Download Drugs for peptic ulcer, emesis and reflux disorders

Drugs for peptic ulcer, emesis
and reflux disorders
Dr. Rishi Pal
Assistant Professor
Physiology of gastric secretion
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Stomach secretes 2-3 liters of gastric juice
/day.
Chief/peptic cells secrete pepsinogen.
Parietal or oxyntic cells secrete acid and IF.
Superficial epithelial cells secrete alkaline
mucus and bicarbonates.
Regulation of gastric acid secretion
Ach
 Histamine
 Gastrin
 prostaglandin-E2
Phases of gastric acid secretion
 Basal, cephalic and hormonal
 Membrane bound proton pump (H+)
 K+ ATPase
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Peptic ulcer
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1.
2.
3.
Damage to the mucosa and deeper tissue
exposed to acid and pepsin is known as
peptic ulcer.
Causes of peptic ulcer :H. pylori infection
Use of NSAIDS
Stress
Classification of the drugs used in peptic ulcer
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Drugs that inhibit gastric acid secretion
1.
Proton pump inhibitors: omeprazole, esomeprazole,
lansoprazole, pantoprazole, rabeprazole.
H2-receptor antagonists: cimetidine, ranitidine,
famotidine, roxatidine,nizatidine
Antimuscarinic agents (anticholinergics): pirenzepine,
telenzepine
Prostaglandin analogs: misoprostol, enprostil.
2.
3.
4.
5.
Anti-peptic ulcer drugs
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Ulcer protective
sucralfate, and bismuth subcitrate (CBS)
Drugs that neutralize gastric acid (antacids)
a)
b)
Systemic antacids: sodium bicarbonate and sodium citrate.
Non systemic antacids: magnesium hydroxide, magnesium
trisilicate, aluminum hydroxide, and calcium carbonate.
Anti-peptic ulcer drug
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Anti- H. pylori drugs
Amoxicillin, tetracycline, clarithromycin,
metronidazole, tinidazole, bismuth
subsalicylate, H2-antagonists and PPIs.
Proton pump inhibitors
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Proton pump, K+-ATPase membrane bound enzyme play an
important role in the final step of gastric acid secretion (basal
and stimulated).
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Omeprazole is the prototype drug: these are prodrugs and
activated to sulfenamide at acidic pH. Activated form binds
covalently with SH group of H+ pump and irreversibly
inactivates it.
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PPIs administered orally 30 min. before meal. Half life short
(1.5 hr), acid secretion suppressed for upto 24 hr.
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Enteric coated form or powder containing
sodium bicarbonate.
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i.v. formulations available for esomeprazole,
lansoprazole, pantoprazole and rabiprazole.
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They are highly bound to plasma proteins;
extensively metabolized in liver and
metabolites secreted in urine.
Therapeutic uses of PPIs
1. Peptic ulcer disease
Duodenal ulcer disease
 Gastric ulcer
 Acute bleeding ulcer
 H. pylori-associated ulcer
 Stress ulcers (curling ulcers)
 NSAIDs induced ulcers
2. Gastroesophegial reflux disease (GERD)
3. Zollinger’-Ellison syndrome.
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Adverse effects of PPIs
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Headache, diarrhoea and abdominal pain.
Skin rashes and arthralgia.
May decrease vit B12 absorption
Increase rate of infection and fracture of bones.
Drug interactions: omeprazole can inhibit
metabolism of phenytoin, warfarin, diazepam. PPIs
decreases bioavailability of itraconazole, iron salts,
etc
H2-Receptor antagonists
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Mechanism of action:
Competitively block H2 receptors on parietal
cells.
Suppress all phases of acid secretion.
Most effective in suppressing nocturnal acid
secretion.
Less potent than PPIs.
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Administered orally and well absorbed.
Metabolized in liver.
Cimetidine, ranitidine and famotidine
available for i.v. administration
Nizatidine has high bioavailability (100%)
Therapeutic uses of H2 blockers
Peptic ulcer disease
Duodenal ulcer disease
 Gastric ulcer
 Acute bleeding ulcer
 H. pylori -associated ulcer
 Stress ulcers (curling ulcers)
 NSAIDs induced ulcers
2. Gastroesophegial reflux disease (GERD)
3. Zollinger’-Ellison syndrome.
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Anticholinergic agents
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Pirenzepine
Telenzepine
Selective M1-receptor blocker
Inhibit acid secretion
Not commonly used because of their low
efficacy and anticholinergic effects.
