Pharm - S2B1 - Hemato/immunopharamacology 5

Front 1

2 corticosteroids used in immunopharmacology

Back 1

1. Prednisone

2. Methylprednisone

Front 2

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

Back 2

1. prostaglandin
2. leukotriene
3. T-cell subpopulations = helper and suppressor
4. cellular
5. humoral
6. leukocyte infiltration
7. mediators

***inhibit Phospholipase A2

Front 3

What is the major advantage of Prednisone over other drugs such as Methotrexate and Cyclophosphamides

Back 3

Not toxic to Myeloid and Erythroid stem cells = no anemias

Front 4

ADR of this immunosuppressive agent can cause Adrenal gland suppression = Cushing-like side effects = weight gain, HTN

Back 4

Prednisone

Front 5

Prednisone is used as immunosuppressive agent for these 3 things

Back 5

1. Organ transplantation
2. Autoimmune diseases
3. Bronchial asthma

Front 6

Azathioprine is converted to __1__ by __2__ and then to __3__ by __4__

Back 6

1. 6-mercaptopurine
2. Glutathione-S-transferase
3. 6-thiouric acid
4. Xanthine Oxidase

Front 7

You must reduce the dose of Azathioprine in patients with this deficiency

Back 7

Thiopurine Methyltransferase deficiency

*also Glutathione-S-transferase deficiency

Front 8

Antimetabolite derivative of 6-mercaptopurine that interferes with the METABOLISM and SYNTHESIS of Nucleic Acids → inhibits cell proliferation

Back 8

Azathioprine

Front 9

Azathioprine is toxic to __1__ following __2__ exposure

Back 9

1. proliferating lymphocytes
2. antigen

Front 10

What are the adverse effects of Azathioprine?

Back 10

1. Leukopenia
2. Anemia
3. Thrombocytopenia

Front 11

What are the adverse effects of Azathioprine at high doses?

Back 11

1. Skin rashes
2. Fever
3. NVD
4. GI disturbances

Front 12

What 2 things increase the adverse effects of Azathioprine?

Back 12

1. Kidney disease

2. Allopurinol (Xanthine oxidase inhibitor)

Front 13

What are the 2 uses of Azathioprine?

Back 13

1. Kidney transplantation
2. Autoimmune diseases

Front 14

This is the most potent immunosuppressive agent

Back 14

Cyclophosphamide

Front 15

What does Cyclophosphamide destroy?

Back 15

Proliferating lymphoid cells in addition to some quiescent cells

Front 16

What are the uses of Cyclophosphamide?

Back 16

1. Organ transplantation
2. Autoimmune diseases

Front 17

What is Methotrexate's mechanism of action?

Back 17

inhibits Dihydrofolate reductase = blocks folate requiring rxns in the biosynthesis of nucleotides needed for cell proliferation

Front 18

Immunopharmacologic drug that is toxic to proliferating lymphocytes following antigen exposure

Back 18

Methotrexate = DHFRI

Front 19

What are the 3 clinical uses of Methotrexate?

Back 19

1. Prophylaxis for graft vs. host syndrome for BM transplantation in Leukemia patients
2. Active RA
3. Psoriasis

Front 20

What is the source of Cyclosporine?

Back 20

Polypeptide antibiotic produced by certain fungi

Front 21

Complexes with Cyclophilin → inhibits Calcineurin = blocks production of CYTOKINES by ANTIGEN-STIMULATED T-HELPER CELLS that otherwise stimulate T-cell growth and differentiation

Back 21

Cyclosporine

Front 22

What does Cyclosporine not affect?

Back 22

1. suppressor T-cells

2. T-cell independent, antibody-mediated immunity

Front 23

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

Back 23

Cyclosporine

Front 24

How is Cyclosporine administered?

Back 24

Orally

Intravenously

Front 25

Cyclosporine:
-after oral administration, roughly __1__% is absorbed due to __2__

Back 25

1. 20-50%

2. "first-pass" metabolism

Front 26

What CYP is Cyclosporine metabolized extensively by?

Back 26

CYP 3A4

*metabolized to at least 25 metabolites, some of which are biologically active

Front 27

What are the 9 drugs that decrease the clearance of Cyclosporine via inhibition of hepatic microsomal enzymes (hint)

Back 27

1. Androgens
2. Clarithromycin
3. Diltiazem
4. Erythromycin
5. Estrogens
6. Nefazodone
7. Nicardipine
8. Verapamil
9. Azole antifungal drugs

Hint 27

DAVE CANEN increases Cyclosporine

Front 28

Drugs that increase the clearance of Cyclosporine by stimulating its metabolism may lead to what?

