Immunomodulatory drugs (review sesh)

Question 1

drugs to treat signal 1 (TCR + MHC)

Answer 1

CNIs (calcineurin inhibitors)

Cyclosporin and tacrolimus

Question 2

drugs to treat signal 2 (costimulation)

Answer 2

abatacept and belatacept

Question 3

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

Answer 3

daclizumab, basiliximab (anti CD25, blocks IL2 receptor)

sirolimus (mTOR inhibitor)

MMF, azathioprine, leflunomide (DNA synthesis inhibitors)

Question 4

drugs to suppress inflammation

Answer 4

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

Question 5

3 drugs to block T cell migration

Answer 5

natalizumab
fingolimod
IFN-beta -

Question 6

drugs to block type 1 hypersensitivity (for anaphylaxis)

Answer 6

omalizumab and epinephrine

Question 7

calcineurin inhibitors

Answer 7

CNIs
cyclosporin A (CsA) and tacrolimus

Question 8

mechanism of CNIs (CsA and tacrolimus)

Answer 8

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)

Question 9

what are CNIs used to treat?

major side effect?

Answer 9

allograft rejection, autoimmune diseases, or chronic dry eyes

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

Question 10

sirolimus

Answer 10

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

Question 11

2 inhibitors of DNA synthesis?

Answer 11

MMF (mycophenolate mofetil)
and
azathioprine

Question 12

side effects of DNA inhibitors (MMF and azathioprine)

Answer 12

GI distress and leukopenia

Question 13

MMF (mycophenolate mofetil)

Answer 13

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!)

Question 14

lymphocytes can only derive nuleotides from….

Answer 14

de novo synthesis

Question 15

azathioprine

Answer 15

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

Used to prevent organ rejection and for RA

Question 16

DMARDs

Answer 16

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

methotrexate and leflunamide

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

Question 17

what is 1st line for RA?

contraindicated when?

Answer 17

methotrexate

pregnancy

Question 18

methotrexate

Answer 18

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)

Question 19

leflunamide

Answer 19

a DMARD

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

Side effect: GI distress

Question 20

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

Answer 20

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

Question 21

abatacept and belatacept

Answer 21

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

Question 22

daclizumab and basaliximab

Answer 22

anti CD-25 mAbs

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

Question 23

sirolimus is ONLY used for what type of transplant?

Answer 23

renal

Question 24

akinakra

Answer 24

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

used for RA

Question 25

three TNFalpha inhibitors?

Answer 25

infliximab
adalimumab
etanercept

Question 26

infliximab
adalimumab
etanercept

Answer 26

TNF alpha inhibitors

used to treat RA, crohns, colitis, and psoriasis

Question 27

side effects of TNF alpha inhibitors

Answer 27

increased susceptibility to infection and malignancy

Question 28

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

Answer 28

rituximab

relimumab

Question 29

rituximab

Answer 29

antiBcell
anti-CD20
used for RA

Question 30

Belimumab

Answer 30

anti-B cell

anti-BAFF

used for SLE

Question 31

drugs used to treat multiple sclerosis

what do they do?

Answer 31

natalizumab
fingolimod
IFN-beta

inhibit T cell migration

Question 32

natalizumab

Answer 32

(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)

Question 33

fingolimod

Answer 33

(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

Question 34

IFN beta

Answer 34

for relapsing MS

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

Question 35

2 drugs for type 1 hypersensitivity (treatment for anaphylaxis)

Answer 35

omalizumab

epinephrine

Question 36

omalizumab

Answer 36

(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

Question 37

epinephrine

Answer 37

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

Question 38

drugs that decrease cyp3a4 metabolism

Answer 38

erythromycin
ketoconazole
contraceptives
cimetidine

Question 39

drugs that increase cyp3a4 metabolism

Answer 39

phenytoin
rifampicin
phenobarbitone
sulphadimidine and trimethoprim
isoniazid