Cox Flashcards
COX
Converts arachidonic acid into prostanoids (prostaglandins, protacyclin, TXA2)
At site of injury catalyzes synthesis of PGE2 and PGI2 (prostacyclin) which promote inflammation and sensitize receptors to painful stimuli
PGE2, PGI2, TXA2 all act locally, do not effect distant sites
COX in the uterus lol
Promote contractions at term
COX-1
Housekeeping. Protects gastric mucosa and supports renal function and platelet aggregation
COX-2
Produced at site of injury, mediates inflammation and sensitizes receptors to painful stimuli
In the brain mediates fever and perception of pain
Supports kidney function
Promotes vasodilation
Contributes to butt cancer
Inhibition of COX-1
Gastric erosion/ulceration
Bleeding tendencies
Renal impairment
Protects against MI and stroke
Inhibition of COX-2
Suppression of inflammation Alleviation of pain Reduction of fever Protects against butt cancer Renal impairment, promotion of MI and stroke secondary to suppressing vasodilation
Stomach and COX
Cox 1 gastric protection Increased bicarb secretion Increased mucus production Decreased acid secretion Maintenance of submucosal blood flow
Blood vessels and COX
Cox 2 promotes vasodilation
Kidney and COX
COX-1 and COX -2 cause renal vasodilation and promote renal perfusion
Injured tissue COX
COX 2 causes inflammation and pain at local injury site
Also causes fever and pain in the brain
First and second gen cox inhibitors
First inhibit COX-1 and 2
Second inhibit only COX-2 (in theory much safer, in practice may be more dangerous)
Aspirin
Reduction of inflammation pain and fever from COX-2 inhibition
COX-1 inhibition inhibits platelet aggregation
Only irreversible inhibitor of the NSAIDs
Metabolism, distribution, excretion of ASA
15-20 minute half life, converted to salicylic acid (active metabolite) which is 2 hours to 20 hours depending on dose Extensively bound (80-90%) to albumin, boob juice and CNS Excretion highly dependent on urinary pH, raising pH of urine 6-8 can increase rate of excretion 4X
Plasma salicylate levels
100mcg/mL in low therapeutic doses
150-300mcg/mL for anti inflammatory
Toxicity at 400mcg/mL
ASA uses
Inhibits pain from COX-2 (good for headaches, joint pain, but no good for visceral)
Inhibits inflammation from COX-2 (higher doses needed)
Inhibits fever from COX-2 (inhibits pyrogen induced synthesis of prostaglandins) COX in uterus causes contraction so NSAIDS are good for dysmenorrhea
Inhibit platelet aggregation from COX-1
Why does ASA effect stomach
COX-1 inhibition leads to: Increased secretion of acid and pepsin Decreased production of cytoprotective mucus and bicarb Decreased submucosal blood flow ASA directly irritates PPI or H2 antagonist
ASA BP
Stop 1 week prior to major, don’t stop for minor
Reduces ischemic stroke risk but increases hemorrhagic. BP should be under 150/90 before starting
ASA kidneys
Acute impairment from ASA causes retention of Na and H2O and edema
Risks are age, hypovolemia, hepatic issues, heart failure
Salicylism
Tinnitus, sweating, headache, dizziness, acid-base disturbances.
Sometimes just need a break then a lower dose after symptoms resolve.
Aspirin OD signs and symptoms
N/V abdo pain, tinnitus lethargy dizziness
High body temp, increased resp rate, resp alkalosis, metabolic acidosis, hypokalemia, hypoglycemia, hallucinations, confusion, seizure, cerebral edema and coma, pulmonary edema causes cardiopulmonary arrest
Pathophysiology of ASA OD
Phase I: Direct resp stimulation results in respiratory alkalosis, resulting in bicarb and K+ being excreted in urine. Lasts 12 hours
Phase II: Paradoxic aciduria in presence of resp alkalosis, occurs after enough K+ has been lost. Starts a few hours in lasts 12-24 hours
Phase III: Dehydration, hypokalemia, progressive metabolic acidosis. 4-6 hours in infants and 24 hours later in adults
Toxic ASA dose typically
Greater than 150mg/kg
Moderate at 300mg/kg
Severe between 300-500mg/kg
100mg/kg per day for two or more days
Reyes syndrome
20-30% mortality rate
Don’t give in children or teens suspected of having influenza or chickenpox
Use tylenol
Fatty liver and encephalopathy
Reyes syndrome presentation
Rash on palms of hands and feet Persistent heavy vomiting Generalized lethargy Confusion, nightmares, Stupor, hyperventilation, hyperactive reflexes, coma, resp arrest Mostly in children, more mild in adults
ASA pregnancy
Prostaglandins help keep ductus arteriosus patent inhibition may induce closer
Class D
Other birth defects
ASA induced asthma
Acute rhinorrhea, lead to generalized uticaria, bronchospasm, laryngeal edema and shock
COX-1 inhibition triggers leukotrienes which cause symptoms
Epi is treatment
ASA and other NSAIDS
Compete with COX-1 and diminish aspirin effect.
Since max effects hit in 1 hour after ASA, if given 2 hours before other NSAID it should still work
Non-aspirin first gen NSAIDS
Reversible inhibition of COX-1 and 2 None approve for pregnancy All have antiinflam, analgesic and antipyretic properties All effect GI and kidneys All increases risk of MI and stroke
Other NSAIDS indicated before aspirin in
RA, OA, fever, bursitis, tendinitis, pain control, dysmenorrhea
Ibuprofen (related to aleve)
Fever, pain, arthritis
Usually best one for dysmenorrhea (inhibits COX in uterine smooth muscle)
Very good for closing ductus arteriosus
Less bleeding
Steven-Johnson syndrome
Rare ibuprofen hypersensitivity can result in blistering of skin and mucus membranes, scarring blindness death
Naproxen
Highly selective for COX-1
Diclofenac
Voltaren
Also comes orally
When its in a cream, 5% compared to oral is absorbed, but still has as good of effects.
Ketorolac
Power analgesic with minimal antiinflammatory actions
Begins 30 minutes in, peaks 1-2 hours, persists 4-6 for parenteral
Coxibs
COX-2 inhibitors
Theory it should be safer for GI sides (there may be fewer GI sides)
Impairs renal function causing HTN and edema, increasing chance of MI and stroke
Acetaminophen
Analgesic and antipyretic properties equal to aspirin, no anti inflammatory action or antiplatelet function
Most used analgesic in the US
MOA acetaminophen
Inhibition of COX, but only in CNS (minimal peripherally)
Inability to inhibit COX peripherally explains why it has no antiinflam, gastric, renal or platelet effects
Acetaminophen metabolism
Major pathway acetaminophen undergoes conjugation with glucoronic acid to form non-toxic metabiloite
Minor pathway oxidized by P450 and N-acetyl-p-benzoquinoneimime. Converts to non toxic form with glutathione.
Tylenol liver damage
50% of all liver failure from tylenol
Fasting, booze, and 4g+ a day increase risk
Acetaminophen OD presentation
N/V diarrhea, sweating, abdo pain
48-72 hours after is when liver damage appears
Acetylcysteine is 100% effective in first 8-10 hours, can be good for up to 24 hours
