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Pharmacology Exam IV > Immunosuppressants > Flashcards

Immunosuppressants Flashcards

1
Q

Glucocorticoids Broad MOA’s (2)

A

Genomic - ALTERATION OF GENE EXPRESSION through binding to DNA or transcription factors

Non-genomic - ALTERING CELL SIGNALING AND CELL MEMBRANE PERMEABILITY

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2
Q

Glucocorticoids effects (4)

A

Rapid decrease in PERIPHERAL BLOOD LYMPHOCYTES

Downregulate PRO-INFLAMMATORY CYTOKINES (IL-1, IL-6, TNF-a, IFN-g)

Inhibits IL-2 PRODUCTION by T cells

Reduces NEUTROPHIL CHEMOTAXIS AND LYSOSOMAL ENZYME RELEASE

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3
Q

Glucocorticoid Therapeutic uses (4 broad categories)

A

Transplant rejection
GVHD in BM transplant
Blocking cytokine storm in transplant recipients with muromonab-CD3
Autoimmune disorders - (RA, SLE, Psoriasis, IBD, Allergies, MS)

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4
Q

Glucocorticoid Adverse effects (name a few)

A 
growth retardation
infection
poor wound healing
HTN
avascular necrosis of bone
cataracts
hyperglycemia
adrenal crisis
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5
Q

Low Dose Glucocorticoids

A

less than 7.5 mg prednisone equivalent per day

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6
Q

Medium Dose glucocorticoids

A

between 7.5 and 30 mg

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7
Q

High dose glucocorticoids

A

between 30 mg and 100 mg

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8
Q

Very High Dose glucocorticoids

A

> 100 mg prednisone equivalent per day

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9
Q

Pulse Therapy glucocorticoids

A

> 250 mg prednisone equivalent per day for 1 day or a few days

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10
Q

Cyclosporine MOA

A

suppresses T cell mediated immunity

forms a COMPLEX WITH CYCLOPHILIN - then BINDS CALCINEURIN - preventing phosphorylation of NFAT

NFAT ULTIMATELY CANNOT PROMOTE T CELL CYTOKINE PRODUCTION

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11
Q

Cyclosporine uses?

adverse effects?

A

transplants - kidney, liver, heart
RA
Psoriasis
combined with other agents

NEPHROTOXIC
HTN
Hyperlipidemia
Tremors
Gingival hyperplasia
Hirsutism
Increased risk of skin cancer
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12
Q

Cyclosporine drug-nutrient interaction

A

GRAPEFRUIT JUICE

increases blood concentration of cyclosporin - increased risk of toxicity

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13
Q

Tacrolimus MOA

A

CALCINEURIN INHIBITOR

ultimately INHIBITS NFAT FROM PROMOTING T CELL CYTOKINE PRODUCTION

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14
Q

Tacrolimus vs Cyclosporine

A

easier to monitor blood concentrations

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15
Q

Tacrolimus therapeutic use

Adverse reactions?

Drug-nutrient interaction?

A

allograft rejection prevention

nephrotoxic
HTN
DM
Neurotoxic

GRAPEFRUIT JUICE - increases blood levels

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16
Q

Azathioprine MOA

A

PURINE ANTI-METABOLITE - metabolized to 6-Mercaptopurine

metabolites INCORPORATED INTO DNA - PREVENTS LYMPHOCYTE PROLIFERATION

17
Q

Azathioprine therapeutic uses

Need to monitor what?

A

organ transplants
RA
Crohns, MS

CBC AND LFT’s

18
Q

Azathioprine adverse effects

A

Bone marrow suppression - LEUKOPENIA, thrombocytopenia, anemia
HEPATOTOXIC
Infection susceptibility
Increased cancer risk

19
Q

Mycophenolate mofetil MOA

A

PRODRUG

hydrolyzed to active drug MPA - SELECTIVE INHIBITOR OF INOSINE MONOPHOSPHATE DEHYDROGENASE

prevents proliferation of B and T cells

20
Q

Mycophenolate mofetil therapeutic uses

A

transplant rejcetion

SLE

21
Q

Adverse reactions of mycophenolate mofetil

A

hematologic (leukopenia, RBC aplasia)
GI (diarrhea, vomiting)

CMV infection
Congenital abnormalities if used during pregnancy

22
Q

Sirolimus MOA

A

Inhibits proliferation of T cells by BINDING FKBP

INHIBITS mTOR - essential for cell cycle progression by INHIBITING p27kip

23
Q

Sirolimus therapeutic uses

A

organ transplants

renal transplants who can’t tolerate calcineurin inhibitors

24
Q

Anti-thymocyte globulin MOA

A

ANTIBODIES THAT BIND CD 2, 3, 4, 8, 11a, 18, 25, 45, HLA I and II on T lymphocytes

DEPLETE CIRCULATING T-LYMPHOCYTES

through COMPLEMENT MEDIATED TOXICITY OR INHIBITION OF LYMPHOCYTE FUNCTION

25
Q

Anti-thymocyte globulin therapeutics

A

induction immunosuppression

prophylactic immunosuppression

treatment of acute rejection

26
Q

anti-thymocyte globulin adverse effects

A 
CYTOKINE STORM
serum sickness
leukopenia/thrombocytopenia
malignancy
infection
27
Q

Muromonab-CD3 MOA

A

BINDS AND INHIBITS CD-3

causes DEPLETION OF T-LYMPHOCYTES

complement activation or inactivation of cells themselves

28
Q

Muromonab-CD3 adverse reactions

A

CYTOKINE STORM

tremor, nausea, vomiting, diarrhea, myalgia, arthralgia, weakness

potentially FATAL - anaphylaxis, pulm edema, ARDS, cardiac arrest, infection, neoplasms

29
Q

Anti-TNF antibodies (3)

which ones are which (human, mouse, etc.)

A

Infliximab - partial human, partial mouse
Adalimumab - human IgG1
Etanercept - part TNF-a receptor, part human IgG

30
Q

Anti-TNF-alpha agents therapeutic uses

A

RA, CROHNS, UC

ankylosing spondylitis, plaque psoriasis, psoriatic arthritis

31
Q

Anti-TNF-alpha agents adverse

A

increased risk of infections

increased risk of lymphomas, other malignancies

Pharmacology Exam IV (12 decks)

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