PHARM_MSK_MS2

NONSALICYLATE NSAID

RELATIVELY SELECTIVE FOR COX-2

• RA AND OA
• --ALL NSAIDS EQUAL IN Tx

ANKYLOSING SPONDYLITIS

Tx ELDERLY w Hx OF GI BLEED CAUSED BY AN NSAID

SOME INH OF LIPOXYGENASE

SHORT t1/2 < 6hrs

NONSALICYLATE NSAID

SOME INH OF LIPOXYGENASE

PHARM PROPERTIES UNRELATED TO INH OF PG SYNTHESIS

HIGH INCIDENCE OF CNS SIDE EFFECTS, ESP IN ELDERLY

SHORT t1/2 < 6hrs

NONSALICYLATE NSAID

LONG t1/2 > 15hrs

COX-2 INH

t1/2 = 10hrs

• THERA
• --Tx OA and RA
• --PRIMARY DYSMENNORHEA
• --POST-OP SURG & DENTAL PAIN
• --PREVENTION OF COLORECTAL CANCER & ALZ?
• --NO EFFECT ON PLATELET AGG OR BLEEDING TIME
• --NON INTERFERENCE w ANTIPLATELET ACT OF ASPIRIN

COX-2 NEC FOR KIDNEY FUNCTION AND INVOLVED IN PULMONARY PHYSIOLOGY

NO ANAPHYLACTOID-LIKE REACTIONS IN Pts w SUCH REACTION FROM NSAIDS

MAY STILL CAUSE GI ULCERATION IN Pts w Hx OF GI BLEED FROM NSAIDS

PGE ANALOG

• Tx GASTRIC EROSION AND ULCERATION CAUSED BY NSAIDS AND CORTICOSTEROIDS
• --COMBO w DICLOFENAC

• ADVERSE
• --DIARRHEA
• --ABD PAIN & CRAMPING

• PGE
• --INH RELEASE OF NE PRESYNAPTIC AND VASODILATE POSTSYNAPTIC TO ANTAGONIZE NE
• --WORK TO ATTENUATE INC IN BP IN VASC SMOOTH MUSC
• --IN KIDNEY: ATTENUATE EFFECT OF ADH ON COLLECTING DUCT TO PREVENT HYPONATREMIA

• PGE IN STOMACH
• --INH ACID SECRETION
• --STIM MUCOUS SECRETION
• --INC BICARB
• --INC MUCOSAL BLD FLOW
• --STIM CELL GROWTH & REPAIR

"BIOLOGIC" DMARD

MONOCLONAL Ab FOR Tx OF Rh

SOLUBLE TNF RECEPTORS THAT BIND TNF-a IN THE BLD AND JOINTS

• ADVERSE
• --INC RISK OF INFEC
• --REACTIVATION OF LATENT TB
• --TRANSIENT NEUTROPENIA

• ETANERCEPT
• INFLIXIMAB
• ADALIMUMAB
• ABATACEPT

DISEASE MOD ANTI RHEUM DRUGS

"BIOLOGIC" DMARDs

MOA SAME AS ETANERCEPT -- BINDS TNF-a IN BLD & JOINTS

Tx Rh AND PSORIATIC ARTH, ANK SPOND, CROHN'S Dz

• ADVERSE
• --INC RISK OF INFEC
• --REACTIVATION OF LATENT TB

"BIOLOGIC" DMARD

T-CELL CO-STIM BLOCKER

COMBOs BINDING PORTION OF CTLA-4 TO Fc PART OF Ig --> INH OF T-CELL ACTIVATION BY BINDING TO APC

USED ON Pts WHO FAILED THERAPY w OTHER DMARDs AND TNF-a ANTAGS

• ADVERSE
• --INC RISK OF INF

nLLY CTLA-4 RELEASED BY ACTIVATED T-CELLS TO INH FURTHER T-CELL ACTIVATION AND BINDS TO CD80/86 (B7) ON APC

T-CELL CD28 BINDS TO CD80/86 (B7) ON APC FOR ACTIVATION

"BIOLOGIC" DMARD

IL-1 RECEPTOR ANTAGONIST

Tx Rh

• ADVERSE
• --INC RISK INFEC

nL -- IL-1 IS PROINFLAM THAT INC DEGRAD OF CART & STIMS OSTEOCLAST.

IL-1 --> ATP --> INH IkK --> IkB PHOSED --> NFkB RELEASED AND ENTERS NUC

GOUT

BINDS TUBULIN TO INH MICROTUBULES --> INH LEUKO MIGRATION AND PHAGO

• TOXIC
• --DIARRHEA
• --ABD PAIN
• --ALOPECIA
• --BM DEPRESSION
• --MYOPATHY

NON SALICYLATE NSAID

USED IN PLACE OF COLCHICINE FOR ACUTE ATTACKS

INH OF PGs SYNTH PREVENTS PHAGO OF URATE CRYSTALS BY SYNOVIOCYTES AND MACROs

GOUT

INC RENAL EXCRETION OF URATE

BEGIN 2-3 WEEKS AFTER ACUTE ATTACK

GOUT

INH XANTHINE OXIDASE

PREVENT HYPOXANTHINE AND XANTHINE CONVERSION TO URIC ACID

FEBUXOSTAT MORE EFFECTIVE THAN ALLO IN DEC PLASMA URATE CONC

SOME Pts THAT DON'T RESPOND TO ALLO WILL RESP TO FEBUX

LONG-TERM FEBUX Tx DEC GOUT "FLARES" AND DEC SIZE & # OF TOPHI

FEBUX MORE EXPENSIVE