Transcript Physiology of GI motility and secretion

GI DRUGS
 ANTIDIARRHEALS
 LAXATIVES
 ANTIEMETICS
 DRUGS FOR INFLAMMATORY BOWEL DISEASE.
 TREATMENT OF IRRITABLE BOWEL
SYNDROME
GI MOTILITY AND
SECRETION
Colonic function is subject to complex
sets of regulatory influences.
NEURAL PATHWAYS
CNS -both sympathetic and
parasympathetic innervation.
Myenteric nervous system.
OTHER PATHWAYS
Hormonal –somatostatin, opioids, ADH,
prostaglandins, VIP.
Immunological.
GI MOTILITY
Proper movement of nutrients, wastes,
electrolytes and water thru the intestine
depends on a balance of absorption and
secretion of water and electrolytes by the
intestinal epithelium.
GI MOTILITY
Neurohumoral mechanisms, pathogens
and drugs can alter uptake and secretory
processes.
GI MOTILITY
Altered GI motility contributes to
diarrhea or constipation.
Drugs can stimulate or reduce intestinal
motility.
GI MOTILITY
 GI motility is also an important component of
vomiting.
 During nausea and vomiting there is inhibition
of gastric motility
 Enhanced gastric emptying is a significant
aspect of the actions of some antiemetics.
TREATMENT OF DIARRHEA
PATHOBIOLOGY
 Excessive fecal loss of fluid and electrolytes.
 Due to a combination of increased motility,
decreased fluid absorption and increased fluid
secretion.
 Dehydration and electrolyte imbalances occur.
CAUSES
Infections.
Malabsorption-e.g. lactose, sorbitol,
olestra.
Allergy/inflammation.
Intoxication and drug reactions
(preformed enterotoxins, alcohol, some
antibiotics, antacids and laxatives).
Hormone secreting tumors.
TREATMENT OF
DIARRHEA
The aim is to enhance intestinal absorption
of water or decreasing intestinal motility.
Treatment is generally nonspecific.
NONDRUG APPROACHES
Patience
TREATMENT OF
DIARRHEA
Supportive therapy and oral rehydration
therapy.
PHARMACOTHERAPY
Reserved for patients with significant or
persistent symptoms.
TREATMENT OF DRUG
CAUSED DIARRHEA
Adjustment of dosage or change in
medication is preferred to the use of an
antidiarrheal agent especially on a long
term basis.
ANTIBIOTICS
Usually not required.
Infectious agent must be matched with
the appropriate antibiotic.
Improper use encourages resistance.
OPIOIDS
 Mainstay of nonspecific drug therapy.
 Agonists for myenteric opiate receptors.
 Anti-secretory and anti-motility properties.
 Effective vs. moderate to severe diarrhea.
OPIOIDS
 Codeine and paregoric are effective but have a
high abuse potential.
 Synthetic opioids are preferred because they
penetrate poorly into the CNS and produce
antidiarrheal effects at doses that produce few
central effects.
OPIOIDS
Diphenoxylate has some abuse potential
(atropine added)(Lomotil) .
Loperamide (Immodium) is highly
specific for intestinal opiate receptors.
TRAVELERS DIARRHEA
The combination of loperamide and an
antimicrobial drug is probably the best
treatment for most patients with
travelers diarrhea (effective alone also).
Ciprofloxacin (or another quinolone) is
usually the DOC.
OPIOIDS-ADVERSE EFFECTS
With excessive use or overdose.
CNS depression, constipation,
inflammatory conditions of the colon and
megacolon.
BISMUTH SUBSALICYLATE
AND SUBCITRATE
Some anti-secretory and antiinflammatory properties but also
antibacterial activity.
Nausea and abdominal cramps also are
relieved.
Prophylaxis and treatment of travelers
diarrhea.
ADVERSE REACTIONS
Staining of oral and anal tissues.
Tinnitus.
SOMATOSTATIN ON THE GI
TRACT
Multiple actions.
Inhibition of gastric acid and pepsin
secretion.
Inhibition of endocrine secretions.
Inhibition of intestinal fluid and
bicarbonate secretion.
Decrease of smooth muscle contractility.
Half-life is too short to be useful as a drug.
OCTREOTIDE
Peptide analog of somatostatin.
Effective for the diarrhea associated with
some hypersecretory tumors and AIDS related diarrhea.
Short-term therapy may produce nausea
and GI upset.
BULK-FORMING AND
HYGROSCOPIC AGENTS
For mild diarrhea.
