Resistance to Methotrexate develops due to?
What is a key difference between fosphenytoin and phenytoin?
Which of the following is NOT a mechanism of action of theophylline in bronchial asthma?
Omalizumab is primarily used in the treatment of which condition?
Which of the following is a selective serotonin and norepinephrine reuptake inhibitor?
What is the antidote for Ethylene Glycol?
Which of the following is the mechanism of action of tetanospasmin ?
Which antibiotic is Actinomycosis sensitive to?
Which of the following potassium-sparing diuretics was the first to be shown to reduce cardiac mortality in chronic heart failure patients?
All are true regarding Sunitinib except which of the following?
NEET-PG 2012 - Pharmacology NEET-PG Practice Questions and MCQs
Question 11: Resistance to Methotrexate develops due to?
- A. Rapid proliferation of cancer cells
- B. Thymidylate kinase deficiency
- C. Thymidylate synthetase deficiency
- D. Increased production of dihydrofolate reductase (DHFR) (Correct Answer)
Explanation: ***Increased production of dihydrofolate reductase (DHFR)*** - Methotrexate acts by inhibiting **dihydrofolate reductase (DHFR)**, an enzyme essential for **folate metabolism** and DNA synthesis. - An **increased production of DHFR** (through gene amplification or overexpression) by cancer cells allows them to bypass the drug's inhibitory effects, leading to resistance. - This is the **most common mechanism** of methotrexate resistance. *Rapid proliferation of cancer cells* - While **rapid cell proliferation** is a characteristic of cancer, it doesn't directly explain resistance to methotrexate. - Methotrexate targets fast-dividing cells (S-phase specific), so rapid proliferation often makes them **more susceptible**, not resistant, as long as the drug's mechanism is effective. *Thymidylate kinase deficiency* - **Thymidylate kinase** is involved in the phosphorylation of **thymidine** to produce **dTMP** (deoxythymidine monophosphate). - A deficiency in this enzyme would likely hinder DNA synthesis, potentially increasing sensitivity to DNA-targeting agents, rather than causing resistance to methotrexate. *Thymidylate synthetase deficiency* - **Thymidylate synthetase** converts dUMP to dTMP using **5,10-methylene-THF** as a cofactor. - Methotrexate **indirectly inhibits** thymidylate synthetase by depleting tetrahydrofolate cofactor pools through DHFR inhibition. - A **deficiency** of this enzyme would not cause resistance; rather, **increased thymidylate synthetase** expression can be an alternative resistance mechanism, though less common than DHFR overexpression.
Question 12: What is a key difference between fosphenytoin and phenytoin?
- A. Can be used in absence seizures
- B. Can be mixed with saline (Correct Answer)
- C. Can be given orally
- D. It is the drug of choice for myoclonic seizures
Explanation: **Can be mixed with saline** - **Fosphenytoin** is a water-soluble prodrug that is converted to phenytoin in the body; its solubility allows it to be **mixed with saline** solutions for intravenous administration, minimizing the risk of precipitation. - Unlike phenytoin, fosphenytoin's formulation avoids the need for propylene glycol, which is associated with adverse cardiovascular effects and makes phenytoin incompatible with saline. *Can be used in absence seizures* - Neither **fosphenytoin nor phenytoin** is effective for treating **absence seizures**, and they can sometimes worsen them. - **Ethosuximide** or **valproic acid** are the drugs of choice for absence seizures. *Can be given orally* - While **phenytoin** is commonly available in oral forms (capsules, chewable tablets, suspension), **fosphenytoin** is primarily designed for **parenteral administration** (intravenous or intramuscular). - Fosphenytoin is a prodrug that is rapidly converted to phenytoin *in vivo*, but it is not typically available or indicated for direct oral administration. *It is the drug of choice for myoclonic seizures* - Neither **fosphenytoin nor phenytoin** is the drug of choice for **myoclonic seizures**; they can exacerbate this type of seizure. - **Valproic acid** and **levetiracetam** are preferred treatments for myoclonic seizures due to their broader spectrum of activity.
