Pharmacology: NSAIDs Flashcards
Salicyclates
non selective NSAIDs
aspirin- upper GI disturbances, low cost, and long history of safety
salsalate
diflunisal- no antipyretic effect, less GI irritation than aspirin
Acetic Acids
non selective NSAIDs tolmetin diclofenac indomethacin- upper GI disturbances, very potent, CNS disturbances sulindac- long half life nabimetone
Propionic Acids
non selective NSAIDs
ibuprofen, naproxen (considered safest), ketoprofen, fenoprofen, flurbiprofen, oxaprozin
All: lower toxicity
Pyrazolones
non selective NSAIDs
piroxicam
Partially Selective COX-2 Inhibitors
non selective NSAIDs
etodolac and meloxicam
Selective COX-2 Inhibitors
Celecoxib
lower GI irritation and potential to increase MI and stroke
COX-1 vs. COX-2
COX1- housekeeping enzyme and inhibited by NSAIDs
COX2- induced by oxidative stress, injury, ischemia, seizures, neurodegenerative diseases
Not different in function, just their availability
COX1 is always present and COX2 must be induced to be present
Prostaglandins provide protection, so if given NSAIDS, some people can have GI side effects/bleeding because GI isn’t being protected from acid
Aspirin
Aspirin – the minute in circulation, salicyclic acid is only part left
Irreversibly inhibits platelet COX to cause anti-platelet effects
COX 1 or COX2 is a permanent action
Only takes about 20 minutes to get to the proper concentration and after 4 hours it will be eliminated
Platelets don’t have the nuclei, synthesis of proteins, or DNA, so basically you cannot synthesize cyclooxygenase
About every mL there are about 300 platelets, you just need a baby aspirin because it will make all the cyclooxygenase
It will take complete turnover of the platelets to get rid of it in about 10 days
NSAIDs vs. Acetaminophen
Lower temperature, pain, and inflammation = NSAIDs
Acetaminophen: weak in anti-inflammation (tylenol)
Actions of NSAIDs
Analgesic: PGE2 sensitizes nerve endings to bradykinin, histamine etc
Antipyretic: PGE2 elevates the temperature set point of anterior hypothalamic thermoregulatory center and thereby induces fever
Anti-inflammatory: NSAIDs inhibit inflammation due to PGs but do not stop underlying disease
Therapeutic and Toxic Effects of Salicylates
high concentration: coma, dehydration, and intoxication
middle concentration: tinnitus, central hyperventilation
below middle: anti-inflammatory (between 10-50 mg/dL)
low concentration: gastric bleeding
Salicylates Drug Interactions
With antacids: reduced rate of aspirin absorption
With heparin or oral anti-coagulants: hemorrhage
With probenecid or sulfinpyrazone: gout
Incidence of Gastro-duodenal Ulcers
from greatest to least incidence:
naproxen, ibuprofen, diclofenac, and celexib
Adverse Effects of NSAIDs: CNS, cardiovascular, and GI
Central nervous system: headaches, tinnitus, dizziness.
Cardiovascular: fluid retention, hypertension, edema, and rarely, myocardial infarction and congestive heart failure (CHF).
Gastrointestinal: abdominal pain, dysplasia, nausea, vomiting, and rarely, ulcers or bleeding.
Adverse Effects of NSAIDs: hematologic, hepatic, pulmonary, skin, and renal
Hematologic: rare thrombocytopenia, neutropenia, or aplastic anemia.
Hepatic: abnormal liver function test results and rare liver failure.
Pulmonary: asthma
Skin: rashes, pruritus
Renal: renal insufficiency, renal failure, hyperkalemia, and proteinuria
