IBD meds

ex of aminosalicylates

balsalazide

mesalamine

olsalazine

sulfasalazine

indications for aminosalicylates

UC tx, great for LT control of dz and maintaining remission

off label-

• crohns (mesalamine)

• RA (sulfasalazine)

what aminosalicylate is most versatile

mesalamine- crohns dz

which amino salicylate can off label treat RA?

sulfasalazine

MOA of aminosalicylates

anti-inflammatory

blocks production of inflammatory response by inhibiting cyclooxygenase and prostaglandins

free radical scavenger

contraindications of aminosalicylates

SULFA allergy for just sulfasalazine!!

may be evidence that there is not cross reactivity btwn sulfonamide abx and non abx sulfonamides

PK of aminosalicylates

5-ASA prodrugs

• sulfasalazine, olsalazine, balsalazide

prodrugs broken down by colonic bacteria into active 5-ASA→ ASO bonds (nitrogen bonds) broken

mesalamine is 5-ASA- other drugs broken down into mesalamine

where do aminosalicylates act?

mesalamine-

• pH release tablets release in ileum

• delayed release act on whole colon

other aminosalicylates just act in colon

dosage forms of aminosalicylates

depends on dz location

oral- delayed release to make sure drug gets to colon

• sulfasalazine

• balsalazide

• olsalazin

• mesalamine

rectal- enema or suppository

• mesalamine

PGX of aminosalicylates

G6PD stressors just for sulfasalazine - monitor for hemolytic anemia

ADE of aminosalicylates

abdominal pain, n/v, diarreha

headache

rash

photosensitivity and lupus

Sulfasalazine specific ADE:

may cause skin and urine to turn yellow

G6PD stressor

drug interactions with aminosalicylates

antacids, H2RA, PPIs- prematurely dissolve coating before colon

ASA- inc GI side effects

sulfasalazine prevents folic acid absorption- supplement

how to solve the problem of antacids/PPIS/H2RA dissolving aminosalicylates before they reach the colon?

stop the antacid if able

what dosing of mesalamine may be the most effective

combo of oral and rectal in distal UC

where do oral meds reach in the colon

end of small intestine and up to the end of the transverse Colon

where do enemas reach in the colon

reach the splenic flexure (top of descending colon)

where do suppositories act

rectum and 15 cm beyond anal verge

ex of corticosteroids

prednisone

budesonide

hydrocortisone

indications for corticosteroids

short term symptom control- short time, lowest effective dose

use enemas or suppositories for distal dz

MOA of corticosteroids

dec inflam

suppress the immune system

dosing of corticosteroids

oral

• prednisone

• budesonide

rectal

• budesonide

• hydrocortisone

what drug class specifically treats UC and which treats Crohns specifically?

Crohns- methotrexate

UC- Cyclosporine

ex of thiopurines

azathioprine

mercatopurine

indications of thiopurines

off label long term tx crohns and UC

not immediate suppression- 3-6 months for max effect

allow for corticosteroid dose reduction

sulfasalazine specific ADE

may cause skin and urine to turn yellow

G6PD stressor

MOA of thiopurines

purine analogs - inhibit DNA or RNA synthesis

azathioprine metabolized into active 6-mercaptopurine

PGX of thiopurines

2 genes involved:

• TPMT

• NUDT15

6-MP forms TGNs that incorporate into DNA/RNA of cells

TPMT inactivates 6-MP

if 2 non functional TMPT alleles→ poor metabolizers, can’t inactivate 6-MP→ high levels of toxicity!

NUDT15- reduces ability of TGNs to incorporate into DNA

PGX recommendations for thiopurines

TPMT poor metabolizer→ drastically reduce dose or use diff drug if tx non malignant prob

Do TMPT testing- dosing based on this, reduces likelihood of acute myelosupression

ADE of thiopurines

myelosuppression- pancytopenia

infection risk

hepatotoxicity

pancreatitis

drug interactions with thiopurines

mesalamine- inhibits TPMT

warfarin- dec effectiveness of warfarin

dosing for thiopurines

oral

TMPT testing prior to starting therapy

monitoring thiopurines

CBC

• every week for 1 nth, then twice a month for the next 2 mths, once a mth after

• monitor more w dosage changes

LFTs

• every 3 mths

ex of TNF- alpha inhibitors

adalimumab (Humira)

certolizumab

golimumab

infliximab (Remicade)

indications for TNF-alpha inhibitors

severe crohns and UC

resistant dz to steroids or immunosuppression

if pts don’t respond to one, won’t usually respond to another in the class

MOA of TNF-alpha inhibitors

block and bind to TNF-alpha expressed in bowel wall

ADE of TNF-alpha inhibitors

inj site rxns

do not start in infected patients and stop therapy if infection develops

• inc risk of serious infections- tb, hep b

inc risk of lymphoma

monitoring TNF-alpha inhibitors

CBC and LFTs

give vaccines prior to starting therapy!

