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RA Pharmacology

Pharmacology of drugs used in RA

QuestionAnswer
What is the MOA of hydroxychloroquine? Decreases IL-1 synthesis, phospholipase A2 (no arachidonic acid) and chemotaxis
What are the key side effects associated with hydroxychloroquine? Retinal toxicity, retina detachment, blurred vision, headache, dizzyness, lichenoid skin eruptions, psoriasis, alopecia, hair bleaching. Can cause T wave and QRS abnormalities in combination with other drugs.
What is the MOa of methotrexate? Folic acid antagonist - dihydrofolate reductase inhibitor Prevents regeneration of tetrahydrofolate from dihydrofolate, preventing cell proliferation Reduces 5-lipoxygenase pathway (leucocytes) and interluekin 1 Auto immune supression
What are some of the toxicity issues associated with methotrexate? Myleosuppression, thrombocytopenia, mucositis, pneumonitis and pulmonary fibrosis, embryos, hepatic fibrosis and cirrhosis in chronic doses, caution with poor renal function and combination with other renallly cleared drugs
What else is methotrexate used for? Anticancer agent for all childhood cancers, choriocarcinomas, osteosarcomas, brain, breast, supp to non-hodgkin's lymphoma, oragn transplants, crohns, psoriasis, ectopic pregnancy
Which one of the TNF-a inhibitors isn't a MAB? Eternacept
What is the MOA of TNF-a inhibitors? Bind to TNF-a and inhibit its activity
What is the dose and frequency of etanercept? 50mg once a week SC or 25mg SC twice a week
What is the dose and frequency of infliximab? 3mg/kg via IV infusion for adults every 4-8 weeks. Plasma half life over 1 week.
True or false: adalimumab is a fully humanised MAB and is also used to treat psoriasis and IBD? True
What is the dose and frequency of adalimumab? 40mg SC injection every 2 weeks. Plasma half life is 2 weeks
What is the dose and frequency of golimumab? 50mg SC every month. Plasma half life 2 weeks.
What is the dose and frequency of certolizumab? 400mg SC to start, then 200mg SC every 2 weeks or 400mg every 4 weeks.
True or false: all of the TNF-a inhibitors/cytokine modulators are classified as clinically equivalent. True
What is the MOA of anakinra? It is a IL-1 receptor antagonist, neutralising the effects of IL-1.
What is the dose and frequency of anakinra? 100mg SC daily
True or false: you can combine anakinra with TNF-a drugs? False
What is the MOA of Tocilizumab? It is a IL-6 targeting antibody, blocking the effects of IL-6 by blocking the IL-6 receptor.
What is the dose and frequency of tocilizumab? 8mg/kg via IV infusion every 4 weeks.
What are the key monitorings for tocilizumab? AST and ALT levels, LDL levels
Name the JAK kinase inhibitors Tofacitinib and baricitinib
What is the MOA of the Jak kinase inhibitors? Stops the binding and phosphorylation of the Stat protein to JAK, preventing cell proliferation of pro-inflammatory cytokines. This inhibits cell proliferation and activation of T lymphocytes
What is the dose and frequency of the jak kinase inhibitors? T: 5mg tabs bd B: 2-4mg 1 d
What metabolic substrates are the Jak kinase inhibitors? CYP3A4 and CYP2C19
How do gold salts induce remission in RA? Decrease lymphocyte proliferation, decrease release and activity of lysosomal enzymes, decrease production of O2 radicals, decrease chemotaxis from neutrophils, decrease mast cell mediator release.
Where do gold salts accumulate? In synovial joints and circulating macrophages. Accumulates and builds to a critical threshold and then has an effect.
What is the MOA of D-Penicillamine? Decreases collagen formation, rheumatoid factor and immune complex in the synovial fluid and blood.
True or False: Leflunomide is a pro-drug True
What is the mechanism of action of leflunomide? De novo pyrimidine synthesis inhibitor. (Blocks pyrimidine synthesis)
What is the dose and frequency of leflunomide? Loading dose of 100mg d for 3 days, then 10-20mg d
Which drug is a recombinant of E.Coli? Anakinra
Which JAKs do tofacitinib and baricitinib inhibit? T: JAK 1,2,3 B: JAK 1, 2
How is D-Penicillime excreted? 80% excreted renally
What are the ADR's of D-penicillime? GI, taste disturbances, nausea, vomiting, anorexia, leukopenia, aplastic anaemia, rashes, stomatitis, proteinuria
What are the precautions with leflunomide? Inhibits CYP2C9-impacts phenytoin and warfarin, can cause liver toxicity/liver failure if given with other drugs that can damage the liver (e.g.methotrexate), highly teratogenic, 6 month wash out if breast feeding
What are the ADR's of leflunomide? NVD, hair loss, weight loss, weakness, headache, dizziness, pneumonia, peripheral neuropathy
What is the MOA of Indomethacin? Non selective COX inhibitor, has central analgesic effects, inhibits PMN motility, supresses uterine contractions, accelerates closure of ducus arteriosus in neonates.
What are the ADR's of Indomethacin? Usual NSAID ADR's, plus headache, vertigo, dizziness and confusion.
True or false: Indomethacin needs to be taken with food. True Has high toxicity-use is limited.
Created by: LDM
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