internal Medicine (14)Microbiology (2)Obstetrics and Gynecology (3)Ophthalmology (2)Orthopaedics (2)Pathology (5)Pediatrics (2)Pharmacology (16)Physiology (5)Psychiatry (6)Radiology (1)Surgery (2)

Empirical drug of choice for treatment of meningococcal meningitis is:-

Which of the following aminoglycosides is most cochleotoxic:-

Zileuton is:-

Which among the following is an iron chelator?

Which of these is the best for management of methanol poisoning?

Many drugs are used as rescue therapy for preventing the adverse effects of anticancer drugs. Folinic acid is used in:-

Ritodrine is a:-

Mechanism of action of Pemetrexed is:-

All of the following statements about pralidoxime in organophosphate poisoning are true except:-

Q10

Atorvastatin is used as an anti-dyslipidemic drug. These drugs inhibit their target enzyme by:-

FMGE 2017 - Pharmacology FMGE Practice Questions and MCQs

Question 1: Empirical drug of choice for treatment of meningococcal meningitis is:-

A. Cefotetan
B. Cefoxitin
C. Gentamicin
D. Ceftriaxone (Correct Answer)

Explanation: ***Ceftriaxone*** - As a **third-generation cephalosporin**, **Ceftriaxone** provides excellent coverage against common bacterial causes of meningitis, including *Neisseria meningitidis*. - It achieves high concentrations in the **cerebrospinal fluid (CSF)**, making it highly effective for CNS infections. *Cefotetan* - **Cefotetan** is a **second-generation cephalosporin** that has limited CSF penetration and less reliable coverage against common meningitis pathogens. - While it has activity against some gram-negative bacteria, it is not considered a first-line agent for empirical treatment of meningitis. *Cefoxitin* - **Cefoxitin** is also a **second-generation cephalosporin** with limited ability to cross the blood-brain barrier, making it unsuitable for treating meningitis. - Its spectrum of activity is more focused on anaerobic bacteria and some gram-negative organisms, not typically the main culprits in meningitis. *Gentamicin* - **Gentamicin** is an **aminoglycoside antibiotic** that has poor penetration into the CSF and is less effective as a monotherapy for meningitis. - It is often used in combination with other antibiotics, but not as an empirical monotherapy for suspected meningococcal meningitis.

Question 2: Which of the following aminoglycosides is most cochleotoxic:-

A. Streptomycin
B. Amikacin
C. Gentamycin (Correct Answer)
D. Minocycline

Explanation: ***Gentamycin*** - **Gentamycin** is known to be the most **cochleotoxic** aminoglycoside, causing irreversible damage to the hair cells in the cochlea [1]. - This toxicity can lead to **permanent hearing loss** and **tinnitus** due to its selective accumulation in inner ear fluids [2]. *Streptomycin* - While streptomycin can cause ototoxicity, its primary adverse effect is vestibulo-toxicity, affecting **balance** more than hearing [2]. - It mainly targets the hair cells of the semicircular canals and otolithic organs, leading to **vertigo** and ataxia [3]. *Amikacin* - Amikacin is also an ototoxic aminoglycoside but is generally considered **less cochleotoxic** than gentamycin. - Its ototoxic effects are comparable to gentamicin, but it is often reserved for infections resistant to other aminoglycosides. *Minocycline* - Minocycline is a **tetracycline antibiotic**, not an aminoglycoside, and is not associated with significant ototoxicity. - Its side effects typically include photosensitivity, gastrointestinal upset, and **vestibular dysfunction** (dizziness, vertigo) in some patients, distinct from cochlear damage.

Question 3: Zileuton is:-

A. Phospholipase inhibitor
B. Leukotriene receptor antagonist
C. 5-Lipoxygenase inhibitor (Correct Answer)
D. Cyclooxygenase inhibitor

Explanation: ***5-Lipoxygenase inhibitor*** - **Zileuton** specifically inhibits **5-lipoxygenase**, an enzyme crucial for the synthesis of **leukotrienes**. - By blocking this enzyme, zileuton reduces the production of **pro-inflammatory leukotrienes**, which are involved in the pathophysiology of **asthma**. *Phospholipase inhibitor* - **Phospholipase A2 inhibitors** like **corticosteroids** act upstream by preventing the release of **arachidonic acid**, a precursor to both prostaglandins and leukotrienes. - Zileuton's action is more specific to the **leukotriene pathway**, occurring after arachidonic acid is already formed. *Cyclooxygenase inhibitor* - **Cyclooxygenase (COX) inhibitors** (like NSAIDs) block the synthesis of **prostaglandins** and **thromboxanes** from arachidonic acid. - Zileuton does not affect the COX pathway but rather targets the **lipoxygenase pathway**. *Leukotriene receptor antagonist* - **Leukotriene receptor antagonists** (e.g., Montelukast, Zafirlukast) block the binding of leukotrienes to their receptors, preventing their downstream effects. - While both target the **leukotriene pathway**, zileuton works by **inhibiting their production**, not their receptor binding.

