Flashcards in Pharmacology: Immuno-Modulating Drugs Deck (138)
RA, SLE, Scleroderma, Sjogren's Syndrome, Goodpasture Syndrome, Wegener's Granulomatosis, Polymyalgia Rheumatica, and Guillane-Barree Syndrome are all examples of what?
Systemic Autoimmune Diseases
Type I DM, Hasimoto's Thyroiditis, Graves Disease, Celiac disease, Crohn's disease, UC, Addison's disease, Primary biliary cirrhosis, Sclerosine Cholangitis, and autoimmune hepatitis are all examples of what?
Localized Autoimmune Diseases
What are 2 branches of the immune system?
1. Innate: Nonspecific (1st line of defense)
2. Adaptive: Specific (2nd line of defense- Protects/Re-Exposure)
Both the innate and adaptive immune system have what 2 types of components?
Cellular and Humoral
Name 6 examples of glucocorticoids presented in class.
What is the MOA of glucocorticoids?
1. Regulate gene expression
2. Inhibits synthesis of eicosanoids
What type of immunity to glucocorticoids interfere with?
What are the 4 anti-inflammatory effects of corticosteroids?
1. Redistributes components of cellular immunity
2. Inhibits function and secretions of antigen-presenting cells
3. Inhibits synthesis of pro-inflammatory eicosanoids
4. Decrease release of histamines by basophils and mast cells
What types of cells are redistributed by corticosteroids?
Neutrophils, lymphocytes (T and B cells), eosinophils, basophils
What pro-inflammatory eicosanoids are inhibited by corticosteroids?
Prostaglandins, leukotrienes, and thromboxanes
How do corticosteroids inhibit the synthesis of pro-inflammatory eicosanoids?
The decrease the expression of COX
(also decrease expression of COX-2)
What are the 4 autoimmune conditions corticosteroids are used for?
2. Autoimmune hemolytic anemia
3. Acute glomerulonpehritis
4. Auto-reactive tissue disorders
What types of transplants are corticosteroids used for?
Renal, heart, Liver, BM
What are corticosteroids the first line immunosuppressive agents for?
1. Solid organ recipient
2. Hematopoietic stem cell transplant recipients
Corticosteroids have a really long list of toxicities... name them.
-Hyperglycemia (insulin resistance-steroid diabetes)
-Hypothalamic – pituitary axis (HPA) suppression
-Adrenal insufficiency (AI) [isolated glucocorticoids deficiency with normal aldosterone secretion]
-Retention of Na, H2O (mineralocorticoids)
-Causes muscle weakness on withdrawal
-Growth hormone inhibition
-Delayed wound healing
What is the MOA of Cyclosporine or Sandimune?
It binds cyclophilin, inhibits T-cell activation, decreases IL-2, IL-3, and IFN-gamma
What are 5 of the main clinical uses for cyclosporine?
1. Immune disorders
2. Human organ transplant
3. GVHD (Post-Hematopoietic stem cell transplant)
4. Dry eye syndrome
5. Ocular GVHD
True or False: Cyclosporine has an inhaled formula?
FALSE... but one is in the works
What types of transplants is cyclosporine used for?
Kidney, liver, pancreas, cardiac
What is cyclosporine combined with as standard prophylaxis for GVDH after an allogenic stem cell transplant?
What specific autoimmune diseases is cyclosporine used for?
Uveitis, RA, Psoriasis, Asthma
What are the 2 forms cyclosporine is given in?
Oral or IV
What metabolizes cyclosporine and what is the consequence of this?
P450 CYP3A4 (in liver)
-Results in a lot of multidrug interactions
What is the concern with drug interactions and cyclosporine?
Drugs that diminish the liver enzyme system will INCREASE cyclosporine blood levels
What are some drugs that will interact with cyclosporine and INCREASE cyclosporine blood levels?
6. Oral Contraceptives
What is another concern with drug interactions and cyclosporine?
Worry about drugs that cause induction of the microsomal liver enzyme system and DECREASE the half-life and blood levels of cyclosporine
What are some drugs that interact with cyclosporine and DECREASE cyclosporine blood levels and half-life?
Cyclosporine slso has a very long lists of toxicities name them.
-Altered mental status
-Induces TGF-, promotes tumor invasion and metastasis, incidence of lymphomas, Kaposi’s sarcoma
What's the cyclosporine toxicity she noted as important and is in green on our PPT?
Induces TGF-, promotes tumor invasion and metastasis, incidence of lymphomas, Kaposi’s sarcoma