pharmacology of IBD agents

trexall generic

methotrexate

rhematrex generic

methotrexate

lialda generic

mesalamine

apriso generic

mesalamine

pentasa generic

mesalamine

asacol generic

mesalamine

delzicol generic

mesalamine

sandimune generic

cyclosporine

gengraf generic

cyclosporine

neoral generic

cyclosporine

xeljanz generic

tofacitinib

what are the two forms of idiopathic IBD

ulcerative colitis and crohn’s disease

what is ulcerative colitis

mucosal inflammation confined to rectum and colon

what is crohn’s disease

transmucosal inflammation that effects any part of GI but mostly ileum

what is a major symptom of IBD

bloody diarrhea

what happens immunologically in crohn’s disease

increased Th1 — increase cell mediated immunity, decrease humoral immunity

what happens immunologically in ulcerative colitis

increased Th2 — decrease cell mediated immunity, increase humoral mediated immunity

what is used to treat active to moderate ulcerative colitis

aminosalicylate → prednisone → add azothioprine or 6-mercaptopurine if no response

what is used to treat active to severe ulcerative colitis

IV hydrocortisone or methylprednisolone → PO prednisone + aminosalicylate upon remission

what is first line for remission in ulcerative colitis

olsalazine

what is used to treat mild to moderate crohn’s disease

aminosalicylate → metronidazole

what is used to treat active moderate to severe crohn’s disease

prednisone PO or methylprednisolone IV → no response add infliximab → no response add azathioprine → remission taper off prednisone

what is used for remission in crohn’s disease

aminosalicylates + infliximab, azothioprine, methotrexate, or 6-mercaptopurine

what anti-inflammatory drugs are used for IBD

aminosalicylates — AZO compounds or mesalamine compounds

what are the AZO compounds used in IBD

sulfasalazine (azulfidine), olsalazine (dipentum), balsalazide (colazal)

what are the mesalamine compounds used in IBD

pentasa, azacol, rowasa, canasa, lialda

what immunosuppressants are used in IBD

glucocorticoids, immunomodulators,

anti-TNFa, adhesion molecule antagonist, interleukin receptor antagonist

janus kinase inhibitor, SP-1 modulator

what is the mechanism of aminosalicylates

anti-inflammatory that works to inhibit the synthesis of prostaglandins in the colon, interferes with production of inflammatory cytokines, and inhibits cellular functions of natural killer cells/mucosal lymphocytes/macrophages

what are ADRs for olsalazine

watery diarrhea, abdominal pain

what is the best tolerated AZO compound

balsalazide

which AZO compound is the least expensive but has the highest ADRs

sulfasalazine

what are ADRs for sulfasalazine

sulfa allergy, headache, rash, NVD, bone marrow suppression, yellow/orange discoloration of skin and urine

what aminosalicylate has an interaction with folic acid

sulfasalazine

how do glucocorticoids work

inhibit production of inflammatory cytokines, phospholipid A, and nitric oxide synthase

when is IV methylprednisolone used for IBD instead of prednisone/prednisolone

in severely ill patients

what are the advantages of using hydrocortisone suppositories or enemas

maximize colonic absorption, decrease systemic absorption, decrease systemic ADRs

what are the advantages of using budesonide CR

releases the drug in the distal ileum and colon — less ADRs than prednisone and prednisolone but also less effective

what type of diet should patients being treated with corticosteroids be on

high-protein, potassium enriched

how do thiopurines work

suppress purine nucleotide metabolism and decreases DNA synthesis → inhibit cell division and proliferation

what metabolizes azathioprine to 6MP

glutathione sulfhydryl

what is the half life of azathioprine, 6MP, and 6TG

azathioprine and 6MP — short

6TG — days, concentrates in cells

how should 6-mercaptopurine be taken

on an empty stomach

what are drug interactions with thiopurines

allopurinol — decrease dose of azathioprine due to leukopenia

what are ADRs of thiopurines

N/V, hepatotoxicity

what are boxed warnings for thiopurines

lymphoma, leukopenia, thrombocytopenia

what should be monitored in thiopurine therapy

CBC and LFTs

how does methotrexate work at low doses

folate antagonist → inhibits AICAR transformylase and TYMS → increase AICAR → increase adenosine → decrease IL2, decrease inflammation

