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Question 1Pharmacology and Therapeutics
Which laboratory parameter is used to monitor the anticoagulant effect of warfarin?
- International normalized ratio (INR) Correct answer.
- Bleeding time
- Activated partial thromboplastin time (aPTT)
- Platelet count
Explanation
Warfarin inhibits vitamin K epoxide reductase, reducing synthesis of functional factors II, VII, IX and X. Factor VII has the shortest half-life and the prothrombin time, reported as the INR, reflects the extrinsic pathway, making it the standard monitoring test.
Question 2Pharmacology and Therapeutics
A patient develops a persistent dry cough two weeks after starting enalapril. Which mechanism best explains this adverse effect?
- Accumulation of bradykinin in the airways Correct answer.
- Blockade of beta-2 adrenergic receptors
- Direct histamine release from mast cells
- Inhibition of cyclooxygenase-1
Explanation
Angiotensin-converting enzyme also acts as kininase II and degrades bradykinin. When the enzyme is inhibited, bradykinin and substance P accumulate in the respiratory tract and provoke a dry cough in a subset of patients. Switching to an angiotensin receptor blocker usually resolves it.
Question 3Pharmacology and Therapeutics
Which agent is the specific antidote for respiratory depression caused by opioid overdose?
- Atropine
- Flumazenil
- Naloxone Correct answer.
- N-acetylcysteine
Explanation
Naloxone is a competitive antagonist at mu-opioid receptors that rapidly reverses opioid-induced respiratory depression and sedation. Because its half-life is shorter than that of many opioids, repeat doses or an infusion may be needed.
Question 4Pharmacology and Therapeutics
Omeprazole reduces gastric acid secretion by which mechanism?
- Irreversibly inhibiting the parietal cell H+/K+-ATPase Correct answer.
- Blocking muscarinic M3 receptors on parietal cells
- Blocking histamine H2 receptors on parietal cells
- Neutralizing gastric acid directly in the lumen
Explanation
Proton pump inhibitors are acid-labile prodrugs that accumulate in the acidic secretory canaliculus of the parietal cell, where they are activated and covalently bind the H+/K+-ATPase. This irreversible inhibition suppresses the final common step of acid secretion.
Question 5Pharmacology and Therapeutics
In first-order (linear) elimination, the amount of drug removed per unit of time is:
- Proportional to the square of the plasma concentration
- Proportional to the plasma drug concentration Correct answer.
- Zero until the concentration exceeds the Michaelis constant
- Constant regardless of the plasma concentration
Explanation
In first-order kinetics the elimination rate is directly proportional to plasma concentration, so a constant fraction of the drug is removed per unit time and the half-life is constant. This contrasts with zero-order (saturable) elimination, in which a fixed amount is removed per unit time.
Question 6Pharmacology and Therapeutics
Which instruction best improves the absorption of oral levothyroxine?
- Take it together with calcium carbonate supplements
- Take it with breakfast and a glass of milk
- Take it on an empty stomach 30 to 60 minutes before breakfast Correct answer.
- Take it at bedtime together with an antacid
Explanation
Levothyroxine absorption is reduced by food and by polyvalent cations, so it should be taken on an empty stomach with water and separated from meals by at least 30 minutes. Calcium, iron, and antacids should be taken several hours later.
Question 7Pharmacology and Therapeutics
Which mechanism primarily accounts for gastric ulceration during long-term ibuprofen use?
- Stimulation of gastric histamine release
- Direct blockade of parietal cell H2 receptors
- Inhibition of cyclooxygenase-1 and reduced protective prostaglandin synthesis Correct answer.
- Increased gastric bicarbonate and mucus secretion
Explanation
Non-selective NSAIDs inhibit cyclooxygenase-1, lowering prostaglandin synthesis in the gastric mucosa. Prostaglandins normally increase mucus and bicarbonate secretion and maintain mucosal blood flow, so their loss predisposes to erosions and ulcers.
Question 8Pharmacology and Therapeutics
Which constellation of effects is most characteristic of antimuscarinic drugs such as oxybutynin?
