Antiemetics/ Antivertigo agents- include
  Phenothiazines-
     Chlorpromazine                 Nausea /Vomiting   
     Triflupromazine                 Nausea /Vomiting
      Perphenazine                   Nausea /Vomiting
      Promethazine                   Nausea /Vomiting      Motion Sickness
      Prochlorperazine             Nausea /Vomiting
    Others-
      Metoclopramide              Nausea /Vomiting
   
Anticholinergics-
    Antihistamines-
      Cyclizine                          Nausea /Vomiting      Motion Sickness
      Meclizine                         Nausea /Vomiting      Motion Sickness      Vertigo
      Buclizine                                                               Motion Sickness
      Diphenhydramine           Nausea /Vomiting      Motion Sickness      Vertigo
      Dimenhydrinate              Nausea /Vomiting      Motion Sickness       Verigo

    Others-
      Trimethobenzamide      Nausea /Vomiting
      Scopolamine                                                       Motion sickness
 
  Miscellaneous-
     Diphenidol                       Nausea /Vomiting                                         Vertigo
     Benzquinamide                Nausea /Vomiting
     Phosphated carbh }        Nausea /Vomiting
     hydrated  solution  }
     Hydroxyine                       Nausea /Vomiting
     Corticosteroids                Nausea /Vomiting
     Cannabinoids                   Nausea /Vomiting   

Refer -Chlorpromazine

Interacting drugs - summary

Metoclopramide +

Alcohol
 Metoclopramide  increase the rate of absorption  of alcohol  by decreasing the time it takes to reach the small intestine where it is  rapidly absorbed

Cimetidine
 bioavailalability of Cimetidine reduced due to decreased  absorption as a result of faster gastric transit time.
                              
Cyclosporine
 a faster gastric emptying time  allow for an increase in cyclosporine  absorption,  increasing its immunosuppressive and toxic effects.

Digoxin
 Digoxin absorption,plasma levels and therapeutic effects decreased. The capsule, elixir and tablets with high dissolution rate are least   affected.

Metoclopramide + Levodopa   or  Levopdoa +  Metoclopramide
 These agents have opposite effects on dopamine receptors. The bioavilability of levodopa  increased and   levodopa may decrease  the effects of metoclopramide   on gastric emptying and lower esophageal pressure.   Metoclopramide is relatively  contraindicated
  in Parkinsons disease                                                     

MAO inhibitors
 since metoclopramide releases catecholamines in patients  with essential hypertension  use cautiously if at all,    in patients receiving MAO inhibitors

Succinyl chloline  
 by inhibiting plasma cholinesterase, Metoclopramide increase  the neuromuscular blocking effect of Succinylcholine

Anticholinergic/ Narcotic analgesics
 the effects  of Metoclopramide on GI motility are antogonised by  these agents   

Nausea and vomiting.

Antiemetics/ Antivertigo agents- include
  Phenothiazines-
     Chlorpromazine                 Nausea /Vomiting    
     Triflupromazine                 Nausea /Vomiting
      Perphenazine                   Nausea /Vomiting
      Promethazine                   Nausea /Vomiting      Motion Sickness
      Prochlorperazine             Nausea /Vomiting
    Others-
      Metoclopramide              Nausea /Vomiting
    
Anticholinergics-
    Antihistamines-
      Cyclizine                          Nausea /Vomiting      Motion Sickness
      Meclizine                         Nausea /Vomiting      Motion Sickness      Vertigo
      Buclizine                                                               Motion Sickness
      Diphenhydramine           Nausea /Vomiting      Motion Sickness      Vertigo
      Dimenhydrinate              Nausea /Vomiting      Motion Sickness       Verigo

    Others-
      Trimethobenzamide      Nausea /Vomiting
      Scopolamine                                                       Motion sickness
 
  Miscellaneous-
     Diphenidol                       Nausea /Vomiting                                         Vertigo
     Benzquinamide                Nausea /Vomiting
     Phosphated carbh }        Nausea /Vomiting
     hydrated  solution  }
     Hydroxyine                       Nausea /Vomiting
     Corticosteroids                Nausea /Vomiting
     Cannabinoids                   Nausea /Vomiting    

Refer -Chlorpromazine

Approximately 20% to 30% of the patients experience side effects that are usually mild, transcient and  reversible upon drug withdrawal. Incidence also correlates with mild dose and duration of  metaclopramide use.