• pneumococcal, flu, Hep a and B, Tdap

contraindications of TNF-alpha inhibitors

DO NOT GIVE LIVE VAX

dosing of TNF-alpha inhibitors

all injectable!

all MAB are injectable

can we give TNF-alpha inhibitors in pregnancy?

yes!

ex of interleukin blockers

risankinzumab (skyrizi)

istekinumab (stelara)

have kin in middle!

indications for interleukin blockers

Crohns and UC

1st line or second line after TNF-alpha inhibitor

MOA of interleukin blockers

block interleukins to interfere with cytokines

efficacy of interleukin blockers

stelara- most established, biosimilars available

skyrizi- newer, more expensive

ex of JAK inhibitors

tofacitinib (xeljanz)

upadacitinib (rinvoq)

indications of JAK inhibitors

Crohns and UC post TNF- alpha blockers

MOA of JAK inhibitors

prevent activation of intracellular mediators involved in immune response

ADE of JAK inhibitors

URIs

Herpes zoster

TB

high ALT/AST

dyslipidemia

cytopenias

dosing of JAK inhibitors

ORAL!

BBW of JAK inhibitors

thrombosis

lymphoma

TB

serious infections

CV events

safety when using JAK inhibitors

no live vaccines!

NO PREG

do not use with other biologics

can you use JAK inhibitors in pregnancy?

NO

ex of S1P receptor modulators

etrasimod (velsipity)

ozanimod (zeposia)

end in mod→ modulators!

indications for S1P receptor modulators

UC in pts that have exhausted other biologicsM

MOA of S1P receptor modulators

blocks T cells from leaving lymph nodes and moving into blood

ADE of S1P receptor modulators

flu like symptoms

inc risk of herpes

bradycardia/AV block

contraindications of S1P receptor modulators

lots of CV contraindications!!

AV block, sick sinus syndrome

bradycardia

MI

heart failure class ¾

stroke/TIA

dosing of S1P receptor modulators

oral

safety when using S1P receptor modulators

no live vax

no preg

ex of immunosuppressants

methotrexate

cyclosporine

methotrexate indications

crohns in resistant dz

MOA of methotrexate

blocks DNA synthesis

contraindications of methotrexate

PREGNANCY

alcoholism/alcoholic liver dz

ADE of methotrexate

hepatotoxicity and myelosuppression do

dosing of methotrexate

only injectable, weekly doses

give with folic acid

monitoring methotrexate

CBC

LFTs

BMP- monitor renal

TB skin test

cyclosporine indications

UC severe resistant dz

rescue to avoid colectomy

MOA of cyclosporine

inhibits T cell activation to prevent T cell expansion

contraindications of cyclosporine

abn renal func

uncontrolled HTN

cancer

ADE of cyclosporine

N/V/D

hypertension - reversible

nephrotoxic -irreversible if chronic tx

drug interactions with cyclosporine

CYP3A4 inhibitors - cyclosporine may increase concentration of med

NSAIDs

potassium sparing diuretics - high potassium

dosing cyclosporine

IV

monitoring cyclosporine

CBC

LFT

BMP

Lipids

TB skin test

BP

probiotics indications

dietary management of UC and IBD

MOA of probiotics

reestablish healthy GI microbiota

anti inflammatory

8 strains of bacteria

ADE of probiotics

rare

bloating

dosing probiotics

capsules, powder

many OTC, VSL3- Rx

what IBD meds are safe for use in pregnancy

aminosalicylates

CCS

thiopurines- continued tx

TNF- alpha inhibitors

Interleukin blockers

what IBD meds you should avoid in pregnancy

S1 receptor modulators

cyclosporine

what IBD meds MUST you avoid in pregnancy

JAK inhibitors

methotrexate