Pharmacology

Question 1

Acetaminophen

Answer 1

Mechanism: reversibly inhibits COX. mostly acts in CNS. inactivated peripherally
Use: antipyretic (CNS), analgesic. NOT antiinflammatory (doesnt act peripherally). Used in children with viral infection to avoid aspirin use
Adverse effects: hepatic necrosis (metabolite NAPQI depletes glutathione and is toxic to hepatocytes) - N-acetylcysteine is antidote (regenerates glutathione)

Question 2

Aspirin

Answer 2

Irreversibly inhibits COX 1+2 via acetylation. decreases TXA2 and prostaglandins. causes increased bleeding time (no effect on PT, PTT). effect lasts until new platelets synthesized
USE:
low dose (<300mg): anti-platelet aggregation
Medium (300-2400): antipyretic and analgesic
High (2400-4000): anti-inflammatory
Adverse effects: tinnitus (VII), early respiratory alkalosis followed by mixed metabolic acidosis-respiratory alkalosis. Acute renal failure and interstitial nephritis, GI bleeding, gastric ulceration, Reye syndrome risk in children, allergic reaction

Question 3

Celecoxib

Answer 3

Reversibly and selectively inhibits COX2. blocks prostaglandins but not TXA2
Use: anti-inflammatory + pain relief –> RA, OA
Adverse effects: risk of thrombi, sulfa allergy
NOTE: GI is spared unlike with other NSAIDs

Question 4

ketorolac

Answer 4

NSAID - reversibly block COX (blocks prostaglandin synthesis)
Use: antipyretic, analgesic, anti-inflammatory
Adverse effects: gastric ulcer, interstitial nephritis, renal ischemia (prostaglandins dilate afferent arteriole), aplastic anemia

Question 5

Diclofenac

Answer 5

NSAID - reversibly block COX (blocks prostaglandin synthesis)
Use: antipyretic, analgesic, anti-inflammatory
Adverse effects: gastric ulcer, interstitial nephritis, renal ischemia (prostaglandins dilate afferent arteriole), aplastic anemia

Question 6

Meloxicam, piroxicam

Answer 6

NSAID - reversibly block COX (blocks prostaglandin synthesis)
Use: antipyretic, analgesic, anti-inflammatory
Adverse effects: gastric ulcer, interstitial nephritis, renal ischemia (prostaglandins dilate afferent arteriole), aplastic anemia

Question 7

ibuprofen, naproxen

Answer 7

NSAID - reversibly block COX (blocks prostaglandin synthesis)
Use: antipyretic, analgesic, anti-inflammatory
Adverse effects: gastric ulcer, interstitial nephritis, renal ischemia (prostaglandins dilate afferent arteriole), aplastic anemia

Question 8

Indomethacin

Answer 8

NSAID - reversibly block COX (blocks prostaglandin synthesis)
Use: antipyretic, analgesic, anti-inflammatory. CLOSES PDA (CI in third trimester)
Adverse effects: gastric ulcer, interstitial nephritis, renal ischemia (prostaglandins dilate afferent arteriole), aplastic anemia

Question 9

Leflunomide

Answer 9

Mechanism: reversibly inhibits dihydroorotate dehydrogenase - prevents pyrimidine synthesis - suppresses T cell proliferation
USE: RA, OA
Adverse effects: Hepatoxicity, teratogenic, diarrhea, HTN

Question 10

Alendronate, ibandronate, risedronate, zoledronate

Answer 10

Bisphosphonates
Mechanism: pyrophosphate analogs. bind hydroxyapatite in bone and inhibit osteoclasts
Use: osteoporosis, hypercalcemia, paget disease of bone, metastatic bone disease, osteogenesis imperfecta
Adverse effects: Esophagitis (prevent by taking with water and remaining upright for 30 mins), osteonecrosis of jaw, atypical femoral stress fractures

Question 11

Teriparatide

Answer 11

Recombinant PTH analog - increases osteoblastic activity when give in pulsatile manner
Use: Osteoporosis (causes bone growth compared to antiresorptive therapy)
Adverse effects: increased risk of osteosarcoma. CI in patients with pagets or unexplained elevated alkaline phosphatase. Also CI in aptients with prior cancer or radiation. Causes transient hypercalcemia

Question 12

Probenecid

Answer 12

Gout drug
Mechanism: inhibits reabsorption of uric acid in the kidney. Also prevents excretion of certain drugs including penicillin and cidovir
Adverse effect: can precipitate uric acid calculi

Question 13

Allopurinol

Answer 13

Gout drug
Mechanism: competitive inhibitor of xanthin oxidase which decreases conversion of hypoxanthine and xanthine to uric acid
Other Uses: prevention of Tumor lysis syndrome -ie. urate nephropathy (leukemia and lymphoma)
Adverse effects: increase concentration of azathioprine and 6-MP which can result in toxicity (these drugs are metabolized by XO)

Question 14

Pegloticase

Answer 14

Severe refractory gout

Mechanism: catalyzes conversion of uric acid to the more water soluble allantoin

Question 15

Febuxostat

Answer 15

Same action as allopurinol

Question 16

Colchicine

Answer 16

Acute and prophylactic gout treatment
Mechanism: binds and stabilizes tubulin which inhibits microtubule polymerization. Impairs neutrophil chemotaxis and degranulation
Side effects: diarrhea, neuromyopathic effects

Question 17

Acute gout treatment

Answer 17

NSAIDs, caution with salicylates because can decrease uric acid excretion at low doses
Glucocorticoids
Colchincine

Question 18

Etanercept

Answer 18

Fusion protein (decoy receptor for TNF-alpha) - produced via recombinant DNA
Use: RA, psoriasis, ankylosing spondylitis
Adverse effects: predisposition to infection, including TB reactivation (TNF important in granuloma formation) - always treat TB first. Drug induced SLE

Question 19

Infliximab

Answer 19

Anti-TNF-alpha monoclonal Ab.
USE: IBD, RA, ankylosing spondylitis, psoriasis
Adverse effects: predisposition to infection, including TB reactivation (TNF important in granuloma formation) - always treat TB first. Drug induced SLE

Question 20

Adalimumab

Answer 20

Anti-TNF-alpha monoclonal Ab.
USE: IBD, RA, ankylosing spondylitis, psoriasis
Adverse effects: predisposition to infection, including TB reactivation (TNF important in granuloma formation) - always treat TB first. Drug induced SLE

Question 21

Certolizumab

Answer 21

Anti-TNF-alpha monoclonal Ab.
USE: IBD, RA, ankylosing spondylitis, psoriasis
Adverse effects: predisposition to infection, including TB reactivation (TNF important in granuloma formation) - always treat TB first. Drug induced SLE

Question 22

Golimumab

Answer 22

Anti-TNF-alpha monoclonal Ab.
USE: IBD, RA, ankylosing spondylitis, psoriasis
Adverse effects: predisposition to infection, including TB reactivation (TNF important in granuloma formation) - always treat TB first. Drug induced SLE