Rhuem Flashcards
Acetaminophen- what are the uses, mechanism and side effects?
Uses- pain and fever, (kids use instead of aspirin to avoid Reye’s syndrome)
Mechanism- reversible inhibition of COX, mainly in CNS
Side effects- hepatic necrosis, treat w N-acetylcysteine
Pharmokinetics: 90% is metabolized in the liver by sulfination and glucoronide conjugation -> non-toxic metabolite; 10% is excreted un-metabolized or metabolized by P450 into NAPQI which is toxic
–> N-acetylcysteine (NAC) acts as glutathione substitute and binds toxic metabolite, sulhydryl groups enhance non-toxic sulfation elimination of acetaminophen
Aspirin- uses, mech and side effects
Uses- headache, pain, fever, cardiovascular disease
Mechanism- irreversibly inhibits COX1 and COX2, suppressing thromboxane and prostaglandins
Side effects- Reye’s disease, tinnitus, peptic ulcers, mixed acidosis alkalosis, nephropathy
Celecoxib- uses, mechanism, and side effects
Uses- RA, Osteoarthritis
Mechanism- reversibly and selectively inhibits COX2 (COX1 spared-> prevents gastric mucosa damage unlike NSAIDs and spares platelet fxn as TXA2 depends on COX1)
Side effects- Increase risk of thrombosis, sulfa allergies
NSAIDs- list examples, uses, mechanisms, side effects
Ex: ibuprofen, naproxen, indomethacin, ketorolac, diclofenac
Use: antipyretic, analgesic, anti-inflammatory, close PDA (indomethacin)
Mechanism: reversible inhibition of COX 1&2, block prostaglandin synthesis
Side effects- interstitial nephritis, gastric ulcer (PGEs protect gastric mucosa), renal ischemia (PGEs vasodilate afferent arteriole)
Bisphosphonates
What are examples, uses, the mechanism and side effects?
Examples: Alendronate, “-dronates”
Uses: Osteoporosis, hypercalcemia, Paget disease
Mechanism: Pyrophosphate analogs, bind hydroxyapatite in bone, inhibits osteoclast activity
Side effects- Corrosive esophagitis (patients should take with water and sit upright 30min), osteonecrosis of jaw
Teriparatide
What is the clinical use, mechanism and toxicity?
Use: Osteoporosis (increase bone growth compared to anti-resporptive therapies such as bisphosphonates)
Mechanism: PTH analog given subcutaneously daily. Increases osteoblastic activity
Toxicity: Transient hypercalcemia. Increase risk of osteosarcoma (rodent studies)
What are chronic (preventative) and acute treatments for gout?
Chronic: Allopurinol (inhibits xanthine oxidase), Febuxostat (XO inhibitor), Pegloticase (recombinant uricase catalyzes UA to allantoin which is more soluble), Probenecid (inhibits reabsorption of UA in PCT, can inhibit penicillin secretion and precipitate UA calculi)
Acute: NSAIDs (naproxen, indomethacin),Colchicine (inhibits MT polymerization by binding tubulin impairing PMN chemotaxis and degranulation-> can be used acutely or chronically) do NOT give salicylates–> need very high doses, Glucocorticoids if NSAIDs and colchicine contraindicated
What is the mechanism of TNF-alpha inhibition and what are the general side effects and uses?
Mechanism: TNF-alpha is a cytokine and master regulator of immune response, TNF-alpha is released by macrophages to recruit and activate leukocytes and also induces and maintains granulomas. –> TNF-alpha inhibitors decrease immune response and cause granulomas to break down
Uses: Crohn’s disease, RA, Juvenile RA, psoriasis, ankylosing spondylitis
Side effects: increase risk of infection, reactivation of TB due to granuloma breakdown
Enteracept
What are the clinical uses and mechanism?
Mechanism: TNF alpha decoy receptor
Uses: RA, psoriasis, ankylosing spondylitis
Infliximab
What is the mechanism of action? Name another drug with same mechanism. What are the clinical uses?
Mechanism: anti-TNFalpha monoclonal antibody
Another drug: Adalimumab
Uses: IBD, RA, ankylosing spondylitis, psoriasis
What is the treatment for acute gouty arthritis
1st line: NSAIDs (avoided if hepatic or renal dysfunction and in elderly)
2nd line: colchicine (due to side effects)
3rd line: glucocorticoids (if contraindication to NSAIDs and colchicine)
What can be used to treat psoriasis?
Acitretin - synthetic retinoid, Contraindicated in pregnancy since teratogen
Calcipotriol and other vitamin D analogs - topical treatment
