Gastrointestinal Drugs

Disease
Drugs for Acid-Peptic Disorders
of GIT
Eradication of Helicobacter pylori (Antibiotic/Inhibition of
Acid)
Proton Pump Inhibitors (Omeprazole)
Histamine (H2) Receptor Antagonists (Cimetidine,
Ranitidine)
Anticholinergics
Prostaglandins (Misoprostol)
Antacids
Mucoprotective Drugs (Sucralfate)
Emesis and anti emesis
Drugs for Motility Disorders
Prokinetics (Metoclopramide)
Laxatives (Bran)
Antidiarrheal (Opioids)
 Pathogenesis of peptic ulcer
1. Aggressive factors↑
Helicobacter Pylori ( H. Pylori)
gastric acid and pepsin
2. Defensive factors↓
mucus-bicarbonate barrier
prostaglandins
NSAIDS
Classification of drugs :
i. Antacids
ii. Agents decreasing secretion of gastric acid
iii. Agents protecting mucosal barrier
iv. Agents eradicating helicobacter pylori
 Ⅰ 　 Antacids
weak bases : Mg(OH)2 , Al(OH)3 ,
CaCO3 , NaHCO3
actions:
1) prevent injury from H+
2) neutralize gastric acid → reduce gastric acidity→ reduce
peptic activity
3) protect face of ulcer( Mg2SiO8 Al(OH)3 )
Ⅱ 　 Agents reducing secretion of gastric acid
Regulation of gastric acid secretion

Proglumide
Drugs reducing secretion of gastric acid
(1) H2-receptor antagonists
(2) Antimuscarinic agents
(3) Inhibitors of the proton pump
(4) gastrin-receptor antagonists
 H2-R antagonists

Cimetidine, Ranitidine, Famotidine , Nizatidine

[Actions]
Competitively block the binding of histamine to H2 receptor.
Completely inhibit gastric acid secretion induced by histamine.
characteristics
Regulation of gastric acid secretion

Proglumide
 Inhibitors of the proton pump
Omeprazole, lansoprazole, pantoprazole

 Inhibits H+ being transported to gastric lumen through

inhibiting the proton pump.
 Potent and long-lasting effect: Can inhibit over 95% of gastric
acid secretion.
 Also inhibit release of peptin and H.P
Regulation of gastric acid secretion

Proglumide
 Antimuscarinic agents
Muscarinic receptor stimulation increase gastrointestinal motility
and secretion.
So cholinergic antagonists can be used as adjuncts in the
management of peptic ulcer disease and Zollinger-Ellison
syndrome, particularly in patients refractory to standard
therapies.
Regulation of gastric acid secretion

Proglumide
 Antimuscarinic agents
In contrast to the classic anticholinergics, the relatively specific
M1-receptor antagonist, Pirenzepine is a good choice as an anti-
secretory agent.
Because it suppresses basal and stimulated gastric acid secretion
at doses having a minimal effect on other organs (salivary glands,
the heart and eye.)
Ⅲ Agents protecting mucosal barrier

(1)Prostaglandins
(2)Mucosal protective agents
Prostaglandins
• prostaglandins E2 and I2, produced by the gastric mucosa,
inhibit secretion of gastric acid and stimulate secretion of
mucus and bicarbonate (cytoprotective effect) .
• A deficiency of prostaglandins is thought to be involved in the
pathogenesis of peptic ulcers.
 Misoprostol: a stable analog of PGE2

(1) inhibits secretion of gastric acid and stimulate secretion of

mucus and bicarbonate.
(2) dilate blood vessel of mucous membrane.
(3) currently the only agent approved for prevention of gastric
ulcers induced by NSAIDs.
(4)less effective than H2-receptor antagonists for acute treatment
of peptic ulcers.
(5)produces uterine contractions and is contraindicated during
pregnancy.
 Mucosal protective agents
These compounds, known as cytoprotective ones , have several
actions that enhance mucosal protection mechanisms, thereby
preventing mucosal injury, reducing inflammation and healing
existing ulcers.
 Mucosal protective agents
Sucralfate
1)In water or acidic solutions it forms a viscous, tenacious paste
that binds selectively to ulcers or erosions for up to 6 hours.
2)Also stimulates prostaglandin release and mucus and
bicarbonate output.
3)Promote effects of growth factors
4)Inhibit H.P
 Mucosal protective agents
colloidal bismuth sub citrate
1) binds to an ulcer crater, coating it and protecting it from
acid and pepsin.
2) Inhibits the activity of pepsin
3) increases mucous secretion
4) increase prostaglandin synthesis
5) helps to eradicate H. pylori
 Antimicrobial agents
Optimal therapy of patients with peptic ulcer disease who are
infected with H.Pylori requires antimicrobial treatment.
Eradication of H.Pylori results in rapid healing of active peptic
ulcers
and low recurrence rates. Metronidazole, tetracycline, amoxiciliin,
etc. Often combined with other drugs.
 Prokinetic Drugs
Substances which enhance transit of materials through the GI tract;
Increase neuromuscular transmission
 Prokinetic Drugs - Cholinomimetics
(Carbachol; Bethanechol)
Actions
Muscarinic receptor agonist
Increase force of contraction
Little effect on intestinal transit
Adverse Side-effects
Cardiovascular (hypotension, bradycardia)
Urinary Bladder (increase voiding press., decrease capacity)
Exocrine Glands (increase secretions)
Eye (pupil constriction and loss of accommodation)
 Prokinetic Drugs – Metoclopramide
Metoclopramide is an antiemetic and improves gastric emptying –
indirectly releases acetylcholine