Hydrophilic colloids (psyllium,
polycarbophil and CMC).
Kaolin and other clays.
BILE ACID SEQUESTRANTS
Used in bile salt-induced diarrhea, as in
patients with resection of the distal ileum.
CONSTIPATIONPATHOPHYSIOLOGY
Decreased intestinal and colonic motility
and excessive fluid uptake.
It is not a disease but a symptom that
may result from a broad variety of
underlying causes.
CAUSES
Congenital.
Inadequate dietary fiber and fluid
ingestion.
Ignoring defecatory urge.
Drugs and toxins.
Neurogenic, metabolic and endocrine
conditions.
Structural abnormalities in the GI tract.
AIM OF THERAPY
To increase the water content of the feces
and to increase intestinal motility.
TYPES OF THERAPY
NonDrug Approaches
Laxatives
Enemas
NONDRUG APPROACHES
Increasing water and fiber content of the
diet, appropriate bowel habits and by
exercise and bowel training.
LAXATIVES
Promote passage of the stools.
Overused by the public due to
misconception of what is normal.
LAXATIVES
 Constipation.
 Used prior to surgical, radiological and
endoscopic procedures where an empty colon is
desirable.
 To help maintain soft stools in patients with
anorectal disorders such as hemorrhoids and in
patients with irritable bowel syndrome and
diverticulitis.
CONTRAINDICATIONS
Obstruction
Megacolon and megarectum
ENEMAS AND SUPPOSITORIES
Adjuncts to bowel preparation regimens.
Glycerin suppositories (acts as
hygroscopic agent and lubricant)
LAXATIVES
 Precise mechanism of action of many laxatives
remains unknown.
 Three or four common groups can be
described.
 Bulk forming laxatives, saline and osmotic
laxatives, stimulant laxatives and stool
softeners.
BULK FORMING
LAXATIVES
Increase fecal mass and stimulate colonic
stretch receptors.
Promote fluid retention in feces.
Natural or semisynthetic polysaccharides
and cellulose derivatives.
ADVERSE EFFECTS
 Relatively safe and rarely abused.
 Allergic reactions.
 Flatulence occurs occasionally (as well as bloating and
abdominal pain).
 Intestinal obstruction and impaction may occur.
 Some preps may release Ca++
Dietary fiber, psyllium and
methylcellulose
Poorly digested fibers or digested by
colonic bacteria.
CALCIUM
POLYCARBOPHIL
Synthetic resin that absorbs large
amounts of water.
SALINE AND OSMOTIC
LAXATIVES
Poorly and slowly absorbed, act by their
osmotic properties in the luminal fluid.
Increase fluid retention in stools or
increase luminal fluid contents. This
stimulates peristalsis.
May produce inflammatory mediators.
SALINE LAXATIVES
(MgSo4, Mg(OH)2, MgCitrate, Na
Phosphate).
Poorly absorbed ions that favor osmotic
movement of water into the lumen.
SALINE LAXATIVES
 Use caution or avoid in patients with congestive
heart failure and renal impairment and in the
elderly.
 Some have bitter taste.
 Excessive evacuation of intestinal contents is
possible.
NONDIGESTABLE SUGARS
AND ALCOHOLS
 Glycerin,lactulose, sorbitol, mannitol.
 Poorly absorbed carbohydrates that favor
osmotic movement of water into the intestinal
lumen.
 Resistant to digestion.
 Relatively safe.
LACTULOSE, SORBITOL AND
MANNITOL
Nonabsorbable sugars that are
hydrolyzed in the intestine to organic
acids which acidify the luminal contents
and osmotically draw water into the
lumen, stimulating motility.
LACTULOSE
Used also to treat hepatic
encephalopathy.
Drop in luminal pH that accompanies
hydrolysis to short chain fatty acids in
the colon results in trapping of NH3.
POLYETHYLENE GLYCOL
(PEG)-ELECTROLYTE
 Long-chain PEG’s are poorly absorbed and retain
added water by virtue of their high osmotic nature.
 Prepared with an isotonic mixture of Na sulfate,
bicarbonate, chloride and KCL (avoids transfer of
ions).
 Used prior to colonoscopy and other bowel procedures.
 Used to treat constipation in difficult cases.
STIMULANT LAXATIVES
Promote accumulation of water and
electrolytes in the colonic lumen.
Stimulate peristalsis.
STIMULANT LAXATIVES
 Direct effects on enterocytes, enteric neurons
and muscle.