Extrapyrimidal symptoms- Acute dystonic reactions, the most common type of EPS associated with metaclopramide, occur in approximately  0.2% of patients treated with 30 to 40mg/day.

In cancer chemotherapy patients receiving  1 to 2mg/kg/dose, the incidence is 2% in
 patients > 30 years of age and 25% in children and young adults who have not had prophylactic of dophenhydramine.

Symptoms include involuntary movements of limbs, facial grimacing,toricolis, oculogyric crisis,  rhythmic protrusion of tongue, bulbur type speech, trismus, opisthotonus, (tetanus type reactions) and rarely stridor and dyspnea possibly due to laryngospasm.
Ordinarily these symptoms are readily reversed by diphenhydramine.

Parkinson-lke symptoms may include bradykinesia, tremor, cogwheel rigidity, mask-like faces Tardive dyskinesia most frequently is characterized by involuntary moveements of the tongue, face, mouth, or jaw, and sometimes by involuntary movemrents of the trunk or extremities, movements may be choreoathetotic in appearance

CNS-  Restlessness, drowsiness, fatigue,of anxiety, lassitude, dizziness, anxiety, dystonia,
 insomnia, headache, myoclonus, confusion, mental depression with suicidal ideation, convulsive  seizures, hallucinations

Allergic reaction- a few cases of rash, urticaria, bronchospasm, especially in patients with a history  of asthma. Rarely angioedema, including laryngeal edema.

GI- nausea, and bowel disturbances, primary diarrhea

Cardiovascular- Hypotension, hypertension, superventricular tachycardia, bradycardia

Endocrine- galactorrhea, amenorrhoea, gynaecomastia, impotence secondary to hyperolactinemia,  fluid retention, secondary to transcient elevation of aldersterone. Elevated  serum prolactin levels  may cause galactorrhea, reversible amenorhea, nipple tenderness and gynaecomastia in males.

Hematologic- neutropenia, leukopenia, agranulocytosis, methomoglobinemia (especially with  overdosage in neonates)  

Miscellaneous- Urinary frequency, incontinence, visual disturbances, porphyria, neuroleptic  malignant syndrome (NMS) potentially fatal is comprised of the symptom complex of hyperthermia  altered consciousness.
 Muscular rigidity, and autonomus dysfunction, transcient flushing of the face  and upper body without  alterations in vital signs, following high IV doses, case of hepatotoxicity  characterised by such  findings as jaundice,and altered liver function tests, when metoclopramide  was administered  with other drugs with known hepatotoxic potential.

 

G.I.Haemorrhage,mechanical obstruction/perforation, in G.I.tract,hypersens to the drug. Patients with phaecochromo-cytoma,epilepsy,parkinsonism.

Special Precautions:
Pregnancy, lactation, renal or hepatic impairment, prophyria.

Warnings

Depression- has occured in patients with or without previous history of depression. Symptoms have ranged from mild to severe and have included suicidal ideation and suicide. Give metoclopramide  to patients with a history of depression only if the expected benefits outweigh the potential risks.

Extrapyrimidal symptoms- manifested primarily as acute dystonic reactions,occur in approximately  0.2% to 1% of the patients treated with usual adult dosage of 30 to 40mg/day. These usually are seen during the first 24 to 48 hours of treatment, occur more frequently in children and young adults, and are more frequent in high doses used in prophylaxis of vomiting due to cancer chemotherapy.
 If these symptoms occur, they usually subside following 50mg diphenhydramine IM. Benzotropine  1 to 2mg IM may also be used to revese these reactions.

Parkinson-lke symptoms-have occured more commonly within first 6 months after beginning treatment with metoclopramide, but occassionally after long periods. These symptoms generally subside within 2 to 3 months following discontinuance of metoclopramide.i

Give metoclopramide  catiously,if at all to patients with pre-exixting Parkinsons disease, since such patients may  experience exacerbation of parkinsons symptoms when taking metoclopramide

Tardive dyskinesia- a syndrome consisting of potentially irreversible , involuntary ,dyskinetic  movements may develop in patients with metoclopramide. Although the prevalence of such  symptoms appears to be the highest amongst the elderly, especially elderly women, it is   impossible  to predict which patients are likely to develop the syndrome.
 Both the risk of   developing the  syndrome and the likelihood that it will become irreversible are  believed to  increase with the duration of treatment and the total cumulative dose.
Therefore use of  metoclopramide for the  symptomatic control of tardive dyskinesia is not
recommended.  