- Bronchoconstriction with increased airway secretions
- Salivation, lacrimation, and urination
- Bradycardia, diarrhea, and miosis
- Dry mouth, urinary retention, and blurred vision Correct answer.
Explanation
Muscarinic blockade reduces parasympathetic tone, producing dry mouth, constipation, urinary retention, mydriasis with blurred vision, and tachycardia. These effects are predictable extensions of the mechanism and limit tolerability in older adults.
Question 9Pharmacology and Therapeutics
Which antihypertensive is most appropriate for a 30-year-old with moderate persistent asthma and no other comorbidity?
- Amlodipine Correct answer.
- Timolol
- Propranolol
- Nadolol
Explanation
Propranolol, nadolol, and timolol are non-selective beta-blockers that block beta-2 receptors in the airway and can precipitate bronchospasm in asthma. Amlodipine, a dihydropyridine calcium channel blocker, has no beta-adrenergic activity and is a safer choice.
Question 10Pharmacology and Therapeutics
Which adverse effects are most closely associated with aminoglycosides such as gentamicin?
- Bone marrow suppression and alopecia
- Hepatotoxicity and photosensitivity
- Nephrotoxicity and ototoxicity Correct answer.
- Pulmonary fibrosis and thyroid dysfunction
Explanation
Aminoglycosides accumulate in proximal tubular cells and in cochlear and vestibular hair cells, producing dose- and duration-related nephrotoxicity and ototoxicity. Monitoring of renal function, levels, and duration of therapy reduces this risk.
Question 11Pharmacology and Therapeutics
Metformin should be temporarily withheld in which situation because of an increased risk of lactic acidosis?
- Well-controlled hypothyroidism
- Stable exertional angina
- Mild seasonal allergic rhinitis
- Acute decompensated heart failure with renal hypoperfusion Correct answer.
Explanation
Metformin is cleared renally and inhibits mitochondrial respiration, so conditions causing tissue hypoperfusion or renal impairment increase lactate accumulation. Acute decompensated heart failure with hypoperfusion is a classic reason to hold the drug until the patient is stable.
Question 12Pharmacology and Therapeutics
A patient stabilized on simvastatin is prescribed clarithromycin for pneumonia. What is the principal concern?
- Loss of statin efficacy from enzyme induction
- Increased risk of myopathy from CYP3A4 inhibition Correct answer.
- Increased renal clearance of simvastatin
- Displacement of simvastatin from plasma proteins
Explanation
Clarithromycin is a strong inhibitor of CYP3A4, the enzyme that metabolizes simvastatin. Plasma statin concentrations rise several-fold, increasing the risk of myopathy and rhabdomyolysis, so the statin is usually paused or an interacting antibiotic avoided.
Question 13Pharmacology and Therapeutics
A woman using a combined oral contraceptive is started on rifampin for tuberculosis. What is the most appropriate advice?
- Use an additional or alternative contraceptive method during therapy Correct answer.
- No change is needed because rifampin does not affect hormones
- Take the contraceptive at the same time as rifampin to block the interaction
- Double the contraceptive dose for the first week only
Explanation
Rifampin is a potent inducer of CYP3A4 and P-glycoprotein, accelerating estrogen and progestin metabolism and reducing contraceptive efficacy. A backup or alternative method should be used throughout rifampin therapy and for several weeks afterwards.
Question 14Pharmacology and Therapeutics
Which drug combination carries the greatest risk of QT prolongation and torsades de pointes?
- Metformin and glipizide
- Azithromycin and ondansetron Correct answer.
- Amoxicillin and paracetamol
- Loratadine and saline nasal spray
Explanation
Azithromycin and ondansetron both delay cardiac repolarization by blocking the rapid delayed rectifier potassium current. Combining them produces additive QT prolongation and increases the risk of torsades de pointes, particularly with hypokalemia or bradycardia.
Question 15Pharmacology and Therapeutics
Flumazenil must be used cautiously in benzodiazepine overdose mainly because it can:
- Precipitate seizures, especially in chronic benzodiazepine users Correct answer.
