NSAIDs Pathway Flashcards
When injury occurs, what is the pathway that is activated?
Phospholipase A2
Activation of phospholipase A2 catalyzes hydrolysis of…
Arachidonic acid from phospholipids in the cell membrane
What do NSAIDs do to this pathway?
Inhibit cyclooxygenase enzymes
NSAIDs
- inhibit cyclooxygenase
Inhibits prostaglandins (PGs) synthesis with both beneficial and unwanted effects
Cyclooxygenase enzyme
Converts Arachidonic acid to prostaglandins (PGs) and thromboxane A2
Prostacyclin (PGI)
Released from vascular endothelial cells to prevent platelet aggregation
Thromboxane A2
Stimulates platelet aggregation when blood vessels are injured
Other PGs
PGE1
PGE2
PGE2a
Other PGs are involved in
Pain
Inflammation
Fever
GI cytoprotection
Vasodilation
Maintain renal blood flow
NSAIDs inhibit cyclooxygenase (COX) pathway
- increasing what?
Lipoxygenase pathway
NSAIDs inhibit cyclooyxgenase
- increasing lipoxygenase pathway
Those with respiratory disease become more susceptible to bronchospasm
5-lipoxygenase enzyme
Converts arachidonic acid to leukotrienes
Leukotrienes
Mediate allergy-induced bronchoconstriction
Where are leukotrienes produced?
Mainly in inflammatory cells (mast cells, basophils, eosinophils, macrophages and polmorphonuclear leukocytes)
What blocks 5-lipoxygenase
Zileuton- anti-asthmatic agen
What blocks leukotriene receptors
Montelukast (singulair) and zafirlukast
- controlling the symptoms of asthma and bronchoconstriction
COX-1
Expressed in the stomach to produce PGs
COX-1
- PGs produce?
Cyotprotectin in the GI tract by inhibiting gastric acid secretions
Increasing bicarbonate release
Promoting mucus secretion
NSAIDs inhibit what?
Both COX-1 and COX-2 enzymes
Non-selective NSAIDs
- inhibitation of COX-1
GI side effects
bleeding
Gastric ulcers
COX-2 inhibitors
Spare COX-1 induced synthesis of PGs, preserving the integrity of the lining of the GI tract
MOA of NSAIDs
Blockade of prostaglandin synthesis via inhibition of the enzyme cyclooygenase (COX)
Nonselective COX-1 and COX-2 inhibitors
Acetylsalicyclic acid (asprin)
Ibuprofen
Naproxen
NSAIDs properties
Antipyretic
Analgesic
Anti-inflammatory
Aspirin (acetylsalicylic acid)
Covalently binds and irreversibly inhibits COX-1 and COX-2 enzymes of the platelets (prevents platelet aggregation)
Single dose of aspirin will..
Inhibit platelet COX for 8-11 days (life of the platelet)
Adverse effects and contraindications of Aspirin
High doses cause salicylism (tinnitus, vertigo, hearing loss)
Contraindicated in children and teenagers with chickenpox and influenza
Adverse effects and contraindications
- Chickenpox and influenza
Tied to Reye’s disease, which is a potentially fatal disease accompanied by liver damage and encephalopathy
When should patients stop taking aspirin?
One week prior to surgery or dental procedures d/t tendency of aspirin increasing clotting time and cause excessive bleeding
When taking Aspirin what do you avoid?
Taking it during pregnancy and breast-feeding
Non-selective COX inhibitors
Ibuprofen (Motrin-OTC, Advil-OTC)
Naproxen (aleve-OTC, Naprosyn)- longer half-life
Ketorolac
Ketorolac
Moderate to severe pain and limited to 5 day treatment
Increased incidence of peptic ulcers
Ketorolac
- Do not use with who?
Patients with renal impariement
Celecoxib (celebrex)
Less GI bleeding/irritation
Celecoxib
- Contraindications
Patients allergic to sulfonamides
Avoid in patients with Renal, CV, and cerebrovascular disease (increased risk of heart attack and stroke)
Celecoxib inhibits
CYP2D6 resulting in severe drug interactions
Acetaminophen MOA
Unclear
Acetaminophen effects
Analgesic and antipyretic
Acetaminophen is a weak
COX-1 and COX-2 inhibitor in peripheral tissues
Not an NSAIDs
Acetaminophen bc it lacks anti-inflammatory or anti-platelet effects
Clinical uses of acetaminophen
Mild to moderate pain (HA, myalgia, postpartum pain)
Acetaminophen is preferred for what?
During pregnancy and breastfeeding
Where is acetaminophen metabolized
Liver
What is generated?
minor toxic metabolite that is conjugated to glutathione in the liver and excreted in the kidney
Acetaminophen
- Overdose or standard dose patients with liver impairment
Toxic metabolite accumulates and induces liver damage
Hepatic renal tubular necrosis may occur
How to treat overdose of acetaminophen
Use n-acetylcysteine within 8 hours of overdose bc it binds to the toxic metabolite and counteracts acetaminophen toxicity
Acetaminophen
Tylenol
