B.27. General properties of NSAIDS. Acetylsalicylic acid.

Question 1

what is the mechanism of NSAID’s?

Answer 1

inhibition of cyclooxygenase enzymes:
COX-1–> constitutive expression. in platelets, kidneys and GI, where it acts to synthesize TXA₂ and prostaglandins
COX-2–> inducible expression. in the brain and at site of inflammation.

Question 2

what are the effects of NSAID’s?

Answer 2

anti-platelet (aspirin)
analgesics
antipyretics (fever reduction)
anti-inflammatory

Question 3

is Aspirin reversible or irreversible inhibition?

Answer 3

irreversible inhibition of COX enzymes

*most NSAID’s are reversible

Question 4

how is Aspirin (acetylsalicylic acid) given?

Answer 4

orally

Question 5

what are the dose-dependent effects of Aspirin?

Answer 5

low dose (<300mg)-->anti-platelet aggregation effect (post MI prophylaxis)
medium dose (300-2400mg)--> analgesic and anti-pyretic effects (prostaglandins PGE₂ ↓)
high dose (2400-5000mg) --> anti- inflammatory effect (prostacyclin ↓)

Question 6

what type of elimination does aspirin have?

Answer 6

renal

Question 7

when giving low-dose aspirin, what order elimination does it have?

Answer 7

first order–> T1/2 3-5 hours

Question 8

what are the adverse effects of Aspirin?

Answer 8

GI irritation --> PUD, GI bleeding
renal damage --> AKI, interstitial nephritis
Tinnitus
vertigo
hearing loss
↑ bleeding time
chondrotoxicity 
hyperuricemia (low- medium dose), uricosuria (high-dose) 
NSAID's induced asthma--> "aspirin asthma" 
hypersensitivity reaction 
hyperthermia
uterus relaxation (labor prolongation)
Reye syndrome (children)

Question 9

when is Acetylsalicylic acid contraindicated?

Answer 9

pregnancy (closing botallo duct)

children (Reye syndrome), unless they have Kawasaki’s disease

Question 10

Misoprostol can be used for

Answer 10

prevention and treatment of NSAID’s-induced GI irritation/ulcers
it’s a prostaglandin PGE₁ analogue

Question 11

management of acute overdose of aspirin

Answer 11

gastric lavage
activated charcoal
ventilation support
symptomatic management of acid-base and electrolyte imbalance
↑ urine volume and urine alkalization may enhance renal elimination

Question 12

what is the effect of activated charcoal on aspirin

Answer 12

alkalinization of the serum pulls the aspirin from the CNS

Question 13

what type of acid-base disturbance does Salicylate toxicity present with?

Answer 13

mixed

respiratory alkalosis and metabolic acidosis

Question 14

what causes “Aspirin asthma”?

Answer 14

increased levels of leukotrienes

Question 15

why can Aspirin cause GI bleeding?

Answer 15

because the prostaglandins cytoprotective effects ↓

Question 16

when giving high-dose aspirin, what order elimination does it have?

Answer 16

zero-order–> T1/2 up to 15 hours