MSK Flashcards
Hydroxychloroquine
Use: active RA, SLE, dermatological conditions worsened by sunlight
MOA: unknown. Interferes with malaria parasite’s ability to proteolyses Hb, preventing normal growth. Raises pH in human organelle, inhibiting Ag processing, interferes with MHC II, inhibits APC and reduces the inflammatory response.
Adverse effects: abdo pain, decreased appetite, diarrhoea, emotional lability, headache, nausea, skin reactions, vision disorder, vomiting. Toxic in OD.
Cautions: acute porphyria, diabetes, G6PD deficiency, maculopathy, myasthenia gravis, psoriasis, neuro disorder, GI disorder, pregnancy, hepatic impairment, renal impairment.
Interactions: absorption decreased by antacids and calcium carbonate. Decreases efficacy of some vaccines.
Leflunomide
Use: moderate-severe active RA
MOA: prodrug, MOA undetermined but thought to regulate autoimmune lymphocytes.
Adverse effects: abdo pain, accelerated hair loss, decreased appetite, asthenia, diarrhoea, dizziness, GI disorder, headache, leucopenia, nausea, oral disorder, paraesthesia, peripheral neuropathy, skin reactions, tendon disorder, vomiting, weight decreased
Cautions: anaemia, hx of TB, impaired BM function, leucopenia, thrombocytopenia
CI: serious infection, severe hypoproteinaemia, severe immunodeficiency
Interactions: risk of generalised infection with vaccines
Sodium aurothiomalate
Use: active progressive RA
MOA: unknown, but does inhibit PG synthesis
Adverse effects: lots
Cautions: elderly, eczema, hx of enterocolitis, hx of urticaria, pulmonary fibrosis
CI: exfoliative dermatitis, hx of blood disorder, hx of BM aplasia, SLE
Interactions: ACEi (increases risk of hypersensitivity)
Adalimumab
Use: plaque psoriasis, RA, psoriatic arthritis, ankylosing spondylitis, Crohn’s, UC, uveitis
MOA: binds to TNF-alpha and inhibits its interactions. Also lyses surface TNF-expressing cells. Reduces inflammatory and immune response.
Adverse effects: lots
Cautions: demyelinating disorder, malignancy, active infection, Hep B, TB
CI: moderate-severe HF, severe infection
Interactions: vaccines
Etanercept
Use: moderate-severe RA, active and progressive psoriatic arthritis, severe active ankylosing spondylitis, moderate-severe plaque psoriasis (all where other DMARDs have failed)
MOA: form of a TNF receptor which binds two TNF molecules and removes them from circulation. Reduces normal inflammatory and immune responses.
Adverse effects: cystitis, fever, hypersensitivity, increased risk of infection, pain, skin reactions, swelling
Cautions: TB, severe alcoholic hepatitis
CI: active infection, pregnancy and breast feeding
Interactions: vaccines
Infliximab
Use: severe active Crohn’s, severe active UC, RA (with methotrexate), ankylosing spondylitis, psoriatic arthritis, plaque psoriasis
MOA: monoclonal Ab which binds to TNF-alpha and prevents it interacting with its receptors. Results in downregulation of systemic and local pro-inflammatory cytokines, reduction of lymphocyte and leucocyte migration to sites of inflammation, induces apoptosis of TNF-producing cells, increase levels of NFkB inhibitors.
Adverse effects: abscess, alopecia, anaemia, arrhythmia, arthralgia, chills, constipation, decreased leucocyte, depression, diarrhoea, dizziness, fatigue, fever, GI discomfort, haemorrhage, headache, hepatic disorder, infection, nausea, neutropenia
Cautions: demyelinating disorder, malignancy, Hep B, TB
CI: moderate/severe HF, severe infection
Interactions: vaccines
Anakinra
Use: RA with methotrexate
MOA: binds competitively to IL-1 receptor, inhibiting action of elevated levels of IL-1 (which normally results in cartilage degradation and bone resorption)
Adverse effects: headache, infection, neutropenia, thrombocytopenia
Cautions: elderly, hx of asthma, hx of recurrent infection
CI: active infection, neutropenia, pre-existing malignancy
Interactions: any drug which increases risk of myelosuppression, vaccines
Tocilizumab
Use: moderate-severe RA (alone or with methotrexate), giant cell arteritis
MOA: binds IL-6 receptors, preventing IL-6 mediated inflammation
Adverse effects: abdo pain, conjunctivitis, cough, dizziness, dyslipidaemia, dyspnoea, GI disorder, headache, hypersensitivity, HTN, infection, leucopenia or neutropenia, peripheral oedema, skin reaction
Cautions: hx of diverticulitis/ulceration/recurrent infection, low neutrophil or platelet counts, TB, monitor dose with renal impairment
CI: neutropenia, severe active infection, pregnancy, hepatic impairment
Interactions: vaccines. Decreases exposure to warfarin, verapamil, theophylline, statin, phenytoin, -pines, diltiazem, Benzos
Abatacept
Use: moderate-severe RA, active psoriatic arthritis
MOA: selective costimulation modulator. Inhibits T cell activation by binding to CD80 and 86, inhibiting the delivery of second co-stimulatory signals required for activation of T cells.
