03 Inflammation and anti-inflammatory drugs Flashcards by Emma :)

3.01 NSAIDs

Ibuprofen - actions

analgesic for inflammatory pain, antipyretic, anti-inflammatory

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3.01 NSAIDs

Ibuprofen - MOA

reversible inhibition of COX-1
weak inhibition of COX-2

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3.01 NSAIDs

Ibuprofen - abs/distrib/elim

given orally
half-life 2h

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3.01 NSAIDs

Ibuprofen - clinical use

inflammatory conditions (e.g. rheumatoid disease, osteoarthritis, musculoskeletal disorders)
dysmenorrhoea

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3.01 NSAIDs

Ibuprofen - adverse effects

GIT disturbances, including gastric bleeding
headache, dizziness less commonly
allergic reactions occasionally
renal toxicity rarely

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3.01 NSAIDs

Ibuprofen - special points

increased adverse effects if combined with other NSAIDs
used to close patent ductus arteriosus

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3.01 NSAIDs

Ibuprofen - similar drugs

diclofenac (moderate potency, half-life 1-2h)
ketoprofen (half-life ~2h)
naproxen (more potent, half-life 10-14h)
ketorolac (half-life 4-10h, COX-1 selective)
piroxicam (half-life 57h, GIT toxicity common, COX non-selective)

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3.02 NSAIDs

Aspirin - actions

analgesic for inflammatory pain, antipyretic, anti-inflammatory, inhibits platelet aggregation

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3.02 NSAIDs

Aspirin - MOA

irreversible acetylation of cyclooxygenases
weakly COX-1 selective

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3.02 NSAIDs

Aspirin - abs/distrib/elim

given orally, but also available as suppository
rapid hydrolysis (30min) to salicylate but effects last longer because the COX has been inactivated and new enzyme must be produced

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3.02 NSAIDs

Aspirin - clinical use

antithrombotic in MI (main use)
other NSAIDs are preferred for anti-inflammatory action and analgesia in musculoskeletal conditions

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3.02 NSAIDs

Aspirin - adverse effects

GIT disturbances, especially gastric bleeding
in high dosage can cause ‘salicylism’ (tinnitus, vertigo, reduced hearing)
allergic reactions occasionally
renal toxicity rarely
can cause the potentially fatal Reye’s syndrome (encephalopathy and liver disorder) in children after a viral infection

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3.02 NSAIDs

Aspirin - special points

should not be used in children
can cause increased effect of warfarin resulting in bleeding
should not be used for gout because it reduces urate excretion and interferes with the action of uricosuric agents

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3.03 NSAIDs

Paracetamol - actions

analgesic, antipyretic, has little anti-inflammatory action

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3.03 NSAIDs

Paracetamol - MOA

inhibition of COX-1, COX-2 and also the recently identified COX-3 which occurs predominantly in the CNS

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3.03 NSAIDs

Paracetamol - abs/distrib/elim

given orally
half-life 2-4h
inactivated in the liver

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3.03 NSAIDs

Paracetamol - clinical use

mild to moderate pain, especially headache

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3.03 NSAIDs

Paracetamol - adverse effects

few and uncommon with therapeutic doses
toxic doses cause firstly nausea and vomiting and then 24h later potentially fatal liver toxicity

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3.04 COX-2 INHIBITORS

Celecoxib, etoricoxib, parecoxib - actions

analgesic, antipyretic, anti-inflammatory
no antiplatelet action

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3.04 COX-2 INHIBITORS

Celecoxib, etoricoxib, parecoxib - MOA

selective inhibition of COX-2 - the enzyme that is induced in areas of inflammation
celecoxib is 10-20 × more active on COX-2 than COX-1 - the constitutive enzyme that generates physiologically important prostaglandins

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3.04 COX-2 INHIBITORS

Celecoxib, etoricoxib, parecoxib - abs/distrib/elim

given orally
half-life ~11h
inactivated in the liver

3.04 COX-2 INHIBITORS

Celecoxib, etoricoxib, parecoxib - clinical use

rheumatoid arthritis, osteoarthritis, ankylosing spondylitis
offered to patients for whom treatment with conventional NSAIDs would pose high probability of serious gastrointestional side effects - although they can still occur with COX-2 inhibitors (coxibs)

3.04 COX-2 INHIBITORS

Celecoxib, etoricoxib, parecoxib - adverse effects

several coxibs have been withdrawn following claims of cardiovascular and other toxicity (renal and liver)
new-onset hypertension, fluid retention
celecoxib, etericoxib and parecoxib are currently available for clinical use in the United Kingdom

3.05 DMARDs

Immunosuppressive disease-modifying anti-rheumatoid drug: methotrexate - actions

marked anti-inflammatory action in rheumatoid disease
cytotoxic in the larger doses used to treat cancer

3.05 DMARDs Immunosuppressive disease-modifying anti-rheumatoid drug: methotrexate - MOA

folate antagonist and thus interferes with thymidylate synthesis (which is essential for DNA synthesis)

