Pharmacology of drugs affecting GIT

Peptic Ulcer Disease Imbalance between mucosal defensive

factors and aggressive factors Major defensive – mucus and bicarbonate Major aggressive – gastric acid, H. pylori,

nonsteroidal anti-inflammatory drugs, pepsin

Defensive factors Prevent the stomach and duodenum from being

harmed (self-digestion). Mucus – continually secreted, protective effect Bicarb – secreted from endothelial cells,

neutralized hydrogen ions Blood flow – good blood flow helps to maintain

mucosal integrity Prostaglandins – stimulate secretion of bicarb and

mucus and help promote blood flow, suppress secretion of gastric acid

Aggressive factors Helicobacter pylori – gram negative

bacteria, can live in stomach and duodenum

May breakdown mucus layer, inflammatory response to presence of the bacteria may breakdown defenses, also produces urease – forms CO2 and ammonia which are toxic to mucosa

PepsinSmoking

NSAIDS – inhibit the production of prostaglandins

Decrease blood flow, decrease mucus production and bicarb synthesis, promote gastric acid secretion

Gastric Acid – also needs to be present for ulcer to form – activates pepsin and injures mucosa

Nondrug therapy Diet – change in eating pattern, 5-6 small

meals a day Smoking cessation, NSAID and ASA

should be avoided whenever possible, avoid alcohol

Antibacterial drugs Combinations must be used Bismuth – disrupts cell wall of H. pylori,

pepto-bismol Clarithromycin – inhibits protein synthesis Amoxicillin – disrupts cell wall, good

when given with omeprazole Tetracyclin – inhibits protein synthesis Metronidazole – resistance,

Histamine 2-receptor antagonists Suppress secretion of gastric acid (activation of

H2 receptors promotes secretion of gastric acid) Cimetidine - first available, oral, IV, IM May take up to twelve weeks for ulcer to be

healed Therapeutic uses – ulcers, GERD, Zollinger-

ellison syndrome, aspiration pneumonitis, heartburn, indigestion

Proton Pump Inhibitors Suppress secretion of gastric acid Omeprazole – prilosec – prodrug that

converts to active form in parietal cells of stomach – inhibits enzyme that generates gastric acid

Ulcers, GERD, Zollinger-Ellison syndrome May contribute to development of gastric

tumors?

Sucralfate Creates a protective barrier against acid

and pepsin Form sticky gel that coats ulcer portion Given every 6 hours Very few side effects – minimal systemic

absorption

misoprostol Cytotec – prevention of gastric ulcers

caused by long-term NSAID therapy Replacement for endogenous

prostaglandins

Antacids Peptic ulcers and GERD Neutralize acid Dosing – 7 times per day

AlmagelCombined drug which contains gel of aluminum hydroxide, magnesium oxide and D-sorbit

170 ml bottles

Schemes of combined treatment of gastric ulcer

De-nol + amoxycillin

De-nol + metronidazole

Omeprazole + amoxycillin + clarythromycin

De-nol + clarythromycin + metronidazole

De-nol + controlok + amoxycilin + clarythromycin

Laxatives Laxative effect – production of a soft

formed stool over a period of 1 or more days

Catharsis – prompt, fluid evacuation of the bowel, more intense

Function of the colon – water and electrolyte absorption

Bowel evacuation – individual Dietary fiber

Indications for laxative use Pain associated with bowel movements To decrease amount of strain under certain

conditions Evacuate bowel prior to procedures or

examinations Remove poisons To relieve constipation caused by

pregnancy or drugs

Just because laxatives are available without a prescription doesn't mean that they're without risk.

Warning: Use of stimulant laxatives over a long period may lead to dependence and might permanently damage intestine and colon

Classifications I – osmotic (high doses) II – osmotic (low doses), stimulant except

castor oil – most frequently abused III – bulk-forming, surfactant

Bulk-forming Identical to fiber – soften fecal mass,

increasing bulk Temporary treatment of constipation,

preferred for patients with inflammatory bowel diseases

May help with diarrhea

Adverse reactions Not absorbed – no systemic effects Must take with sufficient water Intestinal, esophageal obstruction Metamucil, citrucel

Surfactant laxatives Bisacodyl, castor oil Stimulate intestinal motility Increase water and electrolytes in intestinal

lumen Produce stool within 6-12 hours

Bisakodil

Guttalax

Miscellaneous laxatives Mineral oil Lactulose Glycerin suppository Polyethylene glycol-electrolyte solutions

Laxative abuse Most common cause of constipation Teaching

Choleretics of plant origin

Stigma of cornStigma of corn

Common immortelleCommon immortelle

Dog-roseDog-rose

Tocopherole acetate (Tocopheroli acetas)Vitamin E is produced in many forms: 5 %, 10 % and 30 % oil solution in 10, 20 and 50 ml bottles; elastic

capsules with 0,1 and 0,2 ml of 50 % solution in oil; ampoules with 1 ml of 5 %, 10 % and 30 % oil solutions.

Carsil Legalon

Mechanism of action of legalon

Essentiale Is produced in 5 ml ampoules and in capsules

Lipostabil

Pancreatin (Panсreatinum) Is produced in 0,25 g and 0,5 g dragee (tablets).

Panzynorm forte

Festal, Enzistal, Mezym-forte

No-spa, nicospan

Baralgin

Bil-berries St. John’s wort

Pepper mint Chamomile