B.29-immunopharmacology 1 (cytotoxic agents, retinoids) +autoimmune diseases Flashcards
list the cytotoxic agents
cyclophosphamide methotrexate azathioprine, 6-MP (6-mercaptopurine) leflunomide mycophenolic acid
what is cyclophosphamide?
alkylating agent
how are the cytotoxic agents given?
oral or parenteral
except for leflunomide–> only oral
how is leflunomide and teriflunomide given?
oral
what is methotrexate?
anti-metabolite
inhibitor of dihydrofolate reductase
what is the mechanism of azathioprine and 6-MP?
inhibits de-novo purine synthesis
what is the mechanism of mycophenolic acid?
inhibits de novo GTP synthesis
*B and T cells are suppressed
what is the mechanism of leflunomide and teriflunomide?
inhibit de-novo pyrimidine synthesis
which cytotoxic agent requires hepatic P450 activation?
cyclophosphamide
why do we need adequate hydration in methotrexate?
to prevent urinary crystallization
from when is azathioprine effective?
after 12 weeks of starting therapy
indications for cyclophosphamide
hematological malignancies breast and ovarian cancer autoimmune diseases (SLE, GN, vasculitis)
indications for methotrexate
hematological malignancies
CNS and other solid tumors
Autoimmune diseases (RA, psoriasis)
indications for azathioprine and 6-MP
hematological malignancies
autoimmune diseases (SLE,RA)
IBD
indications for mycophenolic acid
solid organ transplantation autoimmune diseases (SLE, GN, myasthenia, psoriasis)
indications for leflunomide, teriflunomide
autoimmune diseases (RA, multiple sclerosis)
side effects for cyclophosphamide
myelosuppression
GI distress
hemorrhagic cystitis
what is given as an antidote for the damage of the bladder from cyclophosphamide?
mesna
SE from methotrexate
myelosuppression
toxic effects on skin and GI mucosa
pulmonary fibrosis (in chronic use)
what reduces the toxic effect of methotrexate?
folinic acid
don’t combine azathioprine or 6-MP with…
allopurinol
SE of azathioprine and 6-MP
myelosuppression
hepatotoxicity
SE of mycophenolic acid
myelosuppression
GI distress
which cytotoxic agent is used in combination with cyclosporine?
mycophenolic acid
SE of leflunomide and teriflunomide
GI irritation
hepatotoxicity
teratogenic
when are glucocorticoids used to suppress immunologic reactions?
organ transplantation
hematologic malignancies
management of acute flare-ups in RA
NSAIDS
Corticosteroids
disease-modifying anti-rheumatic drugs (DMARD’S) for RA
methotrexate (1st line agent) chloroquine, hydroxychloroquine leflunomide sulfasalazine (5-ASA) cyclosporine tofacitinib
what is the first-line agent for RA? out of DMARD’S..
methotrexate
drugs used for mild IBD
5-ASA
glucocorticoids - budesonide (topical, oral)
biological therapy for RA
anti-TNF𝝰 (infliximab) CTLA-4 fusion protein (abatacept) IL-1 receptor antagonist (anakinra) IL-6 receptor antagonist (tocilizumab) anti-CD20 (rituximab)
drugs used for moderate IBD
glucocorticoids-prednisone (oral, IV)
azathioprine, 6-MP
methotrexate
drugs used for severe IBD
cyclosporin
anti-TNF𝝰 (infliximab)
anti-IL-12 and IL-23 (ustekinumab)
anti- integrin 𝝰₄β₁ (natalizumab), anti-integrin 𝝰₄β₇ (vedolizumab)
topical agents for psoriasis
PUVA therapy (psoralen and ultraviolet A)
glucocorticoids
vitamin D
retinoids - vitamin A
systemic agents for psoriasis
acitretin (vitamin A derivative)
dimethyl fumarate
apremilast (↓ expression of inflammatory cytokines)
immunosuppressive agents- cyclosporin, methotrexate
biological therapy for psoriasis
anti-IL-12 and IL-23 (ustekinumab)
IL-17 antagonists
anti-TNF𝝰 (infliximab)
what does acitretin do?
inhibit the synthesis of keratin precursors
what does vitamin D topical do?
inhibits keratinocyte proliferation
what do retinoids -vitamin A do?
inhibition of cell proliferation and differentiation via binding to nuclear retinoid receptors
what are the topical agents for atopic dermatitis (eczema)?
pimecrolimus
glucocorticoids
what is pimecrolimus?
topical calcineurin inhibitor
what are the systemic agents for atopic dermatitis?
glucocorticoids
cyclosporin
anti-IL-4 receptor 𝝰 (dupliumab)
what are the antimetabolites given in MS?
teriflunomide
cladribine
what is cladribine?
purine analogue chemotherapeutic agent
what is given for leukocyte suppression in MS?
anti-CD52 (alemtuzumab)
T-cell suppression for multiple sclerosis
anti- integrin 𝝰₄β₁ (natalizumab)
sphingosine -1 phosphate receptor modulator (fingolimod)
B-cell suppression for multiple sclerosis
anti- CD20 (ocrelizumab)
other agents for multiple sclerosis
interferon β
glatiramer
dimethyl-fumarate
fampridine
what does dimethyl fumarate do?
has an anti-oxidant effect
what does fampridine do?
K channel inhibition–> improves motor function
