B.29-immunopharmacology 1 (cytotoxic agents, retinoids) +autoimmune diseases

Question 1

list the cytotoxic agents

Answer 1

cyclophosphamide
methotrexate
azathioprine, 6-MP (6-mercaptopurine)
leflunomide 
mycophenolic acid

Question 2

what is cyclophosphamide?

Answer 2

alkylating agent

Question 3

how are the cytotoxic agents given?

Answer 3

oral or parenteral

except for leflunomide–> only oral

Question 4

how is leflunomide and teriflunomide given?

Answer 4

oral

Question 5

what is methotrexate?

Answer 5

anti-metabolite

inhibitor of dihydrofolate reductase

Question 6

what is the mechanism of azathioprine and 6-MP?

Answer 6

inhibits de-novo purine synthesis

Question 7

what is the mechanism of mycophenolic acid?

Answer 7

inhibits de novo GTP synthesis

*B and T cells are suppressed

Question 8

what is the mechanism of leflunomide and teriflunomide?

Answer 8

inhibit de-novo pyrimidine synthesis

Question 9

which cytotoxic agent requires hepatic P450 activation?

Answer 9

cyclophosphamide

Question 10

why do we need adequate hydration in methotrexate?

Answer 10

to prevent urinary crystallization

Question 11

from when is azathioprine effective?

Answer 11

after 12 weeks of starting therapy

Question 12

indications for cyclophosphamide

Answer 12

hematological malignancies 
breast and ovarian cancer 
autoimmune diseases (SLE, GN, vasculitis)

Question 13

indications for methotrexate

Answer 13

hematological malignancies
CNS and other solid tumors
Autoimmune diseases (RA, psoriasis)

Question 14

indications for azathioprine and 6-MP

Answer 14

hematological malignancies
autoimmune diseases (SLE,RA)
IBD

Question 15

indications for mycophenolic acid

Answer 15

solid organ transplantation 
autoimmune diseases (SLE, GN, myasthenia, psoriasis)

Question 16

indications for leflunomide, teriflunomide

Answer 16

autoimmune diseases (RA, multiple sclerosis)

Question 17

side effects for cyclophosphamide

Answer 17

myelosuppression
GI distress
hemorrhagic cystitis

Question 18

what is given as an antidote for the damage of the bladder from cyclophosphamide?

Answer 18

mesna

Question 19

SE from methotrexate

Answer 19

myelosuppression
toxic effects on skin and GI mucosa
pulmonary fibrosis (in chronic use)

Question 20

what reduces the toxic effect of methotrexate?

Answer 20

folinic acid

Question 21

don’t combine azathioprine or 6-MP with…

Answer 21

allopurinol

Question 22

SE of azathioprine and 6-MP

Answer 22

myelosuppression

hepatotoxicity

Question 23

SE of mycophenolic acid

Answer 23

myelosuppression

GI distress

Question 24

which cytotoxic agent is used in combination with cyclosporine?

Answer 24

mycophenolic acid

Question 25

SE of leflunomide and teriflunomide

Answer 25

GI irritation hepatotoxicity teratogenic

Question 26

when are glucocorticoids used to suppress immunologic reactions?

Answer 26

organ transplantation | hematologic malignancies

Question 27

management of acute flare-ups in RA

Answer 27

NSAIDS | Corticosteroids

Question 28

disease-modifying anti-rheumatic drugs (DMARD'S) for RA

Answer 28

``` methotrexate (1st line agent) chloroquine, hydroxychloroquine leflunomide sulfasalazine (5-ASA) cyclosporine tofacitinib ```

Question 29

what is the first-line agent for RA? out of DMARD'S..

Answer 29

methotrexate

Question 30

drugs used for mild IBD

Answer 30

5-ASA | glucocorticoids - budesonide (topical, oral)

Question 31

biological therapy for RA

Answer 31

``` anti-TNF𝝰 (infliximab) CTLA-4 fusion protein (abatacept) IL-1 receptor antagonist (anakinra) IL-6 receptor antagonist (tocilizumab) anti-CD20 (rituximab) ```

Question 32

drugs used for moderate IBD

Answer 32

glucocorticoids-prednisone (oral, IV) azathioprine, 6-MP methotrexate

Question 33

drugs used for severe IBD

Answer 33

cyclosporin anti-TNF𝝰 (infliximab) anti-IL-12 and IL-23 (ustekinumab) anti- integrin 𝝰₄β₁ (natalizumab), anti-integrin 𝝰₄β₇ (vedolizumab)

Question 34

topical agents for psoriasis

Answer 34

PUVA therapy (psoralen and ultraviolet A) glucocorticoids vitamin D retinoids - vitamin A

Question 35

systemic agents for psoriasis

Answer 35

acitretin (vitamin A derivative) dimethyl fumarate apremilast (↓ expression of inflammatory cytokines) immunosuppressive agents- cyclosporin, methotrexate

Question 36

biological therapy for psoriasis

Answer 36

anti-IL-12 and IL-23 (ustekinumab) IL-17 antagonists anti-TNF𝝰 (infliximab)

Question 37

what does acitretin do?

Answer 37

inhibit the synthesis of keratin precursors

Question 38

what does vitamin D topical do?

Answer 38

inhibits keratinocyte proliferation

Question 39

what do retinoids -vitamin A do?

Answer 39

inhibition of cell proliferation and differentiation via binding to nuclear retinoid receptors

Question 40

what are the topical agents for atopic dermatitis (eczema)?

Answer 40

pimecrolimus | glucocorticoids

Question 41

what is pimecrolimus?

Answer 41

topical calcineurin inhibitor

Question 42

what are the systemic agents for atopic dermatitis?

Answer 42

glucocorticoids cyclosporin anti-IL-4 receptor 𝝰 (dupliumab)

Question 43

what are the antimetabolites given in MS?

Answer 43

teriflunomide | cladribine

Question 44

what is cladribine?

Answer 44

purine analogue chemotherapeutic agent

Question 45

what is given for leukocyte suppression in MS?

Answer 45

anti-CD52 (alemtuzumab)

Question 46

T-cell suppression for multiple sclerosis

Answer 46

anti- integrin 𝝰₄β₁ (natalizumab) | sphingosine -1 phosphate receptor modulator (fingolimod)

Question 47

B-cell suppression for multiple sclerosis

Answer 47

anti- CD20 (ocrelizumab)

Question 48

other agents for multiple sclerosis

Answer 48

interferon β glatiramer dimethyl-fumarate fampridine

Question 49

what does dimethyl fumarate do?

Answer 49

has an anti-oxidant effect

Question 50

what does fampridine do?

Answer 50

K channel inhibition--> improves motor function