immuno drugs

Question 1

Cyclophosphamide

Answer 1

Cytotoxic and Antiproliferative Agent (T and B)

pro-drug, needs to be activated by cP450
cell cycle-nonspecific (CCNS) alkylating agent (entire cycle)

tx: anti-cancer agent, sev. rheumatologic conditions
suppressive: infections may happen
* SIGNAL 3*: can inactivate cell cycle

Question 2

cyclophosphamide SEs: short term

Answer 2

GI: Nausea, vomiting, diarrhea; stomatitis; abdominal discomfort or pain.

Dermatologic: Alopecia (frequent).

Question 3

Azathioprine [ImuranR]

Answer 3

Cytotoxic and Antiproliferative Agent (T*>B cells)

derivative of 6-mercaptopurine (anti-metabolite)

cell cycle specific: only targets S phase
inhibits adenosine deaminase

kidney transplants
RA

SIGNAL 3

Question 4

Azathioprine [ImuranR] SEs: short and long term

Answer 4

GI: N/V (12%), diarrhea

2. Hematologic: leukopenia or thrombocytopenia, macrocytic anemia, severe bone marrow depression. dose-related
3. GU: temporary depression in spermatogenesis and reduction in sperm viability and sperm count

Pregnancy category D (fetal harm)*

may cause serious infections
carcinogen


Question 5

Methotrexate [RheumatrexR]

Answer 5

Cytotoxic and Antiproliferative Agent (T and B)

inhibits dihydrofolic acid reductase (THF)
cell cycle specific
-targets 2nd phase of imm. response

tx for RA, Crohn’s, malignancy

SIGNAL 3

Question 6

Methotrexate [RheumatrexR] potential for toxicity from high-dose regimens or delayed excretion is reduced by ??? during the final phase of methotrexate plasma elimination

Answer 6

leucovorin calcium

protects normal cells

Question 7

Methotrexate [RheumatrexR] SEs

Answer 7

GI: N/V/D, stomatitis
*hepatotoxicity 
*nephrotoxicity
*obstructive pulmonary disease (COPD)
infections

Question 8

Cyclosporine [SandimmuneR]

Answer 8

T-Cell Suppressant

comes from a fungus

inhibits SIGNAL 1 by inhib. calcineurin phosphatases

inhib. IL-2–>inhib. T cell activation
suppresses CMI, some humoral immunity,
*reversible inhib.

Question 9

Cyclosporine [SandimmuneR] may be affected by concomitant use of ???

because it requires ?? for metabolism

Answer 9

HIV protease inhibitors
anticonvulsants
azole antifungals

cytochrome P450 3A enzymes

Question 10

Cyclosporine [SandimmuneR] SEs

Answer 10

nephrotoxicity (mild–>chronic progressive)

(peritubular cap. congesion, interstitial fibrosis w. tubular atrophy)

HTN

*can cross placenta!: terotgen

Question 11

Cyclosporine [SandimmuneR] uses

Answer 11

organ transplants (take with corticosteroids, azathioprine)

RA

psoriasis

Question 12

MYCOPHENOLATE MOFETIL [CellceptR]

Answer 12

T-Cell Suppressant

reversible inhibitor of inosine monophosphate dehydrogenase (IMPDH)–>
inhib guanosine nucleotide synthesis

(affects T and B cells)

SIGNAL 3

Question 13

MYCOPHENOLATE MOFETIL [CellceptR] SEs

Answer 13

GI
severe neutropenia

use in combo with cyclosporine, corticosteroids

Question 14

Muromonab-CD3 (Orthoclone OKT3R)

Answer 14

T- cell suppressant

murine monoclonal Ab (IgG2a) blocks TCR (CD3) Ag

block calcineuria–>block IL-2–>block cell cycle/clonal expansion

tox: hypersn to murin products
* SIGNAL 1*

Question 15

Lymphocyte Immune Globulin (AtgamR)

Answer 15

T-cell suppressant

• SIGNAL 1*
  tox: may cause hypersn: prepped from horse IgG

risk for systemic infection

use with antimetabolite/cortster.

don’t use in pregnancy

Question 16

Daclizumab (ZenapaxR)

Answer 16

T-cell suppressant

“humanized” (90%)
binds to the IL-2 receptor (vs. CD3) blocks IL-2

tox: GI
* SIGNAL 3*

Question 17

RHo Immune Globulin (RhoGamR)

Answer 17

Ab agains Rh Ag

immunosuppressive:
prevents Rh- mother from becoming sensitized to Rh Ag–>prevents hemolytic disease of the newborn (42-96 hrs)