Prostaglandin analogues
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Misoprostol effective orally for prevention
and treatment of NSAID-induced duodenal
ulcers.
Inhibit gastric acid secretion.
Increase bicarbonate and mucus secretion.
Common side effects:
Diarrhoea and abdominal cramps.
Containdicated in pregnancy
Ulcer protective
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Sucralfate : it is complex aluminum hydroxide
and sulphated sucrose.
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Polymerized to form sticky gel that adheres
to the ulcer base and protects it.
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Form barrier against acid-pepsin.
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Increase mucus-bicarbonate secretion.
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Given orally empty stomach.
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Reduced absorption of digoxin, tetracyclines,
ketoconazole, fluoroquinolones. etc.
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Concurrent use of PPIs, H2 blocker should be
avoided.
Bismuth containing preparation
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Bismuth salisylates and colloidal bismuth subcitrate.
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React with protein in the base of ulcer and protect it
from peptic digestion.
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Stimulates secretion of PGE2, mucus and
bicarbonate.
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Anti-microbial effects against H. pylori.
Drugs that neutralized gastric acid
Ideal antacids
1.
2.
3.
4.
Insoluble and neutralize acid
Should not liberate CO2
Non-absorbable
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.
Antifoaming agents
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Methylpolysiloxane
Oxethazaine
Sodium alginate
Anti H. pylori agents
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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
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To prevent or delay development of resistant
organism.
Prevent relapse
Promote rapid ulcer healing
Eradicate H. pylori infection
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Treatment for 1 or 2 weeks required
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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.
Emetics and antiemetics pathways
Emetics and antiemetics
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Mechanism of vomiting
Pregnancy, infection, drugs, radiation, painful
stimuli, motion sickness, metabolic and
emotional disturbances.
Neurotransmitters involved Ach,
histamine,5HT and dopamine.
Emetics
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Mustard
Common salt
Ipecac
Apomorphine
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Used for certain poisoning cases
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Contraindications for emetics
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Emetics
Children
Unconscious patient
Corrosive and caustic poisoning
CNS Poisoning
Kerosene poisoning
Antiemetics
Classification of antiemetics
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Anticholinergics: scopolamine, dicycloamine
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Antihistamines (H1-blockers): dimenhydrinate,
diphenhydramine, cyclizine,meclizine,
hydroxyzine,promethazine,doxylamine, cinnarizine
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5HT3-receptor antagonists: ondansetron,
granisetron, dolasetron, palonosetron
Antiemetics
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Prokinetic agents: metoclopramide,
domperidone
Neuroleptics: chlorpromazine, fluphenazin,
prochlorperazine, haloperidol
Cannabinoids: dronabinol
Adjuvant antiemetics: glucocorticoids,
benzodiazepines
Anticholinergics as antiemetic
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Scopolamine for motion sickness, it blocks
afferent impulses from vestibular apparatus
to the vomiting center by its anticholinergic
action.
Its sedative effects also contributes for its
antiemetic effect.
Scopolamine not effective in other types of
vomiting.
Antihistamine H1 blocker as antiemetic
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Motion sickness, morning sickness, post
operative and other types of vomiting.
Dimenhydrinate, diphenhydramine,
doxylamine, promethazine, cyclizine,
meclizine.
Have sedative and anticholenergic action.
Meclizine has longer duration of action.
5HT3-receptor antagonist as antiemetic
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Ondensetron is prototype drug
Granisetron, dolasetron,palanosetron.
Blockade of 5HT3 receptor on vagal afferent in the
gut also block 5HT3 receptors in CTZ & STN.
Used for anticancer drug-induced nausea and
vomiting, effective in hyperemesis of pregnancy,
postoperative and post radiation vomiting but not
effective in motion sickness.
5HT3 receptor antagonist
Prokinetic drugs
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Drugs promote coordinated movements of
upper GIT and hasten gastric emptying are
called prokinetic drugs.
Metoclopramide: D2 receptor antagonist
Have central and peripheral action.
Enhance release of Ach from myentric
neurons.
Used in GERD
Mechanisms
Prokinetic effects
Neuroleptics
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Prochlorperazine
Used for vomiting due to systemic infection,
drugs, uraemia.
Cannabinoids: dronabinol used for cancer
chemotherapy
Adjuvant antiemetics: glucocorticoids,
benzodiazepines.
Anti emetics