SYSTEMIC
PHARMACOLOGY
Dr. Kabiru Abubakar
(B. Pharm., MSc., PhD)
Associate Professor (Pharmacology)
American International University of West Africa
Gastrointestinal & Biliary System
GASTROINTESTINAL TRACT (GIT) PHARMACOLOGY
• Gastro intestinal (GI) disorders account for minor, day to
day complains as well as major health problems.
• In most cases, dietary interventions can improve
symptoms that are caused, for example, by poor eating
habits, but if these measures are not successful,
pharmacological interventions have to be employed.
• Major diseases of the GIT includes but not limited to
Peptic ulcer disease (PUD), diarrhoea and constipation .
GASTROINTESTINAL TRACT (GIT) PHARMACOLOGY
• Diarrhoeal disease causes fluid and electrolyte imbalance,
and are usually treated with correction of the imbalance by
oral or intravenous fluid and electrolyte replacement
therapy.
• Constipation on the other hand is usually treated by use of
Laxatives or Purgatives
• Laxatives include Al, Mg and sodium salts, while
Purgatives include mineral oils such as Liquid paraffin,
PEPTIC ULCER DISEASE (PUD)
• The term peptic ulcer refers to any ulcer in an area where the mucosa
is bathed with HCL and pepsin of gastric juice (ie the stomach and
upper part of the duodenum).
• Damage to the mucosa and deeper tissue exposed to acid and pepsin is
known as peptic ulcer.
• Drugs that are effective in peptic ulcer either reduce gastric acid
secretion or increase mucosal resistance to acid-pepsin attack.
• Peptic ulcers however healed will always reoccur without continuous
administration of drugs.
Causes of Ulcer
• Causes of Ulcer:
• H. pylori,
• NSAID use,
• Stress
• Chronic infection of the stomach with Helicobacteria pylori is an important
aetiological factor in peptic ulcer formation
• H. pylori is implicated in about 95% of duodenal ulcers and 70% of stomach
ulcers
• H. pylori infection causes hypergastrinaemia, which in turn causes
Classification of the drugs used in peptic ulcer
Drugs that inhibit gastric acid secretion
1. Proton pump inhibitors: omeprazole, esomeprazole,
lansoprazole, pantoprazole, rabeprazole.
2. H2-receptor antagonists: cimetidine, ranitidine,
famotidine, roxatidine,nizatidine
3. Antimuscarinic agents (anticholinergics): blocks the
Muscarinic (M1 cholinergic receptors).They include
Pirenzepine, Telenzepine
4. Prostaglandin analogs: misoprostol, enprostil.
Anti-peptic ulcer drugs
• Ulcer protective
sucralfate, and bismuth subcitrate (CBS)
Drugs that neutralize gastric acid (antacids)
a) Systemic antacids: sodium bicarbonate and sodium citrate.
b) Non systemic antacids: magnesium hydroxide, magnesium
trisilicate, aluminum hydroxide, and calcium carbonate.
Anti-peptic ulcer drug
• Anti- H. pylori drugs
• Amoxicillin, tetracycline, clarithromycin,
metronidazole, tinidazole, bismuth subsalicylate,
H2-antagonists and PPIs.
Proton pump inhibitors
• Proton pump, K+-ATPase membrane bound enzyme play an
important role in the final step of gastric acid secretion (basal
and stimulated).
• Omeprazole is the prototype drug: these are prodrugs and
activated to sulfonamide at acidic pH. Activated form binds
covalently with SH group of H+ pump and irreversibly
inactivates it.
• PPIs administered orally 30 min. before meal. Half life short
(1.5 hr), acid secretion suppressed for up to 24 hr.
Proton Pump Inhibitors
• Indications: Single daily administration can inhibit acid secretion 100%
• Effective in Reflux, duodenal and gastric ulcer, Multiple endocrine
neoplasia (MEN) and Zollinger-Ellison syndrome.
• S/E Well tolerated but have been reported to cause diarhea
H2-Receptor antagonists
• Mechanism of action: Competitively block H 2
receptors on parietal cells; Suppress all phases of
acid secretion.
