GI Tract Flashcards
Different types and uses of GI drugs
1- For peptic ulcer
2- For chemo-induced emesis control
3- Antidiarrheals
4- Laxatives
5- For IBDs
Peptic ulcer causes
1- NSAIDs
2- H. Pylori (70% of gastric, 90% of duodenal)
3- Increased acid
4- Inadequate mucosal defense
Peptic ulcer treatment approaches
1- Antimicrobial: For H. Pylori
2- Decrease acid secretion: H2 antagonists & proton pump inhibitors
3- Neutralize gastric acid: Non-absorbable antacids
4- Enhance mucosal defense: Misoprostol, sucralfate
5- Stop smoking
Decrease gastric acid secretion
- H2 receptor antagonist (Inhibition of H/K-ATPase proton pump)
- Prostaglandins
- Antimuscarinic agents (Anticholinergics)
H2 receptor antagonist
Mechanism, Use time, Examples
- Block binding of histamine to H2 receptor
- So reduce cAMP concentration
- So decrease secretion of acid
- Basal, food stimulated & nocturnal secretion decrease after single dose
- More acid at nights so used mostly at nights
- -TIDINE:
- Cimetidine
- Ranitidine
- Famotidine
- Niatidine
Histamine effects
- Adenylyl cyclase activation:
- Increases cAMP
- Activates PKA
What does PKA do?
- Phosphorylation of skeletal proteins
- Moves H-K ATPase from cytoplasm to membrane
Acetylcholine & Gastrin on calcium
Increases intracellular Ca2+
Muscarinic receptor (Acethylcholine)
Increases 4 things:
- Peristalsis
- Secretions
- Sphincter opening
- Smooth muscle contraction
Cimetidine
mechanism, side effects
- Blocks H2 receptor, decreases acid
Side effects: - Tachycardia
- Cirrhosis (overdose with other drugs)
- Gynecomastia (in men)
- Galactorrhea (in women)
- Bleeding w/ Warfarin
Nizatidine
First pass effect
- Less affected by first pass effect
First pass effect:
Drug destroyed in liver before reaching circulation
Therefore less oral form & more injection
Anti-acids
Example, mechanism
- Al(OH)3 constipation
- Mg(OH)2 diarrhea
- Neutralize acid, increase pH
Protectants
Examples
- Carbenoxolone
- Sucralfate
Proton pump inhibitors
PPI
Examples, Mechanism, Clinical use, Half life
- Omeprazol, Pantoprazol, Esomeprazol
- Inhibit H-K ATPase pump in parietal cells
- Bioavailability decreases by 50% with food (mornings 1h before breakfast)
Clinical use: - Reflux
- Peptic ulcers
- Ulcer from H. pylori
- NSAIDs ulcer
- Peptic ulcer prevention
- Before stomach tumor treatment
Half life: 1-1.5h but 24h effect - Stronger than H2 blockers, almost 0 acid
- Negative feedback causes histamin, gastrin & acethylcholine increase
PPI side effects
- B12 decrease in long term
- Decrease mineral absorption
- Increase lung & GI infection (destroying acid wall)
Prostaglandins
Examples, mechanism
- PGE 1 (Decrease acid secretion & strengthen stomach mucous)
- Misoprostol (PGE 1 analog, Decreases NSAIDs, Increase bicarbonate, Induce miscarriage)
- Bismuth subsalicylate
Anti-cholinergics
(Anti-muscarinic, Atropinic)
Mechanism, example
Mechanism:
- Stimulates vagus nerve, then
- Acethylcholine secretion, then
- Muscarinic receptor stimulation, then
- Peristalsis
Vagus nerve:
1. Contractions
2. Increase peristalsis
3. Sphincter loosening
4. Increase secretions
Examples:
1. Atropine (not good for stoamch, good for salivary & sweat glands, lung, eyes)
2. Dicyclomine
3. Clidinium c (only M1 receptor block)
Cholinergics
Overdose causes peptic ulcer
- Carbachol
- Bethanechol
- Pilocarpin
- Acethylcholine
- Organophosphates
Peptic ulcer approach
- Histamine: H2 blocker
- Vagus nerve: anti-muscarinic
- Bacteria: Ab (3 antibiotics, 1 won’t work)
- Weak mucosal layer: Protectants, honey, licorice, no smoking
Diseases related to peptic ulcer
- Zollinger-Ellison syndrome & Hypercalcemia: Increased gastrin
- Diseases w/ severe vomitting: Hypochloremic metabolic alkalosis
GERD
Risk factor, treatment
- Asthmatics more susceptible
- Some asthma drugs: theophylline
Treatment:
1. Histamin receptor inhibitors
2. Antacids
3. PPI
4. Baclofen (Decreased sphincter loosening (GABA B agonist))
Cholinomimetics
Example, Side effect
- Neostigmine
- Bethanechol & Carbachol
Side effects: Menstruation problems, Gynecomastia, Prolactin increase
NOT diarrhea
D2 dopamine antagonists
-
Domperidone:
1. Penetrates BBB
2. Anti diarrhea & vomit
3. Increases GI motility
4. Drug resistant hiccups -
Metoclopramide:
FOR:
GERD, Drug resistant hiccups, Gastric emptying problems, Indigestion, Vomit prevention
Chronic use: Parkinsonism symptoms, Extrapyramidal problems, Hyperprolactinemia
Laxatives
types
- Bulk-producing: methylcellulose, psyllium
- Stool surfactants: glycerin supp, docusate
- Osmotics: Mg citrate, Na phosphate
- Sorbitol, Lactose: Chronic (can cause flatulence)
- Polyethylene Glycol (PEG)
- Cl channel activators: Lubiprostone, Linaclotide
- 5HT3 antagonists & 5HT4 agonists
- Opioid receptor antagonists & 5HT4 antagonists (chronic constipation)
Antidiarrheals
- Opioid agonists: loperamide, diphenoxylate
- Bile Acid Sequestrants: Cholestyramine, Colestipol
- Somatostatin: Gastrin, glucagon, GH & insulin inhibitor & Vasoactive peptid
- Clonidine
- Botax
- Cisapride
Octreotide & somatostatin mimetic
Use, Side effects
Use:
- Intestine & pancreas secretion inhibitor
- Dumping syndrome
- Gastric carcinoid
- Hypophysis tumors (Acromegaly)
Side effects:
- Pancreas secretion problem
- Low DEKA vits
- Stomachache
- Flatulence & Diarrhea
- Bile stones
- Hyperglycemia
- Weak hypoglycemia
Drugs for IBS
combination
Loperamide + Fiber supplements + MOM + Osmotic laxatives + TCAs
Anti-spasms
- Hyoscine
- Dicyclomine
- 5HT3 antagonists (-setron):
Alosetron, ondansteron, graniseron, palonosetron
Systems in vomitting
Receptors
- Cholinergic M1
- Histaminergic H1
- Serotonin 5HT3
- Neurokinin NK1
