Immunosuppressant Pharmacology Flashcards
Prednisone (glucocorticoids)
Synthetic glucocorticoid medication used to treat inflammatory diseases and to prevent organ transplant rejection.
Side effects prednisone (glucocorticoids)
Osteoporosis, immunosuppression, hyperglycemia
Long term side effects of prednisone
Ocular disorders, like cataracts and glaucoma, ulcers and cushing syndrome
Why should patients be tapered off prednisone
Adrenal insuffiency can develop
MOA prednisone
It is a glucocorticoid, so it upregulated anti inflammatory proteins, decreasing immune activity (inflammation) additionally they regulate the metabolism of glucose
Indications for prednisone
Inflammatory conditions (asthma, COPD, Rheumatic disorder, hives, allergic reactions, IBD) Organ transplant rejection
Side efffects prednisone
Cataracts and open angle glaucoma, Cushing , ostoporosis, immunosuppression , hyperglycemia, ulcers
Prednisone and cataracts and open angle glaucoma
Increased production of free radicals along with high osmotic movement of glucose in the lens of the eye. Get eye exams every 6mo
Cushing and prednisone
Excess glucocorticoid give rapid weight gain, central obesity, moon faces, buffalo hump and abdominal striae,
Excess mineralocorticois can also lead to hyperkalemia and fluid loss
Prednisone and osteoporosis
Steroid induced
Patients should take prophylactic vitamin D
K
Kids on prednisone
Growth retardation due to inhibition of osteoblasts function and decrease GI ca absorption
Prednisone and immunosuppression
All glucocorticoids lead to immunosuppression
Infections!
Why not give prednisone people live vaccines
Immunosuppression
Hyperglycemia prednisone
Alter glucose metabolism
Glycosuria
Ulcer prednisone
Peptic ulcers, impaired ulcer healing
Don’t take if have ulcers
Adrenal insuffiency prednisone
The body decreases adrenal output of steroid hormones . So don’t abruptly stop you should taper
Cyclosporine (sandimmune)
Immunosuppressant medication used to prevent organ rejection in transplant patients as is also indicated in the treatment of psoriasis and rheumatoid arthritis.
MOA ciclosporin
Inhibits an enzyme Called calcineurin that is responsible for production of cytokines, such as il2
IL2 suppression
Decrease B cell and cytotoxic T cell production effectively suppressing the patients immune system
What should patients taking cyclosporin not take
Grapefruit juice as it prevents the drug from being metabolized and can lead to toxicity
When combined with other immunosuppresssants, cyclosporin can increase a patients risk of developing ___
Lymphomas
MOA cyclosporin
Immunosuppressant by inhibiting an enzyme called calcineurin that is responsible for production of cytokines such as IL2
Inhibition of calcineurin by cyclosporin
Suppresses IL2 which are responsible for producing B cells and cytotoxic T cells. Suppress immune system
Indications for cyclosporin
Prevent transplant rejection
Psoriasis
RA
Cyclosporin and transplant
Given with glucocorticoid, used to prevent organ rejection in transplant patients. Does not suppress the bone marrow
Psoriasis and cyclosporin
Psoriasis causes overproduction of keratinocytes or skin cells
Inflammatory T cells play a key role int he development of this disorder and are likely responsible for secreting cytokines that lead to excessive proliferation of keratinocytes.
