Derm/Musc Drugs Flashcards
(67 cards)
Acetaminophen
What is the active metabolite
Agonist & inhibitor at what receptor?
Class: Weak COX Inhibitor
- Strong analgesic (non-opioid)
- Antipyretic
- Very weak antiinflammatory activity
Rx:
-Analgesia in children
AE:
-Fatal liver disease if overdose
Note: AM404 is active metabolite, which:
- Agonist at **TRPV1 channel **
- Agonist Cannabinoid CB1 receptor
- Inhibits endogenous cellular CB uptake
- Inhibits COX-1 and COX-2.
Aspirin
Class: Nonselective / COX-1 Inhibitors
MOA:
- Irreversible acetylation (inactivation) of COX (non-selective)
- Analgesia
- antipyresis
- antiinflammation
- inhibits thrombosis (post-MI)
AE:
- GI irritation
- Asthma Exacerbation
- prolonged bleeding time
- prolonged gestation
- inhibits renal function
Diclofenac
Class: Nonselective / COX-1 Inhibitors
Phase 1: Competitive, time dependent, reversible COX inhibitor.
Phase 2: with time, conformational change with tighter binding. Class 2 NSAID.
Etodolac
Inhibits COX-2 prostaglandins that mediate inflammation, fever, and pain without blocking the GI/renal injuring PGs (COX-1).
Ibuprofen
competitive, reversible COX inhibitor, competes with arachidonic acid for COX active site. Class 1 NSAID.
Indomethacin
Phase 1: Competitive, time dependent, reversible COX inhibitor. Phase 2: with time, conformational change with tighter binding. Class 2 NSAID.
Ketorolac
Effective perenteral opioid alternative, COX-1 selective. Analgesia with minimal toxicity, for use IM (slower) or IV (faster), with prolonged IM effect allowing longer dosing interval.
Naproxen
competitive, reversible COX inhibitor, competes with arachidonic acid for COX active site. Class 1 NSAID.
Celecoxib
Inhibits COX-2 prostaglandins that mediate inflammation, fever, and pain without blocking the GI/renal injuring PGs (COX-1).
Diclofenac
Inhibits COX-2 prostaglandins that mediate inflammation, fever, and pain without blocking the GI/renal injuring PGs (COX-1).
Hydroxycholorquine
Antimalarial, unknown mechanism, accumulates in lysosome. Decreases neutrophils chemotaxis, phagocytosis and superoxide synthesis. Inhibits TLR-9 signaling.
Leflunomide
Mechanism?
AE
Pyrimidine synthesis inhibitor - inhibits dihydrochloorate (rUMP synthesis) - wich inhibits autoreactive T cells activation and auto-antibodies by B cells
AE - Diarrhea, Elevation of liver enzymes
***Cholestiramine increases clearence
Methotrexate
Very potent antiinflammatory, used with anti-TNF’s to prevent anti-anti-TNF Abs. Inhibits DHF to THF converison by DHF reductase, to block purine synthesis. Strong effecton decreasing joint pain index. Increase dose if disease not well-controlled. If no responde alone, can add sulfasalazine and hydrochlorquine, leflunomide, anti-TNF agent, anakinra, abatacept. Triple therapy = MTX + SSZ + HCQ (not as good as anti-TNF).
Sulfasalazine
sulfapyridine and salicylate bound by axo group. Unknown mechanism.
Etanercept
soluble TNF receptor bound to TNF-a, mimics cel-surface receptor.
Anakinra
Use as a Disease Modifying Anti-Rheumatic Drug
IL-1 receptor antagonist
Golimumab
Neutralizes soluble and cell-bound TNF-a/b.
Adalimumab
Neutralizes soluble and cell-bound TNF-a/b.
Infliximab
Mechanism
AE?
Major complication
Neutralizes soluble and cell-bound TNF-a
AE - Upper Respiratory Infection, nausea, cough, headache
***TB reaction
Allopurinol
Xanthine oxidase inhibitor (hypoxanthine analogue), metabolized to oxipurinol, which is the clinically effective XO inhibitor. Has a short t1/2, but oxipurinol has t1/2 = 14-26 hours (prolonged if decreased GFR). Max effect in 4-14 days.
Colchicine
Mechanism?
AE?
Alkaloid derivative of meadow saffron. . Readily bioavailable (> binds soluble, non-polymerized tubulin, forms complex preventing elongation/contraction of dynamic tublin polymers >> blocks cell division, signal transduction, regulation of gene expression, migration, and secretion. Arrests growth (low concentration) and promotes depolymerization (high concentration) and arrests cell at metaphase = antiinflammatory and PMN phagocytosis disruption. Also binds leukocyte membrane proteins. Biliary and stool excretion (enterohepatic circulation), with major eleimination by ABCB1 (GI tract), minor elimination by CYP3A4 (enteric and hepatic cytochrome). Also Renal elimination.
AE - Nausea Vomiting Diarrhea, hair loss , myopathy**, bone marrow suppresion
Probenecid
AE?
Targets URAT-1 urate transporter in proximal tubule = uricosuric. Oral, well-absorbed, t1/2= 6-12 hours, rapid hepatic metabolism and urinary excretion. Inhibits urate-anion exchange at proximal tubule to block reabsorption. Ineffective at CrCl <60 ml/min. Take with fluids, alkalinize urine, monitor urate, CBC, LFTs, creatinine.
AE: GI irritation, rash
P works in the P(roximal tubule)
Febuxostat
Oral, nonpurine analogue inhibitor of xanthine oxidase. Can inhibit oxidized and reduced XO forms. T1/2 4-18 hours, metabolized hepatically. Activity is not altered in mild to moderate renal insufficiency.
Hydrocortisone
Synthetic cortisol, ~90% circulates bound to corticosteroid binding globulin, 5-10% circulates free. Metabolized by liver, 60-90 min t1/2. 30% excreted in urine as dihydroxy ketones. Binds cytosolic receptor, dimerizes, translocates to nucleus where binds glucocorticoid response elements to upregulate or repress transcription of many proteins (20-30%), with variable action depending on cell type. Can also activate signaling pathways before entering nucleus = rapid steroid actions (prior to transcriptional changes). Example is phosphorylation and release of annexin-1, a potent antiinflammatory agents that blocks the mobilization of lymphocytes and release of inflam mediators.
