Cyclosporine

(pp 630 text)

mech of action: 

inhibits interleuken 1,2 receptor production.

inhibits T-cell interaction and responsiveness

used for:

rheumatoid arthritis

possibly systemic lupus erythematus

pharmakinetics:

metabolized by CYP3A

Grapefrui increases bioavailability

Leflunomide

(pp 631 text)

Mech of Action:

rapid conversion in intestine & plasma =A77-1726

inhibits dihydroorotate dehydrogenase

inhibit T-cell proliferation

inhibit B-cell autoantibodies production

Indications:

Rheumatoid Arthritis (include inhibition bone damage)

Adverse Effects:

diarrhea

dose dependent liver enzyme elevation

contraindicated in pregnancy

Methotrexate

(pp 631 text)

Mech of Action:

1) low dose inhibit AICAR

2)inhibits proliferation, stimulates apoptosis in immune-inflammatory cells.

Indications:

DMARD of 1st choice Rx Rheumatoid Arthritis

Pharmakinetics:

excreted in urine/bile
Adverse effects:

nausea/mucosal ulcers most common

Sulindac

(pp 628 text)

sulfoxide prodrug

reversibly metabolized to active

excreted in bile > reabsorbed from intestine

indications:

Rheumatic dz

supress familial intestional polyposis

*may inhibit CA

side effects:

Steven Johnsons (SJS)

reversible liver damage

Tolometin

(pp 628 text)

nonselective COX inhibitor

NOT OFTEN USED

NOT EFFECTIVE AGAINST GOUT

Adverse reactions:

thrombocytopenia (rare)

Naproxen

(pp 628 text)

Napthylpropionic acid derivative

only NSAID single entantiomer

indications:

Rheumatologic (available as oral suspension, slow release, OTC, topical, ophthalmic drop)

Adverse:

GI bleed 2x > OTC Ibuprofen 

Etodolac

(pp 627 text)

 Ibuprofen

(pp 627 text)

simple derivative of phenylpropionic acid

equivalent to 4g ASA (as NSAID)

CLOSES PATENT DUCTUS ARTERIOSUS

contraindications:

don't use individuals with nasal polyps, angioedema.

adverse drug reactions:

ASA

Diclofenac

(pp 626 text)

phenylacetic acid derivative

nonselective COX inhibitor

Celebrex/Celecoxib

(pp 626 text)

COX 2 inhibitor

sulfonamide

metabolized by CYP2C9

adverse reactions:

rash

ocassionally interacts with warafin

Allopurinol

(pp 638 text)

standard of care for GOUT

prophylaxis

mech of action:

inhibits xanthine oxidase > reduces total uric acid

Febuxostat

(pp 639 text)

Colcochine

(pp 636 text)

alkaloid isolated from autumn crocus

Indicated:

Was 1st line Gout drug (supplanted by NSAIDS)

prophylaxis now

Gouty Arthritis

prevent mediterranean fever

Mech of action:

binds to intercellular protein tubulin > inhibits formation of leukotrine B4

Adverse:

IV very toxic to bone marrow

diarrhea,nausea, vomiting

Abatacept

(pp 629 text)

Mech of action:

inhibits T-cell activation

Indications:

moderate to severe RA

slows radiographic pregression

Side effects:

increased risk of URI infection

Azathioprine

(pp 629-630 text)

Mech of Action:

6-Thioguanine (active form)

supresses:  inosinic acid synthesis,B,T-cell function, Ig production, interleuken-2 secretion

Pharmcokinetics:

bimodal (rapid 4x > slow)

Indicated:

RA, psoriatic arthritis, reacitve arthritis, polymyositis, S'lupus erythematous, Bechet's dz

Adverse:

bone marrow sup, GI, increase risk inf 

Cyclophosphamide

(pp 630 text)

Mech of action:

major metabolite is phosphoramide mustard which cross links DNA to prevent cell replication.

supresses T,B cell

Indications:

RA

systemic lupus erythematous

vasculitis

Wegener's granulomatosis

severe rheumatic dzs