NSAID

Mechanism: Nonselective, irreversible inhibitor of COX-1 and COX-2; peripheral and CNS effects contribut to pain relief; prevents sensitization of pain receptor; inhibit prostaglandin synthesis; inhibits cytokine production too

Use: mild to moderate pain, fever, decrease platelet action, decrease MI and colon CA

Effects: Analgesic (only inflammatory), antipyretic (only febrile and hyperthermia), anti-inflammatory, antiplatelet effects (ACA only); Centrally, acts on hypothalamic area and reduces fever and malaise; binds plasma proteins (50-90%)

Renal excretion - alkalinization of urine promotes excretion (its an acid)

Contraindications - hypoprothrominemia, vit K deficiency, hemophilia, severe hepatic damage (low coag factors), aspirin allergy, pre sx or labor

Pharmacokinetics: slowly crosses BBB, rapidly hydrolyzed in plasma, liver and RBCs; excreted by kidneys

Adverse effects: resp alk, then metabolic and respiratory acidosis (high doses will inhibit resp center); salicylism, hypersensitivity (skin rashes), reye's syndrome (cerebral edema in children with viral infections

Dose dependent toxicities: low-high = resp alkalosis followed by resp depression then resp acidosis; increased bleeding time; low-high = decreased uric acid excretion increased (increased plasma urate) -> increased uric acid excretion (decreased plasma urate, too much ASA though for GI); aspirin astham (increased leukotrienes); GI bleed; renal damage, ARF, nephritis; 

Dx interactions: Decreases effects of beta blockers, ACE inhibitors; increases anticoagulant, insulin release (DM drugs), bleeding from antineoplastic agents, GI ulcer from corticosteroids; antacids changed absorption; Diuretic decrease ASA effects; Increased effect from NSAIDS, penicillins, platelet inhibitors, salicylates, sulfonamides, thrombolytic agents

Other Salicylates: Sodium Salicylate (Uracel-5)

Methyl Salicylate (Oil of Wintergreen)

 Diflunisal (Dolobid)

NSAID: COX-2 inhibitor

Mechanism: Selective COX-2 inhibitor; cause less gastropathy and risk of GI bleed; *Platelets only contain COX-1*

Use: analgesia if PUD hx but not active

Adverse reactions: Increased risk of CV disease (PGI2 inhibition leads to imbalance and increased TXA2! = platelet aggregation/vasoconstriction)

Contraindications: GI disease, asthma, breast feeding, pregnancy, renal failure, sulfonamide hypersensitivity

Non-specific COX inhibitors: Indole/indene acetic acids

Mechanism: very potent AI AR (cox enzymes) inhibit phospholipase, reduces PMN migration

Use: Patent ducturs arteriosus

High incidence of side effects: GI, CNS, Lung broncoconstriction, agranulocytosis, aplastic anemia, nephrotoxicity, hepatotoxicity, hypersensitivity rxns

Sulindac (Clinoril) = less nephtrotoxic than other NSAIDS; severe GI adverse effects including pancreatitis

Nonspecific COX inhibitors; Anthranilic acids (fenemates)

Nonspecific COX inhibitors; Heteroaril acetic acids

Potent COX inhibitor; increased risk of CV disease

Ketorolac = post-surg. pain

Non-specific COX inhibitor: Propionic Acid Derivitive

DOC

Use: RA, osteoarthritis

Effects: anti-inflammatory, antipyretic, analgesic

Drug interactions: combo with ASA decreases effect on platelet aggregation

Pharmacokinetics: excretion by kidney (unchanged, also metabolite); excretion complete in 24 hrs

Lowest incidence of side effects: GI, CNS (dizzy etc.), slight transient increase in serum enzymes; hyperuricemia, decrease in plt aggregation; cross sensitivity with aspirin and other NSAIDS

Other Drugs: Naproxen (Anaprox, Naprosyn) - claim to fame is long half life

Fenoprofen (Nalfon)

Flurbiprofen (Ansaid)

Ketoprofen (Orudis)

Oxaprozin (Daypro)

Fenbufen (Cinopal)

Different Actions:

Mechanisms:

Pharmacokinetics:

Use: Analgesic if pt has ACTIVE PUD; alternative to aspirin for analgesic and antipyretic effects: DOES NOT INHIBIT COX ENZYMES! NOT ANTI-INFLAMMATORY!!!; prefferred for aspirin allergic pts, coag disorders (hemophilia), PUD hx, gouty arthritis, children; NOT as effective for RA

Adverse effects/tox: lacks severeal undesirable side effects (ulcerogenic, blood clotting defects, acid-base imbalance, auditory tox); OD = fatal hepatic necrosis (10-16 gm tox adult, 25 fatal) -> hepatic encephalopathy, coma/death (tox from reduced glutathione); allergic respons, few cases of adverse effects on blood (neutro- pan- leuko- cytopenia)