Question 4: Which among the following is an iron chelator?

A. BAL
B. Desferrioxamine (Correct Answer)
C. EDTA
D. Penicillamine

Explanation: ***Desferrioxamine*** - **Desferrioxamine** is a specific iron chelator used to treat **acute iron poisoning** and chronic iron overload, such as in patients with **thalassemia** requiring frequent transfusions. - It works by binding to free iron in the bloodstream and promoting its **excretion via urine**. *BAL* - **BAL (dimercaprol)** is primarily used as a chelating agent for **heavy metal poisoning**, particularly **arsenic, mercury, and lead** [1], [2]. - While it can chelate some metals, its affinity and primary use are not for iron. *EDTA* - **EDTA (ethylenediaminetetraacetic acid)** is a chelator often used for **lead poisoning** [1], [2] and hypercalcemia. - It has a high affinity for various divalent and trivalent metal ions [2], but it is not the primary or most specific iron chelator. *Penicillamine* - **Penicillamine** is a chelating agent primarily used for the treatment of **copper overload** in **Wilson's disease**. - It is also used in the treatment of severe **rheumatoid arthritis** and **cystinuria**, but not typically for iron chelation.

Question 5: Which of these is the best for management of methanol poisoning?

A. Fomepizole (Correct Answer)
B. Naltrexone
C. Disulfiram
D. Acamprosate

Explanation: ***Fomepizole*** - **Fomepizole** is a competitive inhibitor of **alcohol dehydrogenase**, the enzyme responsible for metabolizing methanol into toxic metabolites like formic acid. - By inhibiting this enzyme, it prevents the formation of these toxic metabolites, thereby reducing organ damage and metabolic acidosis in methanol poisoning. *Naltrexone* - **Naltrexone** is an **opioid receptor antagonist** used in the treatment of alcohol and opioid dependence. - It does not have any direct action on the metabolism of methanol or its toxic byproducts. *Disulfiram* - **Disulfiram** inhibits **aldehyde dehydrogenase**, leading to an unpleasant reaction when alcohol is consumed (flushing, nausea, vomiting). - It is used for alcohol cessation and has no role in the management of methanol poisoning. *Acamprosate* - **Acamprosate** is a medication used to reduce alcohol cravings in individuals recovering from alcohol dependence, possibly by modulating **glutamate neurotransmission**. - It does not directly affect the metabolism of methanol or mitigate its toxic effects.

Question 6: Many drugs are used as rescue therapy for preventing the adverse effects of anticancer drugs. Folinic acid is used in:-

A. Cyclophosphamide toxicity
B. Doxorubicin toxicity
C. Methotrexate toxicity (Correct Answer)
D. Cisplatin toxicity

Explanation: ***Methotrexate toxicity*** - **Folinic acid (leucovorin)** is a reduced folate that bypasses the metabolic block caused by **methotrexate** on dihydrofolate reductase. - It replenishes the body's **folate stores** and protects healthy cells from methotrexate's cytotoxic effects, particularly in the bone marrow and gastrointestinal tract. *Cyclophosphamide toxicity* - **Cyclophosphamide** toxicity, primarily hemorrhagic cystitis, is prevented by **mesna** (2-mercaptoethane sulfonate). - Mesna inactivates the urotoxic metabolite **acrolein** in the urine, preventing bladder damage. *Doxorubicin toxicity* - **Doxorubicin** causes cardiotoxicity, which can be mitigated by the iron-chelating agent **dexrazoxane**. - Dexrazoxane reduces the formation of **free radicals** that contribute to doxorubicin-induced myocardial damage. *Cisplatin toxicity* - **Cisplatin** toxicity, especially nephrotoxicity, is largely prevented by **aggressive hydration** and administration of **diuretics**. - **Amifostine** is another agent that can reduce cisplatin-induced nephrotoxicity, neurotoxicity, and ototoxicity by acting as a cytoprotectant.

Question 7: Ritodrine is a:-

A. β antagonist
B. α agonist
C. β2 agonist (Correct Answer)
D. α1 antagonist

Explanation: ***β2 agonist*** - Ritodrine is a **selective beta-2 adrenergic receptor agonist** primarily used as a **tocolytic agent** to relax the uterus and stop premature labor. - Its action involves stimulating **beta-2 receptors** in the myometrium, leading to decreased intracellular calcium and uterine smooth muscle relaxation. *α1 antagonist* - Alpha-1 antagonists block **alpha-1 adrenergic receptors**, causing vasodilation and are used to treat conditions like **hypertension** or **benign prostatic hyperplasia**. - Ritodrine's mechanism is distinct, as it targets beta-2 receptors, not alpha-1. *β antagonist* - Beta antagonists (beta-blockers) block **beta adrenergic receptors** (beta-1, beta-2, or both) and are used for conditions like **hypertension**, **angina**, or **arrhythmias**. - Ritodrine is an agonist, meaning it activates receptors, rather than blocking them. *α agonist* - Alpha agonists stimulate **alpha adrenergic receptors**, causing vasoconstriction and increased blood pressure, as seen with agents like **phenylephrine**. - Ritodrine specifically targets beta-2 receptors, leading to opposite effects like smooth muscle relaxation in the uterus and bronchi.

