PHARMACOLOGY OF GASTROINTESTINAL DRUGS (PT 2)

Mucosal prostaglandins

appear to be important in stimulating mucus and bicarbonate secretion and mucosal blood flow.

MUCOSAL PROTECTIVE AGENTS

A number of agents that potentiate these mucosal defense mechanisms are available for the prevention and treatment of acid peptic disorders.

SUCRALFATE

• MOA is unclear. It is believed that the negatively charged sucrose sulfate binds to positively charged proteins in the base of ulcers or erosion, forming a physical barrier that restricts further caustic damage and stimulates prostaglandin and bicarbonate secretion.

SUCRALFATE

USES 

• prevention of stress related bleeding (instead of using antacids, H2 blockers, and PPIs due to increased risk of nosocomial pneumonia).

PROSTAGLANDIN ANALOGS

drug

misoprostol

misoprostol

brand name 

Cytotec 

misoprostol

a methyl analog of PGE 1

PROSTAGLANDIN ANALOGS

moa

• Has both acid inhibitory and mucosal protective properties.

PROSTAGLANDIN ANALOGS

use

• For the prevention of NSAID induced ulcers in high risk patients.

PROSTAGLANDIN ANALOGS

ade

• Abortion

• Diarrhea

exacerbation of Inflammatory Bowel Disease

BISMUTH COMPOUNDS

drugs

• Bismuth subsalicylate

• Bismuth subcitrate potassium

BISMUTH COMPOUNDS

• MOA is unknown. But bismuth coats ulcers and erosions, creating a protective layer against acid and pepsin.

• May also stimulate prostaglandin mucus and bicarbonate secretion.

Bismuth compounds have direct_ 

antimicrobial activity against H. pylori.

BISMUTH COMPOUNDS

ade

• harmless blackening of stool

• encephalopathy (with prolonged use).

DRUGS STIMULATING GASTROINTESTINAL MOTILITY

• Cholinomimetic agents

• Metoclopramide & Domperidone

• Macrolides

THE ENTERIC NERVOUS SYSTEM

• considered to be the “third” division of the autonomic nervous system.

THE ENTERIC NERVOUS SYSTEM

• In contrast to the other divisions,

• it can perform many functions independently of the central nervous system

THE ENTERIC NERVOUS SYSTEM

• it is an _

• independent, though connected network of nerve fibers that innervate the viscera (GIT, pancreas, gall bladder).

THE ENTERIC NERVOUS SYSTEM

• Although there are at least 14 serotonin receptor subtypes,

5HT drug development for gastrointestinal applications to date has focused on 5-HT₃ receptor antagonists and 5-HT₄ receptor agonists

gents which have effects on gastrointestinal motility and visceral afferent sensation are used in the treatment of

Irritable Bowel Syndrome and Antiemetic Agents

CHOLINOMIMETIC AGENTS

neostigmine

NEOSTIGMINE

acetylcholinesterase inhibitor

NEOSTIGMINE

• An acetylcholinesterase inhibitor that can enhance 

• Gastric

• small intestine

• colonic emptying.

NEOSTIGMINE

use 

for the treatment of hospitalized patients with acute large bowel distention (known as Ogilvie’s syndrome)

METOCLOPRAMIDE & DOMPERIDONE

moa 

• D₂-receptor antagonists.

• Activation of dopamine receptors inhibits cholinergic smooth muscle stimulation.

METOCLOPRAMIDE & DOMPERIDONE

these agents:

• increase esophageal peristaltic amplitude, 

• increase lower esophageal sphincter pressure, and 

• enhancegastric emptying.

Metoclopramide & domperidone also blocks

CRTZ of the medulla, resulting in potent antinausea and antiemetic action.

METOCLOPRAMIDE & DOMPERIDONE

clinical uses 

• FOR GERD

• IMPAIRED GASTRIC EMPTYING

• NONULCER DYSPEPSIA

• PREVENTION OF VOMITING

• POSTPARTUM LACTATION STIMULATION

METOCLOPRAMIDE & DOMPERIDONE

clinical uses : FOR GERD

Prokinetic agents are used mainly in combination with antisecretory agents in patients with regurgitation or refractory heartburn.

METOCLOPRAMIDE & DOMPERIDONE

clinical uses : IMPAIRED GASTRIC EMPTYING

used in patients with delayed gastric emptying due to postsurgical disorders (vagotomy, antrectomy), and diabetic gastroparesis.

METOCLOPRAMIDE & DOMPERIDONE

clinical uses : NONULCER DYSPEPSIA

for symptomatic improvement in a small number of patients with chronic dyspepsia

METOCLOPRAMIDE & DOMPERIDONE

clinical uses : PREVENTION OF VOMITING

potent antiemetic action; used for the prevention and treatment of emesis

METOCLOPRAMIDE & DOMPERIDONE

clinical uses: POSTPARTUM LACTATION STIMULATION

domperidone is sometimes recommended to promote postpartum lactation

ADVERSE EFFECTS

metoclopramide (CNS)

• Restlessness

• drowsiness, 

• insomnia, 

• anxiety, 

• Agitation

occur in 10-20% of patients

ADVERSE EFFECTS

METOCLOPRAMIDE (extra-pyramidal effects)

• Dystonias

• akathisia, 

• parkinsonian features

due to central dopamine receptor blockade

ADVERSE EFFECTS

dromperidone 

• Safe because it does not cross the blood-brain barrier.

