NSAIDs, acetaminophen & drugs used in RA & gout

Question 1

Aspirin

Answer 1

• MOA
• acetylation of COX-1 and COX-2 results in decreased prostaglandin synthesis
• Clinical
• analgesia, antipyretic, anti-inflammatory, antithrombotic
• prevention of colon cancer
• Kinetics
• duration of action longer than t_1/2 due to irrevelrsible COX inhibition
• Tox, int.
• GI toxicity, nephrotoxicity, increased bleeding time
• hypersensitivity reaction due to increased leukotrienes (e.g. asthma)
• tinnitus, hyperventilation, metabolic acidosis, hyperthermia, coma

Question 2

Ibuprofen

Answer 2

• MOA
• reversible inhibition of COX-1 and COX-2 results in decreased prostaglanding synthesis
• Clinical
• analgesia, antipyretic, anti-inflammatory
• closure of patent ductus arteriosus
• Kinetics
• rapid metabolism and renal elimination
• Tox, int.
• GI toxicity, nephrotoxicity
• hypersensitivity due to increased leukotrienes, interference with aspirin’s antithrombotic action

Question 3

Celecoxib

Answer 3

• MOA
• selective, reversible COX-2 inhibition resulting in decreased prostaglandin synthesis
• Clinical
• analgesia, antipyretic, anti-inflammatory
• Kinetics
• hepatic metabolism
• Tox, int.
• nephrotoxicity, hypersensitivity due to increased leukotrienes, less risk of GI toxicity than nonselective NSAIDs
• greater risk of thrombosis than nonselective NSAIDs

Question 4

Acetaminophen/paracetamol

Answer 4

• MOA
• unknown, weak COX inhibitor
• Clinical
• analgesia, antipyretic
• Kinetics
• hepatic conjugation
• Tox, int.
• hepatotoxicity in overdose - antidote is N-acetylcysteine
• hepatotoxicity is more likely with chronic alcohol consumption (CYP induction)

Question 5

Methotrexate

Answer 5

• MOA
• inhibition of dihydrofolate reductase
• cytotoxic to rapidly dividing immune cells
• Clinical
• anticancer, rheumatic disorders
• Kinetics
• renal elimination
• Tox, int.
• nausea, mucosal ulcers, hematotoxicity, hepatotoxicity, teratogenicity

Question 6

Colchicine

Answer 6

• MOA
• inhibition of microtubule assembly decreases macrophage migration and phagocytosis
• Clinical
• chronic and acute gout, familial mediterranean fever
• Kinetics
• oral
• Tox, int.
• diarrhea, severe liver and kidney damage in overdose

Question 7

Probenecid

Answer 7

• Uricosuric
• MOA
• inhibition of renal reuptake of uric acid
• Clinical
• chronic gout, prolongation of antimicrobial drug action
• Kinetics
• oral
• Tox, int.
• exacerbation of acute gout, hypersensitivity reactions, inhibits renal tubular secretion of weak acids such as methotrexate

Question 8

Allopurinol

Answer 8

• MOA
• active metabolite irreversibly inhibits xanthine oxidase and lowers production of uric acid
• Clinical
• chronic gout, adjunct to cancer chemotherapy
• Kinetics
• oral, activated by xanthine oxidase
• Tox, int.
• GI upset, hypersensitivity reactions, bone marrow suppression