GOUT AND IMMUNOPHARMACOLOGY Flashcards
(28 cards)
What causes gout?
Increased uric acid due to overproduction (10%) or underexcretion (90%), leading to monosodium urate crystal deposition in joints and tissues
What enzyme does allopurinol inhibit and what is its effect?
Xanthine oxidase inhibitor; decreases uric acid synthesis
What are the key adverse effects of allopurinol?
Rash, hypersensitivity, GIT upset, interaction with azathioprine/mercaptopurine
What is colchicine’s mechanism of action?
Inhibits microtubule polymerization in neutrophils, reducing migration and inflammation
What is the maximum colchicine dose during acute gout?
2.5 mg in 24 hours; not more than 6 mg over 4 days
What drug interactions affect colchicine?
CYP3A4 and P-gp inhibitors increase toxicity risk (e.g. macrolides, cyclosporine)
What is probenecid’s mechanism and contraindication?
Inhibits URAT1 transporter, increasing uric acid excretion; contraindicated in renal failure, urate nephropathy
What is the MOA of glucocorticoids?
Bind cytoplasmic receptors → translocate to nucleus → bind GREs → inhibit cytokines, COX-2, phospholipase A2
Key side effects of long-term glucocorticoid use?
Osteoporosis, Cushingoid features, adrenal suppression, hypertension, diabetes, infections
Why taper glucocorticoids after long-term use?
To prevent adrenal insufficiency due to HPA axis suppression
Prednisone vs. prednisolone?
Prednisone is a prodrug; converted to active prednisolone in the liver
Examples of Glucocorticoids?
hydrocortisone
prednisone
prednisolone
methylprednisolone
dexamethasone
betamethasone
MOA, class and roles of cyclosporine and tacrolimus?
Calcineurin inhibitors; prophylaxis and treatment of transplant rejection; Inhibit calcineurin → block NFAT activation → ↓ IL-2 → ↓ T-cell activation
Pharmacokinetics of cyclosporine?
Low, variable oral bioavailability; CYP3A4 metabolism; excreted in bile
What is the main adverse effect of calcineurin inhibitors?
Nephrotoxicity; also hypertension, neurotoxicity, hyperglycaemia
Key counselling point for tacrolimus?
Avoid food at administration; therapeutic drug monitoring needed
MOA, class and roles of mycophenolate mofetil?
Antiproliferative agent; antimetabolite; Inhibits IMPDH → ↓ guanine synthesis → ↓ lymphocyte proliferation and function
What is the key adverse effect of mycophenolate?
Myelosuppression, GI upset, infections, teratogenic
MOA, class and role of sirolimus and everolimus?
mTOR inhibitors; antimetabolite; Bind FKBP-12 → inhibit mTOR → block cytokine-driven T-cell proliferation
Adverse effects of sirolimus/everolimus?
Hyperlipidaemia, mouth ulcers, myelosuppression, pneumonitis (sirolimus)
MOA of methotrexate?
Inhibits dihydrofolate reductase → ↓ thymidylate and purine synthesis → ↓ lymphocyte proliferation
Methotrexate toxicity and monitoring?
Hepatotoxicity, myelosuppression, stomatitis; monitor LFTs, FBC, U&E
Azathioprine metabolism and implication?
Converted to 6-MP then 6-TG; TPMT deficiency increases toxicity risk
Cyclophosphamide toxicity?
Hemorrhagic cystitis (acrolein), sterility, myelosuppression; use mesna + fluids
