NSAIDs_PHARM Flashcards
MOA
COX
Cyclooxygenase
- formation of prostanoids from AA
- prostaglandin E2 (PGE2)
- prostacycline (PGI2)
- Thromboxane A2 (TXA2)
Function of
COX1
Found in all tissues
“housekeeping” or “good COX”
- Conversion AA to TXA2
- Platelet activation
- Aggregation and vasoconstriction
- Increase mucous, bicarb
- decrease acid
- increase GI blood flow
- Increase renal blood flow
Function of COX2
Bad Cox
Blood vessels
- inflammation
- pain
- MI, stroke, clots
Gastric
- Colon cancer
Uterus
- uterine contractions
Renal
- increase blood flow
Brain
- fever, pain
First generation COX inhibitors
List
MOA
- Aspirin (irreversible COX inhibition)
ASA acetylsalicylic acid (aspirin)
magnesium salicylate
sodium salicylate
salsalate
- Non-aspirin NSAID (reversible COX inhibition)
ibuprophen
naproxen
indomethacin (*highest stroke risk)
diclofenac
* less gastric bleeding
* superior dysmenorrhea
*trial and error
respond to 1 > than other
personalized response
Second generation COX inhibitors
List
MOA
Inhibition COX2 only
Celecoxib
Non- antiinflammatory COX inhibitor
Acetaminophen
COX inhibition in CNS only
Indication
First generation NSAIDs
- pain
- fever
- inflammation
- dysmenorrhea
Dosage
First generation NSAIDS
< 81mg anti-platelet
325 mg pain, fever, anti-platelet
>325mg inflamation
MOA
first generation NSAIDs
Inhibition COX1 and COX2 and formation prostanoids (PGE2, PGI2, TXA2)
- Analgesia
- prevention formation prostaglandins (PGE2)
- pain receptors not stimulated in PNS - Anti-pyretic
- prevention prostaglandins in hypothalamus
- hypothalamus set point stays the same - Anti-platelet aggregation
- COX 1 inhibition
- no TXA2
- vasodilation, platelets remain inactivated - Anti-cancer (colon, breast, prostate)
- COX 2 inhibition (promotes tumor growth and metastasis)
- Cancer cells express high level of COX 2
first generation NSAID
Contraindications
- PUD, bleeding, hemorrhages
- anti-coagulation, anti-platelets, Vitamin K deficiency, bleeding disorders
- angina pectoris, heart disease, CHF
- hypersensitivity
- hypertension BP > 150mmHg
- older adults (salicylism)
- children (reye’s syndrome)
- smokers
- alcoholism (> 3 drinks per day)
- kidney and liver disease
- pregnancy and breastfeeding
first generation NSAID
SE
GI
- gastritis
- ulcers
- bleeds
- anemia
Rx.
PPI
H2 blocker
H. pylori urea breath test
D/C smoking, alcoholism, old age, PUD
S&S of Salicylism
- tinnitus
- sweating
- head ache
- dizziness
- hypotension
- decreased LOC
- increase RR
S&S Reye’s syndrome
- brain encephalopathy, decreased LOC
- fatty liver
- organ failure
AE of NSAID and preganncy
- premature closure ductus artereosus
- ICH
- still birth
- ICH
- low birth weight
- anemia
- prolonged labour, hemorrhage
Drugs to avoid on NSAIDS
- anti-platelets
- anti-coagulants
- glucocorticoids
- alcohol
- smoking
- ACE inhibitors, ARBs (renal failure)
- vaccinations
Contraindication NSAIDs
infants
children (reye’s syndrome)
older (salicylism, CHF, renal failure, BP)
pregnancy (ductus arteriosus, still birth)
Rules for prescribing NSAID
- lowest dosage
- shortest time
personalized response to first generations NSAIDs (trial and error)
irreversible inhibition aspirin
aspirin = no to infants/children, higher bleeding risk
non-aspirin = MI and stroke increased risk, SJS
SE
non-aspirin NSAID
- less GI bleeding
- MI, stroke
- SJS
Second generation COX
list
MOA
Celecoxib
inhibition COX2
- GI: decrease mucous, bicarb, increase acid, decrease blood flow
- kidney: decrease blood flow
- decrease PGE2 (Pain, fever, inflammation), PGI2 (decrease vasodilation)
- cancer: decrease solid tumor growth
- uterus: decrease contraction
Celecoxib
SE
GI
- gastritis
- GI bleeding
CV
- MI, stroke, angina, CHF precipitation
Kidney
- kidney failure
Contraindications/caution
Celecoxib
- heart disease, angina
- kidney disease
- PUD, GI bleeding
- sulfa allergies
- pregnancy/breast feeding/ children
prophylactic prescription NSAIDs
PPI
- proton pump inhibitor
H2 blocker
- histamine 2 blocker
- increase mucous, bicarb, decrease acid
Example
Non-antiinflammatory NSAID
Acetaminophen
- inhibition COX in CNS
- not in the PNS
- no effect on inflammation
Indication for
first generation NSAIDS
- pain
- fever
- inflammation
- anti-platelet
- cancer
Indication for
Second generation NSAID
FAP (familial adenomatous polyposis)
RA, OA, ALS
Acetaminophen MOA
blockage COX in CNS
1. antipyretic
2. analgesia
*not for inflammation
Acetaminophen daily dosage limit
4 g per day
< 3 g per day (fasting, anorexia, alcoholism)
Leading cause of liver failure
acetaminophen overdose
S&S acetaminophen overdose
48 hours post ingestion
sweating, nausea/vomitting/diarrhea, RUQ painAn
Antidote for acetaminophen overdose
acetylcysteine
must be given < 24 hour mark
glutathione substitutionL
Pathway metabolism Acetaminophen in the liver
- major pathway
- glutathione conjugation - minor pathway
- cyp450 enzyme
- toxic metabolite formation
- liver failure/damage
*alcoholics
*acetaminophen overdose
*anorexia
SE of acetaminophen
- liver inflammaiton/failure
- SJS, TENS, AGEF
- hypertension
- rebound head aches
Safety acetaminophen
- safe in renal failure, old, young, pregnancy
