NSAIDS Flashcards
COX 1
- constitutive enzyme involved in tissue homeostasis.
- Dominant Isoform in Gastric Epithelial cells and is a major source of cytoprotective prostaglandin formation.
COX 2
What induces its production?
where is it constitutively found?
- Induced by growth factors; tumor promoters and cytokines.
- Major source of eicosanoids in inflammation and cancer
- Constitutive in Kidney and brain
- Endothelial COX 2 is the major source of vascular prostacyclin.
NONSELECTIVE COX INHIBITORS
"PAID IN Keys" Aspirin Diclofenac Ibuprofen Indomethacin Ketotolac Naproxen Piroxicam
COX 2 SELECTIVE INHIBITORS
Celecoxib (more selective and associated with thrombotic events)
Meloxicam (not as selective)
DOC for closure of ductus arteriosus
Indomethacin (NSAID)
Adverse effects of NSAIDS
GI effects
Cardiovascular effects
Renal effects
Aspirin Hypersensitivity
Relative risk GI Adverse effects by drug use:
"CIA DNIes Pirating" Lowest risk - Celecoxib Low Risk - Ibuprofen - Aspirin - Diclofenac Medium RisK - Naproxen - Indomethacin High risk - Piroxicam
In what conditions should NSAIDs be avoided and why?
What alternatives can be used?
Avoid in pt.s with HT; HF or CKD In these people NSAIDs can: - Elevate BP - Reduce action of anti-hypertensive agent - cause fluid retention - Worsen Kidney Function
Alternatives such as acetaminophen; tramadol or opioids should be considered.
what is the Triple Whammy
Risk of Kidney injury when ACEI (or ARB) is combined w/ a diuretic and NSAID
NSAIDS: constrict the afferent and reduce GFR
ACEIs: Dilate the efferent arteriole and reduce GFR
Diuretics reduce volume and GFR
Monitor patients for Creatinine and potassium levelWhats
Aspirin and other salicylates have been associated with what disease?
CIs?
Reye’s syndrome
CI:
- in children and young adults less than 20 years old w/ fevers associated with viral illness.
- Pregnancy
DOC for antipyresis in children and teens:
Acetaminophen
- reduces risk of reyes syndrome seen w/ aspirin use
Ibuprofen can also be used.
Salicylates include:
Aspirin (acetyl salicylate)- only irreversible acetylator
Magnesium choline salicylate
Sodium salicylate
Salicyl salicylate
Salicyates MOA:
Uncouple oxidative phosphorylation which leads to elevated CO2 and increased respiration.
Higher doses stimulate the respiratory center resulting in hyperventilation.
Salicylates effects on platelets?
What does this prolong?
Aspirin irreversibly inhibits TXA2 production in platelets
Platelets lack nuclei and cannot synthesize new enzyme.
- prolongs bleeding time
Acetaminophen
Analgesic and antipyretic drug
No anti-inflammatory or antiplatelet effects
Technically not an NSAID`
ANALGESIC ACTIONS
PGE2 role in pain?
NSAID role?
What kind of pain are NSAIDs superior to OPIOIDs?
- PGE2 sensitizes nerve endings to the action of chemical mediators released by the inflammatory process.
- By decreasing PGE2 synthesis, NSAIDs repress the sensation of pain.
- NSAIDs are superior to opioids in pain due to inflammation.
What kind of pain can NSAIDs treat?
- NSAIDs are used for the treatment of mild to moderate pain, especially the pain of inflammation.
- Many NSAIDs are approved for the treatment of:
- Rheumatoid arthritis
- Osteoarthritis
- Acute gouty arthritis
what NSAIDs are not used to treat gout?
Why?
- All other NSAIDs except aspirin, salicylates, and tolmetin can be used to treat acute gout.
- Aspirin is not used for gout:
- It inhibits urate excretion at low doses.
- May increase risk of renal calculi at high doses.
- Tolmetin is ineffective in gouty arthritis for unknown reasons.
