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Flashcards in MSK Drugs Deck (36):
1

Two main pathways for arachidonic acid metabolism

1. Lipoxygenase --> Leukotrienes
2. COX pathways (COX-1, COX-2) --> Prostaglandins, Thromboxane

2

LBT4

Attracts neutrophils

3

LTC4, LTD4, LTE4

Function in bronchoconstriction, vasoconstriction, contraction of smooth muscle and increase in vascular permeability

* Target of anti-leukitriene medications in asthma

4

PGI2

Inhibits platelet aggregation and promotes vasodilation

PGI = "Platelet Gathering Inhibitor"

5

Prostaglandins (PGE2, PGF2)

- Increase uterine tone
- Decrease vascular tone
- Decrease bronchial tone

** Aspirin causes wheezing because these prostaglandins are blocked due to COX inhibiton so only bronchoconstriction causing leukotrienes are left

6

Thromboxane

- Increase platelet aggregation
- Increase vascular tone
- Increase bronchial tone

7

Aspirin: Mechanism

IRREVERSIBLY inhibits COX-1 and COX-2 by acetylation which decreases thromboxane and prostaglandins

- Increase bleeding time
- No effect on PTT, PT

8

Aspirin: Clinical Use

Low dose (< 300 mg/day): decreased platelet aggregation

Intermediate dose (300 - 2400 mg/day): antipyretic and analgesic

High dose (2000 - 4000 mg/day): anti-inflammatory

9

Aspirin: Toxicity

Gastric ulceration (due to COX-1 inhibition which maintains GI mucosa)
- Tinnitus
- Chronic use can lead to renal failure, interstitial nephritis and upper GI bleeding
- Reye's syndrome when used in children for tx of viral infection
- Aspirin- induced asthma, Hyperventilation (respiratory alkalosis)

10

NSAIDS

Ibuprofen, Naproxen, Indomethacin, Ketorolac, Diclofenac

11

NSAIDs: Mechanism

REVERSIBLY inhibit cyclooxyenase (both COX-1 and COX-2). Block prostaglandin synthesis

12

NSAIDs: Clinical Use

Antipyretic, analgesic, anti-inflammatory

13

Tx for PDA closure

Indomethacin

14

NSAIDs: Toxicity

Interstitial nephritis
Gastric ulcer
Renal ischemia (PG vasodilate afferent arteriole

15

COX-2 inhibitors

Celecoxib

16

COX-2 Inhibitors (Celecoxib) : Mechanism

Reversibly inhibit COX-2, which is found in inflammatory cells and vascular endothelium and mediates inflammation and pain

- Spares GI lining (normally maintained by COX-1
- Spares platelet function as platelet normally associated with COX-1

17

Celecoxib (COX-2 inhibitor): Toxicity

Increased risk of thrombosis (can lead to acute MI). Sulfa allergy

18

Acetaminophen

Reversibly inhibits COX, mostly in CNS. Inactivated peripherally

19

Acetaminophen: Clinical use

Antipyretic, Analgesic, but not anti-inflammatory. Used instead of aspirin to avoid Reye's syndrome in children with viral infection

20

Acetaminophen: Toxicity

Overode produces hepatic necrosis as acetaminophen depletes glutathione (which protects against free radicals) and form toxic liver tissue.

21

Tx for acetaminophen overdose

N-acetylcysteine - regenerates glutathione depleted with acetaminophen use

22

Bisphosphonates

ends in -dronates
Alendronate

23

Bisphosphonate: Mechanism

- Pyrophosphate analog (critical component of hydroxyapatite in bone)
- Bind hydroxyapatite in bone
- Inhibits osteoclast activity

24

Bisphosphonate: Clinical Use

Osteoporosis
Hypercalcemia
Paget's disease of bone

25

Bisphosphonate: Toxcity

Corrosive esophagitis (advise patients to sit up when taking)
- Osteonecrosis of jaw (contraindicated during dental work)

26

Chronic gout drugs

Allopurinol, Febuxostat, Probenecid, Colchicine

27

Allopurinol

Inhibits xanthine oxidase which decreases conversion of xanthine to uric aic
- Used in lymphoma and leukemia to prevent tumor lysis - associated with urate nephropathy
- Increase concentrations of azathioprine and 6-MP (both normally metabolized by xanthine oxidase)

28

Discuss salicylates and drug use

Don't give salicylates. All but high doses suppress uric acid clearance.

29

Febuxosate

Inhibit xanthine oxidase

30

Probenecid

Inhibits reabsorption of uric acid in PCT (also inhibits secretion penicillin)

31

Colchicine

Binds and stabilizes tubulin to inhibit polymerixation, impairing leukocyte chemotaxis and degranulation

** GI side effects, especially if given orally

32

Acute gout drugs

NSAIDs, Glucocorticoids (can be given orally or intraarticular)

33

TNF-alpha inhibitors

Etanercept, Infliximab, Adalimumab

34

Discuss TNF-alpha inhibitors and Infection

Can predispose to infection including reactivation of latent TB since TNF blockage prevents activation of macrophages and destruction of phagocytosed microbes

35

Etanercept

Fusion protein (receptor for TNF-alpha + IG1Fc) produced by recombinant DNA

- Is a decoy TNF receptor

- used for Rheum Arthritis, Psoriasis, Ankylosing Spondylitis

36

Infliximab, Adalimumab

Anti-TNF-alpha monoclonal antibody

- Used for Crohn's, Rheum Arthritis, Ankylosing Spondyltis, Psoriasis