Actions
Dopamine D2 receptor
antagonist
5-HT4 receptor agonist
Ganglionic stimulant
 Prokinetic Drugs – Domperidone
Domperidone is an antiemetic and improves gastric emptying
• Actions
Dopamine receptor
antagonist
Ganglionic stimulant
 Prokinetic Drugs - Additional
Compounds
Erythromycin
Motilin agonist
Antibacterial
Diarrhea
Motilin (22 amino acid active peptide)
Agonist for the Motilin receptor
Stimulates gastric emptying
 Constipation

Usually effectively treated with dietary modification.

Only if this fails should laxatives be used.
Therapy:
1. Bulking agents
2. Osmotic laxatives
3. Stimulant drugs
4. Stool softners
Laxatives
 Bulk Laxatives
Psyllium
Bran
Methylcellulose
 Cont…
Saline and Osmotic Laxatives
Nondigestible sugars and alcohols
Lactulose (broken down by bacteria to acetic and lactic acid,
which causes the osmotic effect)
Salts
Milk of Magnesia (Mg(OH)2)
Epsom Salt (MgSO4)
Glauber’s Salt (Na2SO4)
Sodium Phosphates (used as enema)
Sodium Citrate (used as enema)
Polyethylene glycol
Stool Softners - Emollients
Docusate sodium (surfactant and stimulant)
Liquid Paraffin (oral solution)
Glycerin suppositories
 Irritant/Stimulant Laxatives-
Cathartics
-Increases intestinal motility
-Irritate the GI mucosa and pull water into the lumen
-Indicated for severe constipation where more rapid effect is required (6
8 hours)

•Castor Oil - From the Castor Bean

•Senna - Plant derivative
•Bisacodyl
•Lubiprostone -PGE1 derivative that stimulates chloride channels,
producing chloride rich secretions
Diarrhea is Associated with Excessive
Flow Through the Lumen of the Bowel
Normal Diarrhea

Net fluid
Net fluid
absorption
accumulation

Increased
Normal mixing propulsive
and propulsive contractions
contractions
Decreased mixing
contractions

Normal Flow Increased Flow

 The Goals of Antidiarrheal Therapy
are to Correct the Pathophysiology
Goals:
 Eliminate cause;
 Decrease fluid accumulation in lumen;
 Decrease propulsive contractions;
 Increase mixing contractions.
 Antidiarrheal Agents - Opioids
Agonist at mu opioid receptors;
Decreases fluid secretion;
Increases fluid absorption;
Decreases propulsive contractions;
Increases segmenting contractions;
Delays gastric emptying.
Analgesics that can be used as
Antidiarrheal Agents
Morphine
Codeine
Antidiarrheal Agents - Loperamide

Mu opioid agonist
Very little distribution into CNS
Low addiction liability

Side Effect
Constipating
 Antidiarrheal Agents -
Anticholinergics
Muscarinic antagonists
Decrease propulsive contractions
Decrease cholinergic secretions
 ANTIFLATULANTS
Used to relieve the painful symptoms associated with gas
Simethicone (a detergent)
Alters elasticity of mucus-coated bubbles, causing them to break
Large bubbles -> smaller bubbles, and less pain
Used often, but limited data regarding effectiveness
 Pathophysiology of Emesis
Cancer Cerebral cortex
chemotherapy
Opioids Smell
Sight Anticipatory emesis
Thought
Chemoreceptor Vestibular
Vomiting Centre
Trigger Zone Motion nuclei
(medulla) sickness
(CTZ) Muscarinic, 5 HT3 & Muscarinic
(Outside BBB) Histaminic H1 Histaminic H1
Dopamine D2
Chemo & radio therapy
5 HT3,, Gastroenteritis
Opioid Receptors
Pharynx & GIT
5 HT3
receptors
Antiemetics
Antiemetic Therapeutic Sites -
Summary