Tx of acetaminophen intoxications: Gastric emptying, forcer diuresis, hemodialysis, N-acetylcysteine (Mucomyst), give within 10-12 hrs of intoxication; (won't die with remote in hand)

Side effects: less side effects than ASA, but metabolite causes free radical in liver and leads to hepatic necrosis in OD; allergic response, neutropenia/pancytopenia/leukopenia, dose dependent hepatic necrosis (With reduced glutathione), elevated serum transaminase; if alcoholic, CYP450 induced, increasing toxic metabolite load

Disease modifying anti-rhematic drug (DMARDS); Gold Salt

Mechinsim: unknown -> inhbit phagocytosis, uncoupel oxidative and inhibit cellular respiration, stabilize lysosomal membrane and inhibit actions of lysosomal enzymes, react with proteins (sulfhydryl groups), inhibit proteolytic enzymes of leukocytes, prevent prostaglandin synthesis, suppress cellular immunity

Pharmacokinetics: administered parenterally; steady state in 1-2 months; fecal/renal elimination

Side effects: bone marrow damage, dermatitis, enterocolitis, jaundice, peripheral neuropathy

Other Drugs: Auranofin (Ridaura)- oral

Gold Sodium Thiomalate (Myochrysine)   

Wilson's disease tx too

Disease MOdifying Anti-Rhematic Drug (DMARD); Gold Salts

Mechanism: a chelating agent for RA; inhibits formation of collagen; depresses IgM rheumatoid factor in blood; decreases T-cell activity (not B-cell_

Pharmacokinetics: protein binding 80% (albumin); uncomplexed penicillamine is metabolized in liver then excreted in urine/feces

Side effects: high incidence; pruritis/rash, thrombocytopenia, leukocytopenia, agranulocytosis, aplastic anemia; proteinuria, hypoablumineaia, nephrotic syndrome; lupus like disease, pemphigus, goodpasture's syndrome, myasthenia gravis, polymyositis, stenosing alveolitis

RA

Mechanism: antihistamine, anticholinesterase, antiprotease; inhibits prostaglandin synth; inhbitis biosynth of mucopolysaccharide, inhibits, chemotactic stimuli of phagocytosis, stabilized lysosomes; reacts with nucleic acids and tissue proteins

Pharmacokinetics: widely distributed into body tissues; high affinity for melanin (so in epidermis/retina); partially metabolized in liver; t1/2 = 50 days!

Side Effects: pruritis, hemolysis, ototoxicity, retinopathy, peripheral neuropathy

DMRAD; Gold Salt

Mechanism: inhibits arachidonic acid metabolism by COX inhibition; inhibits leukotriene synth.

Pharmacokinetics: metabolized by liver; excreted in urine; lower dose in pts with renal impairment

Side effects: sulfonamide and salicylate side effects (large SE profile); GI, hepatitis, blood dyscrasias (rare)

DMRAD

Crohns and RA

Mechanism: Monoclonal Antibody (IgG1k) targeted against TNF-a (chimeric); murine/human regions on same ab

Pharmacokinetics: IV, vascular compartment, T1/2 8-9.5 days

Side effects: infusion rxns, headache, nausea/vomiting, diarrheea, dizzines, etc

Contraindications: Pregnancy, breast feeding, children infections (TB etc.)

DMRAD

Mechanism: chimeric monoclonal ab (IgG); binds CD20 (B cells antigen on pre-B and mature b-lymphs-> CD20 on >90% of B-cells in NHL; 

Pharmacokinetics: IV

Side effects: infusion rxns, hypersensitivity rxns, fever, chills, rash etc.

RA

Mechanism: IgG1 monoclonal ab; specific for TNF-a; 

Pharmacokinetics: subq; 

Side effects: rash, flu like, fatigue, headache, pruritis, nausea/vomiting

RA

Mechanism: dimeric fusion protein NOT MONOCLONAL AB; binds TNF receptor, inactivating it; no TNF production/serum level effects

Pharmacokinetics: subq; t1/2 102 hrs

Side effects: injection site rxn, infections, increases Ab formation

RA

fully human recombinant fusion protein, a costim or 2nd signal blocker of T cell activation

IV

RA

Mechanism: inhibits dihydroorotate dehydrogenase (mitochondrial enzyme that catalyzes de novo pyrimidine synth); inhibits cytokine and gf receptor; inhibit COX-2

PHK:  oral, T1/2 16 hrs

Side effects: GI, oral ulcer, elevated hepatic enzymes

RA

Effects: prodrug for immunosuppressive agent mycophenolic acid; inhibits lymphocyte purine synth by inhibiting inosine monophosphate dehydrogenase (IMPDH)

PHK: 

RA

recombinant non-glycosylated human interleukin-1 receptor antagonist (IL-1Ra)

RA

Janus kinase inhibitor (cytokine pathway); inhibits JAK1 and JAK3 (JAK 2 to lesser extent)

contraindicated in TB and malignancies