Drug Interactions and Adverse Effects Flashcards

A patient starting HAART for HIV is told about immune reconstitution inflammatory syndrome (IRIS). When does IRIS typically occur?

Answer: Within 4–8 weeks of starting antiretroviral therapy as the immune system recovers and responds to subclinical infections

IRIS occurs weeks to months after starting effective ART when the recovering immune system mounts a vigorous inflammatory response to previously subclinical or partially treated opportunistic infections (e.g., TB, MAC, PCP, CMV). Patients with very low CD4 count at baseline are at highest risk.

A pharmacist identifies that a patient on sirolimus (rapamycin) has been started on ketoconazole. What is the concern?

Answer: Ketoconazole strongly inhibits CYP3A4 and P-glycoprotein, causing massive increases in sirolimus levels — nephrotoxicity, thrombocytopenia risk

Sirolimus (mTOR inhibitor) has a narrow therapeutic index and is extensively metabolized by CYP3A4 and transported by P-glycoprotein. Ketoconazole (strong CYP3A4/P-gp inhibitor) increases sirolimus levels up to 10–20 fold, causing serious toxicity. Co-administration is contraindicated; if unavoidable, dramatic dose reduction and level monitoring are required.

A patient develops hypersensitivity syndrome (DRESS) 3 weeks after starting allopurinol. What is the most important risk factor for this reaction in the Saudi population?

Answer: HLA-B*5801 allele — strongly associated with allopurinol-induced SJS/TEN/DRESS in Asian and some Middle Eastern populations

HLA-B*5801 is strongly associated with severe cutaneous adverse reactions (SCAR) to allopurinol, including SJS, TEN, and DRESS. Prevalence of HLA-B*5801 is higher in Asian populations (Han Chinese, Thai, Vietnamese) and significant in some Middle Eastern populations. Pre-treatment genetic screening is recommended in high-prevalence populations.

A patient on warfarin starts St. John's Wort for depression. What is the expected INR change?

Answer: INR will decrease — St. John's Wort induces CYP2C9 and P-glycoprotein, increasing warfarin clearance

St. John's Wort is a potent inducer of CYP2C9, CYP3A4, and P-glycoprotein. For warfarin (CYP2C9 substrate), induction increases warfarin clearance, reducing plasma levels and INR — potentially causing therapeutic failure (stroke in AF). Patients on warfarin must avoid St. John's Wort.

A patient develops peripheral neuropathy after 6 months of isoniazid therapy. What is the cause and treatment?

Answer: INH competitively inhibits pyridoxine (vitamin B6) metabolism — treat with pyridoxine supplementation

Isoniazid inhibits pyridoxine (vitamin B6) phosphokinase and competes with pyridoxal phosphate, causing functional B6 deficiency. This leads to peripheral neuropathy (paresthesias, burning pain). Preventive pyridoxine supplementation (25–50 mg/day) is co-prescribed, especially in at-risk groups (elderly, diabetics, malnourished, pregnant women).

A patient on tacrolimus after kidney transplant develops diabetes mellitus. What is the mechanism?

Answer: Calcineurin inhibitors impair pancreatic beta-cell function and reduce insulin secretion — new-onset diabetes after transplant (NODAT)

New-onset diabetes after transplant (NODAT) occurs in 10–40% of patients on calcineurin inhibitors (tacrolimus > cyclosporine). The mechanism involves impaired insulin gene transcription (calcineurin inhibition blocks IL-2 signaling in beta cells) and reduced insulin secretion. Risk is higher with tacrolimus than cyclosporine.