It suppresses the production of cytokines
Cyclosporin and RA
Immune system produces cytokines that attack synovial tissue, producing inflammation and joint destruction . Cyclosporine is used to suppress the production of cytokines thus slowing the progression of the disease
Why monitor the plasma levels of cyclosporine
Must be maintained to protect against organ transplant rejection
Why avoid grapefruit juice on cyclosporin
Prevents drug from being metabolized
Risk of lymphoma with cyclosporin
When combined with other immunosuppressants
Cyclosporin (sandimmune) side effects
Nephrotoxicity, hepatotoxicity, infection, hypertension, tremor, hirsutism, gynecomastia, gingival hyperplasia, hyperkalemia
Nephrotoxicity with cyclosporin
Causes severe kidney damage characterized by decreased renal blood flow and decreased glomerular filtration
Hepatotoxicity cyclosporin
Liver damage
Monitor AST, ALT
Infections nd cyclosporin
From immune suppression
Does cyclosporin cause bone marrow suppression
No however leukopenia may occur
Cyclosporin and hyperkalemia
Cause retention of potassium
Hypomagnesia and cyclosporine
Can lead to nephrotoxicity, resulting in mg wasting and hypomagnesemia
Tacrolimus (prograf)
Immunosuppressant for organ rejection prevention and also used in atopic dermatitis
MOA tacrolimus
Works by inhibiting an enzyme called calcineurin that is responsible for production of cytokines such as IL2
Suppression of IL2
Decreases B cell and cytotoxic T cell production, effectively suppressing the patients immune system
Why should patients on tacrolimus not drink grapefruit juice
Prevents metabolism and lead to toxicity
Tacrolimus can increase a patients risk of developing ___ ___
Malignant lymphomas
MOA tacrolimus
Inhibit calcineurin reduce IL2 so B and Cytotoxic T cells not helped
Indications for tacrolimus
Transplant rejection Atopic dermatitis (eczema)
Atopic dermatitis and tacrolimus
Topical ointment for treating it
Works locally to suppress the release of inflammatory mediators, effectively decreasing inflammation associated with atopic dermatitis
Tacrolimus side effects
Nephrotoxicity Neurotoxicity Infectiondiarrhea Nausea Vomiting Hypertension Hyperkalemia Hyperglycemia GI distress
Neurotoxicity seen with tacrolimus
Headache, tremor, insomnia
Why tacrolimus give hyperglycemia
Increasedglucose levels as can interfere with insulin secretion int he body
Methotrexate (MTX)
Antimetabolite and disease modifying antiheumatic drug (DMARD) that acts by inhibiting dihydrofolate reductase
how does methotrexate work
Inhibit dihydrofolate reductase
Stops production of dTMP (thymidine) which is necessary for DNA , RNA and protein synthesis, thus resulting in cell death
Side effects methotrexate
Myelosuppression (which can be treated with leucovorin), microcytic anemia, hepatitis, teratogen is effects and oral mucositis
Indications for methotrexate
RA, cancer, medical abortion
RA and MTX
Decreases severity of arthritis,
Look at CBC, AST, ALT
Cancer MTX
Results incell death or rapidly dividing cancer cells. Use in leukemia’s, lymphomas, choriocarcinoma and sarcomas
Medical abortion and methotrexate
Followed by vaginal misoprostol
Up to 49 days gestation
Why is MTX+ misoprostol inferior to mifepristone+ misoprostol for medical abortion
The interval between treatment and complete abortion is longer
MTX is used for treatment of small, unruptured ectopic pregnancies
MOA MTX
Folic acid analog-prevent folic acid metabolism and thus thymidine production because it has a much higher affinity for dihydrofolate reductase than folic acid
Inhibits dihydrofolate reductase-without it MTX binds competitively inhibits the biologically active form of folic acid, THF cannot be reformed
Side effects MTX
Pulmonary fibrosis, myelosuppression , microcytic anemia, hepatitis, teratogenic, mucositis
How revers myelosuppression from MTX
Leucovorin which has vitamin activity equivalent to that of folic acid but does not require dihydrofolate reductase to be converted to its biologically active form. This quickly allows thymidine levels to be restored so that DNA RNA and protein synthesis can occur
Microcytic anemia and MTX
Results in functional defiency of folic acid,
What is microcytic anemia
Mean corpuscular volume being greater than 100
Azathioprine (imuran)
Immunosuppressant used in organ transplant and to treat autoimmune disorders
MOA azathioprine
Prodrug, or precursor, to 6-mercaptopurine, which interferes with nuclei acid and DNA synthesis
What cells are effected by azathioprine
proliferating cells like T and B cells leading to myelosuppression
What metabolizes azathioprine
Zanthine oxidasse
Patients taking allopurinol should reduce AZA dose. Why
Allopurinol inhibits xanthine oxidase
Patients with IBD taking azathioprine also runt he risk of developing acute __-
Pancreatitis
MOA azathioprine
Antimetabolite-competes with metabolites and interfere with cell function 9cancer treat bc cells are dividing!)
-makes 6-mercaptopurine (AZA quickly converted to 6MP)
Inhibits synthesis of nuclei acid (inhibiting purine synthesis, structure of RNA DNA is altered)
AZA->6MP
Via nonenzymatic nucleophilic attack by compounds found in rbc and other tissues
What does 6MP do
Active form of AZA which is a thiopurine that interferes with DNA synthesis
Indications for AZA
Autoimmune disorders
Kidney transplant
What autoimmune disorders can be treated with AZa
SLA, croons, RA
Side effects AZa
Myelosuppression
Increased toxicity with allopurinol use
Pancreatitis
Malignancy
AZA myelosuppression
Severe bone marrow suppression
Can get leukopenia, thrombocytopenia, anemia’s including microcytic anemia, and/or pancytopenia may be seen in patients taking AZa
Malignancy from AZA
Bc it immunosuppresses can get lymphoma, particularly skin.
Post transplant lymphoma and hepatosplenic T cell lymphoma (HSTCL)
Inform patients of risks before take it
