Musculoskeletal, Skin, and CT Pharm Flashcards
Membrane phospholipids are cleaved by phospholipase A2 into arachidonic acid. Arachidonic acid under lipoxygenase will form 5-HPETE –> leukotrienes. There are LTC4, LTD4, LTE4, and LTB4. Which one is not like the others?
LTB4 is a neutrophilic chemotactic agent like bacterial products, IL-8 and C5a.
LTC4, LTD4, and LTE4 aka “slow reacting substances of anaphylaxis” mediate symptoms of allergies/asthma = increased bronchial tone (bronchoconstriction/bronchospasm), vasoconstriction and increased vascular permeability
Membrane phospholipids are cleaved by phospholipase A2 into arachidonic acid. Arachidonic acid under COX can make prostaglandins, prostacyclin and thromboxane. COX-1 or COX-2 is responsible for making thromboxane? What does TXA2 do?
COX-1 is specific making thromboxane which is responsible for plt aggregation and increasing vascular tone.
COX-1 and COX-2 can make prostaglandins and prostacyclin. List them and their side effects.
- prostacyclin (PGI2): inhibit plt aggregation, decrease vascular tone (complete opposite of thromboxane)
- prostaglandins:
- PGE1 = decrease vascular tone
- PGE2 = increase uterine tone
- PGF2 = increase uterine tone
Acetaminophen reversibly inhibits COX, mostly in CNS. It is inactivated peripherally. What are clinical uses?
clinical uses: anti-pyretic, analgesic, but not ANTI-INFLAMMATORY; used instead of aspirin to avoid Reye syndrome in children with viral infection
Explain what overdosing on acetaminophen can do? What’s the antidote
overdose produces hepatic necrosis, acetaminophen metabolite (NAPQI) depletes glutathione and forms toxic tissue byproducts in liver.
N-acetylcysteine is antidote -generates glutathione.
When someone is dehydrated (diarrhea, vomiting), how come you should be wary of giving NSAIDs?
NSAIDs block COX which will inhibit prostaglandin production. NO prostaglandins = no vasodilation of afferent arteriole = no increase in GFR that is very much needed during dehydration.
Aspirin is an NSAID. Explain its mech of action
Irreversibily inhibits COX-1 and COX-2 via acetylation, which decrease synthesis of TXA2 and prostaglandins.
decrease plt aggregation = increase bleeding time
but no effect on PT, PTT.
Explain the uses of aspirin. be specific in terms of dosing.
- Low dose (<300 mg/day): decrease plt aggregation
- intermediate dose (300-2400 mg/day): anti-pyretic and analgesic
- high dose (2400-4000 mg/day): anti-inflammatory
What are some side effects of aspirin toxicity?
- gastric ulceration
- tinnitus (CN VIII)
- chronic use can lead to acute renal failure, interstitial nephritis, GI bleeding
- risk of reye syndrome w/ aspirin for viral infections
- causes resp alkalosis early, but transitions to mixed metabolic acidosis-resp alkalosis
Celecoxib is a selective COX-2 inhibitor that is found in inflamm cells and vascular endothelium. Being a COX-2 inhibitor spares COX-1 which has what effects?
COX-1 maintains GI mucosa and responsible for making thromboxanes
so someone on celecoxib will have decreased prostaglandins but normal thromboxane levels. Therefore, there is an increased risk of thrombosis b/c pro-thrombotic activties of TXA2 are unopposed since there’s less prostacyclins and prostaglandins.
What kind of allergy will exclude you from taking celecoxib?
sulfa allergy
What are the 2 clinical uses of celecoxib
rheumatoid arthritis
osteoarthritis
Other NSAIDs besides aspiring reversibly inhibit COX-1 and COX-2 that are anti-pyretic, analgesic and anti-inflammatory. List the 5 NSAIDs in first aid.
Ibuprofen naproxen indomethacin ketorolac diclofenac
Which NSAID is used to close PDA?
indomethacin
What are 3 toxicities assoc with NSAID use
1) interstitial nephritis
2) gastric ulcer
3) renal ischemia
