Musculoskeletal/Skin/CT- Pharmacology Flashcards
What breaks down membrane phospholipids to arachidonic acid?
phospholipase A2
What drugs prevent the action of phospholipase A2?
corticosteroids (e.g. cortisone, hydrocortisone, prednisone,, dexamethasone)
What two things can happen to arachidonic acid?
1) lipoxygenase can convert it to 5-HPETE
2) COX1/2 can convert it to the cyclic endoperoxides (prostacyclin (PGI2), prostaglandins, and thromboxane (TXA2))
What drug can inhibit the action of lipoxygenase?
Zileuton (used in tx of asthma)
5-HPETE is converted to leuktrienes such as LTC4, LTD4, LTE4, and LTB4. What does LTB4 do?
neutrophil chemotaxis
5-HPETE is converted to leuktrienes such as LTC4, LTD4, LTE4, and LTB4. What do LTC4, LTD4, and LTE4 do?
increase bronchial tone
What are some leukotriene (mostly LTC4, LTD4, LTE4) receptor anatagonists?
Montelukast (asthma tx), Zafirlukast
What drugs inhibit COX1 and COX2?
Aspirin (irreversible)
NSAIDs (indomethacin, Ibuprofen, Naproxen, Ketorlac, Diclofenac)
What is an exclusive COX-2 inhibitor?
Celecoxib
What does PGI2 do?
decrease platelet aggregation and vascular tone (inhibitor= epoprostenol)
What does PGE1 do?
decrease vascular tone (inhibitor= alprostadil)
What does PGE2 and PGF2 do?
increase uterine tone (inhibitor PGE2= dinoprostone; inhibitor PGF2= carboprost)
What does acetominophen (Tylenol) do?
reversibly inhibit COX, mostly in the CNS. Inactivated peripherally
What are the uses of Tylenol?
antipyreitc, analgesic, but NOT anti-inflammatory
Viral infections in children (do not use Aspirin; Reyes syndrome)
What are the AEs of acetaminophen?
hepatic necrosis in overdose due to accumulation of NAPQI (antidote= N-acetylcysteine)
How does aspirin work?
irreversibly inhibits COX1 and COX2 via acetylation, which decreases the synthesis of TXA2 and prostaglandins
What effect does aspirin have on BT, PT, and PTT?
increased BT
no effect on PT or PTT
What are the uses of aspirin?
Low dose (less than 300mg/day): decrease platelet agg
Medium dose (300-2400mg/day): antipyretic and analgesic
High dose (2400-4000mg/day): anti-inflammatory
What are the AEs of aspirin?
gastric ulceration
tinnitus
chronic use can lead to acute renal failure, interstitial nephritis, GI bleeding
Reyes syndrome in children
What effect does aspirin have on pH?
causes respiratory alkalosis early, but transitions to mixed metabolic acidosis-respiratory alkalosis
What advantage does Celecoxib have?
it reversibly inhibits specifically COX2, which is found in inflammatory cells and vascular endothelium and mediates inflammation and pain but spares COX-1, which helps maintain gastric mucosa. Thus, does not have the corrosive effects of other NSAIDs on the GI lining.
Also spares the function of TXA2 (plateley aggregator)
What are the main uses of celecoxib?
rheumatoid arthritis and osteoarthritis
What are the AEs of celecoxib?
risk of thrombosis and sulfa allergy
What are the AEs of NSAIDs (e.g. Indomethacin, naproxen, ibuprofen)?
interstitial nephritis, gastric ulcer, renal ischemia
What is Aledronate?
a bisphosphonate, a pyrophosphate analog that binds hydroxyapatite in bone, inhibiting osteoclast activity for tx of osteoporosis, hypercalcemia, and Paget disease of bone
What are the main AEs of bisphosphonates?
corrosive esophagitis, jaw osteonecrosis
What is Teriparatide?
rcombinant PTH analog given subQ daily to increase osteoblastic activity for tx of osteoporosis
What are the drugs used for tx of chronic gout (preventative)?
-allopurinol, febuxostat, pegloticase, and probenecid
What does allopurinol do?
inhibits xanthine oxidase after being converted to alloxanthine, and decreases conversion of xanthine to uric acid
What is another use of allopurinol?
lymphoma and leukemia to prevent TLS associated urate nephropathy
Allopurinol increases the conc of what drugs?
azathiopurine and 6-MP (both normally metabolizes by xanthine oxidase)
What does feboxustat do?
inhibit xanthine oxidase
What is Pegloticase?
a recombinant uriace that catalyzes the metabolism of uric acid to allantion (a more water soluble product)
How does probenecid help in gout tx?
it inhibits reabsorption of uric acid in the proximal convoluted tubules (also inhibits secretion of penicillin)
How is an acute gout attack tx?
NSAIDs, steroids, and colchicine
What are the main NSAIDs used for gout tx?
indomethacine and naproxen
How does colchicine work?
It binds and stabilizes tubulin to inhibit microtubules polymerization, impairing neutrophil chemotaxis and degranulation