- Cause profound hypoglycemia
- Irreversibly block GABA-A receptors
- Precipitate opioid withdrawal
Explanation
Flumazenil competitively antagonizes the benzodiazepine binding site on the GABA-A receptor. Removing benzodiazepine-mediated inhibition can provoke seizures in patients with chronic benzodiazepine use, co-ingestion of proconvulsant drugs, or underlying seizure disorders.
Question 16Pharmacology and Therapeutics
Which adverse effect is most characteristic of empagliflozin?
- Hypoglycemia when used as monotherapy
- Weight gain with fluid retention
- Hyperkalemia requiring potassium binders
- Genital mycotic infections Correct answer.
Explanation
SGLT2 inhibitors increase urinary glucose excretion, which promotes fungal growth in the genital tract and causes vulvovaginal candidiasis or balanitis. They also cause mild weight loss and carry a low intrinsic risk of hypoglycemia when used alone.
Question 17Pharmacology and Therapeutics
A patient stable on lithium develops vomiting and diarrhea during gastroenteritis. Which action is most appropriate?
- Hold lithium and urgently measure serum lithium and electrolytes Correct answer.
- Increase the lithium dose to compensate for losses
- Reassure the patient, because lithium levels are unaffected by dehydration
- Add a thiazide diuretic to stabilize lithium levels
Explanation
Lithium is eliminated by the kidney and is reabsorbed in the proximal tubule alongside sodium. Volume depletion increases proximal sodium and lithium reabsorption, raising serum lithium concentrations and risking toxicity, so the drug should be held and levels checked promptly.
Question 18Pharmacology and Therapeutics
A patient taking sertraline is prescribed tramadol. Which findings most suggest serotonin syndrome?
- Bradycardia, hypotension, and hypothermia
- Dry skin, constipation, and urinary retention
- Agitation, hyperthermia, clonus, and hyperreflexia Correct answer.
- Miosis, bradypnea, and sedation
Explanation
Serotonin syndrome results from excessive serotonergic activity and presents with altered mental status, autonomic hyperactivity, and neuromuscular excitation such as clonus and hyperreflexia. Tramadol inhibits serotonin reuptake and can precipitate this when combined with an SSRI.
Question 19Pharmacology and Therapeutics
Why should doxycycline be separated from calcium or iron supplements by at least two hours?
- Calcium increases hepatic metabolism of doxycycline
- Divalent cations chelate tetracyclines and reduce their absorption Correct answer.
- Iron enhances renal excretion of doxycycline
- Supplements increase the risk of photosensitivity
Explanation
Tetracyclines form insoluble chelate complexes with polyvalent cations such as calcium, magnesium, iron, and aluminium. These complexes are poorly absorbed, so doses must be separated from supplements, antacids, and dairy products.
Question 20Pharmacology and Therapeutics
Grapefruit juice raises plasma concentrations of some dihydropyridine calcium channel blockers because it:
- Induces hepatic CYP2C9 activity
- Inhibits intestinal CYP3A4-mediated first-pass metabolism Correct answer.
- Displaces the drug from albumin binding sites
- Increases gastric pH and drug ionization
Explanation
Furanocoumarins in grapefruit juice irreversibly inhibit CYP3A4 in the intestinal wall, reducing presystemic metabolism of substrates such as felodipine and nifedipine. Systemic bioavailability rises, which can cause hypotension and flushing.
Question 21Pharmacology and Therapeutics
A patient with digoxin toxicity has a serum potassium of 6.8 mmol/L, bradycardia, and ventricular arrhythmia. Which therapy is most specific?
- Charcoal hemoperfusion
- Intravenous calcium chloride
- Oral sodium polystyrene sulfonate alone
- Digoxin-specific antibody fragments Correct answer.
Explanation
Digoxin-specific Fab fragments bind digoxin in the circulation and tissue, neutralizing its inhibition of the sodium-potassium ATPase and reversing both the arrhythmia and the hyperkalemia. Hyperkalemia in this setting reflects extracellular potassium shift and is a marker of severe toxicity.
Question 22Pharmacology and Therapeutics
For serious MRSA infections, the preferred pharmacokinetic target for intravenous vancomycin is:
- A peak concentration of 40 to 60 mg/L
- A trough concentration of 5 to 10 mg/L
- Time above the MIC for 100 percent of the dosing interval
- An AUC24/MIC ratio of 400 to 600 mg·h/L Correct answer.
