MSS Pharmacology

Question 1

What does the Lipoxygenase pathway yield?

Answer 1

Leukotrienes

Question 2

What is LTB₄?

Answer 2

Neutrophil chemotatic agent

Question 3

What do LTC₄, D₄ & E₄ function in?

Answer 3

Bronchoconstriction, vasoconstriction, contraction of sm & inc vascular permeability

Question 4

What do PGI₂ do?

Answer 4

Inhibits platelet aggregation & promotes vasodilation

(Platelet-Gathering-Inhibitor)

Question 5

What is the MOA of aspirin?

Answer 5

Irreversibly inhibits COX-1 & COX-2 by acetylation, which dec synthesis of both thromboxane A2 (TXA2) & PG. Inc bleeding time. Nof affect on PT, PTT. Type of NSAID

Question 6

Clinical use of aspirin

Answer 6

• Low dose: (<300mg/day) dec platelet aggregation
• Indermediate dose (300-2400 mg/day) antipyretic & analgesic
• High dose (2400-4000 mg/day) anti-inflam

Question 7

What can aspirin toxicity cause?

Answer 7

• Gastric ulceration
• Tinnitus (CN VIII)
• Chronic use can l/t acute renal failure, intersitial nephritis, & upper GI bleeding
• Risk of Reye’s synd in children tx w/ apsirin for viral infection
• Stim resp centers, causing hyperventilation & resp alkalosis

Question 8

What are examples of NSAIDs?

Answer 8

• Ibuprofen
• Naproxen
• Indomethacin
• Ketoralac
• Diclofenac

Question 9

What is the MOA of NSAIDs?

Answer 9

Reversibly inhibits COX 1 & 2 & blocks PG synthesis

Question 10

What are the clinical uses of NSAIDs?

Answer 10

• Antipyrenic
• Analgesic
• Anti-inflam
• Indomethacin is used to close a PDA

Question 11

What can NSAID toxicity cause?

Answer 11

• Interstitial nephritis
• Gastric ulcer (PG’s protect gastric mucosa)
• Renal ischemia (PG vasodilate afferent arteriole)

Question 12

What is the MOA of COX-2 inhibitors (celecoxib)?

Answer 12

Reversibly inhibit specifically the COX isoform 2, which is found in inflam cells & vascular endothelium & mediates inflam & pain. Spares COX-1 & TXA₂

Question 13

What is the clinical use of COX-2 inhibitors?

Answer 13

Rheumatoid arthritis & osteoarthritis; pts w/ gastritis or ulcers

Question 14

What can COX-2 inhibitor toxicity cause?

Answer 14

Inc risk of thrombosis; sulfa allergy

Question 15

What is the MOA of Acetaminophen?

Answer 15

Reversibly inhibits COX, mostly in CNS. Inactivated peripherally

Question 16

What are the clinical uses of Acetaminophen?

Answer 16

• Antipyretic
• Analgesic but not anti-inflam
• Used instead of aspirin to avoid Reye’s synd in children w/ viral infection

Question 17

What can Acetaminophen toxicity cause?

Answer 17

Overdose produces hepatic necrosis; acetaminophen metabolite depletes gluthione & forms toxic tissue adducts in liver. N-acetylcysteine is antidote-regenerates glutathione.

Question 18

What is an example of a bisophosphonates?

Answer 18

Alendronate, other -dronates

Question 19

What is the MOA of Bisphosphates?

Answer 19

Pyrophosphate analogs; bind hydroxyapatite in bone, inhibiting osteoclast activity

Question 20

What are the clinical uses of Bisphosphonates?

Answer 20

• Osteoporosis
• Hypercalcemia
• Paget’s dz of bone

Question 21

What can Bisphosphonate toxicity cause?

Answer 21

Corrosive esophagitis, osteonecrosis of the jaw

Question 22

What are the chronic gout drugs?

Answer 22

• Allopurinol
• Febuxostat
• Proenecid
• Colcchicine

Question 23

What are the Acute gout drugs?

Answer 23

• NSAIDs (naproxen, indomethacin)
• Glucocorticoids (oral or intraarticular)

Question 24

What is the MOA of Allopurinol?

Answer 24

Inhibits xanthine oxidase, dec conversation of xanthine to uric acid

Question 25

What is Allopurinol used for?

Answer 25

* Gout * Lymphoma & leukemia to prevent tumor lysis- assoc w/ urate nephropathy

Question 26

What can Allopurinol inc conc of?

Answer 26

Azathioprine & 6-MP (both normally metabolized by xanthine oxidase)

Question 27

What can you not give Allopurinol w/?

Answer 27

Don't give w/ salicylates; all but the highest doses depress uric acid clearance. Even high doses (5-6g/day) have only minor uriosuric activity

Question 28

What is the MOA of Febuxostat?

Answer 28

Inhibits xanthine oxidase

Question 29

What is the MOA of Probenecid?

Answer 29

Inhibits reabsorption of uric acid in PCT (also inhibits sec of penecillin)

Question 30

What is the MOA of Colchine?

Answer 30

Binds & stabilizes tubulin to inhibit polymerization, impairing leukocyte chemotaxis & degranulation

Question 31

What are the TNF-alpha inhibitors?

Answer 31

* Etanercept * Infliximab * Adalimumab

Question 32

What can all TNF-alpha inhibitors cause?

Answer 32

Predispose to infection including reactivation of latent TB since TNF blockade prevents activation of macro & destruction of phagocytosed microbes

Question 33

What is the MOA of Etanercept?

Answer 33

Fusion protein (recptor for TNF-alpha + IgG₁ Fc), produced by recombiant DNA

Question 34

What are the clinical uses of Etanercept?

Answer 34

* Rheumatoid arthritis * psoriasis * Ankylosing spondylitis

Question 35

What is the MOA of Infliximab & Adalimumab?

Answer 35

Anti-TNF-alpha monoclonal Ab

Question 36

What are the clinical uses of Infliximab & adalimumab?

Answer 36

* Chron's dz * Rheumatoid arthritis * Anklylosing spondylitis * Psoriasis