• Neuropsychiatric and extrapyramidal effects are rare.

MACROLIDES

erythromycin

ERYTHROMYCIN

• It can directly stimulate motilin receptors on gastrointestinal smooth muscle and promote the onset of a migrating motor complex.

ERYTHROMYCIN

use 

•  patients with acute upper gastrointestinal hemorrhage to promote gastric emptying of blood before endoscopy. 

LAXATIVES

• Bulk-forming laxatives

• Stool surfactant agents (softeners)

• Osmotic laxatives

• Stimulant laxatives

• Chloride secretion activators

Patients not responding to dietary changes or fiber supplements should undergo

medical evaluation before initiating long-term laxative treatment.

BULK-FORMING LAXATIVES

PSYLLIUM & METHYLCELLULOSE

PSYLLIUM & METHYLCELLULOSE

• Bulk-forming laxatives are indigestible, hydrophilic colloids that absorb water, forming a bulky, emollient gel that distends the colon and promotes peristalsis.

STOOL SURFACTANT AGENTS (STOOL SOFTENERS)

• docusate

• glycerin suppository 

• mineral oil 

• docusate

• glycerin suppository 

• mineral oil 

• These agents soften stool material, permitting water and lipids to penetrate.

• They may be administered orally or rectally.

• These agents are used to prevent and treatfecal impaction in young children and debilitated adults

• docusate

• glycerin suppository 

• mineral oil 

long-term use 

•  can impair absorption of fat-soluble vitamins (A, D, E, & K)

OSMOTIC LAXATIVES

• nonabsorbable sugars or oils 

• balanced polyethylene glycol

NONABSORBABLE SUGARS OR SALTS

drugs 

• Magnesium hydroxide,

• Sorbitol

• Lactulose

NONABSORBABLE SUGARS OR SALTS

• These agents may be used for the treatment of acute constipation or the prevention of chronic constipation.

BALANCED POLYETHYLENE GLYCOL

Lavage solutions are commonly used for complete colonic cleansing before gastrointestinal endoscopic procedures.

BALANCED POLYETHYLENE GLYCOL

the solution is designed so that 

• no significant intravascular fluid or electrolyte shifts occur.

STIMULANT LAXATIVES (CATHARTICS)

• These agents induce bowel movements through a number of poorly understood mechanisms

STIMULANT LAXATIVES (CATHARTICS)

direct stimulation of the: 

• enteric nervous system 

• colonic electrolyte

• fluid secretion.

Cathartics may be required on

a long-term basis, especially in patients who are neurologically impaired and in bed-bound patients in long- term facilities 

STIMULANT LAXATIVES (CATHARTICS)

• anthraquinone derivatives

• diphenylmethane derivatives 

ANTHRAQUINONE DERIVATIVES

agents 

• aloe

• senna

• cascara 

ANTHRAQUINONE DERIVATIVES

• These laxatives are poorly absorbed after hydrolysis in the colon, producing a bowel movement in 6-12 hours when given orally, and 2 hours when given rectally.

ANTHRAQUINONE DERIVATIVES

ade

melanosis coli, or a characteristic brown pigmentation of the colon.

DIPHENYLMETHANE DERIVATIVES

drug

bisacodyl 

DIPHENYLMETHANE DERIVATIVES

bisacodyl is used in _

• treatment of acute and chronic constipation.

DIPHENYLMETHANE DERIVATIVES

• It induces a bowel movement within 6-10 hours when given orally, and 30-60 minutes when given rectally.

It has minimal systemic absorption and appears to be safe for acute and long-term use.

CHLORIDE SECRETION ACTIVATORS

• lubiprostone

• linaclotide 

• plecanatide 

LUBIPROSTONE

• A prostanoic acid derivative, labeled for use in chronic constipation and irritable bowel syndrome (IBS) with predominant constipation.

LUBIPROSTONE

acts by 

• stimulating the type 2 chloride channel (CIC-2) in the small intestine.

• The increase in chloride-rich fluid secretion into the intestine, stimulates intestinal motility and shortens intestinal transit time. 

LINACLOTIDE & PLECANATIDE

• A short-amino acid peptides that stimulates intestinal chloride secretion through a different mechanism by binding to and activating guanylate cyclase-C on the luminal surface.

• This leads to increasedintracellular and extracellular cGMP with activation of the cystic fibrosis transmembrane conductance regulator (CFTR), followed by chloride-rich secretion and acceleration of intestinal transit.

LINACLOTIDE & PLECANATIDE

appproved for _

• treatment of chronic constipation.