10. GI drugs Flashcards
ach and gastric pathways to produce acid
phospholipase c
ip3 and dag
ca release
histamine and proostaglandins pathways
g coupled
camp
protein kinase
antacids
Antacids are basic compounds that used to neutralize hyperacidity of the gastric contents.
antiacids Broadly classified in to:
1) Non-systemic or local, and
2) Systemic antacids.
local define plus example
Local/non-systemic antacids : which are non absorbable from GIT & preferable in the treatment of peptic ulcer than the absorbable(systemic) antacids. they include:
Magnesium hydroxide/magnesium trisilicate, aluminum hydroxide
local antiacids differ in
Differ in terms of acid neutralizing capacity, onset and duration of action, and adverse effects
Magnesium hydroxide
Magnesium hydroxide has very good acid neutralizing capacity, rapid onset and relatively short duration of action
causes diarrhea with prolonged use
Aluminum hydroxide
Aluminum hydroxide has relatively low acid neutralizing capacity, slow onset but prolonged duration of action
causes constipation with prolonged use due to aluminum’s smooth muscle relaxant and mucosal astringent action
Aluminum hydroxide binds ………. in the intestine and prevents its absorption
phosphate
Rebound acidity is mild and brief upon withdrawal of both
Calcium carbonate is a potent and rapidly acting(but not commonly used)
because
Liberates carbon dioxide can cause distention and discomfort
Calcium diffuses in to gastric mucosa increase HCl production directly by parietal cells(rebound acidity more marked)
Combinations of magnesium and aluminum salts are preferred b/c:
Adverse effects will cancel out( diarrhea and constipation)
Rapid action of magnesium salts combined with long action of aluminum salts maximizes the beneficial effects
Different combination preparations are available
sodium bicarbonate rarely used as gastric antacid b/c:
Produces carbon dioxide in stomach → cause distention, discomfort and ulcer perforation
Alters(increases) the pH of blood & other body fluids
Effect is short lasting and rebound acidity
H2 antagonists
define plus type
Counteract the hypersecretory effect of the endogenous histamine.
reversible competitive antagonists
Include: cimetidine(prototype), ranitidine, nizatidine, famotidine
All have equal efficacy but differ in terms of
potency
Cimetidine
inhibits cytochrome P450 and can slow metabolism and, thus, potentiate the action of several drugs ( warfarin, diazepam, phenytoin, quinidine, carbamazepine etc.)
side effects of cimetedine
It has antiandrogenic effect that manifest as gynecomastia, loss of libido, impotence, decreased sperm count
displacement of dihydrotestosterone from androgen receptors and increased prolactin release and inhibits degradation of estradiol by the liver
Uses of H2 antagonists
Duodenal ulcer
Gastric ulcer
Stress ulcers and gastritis
Zollinger-Ellison syndrome
GERD
However, b/c of higher efficacy of PPIs and equally good tolerability, they are not first-line agents
Proton Pump Inhibitors(PPIs)
dfine plus example
Are prodrugs activated in acidic environment of parietal cells’ canaliculi(charged form binds the enzyme)
Can be inactivated in the stomach and the presence of food decreases their bioavailability(given one hour before meal)
Example: Omeprazole(prototype), lansoprazole, pantoprazole, esomeprazole…
Mechanism of Action of ppi
Irreversibly bind to H+/K+ ATPase enzyme and inhibit it.
Steady state concentrations cause 80-98% inhibition of acid secretion.(Although their half-lives are 1-2 hours have long lasting effect; once daily administration
Duodenal ulcer heals faster than gastric ulcer(healing can be enhanced by 40 mg in both DU and GU)
ppi use
1) Peptic ulcer(omeprazole 20 mg is equally or more effective than H2 blockers)
Duodenal ulcer heals faster than gastric ulcer(healing can be enhanced by 40 mg in both DU and GU)
Are drugs of choice for NSAIDs-induced peptic ulcers
Can prevent relapse also
2) Bleeding peptic ulcer: acid enhances clot dissolution promoting ulcer bleed
Suppression of gastric acid facilitates clot formation reducing blood loss & rebleed
3) Stress ulcers
4) GERD
5) Zollinger-Ellison syndrome
6) Prophylaxis of aspiration pneumonia
Cytoprotective(ulcer protective) Agents
define plus drugs
Enhance mucosal protective mechanisms
Some may reduce acid secretion and exert antibacterial activity as well
Drugs include: sucralfate, colloidal bismuth subcitrate, tripotassium dicitratobismuthate, misoprostol
Sucralfate used for
Used for stress ulcers, erosions, PUD
Sucralfate
Attracted to and binds to
the base of ulcers and erosions, forming a protective barrier over these areas and protects the areas from acid and pepsin, action entirely local
sucralfate also augments gastric mucosal synthesis
of
prostagladin
sucralfate is Preferred in patients who
continue to smoke
Antacids should not be taken with sucralfate as its action requires
acid pH
Misoprostol
Synthetic prostaglandin analogue
Prostaglandins have cytoprotective activity:
Protect gastric mucosa from injury by enhancing local production of mucus or bicarbonate
Acid secretion and gastrin production are inhibited
Helps to maintain mucosal blood flow
Major problems in the use of misoprostol are
abdominal cramps, diarrhea, uterine bleeding, abortion
Colloidal bismuth subcitrate:
water soluble but precipitates at pH < 5
It heal 80-90 % of ulcers at 8 weeks
Possible mechanisms of action:
of colloid bismuth subcitrate
Stimulation of mucosal prostaglandin production
Formation of a coat on the ulcer
Detaches H. pylori from the surface of mucosa and kills it
Triple Therapy for H. pylori
One PPI plus 2 antibiotics each BID for 2 wks.