Back 28

Graft rejection

Front 29

What are 4 drugs / groups of drugs that may lead to increased Cyclosporine clearance? (hint)

Back 29

1. Nafcillin
2. Omeprazole
3. Rifampin
4. Anticonvulsants
- Carbamazepine
- Phenytoin
- Phenobarbital
- Primidone
- St. John's Wort

Hint 29

"NORA" clears Cyclosporine and causes Graft Rejection

Front 30

What is the most common adverse effect of Cyclosporine?

What is a less common effect?

Back 30

Nephrotoxicity

Seizures

Front 31

What is used to minimize the Nephrotoxicity of Cyclosporine?

Explain its mechanism of action

Back 31

Clonidine

Alpha-2 agonist -> decreases sympathetic outflow = decrease in vasoconstriction of the kidney vessels = decreases Ischemic Kidney

Front 32

Additive nephrotoxicity of Cyclosporine occurs if it is administered with what other nephrotoxic agents? (6) (Hint)

Back 32

1. Amphotericin B
2. Acyclovir
3. Aminoglycosides
4. Foscarnet
5. NSAIDs
6. Vancomycin

Hint 32

Cyclosporine is A FAN of VAns that hurt the kidneys

Front 33

What is the main use of Cyclosporine?

What other things is it used for?

Back 33

Main: to prevent Allograft rejection

Others: autoimmune conditions
- Uveitis
- Psoriasis
- Type 1 Diabetes
- RA
- IBD
- certain Nephropathies

Front 34

Macrolide derived from a fungus with similar pharmacokinetics to Cyclosporine

Back 34

Tacrolimus

Front 35

More effective in ACUTE REJECTION than in chronic rejection and is a MORE POTENT immunosuppressant than cyclosporine

Back 35

Tacrolimus

Front 36

Compare the Tacrolimus adverse effects in relation to Cyclosporine

Back 36

Overall Tacrolimus adverse effects are greater than Cyclosporine

BUT, kidney toxicity is less than cyclosporine

Front 37

Tacrolimus:
1. Administration?
2. Uses

Back 37

1. Oral & Parenteral

2. Prophylaxis of Liver allograft rejection
-effective for other organ transplants as well

Front 38

This is a prodrug for the immunosuppressive agent Mycophenolic acid

Back 38

Mycophenolate Mofetil

Front 39

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

Back 39

Mycophenolate Mofetil

Front 40

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

Back 40

Mycophenolate Mofetil

Front 41

-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

Back 41

Etanercept (Enbrel)

Front 42

What is Infliximab?

Back 42

Chimeric monoclonal antibody that binds TNF-alpha

Front 43

How is Infliximab administered and what is its terminal half-life?

Back 43

IV infusion -> given at week 0, 2, 6 and thereafter, every 4-8 wks

8-12 days

Front 44

Infliximab is given with __1__ for the treatment of __2__

Back 44

1. Methotrexate

2. Rheumatoid Arthritis

Front 45

Antibody used for Crohn's Disease when conventional therapy fails

Back 45

Infliximab

Front 46

What is the adverse effect of Infliximab?

Back 46

may develop serious infections

Front 47

monoclonal antibody that neutralizes TNF-alpha by binding to it and blocking its interaction with the p55 and p75 cell surface TNF receptors

Back 47

Adalimumab

Front 48

Neutralizes TNF-alpha and is given SUBCUTANEOUSLY every other week to patients who have had inadequate response to atleast one other DMARD

Back 48

Adalimumab

Front 49

What is Antithymocyte globulin?

Back 49

Horse antibody against human T-lymphocytes

*also known as Lymphocyte Immune Globulin

Front 50

What does Antithymocyte globuin reduce the number of?

Back 50

Circulating thymus-dependent lymphocytes, which alters T-cell function and ultimately affects cell-mediated immunity

Front 51

Antibody that:
1. manages allograft rejection in Renal transplant patients
2. manages moderate to severe Aplastic Anemia in those unsuited for BM transplants

Back 51

Antithymocyte globulin

Front 52

This is a parenteral monoclonal antibody of murine origin that targets CD3/TCR receptor complex

Back 52

Muromonab-CD3

Front 53

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

Back 53

Muromonab-CD3

Front 54

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)

Back 54

Daclizumab

Basiliximab

Hint 54

Da-cliz and Basil inhibit IL-2

Front 55

2 drugs that are used prophylactically in combo with Cyclosporine in patients undergoing Kidney transplantation

Back 55

Daclizumab

Basiliximab

Front 56

Aside from being used in Rh-negative women, what else is Rh[D] Immune Globulin used to treat?

Back 56

Idiopathic Thrombocytopenic purpura

Front 57

This is an antibody to the surface protein of RSV and is used prophylactically to prevent RSV infection

Back 57

Palivizumab

Hint 57

"Paliv iz" RSV's enemy

Front 58

What is used to TREAT serious RSV infections?

