DRUGS ACTING ON THE GASTOINTESTINAL SYSTEM

PEPTIC ULCERS• Erosions in the lining of the stomach and adjacent

areas of the GIT• Burning pain, hours after meals• Drugs used to treat, prevent or aid in the healing of

these ulcers• Actual cause is not really known• Caused by excessive acid production-> neutralize

acid or blocking PNS -> decrease normal GI activity and secretions

• Caused by H. pylori bacteria

PEPTIC ULCERSDrugs used to treat ulcers:a. histamine-2 antagonists – block the release of

hydrochloric acid in response to gastrinb. antacids – interact with acids at the chemical level to

neutralize themc. proton pump inhibitors – suppress the secretion of

hydrochloric acid into the lumen of the stomachd. antipeptic agents – coat injured area in the stomach

to prevent further injury from acide. prostaglandins – inhibit the secretion of gastrin and

increase the secretion of the stomach, providing buffer

HISTAMINE-2 ANTAGONISTS• Selectively block H2 receptors-> located in the

parietal cells• Blocking them prevents gastrin -> prevents release

of histamine; stimulation of receptors-> production of HCl acid; prevents acid reflux

• cimetidine (Tagamet)- first class developed; antiadrenergic effects; oral and parenteral

• ranitidine (Zantac) – longer acting; more potent; oral and parenteral (twice a day)

• famotidine (Pepcid) – similar to ranitidine in terms of actions and A/E, but it is much more potent; can be given to children

HISTAMINE-2 ANTAGONISTSTHERAPEUTIC ACTION:• selectively block histamine-2 receptor sites -> reduction in

gastric acid secretion and pepsin productionUSES:• short-term treatment of active duodenal ulcer, benign

gastric ulcer (reduction in the overall acid level can promote healing and decrease discomfort)

• prophylaxis of stress-induced ulcers and acute upper GI bleeding (blocking acid protects the stomach lining – at risk because of decreased mucus assoc with stress)

• treatment of erosive gastroesophageal reflux (decreasing regurgitated acid-> healing, decrease pain)

• relief symptoms of heartburn, acid indigestion, sour stomach

HISTAMINE-2 ANTAGONISTSPHARMACOKINETICS:• A: oral; D: crosses placenta and BM; M: liver; E: urine CONTRAINDICATIONS:• allergies • CAUTIONS:pregnancy, lactation, hepatic/renal dysfunctioncare for prolonged use -> may mask more serious problems • ADVERSE EFFECTS:diarrhea, constipation, dizziness, headache, somnolence, confusion,

arrhythmias, hypotension (IM/IV; prolonged use); gynecomastia, impotence

ANTACIDS• inorganic chemicals -> neutralize stomach acid; OTC• frequent administration leads to acid rebound• neutralizing the stomach contents to an alkaline

level stimulated gastrin production to cause an increase in acid production and return the stomach to its normal acidic state

• choice of antacids depends on A?E and absorption factors

• sodium bicarbonate – oldest• calcium bicarbonate – causes constipation and acid

rebound

ANTACIDS• magnesium salts (Milk of Magnesia) – very effective in

buffering acid; causes diarrhea; nerve damage; coma; DOC for pregnancy and lactation (not systemic)

• aluminum salts (Amphojel) – do not cause acid rebound, but not very effective; severe constipation, hypophosphatemia -> Ca imbalance

• magaldrate (Lowsium, Riopan) –combination; decrease GI A/E, may cause rebound hyperacidity and alkalosis; Maalox = Ca + Al buffers acid and neither constipation and diarrhea;

• MylantaII- antigas agent; 1-3 hrs after meals• antacids greatly affect the absorption of other drugs->

separate from other meds 1-2 hrs

ANTACIDSTHERAPEUTIC ACTIONS:• neutralizes stomach acid by direct chemical reaction USES:• symptomatic relief of upset stomach assoc with

hyperacidity, hyperacidity assoc with PUD, gastritis, esophagitis, gastric hyperacidity

CONTRAINDICATIONS:• allergies

ANTACIDSCAUTIONS:• electrolyte imbalance, GI obstruction, allergy, renal

dysfunction, pregnancy and lactation, acid-base imbalance

ADVERSE EFFECTS:• related to acid-base levels and electrolytes;

rebound acidity; nausea, vomiting, neuromuscular changes, headache, irritability, muscle twitching, coma, constipation, diarrhea, fluid retention and CHF

PROTON PUMP INHIBITORS• suppress/inhibiting gastric acid secretion by inhibiting

hydrogen-potassium adenosine triphosphatase (H+, K+-ATPase) enzyme system on the secretory surface -> blocking the final step in acid production -> lowering acid levels in the stomach

• omeprazole (Omepron) – faster-acting; more quickly excreted; used in combination therapy to treat ulcers by H. pylori; heartburn (OTC)

• esomeprazole (Nexium) – longer-acting; not broken down fast; GERD, severe erosive esophagitis

• lansoprazole (Prevacid) – delayed-release form, IV; gastric ulcers, GERD, hypersecretory syndromes, healing duodenal ulcers, eradication of H. pylori

PROTON PUMP INHIBITORSTHERAPEUTIC ACTIONS• act at specific secretory surface receptors to

prevent the final step of acid production -? Decrease the acid level in the stomach

USES: stated above PHARMACOKINETICS:• A: GIT; M: liver; E: urine

PROTON PUMP INHIBITORSCONTRAINDICATIONS: allergies

CAUTIONS: pregnancy and lactation ADVERSE EFFECTS:• dizziness, headache, asthenia, vertigo, insomnia,

apathy, dream abnormalities, diarrhea, abdominal pain, nausea, vomiting, dry mouth, cough, stuffy nose, hoarseness, epistaxis, pruritus, dry skin, back pain, fever