Hypertension- In one study of hypertensive patients, IV metoclopramide released catecholamines.  Use caution in hypertensive patients.

Anastomosis or closure of the gut- giving a promotility drug such as metoclopramide could
theoretically put increased pressure on suture lines following gut anastomosis or closure.
 Although adverse events related to this possibilirty have not been established, consider the
 possibility when deciding whether to use metoclopramide or neogastric suction in the prevention  of postoperative nausea and vomiting.

Carcinogenesis- elevated prolactin levels persist during chronic administration. Use caution if  metoclopramide is contemplated in a patient with previously detected breast cancer.

Pregnancy- Use only when clearly needed and when the potential benefits outweigh the potential  hazards to the fetus.

Lactation- Excercise caution when administering to a nursing mother.

Children-  Infants and children(ages 21 days to 3.3 years ) with symptomatic gastroesophageal reflux have been treated with metoclopramide at a dosage of 0.5mg/kg/day. Symptoms improved the duration of the disease was
shortened and surgery was avoided.

Approved on 1985

Indications:

Nausea and vomiting.

Dosage:
10 to 15mg orally  upto 4 times daily 30 minutes before each meal and at bed time..

Overdosage-  Symptoms                                                   

Drowsiness, disoreientation and extrpyrimidal reactions which are self limiting and usually
disappear within 24 hours.     
Muscle hypertonia, iriitability and agitaion are common.         

Treatment
    
  1. Antichoinergic or antiparkinsons drugs or antihitamines  with anticholinergic properties may help control extrapyrimidal reactions.

  2. Hemodialysis appears ineffective in removing metoclopromide.probably because of small  amount of the drug in blood relative to tissues.

  3. Similarly continous ambulatory peritoneal dialysis does not remove significant amount of the drug.


  4. It is unlikely that dosage would need to be adjusted  to compensate for the loss through dialysis.

  5. Methemoglobinemia has occured in premature infants who were given overdoses of
     metoclopromide.   Methemoglobenemia can be reversed by IV administration of methylene blue.
                   
Missed dose-

1. If you miss a dose of this medicine, take it as soon as possible.
2. However, if it is almost time for next dose, skip the missed dose and go back to your regular dosing schedule.
3. Do not double doses.  

 

For Availability/supplies 

List of entries
 
     1. Indigestion
     2. Heartburn
     3. Dysphagia
     4. Flatulance     
     5. Anorexia
     6. Nausea, Vomiting and Retching
     7. Gastritis     
     8. Diarrhea and Constipation
     9. Irritable bowel syndrome      
     10. Gastrointestinal Reflux
     11. Reflux Oesophagitis
     12. Peptic Ulcer - Zollinger- Ellison Syndrome
     13. Duodenal Ulcer
     14. Gastric Ulcer
     

1. Indigestion

Indigestion is a term frequently used to describe a multitude of symptoms generally appreciated with the distress with the intake of food.To some patients indigestion refers to a feeling that digestion has not proceeded naturally.
They may describe a sense of abdominal fullness, pressure or actual pain. Others may use the term to describe heartburn, belching, distention or flatulence.

Indigestion may occur as a result of disease of the gastrointestinal tract or in association with pathologic states in other organs       

2. Heartburn

Heartburn or pyrosis is a sensation of warmth or burning located substernally or high in the epigastrium. Experimental studies in human beings have shown that esophageal distention or increased motor activity is associated in most subjects with a feeling of fullness and burning in this area.

