Gastrointestinal Drugs

Acid-Related Pathophysiology

The stomach secretes: Hydrochloric acid (HCl) :- digestion and also serves as a barrier to infection

Bicarbonate :- natural mechanism to prevent hyperacidity

Pepsinogen :- enzymatic precursor to pepsin, an enzyme that digests dietary proteins

Intrinsic factor:- glycoprotein that facilitates gastric absorption of vitamin B12

Mucus:- protects the stomach lining from both HCl and digestive enzymes

Prostaglandins (cytoprotective):- serve a variety of anti – inflammatory and protective functions

Glands of the Stomach

Cardiac

Pyloric

Gastric*

* The cells of the gastric gland are the largest in number and of primary importance when discussing acid control

* gastric glands play the most significant role in acid-related disorders.

Cells of the Gastric Gland

Parietal cells

Produce and secrete HCl

Primary site of action for many acid-controller drugs

Hydrochloric Acid

Secreted by the parietal cells when stimulated by food

Maintains stomach at pH of 1 to 4

Secretion also stimulated by: Large fatty meals Excessive amounts of alcohol Emotional stress Caffeine and chocolate

Chief cells

Secrete pepsinogen, a proenzyme

Pepsinogen becomes pepsin when activated by exposure to acid

Pepsin breaks down proteins (proteolytic)

Mucoid cells

Mucus-secreting cells (surface epithelial cells)

Provide a protective mucous coat

Protect against self-digestion by HCl

D- Cell :

Release somatostatin to inhibit HCL secretion.

Acid-Related Diseases

Caused by imbalance of the three cells of the gastric gland and their secretions

Most common: hyperacidity

Patient report symptoms of overproduction of HCl by the parietal cells as indigestion, heartburn, acid stomach

PUD: peptic ulcer disease GERD: gastroesophageal reflux disease Helicobacter pylori (H. pylori)

Bacteria found in GI tract of 90% of patients with duodenal ulcers, and 70% of those with gastric ulcers

Combination therapy is used most often to eradicate H. pylori

Drugs for peptic ulcer

1. Reduction of gastric acid secretion :

A . H2 Antagonists:- Cimetidine ,Famotidine, Ranitidine ,Roxatidine

B. Proton pump inhibitor: - omeprazole, Lansoprazole, Pantoprazole, Rabeprazole, Esomeprazole

C. Anticholinergics : Pirenzepine, Atropine, Propantheline, Oxyphenonium

D. Prostaglandin analogue : Misoprostol

2. Neutralization of gastric acid (Antacid)

A. Systemic : Sodium bicarbonate

B. Nonsystemic : Magnesium hydroxide, Mag. Trisilicate, Aluminium hydroxide gel, Calcium carbonate

3. Ulcer protectives : Sucralfate, Colloidal bismuth subcitrate (CBS)

4. Anti – H. pylori drugs : Amoxicillin, Clarithromycin, Metronidazole, Tinidazole, tetracycline

Types of Acid-Controlling Agents

Antacids (to treat dyspepsia).

H2 antagonists

Proton pump inhibitors

Antacids

A. Systemic :

• Sodium bicarbonate.

( It has a rapid onset and short duration of action since it is highly soluble, and offers rapid relief of pain.)

B. Nonsystemic :

• Magnesium hydroxide, • Mag. Trisilicate,• Aluminium hydroxide,• Calcium carbonate.

The rationale for the use of antacids in peptic ulcer disease lies in the assumption that buffering of H+ in the stomach permits healing.

The buffering agents in the various antacid preparations consist of combinations of ingredients that include sodium bicarbonate, calcium carbonate, magnesium hydroxide, and aluminum hydroxide.

Antacids DO NOT prevent the over-production of acid

Antacids DO neutralize the acid once it’s in the stomach

Quick onset of relief but last for a short duration

Antacids

Given orally 1-3 hrs after meals and bedtime

Single dose provides 120mEq neutralizing capacity--equivalent to one dose of an H2RA

Mg+2 based preparations increase motility Diarrhea

Al+3 based preparations relax smooth muscle Constipation

Carbonate-containing preparations release CO2 Belching, nausea, distension, and flatulence.

Antacids: Drug Effects

Reduction of pain associated with acid-related disorders

Raising gastric pH 1 point (1.3 to 2.3) neutralizes 90% of the gastric acid

Reducing acidity reduces pain

Aluminum Salts

Forms: carbonate, hydroxide

Have constipating effects

Often used with magnesium to counteract constipation

Examples Aluminum carbonate Hydroxide salt Combination products (aluminum and magnesium)

Magnesium Salts

Forms: carbonate, hydroxide, oxide, trisilicate

Commonly cause diarrhea; usually used with other agents to counteract this effect

Dangerous when used with renal failure —the failing kidney cannot excrete extra magnesium, resulting in hypermagnesemia

Examples Hydroxide salt: magnesium hydroxide (MO

M)

Carbonate salt

Combination products aluminum and magnesium

Calcium Salts

Forms: many, but carbonate is most common

May cause constipation

Their use may result in kidney stones

Long duration of acid action may cause increased gastric acid secretion (hyperacidity rebound)

Sodium Bicarbonate

Highly soluble

Buffers the acidic properties of HCl

Quick onset, but short duration

May cause metabolic alkalosis

Sodium content may cause problems in patients with HF, hypertension, or renal insufficiency (fluid retention)

Antacids and Antiflatulents

Antiflatulents: used to relieve the painful symptoms associated with gas

Several agents are used to bind or alter intestinal gas and are often added to antacid combination products.

Antiflatulents

Simethicone

Antacids: Side Effects

Minimal, and depend on the compound used

Aluminum and calcium Constipation

Magnesium Diarrhea

Calcium carbonate Produces gas and belching; often combined with simethico

ne

Antacids: Drug Interactions

Absorption of other drugs to antacids Reduces the ability of the other drug to be absorbe

d into the body

Chelation Produces insoluble complexes Result: reduced drug absorption

Drugs less absorbed when taking antacids include:

Tetracycline, Antifungals Ciprofloxacin Propranolol Captopril

Antacids can also potentiate (make stronger) the following drugs:

Valproic acid: Used to treat epilepsy, bipolar disease and migraines.

Quinidine: cardiac drug used to treat certain heart arrhythmias.

Levodopa: Anti-Parkinson’s drug.

Most medications should be given 1 to 2 hours after giving an antacid

Antacids may cause premature dissolving of enteric-coated medications, resulting in stomach upset.

Be sure that chewable tablets are chewed thoroughly, and liquid forms are shaken well before giving

Caffeine, alcohol, spices may aggravate the underlying GI condition

To be continue…..