Frequent uses of aspirin decreases chances of?
Colon Cancer by 50%
CARDIOVASCULAR ADVERSE EFFECTS
how are they caused by NSAIDs
NSAIDs can increase the risk of CV events (heart attack, stroke, death).
• Adverse CV events are thought to be caused by NSAIDs upsetting the balance between TXA2 and PGI2.
• This may lead to vasoconstriction, platelet aggregation, and thrombosis.
how does Decrease In Renal Blood Flow vary in normal subjects vs patients when it comes to NSAID use?
- NSAIDs have little effect on renal function or BP pressure in normal human subjects.
- However, in patients with CHF, CKD, and other situations in which there is reduced renal perfusion, vasodilating PGs are crucial in maintaining GFR.
- NSAID-induced decreases in PGs may lead to sodium and water retention, edema, increased BP, hyperkalemia, and acute renal failure.
what drug that is no longer used was associated with Analgesic Nephropathy?
Phenacetin
ASPIRIN HYPERSENSITIVITY
Cause?
Symptoms?
•Caused by increase in biosynthesis of leukotrienes. • Due to diversion of arachidonate to lipoxygenase metabolism as a consequence of COX inhibition Symptoms: •Vasomotor rhinitis •Angioedema •Urticaria •Bronchial asthma •Laryngeal edema - Bronchoconstriction •Flushing •Hypotension •Shock
Drug Interactions of NSAIDs affect these drugs in what way?
Corticosteroids?
Warfarin?
- NSAIDs may increase frequency or severity of gastrointestinal ulceration when combined with corticosteroids
- NSAIDs may increase risk of bleeding in patients receiving warfarin.
When are NSAIDs CI’d during pregnancy?
Close to term
All other salicylates except aspirin are?
Reversible
Aspirin uses:
it is a potent?
- Treatment of mild to moderate pain.
- Effective analgesic for rheumatoid arthritis and other inflammatory joint conditions.
- Potent antipyretic (fever).
Aspirin uses in cardiovascular tx are due to?
- Aspirin inhibits platelet aggregation.
* Low doses are used for their cardioprotective effects.
When are salicylates analgesic and antipyretic and anti-inflammatory?
- Salicylates are analgesic and antipyretic at low doses.
- They are anti-inflammatory at higher doses.
- Low doses of aspirin (
Metabolism of aspirin and dose relationship:
how does the dosage affect excretion?
- With doses of aspirin of 1g or more, the conjugation enzymes become saturated and zero-order kinetics are observed.
- The time required to eliminate 50% of the salicylate lengthens as the dose of aspirin increases.
Aspirin AE
- GI: Epigastric distress.
- Blood: Prolonged bleeding time.
- Reye’s syndrome
- Hypersensitivity: Reflects diversion of arachidonate to lipoxygenase metabolism as a consequence of COX inhibition.
Aspirin Uricosuric Effects?
- Low doses of aspirin compete with uric acid for secretion and thus reduce uric acid secretion.
- Large doses compete with uric acid for reabsorption and thus increase uric acid excretion in the urine.
Hepatic effects of aspirin
- Salicylates can cause hepatic injury in patients treated with high doses of salicylates.
- The onset occurs after several months of treatment.
- Reversible upon discontinuation of salicylates.
- Salicylates are contraindicated in patients with chronic liver disease.
Aspirin and pregnancy.
What categories does it induce and at what stage?
- Category C risk during Trimesters 1 and 2
* Category D during Trimester 3.
SALICYLATE INTOXICATION is termed? and includes?
Salicylism
• The syndrome includes headache, dizziness, tinnitus, mental confusion and hyperventilation.
SALICYLATE INTOXICATION:
- How do patients present with acute overdose
- Prolonged exposure?
- What is the main cause of death?
- present w/ mixed respiratory alkalosis and metabolic acidosis.
- Prolonged exposure to high doses of salicylates leads to depression of the medulla, with central respiratory depression and circulatory collapse.
- Respiratory failure is the usual cause of death.
