immuno drugs Flashcards Preview

Pharm > immuno drugs > Flashcards

Flashcards in immuno drugs Deck (36):
1

Cyclophosphamide

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

2

cyclophosphamide SEs: short term

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


Dermatologic: Alopecia (frequent).

3

Azathioprine [ImuranR]

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

4

Azathioprine [ImuranR] SEs: short and long term

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


5

Methotrexate [RheumatrexR]

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

6

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

leucovorin calcium

protects normal cells

7

Methotrexate [RheumatrexR] SEs

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

8

Cyclosporine [SandimmuneR]

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.

9

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

because it requires ?? for metabolism

HIV protease inhibitors
anticonvulsants
*azole antifungals*

cytochrome P450 3A enzymes

10

Cyclosporine [SandimmuneR] SEs

nephrotoxicity (mild-->chronic progressive)

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

HTN

*can cross placenta!: terotgen

11

Cyclosporine [SandimmuneR] uses

organ transplants (take with corticosteroids, azathioprine)

RA

psoriasis

12

MYCOPHENOLATE MOFETIL [CellceptR]

T-Cell Suppressant

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

(affects T and B cells)

*SIGNAL 3*

13

MYCOPHENOLATE MOFETIL [CellceptR] SEs

GI
*severe neutropenia*

use in combo with cyclosporine, corticosteroids

14

Muromonab-CD3 (Orthoclone OKT3R)

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*

15

Lymphocyte Immune Globulin (AtgamR)

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

16

Daclizumab (ZenapaxR)

T-cell suppressant

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

tox: GI

*SIGNAL 3*

17

RHo Immune Globulin (RhoGamR)

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

18

Immune Globulin (GammagardR)

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*

19

Immune Globulin (GammagardR) uses

*hypogammaglobulinemia

*HIV-inf. ped pts

*idiopathic thrombocytopenic purpura

*Guillain-Barre’ syndrome

systemic and local
infections in bone marrow transplantation patients

20

INTERFERON BETA-1b [BetaseronR]

recomb. DNA technology

immunomodulator
trigger signalling cascades

*relapsing-remmitting MS*

21

INTERFERON BETA-1b [BetaseronR] SEs

hypersensitivity

*depression, suicide, other mental disorders*

flu-like symptoms

injection site reactions

22

INTERFERON GAMMA- 1b [ActimmuneR]

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

23

genetic factor of drug reactions

slow vs. rapid acetylators

24

assoc. illnesses that cause drug reactions

PCP develop drug reactions (skin rash to sulfa drugs)

25

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

allergic drug reactions

26

Type 1 hypersensitivity










tx?

Anaphylactic (Immediate)

IgE binds via Fc portion to mast cell/basophil-->crosslink-->mediators released-->histamines, leukotrienes, etc.

prednisone, isoproterenol, epinephrine, theophylline

27

TYPE II hypersensitivity








tx?

Cytotoxic reactions

IgG and IgM
attach to circulating cells

hemolytic disease of newborn
thrombocytopenia, agranulocytosis, autoimmune hemolytic anemia

remove offending drugs
corticosteroids

28

Type III hypersensitivity







tx?

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

29

Type IV hypersensitivity






tx?

CMI (delayed)

Mediated by sensitized T lymphocytes and macrophages
contact dermatitis

corticosteroids

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*

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

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

peripheral ulcerative keratitis in wegener's granulomatosis

tx with oral corticosteroids, *cyclophosphamide*

32

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

produces IL-2-->signalling pathway that activates cell cycle

*cascade blocked by drugs

33

Cyclophosphamide long term side effects

Hematologic: Leukopenia, thrombocytopenia, anemia.

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

34

Azathioprine uses

renal homotransplantation
RA
Crohn's

35

SIGNAL 1 DRUGS

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

36

SIGNAL 3 DRUGS

Cyclophosphamide
Azathioprine
Methotrexate
Mycophenolate mofetil
Daclizumab