Immunomodulatory drugs (review sesh) Flashcards Preview

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Flashcards in Immunomodulatory drugs (review sesh) Deck (39)
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1
Q

drugs to treat signal 1 (TCR + MHC)

A

CNIs (calcineurin inhibitors)

Cyclosporin and tacrolimus

2
Q

drugs to treat signal 2 (costimulation)

A

abatacept and belatacept

3
Q

drugs to treat signal 3 (IL2 + TL2R on tcell)

A

daclizumab, basiliximab (anti CD25, blocks IL2 receptor)

sirolimus (mTOR inhibitor)

MMF, azathioprine, leflunomide (DNA synthesis inhibitors)

4
Q

drugs to suppress inflammation

A

DMARDs: methotrexate and leflunamide
infliximab, etanercept, and adalimumab (TNF inhibitors)
anakinra (IL1 receptor antagonist)

5
Q

3 drugs to block T cell migration

A

natalizumab
fingolimod
IFN-beta -

6
Q

drugs to block type 1 hypersensitivity (for anaphylaxis)

A

omalizumab and epinephrine

7
Q

calcineurin inhibitors

A
CNIs
cyclosporin A (CsA) and tacrolimus
8
Q

mechanism of CNIs (CsA and tacrolimus)

A

block calcineurin
–calcineurin is a phosphatase that normally dephosphorylates NF-AT after Ca influx of T cell binding –> blocking NF-AT mediated IL2 transcription (depletion of IL2 is the result)

9
Q

what are CNIs used to treat?

major side effect?

A

allograft rejection, autoimmune diseases, or chronic dry eyes

nephrotoxocity!!!!
both are metabolized by cyp3a4 so drug interactions!

10
Q

sirolimus

A

blocks mTOR –> prevents cell cycle progression by inhibiting protein synthesis

11
Q

2 inhibitors of DNA synthesis?

A

MMF (mycophenolate mofetil)
and
azathioprine

12
Q

side effects of DNA inhibitors (MMF and azathioprine)

A

GI distress and leukopenia

13
Q

MMF (mycophenolate mofetil)

A

Used in combination with CNIs to reduce nephrotoxicity (allows reduction of CNI dose)

Prodrug that is hydrolyzed to MPA which inhibits de novo purine biosynthesis (lymphocytes can only derive nucleotides from de novo synthesis!)

14
Q

lymphocytes can only derive nuleotides from….

A

de novo synthesis

15
Q

azathioprine

A

Purine analog prodrug that is metabolized to 6-mercaptopurine to disrupt de novo purine synthesis

Used to prevent organ rejection and for RA

16
Q

DMARDs

A

disease modifying anti-rheumatic drugs – used to treat autoimmune diseases

methotrexate and leflunamide

***use 2 or more in combination to treat RA

17
Q

what is 1st line for RA?

contraindicated when?

A

methotrexate

pregnancy

18
Q

methotrexate

A

a DMARD used as 1st line to treat RA

a Folic acid analogue – inhibits dihydrofolate reductase required for nucleoside biosynthesis (inhibits de novo nucleotide synthesis)

Also inhibits AICAR transformylase –> a release of excess adenosine allowing an anti-inflammatory effect

Side effect: teratogenicity and Bone marrow suppression (cytopenias)

19
Q

leflunamide

A

a DMARD

prodrug that is activated to inhibit dihyroorotate dehydrogenase – inhibits pyrimidine biosynthesis

Side effect: GI distress

20
Q

1 -omab
2 -ximab
3 -zumab
4 -umab

A

1 - mouse antibody (most likely to produce hypersensitivity reactions)
2 - mouse sequence grafted onto human Fc
3 - mostly human
4 - completely human Abs

21
Q

abatacept and belatacept

A

CTLA4-Ig

mAbs that block costimulatory signal between B7 and CD28 (blocking T cell activation)

A –> use for RA
B –> use for transplant combo therapy

22
Q

daclizumab and basaliximab

A

anti CD-25 mAbs

prevent IL2receptor (CD25) from binding; used with CNIs and AZA for kidney and heart transplants

23
Q

sirolimus is ONLY used for what type of transplant?

A

renal

24
Q

akinakra

A

anti-IL-1/IL-1R
mAbs used to inhibit infammatory IL1

used for RA

25
Q

three TNFalpha inhibitors?

A

infliximab
adalimumab
etanercept

26
Q

infliximab
adalimumab
etanercept

A

TNF alpha inhibitors

used to treat RA, crohns, colitis, and psoriasis

27
Q

side effects of TNF alpha inhibitors

A

increased susceptibility to infection and malignancy

28
Q

two drugs that deplete B cells (anti B cell antibodies)

A

rituximab

relimumab

29
Q

rituximab

A

antiBcell
anti-CD20
used for RA

30
Q

Belimumab

A

anti-B cell

anti-BAFF

used for SLE

31
Q

drugs used to treat multiple sclerosis

what do they do?

A

natalizumab
fingolimod
IFN-beta

inhibit T cell migration

32
Q

natalizumab

A

(anti-VLA4) – inhibit migration of tcells/luymphocytes to the site of inflammation; block integrin to T cell cannot get it

RISK OF JC virus induced progressive multifocal leukoencephalopathy (PML)

33
Q

fingolimod

A

(S1P1R super agonist) – binds to sphingosine-1 phosphate receptors (S!PRs are used for t cells to exit LNs) and induces downregulation; preventing lymphocytes from migrating out of lymph nodes

Risk of fatal infections

34
Q

IFN beta

A

for relapsing MS

causes decreased T cell proliferation/activation and inhibition of leukocyte migration across BBB

35
Q

2 drugs for type 1 hypersensitivity (treatment for anaphylaxis)

A

omalizumab

epinephrine

36
Q

omalizumab

A

(anti-IgE mAb) – targets part of IgE that binds to Fc on mast cells and basophils; blocks binds of free IgE to mast and basophils without cross-linking IgE that is already bound —

reduces allergy/asthma attacks

37
Q

epinephrine

A

to treat anaphylaxis (systemic allergic reaction); a non-selective alpha and beta adrenoreceptor agonist, rapidly reverses bronchoconstriction (B2) and vasodilation(a1)

38
Q

drugs that decrease cyp3a4 metabolism

A

erythromycin
ketoconazole
contraceptives
cimetidine

39
Q

drugs that increase cyp3a4 metabolism

A
phenytoin
rifampicin
phenobarbitone
sulphadimidine and trimethoprim
isoniazid