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Drugs Used in GI DisordersDrugs Used in GI DisordersDrugs Used in GI DisordersDrugs Used in GI DisordersDrugs Used in GI Disorders
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Drugs Used in GI Disorders
Drug classification; important or main drugs Important drugs kinetics and dynamics Important SE & precaution Clinical used
Kutcharin Phunikhom, MD Department of Pharmacology, Faculty of Medicine, KKU
Objectives
Drugs used in PU /GU/ DU(include GERD)
Antidiarrheal drugs Laxative drugs Drugs used in emesis
Topic outline
Peptic Ulcer Disease (PUD)
Acute/chronic of gastric /duodenal ulcer Erosion of GI tract mucosa Etiologies : -high stress(trauma,burn patients) -drugs/irritants:NSAIDs -H. pylori -smoking -caffeine
In general
Enterochromaffin-like cell, parietal cell, epithelial cell Acetylcholine, histamine, gastrin, prostaglandin Vagus nerve, post ganglionic fiber H2-receptor, gastrin receptor, muscarinic receptor, prostaglandin receptor Adenylate cyclase, proteinkinase, H+/K+ ATPase HCl, mucus, HCO3-
Review: physiology of gastric secretion
HCI secretion by parietal cell
Stimulated acid secretion 1.cephalic phase: smell,taste stimulates the vagus n. 2.gastric phase: -peptides,aa.stimulate the G cell -stomach distension leads to gastrin release 3.intestinal phase: aa.induce acid secretion
M
M
M
PG
PG
G G
H2 H H
G Blood
Vagus N
Postgang. fiber
PG
+
+
+
+ +
H+ pump H
K
-
Ca
Ca
cAMP
Mucus HCO3
Gastric Lumen
Parietal cell
Epithelial cell
ECL
Short diagram on gastric acid control
-Lifestyle changes
-Medications -Surgery
Treatment of PU/GU/DU
Classification of drugs used in PU / GU/DU
Acid inhibition Acid neutralization Protection of mucosa Eradication of Helicobacter pylori Other
(I) Acid Inhibition
1) H2-receptor antagonist
Cimetidine, ranitidine, nizatidine, famotidine roxatidine, lafutidine 80-90 % acid reduction Rapidly absorbed with 1st-pass effect Excreted mainly in urine Adverse effect: relapse, gynecomastia (long term use) DI: CYP450 inhibition (warfarin, diazepam, digoxin,
propranolol, phenytoin, phenobarbital, etc)
M
M
M
PG
PG
G G
H2 H H
G Blood
Vagus N
Postgang. fiber
PG
+
+
+
+ +
H+ pump H
K
-
Ca
Ca
cAMP
Mucus HCO3
Gastric Lumen
Parietal cell
Epithelial cell
ECL
Short diagram on gastric acid control
2) Proton pump inhibitor Omeprazole, lanzoprazole, rabeprazole, pantoprazole Rapidly absorbed, active at acidic pH (enteric coated
capsule) Form irreversible, inactive complex with H+/K+
ATPase 95% plasma protein binding Low adverse effect DI: CYP450 inhibition
M
M
M
PG
PG
G G
H2 H H
G Blood
Vagus N
Postgang. fiber
PG
+
+
+
+ +
H+ pump H
K
-
Ca
Ca
cAMP
Mucus HCO3
Gastric Lumen
Parietal cell
Epithelial cell
ECL
Short diagram on gastric acid control
3) M-receptor antagonist
Pirenzepine, dicyclomine, telenzepine Low effect on acid reduction Adverse effect: general M-receptor effects
(atropine-like effects) Low use now
M
M
M
PG
PG
G G
H2 H H
G Blood
Vagus N
Postgang. fiber
PG
+
+
+
+ +
H+ pump H
K
-
Ca
Ca
cAMP
Mucus HCO3
Gastric Lumen
Parietal cell
Epithelial cell
ECL
Short diagram on gastric acid control
(II) Acid Neutralization
Antacid = anti + acid = alkaline agent Needs no / low absorbed (action mainly in lumen) Also protect mucosa (surface covering) Al-salts, Al(OH)3 - not absorbed, slow onset,
constipation, phosphate deficiency Mg-salts, Mg(OH)2 - low absorbed, rapid onset, diarrhea, Ca-salts, CaCO3 - varied absorption, rapid onset,
hypercalcemia NaHCO3 - readily absorbed, CO2, systemic alkalosis
(III) Protection of mucosa
Sucralfate
Sucrose octasulfate + poly Al(OH)3 Active at acidic pH, polymerization (gel) Increase secretion of mucus, HCO3-, PG Protein denature at ulcer site Increase healing effect Prevent absorption of other drugs Low SE
Carbenoxolone Glycyrrhizic acid
derivative Increase secretion &
viscosity of mucus Inhibit pepsin activity SE: steroidal SE (Na-
water retention, hypokalemia, hypertension)
Misoprostol PG analogue Increase secretion of
mucus & bicarbonate Inhibit acid secretion Effective for long term
usage of NSAIDs SE: uterine stimulation
(IV) Eradication of H.pylori
Triple therapy:- PPI + clarithromycin + amoxycillin (or metronidazole)
G- curved rod dyspepsia gastritis duodenal ulcer painful stomach
Helicobacter pylori
Other dugs Cimethicone Motilium Magesto M.carminative Cisapride
PUD complications Hemorrhage Perforation Obstruction Cancer
4-8 weeks Avoid special food: coca cola, chilly Stress control
PU / GU/DU treatment
Antidiarrheal Drugs
Used when necessary Routine diarrheal treatment : Rehydration ->
antimicrobial agents -> Antidiarrheal agents (antispasmodic / antimotility agents)
Classification : Opioids & others Opioids - opium tincture, diphenoxylate, loperamide Others - Bismuth subsalicylate, octreotide, adsorbent,
astringent
(I) Opioids Agonist at opioid receptors of GI muscle Reduce muscle movement, but increase tone of
contraction of rectal sphincter Reduce fluid & electrolyte secretion in GI Fast action Cause addiction (long term usage) Careful usage in children Lomeramide (ImodiumR), diphenoxylate (LomotilR) -
potency > opium tr.
