2: Immunosuppression in autoimmune shit Flashcards
what happens in Ab-mediated disease?
specific Ab exists which is targeted against a particular Ag (protein) and leads to clinical sx upon the protein’s destruction
examples of Ab-mediated disease
- hemolytic anemia (target on surface of RBCs)
- myasthenia gravis (AChR in NMJ)
- hypoadrenocorticism (adrenal cells)
what happens in immune complex mediated disease?
Abs are produced against proteins in body and combine into large complexes that circulate throughout the body and get stuck
examples of immune complex mediated disease
- SLE (Ab’s against components of cell nucleus)
- rheumatoid arthritis
what happens in Ab and T cell mediated diseases?
exposure to a particular Ag will program for the search and destruction of that particular Ag in the future
examples of Ab and T cell mediated diseases
thyroiditis autoimmune hypothroidism (targets thyroglobulin)
what are the primary drugs used to treat any autoimmune disorder?
corticosteroids - prednisone, prednisolone
how are corticosteroids given?
very high dose initially to induce remission, then slowly lowered dose to a low maintenance dose
why should corticosteroids be avoided long term?
increases risk of infections, ulcers, hyperglycemia, osteoporosis
what do you use if corticosteroids are insufficient?
cyclophosphamide or azathioprine may be added- but must be monitored closely for side effects
cyclophosphamide MOA
interferes w/ DNA synthesis/fxn by alkylation - affects B cells more than T cells
azathioprine MOA
purine antimetabolite that interferes with DNA synthesis - affects rapidly growing cells, such as bone marrow and GI
how long does it take to see results of azathioprine?
several weeks
SE of azathioprine
- leukopenia
- thrombocytopenia
- GI dysfunction
- higher susceptibility to infection and hepatic lesions
azathioprine metabolism
metabolized to give mercaptopurine
MOA of mercaptopurine
interferes with RNA/DNA synthesis after conversion into purine antagonist inside cells - mainly focused on humoral immunity
SE of mercaptopurine
due to bone marrow and GI cell depletion - need regular assessment of possible bone marrow suppression, and liver and pancreatic diseases
MOA of leflunomide
prodrug of an inhibitor of pyrimidine synthesis
uses of leflunomide and PK of it
rheumatoid arthritis
long half life of several weeks
what is it important to measure during cyclosporine therapy?
blood cyclosporine levels b/c varies in absorption and saturates tissues, so doses may need adjusting sometimes
- also interacts with other drugs frequently
- needs a strict diet and dosing schedule
what happens in the allergic state?
immune system overreacts to foreign substances (allergens/antigens) to which it is exposed, resulting in release of histamine and production of lesions in targeted organs
three ways in which allergies manifest
- itching skin (local or generalized) and swelling (esp. face)
- resp: coughing, wheezing, sneezing
- GI: vomit, diarrhea
severe can cause anaphylactic shock
what percent of allergies can be effectively controlled?
90% -topical and systemic treatments
systemic treatment of allergies
includes fatty acids (linoleic, gamma-linolenic) that work in the skin to help reduce the amount and effects of histamine
SE of fatty acids for allergy tx
very few
can be enhanced by antihistamines and biotin
why is it common for a person to have to try multiple antihistamines before they find one that works?
every patient responds differently to each of the antihistamines
MOA of antihistamines
H1 blockers - outcompete histamine for binding site on target
what are common H1 blockers? which ones do not cause drowsiness?
diphenhydramine (benadryl)
promethazine
chlorpheniramine
no sedation:
- rupatadine
- cetirizine
- fexofenadine
what is the most intense allergy therapy?
weekly or montyly injections with allergens to induce desensitization
how can corticosteroids be used for allergies?
SC, IM, or PO but only to treat severe symptoms or after all other options have been exhausted
what corticosteroids are available for injection for allergies?
betamethasone
dexamethasone
methylprednisolone
triamcinolone
