Immunosuppressants used in inflammatory bowel disease

CLASS / DRUG MECH OF ACTION ROUTE METABO USES SIDE EFFECTS

AMINOSALICYLATES no vaccination during salicylate

tx

Mesalamine Inhibits IL1 and TNFa preventing
inflammation primarily in the terminal
ileum / colon
Oral/anal, bacteria cleave azo
bond in ileum / colon, excreted in
feces and urine
1st CHOICE For ulcerative colitis
UC(colon inflam. w/bleeding
[crohns C= strictures])
-Interstitial nephritis:kidney
tubules swell
-not for salicylate allergies or
preg pts

Sulfasalazine An AZO compound that is broken down by Slow vs fast acetylators, not for pregnant pts
bacteria to mesalamine and sulfapyridine bone marrow suppression, allergy, oligospermia, dec
folate absorption

GLUCOCORTICOIDS CHANGE CELL TRANSCRIPTION ROUTE SPECIFIC FOR SEVERITY TO INDUCE REMISSION ONLY MUST SLOWLY TAPER
OF DX GLUCOCORTICOID

Prednisone Diffuse through cell bind to intracellular Oral Mod/severe UC/C Acute: peptic ulcer disease
gluc. Receptor, enter nucleus and inhibit Aldosterone like effects.
Hydrocortisone NFkB which dec inflammatory mediators Rectal and IV Severe UC/C
Delayed: iatrogenic Cushings (inc
Budesonide (enteric Oral Mild C in ileum/prox colon cortisol)
coated)

ANTIMETABOLITES Azathioprine is a Prodrug of 6MP 1st pass liver metabo to active by Induction and maintanence of -Low tmpt pt = bone marrow
HGPRT and inactive by xanthine remission of UC and C, may take suppression
Azathioprine 6MP is imidazole that antagonizes de novo ox and tmpt most inactivation by months of treatment to achieve
pruine biosynthesis xanthine oxidase remission -Inc risk of infection/not for preg
6-Mercaptopurine patients

-w/allopurinol= mercaptopurine
toxicity

CALCINEURIN Inhibits calcineurin (calcineurin is
INHIBITORS intermediate in TCr/CD28 pathway for t-
cell activation) by binding to cyclophilin
Cyclosporine which inhibits calcineurin
IV and oral (not with high fat
meal) 90% bound albumin,
hepatic metabo via CYP3A
For short term severe IBD (C/UC)
and for steroid refractory UC
Inc risk for nephrotoxicity,
hypertension, infections,
malignancy (skin cancer),
hepatotoxicity  monitor ALT
AST

BIOLOGICALS NOT FOR USE WITH BIOLOGICS AS USING BOTH WILL CAUSE INFECTIONS

Infliximab IgG1 monoclonal ab against TNF  IV, elimination is 1st order For Crohns disease Infection, Tb and Hepatitis B
macrophage and lymphocytic apoptosis kinetics reactivation, URI’s, human
infliximab Ab can be made

Natalizumab Limits adhesion and transmigration of Iv, Used for both Multiple Sclerosis Used with slalicylates and
leukocytes by binding to alpha4 subunits and for induction and glucocorticoids
of a4b1/a4b7 integrins to block vcam maintenance of remission in
association moderate to severe Crohns PML (demyelinating dx) can
 occur

Hepatotoxicity

Treatment of disorders of bowel motility and water flux

DOPA D2R D2 receptor antagonism in myenteric Oral, parenteral Short term tx of gastroparesis High prolactin levels
ANTAGONIST plexus, has prokinetic effects (gastric paralysis (gynecomastia ammenorhea,
extrapyramidal effects
Metoclopramide

MOTILIN RECEPTOR Stimulates motilin release from intestinal Short term tx of gastroparesis Spastic bowel contraction 
AGONIST m cells causing increased dumping from and Bezoars – ball of stuff stuck cramps, impaired transit, and
stomach in stomach vomiting
Erythromycin

CHOLINOMIMETICS

Bethanchol Stimulates muscarinic M3 receptors on smooth muscle and at myenteric Used in PAST for GERD and Multiple cholinergic effects so not
plexus symapses gastroparesis used

Neostigmine Achesterase inhibitor allows Ach to stay in IV For acute large bowel distention, Can cause bradycardia, if so give
neuronal cleft longer allowing for enhances GI emptying atropine
prolonged Achr activation