3.05 DMARDs Immunosuppressive disease-modifying anti-rheumatoid drug: methotrexate - abs/distrib/elim

given orally has active metabolite both MTX and metabolite are poly-glutamated (PgMTX) half-life 6-9h

3.05 DMARDs Immunosuppressive disease-modifying anti-rheumatoid drug: methotrexate - clinical use

first-line for rheumatoid arthritis used in psoriasis, ankylosing spondylitis, polymyositis and vasculitis also an anti-cancer agent

3.05 DMARDs Immunosuppressive disease-modifying anti-rheumatoid drug: methotrexate - adverse effects

GIT disturbances dose-related liver toxicity bone marrow depression and pneumonitis can occur

3.06 DMARDs Immunosuppressive disease-modifying anti-rheumatoid drug: sulfasalazine - actions

produces remission of active rheumatoid arthritis according to X-rays, disease progression is reduced

3.06 DMARDs Immunosuppressive disease-modifying anti-rheumatoid drug: sulfasalazine - MOA

in the colon, the salicylic acid moiety is released, absorbed and has anti-inflammatory action

3.06 DMARDs Immunosuppressive disease-modifying anti-rheumatoid drug: sulfasalazine - abs/distrib/elim

given orally only ~15% is absorbed in the GIT half-life 6-16h

3.06 DMARDs Immunosuppressive disease-modifying anti-rheumatoid drug: sulfasalazine - clinical use

rheumatoid arthritis, juvenile arthritis inflammatory bowel disease

3.06 DMARDs Immunosuppressive disease-modifying anti-rheumatoid drug: sulfasalazine - adverse effects

nausea and vomiting, headaches, rashes rarely bone marrow dyscrasias, liver dysfunction about a third of patients discontinue the drug because of adverse effects

3.07 DMARDs Immunosuppressive disease-modifying anti-rheumatoid drug: leflunomide - actions

modifies the immune reaction underlying rheumatoid arthritis through an inhibitory action on activated T cells

3.07 DMARDs Immunosuppressive disease-modifying anti-rheumatoid drug: leflunomide - MOA

gives rise to a metabolite that inhibits dihydrooratate dehydrogenase this results in inhibition of T cell proliferation and decreased production of autoantibodies by B cells

3.07 DMARDs Immunosuppressive disease-modifying anti-rheumatoid drug: leflunomide - abs/distrib/elim

absorbed orally the metabolite undergoes enterohepatic cycling half-life thus ~18 days

3.07 DMARDs Immunosuppressive disease-modifying anti-rheumatoid drug: leflunomide - clinical use

rheumatoid arthritis particularly effective in combination with methotrexate

3.07 DMARDs Immunosuppressive disease-modifying anti-rheumatoid drug: leflunomide - adverse effects

~25% of patients get diarrhoea increased BP, weight gain can occur the long half-life can lead to cumulative toxicity

3.08 URICOSURIC AGENTS Allopurinol, febuxostat - actions

reduces uric acid concentration in the body

3.08 URICOSURIC AGENTS Allopurinol, febuxostat - MOA

inhibits xanthine oxidase and also the biotransformation of purines to xanthine

3.08 URICOSURIC AGENTS Allopurinol, febuxostat - abs/distrib/elim

given orally, well absorbed converted to alloxanthine which has a half-life of ~18-30h and is the moiety that inhibits xanthine oxidase

3.08 URICOSURIC AGENTS Allopurinol, febuxostat - clinical use

to prevent episodes of gout

3.08 URICOSURIC AGENTS Allopurinol, febuxostat - adverse effects

GIT disturbances rashes and blood dyscrasias can occur

3.08 URICOSURIC AGENTS Allopurinol, febuxostat - special points

allopurinol is not used to treat acute attacks of gout - these are treated with NSAIDs allopurinol interferes with the metabolism of oral anticoagulants and can increase the effect of azathioprine and cyclophosphamide

3.08 URICOSURIC AGENTS Allopurinol, febuxostat - similar drugs

probenecid is similar in that it is also uricosuric but it acts by increasing uric acid excretion through an effect on the proximal tubule in the nephron - only used to prevent gouty attacks

3.09 Antigout: colchicine - actions

decreases the pain and inflammation of gouty arthritis

3.09 Antigout: colchicine - MOA

inhibits migration of neutrophils into gouty joints by binding to tubulin and preventing its polymerisation into microtubules neutrophils are reduced to moving with a ‘drunken walk’ it also decreases production of the chemokine leukotriene B4

3.09 Antigout: colchicine - abs/distrib/elim

given orally, well absorbed half-life 9h

3.09 Antigout: colchicine - clinical use

to treat acute episodes of gout also used in treatment of pericarditis

3.09 Antigout: colchicine - adverse effects

diarrhoea, sometimes nausea and vomiting blood dyscrasias can occur

3.09 Antigout: colchicine - special points

it can increase the bone marrow depression caused by other drugs