the russian Flashcards
glucocorticoid drugs
Cortisone, prednisone, triamcinolone,
betamethasone,dexamethasone and
fludrocortisone
glucocorticoid mechanism of action
regulates gene expression
inhibits synthesis of eicosinoids
interferes with cellular immunity
corticosteroids anti inflammatory effect
1) redistribute the components of cellular immunity(neutrophils,eosinophils,basophils,lymphocytes)
2) inhibits the function and secretion of antigen presenting cells
3) inhibits the synthesis of proinflammatory eicosinoids(prostaglandins, leukotrianes and thromboxanes) - also decreases the expression of cox 2
4) decrease the release of histamine by basophils and mast cells
the clinical uses of corticosteroids
ITP autoimmune hemo lytic anemia bone, heart, kidney and liver transplant acute glomerulonephritis auto reactive tissue disorders
first line immunosupressive agents for solid organ and hematopoeitic stem cell transplant recipients
corticosteroids
corticosteroid toxicity
peptic ulcer
osteoperosis
glaucoma
HTN
hyperglycemia (insulin resistance) (steroid diabetes)
Adrenal Insufficiency(AI) - isolated glucocorticoids deficiency with normal aldosterone secretion
hypothalamic - pituatary(HPA) axis suppression
opportunistic infection
cataracts
growth hormone inhibition
delayed wound healing
causes muscle weakness on withdrawel
retention of NA+, H20 (mineralocorticoids)
cyclosporine mechanism of action
binds to cyclophin and inhibits T cell activation and the release of IL-2, IL-3 and IFN
cyclosporine Clinical Indications
- HUMAN ORGAN TRANSPLANT
- selected immune disorders
- treatment of graft vs host disease after hematopoeitic stem cell transplant
- severe dry eye syndrome
- ocular graft vs host disease
- cadaveric transplant of KIDNEY, LIVER, PANCREASE, as well as cardiac transplantation
also used for some autoimmune diseases like UVEITIS, rhumatoid arthiritis, psoriasis and asthma
when combined with methotrexate cyclosporine is standart prophylaxis for graft vs host disease following allogentic stem cell transplant
cyclosporine metabolism
Oral and IV
Primarily metabolized by the P450 CYP3A4 enzyme system in the liver with resultant multidrug interaction
cyclosporine drugs that diminish the liver enzyme system thus increasing its half
drugs that diminish the liver
enzyme system increase the cyclosporine blood levels
Diltiazem, erythromycin, ketoconazole, methyltestosterone and oral contraceptives
cyclosporine drugs that induce the microsomal liver enzyme system
the drugs that reduce the half life and blood levels of cyclosporine include Carbamazepine isoniazid phenobarbital phenytoin rifampin
cyclosporine toxicity
Induces TGF, PROMOTES TUMOR INVASION AND METASTASIS, INCIDENCE OF LYMPHOMAS AND KAPOSIS SARCOMA
also….
nephrotoxicity, seizures, hirsutism, HTN, hyperglycemia, liver dysfunction, hyperkalemia, and altered mental status
tacrolimus drug properties
Tacrolimus
(FK 506) is a macrolideantibiotic
•Similar MOA as cyclosporine
•Binds to immunophilin FK-binding protein (FKBP)
•Tacrolimus is more potent than cyclosporin in
inhibiting immune response
tacrolimus clinical indications
Same indications as cyclosporine, particularly in
organ and stem cell transplantation
•Effective for preventing rejection in solid organ
transplant patients even after failure of standard
rejection therapy, including anti-T-cell antibodies
•It is now a standard prophylactic agent(usually in combination with MTX or mycophenolatemofitel) for graft-versus-host disease
tacrolimus metabolism
Tacrolimus can be administered orally or IV
•Like cyclosporine, tacrolimusis metabolized primarily by P450 enzymes in the liver, with
similar potential for drug interactions
tacrolimus toxicity
Renal, neurotoxicity, hyperglycemia,
hypertension, hyperkalemia, and GI disturbances
none of this was highlighted
Sirolimus Mechanism of Action
Sirolimus binds to immunophilin(FKBP-12) but does not inhibits calcineurin
•It blocks mTOR (mammalian target of rapamycin) !!