Heartburn may occur with organic disease ofthe intestinal tract and is usually associated with gastroesophageal
reflux. This is frequently the case in hiatus hernia

3. Dysphagia

Dysphagia or difficulty in swallowing is a most reliable symptom and indicates the presence of disease or dysfunction
Dysphagia should never be dismissed as emotional disturbance or to be confused with globus hystericus, a term used
to indicate the sensation of a lump or tightness in the throat independent of swallowing
 
4. Flatulance   

A significant amount of flatus is passed each day by normal persons and the complaint of flatulence often reflects
a heightened and embarassing awareness of this natural occurence. Many who complain of gas are in reality
experiencing symptoms ascribable to disordered motility. Excessive passage of of intestinal gas may be the result of
aerophagia or the formation of increased amounts of gas by intestinal bacteria.

5. Anorexia

Anorexia or loss of the desire to eat is a prominant symptom in a wide variety of intestinal and extraintestinal disorders.
Anorexia occurs in many disorders and as a result by itself or of little specific diagnostic value. The mechanism
whereby hunger and appetite are modified in variousdiseases are poorly understood. Anorexia is commonly seen
in diseases of the gastrointestinal tract and the liver.
 
6. Nausea, Vomiting and Retching

Nausea and vomiting may occur independently of each other, but generally they are so closely allied that they may
conveniently be considered together.
Nausea denotes the feeling of imminent desire to vomit,usually referred to the throat or epigastrium.
Vomiting  refers to the forceful oral expulsion of gastric contents.
Retching denotes the labored rhythmic respiratory activity that frequently precedes emesis.
Nausea often precedes or accompanies vomiting. It is usually associated with diminished functional activity of the
stomach and alterations of the motility of the duodenum and small intestine.

7. Gastritis     

Gastritis may be associated with recent alcohol ingestion or with the use of anti-inflammatory drugs, such as aspirin
or indomethicin. Another frequent setting is the development of gastric erosions in stressful situations such as
following major trauma or surgery or in assocaition with severe systemic disease. The occurence of gastritis in burn
victims and patients with increased intracranial pressure is also common.

8. Diarrhea and Constipation

The bowel habits of apparently healthy persons vary widely. For this reasoon, the term diarrhea and constipation
have most meaning when viewed as a change from an individuals customary pattern. Reasonably detailed information
is important in evaluating either abnormality. When  patients complain of diarrhea, it is important to obtain an estimate
of the volume as well as frequency of fecal output and in addition, to directly examine a stool for consistency, blood,
oilness and malodor.

The term constipation may be used by the patient to a variety of changes including reduction in frequency of
defecation, a constant sensation of rectal fullness and incomplete evacuation of feces and sometimes painful
defecation due to hard stools or perianal pathology

9. Irritable bowel syndrome      

The irritable bowel syndrome (also referred to as spastic colon and mucous colitis ) is one of the most frequent
gastrointestinal disorders. This condition is chracterized by periodic or chronic symptoms of diarrhea, constipation
and abdominal pain. These symptoms are generally associated with psychologic stresses, but the anxiety produced by
the bowel disturbance is sometimes regarded by the patient as the fundemental cause of emotional upset. Stools tend
to be thin, fragmented or pelletlike and accompanied by excessive mucus and gas.

10. Gastrointestinal Reflux

Reflux of small amounts of gastric juice into the lower part of the esiphagus is a common event. Its frequency is
increased by over indulgence. Whether reflux occurs and whether it produces symptoms are determined by three
factors
1. the competency of the lower esophageal sphincter , the primary barrier to reflux
2. the irriatant nature of the refuxed material and
3. the sensitivity of the esophageal mucosa to the refluxed material
Although the symptoms of reflux were attributed  in the past to inflammation of the esophagus ie esophagitis. It is
clear that esophagitis is a complication of severe reflux rather than the cause of the symptoms  associated with
reflux.

11. Reflux Oesophagitis

Reflux esophagitis is inflammation of the esophageal mucosa caused by reflux of acid gastric or alkaline intestinal
juice. Esophagitis is the prcursor of the complications of reflux, namely, bleeding, stricture and change in esophageal
epithelium from squamous to columnar. Bleeding is slow and chronic. Acute massive bleeding occassionally occurs
with esophagitis but is usually due to an associated peptic ulcer of the esophagus.

