Immunopharmacology Flashcards
Dexamethasone
Mechanism of Action:
- broadly anti-inflammatory
- binds cytosolic glucocorticoid receptors
- down regulate inflammatory mediators
- inhibit prostaglandin synthesis: PLA2 & COX-2
Use:
- transplant rejection
- autoimmune disorders
- neuropathic & bone pain
- palliative care
Adverse:
- HTN
- Hyperglycemia
- immunosuppression
- psychotic reactions
- cognitive impairment
- myopathy
- Cushing’s syndrome
- osteoporosis
Cyclosporine
Calcineurin inhibitor
Mechanism of Action:
- phosphatase activates NFAT
- NFAT = cytokine induction
- complexes w/cyclophilin
- inhibits calcineurin
Use:
- organ transplant
- uveitis
- rheumatoid arthritis
- psoriasis
Adverse:
- nephrotoxicity
- tremor
- HTN
- hyperglycemia
- hyperlipidemia
- osteoporosis
- hirsutism
- gum hyperplasia
Tacrolimus
Calcineurin inhibitor
Mechanism of Action:
- binds FK-binding protein (immunophilin)
Use:
- organ transplant (kidney, liver or heart)
- atopic dermatitis
- psoriasis
Adverse:
- nephrotoxicity
- neurotoxicity
- HTN
- hyperkalcemia
- GI complaints
- hyperglycemia
Sirolimus
Proliferation signal inhibitor
Mechanism of Action:
- bind FKBP
- inhibits serine-threonine kinase mTOR
- blocks IL-2 driven T-cell proliferation
Use:
- renal transplant
- inhibit restenosis in severe CAD
Adverse:
- myelosuppression
- hepatotoxicity
- diarrhea
- hypertriglyceridemia
- pneumonitis
- headache
Thalidomide
inhibitor of angiogenesis
Mechanism of Action:
- inhibits TNF-a (unclear)
Use:
- erythema nodosum leprosum
- multiple myeloma
Azathioprine
Mechanism of Action:
- purine antimetabolite
- converted to 6-MP
- suppression of B- & T-cell function
- Ig production & IL-2 secretion
- inactivation depends on xanthine oxidase
Use:
- transplant rejection
- rheumatoid arthritis, severe
Adverse:
- BM suppression
- GI disturbances
- inc. infections & malignancies
Methotrexate
Mechanism of Action:
- inhibit AICAR transformylase
- accumulation of AMP
- AMP released & converted extracellularly to adenosine
- adenosine is a potent inhibitor of inflammation
Use:
- rheumatoid arthritis
- psoriasis
- psoriatic arthritis
- ankylosing spondylitis
- systemic lupus erythematosus
Adverse:
- nausea
- mucosal ulcers
- leukopenia
- anemia
- GI ulcerations
- hepatotoxicity
- cirrhosis (rare)
- hypersensitivity pneumonitis
Mycophenolate Mofetil
Mechanism of Action:
- inhibits inosine monophosphate dehydrogenase
- suppresses B- & T-lymphocyte activation
Use:
- transplant rejection
- systemic lupus erythematosus
Adverse:
- nausea
- vomiting
- diarrhea
- abdominal pain
- HTN
- headache
- reversible myelosuppression
Leflunomide
Mechanism of Action:
- prodrug of teriflunomide
- inhibit dihydroorotate dehydrogenase
- dec. UMP levels
Use:
- rheumatoid arthritis
- systemic lupus erythematosus
- myasthenia gravis
Adverse:
- diarrhea
- rash
- reversible myelosuppression
- inc. aminotransferase activity
- cardiogenic & teratogenic
- contraindicated in pregnancy
Cyclophosphamide
Mechanism of Action:
- destroys proliferating lymphoid cells
- alkylates DNA & other molecules in resting cells
Use:
- systemic lupus erythmatosus
- other autoimmune diseases
Adverse:
- infertility
- BM suppression
- hemorrhagic cystitis
- bladder cancer (rare)
- acrolein, urinary toxicities
- inc. risk of infection & malignancy
Tofacitnib
Mechanism of Action:
- inhibit JAK enzymes that stimulate hematopoiesis
- inhibit JAK enzymes that stimulate immune cell function
- dec. circulating NK cells, serum Ig, & CRP
Use:
- rheumatoid arthritis, moderate to severe
Adverse:
- serious infections
- malignancies
Hydroxychloroquine
Mechanism of Action:
- unclear
Use: (+ methotrexate & sulfasalazine)
- rheumatoid arthritis
- systemic lupus erythematosus
Adverse:
- hemolysis, G6PD deficiency
- retinal damage
Sulfasalazine
Mechanism of Action:
- metabolized by bacteria of colon
- sulfapyridine & 5-ASA connected by diazo bond
Use:
- rheumatoid arthritis
- ulcerative colitis
- Crohn’s disease
- ankylosing spondylitis
Adverse:
- nausea
- vomiting
- headache
- rash
- neutropenia
- hemolysis, G6PD deficiency
- thrombocytopenia (rare)
- drug-induced lupus (rare)
Antilymphocyte Globulin (ALG) Antihymocyte Globulin (ATG)
Use:
- stem cell transplant
- solid organ transplant
Rho(D) Immune Globulin
Use:
- Rh hemolytic disease prevention
