Weak bases that react with gastric HCl to

form a salt and water, ↓intragastric acidity

dyspepsia, acid-peptic disorders, heartburn

Reacts rapidly with HCl to produce CO₂ and NaCl

·         CO2 --> gastric distention, belching

·         Unreacted alkali --> metabolic alkalosis

·         NaCl absorption --> exacerbate fluid retention (heart failure, hypertension, renal insufficiency)

“

Excessive doses with dairy can lead to hypercalcemia, renal insufficiency, & metabolic alkalosis (milk-alkali syndrome)

Weak bases that react with gastric HCl to

form a salt and water, ↓intragastric acidity

dyspepsia, acid-peptic disorders, heartburn

Reacts more slowly with HCl to produce CO₂ and CaCl₂

CO₂ -> belching, metabolic alkalosis

milk-alkali syndrome

Also affect bone mineralization

(See CH 42)

Weak bases that react with gastric HCl to

form a salt and water, ↓intragastric acidity

dyspepsia, acid-peptic disorders, heartburn

React slowly with HCl --> H₂O & AlCl

Unabsorbed Al --> constipation

React slowly with HCl --> H₂O & MgCl

Unabsorbed Mg --> osmotic diarrhea

Weak bases that react with gastric HCl to

form a salt and water, ↓intragastric acidity

dyspepsia, acid-peptic disorders, heartburn

Reduce acid secretion by 2 mechanisms:

1) Histamine released from enterochromaffin-like (ECL) cells by gastrin or vagal secretion is blocked from binding to the parietal cell H₂ receptor

2) direct stimulation of the parietal cell by gastrin or acetylcholine has a diminished effect on acid secretion in the presence of H₂ blockade

Effective reduction of nocturnal acid but less effective against stimulated secretion

Very safe

Diarrhea, headache, fatigue, myalgias, constipation (<3%)

GERD, peptic ulcer disease, dyspepsia, prevention of bleeding from stress-related gastritis

CI: pregnancy, nursing

Reduce acid secretion by 2 mechanisms:

1) Histamine released from enterochromaffin-like (ECL) cells by gastrin or vagal secretion is blocked from binding to the parietal cell H₂ receptor

2) direct stimulation of the parietal cell by gastrin or acetylcholine has a diminished effect on acid secretion in the presence of H₂ blockade

Effective reduction of nocturnal acid but less effective against stimulated secretion

Very safe

Diarrhea, headache, fatigue, myalgias, constipation (<3%)

GERD, peptic ulcer disease, dyspepsia, prevention of bleeding from stress-related gastritis

CI: pregnancy, nursing

Reduce acid secretion by 2 mechanisms:

1) Histamine released from enterochromaffin-like (ECL) cells by gastrin or vagal secretion is blocked from binding to the parietal cell H₂ receptor

2) direct stimulation of the parietal cell by gastrin or acetylcholine has a diminished effect on acid secretion in the presence of H₂ blockade

Effective reduction of nocturnal acid but less effective against stimulated secretion

Very safe

Diarrhea, headache, fatigue, myalgias, constipation (<3%)

GERD, peptic ulcer disease, dyspepsia, prevention of bleeding from stress-related gastritis

CI: pregnancy, nursing

“

Inhibits binding of dihydrotestosterone (DHT) to androgen receptors.

Inhibits estradiol metabolism.

Increases serum prolactin levels.

Gynecomastia & impotence (men),

galactorrhea (women)

inhibits P450

“

Potent CYP enzyme inhibitor

Irreversible blockade of H⁺,K⁺-ATPase pump in active parietal cells of stomach;

Inhibit both fasting and meal-stimulated

secretion well, because they block the final common pathway of acid secretion, the proton pump

↓ B₁₂ levels, ↑ gastric bacterial

concentrations, ↑serum gastrin levels, ↑chronic inflammation in the gastric body (risk for adenocarcinoma)

GERD, peptic ulcer disease (H. pylori, NSAID, re-bleeding prevention), dyspepsia, prevention of stress-related mucosal bleeding, gastrinoma

Forms a viscous paste that binds selectively to ulcers or erosions. The negatively charged sucrose sulfate binds to positively charged proteins in ulcers or erosion, forming a physical barrier that restricts further caustic damage and stimulates mucosal prostaglandin & bicarb secretion.