Question 13: Which of the following is NOT a mechanism of action of theophylline in bronchial asthma?
- A. Adenosine receptor antagonism
- B. Increased histone deacetylation
- C. Phosphodiesterase inhibition
- D. Beta-2 receptor stimulation (Correct Answer)
Explanation: ***Beta-2 receptor stimulation*** - Theophylline is a **non-selective phosphodiesterase inhibitor** and an **adenosine receptor antagonist**, but it does not directly stimulate beta-2 receptors. - **Beta-2 receptor agonists** like salbutamol or formoterol are the medications that work by stimulating these receptors to cause bronchodilation. *Phosphodiesterase inhibition* - Theophylline inhibits **phosphodiesterase enzymes**, leading to an increase in intracellular **cAMP** levels. - This increase in **cAMP** promotes bronchodilation by relaxing airway smooth muscle. *Adenosine receptor antagonism* - Theophylline acts as an antagonist at **adenosine receptors**, particularly A1 and A2B. - Antagonism of adenosine receptors can reduce bronchoconstriction and inflammatory mediator release, contributing to its anti-asthmatic effects. *Increased histone deacetylation* - Theophylline, particularly at lower concentrations, increases the activity of **histone deacetylase (HDAC)**. - This action helps to **repress inflammatory gene expression**, which is a unique anti-inflammatory mechanism separate from its bronchodilatory effects.
Question 14: Omalizumab is primarily used in the treatment of which condition?
- A. Breast carcinoma
- B. Asthma (Correct Answer)
- C. Rheumatoid arthritis
- D. Chronic obstructive pulmonary disease (COPD)
Explanation: ***Asthma*** - **Omalizumab** is a **monoclonal antibody** that targets and binds to **immunoglobulin E (IgE)**, preventing it from binding to mast cells and basophils. - By reducing free IgE, omalizumab helps to prevent the release of inflammatory mediators, thereby **reducing allergic reactions and asthma symptoms**, particularly in patients with severe persistent allergic asthma. *Breast carcinoma* - **Omalizumab** is not indicated for the treatment of **breast carcinoma**; treatments for breast cancer typically involve chemotherapy, radiation, surgery, and targeted therapies specific to cancer cells. - Targeted therapies for breast cancer often focus on hormone receptors (e.g., **estrogen receptor**) or growth factor receptors (e.g., **HER2**), not IgE. *Rheumatoid arthritis* - **Omalizumab** is not used for **rheumatoid arthritis (RA)**; RA is an autoimmune disease primarily involving **T-cells and cytokines** like **TNF-alpha** and **IL-6**. - Treatment for RA typically includes **DMARDs** (disease-modifying antirheumatic drugs) and **biological agents** that target specific inflammatory pathways (e.g., **adalimumab**, **etanercept**). *Chronic obstructive pulmonary disease (COPD)* - **Omalizumab** is not indicated for **COPD**, which is primarily characterized by chronic inflammation of the airways and **emphysema**, largely caused by smoking. - COPD management focuses on bronchodilators, corticosteroids, and oxygen therapy, with no role for IgE-targeting therapy.
Question 15: Which of the following is a selective serotonin and norepinephrine reuptake inhibitor?
