Anti-inflammatory drugs

Question 0

Arachidonic acid metabolism

Answer 0

1. COX pathway –> thromboxane, prostaglandin, prostacyclin
   
   • COX-1 and COX-2 mediate
2. Lipoxygenase pathway –> leukotrienes (increase vasoconcstrition, increase bronchial tone) (inhibitors to treat asthma)

Question 1

Arachidonic acid - role in infecton

Answer 1

Cell membrane damage from lysosomal enzymes and phopholipasee A2 –> production

Question 2

NSAID: general therapeutic strategy

Answer 2

inhibit prostaglandin production

Question 3

Glucocorticoid: general how it works; uses; chronic use toxicity

Answer 3

inhibit PLA2 and inhibit COX2 enzyme production
Anti-inflammatory, immune suppression, asthma
chronic use –> iatrogenic Cushing’s syndrome (diabetes, osteoporosis, HTN, moon face)
Cortisone, dexamethasome

Question 4

DMARD treats?

Answer 4

Disease modifying antirheumatic drug
treat RA, immunosuppresant (treat leukemias, lyphomas, abortions)
Methotrexate (MTX)- is a folic acid analog; interferes with THF production

Question 5

Non selective v selective NSAIDs? Pros and cons?

Answer 5

• Nonselective –> more GI toxicity (COX1 is protective)

- Selective Celebrex has more CV risk and HTN, is a sulfonamide –> more rashes

Question 6

Ibuprofen: brand names, treats

Answer 6

Motrin, Advil; RA, OA

Non-selective NSAID

Question 7

Indomethacin: brand name, treats

Answer 7

Indocin; RA, OA, PDA (patent ductus arteriosiis)); normally prostaglandin E1 keeps ductus patent, inhibitors close
Non-selective NSAID

Question 8

Naproxen: brand name, treats

Answer 8

Aleve; OA, RA, inflammation

Non-selective NSAID

Question 9

Celecoxib: brand name; treats; risks

Answer 9

Celebrex; inflammation, OA, RA, anti-pyretic, analgesic
Selective NSAID
Risk for CV and HTN

Question 10

Aspirin unique effects (vs. other non-selective NSAIDs)

Answer 10

Irrev binding to platelet COX –> effect on platelet fxn

Other non-selective NSAIDs are reversible inhibitors

Question 11

Aspirin metabolism

Answer 11

ASA is a weak acid
Acetyl group transferred to COX = irrev inactivate COX (COX normally produces PG H2 which produces TXA2 which is important for platelet aggregation)
(deacetylated ASA = salicylic acid)

Question 12

Aspirin overdose

Answer 12

give bicarb –> alkylinizes the urine which increases excretion rate of salicylate

Question 13

Major uses of aspirin; dose relationship

Answer 13

4As: Anti-inflammatory, analgesic, antipyretic, anticoagulant
<300mg = platelet aggregation
300-2400= antipyretic, analgesic
2400-4000= anti-inflammatory

Question 14

Side effects of ASA

Answer 14

GI effects (nausea, vomit, bleeding); possible tinnitus, increase bleeding time
Chronic: interstitial neprhitis and GI probs, renal failure
Reye's syndrome in kids; often after viral infection; nausea, vomit, encephalopathy, altered liver fxn, altered mental status

Question 15

Signs of ASA overdose

Answer 15

Hyperventilation, CNS depression or respiration

Question 16

ASA is used to treat?

Answer 16

Kawasaki disease (autoimmune diseease of inflamed medium vessels)

• in children under 5
• can cause coronary artery aneurysm in heart
• often viral infection plays role in pathogenesis

Question 17

Acetaminophen: brand name; uses

Answer 17

Tylenol
analgesic, antipyretic (NOT anti-inflammatory)
preferrred for children with viral ifnections

Question 18

Acetaminophen works on?

Answer 18

COX1 and COX2 weak reversible inhibitor in peripheral tissue

Question 19

Acetaminophen toxicity

Answer 19

increase hepatic enzymes
15g –> severe hepatotoxicity w centrolobular necrosis
no more than 4-5g/day
p450 in liver metabolizes –> toxic intermediate accum which deplete glutathione production

Question 20

Treating acetaminophen toxicity

Answer 20

N-acetylcysteine binds toxic intermediate; given within 4-6 hours