Not absorbed, so no systemic adverse effects

Constipation (2%)

upper GI bleeding, prevention of stress related bleeding (administered through nasogastric tube to critically ill patients)

Methyl analog of prostaglandin E₁ (PGE₁)

Acid inhibitory and mucosal protective properties; stimulates mucus & bicarb secretion; enhances mucosal blood flow.

Binds to a prostaglandin receptor on parietal cells, reducing histamine-stimulated cAMP production and causing modest acid inhibition

Diarrhea, cramping, abdominal pain (10-20%)

Fetal abnormalities

CI: pregnancy or childbearing potential (stimulates uterine contractions)

NSAID-induced ulcers

-Coats ulcers and erosions, creating a protective layer against acid and pepsin

-Stimulates secretion of prostaglandin, mucus, bicarb

-Reduces stool frequency/liquidity in acute infectious diarrhea

-Direct antimicrobial effects (against H. pylori) and binds enterotoxins

Harmless blackening of the stool,

harmless darkening of the tongue

prolonged usage may rarely lead to bismuth toxicity → encephalopathy

prevent & treat traveler's diarrhea,

dyspepsia, acute diarrhea

eradification of H. pylori

Dopamine D₂ receptor antagonist (D₂ receptor activation normally inhibits cholinergic smooth muscle stimulation)

↑esophageal peristaltic amplitude, ↑lower esophageal sphincter pressure, enhance gastric emptying

Also block D₂ receptors in the chemoreceptor trigger zone --> anti-nausea, antiemetic

CNS (restlessness, drowsiness, insomnia, anxiety), extrapyramidal (dystonias, parkinsonian features), tardive dyskinesia, elevated prolactin (galactorrhea,

gynecomastia, impotence)

GERD, regurgitation, heartburn, delayed gastric emptying due to postsurgical disorders (vagotomy), dyspepsia, emesis

“Dopamine D2 receptor antagonist

Promote postpartum lactation

Elevated prolactin (galactorrhea,

gynecomastia, impotence); Doesn’t cross BBB (neuro effects rare)

“

Macrolide antibiotic

Directly stimulates motilin receptors on GI smooth muscle, promoting onset of a

migrating motor complex

Ototoxicity

Inhibits P450

gastroparesis (but tolerance rapidly develops), acute upper GI hemorrhage (promote gastric

emptying of blood before endoscopy)

Indigestible, hydrophilic colloids that absorb water, forming a bulky, emollient gel that  distends the colon and promotes peristalsis

Bacterial digestion of plant fibers within the colon may lead to ↑ bloating and flatus

Indigestible, hydrophilic colloids that absorb water, forming a bulky, emollient gel thatdistends the colon and promotes peristalsis

Bacterial digestion of plant fibers within the colon may lead to ↑ bloating and flatus

Indigestible, hydrophilic colloids that absorb water, forming a bulky, emollient gel thatdistends the colon and promotes peristalsis

Bacterial digestion of plant fibers within the colon may lead to ↑ bloating and flatus

Soften stool material, permitting water and lipids to penetrate; administered orally or rectally

Commonly prescribed to hospitalized patients to prevent constipation and straining

Clear, viscous oil that lubricates fecal material, retarding water absorption from the stool

Aspiration can result in lipid pneumonia. Long-term use can impair absorption of fat-soluble vitamins (ADEK)

Prevent and treat fecal impaction in young children and debilitated adults

Balanced, isotonic solution containing an inert, non-absorbable, osmotically active sugar (PEG). ↑stool liquidity due to an obligate ↑in fecal fluid.