Antidiarrheals

u OPIOID AGONIST peripheral u receptor agonist on gi cells Oral, hepatic ester hydrolysis to For nonhematochezic bacterial -Diphenox overdose causes
causing inc colonic transit time and fecal difenoxin induced diarrhea neuro effects give with atropine
Diphenoxylate water absorption while decreasing mass to prevent overdose
movements and gastrocolic reflex Excreted in feces
-UC, ileus, megacolon, toxic
Loperamide Oral, hepatic ox, excreted in megacolon
urine / feces

ANTIMOTILITY
AGENTS

Bismuth Converted to salicylate and bismuth salt Oral Mild nonspecific diarrhea like Stains tongue black and gives
subsalicylate to give both antisecretory, antimicrobial travelers diarrhea dark stool
and anti-inflammatory action
Not for pts with aspirin allergy

Methylcellulose Indigestable colloids that absorb water inc Oral constipation and mild chronic Bloating and increased farting
bulk diarrhea

Cholestyramine Bile acid sequestrant Oral Bile saltinduced diarrhea, C and Bloating farting, constipation,
clostridium difficile diarrhea and fecal impaction may occur

Octreotide Analogue of somatostatin Subq or IV Inhibits severe secratory diarrhea b-12 deficiency, farting, fat in
by hormone secreting tumors stool, cramps. monitor: heart,
(vipomas) liver, kidney, glucose, for kidney
 stones, pancreatitis

Laxatives

BULK FORMING 12-72 Form hydrophilic colloid gels in laxative Bloating, farting , intestinal
AGENTS hrs intestine obstruction in bedridden pts

Psyllium/Methylcellul
ose/

Polycarbophil/Bran

STOOL SOFTENERS 2-3 Docusate reduces oil water laxative Mineral oil aspiration may cause
days surface tension keeping water severe pneumonitis
Docusate and fat in stool
NA/Docusate CA/
Mineral oil softens stool by
Glycerine preventing water loss
suppository /mineral
oil

OSMOTIC LAXITIVES 30 min Nonabsorbable salt retains laxative Acute phosphate nephropathy
water
Mg Citrate/Mg
hydroxide/

Mg sulfate/Na
phosphate

NONABSORB. 1-3 hrs Hydralized to small acids that Laxative Cramps and severe farting
SUGAR/ALCOHOL draw water into lumen
PEG used prior to gi exam
Lactulose/Sorbitol/ Long chain polyglycol draws (colonoscopy)
water
Polyethylene Glycol

STIMULANT 8-10 Promote accumulation of water Senna for opioid induced Bisacodyl shouldn’t be taken with
LAXATIVES hrs and electrolytes and stimulates constipation antacids ppi or h2 blockers
motility
Senna/Cascara/Aloe/ Castor oil prior to gi exam Castor oil can have toxic effects
(colonoscopy)
Bisacodyl/Castor Oil
 u RECEPTOR
ANTAGONISTS

Methylnaltrexone Bind to gi tract u opioid receptor and Subq, minor hepatic metabo, For opioid induced constipation Reduce amt in renal pt
antagonize peripheral opioid effects on renal and fecal excretion when other laxatives don’t work
motility and secretion

Alvimopan Bind to gi tract u opioid receptor and Oral, bound to albumin, For short term post op ileus Inc Myocardial infarcts seen,
antagonize peripheral opioid effects on hydrolyzed by gut flora to active recovery caution in renal / liver failure,
motility and secretion amide, renal and biliary bowel obstruction, Japanese
excretion people, end stage renal dx

Irritable Bowel
Syndrome

5HT3 RECEPTOR Antagonize visceral afferent pain Oral, extensive hepatic For WOMEN with severe Life threatening ischemic colitis,
ANTAGONISTS sensation, delay gastric transit, reduce metabolism CYP2C9, 3A4,1A2 diarrhea predominant IBS obstruction, perforation, toxic
secretion and increase colonic compliance megacolon, colonic ischemia,
Alosetron Renal / biliary excretion death

5HT4 RECEPTOR Stimulates proximal bowel contraction and Oral, binds to glycoprotein, fecal Constipation predominant IBS or Contraindicated in women >55
AGONISTS distal bowel relaxation. excretion chronic idiopathic constipation in
WOMEN <55 yrs old Cardiovascular deaths not for
Tegaserod anyone with HTN or GI probs

Cl CHANNEL Activates type 2 Cl channel on gi epithelial
ACTIVATORS cells creating CL rich secretions that
soften stool increase motility and promote
Lubiprostone spontaneous bowel movement
Oral, metabolism in stomach and
jejunum by reduc / oxidation to
active metabolism M3
Constipation predominant IBS in
WOMEN and chronic idiopathic
constipation in MEN AND WOMEN
Abdominal distention, pain,
diarrhea
Not for pts with diarrhea or bowel
obstruction, not for IBS in men