Exam 5 lecture 4 Flashcards
Therapeutic applications of NSAIDs
Analgesic
Anti-inflammatory
Antipyretic
Antiplatelet effect (aspirin)
What are the 3 phases of inflammatory response
acute- vasodilation (increased permeability)
subacute- Infiltration of neutrophils
Chronic- proliferation
Recruitment of what contributes to inflammatory pain? Why?
Recruitment of Eicosanoids.
They cause arachidonic acid increase
(injury increase= arachidonic acid increase)
They also release cytokines, prostaglandins and thromboxanes which contribute to pain)
What is the CORE function of NSAIDs
Inhibit COX enzymes
What does PLA2 create to make a substrate of COX
arachidonic acid
What does COX-1 do to arachidonic acid?
Forms TXA2- platelet aggregation also has prostaglandin function to create mucus to protect stomach lining.
How does Aspirin act differently from other NSAIDs
Irreversibly inhibits COX enzyme. Other NSAIDs are competitive
therapeutic uses of aspirin
frequently used as prophylaxis for anticoagulation. No tolearnce to analgesia effect. Causes Reyes syndrome in children
What does COX 2 form in the body
forms platelets and acts on nociceptors
Absorption and half life of aspirin
t 1/2 is 15 minutes (salicylate half life is 6-20 hours)
Half life is short but duration is long because it is irreversible
How to increase excretion of Aspirin from urine
Increased excretion with increased urinary PH (IV bicarb)
Clinical features of salicylate poisoning
Mild- Vertigo, tinnitus
Moderate-severe- CNS effects- Respiratory alkilosis, metabolic acidosis, N/V, sweating, delirium, coma
How to treat salicylate/aspirin poisoning
reduce salicylate dose and use dextrose or sodium bicarb to increase urinary PH
What are the different classes of NSAID
salicylate- aspirin
aryl propinoic acid- Ibuprofen, naproxen
Aryl Acetic acid- Indomethacin, diclofenac, ketorolac
Enolic acid- piroxicam, meloxicam
What are the arylpropinoic acids drugs? MOA? t1/2
ibuprofen and naproxen
Reversible COX inhibitors
Ibuprofen-2 hrs
Naproxen- 14 hrs
Which arylacetic acid derivative has increased risk for peptic ulcer? Which is one of the most potent reversible inhibitor of PG biosynthesis? Which is the less toxic derivative for indomethacin? Which one has a high severity and incidence of side effects?
increased risk for peptic ulcer- dicofenac
Most potent reversible inhibitor- Indomethacin
Less toxic derivative of indomethacin- sulindac
Which one has a high severity and incidence of side effects- Indomethacin
When is meloxican cox 2 selective
At low doses
Piroxicam half life
57 hours
Adverse effects of NSAIDs
Renal function
Transient inhibition of platelet aggregation
Inhibition of uterine motility
GI distress/ulceration
Effects of NSAIDs on renal function
increased sodium reabsorption leading to edema
Effect of NSAIDs on inhibition of platelet aggregation
Increased risk of bleeding
Effect of NSAIDs on uterine motility
Therapeutically used to delay pre term birth
NSAID effect on GI
Ulceration
risk increases with long term use and less risk than salicylate NSAIDs
Therapeutic use of Acetaminophen
analgesic and antipyretic
limited antiinflammatory activity
advantages of acetaminophen compared to NSAIDs
No GI toxicity
No effect on platelet aggregation
Disadvantage of acetaminophen compared to NSAIDs
Hepatic necrosis
adverse effects of acetaminophen
Renal toxicity> NSAIDs and Aspirin
Dose dependent hepatic necrosis
What is hepatic necrosis caused by?
increases in toxic acetaminophen metabolites (NAPQI)
Why were COX 2 selective inhibitors withdrawn
Chance of blood clots, stroke and heart attacks