GI Pharmacology II Flashcards
What drug classes are anti-motility agents? (4 drugs)
Antimotility agents:
Loperamide
Diphenoxylate-atropine
Tincture of opium
Eluxadoline
Describe the mechanism of action of anti-motility agents (hint: all opioids)
(all opioid receptor agonists): inhibit peristalsis + prolong transit time,increase viscosity, decrease fluid and electrolyte; increase anal sphincter tone
Loperamide: agonist at u-opioid receptor; decrease gut motility
(causes constipation and nausea)
**can cause additive CNS side effects like sedation + respiratory depression**
Review this slide on the treatment of diarrhea
What class of drugs or agents are adsorbents? (3)
Bismuth subsalicylate
Fiber
Cholestyramine, colestipol, colesevelam
___ such as metamucil works as a bulking agent, while cholestyramine, colestipol and colesevelam function as ___ in the GI system
Fiber such as metamucil works as a bulking agent, while cholestyramine, colestipol and colesevelam function as bile acid-binding resin in the GI system
Ms. Jones is a 20-year-old female who had an ileal resection due to complication from Crohn’s disease. She also carries a history of seizure disorder chronically on Keppra.
She presents to your office with complaint of diarrhea. You suspect bile acid diarrhea given her surgical history and you prescribe cholestyramine.
One month later, she was hospitalized with seizure. What happened?
Pt later developed a seizure likely because she wasn’t taking the meds 2+ hours before all her other medications (recall that bile acid binders needs to be given 2+ hours before taking other medications because they limit absorption)
Describe the mechanism of action of antisecretory agents
What drugs are in this class? (1)
MOA: decrease fluid + electrolyte secretion from stomach + pancreas; anti-motility; intestinal electrolyte absoprtion; inhibit neuroendocrine tumor release of peptides that cause intestinal hypersecretion of electrolytes + water
Drug in this class: Octreotide
**Octreotide = SST analog, inhibits secretion of splanchnic vasodilatory hormones**
*used for variceal bleeds, acromegaly, WIOPoma, carcinoid tumors*
SEs: nausea, cramps, steatorrhea (increased cholelithiasis risk due to CCK inhibition)
Name the different categories of laxatives (4)
Bulk
Softeners
Osmotic
Stimulant
Describe the mechanism of action of bulk laxatives
Bulk laxatives are basically fiber: absorb water + increase fecal mass (anti-diarrheal effects), soften stool consistency
Drugs in this class: carboxymethylcellulose, polycarbophil, psyllium
**may not work in already constipated pts**
Describe the mechanism of action of softener laxatives
Which compounds are in this drug class? (3)
MOA: Lowers barrier of fluid entering intestinal contents (decrease stool surface tension > more water in stool)
Drugs in this class: Docusate, glycerin, mineral oil
Describe the mechanism of action of osmotic laxatives
Which compuds/drugs are in this class? (5)
MOA: increase intestinal water secretion
**also used for hepatic encephalopathy - lactulose!**
Drugs in this class:
Lactulose
Mg(OH)2
Magnesium citrate
Sodium phosphate
Polyethylene glycol - Mirulax
**Might cause electrolyte + volume overload in folks w/ renal heart disease**
Describe the mecahnism of action of stimulant laxatives
Which drugs are in this class? (2)
MOA: alter electrolye transport in intestinal mucosa; increase intestinal motor activity
SE: hypokalemia, protein-losing enteropathy, salt depletion
What are the drug classes used as anti-inflammatory agents in the GI system? (4)
Aminosalicylates
Steroids (glucocorticoids)
Immunomodulators
Biologics
___ are topical anti-inflammatory agents used primarily for ulcerative colitis
Aminosalicylates are topical anti-inflammatory agents used primarily for ulcerative colitis
Drugs in this class:
Sulfasalazine - prodrug activated by colonic bacteria (combo of sulfapyridine + 5-aminosalicylic acid)
5-aminosalicylates: mesalamine, balsalazide, olsalazine
Review the slide below on aminosalicylate side effects
Which drugs are conventional steroids (2)?
Which drugs are non-systemic steroids (2)?
What is each group used for?
conventional steroids: prednisone, methylprednisolone
non-systemic steroids: budesonide
Conventional steroids - induce crohn’s disease + ulcerative colitis remission (moderate - severe disease)
Non-systemic steroids - Controlled ileal + right colon (Entecort) or colonic release (Uceris);
**Entocort – Crohn’s disease, Uceris – Colitis/Crohn’s colitis**
Review the slide below on the side effects of glucocorticoids
Aslo know that with steroids, you really aren’t aiming for long term use
Describe the mechanism of action of 6MP-AZA
MOA: 6-TGN inhibits nucleotide synthesis (revisit cancer lectures if u need to) >> decreased circulating B and T cells >> decreased proinflammatory cytokines/effects
**6-TGN is the active component that is used in the GI system**
*too much 6-TGN - leukopenia and such*
6-MMP is the inactive component. Elevated 6-MMP = hepatotoxicity
(Check TPMT levels BEFORE starting the meds due to some pts having low levels of the enzyme)
Review the slide below on the side effects on 6MP
remember the effects of allopurinol
used to maintain remission in Crohn’s and Ulcerative colitis
Describe the mechanism of action of methotrexate
Recall that methotrexate inhibits DHFR, which prevents the generation of dTMP for nucleotide synthesis
*used to maintain remission in Crohn’s disease;
SE: hepatotoxicitty, interstitial lung disease, myelosuppression, teratogenic - contraindicated in pregaz*
What class of drugs works against TNFalpha and what are they used for?
Why would you need to screen for latent TB and Hep B before using these drugs?
Name the side effects of this drug class (6)
AntiTNF agents - monoclonal Abs against TNFa
Used for induction AND remission of BOTH ulcerative colitis and crohn’s disease
SEs:
TB and Hep reactivation (hence the screening)
Myelosuppression
Increased cancer risk
Psoriasis
Drug-induced lupus
MS-like demyelination
Review the following effects of anti-TNFa drugs
Which drugs are used for CD? UC?
Both CD and UC drugs: Infliximab, Adalimumab
UC only: Golimumab
CD only: Certolizumab pegol
Describe the MOA of anti-integrins
Which drugs are in this class?
MOA: Block leukocyte migration from blood vessels to inflammation sites
Drugs in this class: Natalizumab, vedolizumab
Natalizumab can also be used in MS and neurologic disorders, IBD
*causes increases risk on PML*
Describe the mechanism of action of anti-IL12/23 drugs
Name the drugs that are in this class (1)
MOA: MAb that binds and interferes w/ IL 12 and 23
Drug in this class: Ustekinumab (used for both UC and Crohn’s)
**SEs: squamous cell skin cancer - older pts w/ previous history of nonmelanoma skin cancer; RPLS**
(see slide)
Describe the mechanism of action of guanylate cyclase activators
Which drug is in this class?
MOA: agonise GC receptors in upper & lower GI tract >> increased Cl- + HCO3- >> increased intestinal fluid (also somehow decreases visceral pain)
Drug in this class - Linaclotide
*used for constipation*
Describe the MOA of chlorine channel activators
Which drug is in this class?
MOA: increases fluid secretion into intestinal lumen thru Cl channels; improves fecal transit
Drug in this class: lubiprostone
**bypasses antisecretory effects of opioids, watch in pts w/ liver disease**
Describe the MOA of 5-HT4 agonists
MOA: binds to serotonin receptor (5HT4) w/ high affinity >> stimul8s ACh release >> increased motility (longitudinal muscle contraction, circular muscle relaxation)