- A. Fluoxetine
- B. Venlafaxine (Correct Answer)
- C. Sertraline
- D. Aripiprazole
Explanation: ***Venlafaxine*** - **Venlafaxine** is a commonly used antidepressant that inhibits the reuptake of both **serotonin** and **norepinephrine**, making it an SNRI. - Its dual mechanism of action can be effective for a broad range of depressive and anxiety disorders. *Fluoxetine* - **Fluoxetine** is a **selective serotonin reuptake inhibitor (SSRI)**, primarily affecting serotonin levels in the brain. - It does not significantly inhibit norepinephrine reuptake and, thus, is not classified as an SNRI. *Sertraline* - **Sertraline** is another widely prescribed antidepressant that is also a **selective serotonin reuptake inhibitor (SSRI)**. - It works mainly by increasing serotonin availability in the synaptic cleft. *Aripiprazole* - **Aripiprazole** is an **atypical antipsychotic** medication, often used as an adjunct therapy for depression, but its primary mechanism is partial agonism at dopamine D2 and serotonin 5-HT1A receptors, and antagonism at serotonin 5-HT2A receptors. - It is not classified as a selective serotonin and norepinephrine reuptake inhibitor.
Question 16: What is the antidote for Ethylene Glycol?
- A. Barbiturate
- B. Acetylcysteine
- C. Ferric chloride
- D. Fomepizole (Correct Answer)
Explanation: ***Fomepizole*** - **Fomepizole** is the primary and preferred antidote for ethylene glycol poisoning, as it competitively inhibits **alcohol dehydrogenase**, the enzyme responsible for metabolizing ethylene glycol into its toxic metabolites. - By blocking this enzyme, fomepizole prevents the formation of harmful compounds like **glycolic acid** and **oxalic acid**, which cause metabolic acidosis and kidney damage. - **Ethanol** is an alternative antidote that works by the same mechanism (competitive inhibition of alcohol dehydrogenase) and can be used when fomepizole is unavailable, though fomepizole is preferred due to better safety profile and easier dosing. *Barbiturate* - **Barbiturates** are a class of psychoactive drugs that act as central nervous system depressants, primarily used for sedation, anesthesia, and seizure control. - They have no role in neutralizing or metabolizing ethylene glycol or its toxic byproducts. *Acetylcysteine* - Acetylcysteine is an antidote primarily used for **acetaminophen (paracetamol) overdose**, where it replenishes glutathione stores and detoxifies its toxic metabolite, **NAPQI**. - It does not have any direct antidotal effect against ethylene glycol or its metabolites. *Ferric chloride* - **Ferric chloride** is a chemical compound used in various industrial processes, water treatment, and as a laboratory reagent. - It is highly corrosive and toxic if ingested, but it is not used as an antidote for any type of poisoning, including ethylene glycol.
Question 17: Which of the following is the mechanism of action of tetanospasmin ?
- A. Inhibition of release of GABA and glycine (Correct Answer)
- B. Inhibition of Ach release from synapse
- C. Inhibition of protein synthesis
- D. Activation of adenylyl cyclase
Explanation: ***Inhibition of release of GABA and glycine*** - **Tetanospasmin** is a potent neurotoxin produced by *Clostridium tetani* that acts by blocking the release of inhibitory neurotransmitters, specifically **GABA (gamma-aminobutyric acid)** and **glycine**, from presynaptic terminals in the spinal cord and brainstem. - This inhibition leads to **uncontrolled muscle spasms**, rigidity, and convulsions, characteristic of tetanus, due to the lack of inhibitory signals to motor neurons. *Inhibition of Ach release from synapse* - This mechanism is characteristic of **botulinum toxin** (produced by *Clostridium botulinum*), not tetanospasmin. - Botulinum toxin inhibits the release of **acetylcholine (ACh)** at the neuromuscular junction, leading to flaccid paralysis. *Inhibition of protein synthesis* - This mechanism is associated with toxins like **diphtheria toxin** and **exotoxin A** from *Pseudomonas aeruginosa*. - These toxins inactivate elongation factor-2 (EF-2), thereby blocking protein synthesis and causing cell death. *Activation of adenylyl cyclase* - Toxins such as **cholera toxin** and **pertussis toxin** act by activating adenylyl cyclase, leading to an increase in intracellular cAMP levels. - This mechanism causes effects like severe diarrhea in cholera and respiratory symptoms in whooping cough.
Question 18: Which antibiotic is Actinomycosis sensitive to?
