Musculoskeletal, Skin, and Connective Tissue Pharmacology Flashcards
acetaminophen–mechanism
- reversibly inhibits cyclooxgenase
- mostly in CNS
- inactivated peripherally
acetaminophen–use
- antipyretic
- analgesic
- NOT anti-inflammatory
- used instead of aspirin to avoid Reye syndrome in children with a viral infection
acetaminophen–toxicity
- overdose produces hepatic necrosis
- acetaminophen metabolic (NAPQI) depletes glutathione and forms toxic tissue byproducts in liver
acetaminophen–antidote
- N-acetylcysteine
- regenerates glutathione
aspirin–mechanism
- NSAID that irreversibly inhibits cyclooxygenase (COX-1 and COX-2) by covalent acetylation –> dec synthesis of TXA2 and prostaglandins
- inc bleeding time
- no effect on PT, PTT
- effect lasts until new platelets are produced
aspirin–use
- low dose (<300 mg/day): dec platelet aggregation
- intermediate dose (300-2400 mg/day): antipyretic and analgesic
- high dose (2400-4000 mg/day): anti-inflammatory
aspirin–toxicity
- gastric ulceration
- tinnitus (CN VIII)
- chronic use can lead to:
- acute renal failure
- interstitial nephritis
- GI bleeding
- causes respiratory alkalosis early, but transitions to mixed metabolic acidosis respiratory alkalosis
what are children at risk for if have a viral infection that is treated with aspirin?
Reye syndrome
celecoxib–mechanism
- reversibly inhibits specifically the cyclooxogenase (COX) isoform 2 which is found in inflammatory cells and vascular endothelium and mediates inflammation and pain
- spares COX 1
what are the benefits of using celecoxib over other NSAIDs?
- spares COX-1 which helps maintain gastric mucosa
- so does not have the corrosive effects of other NSAIDs on the GI lining
- spares platelet function as TXA2 production is dependent on COX-1
celecoxib–use
- rheumatoid arthritis
- osteoarthritis
celecoxib–toxicity
- inc risk of thrombosis
- sulfa allergy
name the NSAIDs
- ibuprofen
- naproxen
- indomethacin
- ketorolac
- diclofenac
- meloxican
- piroxican
NSAIDs–mechanism
- reversibly inhibit cyclooxygenase (both COX 1 and 2)
- blocks prostaglandin synthesis
NSAIDs–use
- antipyretic
- analgesic
- anti-inflammatory
- indomethacin is used to close a patent ductus arteriosis
NSAIDs–toxicity
- interstitial nephritis
- gastric ulcer–prostaglandins protect gastric mucosa
- renal ischemia–prostaglandins vasodilate afferent arteriole
leflunomide–mechanism
- reversibly inhibits dihydroorotate dehydrogenase, preventing pyrimidine synthesis
- suppresses T cell proliferation
leflunomide–use
- rheumatoid arthritis
- psoriatic arthritis
leflunomide–toxicity
- diarrhea
- HTN
- hepatotoxicity
- teratogenicity
name the bisphosphonates
- alendronate
- ibandronate
- risedronate
- zoledronate
bisphosphonates–mechanism
- pyrophosphate analogs
- bind hydroxyapatite in bone
- inhibits osteoclast activity
bisphosphonates–use
- osteoporosis
- hypercalcemia
- Paget dz of the bone
- metastatic bone dz
- osteogenesis imperfecta
bisphosphonates–toxicity
- esophagitis
- if taken orally, patients are advised to take with water and remain upright for 30 minutes
- osteonecrosis of jaw
- atypical stress fractures
teriparatide–mechanism
- recombinant PTH analog given subcutaneously daily
- inc osteoblastic activity
teriparatide–use
- osteoporosis
- causes inc bone growth compared to antiresorptive therapies
- ie. bisphosphonates
- causes inc bone growth compared to antiresorptive therapies
teriparatide–toxicity
- transient hypercalcemia
name the chronic gout drugs (preventive)
- allopurinol
- febuxostat
- pegloticase
- probenecid
name the acute gout drugs
- NSAIDs
- glucocorticoids
- colchicine
allopurinol–mechanism
- competitive inhibitor of xanthine oxidase
- decrease conversion of hypoxanthine and xanthine to urate
- increase concentrations of azathioprine and 6 MP
- both normally metabolized by xanthine oxidase
other uses for allopurinol besides gout
- used in lymphoma and leukemia to prevent tumor lysis–associated urate nephropathy
febuxostat–mechanism
- inhibits xanthine oxidase
pegloticase–mechanism
- recombinant uricase that catalyzes metabolism of uric acid to allantoin ( a more water soluble product )
probenecid–mechanism
- inhibits reabsorption of uric acid in the proximal convoluted tubule
- also inhibits secretion of penicillin
- can precipitate uric acid calculi
name the NSAIDs used for gout
- naproxen
- indomethacin
what type of NSAID should not be used for acute gout and why?
- salicylates
- all but the highest doses depress uric acid clearance
- even high doses (5-6 g/day) have only minor uricosuric acitvity
glucocorticoids–mechanism for use in acute gout
- oral
- intra-articular
- parenteral
colchicine–mechanism
- binds and stabilizes tubulin to inhibit microtubule polymerization
- impairs neutrophil chemotaxis and degranulation
colchicine–use
acute and prophylactic use for gout
colchicine–toxicity
GI side effects
name 2 TNF alpha inhibitors
- etanercept
- infliximab, adalimumab
what do TNF alpha inhibitors predispose a patient to and why?
- all TNF alpha inhibitors predispose to infection, including reactivation of latent TB
- b/c TNF is important in granuloma formation and stabilization
etanercept–mechanism
- fusion protein–receptor for TNF alpha + IgG1 Fc
- produced by recombinant DNA
- “Etanercept is a TNF decoy receptor”
- produced by recombinant DNA
etanercept–use
- rheumatoid arthritis
- psoriasis
- ankylosing spodylitis
infliximab, adalimumab–mechanism
- anti TNF alpha monoclonal antibody
infliximab, adalimumab–use
- inflammatory bowel disease
- rheumatoid arthritis
- ankylosing spondylitis
- psoriasis
rasburicase–mechanism
- recombinant uricase that catalyzes metabolism of uric acid to allantoin
rasburicase–use
- prevention and treatment of tumor lysis syndrome
