Drugs which Affect the Functions of the Gastrointestinal Tract.

Drugs which Affect the Functions of the

Gastrointestinal Tract.

Drugs which Affect the Functions of the Gastrointestinal

Tract.• Secretion

stimulants

inhibitors

• Motility

stimulants

inhibitors

Drugs which Affect the Secretion of the Gastrointestinal Tract.

• Stimulants• drugs which increase

the appetite:bitter tincture absinthium tincture insulin aminazinum, amitriptyline, lithium carbonate

• Inhibitors of the appetite-anorexigenous medications:

1) drugs which affect the catecholaminergic system (they excite the CNS) —phepranone, desopimone, sibutramine; mazindol,

2) drugs which affect the serotoninergic system (they inhibit the CNS) –fenfluramine, dexfenfluramine.

Mechanisms of action of apetite affecting drugs

• Stimulants –

Irritation of the receptors of the oral cavity leads to reflex excitation of the centre of hunger located in lateral nuclei of hypothalamus

• Inhibitors –

stimulation of the saturation centre of CNS

Drugs affecting secretion

of the stomach

• 1) drugs which increase the secretion of gastric glands:

• pentagastrin and histamine - are used fordiagnostic purposes. In the case of functional insufficiency of gastric glands these drugs increase the secretion and in organic diseases of the gastric mucous membrane the secretion is not increased.

Drugs for substitution (replacing) therapy

• In the case of organic insufficiency of gastric glands replacing therapy is used:

• natural gastric juice, • pepsin, • diluted HCl, • acidin-pepsin, • Abomin• Festal• Enzystal

2) Gastric antisecretory drugs.1) proton pump inhibitors;

• 2) blockers of H2-histamine receptors;

• 3) M-cholinolytics;• 4) prostaglandin

derivatives (misoprostol);

• 5) ganglion blockers;• 6) blockers of gastrine-

cholecystokinin-B (G-CCK-B) receptors.

• 7) Antacids

Proton pump inhibitors• a) 1st generation agents omeprazole, • pantoprazole, lansoprazole; • b) 2"d generation agents rabeprazole,

esomeprazole. • The mechanism of their action is reversible

inhibition of the proton pump (H*,Na- K*- ATPase) of gastric parietal cells. The function of this pump is secretion of H* ions into the lumen of the stomach instead of K*-ions.

• The inhibition of the proton pump causes the decrease of acid secreting activity of parietal cells. These drugs are active only in acid environment, that provides the selectivity of their action directly on Parietal cells.

Blockers of H2-histamine receptors

• ranitidine, • famotidine, • nizatidine. • The mechanism of these drugs' action is

blockade of H2-histamine receptors located in

the cells of gastric mucous membrane, that prevents the interaction of them with

histamine and leads to decrease of the secretion of hydrochloric acid and less — of

pepsin.

M-cholinolytics• Non-selective• Atropini sulfas• Belladonna drugs, • Plathyphyllin, • metacinium -decrease the influence of nervus

vagus upon the gastric mucous membrane, that leads to reduction of the gastric secretion. Selective M1-blocker

• pirenzepine: inhibits the gastric secretion and increases the stability of the gastric mucous membrane to action of various irritants (gastroprotective action).

Prostaglandin derivatives • Misoprostol inhibits the

secretion of hydrochloric acid due to stimulation of prostaglandin receptors of the gastric mucosa cells. It also increases production of bicarbonates and mucus and exerts gastroprotective action.

Misoprostol• Misoprostol is a drug that

is FDA-approved in the United States for the prevention of NSAID-induced gastric ulcers.

• It is also used (and approved in other countries) to induce labor and as an abortifacient.

ANTACIDS• The mechanism

of action: neutralization of hydrochloric acid, because all drugs

of this qroup belong to weak bases.

• 1) agents which produce carbon dioxide: natrium hydrocarbonate, calcium carbonate

• 2) agents which do not produce carbon dioxide (magnesium hydroxide, magnesium trisilicate, aluminium hydroxide)

ANTACIDS (1st group)• Owing to production of carbon

dioxide these drugs lead to irritation of the gastric mucous membrane and to the development of repeated wave of gastric juice secretion.

