Source: G cells (antrum of stomach)

Action:

• increase gastric H+ secretion
• increase growth of gastric mucosa
• increase gastric motility
• increase HCl secretion by parietal cells
• increase pepsinogen secretion by chief cells
• increase histamine secretion by ECL cells (enterochromaffin like cells)

Regulation:

• increased by stomach distention/alkalinization, amino acids, peptides, Calcium in lumen of stomach, vagal stimulation via GRP.
• decreased by stomach pH < 1.5.

Notes:

• highly increased in Zollinger-Ellison syndrome.
• Phenylalanine and tryptophan are potent stimulators.

member of the gastrin-CCK family

Source:

• I cells (duodenum and jejunum)

Action:

• increases pancreatic secretion
• increases gallbladder contraction
• decreases gastric emptying, sphincter of Oddi relaxation

Regulation:

• increased by fatty acids, amino acids

Notes:

• CCK acts on neural muscarinic pathways to cause pancreatic secretion

Source: S cells (duodenum)

Action:

• increases pancreatic HCO3- secretion
• increases bile secretion
• decreases gastric acid secretion

Regulation:

• increased by acid, fatty acids lumen of duodenum

Notes:

• increased HCO3- neutralizes gastric acid in duodenum, allowing pancreatic enzymes to function.

Source: D cells (pancreatic islets, GI mucosa)

Action:

• decreases gastric acid and pepsinogin secretion
• decreases pancreatic and small intestine fluid secretion
• decreases gallbladder contraction
• decreases insulin and glucagon release

Regulation:

• increased by acid
• decreased by vagal stimulation

Notes:

• Inhibitory hormone
• antigrowth hormone effects (digestion and absorption of substances needed for growth)

Glucose dependant insulinotropic peptide

aka

Gastric inhibitory peptide (GIP)

Source: K cells (D,J)

Action:

• Exocrine: decreases gastric H+ secretion
• Endocrine: increases insulin release

Regulation:

• increased by fatty acids, amino acids, and oral glucose

Notes:

• An oral glucose load is used more rapidly than the equivalent given by IV

Source: Parasympathetic ganglia in sphincters, gallbladder, small intestine

Action:

• increases intestinal water and electrolyte secretion
• increases relaxation of intestinal smooth muscle and sphincters

Regulation:

• increased by distention and vagal stimulation
• decreased by adrenergic input

Notes:

• VIPoma - non-alpha, non-beta islet cell pancreatic tumor that secretes VIP. copious diarrhea.

Action:

• increased smooth muscle relaxation, including lower esophageal sphincter

Notes:

• Loss of NO secretion is implicated in increased lower esophageal tone of achalasia

Source: small intestine

Action: Produces migrating motor complexes (MMCs)

Regulation: increased in fasting state

Notes: Motiilin receptor agonists are used to stimulate intestinal intestinal peristalsis

Source: Parietal cells (stomach)

Action: Vitamin B-12 binding protein (required for B-12 uptake in terminal ileum)

Notes: Autoimmune destruction of parietal cells -> chronic gastritis and pernicious anemia

Source: Parietal cells of stomach

Action: decreases stomach pH

Regulation:

• increased by histamine, ACh, and gastrin
• decreased by somatostatin, GIP, Prostaglandin, and secretin

Notes: Gastrinoma - gastrin secreting tumor that causes continuous high levels of acid secretion and ulcers

Source: Chief cells

Action: Protein digestion

Regulation: increased by vagal stimulation, local acid

Notes: inactive pepsinogen -> pepsin by H+

Source: mucosal cells (stomach, duodenum, salivary glands, pancreas) and brunner's glands (duodenum)

Action: neutralizes acid

Regulation: increased pacreatic and biliary secretion with secretin

Notes: HCO3- is trapped in mucus that covers the gatric epithelium.

Mechanism: Reversible block of histamine H2 receptors - decrease in H+ secretion by parietal cells

Use: peptic ulcer, gastritis, mild esophageal reflux.

Toxicity:

• Cimetidine is a potent inhibitor of P-450;
• it also has antiandrogenic effects (prolactin release, gynecomastia, impotence, decreased libido in males);
• it can cross blood brain barrier (confusion, dizziness, headaches) and placenta.
• Both cimetidine and ranitidine decrease renal excretion of creatinine.
• othe H+ blockers are relatively free of these effects

Examples: Cimetidine, ranitidine, famotidine, nizatidine

(take H2 blockers before you dine)

Mechanism: Irreversibly inhibit H+/K+ATPase in stomach parietal cells.