• SIGNAL 1*
• don’t use in Rh+ pts or Rh- who have dev. Rh Abs

Question 18

Immune Globulin (GammagardR)

Answer 18

IgG and IgM

donor human plasma

agent for replacement thereby
broad spectrum of IgG antibodies against bacterial, viral, parasitic, and mycoplasma antigens

binding to IL-1 α, IL-6, TNF-α, and T-cell receptors–>suppress pathological cytokines and phagos

SIGNAL 1

Question 19

Immune Globulin (GammagardR) uses

Answer 19

• hypogammaglobulinemia
• HIV-inf. ped pts
• idiopathic thrombocytopenic purpura
• Guillain-Barre’ syndrome

systemic and local
infections in bone marrow transplantation patients

Question 20

INTERFERON BETA-1b [BetaseronR]

Answer 20

recomb. DNA technology

immunomodulator
trigger signalling cascades

relapsing-remmitting MS

Question 21

INTERFERON BETA-1b [BetaseronR] SEs

Answer 21

hypersensitivity

depression, suicide, other mental disorders

flu-like symptoms

injection site reactions

Question 22

INTERFERON GAMMA- 1b [ActimmuneR]

Answer 22

immunomodulator

generation of toxic oxygen metabolites (via NADPH oxidase) within phagocytes–>IC killing of organisms

tox: flu-like

tx for CGD:
enhances killing mech. does not fix pt. mutation

Question 23

genetic factor of drug reactions

Answer 23

slow vs. rapid acetylators

Question 24

assoc. illnesses that cause drug reactions

Answer 24

PCP develop drug reactions (skin rash to sulfa drugs)

Question 25

this accounts for 5-20% of all observed adverse drug reactions

Answer 25

allergic drug reactions

Question 26

Type 1 hypersensitivity tx?

Answer 26

Anaphylactic (Immediate) IgE binds via Fc portion to mast cell/basophil-->crosslink-->mediators released-->histamines, leukotrienes, etc. prednisone, isoproterenol, epinephrine, theophylline

Question 27

TYPE II hypersensitivity tx?

Answer 27

Cytotoxic reactions IgG and IgM attach to circulating cells hemolytic disease of newborn thrombocytopenia, agranulocytosis, autoimmune hemolytic anemia remove offending drugs corticosteroids

Question 28

Type III hypersensitivity tx?

Answer 28

Serum Sickness or Arthus Reactions Ab does not attach to circ. cell but rather BV wall: complex attaches Fc portion-->complement-->inc. vasc. perm-->neutrophils aggregate-->hemorrhagic vasculitic lesion remove offending drugs corticosteroids

Question 29

Type IV hypersensitivity tx?

Answer 29

CMI (delayed) Mediated by sensitized T lymphocytes and macrophages contact dermatitis corticosteroids

Question 30

``` case: abd. pain, arthralgia, low grade fever, glomerulonephritis 2 wks tx with prednisolone elevated WBC, CRP CT: thick duodenal and jejunal walls purpuric lesions (jejunum) *IgA deposition, vasculitis* ```

Answer 30

HSP | tx with high-dose gluccorts, tapered, then *cyclosporine*

Question 31

case pain redness in one eye, 2 mos deep violacious episcleral injection, dialed perilimabl vessels and edema corneal thinning elev. CRP ESR test for antineutorphilic cytoplasmic Ab was + OM, wl, epistaxis, SOB Urine: granular red cell, nodular parenchemal casts

Answer 31

peripheral ulcerative keratitis in wegener's granulomatosis tx with oral corticosteroids, *cyclophosphamide*

Question 32

APC presents to T cell via TCR-->signaling pathway-->

Answer 32

produces IL-2-->signalling pathway that activates cell cycle *cascade blocked by drugs

Question 33

Cyclophosphamide long term side effects

Answer 33

Hematologic: Leukopenia, thrombocytopenia, anemia. GU: Amenorrhea, oligospermia, azoospermia, sterility; urinary bladder fibrosis; hematuria; hemorrhagic ureteritis; renal tubular necrosis.

Question 34

Azathioprine uses

Answer 34

renal homotransplantation RA Crohn's

Question 35

SIGNAL 1 DRUGS

Answer 35

``` Cyclosporine Muromonab-CD3 Lymphocyte Immune Globulin (AtgamR) RHo Immune Globulin (RhoGamR) Immune Globulin (GammagardR) ```

Question 36

SIGNAL 3 DRUGS

Answer 36

``` Cyclophosphamide Azathioprine Methotrexate Mycophenolate mofetil Daclizumab ```