Antiinflammation Drugs Flashcards
Propionic acid derivatives
-en
Reversible inhibition of cyclooxygenase
Antipyretic, analgesia, antiinflammatory (larger doses)
Treats rheumatoid, osteoarthritis, ankylosing spondylitis
Better tolerated than aspirin
Not recommended for pregnant or breast feeding
Adverse: GI effects, rash, tinnitus, peripheral edema
Salicylates
Irreversibly inactivate COX
Covalently modifies COX1 and COX2
Acetylates serine reissue in active site of COX
COX1 prevents Arachidonic from binding
COX2 Arachidonic binds but no PG formation
Antipyretic, relief of low pain, anti inflammatory, anti thrombotic
Rheumatoid, inflammatory bowel, osteoarthritis
Side effects: CNS stimulation then depression, tinnitus and hearing loss, Reye’s syndrome, asthma and salicylate poisoning
Acetic acid derivatives
Have “ac” in them except tolmetin
Reversible inhibition of cyclooxygenase, inhibition of neutrophil migration
More for inflammation
For RA no advantage over aspirin
Idomethacin: high incidence and severity of headaches
Etodolac and ketorolac: perioperative pain
Adverse effects: GI and severe headaches
Celecoxib and other COX2 inhibitors
-coxib Used for osteoarthritis and rheumatoid Effective for acute pain Decreased adverse GI effects Lack of platelet effects Not recommended in 3rd trimester Adverse effects: cardiovascular events ( heart attack and stroke-rofecoxib), Stevens Johnson syndrome and toxic epidermal necrolysis
Acetaminophen
Para-aminophenol derivative
Inhibits activity of cyclooxygenase
Weak COX inhibitor in presence of peroxides
Analgesic, antipyretic
NOT antiinflammatory
Side effects: skin rash, allergic reactions, hepatic necrosis
Chronic use associated with increased renal failure
Does not cause GI irritation or platelets/bleeding time
Zileuton
Leukotrienes synthesis inhibitor Treat asthma Inhibits T-lipoxegenase Increased hepatic enzymes Not recommended for people who consume large quantities of alcohol Use limited due to toxicity
Zarfirlukast (accolate) montelukast (singulair)
Leukotrienes receptor Antagonist of CysLT
CysLT receptor mediates airway inflammation, edema, bronchiconstriction, secretion of thick mucus
Drugs decrease chemo tactic movement of inflammatory cells and actions of LTs
Z-inhibits isoforms of cyt p450
Z-used for mild to moderate asthma, taken orally, takes weeks for effect, inflammation decreased and short bronchodilation
Steroids
-one
Immunosuppressive and antiinflammatory
Decrease circulating immune cells, decrease neutrophil adherence, inhibit histamine release, inhibit T more than B lymphocytes
Inhibit production if Arachidonic acid metabolites (induce lipocortin which inhibits PLA2)
Inhibit cytokines release and production
Treat rheumatic disorders, bronchial asthma, skin conditions, inflammatory bowel disease, autoimmune hepatitis, some malignancies
Not immediate effects rely on gene transcription
Continued use: disturb electrolyte balance, hypertension, hyperglycemia, CNS effects, susceptible to infection, delayed wound healing, thinning of skin, muscle wasting, Cushing’s syndrome, increased appetite, weight gain, peripheral edema, glaucoma, peptic ulcer, growth retardation in children
Withdrawal:flare up of disease, adrenal insufficiency
Etanercept (Enbrel)
Mimics action of circulating, soluble form of TNF receptor (TNFR2)
Human fusion protein that combines binding domains of p75 and a human IgG1 Ab
Binds to TNF with high affinity- prevents TNF from binding to cellular receptor
Self administered injections
Side effects: infections, cancer, vasculitis, liver disease
Adalimumab, infliximab, certolizumab pegol
Monoclonal Ab that bind TNF with high affinity and specificity
Adalimumab and certolizumab pegol are human origin
Infliximab is chimeric (25% mouse)
Side effects: fungal infections, TB (certolizumab)
Cytokines targets for antiinflammation
Anakinra-Il-1 receptor antagonist
Il-6 antibodies
Il-10 an antiinflammatory cytokine
Il-4 antiinflammatory cytokine
Tocilizumab
Antiinflammatory
Recombinant humanized monoclonal Ab
Il-6 receptor antagonist
Leflunomide
Inhibits dihydro-orotate dehydrogenase leading to inhibition of pyrimidine synthesis
Decreases proliferation of lymphocytes
at larger doses: Inhibits tyrosine kinases, down regulates cell cycling, suppresses NFkB signaling, decreases glycosylation of adhesion molecules (ICAM-1 and VCAM-1), inhibits production of TNFa and IL-1B
May take months to reach steady state
Undergoes enter obesity circulation-years to eliminate
Adverse effects: liver toxicity, loss of body weight, hypertension for first two months
Must be activated
Hydroxychloroquine
Antiinflammatory
Unknown mechanism
? Decreased Intracellular ph leads to inhibition of inflammatory cell function
Azathioprine
Antiinflammatory
Inhibits synthesis of purines
Metabolized
Soluble form of ICAM-1
Antiinflammatory
Normally a intercellular adhesion molecule
Intercepts inflammatory cells preventing binding and going through cell wall
Omalizumab
Directed against binding site of IgE for high affinity FCC receptor
Inhibits immune system response to allergens
Galtiramer acetate
Simulates myelin basic protein
Binds to MHC class II molecules and competes with myelin Ags for presentation to T cells
MS and inflammatory bowel disease
Cortistatin
Endogenous cyclic neuropeptide binds to immune cells
Experimental colitis
Efalizumab
Recombinant monoclonal Ab against CD11a
Moderate to severe cirrhosis
Abatacept
CTLA4Ig
CD28 costimulus antagonist
Blocks second signal for T cell activation
T cells undergo anergy
Treat RA that is refractory to TNF blockers and other disease modifying drugs
CTLA4 shares 6 amino acid sequence with T cell’s CD28 necessary for binding to CD80 and CD86
Inhibits radiographic progression of disease and decreases joint inflammation and damage
Side effects: headache, nasopharyngitis, and nausea
Colchicine
Treats gout-first line
Inhibits migration and activation of leukocytes
Binds to Tubulin, interferes with function of mitotic spindles
Not analgesic and is not antiinflammatory In other disorders
Use with caution in patients with hepatic, renal and cardiovascular diseases
Contraindicated during pregnancy
Oral admin-nausea vomiting
Diarrhea with toxic doses
Allopurinol and febuxostat
Treat gout
Inhibition of can thine oxidase thus uric acid synthesis
No effect on acute attack
Can be used in patients with compromises renal function and undergoing salicylate therapy
Adverse effects: skin rash (more frequent) GI distress
Sulfinpyrazone
Probenecid
Treat gout
Inhibition of urate reabsorption by anion transporter URAT1
Ineffective in patients undergoing salicylate therapy (salicylates increase reabsorption)
Effectiveness depends on renal function
Acute gouty arthritis may occur during initial therapy
Contraindicated in patients with blood dyscrasias or uric acid kidney stones
Side effects: s: GI irritation, inhibition of platelets, contraindicated with hypersensitivity to phenylbutazone
P: GI irritation, should not be given when patient has peptic ulcers