Adverse effects: asthenia, cough, diarrhoea, dizziness, GI discomfort, headache, HTN, infection, oral ulceration, skin reaction, vomiting
Cautions: elderly
CI: severe infection, breast feeding, pregnancy
Interactions: vaccines,
Rituximab
Use: RA, Non-Hodgkin’s lymphoma, CLL, granulomatosis with polyangiitis and microscopic polyangiitis
MOA: monoclonal Ab which targets CD20 (expressed on B cell surface). It binds to CD20 and mediates B cell lysis.
Adverse effects: alopecia, anaemia, anaphylaxis, arthralgia, asthenia, conjunctivitis, constipation, cough, depression, diarrhoea, fever, headache, hypersensitivity, infection, MI, neutropenia, leucopenia, night sweats, vomiting
Cautions: hx of CVD, chemotherapy, hep B
CI: severe HF, uncontrolled heart disease
Interactions: other drugs which increase risk of myelosuppression, vaccines
Colchicine
Use: acute gout, short-term prophylaxis with allopurinol, prophylaxis of familial Mediterranean fever
MOA: unknown, but thought to disrupt inflammasome complex in monocytes and neutrophils, preventing release of IL-1 (mediates inflammation). Anti-mitotic as it binds in metaphase and prevents elongation of microtubules, stopping growth.
Adverse effects: abdo pain, diarrhoea, N&V
Cautions: cardiac disease, elderly, GI disease
CI: blood disorder, pregnancy, severe hepatic impairment, eGFR <10
Interactions: increased by amiodarone, aprepitant, cyclosporin, clarithryomycin, diltiazem, fluconazole, -nib. Increase risk of rhabdo with statin and vibrates.
Allopurinol
Use: prevent recurrent gout attacks, prevent uric acid and calcium oxalate renal stones, prevent hyperuricaemia and tumour lysis syndrome assoc. with chemo
MOA: inhibits xanthine oxidase, which usually metabolises xanthine (from purines) to uric acid. This lowers plasma uric acid and reduces the precipitation of uric acid in the joints/kidneys.
Adverse effects: starting this drug may trigger or worsen an acute attack of gout; this risk may be reduced by co-prescription of an NSAID or colchicine. Skin rash is a common reaction (mild or serious). Hypersensitivity syndrome may occur (fever, eosinophilia, lymphadenopathy and involvement of organs).
Cautions: dose reduction in severe renal or hepatic impairment
CI: starting the drug in an acute attack of gout, recurrent skin rash, severe hypersensitivity
Interactions: concurrent administration with azathioprine increases risk of toxicity. Co-prescription with ACEi or thiazides increases risk of hypersensitivity reactions, and with amoxicillin increases risk of skin rash
Febuxostat
Use: chronic hyperuricaemia in gout, prophylaxis and treatment of acute hyperuricaemia with initial chemo for haematological disease
MOA: xanthine oxidase inhibitor, decreasing serum uric acid.
Adverse effects: diarrhoea, gout aggravated, headache, hepatic disorder, nausea, oedema, skin reactions
Cautions: give NSAID or colchicine for 6 months after starting to avoid acute attack
CI: HF, IHD, CVD, thyroid disorder, transplant patients
Interactions: increases exposure to azathioprine and mercaptopurine
Rasburicase
Use: prophylaxis and treatment of acute hyperuricaemia, before and during initial chemo, for haematological malignancy and high tumour burden at risk of rapid lysis
MOA: catalyses oxidation of uric acid to an inactive and soluble metabolite
Adverse effects: diarrhoea, fever, headache, nausea, skin reactions, vomiting
Cautions: atopic allergies
CI: G6PD deficiency, pregnancy