Explanation
Vancomycin killing is AUC-dependent, and an AUC24/MIC of 400 to 600 mg·h/L correlates best with efficacy while limiting nephrotoxicity. Current guidance favors AUC-guided dosing over trough-only monitoring for serious infections.
Question 23Pharmacology and Therapeutics
Which agent specifically reverses the anticoagulant effect of dabigatran?
- Protamine sulfate
- Andexanet alfa
- Idarucizumab Correct answer.
- Vitamin K
Explanation
Idarucizumab is a humanized monoclonal antibody fragment that binds dabigatran with high affinity and neutralizes its thrombin-inhibiting activity. Andexanet alfa is used for factor Xa inhibitors, and protamine reverses heparin.
Question 24Pharmacology and Therapeutics
A patient is stable on phenytoin 300 mg daily with a level of 12 mg/L. The dose is increased to 400 mg daily and the level rises to 28 mg/L. Which explanation is most likely?
- Phenytoin absorption increases linearly with dose and accounts for the rise
- Phenytoin has a very short half-life, requiring frequent dose adjustment
- Phenytoin metabolism is saturable, so small dose increases produce disproportionate rises in concentration Correct answer.
- The result must be a laboratory error because concentrations should double
Explanation
Phenytoin is metabolized by a capacity-limited hepatic enzyme system, so at therapeutic concentrations elimination shifts from first-order toward zero-order kinetics. Once the pathway is saturated, a modest dose increase produces a much larger proportional increase in serum concentration, predisposing to toxicity.
Question 25Pharmacology and Therapeutics
Six days after starting unfractionated heparin, a patient's platelet count falls from 280 to 90 x 10^9/L and new arterial thrombosis develops. Which action is correct?
- Switch to low-molecular-weight heparin
- Transfuse platelets and continue heparin therapy
- Continue heparin and monitor the platelet count daily
- Stop heparin and start a non-heparin anticoagulant such as argatroban Correct answer.
Explanation
This presentation is consistent with heparin-induced thrombocytopenia, an immune reaction in which antibodies activate platelets and cause thrombosis rather than bleeding. Heparin must be stopped immediately and a non-heparin anticoagulant started, because platelet transfusions and heparin products can worsen thrombosis.
Question 26Pharmacology and Therapeutics
Which medicine is the first-line treatment for an adult with anaphylaxis?
- Oral prednisolone
- Nebulised salbutamol
- Intramuscular adrenaline
- Intravenous chlorphenamine Correct answer.
Explanation
Intramuscular adrenaline into the anterolateral thigh is the only intervention that reverses the alpha-mediated vasodilatation and oedema, supports the heart and bronchodilates. Antihistamines and corticosteroids act too slowly and do not correct airway obstruction or shock.
Question 27Pharmacology and Therapeutics
Which of the following is a low molecular weight heparin?
- Argatroban
- Alteplase
- Fondaparinux
- Enoxaparin Correct answer.
Explanation
Low molecular weight heparins are depolymerised fragments of unfractionated heparin, of which enoxaparin, dalteparin and tinzaparin are the common examples. They act mainly through inhibition of factor Xa with less effect on thrombin.
Question 28Pharmacology and Therapeutics
A patient started on ramipril develops a persistent dry cough. Which mechanism explains this?
- Accumulation of bradykinin in the airways Correct answer.
- Histamine release from airway mast cells
- Direct stimulation of the cough centre in the medulla
- Blockade of beta-2 adrenoceptors in the airway
Explanation
Angiotensin converting enzyme also degrades bradykinin and substance P, so its inhibition allows these mediators to accumulate in the respiratory tract and provoke cough. Substituting an angiotensin receptor blocker usually resolves the symptom because it does not affect bradykinin breakdown.
Question 29Pharmacology and Therapeutics
Simvastatin lowers LDL cholesterol primarily by inhibiting which enzyme?
- Proprotein convertase subtilisin/kexin type 9
- Cholesteryl ester transfer protein
- HMG-CoA reductase Correct answer.
