Pharma - 4th Asessment - Git Lecture Slides - Ii - 27 Jan 2007

GASTROINTESTINAL DRUGS II Dr. Mariam Yousif PHARMACOLOGY & TOXICOLOGY DEPARTMENT 28/1/2007

OBJECTIVES I. Peptic ulcer * Definition & Pathophysiology * Therapeutic strategies * Drug treatment A. Antimicrobial therapy (treatment of H. pylori) B. Drugs that inhibit or neutralize gastric acid secretion 1. Proton-pump inhibitors (PPI) 2. H2-receptor antagonists 3. Antacids C. Cytoprotective agents

II. Antiemetic Drugs III. Laxatives (Purgatives) 1. Bulk Laxatives 2. Osmotic Laxatives 3. Faecal Softeners 4. Stimulant Purgatives IV. Antidiarrhoeal agents 1. Antimotility agents 2. Adsorbents

II.ANTIEMETIC DRUGS  Anti-emetic drugs are of particular importance as an adjunct to cancer chemotherapy to combat the nausea and vomiting produced by many cytotoxic drugs.  Also useful to treat morning sickness of pregnancy and motion sickness .

Clinical uses of anti-emetic drugs  H1-receptor antagonists (Cinnarizine, Cyclizine) Motion sickness.  Muscarinic receptor antagonists (Hyoscine) Motion sickness.  5-HT3- receptor antagonists (Ondansetron) Cytotoxic anticancer drugs.  Dopamine receptor antagonists (Metoclopramide) Vomiting caused by cytotoxic drugs and GIT disorders.  Cannabinoids (Nabilone) Vomiting caused by cytotoxic anticancer drugs.

.1H1 -Receptor antagonists (e.g. Cyclizine, Cinnarizine)  Effective in motion sickness.  Their peak anti-emetic effect occurs about 4 hours after ingestion.

.2Muscarinic-receptor antagonists (e.g. Hyoscine)  Hyoscine is the most potent agent available for the prevention of motion sickness.  Its anti-emetic action peaks 1-2 hours after ingestion.

.3Hydroxytryptamine (5-HT-53 )-Receptor Antagonists (e.g. Ondansetron) # Effective in preventing and treating vomiting caused by cytotoxic drugs. # Drug of choice in treatment of post operative nausea and vomiting (PONV)

.4Dopamine receptor antagonists (e.g. Metoclopramide)

.5Cannabinoids (e.g. Nabilone)

.6Phenothiazines (e.g. Chlorpromazine)

(III. LAXATIVES (PURGATIVES Used to accelerate the passage of food through the GIT. Before prescribing laxatives it is important to be sure that the patient is constipated and that the constipation is not secondary to an underlying undiagnosed complaint.

Constipation is managed by dietary improvement, eliminating any drugs that can cause constipation, excluding the presence of underlying pathology, and laxatives.

- Prophylactic therapy of constipation. - Abuse of laxatives. - Clinical uses of laxatives.

The transit of food through the intestine may be accelerated by several methods # Increasing the volume of non-absorbable solid residue with bulk laxatives. # Increasing water content with osmotic laxatives. # Altering the consistency of the faeces with faecal softeners. # Increasing the GIT motility and secretion with stimulant purgatives.

.1Bulk laxatives (e.g. Methylcellulose & bran) -Polysaccharide polymers not broken down by normal processes of digestion. -Act due to their capacity to retain water in the gut lumen and promote peristalsis. -Adequate fluid intake must be maintained to avoid intestinal obstruction. Take several days to work but have no serious side effects.

.2Osmotic laxatives Consist of poorly absorbed solutes, the saline purgatives and lactulose. Act by retaining fluid in the bowel by osmosis which accelerates the transfer of the gut contents through the small intestine and results in large volume entering the colon. This causes distension which leads to purgation.

Saline purgatives (saline cathartics) e.g. Magnesium sulphate and magnesium hydroxide -Insoluble salts, remain in the lumen, hold water by osmosis, increase the volume of the faeces. Magnesium salts are useful for rapid bowel evacuation. -Phosphate enemas are useful in bowel clearance before radiology, endoscopy and surgery. Lactulose A semi-synthetic disaccharide of fructose & galactose. Poorly absorbed. Takes 2-3 days to act.

.3Faecal softeners # Docusate sodium is a surface-active compound (surfactant laxative), acts as an emulsifying or wetting agent to produce softer faeces. # Oral preparations act within 1-2 days. # Useful in the management of haemorrhoids and anal fissure. # It is also a weak stimulant laxative.

.4Stimulant purgatives (e.g. Senna, bisacodyl)  Stimulate colonic activity & increase peristalsis (by stimulating enteric nerves), resulting in defecation.  A single dose of senna produces a laxative action within 8 hours.

.4Stimulant purgatives

 Bisacodyl can be given orally, but usually administered as a suppository, causes stimulation of the rectal mucosa, results in peristaltic action and defaecation in 15-30 minutes.  Can cause abdominal cramps.

Mechanism of action of laxatives: Bulk laxatives absorb water and on swelling slowly distend the colon and increase peristaltic motility; osmotic laxatives enhance peristalsis by osmotically increasing the bowel fluid volume; stimulant (irritant) laxatives stimulate the enteric nervous system; fecal softeners increase intestinal fluid secretion.

IV. ANTIDIARRHOEAL AGENTS

 Diarrhoea involves both an increase in the motility of the gastrointestinal tract, along with increased secretion and decreased absorption of fluid.

Three approaches to the treatment Maintenance of fluid and electrolyte balance .(Oral rehydration therapy (ORT

The use of anti-infective agents Usually not necessary, only severe cases may require anti.bacterial therapy

The use of non-antimicrobial antidiarrhoeal agents .Modify the fluid and electrolyte transport

Maintenance of fluid and electrolyte balance ORT will not immediately reduce the volume of diarrhoea, but absorption of the administered electrolytes leads to correction of the electrolyte imbalance, while the body .systems eliminate the pathogens

.(There are several oral formulations (in powder form

:The WHO ORT recommended formulation contains .NaCl, KCl, NaCitrate, Chloride and Glucose

The use of non-antimicrobial antidiarrhoeal agents 1.Antimotility agents  The main pharmacological agents that decrease motility are opiates; e.g. loperamide, diphenoxylate and codeine.  Loperamide is preferred because it penetrates poorly into the CNS, can produce antidiarrhoeal effects at doses that produce fewer central side effects.  Loperamide has a relatively selective action on the gut, acts on µ opiate receptors in the GIT.

 The constipating effect is due to a decrease in the propulsive movements of the tract. The increase in the transit time of the intestinal contents allows for increased absorption of water, the colonic contents therefore become firmer.

 Unwanted effects occur with chronic use; include constipation, abdominal cramps, drowsiness.

.2Adsorbents Main preparations used: kaolin, pectin and magnesium aluminium silicate. # Insoluble substances, not absorbed. Finely divided particles with adsorptive properties because of the high surface area. # Act by adsorbing microorganisms or toxins, or by coating and protecting the intestinal mucosa. # Kaolin has a bulking action, improving stool consistency.

Drug List Cyclizine Hyoscine Lactulose Docusate sodium Senna Bisacodyl Loperamide Codeine Kaolin

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