DRUGS USED IN GIT

DISEASES
DR FIRMALINO

Groups

A. Drugs Used in Acid Peptic Diseases

B. Drugs Promoting Gastrointestinal Motility
C. Anti Emetic Drugs
D.Pancreatic Enzyme Replacement Products
E. Laxatives
F. Drugs Used For Dissolution of Gallstones
G.Drugs Used In The Treatment of Chronic
Inflammatory Bowel Disease
H.Drugs Used in Therapy Of Portal Systemic
Encephalopathy

Gastric acid secretion

Peptic Ulcer Disease

Endoscopy

A. Drugs Used In Acid Peptic

Disease
Antacids
Weak bases
Reduce gastric acidity
Reduce pepsin activity
Has mucosal protection by stimulating
prostaglandin production

Kinds
magnesium hydroxide Mg (OH)2
aluminum hydroxide Al (OH)2
sodium bicarbonate NaHCO3
calcium carbonate

Mechanism of antacid

Clinical uses of antacids

1. if given 1 hr after a meal, it neutralises gastric acid
for 2 hrs
2. if a second dose is given 3 hrs after the meal, it
maintain the effect for up to 24 hrs
3. promotes healing of duodenal ulcer
4. role in gastric ulcer is less clear
5. may be used to relieve the pain of esophagitis,
duodenal & gastric ulcer
6. tablet antacid are generally weaker in neutralizing
capability
a. not recommended for treatment of active peptic
ulcer disease

Adverse reactions
magnesium
diarrhea
hyper magnesemia

aluminum
constipation
hypophosphatemia

combine these 2 to avoid each

others side effect

Gastric Antisecretory Drugs

3 normal agonist / stimulants to gastric
acid secretion
Histamine
Acetylcholine
Gastrin

H2 receptor antagonist

Cimetidine
Ranitidine
Famotidine
Nizatadine

Pharmacodynamics/Pharmacokineti
cs
Decrease food stimulated acid secretion by
90%
Less effective in nocturnal secretion
Also for heartburn & dyspepsia
Effective for promoting healing of duodenal
& gastric ulcer & preventing recurrence
Also for Zollinger Ellison syndrome & gastric
hypersecretory states like systemic
mastocytosis
Preferably given at bedtime for 4 wks

Toxicity
Cimetidine
confusion
reversible gynecomastia
increase prolactin & estrogen
rare w/ ranitidine & famotidine

has hepatotoxic microsomal metabolism of some

drugs like warfarin, theophylline, diazepam,
phenytoin
less w/ ranitidine
no effect w/ famotidine & nizatadine

Famotidine
headache

All drugs
hematologic

Gynecomastia

Anti Muscarinic Agents

Cholinoceptor antagonist
Rarely used since the gastric receptor is
least sensitive to it
Adjunct only

Example
pirenzepine
atropine (hyoscyamine)
scopolamine (hyoscine)
ipratropium

Parasympatholytic effect

pupil dilatation, bronchodilatation

tachycardia, dry mouth
decrease gastric acid secretion
decrease intestinal motility

Proton Pump Inhibitors

Irreversibly inhibits gastric parietal
cell proton pump H+/K+ AT pase by
100%
4 drugs
Omeprazole
Lanzoprazole
Rabaprazole
Pantoprazole

Indications (4-8 wks tx)

Gastric ulcer
Duodenal ulcer
Gastro esophageal reflux disease GERD
Esophagitis
Superior to H2 antagonist & misoprostol in
dealing w/ NSAID induced ulcer
Zollinger Ellison Syndrome
Multiple Endocrine Neoplasia
Systemic Mastocytosis

Toxicity
Develop gastric carcinoid tumors in
rats but not in man

Somatostatin analog
Growth hormone inhibiting hormone
octreotide
Inhibit gastric acid & pancreatic
secretion
Tx of Gastrinoma (Zollinger Ellison
Syndrome
May decrease portal pressure &
reduce variceal hemorrhage

Mucosal Protective Agents

Sucralfate
Aluminum sucrose sulfate
Selective binding to necrotic ulcer tissue &
act as barrier to acid,pepsin,bile
Directly absorbs bile salt
Stimulate prostaglandin synthesis
Not absorbed
Requires acid pH to be activated therefore
should not be used w/ antacid,proton pump
inhibitors,H2 receptors antagonist

Mucosal Protective Agents

Colloidal Bismuth Compounds
Also binds an ulcer tissue,coat it & protect
it from acid & pepsin
inhibition of pepsin
stimulate mucus production
increase prostaglandin synthesis
possible antimicrobial effect on H.pyloni
especially if combined w/ metronidazole &
tetracycline
ulcer healing up to 98%

