2: Immunosuppression in autoimmune shit

Question 1

what happens in Ab-mediated disease?

Answer 1

specific Ab exists which is targeted against a particular Ag (protein) and leads to clinical sx upon the protein’s destruction

Question 2

examples of Ab-mediated disease

Answer 2

• hemolytic anemia (target on surface of RBCs)
• myasthenia gravis (AChR in NMJ)
• hypoadrenocorticism (adrenal cells)

Question 3

what happens in immune complex mediated disease?

Answer 3

Abs are produced against proteins in body and combine into large complexes that circulate throughout the body and get stuck

Question 4

examples of immune complex mediated disease

Answer 4

• SLE (Ab’s against components of cell nucleus)

- rheumatoid arthritis

Question 5

what happens in Ab and T cell mediated diseases?

Answer 5

exposure to a particular Ag will program for the search and destruction of that particular Ag in the future

Question 6

examples of Ab and T cell mediated diseases

Answer 6

thyroiditis 
autoimmune hypothroidism (targets thyroglobulin)

Question 7

what are the primary drugs used to treat any autoimmune disorder?

Answer 7

corticosteroids - prednisone, prednisolone

Question 8

how are corticosteroids given?

Answer 8

very high dose initially to induce remission, then slowly lowered dose to a low maintenance dose

Question 9

why should corticosteroids be avoided long term?

Answer 9

increases risk of infections, ulcers, hyperglycemia, osteoporosis

Question 10

what do you use if corticosteroids are insufficient?

Answer 10

cyclophosphamide or azathioprine may be added- but must be monitored closely for side effects

Question 11

cyclophosphamide MOA

Answer 11

interferes w/ DNA synthesis/fxn by alkylation - affects B cells more than T cells

Question 12

azathioprine MOA

Answer 12

purine antimetabolite that interferes with DNA synthesis - affects rapidly growing cells, such as bone marrow and GI

Question 13

how long does it take to see results of azathioprine?

Answer 13

several weeks

Question 14

SE of azathioprine

Answer 14

• leukopenia
• thrombocytopenia
• GI dysfunction
• higher susceptibility to infection and hepatic lesions

Question 15

azathioprine metabolism

Answer 15

metabolized to give mercaptopurine

Question 16

MOA of mercaptopurine

Answer 16

interferes with RNA/DNA synthesis after conversion into purine antagonist inside cells - mainly focused on humoral immunity

Question 17

SE of mercaptopurine

Answer 17

due to bone marrow and GI cell depletion - need regular assessment of possible bone marrow suppression, and liver and pancreatic diseases

Question 18

MOA of leflunomide

Answer 18

prodrug of an inhibitor of pyrimidine synthesis

Question 19

uses of leflunomide and PK of it

Answer 19

rheumatoid arthritis

long half life of several weeks

Question 20

what is it important to measure during cyclosporine therapy?

Answer 20

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

Question 21

what happens in the allergic state?

Answer 21

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

Question 22

three ways in which allergies manifest

Answer 22

• itching skin (local or generalized) and swelling (esp. face)
• resp: coughing, wheezing, sneezing
• GI: vomit, diarrhea

severe can cause anaphylactic shock

Question 23

what percent of allergies can be effectively controlled?

Answer 23

90% -topical and systemic treatments

Question 24

systemic treatment of allergies

Answer 24

includes fatty acids (linoleic, gamma-linolenic) that work in the skin to help reduce the amount and effects of histamine

Question 25

SE of fatty acids for allergy tx

Answer 25

very few

can be enhanced by antihistamines and biotin

Question 26

why is it common for a person to have to try multiple antihistamines before they find one that works?

Answer 26

every patient responds differently to each of the antihistamines

Question 27

MOA of antihistamines

Answer 27

H1 blockers - outcompete histamine for binding site on target

Question 28

what are common H1 blockers? which ones do not cause drowsiness?

Answer 28

diphenhydramine (benadryl)
promethazine
chlorpheniramine

no sedation:

• rupatadine
• cetirizine
• fexofenadine

Question 29

what is the most intense allergy therapy?

Answer 29

weekly or montyly injections with allergens to induce desensitization

Question 30

how can corticosteroids be used for allergies?

Answer 30

SC, IM, or PO but only to treat severe symptoms or after all other options have been exhausted

Question 31

what corticosteroids are available for injection for allergies?

Answer 31

betamethasone
dexamethasone
methylprednisolone
triamcinolone