Omeprazole(20mg) + Clarithromycin(500mg) + Amoxicillin (1g)
Omeprazole(20mg) + Clarithromycin(500mg) + Metronidazole( 500mg)
Particularly useful in penicillin allergy
Antidiarrheal drugs
Principles of management:
Treatment of fluid depletion, shock and acidosis
Maintenance of nutrition
Drug therapy
anti diarrheal should not be used in patients with
bloody diarrhea, high fever, or systemic toxicity because of the risk of worsening the underlying condition.
Oral rehydration is possible if glucose is added with salt/glucose coupled sodium transport
Drug therapy consists of:
Specific antimicrobial drugs
Nonspecific antidiarrheal drugs
Specific antimicrobials
co-trimoxazole, ciprofloxacin, norfloxacin, ampicillin, tetracycline, and erythromycin
Diarrhea due to protozoa(amebiasis and giardiasis) can be treated with metronidazole and diloxanide furoate
Nonspecific antidiarrheal agents include:
1) Adsorbants
2) Antisecretory drugs
3) Antimotility drugs
Adsorbants include
plus moa
activated charcoal, kaolin
Coat the walls of the GI tract
Bind to the causative bacteria or toxin, which are then eliminated through the stool
Antisecretory drugs include
include sulfasalazine, mesalazine, corticosteroids
Reduce water secretion in to intestine
Used for treatment of inflammatory bowel diseases
Antimotility drugs include
opioids such as loperamide, diphenoxylate and codeine
Decrease propulsive movements and diminish intestinal secretions while enhancing absorption
Uses of Laxatives/ purgatives/ cathartics
Constipation(main use); other uses include:
Expulsion of parasites after antihelimentic use
Clear alimentary tract before surgery and radiological procedures
For management of poisonings
Laxatives should be avoided if there is
an intestinal obstruction, severe abdominal pain, symptoms of appendicitis, ulcerative colitis,
Classes of Laxatives:
Bulk-forming laxatives
Emollient/stool softeners
Osmotic laxatives
Stimulant/ irritant laxatives
Bulk-Forming
MOA plus example
Highly fiber non-digestible and non-absorbable hydrophilic colloids
Absorb water to increase bulk and swell
Distends bowel to initiate reflex bowel activity
Examples: psyllium, methylcellulose
Emollient / Stool softeners
Act by softening stool
Lubricate the fecal material and intestinal walls
Examples: Stool softeners: docusate salts
Lubricants: liquid paraffin (10 ml every 8-12 hrs as required)
Glycerin suppository (1 gm rectally at night after moistening with water)
Osmotic laxatives
Soluble but non-absorbable compounds whose osmotic action draws water in to the intestinal lumen.
Result: bowel distention, increased peristalsis, and evacuation
Examples: magnesium sulfate , Mg(OH)2, magnesium citrate, sodium phosphate, sorbitol, lactulose
Use of osmotic laxatives
Chronic constipation
Bowel diagnostic and surgical preparations
Removal of helminthes and parasites
Stimulant Laxatives
Stimulate intestinal enteric nerves system and leads to increase in intestinal motility and fluid secretion
Examples: castor oil, senna, cascara, bisacodyl
Use
Acute constipation
Diagnostic and surgical bowel preparations
Emetics
Example: ipecac syrup and apomorphine
Emesis should not be induced if the patient has ingested certain
volatile hydrocarbons and caustic substances, CNS stimulants
anti emetics include
Antihistamines
Anticholinergics
Dopamine Antagonists
Phenothiazine Derivatives
5-HT3 receptor antagonists
Antihistamines
Example: Dimenhydrinate, diphenhydramine, and meclizine hydrochloride
block peripheral stimulation of the emetic center.
Most effective in motion sickness
S/E
C/I:
S/E: sedation.
C/I: active work such as driving
Anticholinergics
Example: Atropine, scopolamine (hyoscine)
They block Muscarinic receptors in the GIT and inhibit motility and secretion.
Dopamine Antagonists
Example: Metoclopramide
Dopamine antagonist that centrally inhibits stimulation of the CTZ
decreasing a peripherally associated stimulation of the emetic center.
S/E: drowsiness, fatigue, dizziness, weakness
Phenothiazine Derivatives
Example: Promethazine , Chlorpromazine, prochlorperazine
Act at the CTZ by inhibiting dopaminergic transmission.
They also decrease vomiting caused by gastric irritants, suggesting that they inhibit stimulation of peripheral vagal and sympathetic afferents.
5-HT3 receptor antagonists
ondansetron, granisetron
serotonin receptor antagonists use 3
chemotherapy induced vomiting, disease-induced vomiting, and
post-operative vomiting