(II) Other antidiarrheal
Bismuth subsalicylate: inhibit PG secretion -> inhibit diarrhea
Octreotide: somatostatin receptor binding -> inhibit GI fluid secretion
Adsorbent - charcoal, kaolin, chalk: trap toxin, substance into their suface
Astringent - tea leaves: precipitate surface protein -> reduce diarrhea
Atropine: M-receptor SE
Laxatives Drugs
Foods (mainly plant-based foods Bulk laxative Hydrating agents Stimulant laxative Surfactant laxative Others
Laxative - Purgative - Cathartic
Mostly need water
(I) Foods Laxative
Plant-based foods Almonds, Aloe Vera, Apples, Bananas, Blueberry,
Coconut, Coffee, Grapes, Mangos, Oranges, Papayas Preventing constipation than treating it.
(II) Bulk Laxative
Dietary fiber (natural cellulose), polysaccharide, psyllium seed (MetamucilR), Lemon basil ()
Bind to water ---> increase bulk (mass) ---> stimulate local reflex in colon
Needs water (retain more water) Not absorbed in GI Reduces absorption of other drugs Quite safe (except GI obstruction) Takes days for action (12-72 hrs.)
(III) Hydrating agents (osmotics)
Hyperosmotic agents Sorbitol, glycerin, lactulose drawing water into the bowel SE- withdraw water &
electrolytes into colon lumen Poorly absorbed in GI Fast action (30 min. to 3 hrs.)
Saline laxatives Magnesium salts - Mg(OH)2,
MgSO4, sodium phosphate, sodium biphosphate
Attract and retain water in the hollow of the intestinestool softening .increase intraluminal pressure
Poorly absorbed in GI SE- withdraw water & electrolytes
into colon lumen Fast action (30 min. to 6 hrs.)
(IV) Stimulant Laxative (irritants)
Diphenylmethane derivatives - bisacodyl (DulcolaxR), phenolphthalein
Anthraquinone glycosides - senna, aloe, etc Stimulate local reflex in colon Poorly absorbed Medium action (6-8 hr) Suppository (1-2 hr) SE: abdominal cramp, phenolphthalein ->liver toxic (not
in use now)
(V) Surfactant Laxative (stool-softeners)
Docusate, castor oil Wetting & softening agent - increase water
permeability (fats & water to penetrate the stool) Needs water for effect Slow action (1-3 days) Castor oil also increase peristalsis -> fast action (1-3
hr) --> bowel evacuation before operation SE: abdominal cramp, electrolyte imbalance (castor
oil)
(VI) Other Laxatives
Mineral oil - non absorbed, work as lubricant, slow action (6-8 hrs.), SE: interfere oil-soluble vitamin absorption, oil leakage
Laxative Abuse: Weight control - loss of fluid & electrolytes, interfere normal habit
Controlling System for Emesis Vomiting
Center Sensory Aff.
CNS Pways
CTZ mood
Special sensation
Labyrinth
Motion sickness
Solitary tract nuclei
Endotoxin Drugs
Local Irritants in GI by chemical, bacteria,
virus and cytotoxic drugs
radiation
Emetic & Antiemetic Drugs
Stimulate vomiting center in medulla or outside (CTZ, GI)
Ipecac is used as an antidote for toxic substant ingestion (GI)
Apomorphine (CTZ) & CuSO4 (GI) are mainly used in experiment but not for medicated purpose
Emetic Drugs
Antiemetic Drugs
Block vomiting center or pathways outside medulla Mainly used in motion sickness, pregnancy (morning
sickness), chemotherapy, food poisoning, radiation & post-operation
Antiemesis: D2 antagonist, 5-HT antagonist, H1 antagonist, M antagonist & miscellaneous
dimenhydrinate (DramamineR), diphenhydramine (BenadrylR) -> Motion sickness
SE: Antihistamine SE
H1antagonist
M- antagonist promethazine (PhenerganR), scopolamine (ScopodermR) -
> Motion sickness (caused by labyrynth) SE: similar to Antihistamine SE
D2 antagonist Chlorpromazine (ChlorpromedR), domperidone
(MotiliumR) -> Local irritants, cytotoxic drugs, radiation SE: BP drop , dizziness, abnormal movement in
extrapyramidal system
Ondansetron (ZofranR) -> cytotoxic drugs SE: headache, dizziness
5HT- antagonist
Prokinetics Metoclopramide (PlasilR), -> general vomiting and
morning sickness (careful use) SE: depression, dizziness, abnormal movement in
extrapyramidal system domperidone (MotiliumR)
Dronabinol (MarinolR) -> block CTZ SE: dizziness, dry mouth, hallucination
Misc. The end