- Lipoprotein lipase
Explanation
Statins competitively inhibit HMG-CoA reductase, the rate-limiting enzyme of hepatic cholesterol synthesis. The fall in intracellular cholesterol upregulates LDL receptors, increasing clearance of LDL from plasma.
Question 30Pharmacology and Therapeutics
Which of the following is a GLP-1 receptor agonist?
- Pioglitazone
- Sitagliptin
- Acarbose
- Semaglutide Correct answer.
Explanation
Semaglutide, dulaglutide and liraglutide are incretin mimetics that activate the GLP-1 receptor, increasing glucose-dependent insulin release and slowing gastric emptying. They also suppress appetite and promote weight loss.
Question 31Pharmacology and Therapeutics
Which statement best describes the antiplatelet action of low-dose aspirin?
- It inhibits phospholipase A2 in the platelet membrane
- It reversibly blocks cyclo-oxygenase-2 in platelets
- It irreversibly acetylates platelet cyclo-oxygenase-1 Correct answer.
- It blocks thromboxane A2 receptors on platelets
Explanation
Aspirin acetylates a serine residue on cyclo-oxygenase-1 in platelets, and because platelets cannot synthesise new enzyme the effect lasts for their lifespan of about 7 to 10 days. This suppresses thromboxane A2 production and platelet aggregation.
Question 32Pharmacology and Therapeutics
Long-term metformin use is associated with deficiency of which vitamin?
- Folate
- Vitamin B12 Correct answer.
- Vitamin D
- Thiamine
Explanation
Metformin interferes with calcium-dependent absorption of vitamin B12 in the terminal ileum, and deficiency may appear after several years of therapy. Levels should be checked if anaemia or peripheral neuropathy develops.
Question 33Pharmacology and Therapeutics
Why is carbidopa added to levodopa in Parkinson's disease?
- It increases dopamine release from surviving nigrostriatal neurons
- It slows the hepatic clearance of levodopa by CYP3A4
- It inhibits peripheral aromatic L-amino acid decarboxylase Correct answer.
- It blocks peripheral dopamine receptors to reduce nausea
Explanation
Carbidopa does not cross the blood-brain barrier and blocks decarboxylation of levodopa in the periphery. More levodopa therefore reaches the brain, and less dopamine is formed outside it, reducing nausea, vomiting and cardiac stimulation.
Question 34Pharmacology and Therapeutics
Which drug is the first-line treatment for a child with newly diagnosed absence seizures and no other seizure type?
- Carbamazepine
- Ethosuximide Correct answer.
- Phenytoin
- Gabapentin
Explanation
Ethosuximide blocks T-type calcium channels in thalamic neurons, the pacemaker current responsible for the three-hertz spike-and-wave discharge of absence epilepsy. Valproate is an alternative when generalised tonic-clonic seizures coexist.
Question 35Pharmacology and Therapeutics
Which is the most appropriate initial treatment for an acute attack of gout in a patient with normal renal function?
- Low-dose aspirin for its anti-inflammatory action
- Allopurinol started at a high dose during the attack
- Naproxen, or colchicine if NSAIDs are unsuitable Correct answer.
- Probenecid to increase renal uric acid excretion
Explanation
Acute gout is treated with an NSAID, colchicine or a short course of glucocorticoid to control inflammation. Urate-lowering therapy is not started during an acute attack because rapid shifts in urate can prolong or worsen it, though an existing regimen is continued.
Question 36Pharmacology and Therapeutics
A patient with heart failure taking lisinopril is started on spironolactone. Which laboratory value requires the closest monitoring?
- Serum calcium
- Serum potassium Correct answer.
- Serum phosphate
- Serum sodium
Explanation
Spironolactone blocks aldosterone and reduces renal potassium excretion, while ACE inhibitors reduce aldosterone production, so the two together carry a substantial risk of hyperkalaemia. Potassium and creatinine should be checked at baseline, after one week and after one month.
Question 37Pharmacology and Therapeutics
Which monitoring is essential during long-term amiodarone therapy?
- Quarterly serum calcium, phosphate and magnesium
- Thyroid function, liver enzymes and lung function Correct answer.
