Gastrointestinal Drugs

Antacids

Drugs used to neutralize

gastric acid
(Diarrhea)
(Constipation)

Adverse Effects
Sodium Bicarbonate: Distension, belching, systemic alkalosis, fluid retention
Calcium Carbonate: Distension, belching, systemic alkalosis, hypercalcemia
Al hydroxide and Mg hydroxide: Long acting, constipation/diarrhea (respectively)
Caution in renal insuffiency

Drug interaction:
All antacids reduce absorption of other medications by binding and altering pH
Should be taken 2 hrs before or after other drugs

Therapeutic uses
Peptic ulcers
GERD (relived symptoms, no healing)

Endoscopic view of a gastric ulcer of a 82 year-old female patient

Normal Gastric Mucosa

The pathogenesis of peptic ulcer disease

is not fully understood
Three major factors are recognized:
1. infection with gram-negative Helicobacter pylori
2. increased hydrochloric acid secretion
3. inadequate mucosal defense
against gastric acid

Treatment approaches
include
(1)eradicating H. pylori infection
(2) reducing secretion of gastric acid
or neutralizing the acid after it is released, and/or
(3) Providing agents that protect
the gastric mucosa from damage.

Acid secretion inhibitors

Drugs
used to
lower
gastric
acid
productio
n

Activation of Proton Pump

Inhibitor (PPI) in Parietal Cell

3
4

Basal
Membrane

INHIBITORS OF
PROTON PUMP

Lansoprazole
Omeprazole
Rabeprazole
Pantoprasole
Esomeprosole

Adverse Effects
These drugs have a good adverse effects profile, and are generally
well-tolerated.
The most common adverse effect is diarrhea, particularly with longterm use.
Other rare adverse effects include rash, liver enzyme abnormalities,
and interstitial nephritis.
Long-term treatment with these drugs causes carcinoid tumors in the
stomachs of laboratory animals, but has not been observed in clinical
practice. Always consider whether maintenance treatment is required.
What about the bones?
Interactions
The potential for drug interactions with these drugs is low.
Lansoprazole, omeprazole, and esomeprazole inhibit hepatic cytochrome P450
enzymes to some degree. This effect is not great, but may enhance the actions of
warfarin and phenytoin
Safety
Beware of prolonged treatment with these drugs without a diagnosis; they can
mask the symptoms of gastric malignancy.
Patients with Barrett's esophagus require regular endoscopic follow-up.

P - 15

Drugs
used to
lower
gastric
acid
productio
n

H2
HISTAMIN
E
RECEPTO
R
BLOCKER
S
Cimetidin
e
Famotidin
e
Nizatidin
e
Ranitidin

Mechanism of Action: Competitive blockade of H2 receptors

Pharmacokinetics
- Oral bioavailability: 50%
- Distributed in all organs, including brain.
-A large fraction of these drugs is eliminated as such in the urine,
mainly by tubular secretion.
Therapeutic Uses
When suppression of gastric acid is required.
Healing of gastric and duodenal ulcers.
Reflux esophagitis.
May be used in prophylaxis against gastric ulceration in an ICU.
Use famotidine, nizatidine, or ranitidine in preference to cimetidine,
because of drug interactions with cimetidine.
Contraindications and Cautions
Rule out other upper GI diseases e.g. malignancy
H2 receptor antagonists are less effective than proton pump inhibitors.
Halve the dose in severe renal or hepatic insufficiency.
There is no information on the safety of these drugs in pregnancy. Avoid
using them.

P - 16
Remember H2 receptor blockers are more effective for nocturnal acid
secretion as opposed to food stimulated acid secretion
Adverse effects
The most common are: diarrhea, altered liver function, rash, headache
and dizziness
Cimetidine blocks androgen receptors and may cause gynecomastia, loss
of libido and impotence.

Drugs metabolized by CYP1A2, CYP2C9 and CYP3A4

P - 16

Drug-drug Interactions

Nizatidine, famotidine, and ranitidine do not do th

Absorption of cimetidine is reduced by antacids

Pirenzepine
blocks
cholinergic
receptor
Acetylcholin
e

Cimetidine
blocks H2
histamine
receptor
Histamine

Misoprostol
stimulates
prostaglandin
receptor
Prostaglandin I2
and E2

Gastrin

No activation of
protein kinase

Omeprazole
blocks proton
pump

PARIETAL
CELL
Lumen of
Stomach

Treatment of H. pylori
Infection

P - 20

Urease

Ammonia cloud

Urease
Urease Urease

Urease

Urease

Urease
Urease

Urease

Urea

Urease
Urease

Urease

Urease

NH3

Urease

Urease

H2O
2CO2

Urease

Urease
Urease
Urease

Urease

Type IV secretion system

P - 20

Helicobacter eradication
Use of multiple drugs prevents development
of drug resistance

