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89 Cards in this Set

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2 corticosteroids used in immunopharmacology
1. Prednisone

2. Methylprednisone
Prednisone & Methylprednisone:
-inhibition of __1__ and __2__ synthesis
-Cytotoxic to certain __3__ subpopulations
-Suppress both __4__ and __5__ immunity
-inhibition of __6__ at the site of inflammation
-interference in the function of __7__ of inflammatory response
1. prostaglandin
2. leukotriene
3. T-cell subpopulations = helper and suppressor
4. cellular
5. humoral
6. leukocyte infiltration
7. mediators

***inhibit Phospholipase A2
What is the major advantage of Prednisone over other drugs such as Methotrexate and Cyclophosphamides
Not toxic to Myeloid and Erythroid stem cells = no anemias
ADR of this immunosuppressive agent can cause Adrenal gland suppression = Cushing-like side effects = weight gain, HTN
Prednisone
Prednisone is used as immunosuppressive agent for these 3 things
1. Organ transplantation
2. Autoimmune diseases
3. Bronchial asthma
Azathioprine is converted to __1__ by __2__ and then to __3__ by __4__
1. 6-mercaptopurine
2. Glutathione-S-transferase
3. 6-thiouric acid
4. Xanthine Oxidase
You must reduce the dose of Azathioprine in patients with this deficiency
Thiopurine Methyltransferase deficiency

*also Glutathione-S-transferase deficiency
Antimetabolite derivative of 6-mercaptopurine that interferes with the METABOLISM and SYNTHESIS of Nucleic Acids → inhibits cell proliferation
Azathioprine
Azathioprine is toxic to __1__ following __2__ exposure
1. proliferating lymphocytes
2. antigen
What are the adverse effects of Azathioprine?
1. Leukopenia
2. Anemia
3. Thrombocytopenia
What are the adverse effects of Azathioprine at high doses?
1. Skin rashes
2. Fever
3. NVD
4. GI disturbances
What 2 things increase the adverse effects of Azathioprine?
1. Kidney disease

2. Allopurinol (Xanthine oxidase inhibitor)
What are the 2 uses of Azathioprine?
1. Kidney transplantation
2. Autoimmune diseases
This is the most potent immunosuppressive agent
Cyclophosphamide
What does Cyclophosphamide destroy?
Proliferating lymphoid cells in addition to some quiescent cells
What are the uses of Cyclophosphamide?
1. Organ transplantation
2. Autoimmune diseases
What is Methotrexate's mechanism of action?
inhibits Dihydrofolate reductase = blocks folate requiring rxns in the biosynthesis of nucleotides needed for cell proliferation
Immunopharmacologic drug that is toxic to proliferating lymphocytes following antigen exposure
Methotrexate = DHFRI
What are the 3 clinical uses of Methotrexate?
1. Prophylaxis for graft vs. host syndrome for BM transplantation in Leukemia patients
2. Active RA
3. Psoriasis
What is the source of Cyclosporine?
Polypeptide antibiotic produced by certain fungi
Complexes with Cyclophilin → inhibits Calcineurin = blocks production of CYTOKINES by ANTIGEN-STIMULATED T-HELPER CELLS that otherwise stimulate T-cell growth and differentiation
Cyclosporine
What does Cyclosporine not affect?
1. suppressor T-cells

2. T-cell independent, antibody-mediated immunity
inhibit the production and/or release of various lymphokines including IL-1 and IL-2; in turn, the actions of T-helper cells, the agents of cellular immunity and tissue rejection, are impaired
Cyclosporine
How is Cyclosporine administered?
Orally

Intravenously
Cyclosporine:
-after oral administration, roughly __1__% is absorbed due to __2__
1. 20-50%

2. "first-pass" metabolism
What CYP is Cyclosporine metabolized extensively by?
CYP 3A4

*metabolized to at least 25 metabolites, some of which are biologically active
What are the 9 drugs that decrease the clearance of Cyclosporine via inhibition of hepatic microsomal enzymes (hint)
1. Androgens
2. Clarithromycin
3. Diltiazem
4. Erythromycin
5. Estrogens
6. Nefazodone
7. Nicardipine
8. Verapamil
9. Azole antifungal drugs
DAVE CANEN increases Cyclosporine
Drugs that increase the clearance of Cyclosporine by stimulating its metabolism may lead to what?
Graft rejection
What are 4 drugs / groups of drugs that may lead to increased Cyclosporine clearance? (hint)
1. Nafcillin
2. Omeprazole
3. Rifampin
4. Anticonvulsants
- Carbamazepine
- Phenytoin
- Phenobarbital
- Primidone
- St. John's Wort
"NORA" clears Cyclosporine and causes Graft Rejection
What is the most common adverse effect of Cyclosporine?

