Renal Flashcards
Azathioprine
Use: maintenance of UC/Crohn’s, DMARD in autoimmune conditions when not responding to steroids, prevent organ rejection in transplant
MOA: pro-drug, the main metabolite is 6-mercaptopurine. Inhibits purine synthesis, inhibiting DNA and RNA replication. Metabolism and elimination involves xanthine oxidase and TPMT.
Adverse effects: bone marrow suppression (results in leukopenia and increased risk of infection), nausea, hypersensitivity reactions, vino-occlusive disease, hepatotoxicity, increased risk of lymphoma
Cautions: TMPT phenotypic needs to be done prior to starting. Hypersensitivity reactions should prompt cessation. Dosage reduced in hepatic and renal impairment. Do not initiate treatment in pregnancy.
Interactions: do not prescribe with xanthine oxidase inhibitors (allopurinol) as reduce azathioprine metabolism. Risk of leukopenia increases when prescribe with other myelosuppressive drugs. May reduce effect of warfarin
Cyclophosphamide (alkylating agent)
Use: severe RA, chemotherapy, immune-based renal disease (SLE, GN, Wegener’s)
MOA: 1) attach alkyl groups to DNA bases (preventing DNA synthesis and RNA transcription), 2) DNA damage by forming cross-links, 3) mispairing nucleotides, leading to mutations
Hepatic metabolism
Adverse effects: agranulocytosis, alopecia, anaemia, asthenia, BM disorder, cystitis, fever, HUS, haemorrhage, hepatic disorder, immunosuppression, increased infection risk, mucosal abnormalities, neutropenia
Cautions: avoid in acute porphyria, diabetes, haemorrhage cystitis, previous or concurrent mediastinal irradiation, pregnancy. Caution in hepatic and renal impairment.
Interactions: lots! Vaccinations
Ciclosporin
Use: severe autoimmune disease (UC, RA, atopic dermatitis, psoriasis), transplant or BM immunosuppression, nephrotic syndrome
MOA: calciurie inhibitor, inhibiting T cell activation
Adverse effects: eye inflammation, blurred vision, reduced appetite, diarrhoea, electrolyte imbalance, fatigue, fever flushing, GI upset, hair changes, headaches, hepatic disorder, hyperglycaemia, hyperlipidaemia, HTN, hyperuricaemia, leucopenia, muscle complaints, nausea, peptic ulcer, renal impairment, seizure, skin reactions
Cautions: glaucoma (when used by eye), monitor renal function, hyperuricaemia, active herpes simplex infection, Staph aureus skin infections, lymphoproliferative disorder, malignancy. Avoid in pregnancy, breast feeding and severe renal and hepatic impairment
Interactions: Pomelo juice increases cyclosporin exposure, purple grape juice decreases exposure
Tacrolimus
Use: MOA: Adverse effects: Cautions: Interactions: Transplant immunosuppresion
Trimethoprim
Use: acute lower UTI and prophylaxis of recurrent UTI
Broad activity against gram+ and gram- bacteria (particularly E.coli) but limited by resistance
MOA: inhibits bacterial folate synthesis, slowing bacterial growth (bacteriostasis). Resistance mechanisms incl. reduced IC antibiotic accumulation and reduced sensitivity of target enzymes.
Adverse effects: GI upset, skin rash, severe hypersensitivity reactions, megaloblastic anaemia, leucopenia, thrombocytopenia, hyperkalaemia
Cautions: contraindicated in T1 of pregnancy (NTDs, cleft lip/palate). Use cautiously in folate deficiency, renal impairment, neonates, elderly, HIV infection
Interactions: K+ elevating drugs (ACEi, ARBs, aldosterone antagonists), folate antagonists (methotrexate), drugs that increased folate metabolism (phenytoin)
Nitrofurantoin
Use: acute uncomplicated lower UTI, prophylaxis of recurrent in UTI
Active against most organisms which cause uncomplicated UTIs incl. E.coli and Staph saprophyticus
MOA: metabolised in bacterial cells by nitrofuran reductase. The active metabolite damages bacterial DNA, causing cell death.
Adverse effects: GI upset, immediate and delayed hypersensitivity reactions, turns urine dark yellow/brown. Less commonly causes chronic pulmonary reactions, hepatitis, peripheral neuropathy (due to prolonged use). Can cause haemolytic anaemia in neonates.
Cautions: do not prescribe in pregnant women close to term, babies in first 3 months of life, or renal impairment. Chronic use increases risk of adverse effects.
Interactions: none
Co-amoxiclav (penicillin)
Use: severe, resistant and hospital-acquired infections
Broad spectrum activity against gram+ and gram- cocci and bacilli. However, resistance is increasing. Adding clavulanic acid (beta lactamase inhibitor) restores activity against amoxicillin-resistant strains.
MOA: inhibits enzymes which cross-like peptidoglycan in the cell wall, weakening the cell wall causing cell swelling, lysis and death. Contain a beta-lactam ring which is responsible for bactericidal activity.
Adverse effects: GI upset, antibiotic assoc. colitis, allergy, acute liver injury (self-limiting if treatment is stopped)
Cautions: hx of allergy to penicillin. Use with caution in those at risk of C.diff infection, hx of penicillin-assoc. liver injury and renal impairment (dose reduction).
Interactions: enhance anticoagulant effect of warfarin
Ciprofloxacin (quinolone)
Use: second/third-line treatment (rapid resistance and assoc. with C.diff infection) for UTI (gram-), severe gastroenteritis (Shigella, Campylobacter), LRTI
Broad spectrum particularly against gram-, has significant activity against Pseudomonas aeruginosa
MOA: inhibit DNA synthesis in bacteria. Resistance via preventing IC accumulation of the drug or mutations in target enzymes. Resistance genes spread horizontally between bacteria by plasmids.
Adverse effects: GI upset, immediate and delayed hypersensitivity reactions, neurological effects (lower seizure threshold and hallucinations), inflammation and rupture of tendons, prolongation of QT interval, C.diff colitis
Cautions: use in caution in those at risk of seizures, children and those with other RFs for QT prolongation (cardiac disease, electrolyte disturbance)
Interactions: drugs containing divalent ions (calcium, antacids) reduce absorption/efficacy. Inhibits CYP450 enzymes increasing risk of toxicity of drugs (theophylline). Co-prescription of NSAIDs increases risk of seizures, prednisolone increases risk of tendon rupture. Prescribe in caution with drugs prolonging QT interval (amiodarone, antipsychotics, quinine, macrolide antibiotics, SSRIs)
Gentamicin (aminoglycoside)
Use: severe infections (particularly those of gram- aerobes incl. pseudomonas aeruginosa) e.g. severe sepsis, pyelonephritis, complicated UTI, biliary sepsis, endocarditis. Topical preparation used for bacterial skin, eye or external ear infection.
Main activity is against gram- aerobic bacteria. Inactive against strep and anaerobes.
MOA: bind irreversibly to bacterial ribosomes and inhibit protein synthesis. They are bactericidal. Resistance may develop through reduced cell membrane permeability to ahminoglycosides to acquisition of enzymes which modify the antibiotic. Penicillins weaken the cell wall and so enhance amino glycoside activity by enhancing uptake.
Adverse effects: nephrotoxicity and ototoxicity
Cautions: need to monitor plasma drug concentrations with dose adjustment to prevent renal, cochlear and vestibular damage (esp. in neonates, elderly and those with renal impairment). Do not give to patients with myasthenia graves (can impair neuromuscular transmission)
Interactions: toxicity if co-prescribed with loop diuretics or vancomycin, nephrotoxicity is more likely when co-prescribed with chemo, cephalosporins or vancomycin
