Anti-inflammatory effects:

↓ Platelet aggregation, interferes with kallikrein system, ↓Granulocyte adherence to    damaged vasculature, ↓Chemotaxis of PMNs & macrophages

Anti-platelet: ↓ COX-1 & COX-2

Analgesic effects

Antipyretic effects: ↓ COX & IL-1

Gastric upset, gastric/duodenal ulcers, hepatotoxicity, asthmatic attacks, rashes, renal toxicity

High doses: salicylism (vomiting, tinnitus, ↓ hearing, vertigo)

Used for anti-platelet effect:

↓ incidence of ischemic attacks, unstable angina, coronary artery thrombosis with MI, thrombosis after coronary bypass surgery

Selectively inhibits COX-2

Renal toxicity

↑ risk of thrombotic events

GI upset, peptic ulcers

Fewer GI effects and doesn’t affect platelet aggregation; no cardioprotective effects

Reversibly inhibits both

COX-1 & COX-2

Less fluid retention & GI

ulcers

GI upset, peptic ulcers

Close the patent ductus arteriosus, analgesia

Anti-inflammatory and anti-platelet action ↓ when used with aspirin

Nonselective COX inhibitor

Inhibit phospholipase A & C

Reduce neutrophil migration

↓ T cell & B cell proliferation

Pancreatitis, headache (25%), psychosis (rarely), thrombocytopenia, aplastic anemia, renal papillary necrosis

GI upset, peptic ulcers

Close the patent ductus arteriosus, gout

Inhibits AICAR* transformylase & thymidate synthase

Affects PMN chemotaxis, DHF

reductase, ↓ proinflammatory cytokines

Nausea, mucosal ulcers, hepatotoxicity

CI in pregnancy

Rheumatoid arthritis (1^st choice)

Juvenile chronic arthritis, psoriasis, ankylosing spondylitis, polymyositis, Wegener’s granulomatosis, lupus, vasculitis

Inhibits interleukin-1 and 2 receptor production => inhibits macrophage-T-cell interaction and T-cell responsiveness

Nephrotoxicity

Hyptension, hyperkalemia, hepatotoxicity, gingival hyperplasia, hirsutisim

rheumatoid arthritis (↓ new bony erosions)

Inhibits dihydroorotate dehydrogenase leading to ↓ ribonucleotide synthesis and arrest of cells in G₁ phase =>  ↓ T-cell proliferation and production of autoantibodies by B cells

↑ IL-10 receptor mRNA, ↓ IL-8 receptor type A mRNA, ↓ TNF-α-dependent NF-κB

Diarrhea (25%), ↑ liver enzymes

Mild alopecia, weight gain, ↑BP

CI in pregnancy

Rheumatoid arthritis (inhibit bony damage)

Inhibits CMP dehydrogenase => ↓T-cell proliferation

Interferes w/ WBC adhesion via E&P selectins and ICAM-1

Nausea/vomiting,

hypertension, reversible neutropenia

Renal disease, vasculitis,

Wegner's granulomatosis, Lupus

↓ T-cell response to mitogens

↓ leukocyte chemotaxis

↓ DNA/RNA synthesis

Trap free radicals

Ocular toxicity
dyspepsia, nausea, vomiting, abdominal pain, rashes, nightmares

Malaria, rheumatic disease

Inhibit immune response

Pigmentation changes (anti-rheumatic gold containing compounds)

No longer used due to toxicity &

questionable efficacy

Human IgG₁ anti-TNF antibody that complexes with TNF-α and prevents its interaction with p55 and p75 cell surface receptors => ↓macrophage and T-cell

↑risk of bacterial and macrophage-dependent infection (including TB and other opportunistic infections)

Rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, juvenile idiopathic arthritis, plaque psoriasis, Crohn’s disease

Chimeric IgG₁ antibody that binds to soluble and bound TNF-α => ↓macrophage and T-cell function

↑incidence of bacterial infections (including upper respiratory), activation of latent TB

Rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, Crohn’s disease

Fusion protein made of 2 soluble TNF p75 receptor moieties linked to F_c of human IgG₁; binds TNF-α and inhibits lymphotoxin-α

↑bacterial infections, especially soft tissue infections and septic arthritis, may activate latent TB

Rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, juvenile chronic arthritis, psoriasis

Weak COX 1 and 2 inhibitor in peripheral tissue

Antipyretic and analgesic, but NO anti-inflammatory or platelet aggregation inhibition

↑ hepatic enzymes

Overdose: Hepatotoxicity with centrilobular necrosis, acute

renal tubular necrosis

Treat moderate pain without anti-inflammatory effect

Preferred over aspirin for children with viral infections hemophiliacs, ulcer-prone patients, gout