Cox

Question 1

COX

Answer 1

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

Question 2

COX in the uterus lol

Answer 2

Promote contractions at term

Question 3

COX-1

Answer 3

Housekeeping. Protects gastric mucosa and supports renal function and platelet aggregation

Question 4

COX-2

Answer 4

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

Question 5

Inhibition of COX-1

Answer 5

Gastric erosion/ulceration
Bleeding tendencies
Renal impairment
Protects against MI and stroke

Question 6

Inhibition of COX-2

Answer 6

Suppression of inflammation
Alleviation of pain
Reduction of fever
Protects against butt cancer
Renal impairment, promotion of MI and stroke secondary to suppressing vasodilation

Question 7

Stomach and COX

Answer 7

Cox 1 gastric protection
Increased bicarb secretion
Increased mucus production
Decreased acid secretion
Maintenance of submucosal blood flow

Question 8

Blood vessels and COX

Answer 8

Cox 2 promotes vasodilation

Question 9

Kidney and COX

Answer 9

COX-1 and COX -2 cause renal vasodilation and promote renal perfusion

Question 10

Injured tissue COX

Answer 10

COX 2 causes inflammation and pain at local injury site

Also causes fever and pain in the brain

Question 11

First and second gen cox inhibitors

Answer 11

First inhibit COX-1 and 2

Second inhibit only COX-2 (in theory much safer, in practice may be more dangerous)

Question 12

Aspirin

Answer 12

Reduction of inflammation pain and fever from COX-2 inhibition
COX-1 inhibition inhibits platelet aggregation
Only irreversible inhibitor of the NSAIDs

Question 13

Metabolism, distribution, excretion of ASA

Answer 13

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

Question 14

Plasma salicylate levels

Answer 14

100mcg/mL in low therapeutic doses
150-300mcg/mL for anti inflammatory
Toxicity at 400mcg/mL

Question 15

ASA uses

Answer 15

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

Question 16

Why does ASA effect stomach

Answer 16

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

Question 17

ASA BP

Answer 17

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

Question 18

ASA kidneys

Answer 18

Acute impairment from ASA causes retention of Na and H2O and edema
Risks are age, hypovolemia, hepatic issues, heart failure

Question 19

Salicylism

Answer 19

Tinnitus, sweating, headache, dizziness, acid-base disturbances.
Sometimes just need a break then a lower dose after symptoms resolve.

Question 20

Aspirin OD signs and symptoms

Answer 20

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

Question 21

Pathophysiology of ASA OD

Answer 21

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

Question 22

Toxic ASA dose typically

Answer 22

Greater than 150mg/kg
Moderate at 300mg/kg
Severe between 300-500mg/kg
100mg/kg per day for two or more days

Question 23

Reyes syndrome

Answer 23

20-30% mortality rate
Don’t give in children or teens suspected of having influenza or chickenpox
Use tylenol
Fatty liver and encephalopathy

Question 24

Reyes syndrome presentation

Answer 24

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

Question 25

ASA pregnancy

Answer 25

Prostaglandins help keep ductus arteriosus patent inhibition may induce closer
Class D
Other birth defects

Question 26

ASA induced asthma

Answer 26

Acute rhinorrhea, lead to generalized uticaria, bronchospasm, laryngeal edema and shock
COX-1 inhibition triggers leukotrienes which cause symptoms
Epi is treatment

Question 27

ASA and other NSAIDS

Answer 27

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

Question 28

Non-aspirin first gen NSAIDS

Answer 28

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

Question 29

Other NSAIDS indicated before aspirin in

Answer 29

RA, OA, fever, bursitis, tendinitis, pain control, dysmenorrhea

Question 30

Ibuprofen (related to aleve)

Answer 30

Fever, pain, arthritis
Usually best one for dysmenorrhea (inhibits COX in uterine smooth muscle)
Very good for closing ductus arteriosus
Less bleeding

Question 31

Steven-Johnson syndrome

Answer 31

Rare ibuprofen hypersensitivity can result in blistering of skin and mucus membranes, scarring blindness death

Question 32

Naproxen

Answer 32

Highly selective for COX-1

Question 33

Diclofenac

Answer 33

Voltaren
Also comes orally
When its in a cream, 5% compared to oral is absorbed, but still has as good of effects.

Question 34

Ketorolac

Answer 34

Power analgesic with minimal antiinflammatory actions

Begins 30 minutes in, peaks 1-2 hours, persists 4-6 for parenteral

Question 35

Coxibs

Answer 35

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

Question 36

Acetaminophen

Answer 36

Analgesic and antipyretic properties equal to aspirin, no anti inflammatory action or antiplatelet function
Most used analgesic in the US

Question 37

MOA acetaminophen

Answer 37

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

Question 38

Acetaminophen metabolism

Answer 38

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.

Question 39

Tylenol liver damage

Answer 39

50% of all liver failure from tylenol

Fasting, booze, and 4g+ a day increase risk

Question 40

Acetaminophen OD presentation

Answer 40

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