 Produce a low grade inflammation to promote
water and electrolyte accumul’n.
 Work by complex mechanisms and via several
different mediators (NO,PG’s etc).
ADVERSE EFFECTS
Excessive laxation is common.
Acute cramping and vomiting.
Long-term-electrolyte disturbances, fat
malabsorption, fat-soluble vitamin
deficiency and laxative dependence.
Allergic reactions.
Carcinogenicity.
Laxative abuse.
STIMULANT LAXATIVES
Diphenylmethane derivatives
(phenolphthalein and bisacodyl).
Phenolpthalein-potential carcinogen.
BISACODYL
Enteric coated tablets and suppositories.
Requires hydrolysis for activation so takes
at least 6 hrs.
Suppositories work more rapidly
Don’t use for more than 10 days.
Overdosage can lead to catharsis and fluid
and electrolyte disturbances.
STIMULANT LAXATIVES
Anthraquinone laxatives (1,8dihydroxyanthraquinone and its
glycoside derivatives that are contained
in senna, cascara, rheum (rhubarb) and
aloe.
ANTHRAQUINONES
 Produce giant migrating colonic contractions
and induce water and electrolyte secretion.
 Laxative effects are not seen for 6-12 hrs.
 Adverse effects have limited their use
(melanotic pigmentation and cathartic colon).
CASTOR OIL
Unpleasant taste and potential toxicity on
intestinal epithelium and enteric neurons.
SURFACTANT LAXATIVES
(STOOL SOFTENERS)
 Anionic surfactants.
 Act primarily as stool-wetting and stoolsoftening agents, allowing the mixing of water,
lipids and other fecal material.
 Alter intestinal permeability
 Marginal efficacy in most cases.
ADVERSE EFFECTS-STOOL
SOFTENERS
Mild side effects.
Potential to increase intestinal absorption
and toxicity of other drugs given
concurrently.
DOCUSATES
 Prototype for this group.
 Although they produce only mild side effects
(occasional cramping, rashes, nausea) they
have potential serious effects.
 Docusate sodium (Colace)
DOCUSATES
They increase the intestinal absorption
and toxicity of other drugs administered
concurrently.
Overall their efficacy is slight and their
potential for toxicity is significant.
MINERAL OIL
Penetrates and softens the stool.
Adverse effect profile precludes regular
use.
May interfere with water absorption.
Interferes with absorption of fat soluble
vitamins.
MINERAL OIL
Elicitation of foreign body reactions in
the intestinal mucosa.
Leakage of oil.
Possibility of lipid pneumonitis.
ANTIEMETIC AGENTS
DRUG LIST
Ondansetron
Metoclopramide
Aprepitant
NAUSEA AND VOMITING
 Follows administration of many drugs.
 Accompany infectious and noninfectious GI
disorders.
 Early pregnancy.
 Motion sickness.
 Emergence from general anesthesia.
NEURAL PATHWAYS LEADING
TO EMESIS
Coordinated by the vomiting center.
This center receives input from CTZ.
From vestibular apparatus via the
cerebellum.
From higher brainstem and cortical
structures.
From visceral afferents in the periphery.
From emetic substances in the circulation.
EMETIC RESPONSE
Following stimulation of the vomiting
center, emesis is mediated by various
efferent pathways.
NAUSEA AND VOMITING
 Thought to be protective reflexes.
 Nausea occurs initially followed by reduced gastric
tone, reduced peristalsis and increased tone in the
duodenum and upper jejunum. Gastric reflux then
occurs.
 Accompanied by multiple autonomic phenomena
(salivation, shivering, vasomotor changes).
Higher Centers
cerebellum
Emetic Center
5-HT3 D2 M H1
Solitary tract
nucleus
CNS
Periphery
Memory, fear, dread,
and anticipation
Inner
ear
CTZ
5-HT3 D2
M1
BLOOD BRAIN BARRIER
5-HT3
Stomach
and small int
Sensory
Input
Vagal and
sympathetic
afferents
Glossoph.,
trigeminal affs.
Blood born
emetics
Local
Irritants
Pharynx
(gagging)
NEUROTRANSMITTER
PATHWAYS OF EMESIS
 Serotonin acting at 5-HT3 receptors is an
important emetic signal and transmitter in the
afferent pathways from the stomach and small
intestine, in the CTZ and in the solitary tract
nucleus.
NEUROTRANSMITTER
PATHWAYS OF EMESIS
Dopamine acting at D2 receptors is
implicated in emetic signaling thru the
trigger zone and the solitary tract
nucleus.