12. Peptic Ulcer - Zollinger- Ellison Syndrome

Peptic ulcer is a term used to refer to a group of ulceratrive disorders of the upper gastrointestinal tract,which appears
to have in common the participation of acid pepsin in their pathogensis. The major forms are chronic duodenal and
gastric ulcer. The Zollinger-Ellison syndrome gastrinome may also be considered a form of peptic ulcer.

13. Duodenal Ulcer

Duodenal ulcer is a chronic and recurrent disease. The ulcer is usally deep and sharply demarcated. It tends to
penetrate through the submucosa and often into the muscularis propria. The ulcer floor contains no intact epithelium
and usually consists of a zone of eosinophilic necrosis resting on a base of granulation tissue surrounded by variable
amounts of fibrosis. The ulcer bed may be clear or contain either blood or a proteinaceous exudate with entrapped
erythrocytes and acute and chronic inflammatory cells.

14. Gastric Ulcer

Gastric ulcers, just like as duodenal ulcers, are more common in males. They are also histologically similar to duodenal
ulcers. Gastric ulcers are characterstically deep, extending beyond the mucosa of the stomach. Almost all benign
gastric ulcers are located in the antrum, in a zone immediaterly distal to the junction of the antral mucosa with the
acid-secreting mucosa of the body of the stomach.

 

Refer Chlorpromazine

METOCLOPRAMIDE-

1.May produce drowsiness and dizzines.Observe caution while driving or performing other tasks requiring alertness.
2.Notify physician if involuntary movement of eyes,face or limbs occurs.
3.Take medication 30 minutes before each meal.

4..Allergies- tell your doctor if you have ever had any unusual or allergic reaction to
   metoclopropramide
  Also tell your doctor if you are allergic to any other substances, such as foods, preservatives or dyes.
  
5.Pregnancy - not enough studies have been made. However, metoclopramide has not been shown  to cause birth defects or other problems with animal studies 
 
6..Breast feeding-  although metoclopramide passes into breast milk it has not been reported to  cause problems in nursing babies 

7. Children - premature and full term infants may develop blood problems if given high doses of   metoclopramide
 
8. Elderly-  shuffling walk and trembling and shaking of hands may be especially likely to occur in  elderly patients     after they have taken metoclopramide over a long time. 
   
9. Other medicines - Tell your doctor if you are taking other medicines-

    Central nervous system depressants- use with metoclopramide may cause severe drowsiness
   
10. Other medical problems -    Tell your doctor if you have any other medical problems  -

    Abdominal or stomach bleeding or   Asthma or    High blood pressure or   Intestinal blockage or  Parkinsons disease - metoclopramide may make these conditions worse
       
11. Missed dose - If you miss a dose of this medicine, take it as soon as possible. however, if it is almost time     for the next dose, skip the missed dose. Do not double doses.

12. Storage -  Keep out of reach of children. Store away from heat or direct sunlight. Do not store   the capsule in bathroom, near the kitchen sink, or in other damp places.

13. Outdated medicines - Do not keep outdated medicine or medicine no longer needed. Be sure that any  discarded medicine is out of reach of children.

Pharmacology:
Metoclopramide stimulates motility of the upper GI tract without stimulating gastric,biliary or
pancreatic secretions.Its mode of action is unclear,but it appears to sensitise tissues to the action of acetylcholine.

Pharmacokinetics:
Onset of action is  1 to 3 minutes following IV dose, 10 to 15 minutes following IM administration, and 30 to 60 minutes following oral dose. Effects persists for 1 to 2 hours.
When the drug is taken on an empty stomach,absorption is rapid,with peak concentration
observed in 1 hour.

Metabolism:
Metoclopamide is primarily excreted in the urine(80%) in 24 hours either unchanged(upto 25%) or conjugated to sulfate or glucurinide in the bile. Half-life is approximately 3 to 6 hours. Impaired renal function prolongs the half-life(upto 24 hours). Dialysis effectively removes the drug.

None

Pregnancy:
Use only when clearly needed and when the potential benefits outweigh the the potential hazards to the fetus.

Lactation:
Excercise caution when administerring to a nursing mother.

Children-
Infants and children (ages 21 days to 3.3 years ) with symptomatic gastroesophageal reflux have been treated with metoclopramide at a dosage of 0.5mg/kg/day. Symptoms improved the duration of the  disease was shortened and surgery was avoided.