TMT OF  RA W/ GI BLEEDING (BJE)

MISOPROSTOL + ANY NSAID

    Misoprostol: a stable analog of PGE₁, used to treat the gastric erosion and ulceration caused by NSAI's and  corticosteroids

TMT RA W/ GI BLEEDING PT. CANNOT TOLERATE MISOPROSTOL SIDE EFFECTS

(Real World)

1. CELECOXIB: can still cause ulceration in these pts

or

2. NSAID + H₂ Histamine Receptor Antagonist (FAMOTIDINE): increases stomach pH (can predispose to C. diff)

or

3. NSAID + Proton Pump Inhibitor (PPI i.e. OMEPRAZOLE): suppression of acid secretion by PPI (can predispose to C. diff)

ETANERCEPT

Biologic DMARD: Monoclonal Ab for tmt of RA

MOA: binds TNFα in the blood (soluble) and in the joints (cell bound). This prevents the stimulation of TNFα receptors. Self administered s.c. injection 2x wk

SE: can reactivate TB

INFLIXIMAB

Biologic DMARD: Monoclonal Ab for RA

MOA:binds TNFα in the blood (soluble) and in the joints (cell bound). This prevents the stimulation of TNFα receptors. i.v. infusions at 1, 2, 6 wks; then every 8 wks

SE: reactivation of TB

ADALIMUMAB

Biologic DMARD: Monoclonal Ab for RA

MOA: fully human monoclonal Ab binds TNFα in the blood (soluble) and in the joints (cell bound). This prevents the stimulation of TNFα receptors. Self administered s.c injection every other wk

SE: reactivation of TB

ABATACEPT

Biologic DMARD: T-cell costimulatory blockers.

MOA: a fusion protein that combines the extracellular domain of CTLA-4 w/ the Fc portion of human Ig. High affinity binding to CD80/CD86 (B7 Protein) on the APC prevents the stimulation of the T-cell CD28 receptor which is needed for T-cell activation

TU: RA who failed therapy w/ older DMARDs and TNFa antagonists

SE: increased risk for infection

RITUXIMAB

Biologic DMARD: B-cell depleter.

MOA: A chimeric monoclonal Ab against the CD20 of B lymphocytes which causes B cell apoptosis

TU: RA and non-Hodgkins lymphoma

SE: increased risk for infection

ANAKINRA

Biologic DMARD: IL-1 Receptor Antagonist

MOA: A recombinant IL-1 with the addition of a N-terminal methionine (it has NO intrinsic activity). It binds to the IL-1 receptor and thus blocks the binding of endogenous IL-1 (which is a proinflammatory cytokine which increases the degradation of cartilage)

TU: RA

SE: increased risk for infection

TMT OF GOUT = CRYSTALLINE ARTHRITIS

1. Supression of leukocyte activation: COLCHICINE & INDOMETHACIN

2. Increase renal urate excretion: PROBENECID, SULFINPYRAZONE & LARGE DOSES OF ASPIRIN

3. Reducing urate production: ALLOPURINOL & FEBUXOSTAT

COLCHICINE

MOA: binds to the intracellular protein tubulin to prevent polymerization into microtubules and thus inhibits leukocyte migration and phagocytosis

TU: Acute attacks & prophylaxis of recurretn episodes

SE: diarrhea

Indomethacin often used in place for acute attacks b/c of diarrhea s/e

NSAID (including INDOMETHACIN)

MOA: inhibition of PG synthesis prevents the phagocytosis of urate crystals by synoviocytes and macrophages. Prevents transcription of inflammatory mediators.

TU: initial therapy; acute attacks

PROBENECID, SULFINPYRAZONE & LARGE DOSES OF ASPIRIN

URICOSURIC DRUGS: Increase the renal excretion of urate

MOA: affect the urate transport such that the net reabsorption of uric acid is decreased so the renal clearance of urate is increased.

TU: after several acute attacks have occured (2-3 wks after)

ALLOPURINOL & FEBUXOSTAT

MOA: Inhibit Xanthine Oxidase, the enzyme that converts Hypoxanthine and Xanthine to Uric Acid. The size of the urate pool and plasma urate drops.

Pharm Effects: Reduces serum urate w/out increasing renal uric acid excretion.

Tophaceous urate deposits are reabsorbed. Joint inflammation remits and bone remineralizes

ALLOPURINOL vs FEBUXOSTAT

Febuxostat more effective in Decreasing plasma urate [] in ALL pts

Long term tx w/ Febuxostat Decreases gout "flares" and reduces the size and # of tophi

Febuxostat is more Expensive

TMT OF GOUTY ARTHRITIS

Colchicine

Indomethacin

Probenecid

Allopurinol

Febuxostat

"BIOLOGIC" DMARDS

Etanercept

Infliximab

Adalimumab

Abatacept

Anakinra

NSAIDS

Diclofenac

Indomethacin

Oxaprozin

Celecoxib

DICLOFENAC

Nonsalicylate NSAID

Relative selective for COX-2 & some activity to inhibit lipoxygenase

INDOMETHACIN

Nonsalicylate NSAID

Some  ability to inhibit lipoxygenase

Has pharm properties unrelated to inhibition of PG syn

High incidence of CNS side effects, esp in elderly pts

OXAPROZIN

CELECOXIB

COX-2 Inhibitor; half-life = 10h

TU: tmt of OA, RA, primary dysmennorhea, & post-surgical pain, for pts w/ "aspirin sensitivity"

Has NO effect on platelet aggregation of bleeding time

Has NO interference w/ the antiplatelet effect of Aspirin