Solution is designed so that no intravascular fluid or electrolyte shifts occur

Do not produce cramps or flatus

complete colonic cleansing before endoscopic procedures, chronic

constipation

Induce bowel movements through direct stimulation of ENS, and colonic electrolyte and fluid secretion

Anthraquinone derivatives

Occur naturally in plants

Chronic: brown pigmentation of the

colon (melanosis coli)

Induce bowel movements through direct stimulation of ENS, and colonic electrolyte and fluid secretion

Anthraquinone derivatives

Occur naturally in plants

Chronic: brown pigmentation of the

colon (melanosis coli)

Diphenylmethane derivative

Minimal systemic absorption

acute & chronic constipation,colon cleansing prior to colonoscopy

Stimulates type 2 chloride channel (ClC-2) in the small intestine, increasing chloride-rich fluid secretion. This stimulates intestinal motility and shortens intestinal transit time.

Nausea due to delayed gastric

emptying

Rx: chronic constipation, IBS w/ predominant constipation

CI: pregnancy

Absorbs bacterial toxins and fluid, thus decreasing stool liquidity and number.

Acute diarrhea

Activates μ-opioid receptors in enteric nervous system

Histamine release

Nausea

Nonprescription; does not cross the BBB; no analgesic properties or potential for addiction

Mild cramping but little or no CNS toxicity

Activates μ-opioid receptors in enteric nervous system. Slows motility in gut with negligible CNS effects

Mild cramping

IBS patients with predominant diarrhea

No analgesic properties in standard doses

Higher doses have CNS effects; can

have dependence

Antispasmodic (Anticholinergic)

Inhibits muscarinic cholinergic receptors in enteric plexus and on smooth muscle

Anticholinergic effects (dry mouth,

visual disturbances, urinary retention)

Serotonin 5-HT₃-receptor antagonist

Inhibits unpleasant visceral afferent sensation (nausea, bloating, pain)

Inhibits colonic motility = ↑transit time

5-HT3 receptors in the GI tract normally

activate visceral afferent pain sensation via extrinsic sensory neurons from the gut to the spinal cord/CNS.

Rare but serious GI toxicity; ischemic colitis (some fatal), severe constipation

women with severe diarrhea-predominant IBS

Serotonin 5-HT3 antagonist

Blocks peripheral 5-HT3 receptors on extrinsic intestinal vagal and spinal afferent nerves. Action is restricted to emesis attributable to vagal stimulation (e.g. postop) and chemotherapy

Headache, dizziness, constipation

Small prolongation of QT interval

Postop emesis, cancer chemotherapy

Antipsychotic agent that can be used for its potent antiemetic and sedative effects

Inhibits dopamine and muscarinic receptors.

Sedation

H₁ Antihistamine and Anticholinergic

Sedation, confusion, dry mouth,

cycloplegia, urinary retention

emesis due to chemotherapy, motion

sickness

∆⁹-tetrahydrocannabinol (THC), the major psychoactive chemical in marijuana

Appetite stimulant and antiemetic

CNS marijuana effects:

- Euphoria, dysphoria, sedation,

hallucinations, dry mouth, ↑ appetite

- Autonomic effects - tachycardia,

orthostatic hypotension

Emesis due to chemotherapy

∆⁹-tetrahydrocannabinol (THC), the major psychoactive chemical in marijuana

Appetite stimulant and antiemetic

CNS marijuana effects:

- Euphoria, dysphoria, sedation,

hallucinations, dry mouth, ↑ appetite

- Autonomic effects - tachycardia,

orthostatic hypotension

Emesis due to chemotherapy

Neurokinin 1 (NK₁)-receptor blocker in CNS; interferes with vomiting reflex; no effect on 5-HT, dopamine, or steroid receptors

blocks CNS effects of Sub P (CH 17)

Fatigue, dizziness, diarrhea, CYP interactions

Reduce both early and delayed emesis in cancer chemotherapy