NEUROTRANSMITTER
PATHWAYS OF EMESIS
Substance P/neurokinin 1 receptorsubstance P induces vomiting and binds
to NK-1 receptors in the abdominal
vagus, STN and the area postrema.
NEUROTRANSMITTER
PATHWAYS OF EMESIS
 Histamine and H1 receptors are concentrated in the
solitary tract nucleus as well.
 Cholinergic and histaminergic synapses seem to be
involved in transmission from the vestibular
apparatus to the emetic center.
 Basis for use of H1 receptor antihistamines and
muscarinic cholinergic antagonists in motion
sickness.
EMESIS
Sensory stimuli such as pain and sight
can contribute to vomiting as can the
anticipation of an unpleasant experience.
ANTIEMETIC AGENTS
 5-HT3 antagonists
 D2 antagonists
 NK1 receptor antagonists
 Corticosteroids
 Cannabinoids
 Antihistamines
 Muscarinic antagonists
 Benzodiazepines
ANTIEMETIC AGENTS
A number of useful antiemetics such as
corticosteroids and cannabinoids do not
yet fit into the scheme.
COMBINATIONS
Provide a major improvement in the
ability to reduce nausea and vomiting.
Decrease toxicity associated with some
antiemetics.
5-HT3 ANTAGONISTS
Selective serotonin receptor antagonists
5-HT3 ANTAGONISTS
Ondansetron (Zofran)
Granisetron (Kytril)
Dolasetron (Anzemet)
Palanosetron (Aloxi)
MECHANISM OF ACTION
 5-HT3 antagonists in both the periphery and
CNS.
 Act at several sites critical for emesis.
 No effects on dopamine receptors (lack toxicity
of metoclopramide).
 Differences between the individual drugs
mainly pharmacokinetics.
PHARMACOKINETICS
Orally, IV or IM.
Effective upon once daily administration.
Undergo CYT P450 metabolism.
THERAPEUTIC USES
Prevent or minimize emesis due from
moderate-high doses of chemotherapy
(e.g. cisplatin) and radiation.
Effective vs. hyperemesis of pregnancy
and to a lesser extent postoperative
nausea (not motion sickness).
ADVERSE EFFECTS
 Transient, mild adverse effects including
headache, sedation, light-headedness, dizziness
and constipation.
 Lack extrapyramidal side effects associated
with metoclopramide.
 Minor EKG changes.
D2 ANTAGONISTS
 Antagonists at the D2 dopamine receptor (some
may have 5-HT3 receptor antagonism also).
 Several drugs are in this class including
substituted benzamides (metoclopramide,
phenothiazines, benzimidazole derivatives
(domperidone) and butyrophenones
(haloperidol, droperidol).
METOCLOPRAMIDE (Reglan)
 D2 antagonist and potent antiemetic (at high
doses).
 Prokinetic effects on the intestine (at standard
doses).
 At higher concentrations it also blocks 5-HT3
receptors.
THERAPEUTIC USES AND
TOXICITY
 Reduces cisplatin emesis in most patients and
prevents it in 30-40%.
 The use of high dose metoclopramide is limited
by its antidopaminergic side effects which
include extrapyramidal reactions, anxiety and
depression.
 These side effects are most prominent in
younger patients especially when given orally.
D2 ANTAGONISTS
Phenothiazines
Domperidone
APREPITANT (Emend)
NK1 receptor antagonist.
Very useful vs delayed nausea.
Synergistic with 5-HT3 antagonists.
THERAPEUTIC USES
Used with corticosteroids and serotonin
receptor antagonists to prevent nausea
and vomiting caused by highly
emetogenic anticancer drugs.
ADVERSE EFFECTS
Fatigue and asthenia
Hiccups
Diarrhea and dizziness.
CORTICOSTEROIDS
Mechanism of antiemetic action is not
known.
Possible mechanisms include
prostaglandin blockage and changes in
cell permeability.
THERAPEUTIC USES
Useful in mild to moderate
chemotherapy-induced emesis.
Addition to other antiemetic therapies
enhances the overall antiemetic effect
achieved and can reduce the severity and
incidence of some adverse effects.
THERAPEUTIC USES
Use cautiously in certain patient groups
such as diabetics and patients with a
history of psychiatric disease.
Dexamethasone, methylprednisolone and
occasionally prednisone have been used.