What is a less common effect?
Nephrotoxicity

Seizures
What is used to minimize the Nephrotoxicity of Cyclosporine?

Explain its mechanism of action
Clonidine

Alpha-2 agonist -> decreases sympathetic outflow = decrease in vasoconstriction of the kidney vessels = decreases Ischemic Kidney
Additive nephrotoxicity of Cyclosporine occurs if it is administered with what other nephrotoxic agents? (6) (Hint)
1. Amphotericin B
2. Acyclovir
3. Aminoglycosides
4. Foscarnet
5. NSAIDs
6. Vancomycin
Cyclosporine is A FAN of VAns that hurt the kidneys
What is the main use of Cyclosporine?

What other things is it used for?
Main: to prevent Allograft rejection

Others: autoimmune conditions
- Uveitis
- Psoriasis
- Type 1 Diabetes
- RA
- IBD
- certain Nephropathies
Macrolide derived from a fungus with similar pharmacokinetics to Cyclosporine
Tacrolimus
More effective in ACUTE REJECTION than in chronic rejection and is a MORE POTENT immunosuppressant than cyclosporine
Tacrolimus
Compare the Tacrolimus adverse effects in relation to Cyclosporine
Overall Tacrolimus adverse effects are greater than Cyclosporine

BUT, kidney toxicity is less than cyclosporine
Tacrolimus:
1. Administration?
2. Uses
1. Oral & Parenteral

2. Prophylaxis of Liver allograft rejection
-effective for other organ transplants as well
This is a prodrug for the immunosuppressive agent Mycophenolic acid
Mycophenolate Mofetil
Inhibits the "de novo" PURINE pathway and Is used in conjunction with cyclosporine and corticosteroids for the prevention of rejection in patients with a renal allograft
Mycophenolate Mofetil
Used in conjunction with Cyclosporine and Corticosteroids for the prevention of rejection in patients with a Renal Allograft

Allows usage of LOWER doses of Cyclosporine = lessens adverse effects on kidneys
Mycophenolate Mofetil
-Is a dimeric fusion protein produced by recombinant DNA technology that binds TNF
-It is a soluble TNF receptor
-It is given by injection
-Is effective in the treatment of rheumatoid arthritis (RA) and works by decreasing the effects of TNF
Etanercept (Enbrel)
What is Infliximab?
Chimeric monoclonal antibody that binds TNF-alpha
How is Infliximab administered and what is its terminal half-life?
IV infusion -> given at week 0, 2, 6 and thereafter, every 4-8 wks

8-12 days
Infliximab is given with __1__ for the treatment of __2__
1. Methotrexate

2. Rheumatoid Arthritis
Antibody used for Crohn's Disease when conventional therapy fails
Infliximab
What is the adverse effect of Infliximab?
may develop serious infections
monoclonal antibody that neutralizes TNF-alpha by binding to it and blocking its interaction with the p55 and p75 cell surface TNF receptors
Adalimumab
Neutralizes TNF-alpha and is given SUBCUTANEOUSLY every other week to patients who have had inadequate response to atleast one other DMARD
Adalimumab
What is Antithymocyte globulin?
Horse antibody against human T-lymphocytes

*also known as Lymphocyte Immune Globulin
What does Antithymocyte globuin reduce the number of?
Circulating thymus-dependent lymphocytes, which alters T-cell function and ultimately affects cell-mediated immunity
Antibody that:
1. manages allograft rejection in Renal transplant patients
2. manages moderate to severe Aplastic Anemia in those unsuited for BM transplants
Antithymocyte globulin
This is a parenteral monoclonal antibody of murine origin that targets CD3/TCR receptor complex
Muromonab-CD3
Parenteral monoclonal antibody of murine origin that targets CD3/TCR receptor complex

Treatment of ACUTE allograft rejection in patients who have undergone one of the following transplantations:
1. Kidney
2. Heart
3. Liver
Muromonab-CD3
These 2 drugs are chimeric (murine/human) monoclonal antibodies (IgG1) produced by recombinant DNA technology that block the binding of IL-2 to its receptors (hint)
Daclizumab

Basiliximab
Da-cliz and Basil inhibit IL-2
2 drugs that are used prophylactically in combo with Cyclosporine in patients undergoing Kidney transplantation
Daclizumab

Basiliximab
Aside from being used in Rh-negative women, what else is Rh[D] Immune Globulin used to treat?
Idiopathic Thrombocytopenic purpura
This is an antibody to the surface protein of RSV and is used prophylactically to prevent RSV infection
Palivizumab
"Paliv iz" RSV's enemy
What is used to TREAT serious RSV infections?
Ribavirin
This binds to CD52 antigen on normal and malignant B-lymphocytes
Alemtuzumab

