MSK/Dermo pharmacology

Question 1

MECHANISM Reversibly inhibits cyclooxygenase, mostly in CNS. Inactivated peripherally

CLINICAL USE Antipyretic, analgesic, but not anti-inflammatory. Used instead of aspirin to avoid Reye syndrome in children with viral infection.

ADVERSE EFFECTS Overdose produces hepatic necrosis; acetaminophen metabolite (NAPQI) depletes glutathione and forms toxic tissue byproducts in liver. N-acetylcysteine is antidote—regenerates glutathione.

Answer 1

acetamonphen

Question 2

MECHANISM NSAID that irreversibly inhibits cyclooxygenase (both COX-1 and COX-2) by covalent acetylation -> decrease synthesis of TXA2 and prostaglandins. increase bleeding time. No effect on PT, PTT. Effect lasts until new platelets are produced.

CLINICAL USE Low dose (< 300 mg/day): decrease platelet aggregation. Intermediate dose (300–2400 mg/day): antipyretic and analgesic.

High dose (2400–4000 mg/day): anti-inflammatory.

ADVERSE EFFECTS Gastric ulceration, tinnitus (CN VII), allergic reactions (especially in patients with asthma or nasal polyps).

Chronic use can lead to acute renal failure, interstitial nephritis, GI bleeding. Risk of Reye syndrome in children treated with aspirin for viral infection. Toxic doses cause respiratory alkalosis early, but transitions to mixed metabolic acidosis-respiratory alkalosis.

Answer 2

aspirin

Question 3

MECHANISM Reversibly and selectively inhibits the cyclooxygenase (COX) isoform 2 (“Selecoxib”), which is found in inflammatory cells and vascular endothelium and mediates inflammation and pain; spares COX-1, which helps maintain gastric mucosa. Thus, does not have the corrosive effects of other NSAIDs on the GI lining. Spares platelet function as TXA2 production is dependent on COX-1.

CLINICAL USE Rheumatoid arthritis, osteoarthritis.

ADVERSE EFFECTS increase risk of thrombosis. Sulfa allergy

Answer 3

Celecoxib

Question 4

MECHANISM Reversibly inhibit cyclooxygenase (both COX-1 and COX-2). Block prostaglandin synthesis.

CLINICAL USE Antipyretic, analgesic, anti-inflammatory. Indomethacin is used to close a PDA.

ADVERSE EFFECTS Interstitial nephritis, gastric ulcer (prostaglandins protect gastric mucosa), renal ischemia (prostaglandins vasodilate afferent arteriole), aplastic anemia.

Answer 4

NSAIDs: Ibuprofen, naproxen, indomethacin, ketorolac, diclofenac, meloxicam, piroxicam.

Question 5

MECHANISM Reversibly inhibits dihydroorotate dehydrogenase, preventing pyrimidine synthesis. Suppresses T-cell proliferation.

CLINICAL USE Rheumatoid arthritis, psoriatic arthritis.

ADVERSE EFFECTS Diarrhea, hypertension, hepatotoxicity, teratogenicity.

Answer 5

lefunomide

Question 6

MECHANISM Pyrophosphate analogs; bind hydroxyapatite in bone, inhibiting osteoclast activity.

CLINICAL USE Osteoporosis, hypercalcemia, Paget disease of bone, metastatic bone disease, osteogenesis imperfecta.

ADVERSE EFFECTS Esophagitis (if taken orally, patients are advised to take with water and remain upright for 30 minutes), osteonecrosis of jaw, atypical femoral stress fractures.

Answer 6

Bisphosphonate

Question 7

MECHANISM Recombinant PTH analog. increase osteoblastic activity when administered in pulsatile fashion.

CLINICAL USE Osteoporosis. Causes increase bone growth compared to antiresorptive therapies (eg, bisphosphonates).

ADVERSE EFFECTS increase risk of osteosarcoma (avoid use in patients with Paget disease of the bone or unexplained elevation of alkaline phosphatase). Avoid in patients who have had prior cancers or radiation therapy. Transient hypercalcemia.

Answer 7

teriparatide

Question 8

chronic gout drugs (preventive)

Probenecid- inhibits reabsorption of uric acud in proximal convoluted tubule (also inhibits secretion of penicillin) can precipitate uric acid calculi

Allopurinol-competitive inhibitor of xanthine oxidase–> increase conversion of hypoxanthine and xanthine to urate. also used in lymphoma and leukemia to prevent tumor lysis syndrome-assocaited with urate nephropathy. increased concentration of azathioprine and 6-MP (both normally metabolized by xanthine oxidase

pegloticase- recombinant uricase catalyzing uric acid to allantoin (more water-soluble product)

Febuxostat-inhibit xanthine oxidase

Answer 8

TNF-alpha inhibitor

Etanercept-fusion protein (decoy receptor for TNF-alpha+IgG1 Fc) produced by recombinant DNA clinical use: RA, psoriasis, ankylosing spondylitis

Infliximab, adalimumab, certolizumab, golimumab: anti-TNF-alpha antibody, clinical use: IBD, RA, ankylosing spondulitis, psoriasis

Adverse effect: predisposition to infection, including reactivation of laten TB since TNF is important in granuloma formation and stabilization. can lead to drup-induced lupus