Kinds of Colloid bismuth

bismuth subsalicylate
tripotassium dicitrate bismuthate
toxicity-minimal

Carbenoxolone
Synthetic derivative of glycyrrhizic acid
(from licorice)

Mechanism of action of colloid

bismuth
Increase mucus production, increase
secretion & increase viscosity
Has aldosterone like effect, thus causes
Hpn, fluid retention, hypokalemia

Concurrent use of spironolactone

controls fluid retention but also
abolished ulcer healing effect
Use w/ thiazide prevent Na retention
w/o abolishing ulcer healing effect

Prostaglandin Synthetic
Analog
Produced by gastric mucosa &
inhibits gastric secretion in high
doses by inhibition of histamine
related cAMP production
Example Misoprostol ( Cytotec)

Prevents ulcer induced by NSAID

Toxicity
Diarrhea
Uterine contraction - abortion

Antibiotics

Ampicillin
Amoxicillin
Clarithromycin
Metronidazole
Tetracycline

Dr Warren / Dr Marshall
1979 Dr Warren, a pathologist,
noted H. Pylori in Gastric ulcer biopsy
1984 Dr Marshall swallowed H.
Pylori and developed gastritis / ulcer.
He treated himself w/ antibiotics and
he improved
2005 both were awarded the Nobel
Prize & 1 million dollars for their work

Combination therapy
Not recommended no proven
benefit
Especially if combined w/ a proton
pump inhibitor like omeprazole, the
H2 receptor antagonist even inhibit
omeprazole

Refractory Disease
20% - failure rate especially w/
elderly & smokers
What to do
Increase the dose
Prolong treatment >4 wks
Shift to another H2 antagonist
Shift to proton pump inhibitor
Add antibiotics for H.pylori Clarithromycin, ampicillin

DRUGS PROMOTING INTESTINAL

MOTILITY
Cholinomimetic effect
Agents
Bethanechol
Metoclopramide
Cisapride

 Metoclopramide
Dopamine antagonist thus the anti
emetic effect in cancer tx, emergency
surgery labor, delivery
Enters CNS

Cisapride
Does not enter CNS; increase colon
motility
For gastro esophageal reflux

Metoclopramide / Cisapride
Both causes release of acetylcholine from
cholinergic neurons in enteric myenteric plexus
Also sensitizes intestinal smooth muscle to Ach.
Do not increase gastric & pancreatic secretion
Hasten esophageal clearance, increase lower
esophageal sphincter pressure
Increase gastric emptying
Shorten small bowel transit time

Clinical use
Metocloparamide facilitates small
bowel intubation
Diabetic gastroparesis
Post vagotomy
Gastroesophageal reflux
Can decrease heart burn

Toxicity
cisapride
can cause ventricular arrhythmia

Metoclopramide
Somnolence
Nervousness
Dystomia
Parkinson/tardive dyskinesia
Increase pituitary prolactine release,
galactorrhea, menstrual disorder

Other drugs
Erythromycin
Macrolide antibiotic
Prokinetic effect in stomach increase motility
For diabetic gastro paresis & intestinal pseudo obstruction

Alosetron
5 HT antagonist
Under research for irritable bowel syndrome

Tegaserod
5 HT partial agonist
w/ similar benefit

5 HT
5 hydroxytyptamine Or serotonin
vasoconstrictor
intestinal smooth muscle stimulant & increase motility

ANTI EMETIC DRUGS

Emesis or vomiting is just a manifestation
of a wide variety of conditions
Pregnancy
Motion sickness
GIT obstruction
Peptic ulcer
Drug toxicity (cancer chemo Tx)
MI
Renal failure
Hepatitis

Major anti emetic drugs

H1 antihistamines
Phenothiazines
Metoclopramide
Ondansetron
Marijuana
Corticosteroid
Benzodiazepine

H1 Antihistamines
diphenhydramine , hydroxyzine
has antimuscarinic & sedative effects
particularly effective for nausea &
vomiting of motion sickness due to
depression of the vestibulo cerebeller
pathway (like the anticholinergic
scopolamine)

Phenothiazines
blocks dopamine receptors in
chemoreceptor vomiting trigger zone in the
brain
kinds
prochlorperazine
promethazine

has limited use due to its sedative effect

toxicity
sedation
dystonia reversed by diphenhydramine

Other anti emetic

Metoclopramide - also a dopamine antagonist like
phenothiazine
5 HT (hydroxytryptamine) inhibitors
ondansetron, granisetron, dolasetron
good for cancer chemotherapy
Neurokinin antagonist
under research for delayed emesis & vomiting due to high
dose chemotherapy
Marijuana tetrahydrocannabinol & dronabinal
also for vomiting of cancer chemotherapy
Corticosteriod
dexamethasone, methylprednisolone
mechanism against vomiting is unknown
Benzodiazepine
sedative/hypnotic drug used to control anticipatory nausea &
vomiting