how does methotrexate work at high doses

folate antagonist → inhibit DHF → decrease FH4 and FH2 → inhibit cell mediated immune reaction, decrease PMN, and decrease inflammation

what should be monitored in methotrexate therapy

LFTs

what are ADRs of methotrexate

myelosuppression, severe oral ulceration/stomatitis

NV, increased LFTs

pneumonitis, photosensitivity, alopecia

crystalluria at high doses

what is given in methotrexate overdose

leucovorin

how does cyclosporine work

suppress cell mediated immune reaction

binds cyclophillin → NFAT not formed → decrease IL2 and T/B cells

what are drug interactions with cyclosporine

3A4 inhibitors — ketoconazole, grapefruit juice

3A4 inducers

what are ADRs of cyclosporine

nephrotoxic, neurotoxic, hepatotoxic

increased risk of lymphoma and infection

HTN, gingival hyperplasia

what produces tumor necrosis factor (TNF)

innate immunity, adaptive immunity, and non-immune cells

how does anti-TNF alpha work

inhibit soluble and membrane bound TNF that are pro-inflammatory, inhibit T cell and macrophage functions → decrease cytokine release

what drugs are anti-TNF alpha

infliximab (remicade)

adalimumab (humira)

certolizumab pegol (cimzia)

golimumab (simponi)

what are ADRs of anti-TNF drugs

increased reactivation of latent TB

increased risk of hepatitis B

what is the dosing for infliximab

q2 month IV

what is the dosing for adalimumab

q2 weeks subq

what is the dosing for certolizumab

q4 weeks subq

what is the boxed warning for anti-TNF drugs

increased risk of infections and increased risk of lymphoma

how does natalizumab work

humanized a-4 integrin inhibitor that binds to cell surface receptors of vascular endothelium of GI → blocks migration of lymphocytes into the tissues

what drug is an adhesion molecule antagonist

natalizumab (tysabri) and vedolizumab (entyvio)

what are ADRs of tysabri

infusion reaction, headache, fatigue

increased risk of opportunistic brain viral infection

how does entyvio work

binds a4B7 integrin and blocks interaction of a4B7 integrin with mucosal adhesion on cell adhesion molecule 1

what are ADRs of entyvio

nasopharyngitis, headache, arthralgia

what are indications for tysabri

treatment of moderate to severe crohn’s and multiple sclerosis

what is entyvio indicated for

ulcerative colitis, crohn’s patients intolerant or unresponsive to TNF blockers or immunomodulators

how is entyvio dosed

300 mg IV on 0, 2, and 6 weeks and q8 weeks after

how do IL12/IL23 antagonists work

interfere with interleukin overt expression → decrease T cell activation and disrupt immune cells that cause inflammation

what drugs are IL12/IL23 antagonists

ustekinumab (stelara), risankizumab (skyrizi), and mirikizumab (omvoh)

what are IL12/23 antagonists indicated for

IBD, psoriatic arthritis, plaque psoriasis

what are ADRs of IL12/23 antagonists

pneumonia

increased risk of TB, increased risk of cancer

infusion reaction

how do janus kinase inhibitors work

inhibit janus kinase enzymes that stimulate immune cell functions

what drugs are janus kinase inhibitors

tofacitinib (xeljanz) and upadacitinib (rinvoq)

what are janus kinase inhibitors indicated for

IBD, rheumatoid arthritis

what is the boxed warning for janus kinase inhibitors

increased lymphoma and cancer, heart attack, stroke, blood clot, and death

how does zeposia and velsipity work

blocks lymphocytes ability to emerge from lymph nodes → decrease lymphocytes available for CNS or intestine → decrease inflammation

what are zeposia and velsipity indicated for

relapsing forms of MS and ulcerative colitis

what are ADRs of zeposia and velsipity

macular edema, URI, UTI

HTN, slow HR, increased infection