Clinical use: peptic ulcer, gastritis, esophageal reflux, Zollinger-Ellison syndrome.

Examples: Omeprazole, lansoprazole

Mechanism: binds to ulcer base, providing physical protection, and allows HCO3- secretion to reestablish pH gradient in the mucous layer.

Use: increased ulcer healing, traveler's diarrhea.

Triple therapy of H. pylori ulcers - Metrinidazole, Amoxicillin (or Tetracycline), Bismuth. also, PPI.

Please MAke Tummy Better.

Mechanism: a PGE1 analog. Increased production and secretion of gastric mucous barrier, decreased acid production.

Use: prevention of NSAID-induced peptic ulcers; maintenance of a patent ductus arteriosus. Also used to induce labor.

Toxicity: Diarrhea. contraindicated in women of childbearing potential (abortifacient).

Mechanism: block M1 receptors on ECL cells (decreased histamine secretion) and M3 receptors on parietal cells (decreased H+ secretion).

Use: peptic ulcer (rarely used)

Toxicity: tachycardia, dry mouth, difficulty focusing eyes

examples: Pirenzepine, propantheline

Mechanism: Somatostatin analog

Use: Acute variceal bleeds, acromegaly, VIPoma, and carcinoid tumors

Toxicity: Nausea, cramps, steatorrhea

• can effect absorption, bioavalability, or urinary excretion of other drugs by altering gastric and urinary pH or by delaying gastric emptying. 
• over use can cause:
• Aluminum hydroxide - constipation and hypophashatemia; proximal muscle weakness, osteodystrophy, seizures
• Magnesium hydroxide - diarrhea, hyporeflexia, hypotension, cardiac arrest
• calcium carbonate - hypercalcemia, rebound acid increase
• all can cause hypokalemia

Mechanism: monoclonal Ab to TNF, proinflammatory cytokine.

Use: Crohn's disease, rheumatoid arthritis.

Toxicity: Respiratory infection (including reactivation of latent TB), fever, hypotension.

Mechanism: A combination of sulfapyridine (antibacterial) and 5-aminosalicyclic acid (antiinflammatory). Activated by colonic bacteria.

Use: ulcerative colitis, Crohn's disease

Toxicity: malaise, nausea, sulfonamide toxicity, reversible oligospermia.

Mechanism: 5-HT3 antagonist. Powerful central acting antiemetic.

Use: control vomiting postoperatively and in patients undergoing cancer chemotherapy.

Toxicity: headache, constipation.

Mechanism: D2 receptor antagonist. Increased resting tone, contractility, LES tone, motility. Does not influence colon transport time.

Use: Diabetic and post-surgery gastroparesis

Toxicity: increased parkinsonian effects. Restlessnes, drowsiness, fatigue, depression, nausea, diarrhea, Drug interaction with digoxin and diabetic and diabetic agents. Contraindicated in patients with small bowel obstruction.

5HT3 antagonists

•  (Ondansetron, Granisetron, dolasetron)
• may act in chemoreceptor trigger zone and in peripheral sites.

DA antagonists

• (Phenothiazine, metoclopiramide) 
• blocks D2 receptors in chemoreceptor trigger zone.
• metoclopiramide is also a prokinetic agent

Cannabinoids

• (Dronabinol) 
• active ingredient in marijuana.

Ipecac

• locally irritates the GI tract and stimulates the chemoreceptor trigger zone
• if emesis does not occur in 15-20 minutes, lavage must be used to remove ipecac

Apomorphine

• Dopamine-receptor agonist that stimulates the chemoreceptor trigger zone
• vomiting should occur within 5 min. 

secrete alkaline mucus to neutralize acid contents entering the duodenum from the stomach.

located in the duodenal submucosa (thesse are the only GI submucosal glands). 

Hypertrophy of these glands is seen in peptic ulcer disease.

1. Salivary amylase (ptyalin) - starts digestion, hydrloyzes alpha1-4 linkages to yield disaccharides (maltose and dextrans)
2. pancreatic amylase - highest concnetration in duodenal lumen, hydrolyzes starch to oligosaccharides and disaccharides.
3. oligosaccharide hydrolases - at brush border of intestine, the trate-limiting step in carbohydrate digestion, produces monasaccharides from oligo- and disaccharides.