GI DRUGS ANTIDIARRHEALS LAXATIVES ANTIEMETICS DRUGS FOR INFLAMMATORY BOWEL DISEASE. TREATMENT OF...
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Transcript of GI DRUGS ANTIDIARRHEALS LAXATIVES ANTIEMETICS DRUGS FOR INFLAMMATORY BOWEL DISEASE. TREATMENT OF...
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 anti-inflammatory 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.
CONSTIPATION-PATHOPHYSIOLOGY
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 rapidlyDon’t use for more than 10 days.Overdosage can lead to catharsis and fluid
and electrolyte disturbances.
STIMULANT LAXATIVES
Anthraquinone laxatives (1,8-dihydroxyanthraquinone 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 stool-softening 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).
Blood born emetics
Local Irritants
Emetic Center
Higher Centers
Sensory Input
Memory, fear, dread, and anticipation
Stomach and small int
Pharynx (gagging)
Inner ear
cerebellum
CNS
PeripheryBLOOD BRAIN BARRIER
5-HT3
CTZ5-HT3 D2
M1
Solitary tract nucleus
5-HT3 D2 M H1
Vagal and sympathetic afferents
Glossoph.,trigeminal affs.
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 receptor- substance 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 CorticosteroidsCannabinoidsAntihistaminesMuscarinic antagonistsBenzodiazepines
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 BOWEL-DIRECTED 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 small-bowel 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 5-HT3 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 phenothiazinesBethanecholProkinetic agents-metoclopramide,
cisapride and domperidone
Prokinetic Agents
Cholinergic agentsDopamine receptor antagonists-
domperidone and metoclopramide.Serotonin receptor modulators-cisapride
and metoclopramide.
METOCLOPRAMIDE
CNS effects characteristic of dopaminergic blockade.
Antagonism of emesis induced by apomorphine and ergotamine
HyperprolactinemiaSignificant extrapyramidal symptomsAnxiety,depressionDrowsiness, 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.