PANCREATIC REPLACEMENT
PRODUCTS
Steatorrhea may occur in pancreatic
insufficiency when lipase output is
lower by 100% of normal
Pancreatic enzyme replacement
when given orally is inactivated by
gastric acid pH below 4.0 thus only
about 8% of this ingested lipase
reaches the distal duodenum

 Kinds
Pancreatin
Pancrelipase

Maybe supplemented w/ cimetidine

thus lowering gastric acid secretion &
preserve the enzyme
Toxicity
Renal uric acid stone formation(the enzyme
has high purine content)

Lactose intolerance

LAXATIVES
Kinds
Irritants/stimulants
Bulking laxatives
Stool softener

Constipation

Irritant/Stimulant laxatives
Castor oil
hydrolyzed in upper small intestine to
ricinoleic acid, a local irritant that increase
motility

Cascara, Senna, Aloes

contain emodin alkaloid that cause colon
stimulation 6-8 after ingestion

Phenolphthalein,
Bisacodyl - Dulcolax supp / tab)
colonic stimulants
Sodium Picosulfate(Laxoberal tab, liquid)

Bulking laxatives
Hydrophylic colloids, Prepared from indigestible parts
of fruits, vegetable seeds, Forms gels in the large
intestines, distending it & stimulating peristalsis
Kinds Agar, Psyllium seeds (Metamucil sachet),
Methylcellulose, Bran/vegetable fiber

Saline cathartics non absorbable salts that holds

water & cause distension & peristalsis like Mg citrate
& Mg hydroxide
Polyethelene glycol
Lactulose (duphalac)
synthetic disaccharide (galactose-fructose)
not absorb

osmotic laxative(attracts water)

Sorbitol also non absorbable

Stool Softeners
Emulsify stool & soften it
Kinds
Mineral oil
Glycerin suppository
Dioctyl sodium sulfosuccinate(docusate)

Diarrhea

ANTIDIARRHEAL

Opioids
Inhibit acetylcholine release at presynaptic
opioid receptors & stops intestinal motility

Kinds
Diphenoxylate - weak analog of Meperidine
Loperamide related to haloperidol

Contraindication
Ulcerative colitis may cause toxic
megacolon

ANTIDIARRHEAL
Adsorbent
Kaolin/pectin

DRUGS USED FOR DISSOLUTION OF

GALLSTONES
Only for cholesterol gallstones
Kinds
Chenodiol
Ursodiol

Both can dissolve cholesterol

gallbladder stone 5mm within 2 years
therapy
Cannot dissolve stones with >4%
calcium

 Controversial
`If stone contains <4% calcium, it cannot
be seen on xray as radio opaque and
therefore not readily diagnosed
Patient may have recurrence if treatment is
stopped and may need to be treated for life
If stone causes obstruction before it can be
dissolved, it becomes a surgical emergency

Ursodiol is also being used for primary

biliary cirrhosis

DRUGS USED FOR TREATMENT OF CHRONIC

INFLAMMATORY BOWEL DISORDERS
Ulcerative Colitis
Crohns disease
Kinds
Corticosteroid
Immunosuppressive drugs
Salicylates 5 amino salicylic acid, Mesalamine

Mechanism
Affects arachidonic acid pathway in
pathogenesis of inflammation
Inhibits prostaglandin and leukotriene production

Other kinds
sulfasalazine/Sulfapyridine
toxicity Mallaise, headache, abdominal
discomfort, serum sickness, bone
marrow suppression

olsalazine may cause watery

diarrhea
balsalazide
all salicylates are given orally or by
retention enema

Immunosuppressive agents

Corticosteroid
Hydrocortisone
Prednisone
Oral or retention enema

Cytotoxic drugs
Azathioprine, Cyclosporine,
Mercaptopurine
Helpful in fistulas associated with
Crohns
Toxicity
drug induced pancreatitis

Infliximab
Treatment for imflammatory bowel disorder
A monoclonal antibody directed at TNF, a
protein known to cause inflammation in
Crohns
Toxicity
nausea
serum sickness
serious infection
malignancy(lymphoma)
very expensive $2000/infusion

DRUGS USED IN PORTAL SYSTEMIC

ENCEPHALOPATHY
NEOMYCIN
Non absorbable antibiotic
LACTOSE laxative

Mechanism unclear
Reduced by bacteria to lactic acid/acetic
acid which traps ammonia and other toxins
in intestines causing the encephalophaty

END