ANTIPEPTIC AGENT• eroded ulcer sites in the GIT from further damage by acid and

digestive enzymes• sucralfate (Carafate) THERAPEUTIC ACTIONS:• forms an ulcer-adherent complex at duodenal ulcer sites ->

protecting the sites against acid, pepsin and bile salts -> prevents further breakdown of the area-> healing

USES:• short-term treatment of duodenal ulcers (reduced dose for

maintenance) PHARMACOKINETICS:• A and M: liver; crosses placenta and BM

ANTIPEPTIC AGENTCONTRAINDICATIONS:• allergies; renal failure; undergoing dialysis

CAUTIONS: pregnancy and lactation ADVERSE EFFECTS:• constipation (most common), diarrhea, nausea,

indigestion, gastric discomfort, dry mouth, dizziness, sleepiness, vertigo, skin rash, back pain

PROSTAGLANDIN• used to protect the lining of the stomach in situations that may lead

to serious GI complications• misoprostol(Cytotec) THERAPEUTIC ACTIONS:• inhibits gastric acid secretion and increases bicarbonate and mucous

production in the stomach -> protecting the stomach lining USES:• prevent NSAID-induced gastric ulcers (at meals and at bedtime);

treatment of duodenal ulcers; abortifacient PHARMACOKINETICS:• A: GIT; M: liver; E: urine (crosses placenta and breast milk->should

not be given to pregnants)

PROSTAGLANDINCONTRAINDICATIONS:• Pregnancy (ensure negative pregnancy test within 2

weeks before treatment) • CAUTIONS: allergy and lactation ADVERSE EFFECTS:• Related to GI effects: nausea, diarrhea, abdominal

pain, flatulence, vomiting, dyspepsia, constipation• Effects on uterus: miscarriages, excessive bleeding,

spotting, cramping, dysmenorrhea and other menstrual disorders

LAXATIVES AND ANTIDIARRHEAL AGENTS• Drugs used to affect the motor activity of the GIT • Can speed up or improve the movement of

intestinal contents along GIT in constipation• Also used to increase the tone of the GIT and to

stimulate motility• Can also be used to decrease movement along the

GIT when rapid movement of contents occur in diarrhea

LAXATIVES• Cathartic drugs, used to speed up the passage of

intestinal contents• Chemical stimulants (irritate the lining of GIT), bulk

stimulants (mechanical stimulants), lubricants (helps to move the contents more smoothly)

LAXATIVES: CHEMICAL STIMULANTS• cascara (generic)-intestinal evacuation; senna

(Senekot)-similar to cascara, OTC; castor oil – old, standby, thorough evacuation, starts at the small intestines throughout the rest of the GIT; frequent use is not desirable -> constipation and blocks absorption of fats

• bisacodil (Dulcolax)- DOC preop; oral or rectal

LAXATIVES: BULK STIMULANTS• rapid-acting, aggressive laxatives -> increase the

motility of GIT by increasing the fluid in the intestinal contents

• magnesium sulfate (Epsom salts)-very potent laxative, total evacuation is needed

• magnesium citrate (Citrate of Magnesia)-often used to stimulate bowel evacuation before GI tests and exams

• magnesium hydroxide (Milk of Magnesia) – milder and slower-acting laxative

• lactulose (Chronulac) – alternative choice for patients with CV problems

LAXATIVES: LUBRICATING LAXATIVES• hemorrhoids, rectal surgery, harmed by straining• glycerin(Sani-Supp) –suppository, no systemic effect• mineral oil (Agoral plain) – oldest; not absorbed and

forms and slippery coat around the contents; frequent use can interfere with absorption of fat-soluble vitamins; leakage and staining can develop

LAXATIVESTHERAPEUTIC ACTIONS:• direct chemical stimulation of GIT• production of bulk or increased fluid in the lumen of the

GIT• lubrication of intestinal bolus -> promote passage USES: • short-term relief of constipation; to prevent straining; to

evacuate bowel; to remove poisons; adjunct in anthelmintic therapy

PHARMACOKINETICS:• - A: GIT; D: castor oil is not used during pregnancy

LAXATIVESCONTRAINDICATIONS:• appendicitis, ulcerative colitis -> can lead to rupture

or exacerbation • CAUTION: pregnancy and lactation ADVERSE EFFECTS:• diarrhea, abdominal cramping, nausea; dizziness,

headache, weakness, sweating, palpitations, flushing• cathartic dependence -> laxative abuse, used over

long periods of time

LAXATIVESCONTRAINDICATIONS:• appendicitis, ulcerative colitis -> can lead to rupture

or exacerbation • CAUTION: pregnancy and lactation ADVERSE EFFECTS:• diarrhea, abdominal cramping, nausea; dizziness,

headache, weakness, sweating, palpitations, flushing

• cathartic dependence

ANTIDIARRHEAL DRUGS• block stimulation of GIT; used for diarrhea• loperamide (Imodium) – direct effect on the muscle

layers of GIT->slow peristalsis and allow increased time for absorption of fluid and electrolytes; slowly absorbed, metabolized by liver, excreted by urine and feces; crosses placenta and breast milk

• opium derivatives-> block nerve impulses within the GIT -> stopping peristalsis and diarrhea (diphenoxylate with atropine [Lomotil])

ANTIDIARRHEAL DRUGSTHERAPEUTIC ACTIONS:• slow the motility of the GIT through direct action on

the lining of the GIT to inhibit local reflexes• through direct action on the muscles of the GIT to

slow activity• actions on the CNS receptors USES:• relief symptoms of acute and chronic diarrhea,

prevention and treatment of traveler’s diarrhea