CANNABINOIDS (Dronabinol
and Nabilone)
Therapeutic Uses- reduce emesis due to
moderate emetogenic chemotherapy.
ADVERSE EFFECTS
Hallucinations, disorientation, vertigo
and others limits their use to patients
refractory to or intolerant of other
antiemetic agents.
Concurrent use of prochlorperazine in
low doses can reduce the incidence of
dysphoria that accompanies cannabinoid
administration.
INFLAMMATORY BOWEL
DISEASE (IBD)
Sulfasalazine (Azulfidine)
Non-sulfonamide containing formulations
of mesalamine including Olsalazine and
Balasalazide
Infliximab
INFLAMMATORY BOWEL
DISEASE (IBD)
Inflammation of the colonic and/or
intestinal linings.
Chronic with temporary remissions.
Familial and infectious components.
IBD
Probably results from a cascade of events
and processes initiated by an antigen or
antigens in genetically susceptible
individuals.
SYMPTOMS
Diarrhea
Pain
Bleeding and related deficiencies.
Malabsorption
PATHOLOGY
Immune activation is followed by an
inflammatory response that is mediated
and amplified by several factors
including cytokines, oxygen radicals and
metabolites of arachidonic acid.
TYPES OF DISEASE
Ulcerative colitis- colon/rectum.
Crohn’s disease- extends to small
intestine and deeper into intestinal walls,
fistulas.
TREATMENT OF IBS IS
COMPLEX
Unknown nature of the causative agent.
Chronic and variable nature of the
inflammation.
Variability in goals of therapy.
5-AMINOSALICYLATES
SULFASALAZINE
Conjugate of mesalamine(5-ASA) linked to
sulfapyridine by a diazo bond.
5-ASA is the main therapeutic moiety.
Sulfapyridine accounts for most of the
toxicity.
The azo bond prevents early absorption of
the ASA from the upper small bowel
allowing high conc’ns in the colon.
MECHANISM OF ACTION
 Inhibits prostaglandin and leukotriene
synthesis.
 Reactive oxygen scavengers.
 Antiinflammatory effects-inhibits cytokine
production and immunoglobulin secretion.
THERAPEUTIC USES
Oral use for mild or moderate ulcerative
colitis.
Less certain value for severe colitis (often
given with steroids).
Crohn’s disease is less responsive.
ADVERSE EFFECTS
Fever and malaise.
Nausea, vomiting,headaches, epigastric
discomfort and diarrhea.
Megaloblastic anemia and low sperm
counts.
Allergic reactions.
ADVERSE EFFECTS
Necrolysis, Stevens Johnson syndrome,
pancreatitis, eosinophilic pneumonia.
NONSULFONAMIDE
FORMULATIONS
 Mesalamine(aminosalicylic acid)-enteric
coated, delayed release, microgranules, in a
wax matrix.
 Olsalazine(2 mesalamines linked together).
 Balsalazide(mesalamine linked to an inert
carrier).
CORTICOSTEROIDS
 Prednisone administered orally, parenterally or
rectally (Budesonide also).
 Antiinflammatory and immunosuppressive,
inhibition of production and action of cytokines
and inflammatory mediators.
 Adverse reactions are typical of systemic
corticosteroids.
INFLIXIMAB (Remicade)
Chimeric monoclonal antibody that binds
tumor necrosis factor (TNF).
Given by i.v. injection.
THERAPEUTIC USES
Produces and maintains remissions in CD
and helps promote healing.
ADVERSE EFFECTS
Headache, nausea, and upper respiratory
infections.
Allergic reactions
Immunosuppression.
IMMUNOSUPPRESSIVE
AGENTS
Inhibit lymphocyte proliferation.
Mercaptopurine and azathioprine.
Cyclosporine and methotrexate are also
used.
ANTIBIOTICS
Mainly adjunctive therapy
Mild to moderate Crohn’s disease.
Metronidazole and/or ciprofloxacin.
IRRITABLE BOWEL
SYNDROME
Tegaserod (Zelnorm)
IRRITABLE BOWEL
SYNDROME
A common disorder in which bowel
habits are altered in association with
abdominal pain or discomfort
(prevalence of about 12%).
SYMPTOMS
Abdominal pain, bloating and disturbed
bowel function (diarrhea or constipation
or both alternating)
NONPHARMACOLOGICAL
THERAPIES
Fiber supplements
Elimination diets followed by sequential
reintroduction of specific foods.
Avoidance of dietary excesses, caffeine
and dietary triggers.
Psychotherapy.