- Monthly serum amylase with urinary catecholamines
- Annual plasma metanephrines and serum cortisol
Explanation
Amiodarone is rich in iodine, has a very long half-life and accumulates in tissue, so thyroid dysfunction, hepatotoxicity, pulmonary fibrosis and corneal deposits are the main long-term hazards. Baseline and periodic thyroid function, liver enzymes and pulmonary assessment are therefore required.
Question 38Pharmacology and Therapeutics
Clopidogrel is a prodrug that must be converted to its active metabolite by which enzyme?
- CYP3A4
- CYP2C19 Correct answer.
- Plasma pseudocholinesterase
- CYP2D6
Explanation
Most clopidogrel is hydrolysed by esterases to an inactive acid, and the remainder undergoes two oxidative steps, the key one mediated by CYP2C19, to form the active thiol. Poor metabolisers and patients taking strong CYP2C19 inhibitors such as omeprazole may have reduced antiplatelet effect.
Question 39Pharmacology and Therapeutics
Why are patients observed for several hours after naloxone is given for opioid overdose?
- Naloxone has a much longer half-life than most opioids
- Naloxone can provoke a delayed withdrawal seizure
- Naloxone wears off before the opioid, allowing renarcotisation Correct answer.
- Naloxone accelerates hepatic metabolism of opioids after one hour
Explanation
Naloxone has a plasma half-life of roughly one hour, which is shorter than that of methadone and of many sustained-release opioid formulations. As the antagonist effect fades, residual opioid can cause recurrent respiratory depression, so observation or an infusion is needed.
Question 40Pharmacology and Therapeutics
A 65-year-old woman is starting prednisolone 20 mg daily for 3 months. Which is the most appropriate bone protection?
- Cholecalciferol alone
- Dietary potassium supplementation
- Alendronate with calcium and vitamin D Correct answer.
- A thiazide diuretic
Explanation
Glucocorticoid-induced osteoporosis develops rapidly, so patients expected to take more than 7.5 mg prednisolone daily for over three months need bone-protective therapy. A bisphosphonate together with calcium and vitamin D is standard, supported by bone density assessment.
Question 41Pharmacology and Therapeutics
Which of the following should be avoided in a patient with G6PD deficiency?
- Nitrofurantoin Correct answer.
- Doxycycline
- Ceftriaxone
- Amoxicillin
Explanation
Glucose-6-phosphate dehydrogenase deficiency leaves red cells unable to regenerate reduced glutathione, so oxidant drugs cause haemolysis. Nitrofurantoin, primaquine, dapsone, sulfonamides and chloramphenicol are the classic precipitants.
Question 42Pharmacology and Therapeutics
A man taking tamsulosin is scheduled for cataract surgery. Which action is most appropriate?
- Stop tamsulosin at least 24 hours before the operation
- Substitute finasteride for two weeks before the operation
- Warn the ophthalmologist about floppy iris syndrome Correct answer.
- Give preoperative atropine eye drops to both eyes
Explanation
Alpha-1 blockers cause loss of tone in the iris dilator muscle, producing intraoperative floppy iris syndrome with a risk of iris prolapse and capsule rupture. Stopping the drug shortly before surgery does not reliably prevent it, so the surgeon must be informed so that modified techniques can be used.
Question 43Pharmacology and Therapeutics
Which is the first-line drug for convulsive status epilepticus in the emergency department?
- Intramuscular haloperidol
- Intravenous lorazepam Correct answer.
- Oral carbamazepine
- Intravenous phenytoin
Explanation
A benzodiazepine is the first-line agent, with intravenous lorazepam or, when access is unavailable, intramuscular midazolam. Phenytoin, levetiracetam or valproate are second-line agents added if seizures persist.
Question 44Pharmacology and Therapeutics
Which vitamin is given with isoniazid to prevent peripheral neuropathy?
- Thiamine
- Folic acid
- Riboflavin
- Pyridoxine Correct answer.
Explanation
Isoniazid inhibits pyridoxal kinase and depletes pyridoxine, producing a dose-related peripheral neuropathy. Supplements are routinely given to patients at higher risk, including those who are malnourished, pregnant, diabetic or living with HIV.