• Natrium hydrocarbonate has high neutralizing capacity. It exerts fast but short action, it's well soluble in water, highly absorbable, that may leads to development of systemic alkalosis. Calcium carbonate has moderate neutralizing capacity, action develops fast.

ANTACIDS (2nd group)• Aluminium hydroxide,

magnesium hydroxide and magnesium trisilicate by the antacid activity are a little more effective than sodium hydrocarbonate. Their action develops gradually, but lasts long. Magnesium hydroxide may cause slight laxative action.

Combined drugs • Almagel,

• Phosphalugel,

• Maalox,

• Renni,

• Alumag,

• Gelusil,

• Gastal.

Mucosal protective agents (gastroprotectors)

• 1) agents which create mechanical protection of gastric mucosa - sucralfate, bismuth subsalicylate, De-nol "Potassium dicitrato bismuthate”

• 2) agents which increase the proective properties of mucous barrier and the stability of gastric mucosa to the action of damaqe factors — carbenoxolone, misoprostol

Drugs which exert influence upon the gastric motility.

• 1) agents which promote the gastric motility (prokinetic agents): metoclopramide,

• cisapride,

• domperidone

Agents which promote the gastric motility Metoclopramide and cisapride

have cholinomimetic properties. Both drugs apparently promote release of acetylcholine from cholinergic neurones in the enteric nervous system. In addition to it, metoclopramide blocks D2-dopamine and 5-HT3-serotonin receptors of the CNS, that explains its central effects, including the antiemetic one.

2) Agents which inhibit the gastric motility.

• M-cholinoblockers, • ganglion blockers, • both M-cholino— and

ganlioblockers (buscopane [hyoscine butylbromide], pro-banthine),

• myotropic spasmolytics— papaverine, drotaverine, mebeverine, bencyclane

• calcium channel blockers — pinaverium bromide.

Emetic drugs• 1) agents with direct action :

apomorphine. The mechanism of its action is stimulation of dopamine receptors of the trigger zone.

• 2) agents with indirect (reflex) action: copper sulfate, zinc sulfate and drugs which contain herb of thermopsis and root of ipecacuana. In peroral introduction these drugs irritate stomach receptors, that leads to reflex rise of vomiting.

Antiemetic drugs

• M-cholinoblockers• prokinetic agents• Blockers of 5H-T3-serotonin-

receptors: ondansetron, tropisetron

• D2-dopamino-receptors blockers: Aethaperasinum, Aminasinum, THIETHYLPERAZINE

• Sedatives, tranquilisers, barbiturates

Drugs which affect the intestinal motility

• 1) drugs which decrease the intestinal tone and peristalsis M-cholinolytics (atropine, plathyphyllin, metacinium), ganglion blockers (benzohexonium, pirilenum), myotropic spasmolytics (papaverine, drotaverine, etc.), opium preparations and a phenylpiperidine derivative loperamide.

Loperamide (imodium)

• by its chemical structure has a resemblance to some opioid analgesics. The mechanism of its action is stimulation of u-receptors of the intestine, that leads to inhibition of peristalsis. These drugs are used in spastic colitis, acute and chronic diarrhea

Laxative drugs• 1) bulking agents: saline

laxatives (magnesium sulfate, natrium sulfate), lactulose, sorbitol

• 2) intestinal mucosa irritants: • a) agents of plant origin —

castor oil, drugs which contain anthraquinone glycosides;

• b) synthetic drugs: isaphenine, bisacodyl, natrium picosulfate, phenolphthalein

Laxative drugs• 1) drugs which exert strong

action (they usually act upon the whole intestine) — saline laxatives, castor oil

• 2) drugs which exert moderate action (they act mainly upon the large intestine and partially upon the small one) — synthetic drugs

• 3) drugs which exert slight action (they act upon the large intestine mainly) — anthraquinone glycosides, lactulose, sorbitol,liquid paraffin, docusate.