NONSPECIFIC BOWELDIRECTED THERAPY
Measures to reduce specific symptoms
related to constipation and diarrhea.
TREATMENT OF
CONSTIPATION
 Fiber supplements
 Magnesium salts
 Phosphate salts
 PEG-based laxatives
 Non-absorbed carbohydrates.
ANTIDIARRHEAL AGENTS
Opiate and opioid analogs
Specific Therapies
ANTISPASMODICS
Anticholinergics
Combined sedatives and antispasmodics
TRICYCLIC
ANTIDEPRESSANTS
 Low doses.
 Underlying mechanism is unknown.
 For moderate to severe IBS in which pain is
prominent or when other therapies have failed.
 Combined with antispasmodics.
SSRIs
Have similar efficacy but lack many of
the side effects of the TCA’s
SEROTONIN-3-RECEPTOR
ANTAGONISTS
Activated HT3 receptors stimulate
intestinal motility, secretion and
sensation.
Antagonists reduce colonic transit, and
gastrocolic reflex.
They reduce sensitivity to distention.
ALOSETRON (Lotronex)
Beneficial in women with IBS who did
not have constipation.
Reduces diarrhea and urgency, improved
quality of life.
ADVERSE EFFECTS
Constipation (25-30%).
Ischemic colitis was diagnosed in 1/700
patients and the drug was withdrawn.
Then reintroduced for select patients.
SEROTONIN-4 RECEPTOR
AGONISTS-TEGASEROD
Partial agonist at the HT4 receptor.
Accelerates gastric emptying and smallbowel transit.
Improves symptoms of abdominal
discomfort, bloating and constipation.
TEGASEROD (Zelnorm)
 Approved by the FDA for use for up to 12
weeks in women with constipation predominant
irritable bowel syndrome.
 Side effects are generally mild, with diarrhea,
the most predominant.
 Flatulence and headache also are common.
PROKINETIC AGENTS
Medications that enhance coordinated GI
motility and transit in the GI tract.
Pharmacologically and chemically diverse.
NEURAL REGULATION OF
GASTRIC MOTILITY
Stimulation by cholinergic neurons.
Inhibition by adrenergic neurons.
Modulatory influence of the enteric
nervous system where dopamine and
serotonin play a role. Thus D2 and 5HT3 receptor antagonists as well as 5-HT4
agonists stimulate gastric motility.
ETIOLOGY OF GASTRIC
HYPOMOTILITY
 Symptoms may include nausea, vomiting,
heartburn, postprandial discomfort,
indigestion and gastroesophogeal reflux.
 Causes are unknown in many patients but often
results from diabetic neuropathy a concomitant
of anorexia nervosa and achlorhydria and a
result of gastric surgery.
 Component of a number of G.I. disorders.
TREATMENT
Antiemetic phenothiazines
Bethanechol
Prokinetic agents-metoclopramide,
cisapride and domperidone
Prokinetic Agents
Cholinergic agents
Dopamine receptor antagonistsdomperidone and metoclopramide.
Serotonin receptor modulators-cisapride and
metoclopramide.
METOCLOPRAMIDE
CNS effects characteristic of dopaminergic
blockade.
Antagonism of emesis induced by
apomorphine and ergotamine
Hyperprolactinemia
Significant extrapyramidal symptoms
Anxiety,depression
Drowsiness, dizziness and anxiety
MECHANISM OF ACTION
Dopaminergic antagonist, blocks G.I.
Effects caused by local or systemic
administration of dopaminergic agonists.
May promote release of ACH from
myenteric neurons.
THERAPEUTIC USES
Diabetic gastroparesis.
Esophageal reflux.
Prevention of nausea and vomiting from a
variety of causes including pregnancy.
ADVERSE EFFECTS
Extrapyramidal effects.
CISAPRIDE
 Effects on motility of the stomach and small
bowel closely resemble those of metoclopramide.
 Increases colonic motility and can cause diarrhea.
 Devoid of dopamine antagonist activity. Thus it
does not influence concentration of prolactin in
plasma or cause extrapyramidal symptoms.
THERAPEUTIC USES
Disorders of gastric hypomotility. Efficacy
equals that of metoclopramide and
domperidone without the side effects that
result from dopamine receptor blocakde.
Gastroesophageal reflux disease.
Gastroparetic conditions.
Chronic idiopathic constipation and colonic
hypomotility.
ADVERSE EFFECTS
Transient abdominal cramping and diarrhea.
May increase absorption of diazepam and
alcohol.