Question 8: Mechanism of action of Pemetrexed is:-

A. Topoisomerase inhibitor
B. Dihydrofolate reductase inhibitor
C. Dopamine agonist
D. Thymidylate synthase inhibitor (Correct Answer)

Explanation: ***Thymidylate synthase inhibitor*** - **Pemetrexed** is a **multi-targeted antifolate agent** that primarily inhibits **thymidylate synthase (TS)**, the key enzyme responsible for synthesizing thymidine monophosphate, an essential building block for DNA synthesis. - While pemetrexed also inhibits **dihydrofolate reductase (DHFR)** and **glycinamide ribonucleotide formyltransferase (GARFT)**, its **primary and most clinically significant mechanism** is TS inhibition, making it particularly effective in mesothelioma and non-small cell lung cancer. - This multi-targeted action enhances its cytotoxic effects compared to single-target antifolates. *Dihydrofolate reductase inhibitor* - While pemetrexed does inhibit **DHFR** as part of its multi-targeted mechanism, this is a **secondary action**, not its primary mechanism. - Classical DHFR inhibitors include **methotrexate** and **trimethoprim**, which specifically target this enzyme. - In exam contexts, pemetrexed is best classified by its **primary target: thymidylate synthase**. *Topoisomerase inhibitor* - **Topoisomerase inhibitors** target enzymes that control DNA topology during replication and transcription. - Examples include **irinotecan** and **topotecan** (topoisomerase I inhibitors) and **etoposide** (topoisomerase II inhibitor). - This is not the mechanism of action for pemetrexed. *Dopamine agonist* - **Dopamine agonists** activate dopamine receptors and are used in neurological conditions like Parkinson's disease (e.g., **pramipexole**, **ropinirole**). - This mechanism is completely unrelated to anticancer agents and folate metabolism.

Question 9: All of the following statements about pralidoxime in organophosphate poisoning are true except:-

A. It does not cross blood brain barrier
B. It should be started after 24 hours of poisoning (Correct Answer)
C. Reactivates the AChE enzyme
D. It is given intravenously

Explanation: ***It should be started after 24 hours of poisoning*** - **Pralidoxime (2-PAM)** is most effective when administered **early** in organophosphate poisoning, ideally within minutes to a few hours of exposure. - Delaying administration beyond **24-48 hours** significantly reduces its efficacy because the bond between the organophosphate and **acetylcholinesterase (AChE)** becomes **irreversible** (a process called "aging"). *It does not cross blood brain barrier* - **Pralidoxime** is a **quaternary ammonium compound**, which makes it highly polar and unable to readily cross the **blood-brain barrier**. - Therefore, it primarily reactivates **acetylcholinesterase** in the **peripheral nervous system** but has limited effect on central nervous system symptoms. *Reactivates the AChE enzyme* - **Pralidoxime** works by **reactivating the acetylcholinesterase enzyme** that has been inhibited by organophosphates. - It does this by binding to the organophosphate molecule, thereby freeing the active site of the **AChE enzyme** to metabolize **acetylcholine** again. *It is given intravenously* - **Pralidoxime** is typically administered via **intravenous (IV) infusion** to achieve rapid and sustained therapeutic concentrations. - Due to its poor oral absorption, oral administration is not a suitable route for treating acute organophosphate poisoning.

Question 10: Atorvastatin is used as an anti-dyslipidemic drug. These drugs inhibit their target enzyme by:-

A. Noncompetitive inhibition
B. Competitive inhibition (Correct Answer)
C. Irreversible inhibition
D. Uncompetitive inhibition

Explanation: ***Competitive inhibition*** - Atorvastatin is a **statin**, which acts as a **competitive inhibitor** of **HMG-CoA reductase**, the rate-limiting enzyme in cholesterol synthesis. - It competes with the natural substrate, HMG-CoA, for binding to the **active site of the enzyme**, thereby reducing cholesterol production. *Uncompetitive* - **Uncompetitive inhibitors** bind only to the **enzyme-substrate complex**, not to the free enzyme. - This type of inhibition is characterized by a decrease in both **apparent Vmax** and **apparent Km**. *Noncompetitive inhibition* - **Noncompetitive inhibitors** bind to an allosteric site on the enzyme, distinct from the active site, and can bind to either the **free enzyme or the enzyme-substrate complex**. - This leads to a decrease in the **apparent Vmax** but does not affect Km. *Irreversible inhibition* - **Irreversible inhibitors** form a **strong covalent bond** with the enzyme, permanently inactivating it. - Statins do not form covalent bonds with HMG-CoA reductase; their inhibition is **reversible** upon drug discontinuation.