PHAR 442 Lecture 1: 1. DMARDs and bDMARDs

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28 Jan 2017
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**(cid:449)e do(cid:374)(cid:859)t ha(cid:448)e to k(cid:374)o(cid:449) the pk of a(cid:374)y drugs. Ability to reach therapeutic concentrations in joint capsules w/o reaching toxic serum levels. Drug of choice used in 50-70% of ra patients at lower doses than in cancer (anti-inflammatory in ra at lower doses) Inhibition of: aminoimidazolecarboxamide (aicar) transformylase inhibits degradation of adenosine = anti-inflammatory effects, proinflammatory cytokine production, dihydrofolate reductase = purine synthesis = anti-proliferative effects of immune cells, thymidylate synthetase with secondary effects on polymorphonuclear chemotaxis. Po, sc, weekly weekly dosing is important to catch because some doctors still accidentally put daily dosing could result in fatal overdose. Gi: diarrhea, n/v (cid:1005)(cid:1004)%, hepatoto(cid:454)icit(cid:455) (cid:894) le(cid:895) (cid:1005)5%, cirrhosis (<1%) Folic acid deficiency: due to its dhf reductase inhibitory pathway. Supplement with folic acid 1-2 mg po od or folinic acid (leucovorin) 2. 5-5 mg po once/week (8-12 hrs after mtx) Pregnancy contraindicated because of the inhibition of the folic acid pathway.

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