Back 58

Ribavirin

Front 59

This binds to CD52 antigen on normal and malignant B-lymphocytes

Back 59

Alemtuzumab

*CD52 is also found on
-T lymphocytes
-NK cells
-Macrophages
-Platelets

Front 60

Antibody used to treat Chronic Lymphocytic Leukemia

Back 60

Alemtuzumab

Front 61

Directed towards the CD33 antigen on Leukemic cells and Myelomonocytic cells

Coupled to Calicheamicin, a cytotoxic molecule

Back 61

Gemtuzumab

Hint 61

Tangney (#33) wearing alot of Gems has just relapsed from Acute Myelogenous Leukemia

Front 62

Antibody used to treat Acute Myelogenous Leukemia in adults over 60 years of age in first relapse and have a CD33-positive tumor

Back 62

Gemtuzumab

Front 63

What 2 drugs are used to treat Non-Hodgkins Lymphoma? (hint)

Back 63

1. Rituximab

2. Tositumomab

Hint 63

Ritu Tosits Non-Hodgkins Lymhoma

Front 64

Antibody that binds to CD20 antigen on B-cells

Back 64

Rituximab

Front 65

Targets the CD20 antigen found on PRE-B and MATURE B-lymphocytes

Back 65

Tositumomab

Front 66

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

Back 66

1. Methotrexate
2. TNF antagonist

Front 67

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

Back 67

Tositumomab

Front 68

Monoclonal antibody that binds to HER2 protein on the surface of tumor cells
-used for METASTATIC BREAST TUMORS that over express HER2 protein

Back 68

Trastuzumab (Herceptin)

Front 69

Monoclonal antibody that is an antagonist of Glycoprotein IIb/IIIa receptor of platelets
-is used post-angioplasty and in acute coronary syndromes

Back 69

Abciximab

Front 70

Monoclonal antibody that is directed towards the IgE high affinity Fc receptor on Mast cells

Back 70

Omalizumab

Front 71

Given Subcutaneously every 2-4 weeks for prophylaxis of Asthma and to control symptoms of moderate to severe Asthma not controlled by inhaled steroids

Back 71

Omalizumab

Front 72

What is Bacillus Calmette-Guerin (BCG), live intravesical used to treat? (2)

Back 72

1. Bladder Carcinoma

2. Prophylactic against TB

Front 73

How does BCG treat bladder carcinoma?

Back 73

-it is instilled into the bladder
-causes a local inflammatory rxn with histiocytic and leukocytic infiltration in the urinary bladder

Front 74

What are the adverse effects of BCG?

Back 74

-Several urinary symptoms

-pretty much any kind of malaise

Front 75

Drug that is infamous for causing Phocomelia in the offspring of mothers who took it during pregnancy = arms are attached to the body

Back 75

Thalidomide

Front 76

Immunomodulator drug used to treat Leprosy

Back 76

Thalidomide

Front 77

What is IFN-alpha used to treat? (5)

Back 77

1. Hairy-cell Leukemia
2. AIDS-related Kaposi's sarcoma
3. Condylomata acuminata
4. Chronic HBV
5. Chronic HCV

Front 78

What is IFN-beta produced by?

Back 78

Fibroblasts

Epithelial cells

Front 79

What is IFN-beta used for?
Describe its mechanism

Back 79

Multiple Sclerosis

Exogenous IFN-beta offsets the activity of endogenous IFN-gamma, the agent responsible for triggering autoimmune rxn leading to Multiple Sclerosis

Front 80

What is recombinant IFN-gamma-1b derived from?

Back 80

genetically engineered E. coli

Front 81

What is IFN-gamma-1b used to treat?

Back 81

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

Front 82

What is the most common side effect of all the IFN's?

Back 82

Flu-like symptoms

Front 83

This is a non-glycosylated biosynthetic IL-2 (hint)

Back 83

Aldesleukin

Hint 83

Alde aisle 2

Front 84

Immunomodulator used to treat Metastatic Renal Cell Carcinoma

Back 84

Aldesleukin (IL-2)

Front 85

What 4 diseases is Aldesleukin currently being evaluated for treatment of?

Back 85

1. Acute Myelogenous Leukemia
2. non-Hodgkin's Lymphoma
3. HIV infection
4. Leprosy

Front 86

Immunomodulator that is a synthetic IL-2 that induces proliferation and differentiation of B & T cells, monocytes, macrophages, and CTLs

Back 86

Aldesleukin

Front 87

How is Aldesleukin administered?

Back 87

High dose IV bolus -> significant number of adverse rxns affecting almost every organ system

Front 88

This is a recombinant version of IL-11

Back 88

Oprelvekin (Neumega)

Hint 88

Oprah on channel 11 treats Thrombocytopenia

Front 89

Recombinant IL-11 given subcutaneously once a day to prevent severe chemotherapy-induced Thrombocytopenia

Back 89

Oprelvekin