Day 2- Rheumatoid arthritis and other things Flashcards
What are the CYP3A4 inhibitors(G-PACMAN)?
What are the CYP3A4 inducers?
Is there inflammation always in rheumatoid arthritis?
Grapefruit juice, Protease inhibitors(Navirs or HIV drugs), Azole antifungals(not fluconazole), Cimetidine, Macrolides(not Azithromycin), Amiodarone, Non-DHP calcium channel blockers.
Phenytoin, Carbamazepine, St. Johns Wort, Rifampine.
YES
Who is more prone to rheumatoid arthritis?
What are the 3 big proinflammatory cytokines?
What is the pathophysiology of Rheumatoid Arthritis?
More females(20-60 years old).
TNF-alpha, IL-6, IL-1.
Baseline Immune Function–> Activated T Cells, B cells, & Macrophages–> Significant production of inflammatory cytokines(TNFalpha, IL-6, IL-1)–> inflammation tissue damage.
Does rheumatoid arthritis have insidious onset of symmetrical joint pain, swelling, and morning joint stiffness that worsens over time?
What are some clinical presentations of rheumatoid arthritis?
What lab results tell us about RA?
YES
Malaise, Joint pain, Loss of daily functioning( leading cause of permanent disability for working age individuals), Increased risk for cardiovascular events, Extra-articular manifestations(dry eyes and mouths, vasculitis, pericardidits, lung problems). Early disease <6 months, established is >6 months.
Rheumatoid factor, ACPA, ANA, elevated ESR and CRP.
What joints are usually affected by RA?
What are some non drug RA therapies?
What are the Conventional DMARDS?
Hands, Feet.
physical therapy, exercise, conservation of energy, surgery, NSAIDS, do NOT use acetaminophen. 2nd line option is opioids(give with senna-s or pericolace) and glucocorticoids(often prednisone).
Methotrexate, Leflunomide(Arava), Hydroxychloroquine(plaquenil), Sulfasalzine.
How does methotrexate work?
What special things to know about methotrexate?
How does Leflunomide(LEF, Arava) work?
Disrupt DNA(purine).
CI’d in pregnancy, increased infection risk, thrombocytopenia & leukopenia, liver toxicity(Folic Acid) and pneumonitis(rare), Nausea, Stomatitis(take folic acid), Anorexia. folinic acid(leucovorin) reverses it. Doses <15 mg PO, anything above needs to be >15.
Disrupt DNA(pyrimidine) synthesis.
What special things to know about Leflunomide(LEF, Arava)?
What are sulfalazine’s(MOA unknown) side effects?
What to watch for in Hydroxychloroquine?
Potentially fatal allergies(steven johnson syndrome), thrombocytopenia, leukopenia, teratogenic, liver toxicity, Alopecia, Diarrhea, Rash. LEF can be removed using cholestyramine(Questran).
Hypersensitivity, liver toxicity, oligospermia, thrombocytopenia, photosensitivity, rash, GI complaints, yellow urine discoloration
eye exam, otherwise well tolerated.
What drugs do you avoid with combination therapy and DMARDS?
What 5 drugs target TNF-alpha?
Are Rituximab(CD20 B cell), Abatacept(CD80/86), Tofacitinib(JAK), and Tocilizumab(IL-6 receptor) used for Rheumatoid Arthritis?
Avoid MTX with Leflunomide(due to live toxicity)
Etanercept, Infliximab(given IV), Adalimumab, Golimumab, Certolizumab pegol
YES, Tofacitinib is PO.
What are the CI’s for Biologic agents?
What are additional CI’s for TNF-alpha’s?
When is Abatcept also CI’d?
LIVE VACCINES, cancer risk, TB, opportunistic infections, fungal infeciton, significant systemic bacterial infections, use with another biologic agent including tofactinib anaphylaxis or serious allergic reactions.
Hepatitis B reactivation, Heart failure, demylinating disease, lupus like symptoms.
Demyleinating agents, COPD like symptoms.
When is Rituximab CI’d?
What is toxilizumab and tofacitnib’s CI’s?
Can you use MTX and leflunomide together?
Hep B, Demyelinating disease, Fatal infusion reaction within 24 hours of dose, severe mucocutaneous, cytopenia, cardiac arrhythmia and angina, Bowel obstruction or perforation.
Cytopenia, Bowel obstruction/perforation, Changes in serum lipids and liver functions
NO(liver, gI)
Can you use MTX and NSAID together?
Can you combine biologics?
Can you combine tofacitinib and omeprazole/esomeprazole?
Yes but watch for bleeding
NO(too much liver toxicity)
NO(CYP2C19)(Reduce Tofacitinib)
Can you combine Tofacitinib and CYP3A4 inhibitors and Inducers?
Can you use biologics and methotrexate?
What is the first thing you use in EARLY mild to moderate RA?
Reduce dose for inhibitors, Don’t do for inducers since we don’t know how much to up it to.
Yes(reduced anti-drug antibodies).
Methotrexate monotherapy
What do you start with in Early moderate to high disease activity?
Is established the same guidelines?
What are the most common ways to minimize graft rejection?
Combination DMARDS, combination TNFi +/- MTX, Non-TNF biologic +/- MTX, May add low dose steroids for short duration during flares.
Yes, except in moderate to high you can do Tofacitinib +/- MTX.
Use organs from another person that has optimal transplant genetics and transplant conditions and use immunosuppressants to reduce the activity of the recipient immune system.
What conditions are at higher risk for rejection?
What is a hyperacute rejection?
What is an acute rejection?
African-American, Cadaveric Donor, Previous transplant, transplant for pancreas, lung, or small bowel, high PRA titier, Poor HLA match, ATN.
Onset after minutes and hours, no drug treatment, due to poor matching, quick loss of graft.
Days to weeks/months, usually no loss of graft, treat with steroids, polyclonal or therapeutic monoclonal antibodies(add drug or increase dose)
What is a chronic rejection?
What are the symptoms of graft rejection?
What to know about multiple drugs in achieving immunosuppresion?
happens months to years later, drug therapy ineffective, loss of graft.
Flu like symptoms, fever, pain or tenderness over transplant area, fatigue, loss of kidney function.
Average number is 3, allow for lower doses but increases likelihood of drug drug interactions. As patient ages you can remove some drugs.
What is the MOA for the glucocorticoids?
What drugs inhibit Calcineurin?
How do the antiproliferatives work?
Anti-inflammatory, Alters cytokine production and activity, B-cell Apoptosis. Prednisone.
Cyclosporine, and Tacrolimus.
Mycophenolate Mofetil and Mycophenolic Acid are anti-proliferatives.
