Mixed Deck — All Pharmacology Topics Flashcards

The concept of 'biased agonism' (functional selectivity) refers to:

Answer: A single ligand preferentially activating one downstream pathway over another at the same receptor

Biased agonists stabilize distinct receptor conformations that preferentially couple to G-protein vs. beta-arrestin pathways, enabling therapeutic selectivity.

A patient has chronic kidney disease with a GFR of 20 mL/min. Which pharmacokinetic parameter is most directly affected?

Answer: Renal clearance

Renal clearance is directly reduced in CKD as glomerular filtration rate declines, prolonging drug half-life.

Which drug class does warfarin belong to as its prototype anticoagulant?

Answer: Vitamin K antagonists

Warfarin is the prototype vitamin K antagonist anticoagulant, inhibiting synthesis of clotting factors II, VII, IX, and X.

Therapeutic Drug Monitoring (TDM) is most clinically useful for drugs that exhibit which of the following characteristics?

Answer: A narrow therapeutic range and significant pharmacokinetic variability. [4, 8]

TDM is most valuable for drugs where there is a small margin between the effective concentration and the toxic concentration (a narrow therapeutic range). It is also crucial when there is high inter-individual variability in how the drug is absorbed, distributed, metabolized, and excreted, making standardized dosing unreliable. [4, 8, 16]

A patient on warfarin begins taking amiodarone. What INR adjustment is expected?

Answer: INR will increase; reduce warfarin dose

Amiodarone inhibits CYP2C9, reducing warfarin metabolism and raising INR, so the warfarin dose must be reduced.

Digoxin toxicity is potentiated by hypokalemia because:

Answer: Potassium and digoxin compete for the same binding site on Na/K-ATPase

Potassium and digoxin compete for the same binding site on the Na/K-ATPase; low potassium means less competition and enhanced digoxin binding and toxicity.

Which aminoglycoside antibiotic is most commonly associated with nephrotoxicity and ototoxicity?

Answer: Gentamicin

Gentamicin and other aminoglycosides accumulate in renal proximal tubule cells and cochlear hair cells, causing nephrotoxicity and ototoxicity.

A patient is administered an oral medication that undergoes significant first-pass metabolism. Which of the following statements accurately describes the consequence of this phenomenon?

Answer: The oral dose required to achieve a therapeutic effect will be higher than the intravenous dose.

First-pass metabolism occurs when a drug's concentration is greatly reduced before it reaches systemic circulation, primarily by the liver and gut wall. This reduction in bioavailability means a higher oral dose is needed to achieve the same therapeutic plasma concentration as a dose administered intravenously, which bypasses this effect entirely.

Sacubitril/valsartan (Entresto) improves heart failure outcomes by combining an ARB with an inhibitor of which enzyme?

Answer: Neprilysin

Sacubitril inhibits neprilysin, which normally breaks down natriuretic peptides; blocking it raises BNP/ANP levels, promoting vasodilation and natriuresis.

Which of the following statements most accurately describes the mechanism of action of acyclovir in treating a herpes simplex virus (HSV) infection?

Answer: It is a guanosine analog that, after phosphorylation by viral thymidine kinase, inhibits viral DNA polymerase and causes chain termination.

Acyclovir is a prodrug that is selectively activated in cells infected with herpes viruses. The viral enzyme thymidine kinase monophosphorylates acyclovir. Host cell kinases then convert it to acyclovir triphosphate, which competitively inhibits the viral DNA polymerase and is also incorporated into the growing viral DNA chain, causing chain termination. This specificity for the viral enzyme accounts for its selective toxicity.

Which drug causes mydriasis and cycloplegia by blocking muscarinic receptors in the eye?

Answer: Atropine

Atropine blocks M3 receptors on the iris sphincter and ciliary muscle, causing pupil dilation (mydriasis) and loss of accommodation (cycloplegia).

Which drug is the prototype proton pump inhibitor (PPI)?

Answer: Omeprazole

Omeprazole is the prototype PPI, irreversibly inhibiting H+/K+-ATPase (the proton pump) in parietal cells to profoundly suppress gastric acid secretion.

Which PCSK9 inhibitor is administered as a subcutaneous injection every 2 weeks and significantly reduces LDL cholesterol in statin-intolerant patients?

Answer: Alirocumab

Alirocumab (Praluent) is a PCSK9 monoclonal antibody given every 2 weeks (or monthly at higher dose) that prevents LDL receptor degradation, markedly lowering LDL.

Which pharmacodynamic interaction occurs when two drugs produce an effect greater than the sum of their individual effects?

Answer: Potentiation (synergism)

Synergism (potentiation) describes an interaction where the combined effect exceeds the arithmetic sum of each drug's individual effects.

A patient in septic shock is administered a continuous infusion of a drug that primarily acts as a potent alpha-1 adrenergic agonist to increase blood pressure. Which of the following drugs was most likely administered?

Answer: Phenylephrine

Phenylephrine is a selective alpha-1 adrenergic agonist that causes potent vasoconstriction of arterioles and veins, leading to an increase in systemic vascular resistance and blood pressure. This makes it useful in cases of vasodilatory shock. Isoproterenol and albuterol are primarily beta-agonists, and dobutamine is a beta-1 agonist, which would primarily increase heart rate and contractility without the potent vasoconstriction needed to reverse septic shock.

A patient is diagnosed with VRE (vancomycin-resistant Enterococcus). Which antibiotic is approved for treating VRE infections?

Answer: Linezolid

Linezolid (an oxazolidinone) is FDA-approved for treatment of VRE faecium infections and is active regardless of vancomycin resistance.

Guanethidine lowers blood pressure by which mechanism?

Answer: Depleting norepinephrine from sympathetic nerve terminals

Guanethidine is taken up into adrenergic neurons and depletes norepinephrine stores, preventing sympathetic vasoconstriction.

Fenofibrate primarily lowers triglycerides by activating which nuclear receptor?

Answer: Peroxisome proliferator-activated receptor alpha (PPAR-α)

Fenofibrate activates PPAR-α, which upregulates lipoprotein lipase and reduces apoC-III, enhancing triglyceride-rich lipoprotein clearance.

Which type of drug-receptor interaction is characterized by the formation of a covalent bond, making the interaction essentially permanent?

Answer: Irreversible binding

Covalent bond formation between a drug and receptor results in irreversible binding, as seen with aspirin's acetylation of cyclooxygenase.

What is enterohepatic recirculation and what is its pharmacokinetic effect?

Answer: Reabsorption of bile-excreted drug from the intestine, prolonging its half-life

Enterohepatic recirculation occurs when biliary-excreted drug is deconjugated in the gut and reabsorbed, extending the drug's effective half-life.