Rheumatology Pharm Flashcards
Biological DMARDs
MOA: Tumor-necrosis factor inhibitors
Etanercept (Enbrel)
Adalimumab (Humira)
Infliximab (Remicade)
Anakinra (Kineret)
Abatacept (Orencia)
Strong CYP3A4 inhibitor examples
Clarithromycin
Itraconazole
Ketoconazole
Nefazodone
HIV protease inhibitors
Moderate CYP3A4 inhibitors
Diltiazem
Erythromycin
Fluconazole
Grapefruit juice
Verapamil
P-glycoprotein inhibitors
Cyclosporine
Ranolazine
Amiodarone
Glucocorticoid Effects
Block proinflammatory genes IL-1 alpha and IL-2 beta
Decreases TNF-alpha - direct DNA interaction
Inhibit proinflammatory mediators phospholipase A2, COX2, Nitric oxide synthetase, prostaglandins, leukotrienes, thromboxanes
Decrease leukocyte adherence to vascular endothelium - can’t exit to infection/injury site
Glucocorticoid Inflammatory Suppression
Increased neutrophils = increased wbc production w/ impaired transport and decreased apoptosis
Decreased eosinophils = increased apoptosis, trapped in tissues
Decreased monocytes = decreased accumulation and vasculature migration
Decreased lymphocytes = inhibition of T and B cells -> decreased APCs (macrophage, DC)
Mineralocorticoid activity
Alter sodium transport
Cause fluid retention
Fludrocortisone has high mineralocorticoid effects
Prednisone and Methylpred have less mineralocorticoid activity
Rheumatoid Arthritis Treatment
NSAIDs and steroids for short-term pain
- withdrawal once DMARDs take effect
- NSAIDs do not, and steroids only mildly prevent joint damage
DMARDs used indefinitely unless significant toxicity occurs
-choice of DMARD depends on disease severity, prognosis factors, and patient preference
DMARDs
Disease-Modifying Antirheumatic Drugs
Variable patient response
If no remission w/in 3 months, change DMARD or do combo therapy
Assess efficacy every 3-6 months
Methotrexate (Rheumatrex)
1st line for RA
2-6 week efficacy, 1X/week dosing to reduce toxicity risk
MOA: stimulate adenosine release, decrease neutrophil adhesion, suppress cell-mediated immunity, antiproliferative
Folic acid analog - require 1mg/day folic supplementation
CI: pregnancy, Liver dx, ETOH abuse, GFR <30
Monitor CBC, LFTs, Albumin, Creatinine
SE: Alopecia, myelosuppression, hepatic and pulmonary toxicity
Sulfasalazine (Azulfidine)
2nd line for RA
MOA: inhibit PNM cell migration, decreased lymphocyte response and angiogenesis
90% excreted in feces, only 30% absorbed and returned in bile - coliform bacteria needed to break down
CI: sulfa allergy, pregnancy (D), GU/GI obstruction, porphyria, thrombocytopenia, LFTS >2X ULN, hepatitis
SE: orange-yellow skin pigment, depression, neutropenia, thrombocytopenia
Monitor CBC monthly 3X then q3months
Leflunomide (Avara)
Anti-inflammatory and antiproliferative - decreases joint erosion
MOA: complete dihydrofolate inhibitor - decreased B and T cell proliferation - inhibits pyrimidine synthesis
2 years until women are fertile after use
CI: pregnancy, liver disease, alcoholism
SE: reversible alopecia, hepatoxicity, rash, HTN, myelosuppression
Affects Warfarin, rifampin, and bile sequestrant drugs
Hydroxychloroquine (Plaquenil)
Anti-malarial
Not great for RA - used only with mild RA w/o joint destruction or inflammatory/AI markers
MOA: inhibit lysosomal, IL-1, PMNs, lymphocyte
Toxicity - macular damage - get fundoscopic and VA q6-12 mo
SE: photosensitivity, skin pigment changes, rash, macular damage
Effects BB, cyclosporin, and digoxin levels
TNF Inhibitors
For severe RA
Etanercept (SQ), Infliximab (IV), Adalimumab (SQ)
Decrease joint damage
CI: latent TB (BBW), high infection risk
Use of Remicade w/ MTX decreases risk of infusion reaction, use w/ other TNFI causes too much immunosuppression
SE: Injection reaction, increase risk infection
Anakinra (Kineret)
Immune modulator - recombinant IL-1 receptor antagonist
Decreases joint destruction and inflammation
Decrease dose w/ GFR <30
CI: TNF inhibitor use - increased infection risk
CI: E. coli protein sensitivity, infection, TNFI
SE: reaction @ site, infection, angioedema/anaphylaxis, leukocytopenia
Monitor CBC X3 mo then q4 months for 1 year