Quadruple Therapy
Bismuth Subsalicylate
Metronidazole
Tetracycline
H2 receptor antagonist or PPI

More commonly given for 2 weeks

Gastric acid suppressors for 6-8 weeks
Eradication rate = 90%

P - 21

Mucosal Protective Agents

DRUGS USED TO TREAT PEPTIC

ULCER DISEASE

MUCOSAL
PROTECTI
VE
AGENTS
COLLOID
AL
BISMUTH
SUCRALF
ATE

PROSTAGLAN
DINS (Mucosal
protective)

Misoprost
ol

Structure and protective effect of

Misoprostol
Mucus
Mucus
Mucus
Mucus
Mucus
Low acid secretion
Mucus
Mucus
Mucus
Mucus
Mucus

Chemical structure and protective effect

of Sucralfate

Sucrose
Aluminum Hydroxide
Sulfate

Also stimulates
Prostaglandin
Mucus and
Bicarbonate
release

Ulcer crater

Antiemetics

CTZ
Solitary Tract Nucleus
5-HT3, D2, M1 5-HT3, D2, M1, H1, NK1

Stomach
5-HT3

Solitary Tract Nucleus

5-HT3, D2, M1, H1, NK1

CTZ
5-HT3, D2, M1

Solitary Tract Nucleus

5-HT3, D2, M1, H1, NK1

Cerebellum
M1, H1

Solitary Tract Nucleus

5-HT3, D2, M1, H1, NK1
CTZ
5-HT3, D2, M1

Cerebellum
M1, H1

CTZ
5-HT3, D2, M1

Solitary Tract Nucleus

5-HT3, D2, M1, H1, NK1

Cannabinoids

ANTIEMETIC ACTIVITY

% RESPONSE
AGAINST CISPLATIN CHEMOTHERAPY

Drug
Combinations

Serotonin
antagonist
Substituted
benzamide
Phenothiazine

Dexamethasone
Ondansetron

91%

Dexamethasone
Diphenhydramine
Metoclopramide
Droperidol
Lorazepam
Dexamethasone
Metoclopramide

Butyrophenone
Corticosteroid
Cannabinoid
Antihistamine

76%

63%

Diphenhydramine
Dexamethasone
Metoclopramide

Anticholinergic
Benzodiazepine
Low

High

58%
0%

100%

Anti-diarrheal / Laxative drugs

Diarrhea

Ac u t e :
Increased frequency and / or fluidity of
bow el movements of abrupt onset.
Major causes:
Infectious agents
Tox i n s
Drugs
An x i e t y
Chronic:
Passage of loose stools w ith or without
increased stool frequency for more
than 3 4 w eeks.

Epidemiolo
gy

World w ide more than 1 billion people

suffer one or more episodes of acute
d i a r r h e a e a c h y e a r.

Because of poor sanitation and limited

access to health care diarrhea remains
one of the most common causes of child
mortality in developing countries.
5 8 m i l l i o n d e a t h s p e r y e a r.

Diarrhea and constipation account for

nearly 50% referrals to gastroentrologists

Antidiarrheals
Antimotility Agents
Diphenoxylate, loperamide
Both are meperidine derivatives
Activate presynaptic opioid receptors, inhibit Ach
release (see next slide)

Adsorbents
Kaolin, pectin

Agents that modify fluid/electrolyte transport

NSAIDS
Bismuth subsalicylate (Pepto Bismol)

Lomotil
Diphenoxylate and atropine
Atropine is added to discourage
deliberate overdosage and may also
contribute to anti-diarrheal effect

methscopolamineatropine, scopolamine

CONSTIPATION

Bulk Laxatives

Stimulation of persistalsis by an intraluminal bolus

Osmotically active laxatives

Epsom salt (MgSO4) and Glaubers salt (Na2SO4), the SO4 2- anion is not absorbable so
causes osmotic laxative effect

Mannitol is also an osmotic laxative

Fe c a l s o f t e n e r s ( o r
Emollient laxative)

Docusate Sodium
A surface-active
compound that acts in
the GIT in a manner
similar to a detergent
and produces softer
feces.
It is also a weak
stimulant laxative.