*CD52 is also found on
-T lymphocytes
-NK cells
-Macrophages
-Platelets
Antibody used to treat Chronic Lymphocytic Leukemia
Alemtuzumab
Directed towards the CD33 antigen on Leukemic cells and Myelomonocytic cells

Coupled to Calicheamicin, a cytotoxic molecule
Gemtuzumab
Tangney (#33) wearing alot of Gems has just relapsed from Acute Myelogenous Leukemia
Antibody used to treat Acute Myelogenous Leukemia in adults over 60 years of age in first relapse and have a CD33-positive tumor
Gemtuzumab
What 2 drugs are used to treat Non-Hodgkins Lymphoma? (hint)
1. Rituximab

2. Tositumomab
Ritu Tosits Non-Hodgkins Lymhoma
Antibody that binds to CD20 antigen on B-cells
Rituximab
Targets the CD20 antigen found on PRE-B and MATURE B-lymphocytes
Tositumomab
Rituximab is used in combo with __1__ to reduce the signs and symptoms of RA in adults who had inadequate responses to one or more __2__ therapies
1. Methotrexate
2. TNF antagonist
This drug is used for the treatment of CD-20 positive follicular non-Hodgkin's lymphoma whose disease is refractory to Rituximab and has relapsed following chemotherapy
Tositumomab
Monoclonal antibody that binds to HER2 protein on the surface of tumor cells
-used for METASTATIC BREAST TUMORS that over express HER2 protein
Trastuzumab (Herceptin)
Monoclonal antibody that is an antagonist of Glycoprotein IIb/IIIa receptor of platelets
-is used post-angioplasty and in acute coronary syndromes
Abciximab
Monoclonal antibody that is directed towards the IgE high affinity Fc receptor on Mast cells
Omalizumab
Given Subcutaneously every 2-4 weeks for prophylaxis of Asthma and to control symptoms of moderate to severe Asthma not controlled by inhaled steroids
Omalizumab
What is Bacillus Calmette-Guerin (BCG), live intravesical used to treat? (2)
1. Bladder Carcinoma

2. Prophylactic against TB
How does BCG treat bladder carcinoma?
-it is instilled into the bladder
-causes a local inflammatory rxn with histiocytic and leukocytic infiltration in the urinary bladder
What are the adverse effects of BCG?
-Several urinary symptoms

-pretty much any kind of malaise
Drug that is infamous for causing Phocomelia in the offspring of mothers who took it during pregnancy = arms are attached to the body
Thalidomide
Immunomodulator drug used to treat Leprosy
Thalidomide
What is IFN-alpha used to treat? (5)
1. Hairy-cell Leukemia
2. AIDS-related Kaposi's sarcoma
3. Condylomata acuminata
4. Chronic HBV
5. Chronic HCV
What is IFN-beta produced by?
Fibroblasts

Epithelial cells
What is IFN-beta used for?
Describe its mechanism
Multiple Sclerosis

Exogenous IFN-beta offsets the activity of endogenous IFN-gamma, the agent responsible for triggering autoimmune rxn leading to Multiple Sclerosis
What is recombinant IFN-gamma-1b derived from?
genetically engineered E. coli
What is IFN-gamma-1b used to treat?
Chronic Granulomatous disease
-inherited disorder of phagocytic oxidative metabolism
-potent phagocyte-activating properties that result from enhancement of oxidative metabolism in tissue macrophages and enhancement of antibody-dependent cellular cytotoxicity and NK cell activity
What is the most common side effect of all the IFN's?
Flu-like symptoms
This is a non-glycosylated biosynthetic IL-2 (hint)
Aldesleukin
Alde aisle 2
Immunomodulator used to treat Metastatic Renal Cell Carcinoma
Aldesleukin (IL-2)
What 4 diseases is Aldesleukin currently being evaluated for treatment of?
1. Acute Myelogenous Leukemia
2. non-Hodgkin's Lymphoma
3. HIV infection
4. Leprosy
Immunomodulator that is a synthetic IL-2 that induces proliferation and differentiation of B & T cells, monocytes, macrophages, and CTLs
Aldesleukin
How is Aldesleukin administered?
High dose IV bolus -> significant number of adverse rxns affecting almost every organ system
This is a recombinant version of IL-11
Oprelvekin (Neumega)
Oprah on channel 11 treats Thrombocytopenia
Recombinant IL-11 given subcutaneously once a day to prevent severe chemotherapy-induced Thrombocytopenia
Oprelvekin