NSAIDS/Nonopiods

Question 1

Arachidonic acid pathway

Answer 1

Cell injury -> phospholipase -> arachidonic acid ->COX breaks down arachidonic acid -> PGs (prostacyclin PGI2, PGE2) and thromboxane

NSAIDS block COX activity and push pathway into lipoxygenase -> leukotrienes (MOA for Asthma)

NSAIDS not good for those w asthma

Question 2

PG role in pain and inflammation

Answer 2

Mostly COX -2

Cytokines (TNFa, IL-1, IL-8) liberate PG at sites of inflammation
Act on PG receptors to cause pain and inflammation
Work on dorsal horn of spine: increase sensitivity of adenyklate cyclase to stimulation of pain
Enhance neurotransmitter releases and act post synaptically

Question 3

COX 1 vs COX 2

Answer 3

COX -1 : constitutive and physiologic - around all the time - protective housekeeping
COX -2: inductively during times of inflammation (inflammation and pain)

Question 4

PG housekeeping

Answer 4

1 GI protective: increase blood flow, mucus production, gastric bicarbonate secretion and decrease gastric acid secretion

2. Renal vasodilation (PGE2, PGI2): inhibit sodium and chloride reabsorption, decrease BP, increase blood flow to kidneys
3. fever (PGE2)

4 Uterine contraction (PGE2)- use for menstrual pain

Question 5

Thromboxane activities

Answer 5

Promote platelets aggregation (COX-1)
Vasoconstriction
Vascular proliferation

Prostacyclin is opposites and COX-2

Question 6

NSAID MOA

Answer 6

Reversible inhibit COX-1 in platelets (COX-1 only isoform in platelets)

Indications:
Inflammation, surgery, arthritis (RA,OA)
Pain in multiple disease states: cancer, muscle, bone, menstrual

KILLS MORE PTS BY SERIOUS ADVERSE EFFECTS THEN ANY OTHER MED

Question 7

NSAID adverse effects: GI

Answer 7

1. GI:
   Cox inhibition and local irritation,
   Increased age, concurrent GI problems, smoking, alcohol use, steroid use (risk factors)

Can reduce issues with proton pump inhbitors (misoprostol) and high dose histamine-2 blockers

Ketorlac worse for GI

Question 8

NSAID adverse effects: Renal

Answer 8

Renal patients more dependent on renal blood flow

PGs control renal blood flow: inhibit reabsorption of chloride ions actions of ADH (vasopressin)

ADH normally makes you retain water, PG make you pee
5 mm Hg increase in BP for non selective NSAIDs

NSAIDS can cause salt retention, hyperkalemia, edema

Reduced GFR can precipitate renal failure (ketoraloc)

Question 9

NSAID adverse effects: drug interactions

Answer 9

ACE inhibitors: block production of vasodilator/natiuretic PG - block anti HT effects

Corticosteroids: increase risk of GI ulceration

Warfarin: increase rIsk of bleed

Warfarin, sulfonylureas, methotrexate: displacement from protein binding

Question 10

Acetatmetophen

Answer 10

Peripherally blocks pain impulse generation

Inhibition of hypothalamic heat-regulating venter

Selective COX-2 inhibitor

NO EFFECT on platelet function, NO ANTIINFLAM
Fewer adverse effects then other nonopiod analgesics

USES: mild to mod pain (headache), antipyretic, OA pain

Question 11

Acetatmetophen adverse events

Answer 11

Hepatoxicity

Low dose elimated by glucuronidation, sulfination
High dose: N-hydrocylation -> NAPQI -> mopped up by glutathione (GSH) -> excreted in urine
Overdose: GHS depleted-> NAPQI binds covalently to macromolecules -> apoptosis

Precautions:
Liver disease, alcoholics
Max dosel: 4g/day (less if elderly or alcoholic)

Question 12

Aspirin

Answer 12

Analgesic, antiinflammatorym antipyretic
Antiplateltte effect: irreversibly binds and acetylates active site on COX (thromboxane)

Cardioprotective

Do not use with NSAIDS

Question 13

COX-2 inhibitors

Answer 13

Designed to preserve COX-1

Beneficial anti inflammatory, analgesic, antipyretic effects without GI and platelet effects that are mediated through COX-1

Will not reverse cardioprotective properties of aspirin (not COX-2 mediated)

Reduce GI complications but increase CV events vs traditional NSAIDS
COX-2 also found in CNS and kidney
Cause fluid retention and SBP