• Most effective in suppressing nocturnal acid
• Secretion and less potent than PPIs.
• S/E: Reversible gynaecomastia, elevated serum
prolactin levels and altered oestrogen level in men.
Inhibition of cytochrome P450 metabolism.
Prostaglandin analogues
• Misoprostol effective orally for prevention and treatment of
NSAID-induced duodenal and gastric ulcers.
• Misoprostol is a Prostaglandin E1 analogue that stimulates
production of mucus and other protective factors such as
bicarbonate.
• Common side effects:
• Diarrhoea and abdominal cramps.
• Containdicated in pregnancy
Ulcer protective
• Sucralfate : it is complex aluminum hydroxide and
sulphated sucrose. Form Physical barrier against acid-
pepsin.
• Polymerized to form sticky gel that adheres to the ulcer
base and protects it.
• Warning: Sucralfate should not be taken simultaneously
with PPI or H2 blockers because the drug needs an acid
PH for its action.
Bismuth containing preparation
• Bismuth salicylates and colloidal Bismuth subcitrate.
• Moa similar to sucralfate, React with protein in the base of
ulcer and protect it from peptic digestion.
• Stimulates secretion of PGE2, mucus and bicarbonate.
• 98% ulcer healing reported when combined with Anti-microbial
agents due to increase effects against H. pylori.
Drugs that neutralized gastric acid
Antacids: Antacids are bases that raises the gastric PH by neutralizing gastric
acids, they provide effective treatment for many dyspepsia and symptomatic
relief for many peptic ulcers and oesophageal reflux.
Ideal antacids
1. Insoluble and neutralize acid
2. Should not liberate CO2
3. Non-absorbable
4. Should not disturb acid-base balance
Types of antacids
Systemic: Sodium bicarbonate and Sodium citrate
Non systemic: magnesium hydroxide, magnesium trisilicate, aluminum hydroxide
gel and calcium carbonate
Anti H. pylori agents
• Gram negative, rod shaped bacteria associated with gastritis, duodenal ulcer,
gastric ulcer and gastric carcinoma.
• Cause mucosal inflammation
• Ammonia produced by urease activity damage cells.
• Combination therapy (Use of multiple antibiotics for synergism)
To prevent or delay development of resistant organism.
Prevent relapse
Promote rapid ulcer healing
Eradicate H. pylori infection
• Treatment for 1 or 2 weeks required
Triple therapy x 14 days
Lansoprazole 30 mg BD+ clarithromycin 500 mg BD + Amoxicillin 1 g BD
Quadruple therapy x 14 days
Lansoprazole 30 mg BD + Bismuth subsalicylate 525 mg QID +
Tetracycline 500 mg QID + Metronidazole 500 TDS
After completion of above regimen, PPIs should be continued for six
more weeks.
ANTI EMETICS
• They include drugs like:
• Antihistamines- H1 blockers such as Diphenhydramine
• Phenothiazines- Promethazine, prochloperazine
• 5-HT3 inhibitors- ondansetron
• INDICATIONS: Any condition that is inducing emesis such as
chemotherapy, and GI infection.
LAXATIVES
• Agents use to soften stool and relieve indigestion, classified based on their MOA
as
• 1. Bulk Forming; They are nonabsorbable agents that increase water retention
and stool bulk, which distends the bowel and increase peristalsis.
• They are normally insoluble during the digestive process such as:
• Hydrophilic colloids (from indigestible parts of fruits and vegetables), Agar,
Methycellulose, Bran, Lactulose, sorbitol and saline cathartics (Magnesium
citrate and Magnesium hydroxide)
• 2. Stimulant: Castor oil, Bisacodyl(Dulcolax), Senna and Phenophtalein
Stool softeners
• These agents emulsifies the stool and make it soft and easy to pass
• Examples include:
• Mineral oil (glycerin)
• Suppositories and detergent eg Dioctyl sodium sulfosuccinate
(Docusate)