- A. Streptomycin
- B. Nystatin
- C. Doxycycline
- D. Penicillin (Correct Answer)
Explanation: ***Penicillin*** - **Penicillin** is the **antibiotic of choice** for treating Actinomycosis due to the organism's high sensitivity. - Treatment typically involves a **long course** of high-dose penicillin for several months. *Streptomycin* - **Streptomycin** is an **aminoglycoside antibiotic** primarily used for **tuberculosis** and some gram-negative bacterial infections. - It is **not effective** against Actinomyces species. *Nystatin* - **Nystatin** is an **antifungal medication** used to treat **yeast infections**, particularly Candida. - It has **no antibacterial activity** and thus no role in treating Actinomycosis. *Doxycycline* - While **doxycycline** can be used as an **alternative** in patients allergic to penicillin, it is **not the primary choice**. - Its effectiveness is generally less pronounced than penicillin, and it's reserved for second-line treatment.
Question 19: Which of the following potassium-sparing diuretics was the first to be shown to reduce cardiac mortality in chronic heart failure patients?
- A. Spironolactone (Correct Answer)
- B. Amiloride
- C. Triamterene
- D. Eplerenone
Explanation: ***Spironolactone*** - **Spironolactone** was the first potassium-sparing diuretic shown to reduce **cardiac mortality** in patients with **chronic heart failure** in the **RALES trial** (Randomized Aldactone Evaluation Study). - Its beneficial effects in heart failure are primarily attributed to its **aldosterone receptor antagonist** properties, which counteract the harmful effects of aldosterone on the myocardium and vasculature, rather than just its diuretic effect. *Amiloride* - **Amiloride** is a potassium-sparing diuretic that works by directly inhibiting **epithelial sodium channels (ENaC)** in the collecting duct. - While it helps in potassium conservation, it has not been shown to significantly reduce cardiac mortality in chronic heart failure patients in clinical trials. *Triamterene* - **Triamterene** is another potassium-sparing diuretic that also directly inhibits **ENaC** in the collecting duct, similar to amiloride. - Like amiloride, it is used to prevent hypokalemia but lacks evidence for significant **cardiac mortality reduction** in chronic heart failure. *Eplerenone* - **Eplerenone** is a selective **aldosterone receptor antagonist**, similar to spironolactone, with fewer hormonal side effects. - While it has been shown to reduce **cardiac mortality** in chronic heart failure (e.g., in the EMPHASIS-HF trial), it was introduced later than spironolactone and was not the *first* to demonstrate this benefit.
Question 20: All are true regarding Sunitinib except which of the following?
- A. It inhibits tyrosine kinase receptors
- B. It is excreted primarily in urine (Correct Answer)
- C. It is used for the treatment of GIST
- D. It is used for renal cell carcinoma
Explanation: ***It is excreted primarily in urine*** - **Sunitinib** is predominantly metabolized in the **liver** by CYP3A4 and primarily excreted in the **feces**, not urine. - Its major active metabolite, N-desethyl sunitinib, is also primarily eliminated via the fecal route. *It inhibits tyrosine kinase receptors* - **Sunitinib** is a **multitargeted receptor tyrosine kinase (RTK) inhibitor**. - It blocks several RTKs involved in tumor growth, angiogenesis, and metastatic progression, such as **VEGFR, PDGFR, KIT, and FLT3**. *It is used for the treatment of GIST* - **Sunitinib** is approved for the treatment of **imatinib-refractory** or **imatinib-intolerant gastrointestinal stromal tumors (GIST)**. - Its mechanism in GIST involves inhibiting KIT and PDGFR, which are often mutated and constitutively active in this cancer. *It is used for renal cell carcinoma* - **Sunitinib** is a standard first-line treatment for **advanced renal cell carcinoma (RCC)**. - Its efficacy in RCC is primarily due to its inhibition of VEGFR, which targets the high vascularity characteristic of kidney tumors.