Blocks the response of T cells to cytokines!!!!
- It is a potent inhibitor of B-cell proliferation and immunoglobulin production
- Available only as an oral drug
- Substrate for P450 3A and P-glycoprotein
- Similar clinical use as tacrolimus!!!
Sirulimis Toxicity
Profound myelosuppression, especially thrombocytopenia •Hepatotoxicity •Diarrhea •Hypertriglyceridemia •Headache non of this was highlighted
mycophenolate mofetil MOA
Inosinemonophosphate dehydrogenase (IMPDH) inhibitor!!!!!!!
•MMF is hydrolized to mycophenolic acid, the
active immunosuppressive moiety (MMF –enhanced bioavailability)
mycophenolate mofetil Clinical Indications
Used for solid organ transplant patients for
refractory rejection!!!!!
•In combination with prednisone
•As an alternative to cyclosporine or tacrolimusin
patients who do not tolerate these drugs!!!!
•For prophylaxis to prevent graft-
versus-host disease!!!!.
•Other applications
•Lupus nephritis
•RA
•Dermatologic disorders
mycophenolate mofetil Toxicity
GI (N/V/D and abdominal pain)
Headache
Hypertension
Reversible myelosuppression (primarily neutropenia)
Cytotoxic Agents
Azathioprine Cyclosphosphamide Leflunomide Hydroxychloroquine Other agents •Vincristine •MTX •Cytarabine •Pentostatin
Immuno Suppressive Antibodies
Antilymphocyte & Antithymocyte antibodies
•Indication: management of transplant
Muromonab-CD3
•Indications: autoimmune disorders and transplantation settings
Immune Globulin Intravenous (IVIG)
•Indications: autoimmune disorders, HIV, bone
marrow transplants
Rh0(D) Immune Globulin Micro-Dose
•Indication: prevention of hemolytic disease of
newborns
Hyperimmune Immunoglobulins
•Indications: treatment of respiratory syncytial
virus, cytomegalovirus, varicella zoster, human
herpesvirus 3, hepatitis B, rabies, tetanus,
digoxin overdose
Monoclonal Antibodies
Humanized and chimeric monoclonal antibodies
directed against specific receptors/antigens
- Members
- Alemtuzumab
- Bevacizumab
- Cetuximab
- Gemtuzumab
- Rituximab
- Trastuzumab
Alemtuzumab
Mechanism of action
•Humanized IgG 1 that binds to
CD52!!! on normal and malignant B and T lymphocytes, NK cells, monocytes and macrophages
•Clinical uses
•Treatment of (refractory!!!) B cell LL in patients
treated with alkylating agents and who have failed
fludarabine therapy
•Toxicity
•Lymphopenia, neutropenia, anemia,
thrombocytopenia
Bevacizumab
-MOA - Humanized IgG1 antibody that binds to vascular endothelial growth factor (VEGF) and prevents it from binding to its receptor especially on endothelial cells. Is a new drug which inhibits the formation of blood vessels in Tumors.
-Clinical Indications - Is first line treatment in patients with metastatic colorectal cancer!!! alone or in combination with 5 FU based chemotherapy
Toxicity - GI perf. hemohragge, wound healing problems, HTN and proteinuria
Cetuximab
Mechanism of action
•A human
-mouse chimeric monoclonal antibody
•Targets epidermal growth factor receptor (EGFR)!!
•Binds EGFR and inhibits tumor cell growth via:
•Decrease in kinase activity
•Matrix metalloproteinase activity
•Increased apoptosis
•Clinical uses
•In patients with metastatic colorectal cancer!!(tumor over-expressing EGFR)
Gemtuzumab
•Mechanism of action
•A humanized IgG 4 monoclonal antibody with a
kappa light chain specific for CD33found on leukemic blast cells in 80-90% of pts with AML!!!