Question 45Pharmacology and Therapeutics
A breastfed infant whose mother is taking codeine becomes drowsy and feeds poorly. The most likely explanation is:
- Codeine is actively secreted into breast milk by P-glycoprotein
- The infant has induced CYP3A4 activity from chronic codeine exposure
- The mother is a CYP2D6 poor metaboliser with codeine accumulation
- The mother is a CYP2D6 ultrarapid metaboliser Correct answer.
Explanation
Codeine is a prodrug converted to morphine by CYP2D6, and ultrarapid metabolisers generate unusually high morphine concentrations that pass into breast milk. The infant develops opioid toxicity with sedation, poor feeding and risk of respiratory depression.
Question 46Pharmacology and Therapeutics
Which test should be performed before starting abacavir?
- HLA-B*5701 genotyping Correct answer.
- Thiopurine methyltransferase activity
- Glucose-6-phosphate dehydrogenase assay
- Serum beta-2 microglobulin
Explanation
Abacavir hypersensitivity is strongly associated with the HLA-B*5701 allele. Screening and withholding the drug from carriers reduces the incidence of this potentially fatal reaction, and rechallenge after a reaction is contraindicated.
Question 47Pharmacology and Therapeutics
A patient on phenytoin has a total phenytoin level of 8 mg/L but shows signs of toxicity. Concurrent valproate is most likely to explain this by:
- Increasing active renal tubular secretion of unchanged phenytoin
- Displacing phenytoin from albumin and slowing its metabolism Correct answer.
- Inducing hepatic CYP2C9 and so increasing phenytoin clearance
- Reducing the extent of phenytoin absorption from the gut
Explanation
Valproate both displaces phenytoin from plasma protein and inhibits its metabolism, so the free fraction rises even when the total concentration is within or below the reference range. Free phenytoin should be measured, and hypoalbuminaemia produces the same pattern.
Question 48Pharmacology and Therapeutics
A patient stable on digoxin is started on verapamil. Which interaction is most likely?
- Verapamil induces intestinal P-glycoprotein and lowers digoxin levels
- Verapamil reduces the extent of digoxin absorption from the gut
- Verapamil displaces digoxin from its binding sites in skeletal muscle
- Verapamil inhibits P-glycoprotein, raising digoxin levels Correct answer.
Explanation
Verapamil, amiodarone and quinidine inhibit P-glycoprotein, which mediates both intestinal efflux and renal elimination of digoxin, so serum concentrations rise. The combination also adds to AV nodal depression, so the digoxin dose is usually reduced and levels monitored.
Question 49Pharmacology and Therapeutics
Which combination of factors supports reducing apixaban to 2.5 mg twice daily for stroke prevention in atrial fibrillation?
- An eGFR below 60 mL/min/1.73 m2 together with previous gastrointestinal bleeding
- Age ≥65 years together with treated hypertension and preserved renal function
- Concurrent low-dose aspirin together with poorly controlled type 2 diabetes mellitus
- Age ≥80 years, weight ≤60 kg, or creatinine ≥1.5 mg/dL, with two present Correct answer.
Explanation
The reduced apixaban dose is used when at least two of three criteria are met: age 80 years or older, body weight 60 kg or less, and serum creatinine 1.5 mg/dL or more. Patients meeting none or only one criterion receive the standard 5 mg twice daily.
Question 50Pharmacology and Therapeutics
A 68-year-old man with atrial fibrillation is stable on warfarin with an INR of 2.4. His physician prescribes a 7-day course of trimethoprim-sulfamethoxazole for a urinary tract infection. Which management plan is most appropriate?
- Continue the current regimen and recheck the INR at the next routine visit
- Monitor the INR closely and reduce the warfarin dose Correct answer.
- Switch warfarin to enoxaparin for the duration of the antibiotic course
- Increase the warfarin dose and recheck the INR in two weeks
Explanation
Trimethoprim-sulfamethoxazole inhibits CYP2C9, the enzyme that metabolises warfarin's more potent S-enantiomer, and can also displace warfarin from albumin, so anticoagulant effect rises within days. The safe approach is to anticipate the interaction by checking the INR soon after starting the antibiotic and pre-emptively lowering the warfarin dose, with further checks as needed.