- Clinical uses
- Approved for relapsed CD33 acute myeloid leukemia (AML)!!!!
- Toxicity
- Severe myelosuppression, especially neutropenia
- Significant hepatotoxicity
- Hypersensitivity reactions
Rituximab
Mechanism of action
•Chimeric murine-human monoclonal IgG1that binds to CD20 molecule on malignant B lymphocytes-
-Causes
1 Induction of apoptosis
2 Complement-mediated lysis
3 Antibody-dependent cellular cytotoxicity
•Clinical uses
Approved for the therapy of patients with relapsed or refractory low-grade or follicular, B-cell non-Hodgkin’s lymphoma
Trastuzumab
A recombinant DNA-derived, human monoclonal antibody that binds to the extracellular domain of the human epidermal growth factor receptor HER-2/neu
•Indication: treatment of metastatic breast cancer in patients whose tumors over-express HER-2/
neu
Type 1 Sensitivity
•Allergy to certain drugs occurs when the drug
not capable of inducing an immune response by
itself covalently binds to a host carrier protein
(hapten)
•The immune system detects the drug-hapten conjugate and responds by generating IgE antibodies specific for drug-hapten complex
•Treatment include: prednisone or
desensitization to drugs
Type II Sensitivity
•Autoimmune syndrome
•IgG antibodies bind to drug-modified tissue and
are destroyed by complement system or by
phagocytic cells with Fc receptors
•Immunosuppressive therapy used for severe cases
•Examples: Systemic lupus erythematosus
following hydralazine or procainamide,
autoimmune hemolytic anemia resulting from
methyldopa
Type III sensitivity
–Serum Sickness & Vasculitic Reactions:
•Clinical features: urticarial and erythematous skin
eruptions, arthralgia or arthritis, lymphadenopathy,
glomerulonephritis, peripheral edema and fever
•Immune vasculitis can be induced by different
drugs eg. sulfonamides, penicillin, thiouracil,
anticonvulsants, iodides
•Usually last 6-12 days
•IgM and IgG antibodies involved
•Glucocorticosteroids are useful for treatment
•In severe cases plasmapheresis can be used to
remove offending drug from circulation
Whats used to treat Vasculitis
Vasculitis- inflammation of the blood vessels
- Steroids
- Cyclophosphamide
- Azathioprine
- Plasma exchange
what is goodpastures disease and how to you treat it?
goodpastures disease is an autoimmune disease which causes rapid destruction of the kidneys and bleeding into the lungs.
*anti GBM antibodies which illuminate yellow
Treatment:
1.Prednisolone
2.Cyclophosphamide
3.Plasma exchange
(a mechanical procedure to
remove antibodies from theblood by filtering or
spinning to remove the plasma
what is SLE and how do you treat?
a disease where the bodies own immune system is attacking itself. Has many manifestations. dont forget the ANA immunoflurescence
Treatment:
- Steroids(Prednisolone tabs,methylprednisoloneIV)
- Cyclophosphamide
- Azathioprin
what are the symptoms of sjogrens syndrome and how do you treat?
the moisture secreting glands are amount the first mucous membranes which SS attacks 1.Dry eyes 2.Dry mouth 3.Dental cavities 4.Fatigue 5.Enlarged parotid glands 6.Difficulty swallowing or chewing 7.Change in sense of taste 8.Hoarseness 9.Oral yeast infections (eg candidiasis) 10.Skin rashes or dry skin 11.Vaginal dryness 12.Dry cough that doesn't produce sputum 13.Joint pain, swelling and stiffness TX=HYDROXYCHLOROQUINE
Dermatomyositis
is a connective-tissue disease related to polymyositis characterized by inflammation of the muscles and the skin
Most frequently affects the skin and muscles
May also affect joints, esophagus, lungs, and less
commonly heart
dermatomyositis treatment options
prednisone methotrexate azothioprine mycophenolate hydroxychloroquine chloroquine
how do you treat psoriasis?
betamethasone .05% cream
cyclosporine
