These are drugs used to prevent or suppress vomiting.
  1. Anticholinergics: Hyoscine, Dicyclomine
  2. H1 antihistaminics: Promethazine, Diphenhydamine, Dimenhydrinate, Doxylamine, Meclozine, Cinnarizine
  3. Neuroleptics (D2 Blockers): Chlorpromazine, Triflupromazine, Prochlorperazine, Haloperidol, etc.
  4. Prokinetic drugs: Metoclopramide, Domperidone, Cisapride, Mosapride
  5. 5-HT3 antagonists: Ondansetron, Granisetron, Palonosetron
  6. NK1 receptor antagonists: Arepitant, Fosaprepitant
  7. Adjuvant antiemetics: Dexamethasone, Benzodiazepines, Dronabinol, Nabilone
  • (0.2-0.4 mg oral, i.m.) is the most effective drug for motion sickness.
  • It has a brief duration of action so suitable for only short brisk journies.
  • It produces anticholinergic side effects like dry mouth, sedation, etc.
  • Mechanism of action: by blocking conduction of nerve impulses across a cholinergic link in the pathway leading from the vestibular apparatus to the vomiting centre and has poor efficacy in vomiting of other etiologies.
  • Transdermal patch containing 1.5 mg of it, to be delivered over 3 days has been developed. Applied behind the pinna producing only mild side effects.
  • In addition to its action as a muscarinic antagonist, hyocine butylbromideis a ganglion blocker in man. (1)
  • Intramuscular hyoscine can be used in the treatment of motion sickness. (2)
  • Hyoscine patches are effective in patients with clozapine induced hypersalivation who do not respond oral treatement including oral hyoscine. (3)
  • Hyoscine butylbromide has a strong antimuscarinic action and nicotinic antagonism at higher concentration. The muscle relaxing effect and inhibition of muscarinic nerve activation explains its use as an antispasmodic drug. It has an antisecretory action also. (4)
  • Hyoscine butylbromide is efefctive in significantly reducing the duration of the first stage of labor, and is not associated with any apparent adverse maternal or neonatal outcomes. (5)
  • Intravenous Hyoscine butyl bromide causes pain relief in labor of up to 36% and shortens the duration of active phase without any untoward short term fetal or maternal effects. (6)
  • Hyoscine induces a moderate bradycardia and a marked decrease in salivation and in the duration of the EEG arousal response. (7)
  • There appears to be a time dependent relation to pain reduction following parenteral administration of hyoscine in patients with acute ureteric colic. (8)
  • Hyoscine increased adaptation in the vestibular sensory system and released the oculomotor system from the ascending influence of vestibular and reticular projections. (9)
  • Tu1039 hyoscine is used for polyp detection during colonoscopy. (10)
  • Hyoscine butyl bromide can induce hypotension and bradycardia in patients. (11)
  • Hyoscine butylbromide is more effective than drotaverine in reducing the duration of active phase of labour. There is a significant improvement in the rate of cervical dilatation with hyoscine butylbromide when compared to drotaverine. (12)
  • (10-20 mg oral) has been used for prophylaxis of motion sickness and for morning sickness.
  • It has been cleared of teratogenic potential.
  • A comparison of the affinity of dicyclomine for the noncompetitive recpetor involved with the response to Ach, bradykinin and histamine indicates that each of the agonists is antagonized by dicyclomine through a common mechanism. (13)
  • Dicyclomine hydrochloride is rapidly absorbed following oral administration. The drug and/or its metabolites are detectable in urine within 1 hour. The principal route of elimination is via the urine (79.5%). Excretion also occurs via the feces but to a lesser extent. (8.4%). (14)
  • Dicyclomine has a high affinity for the neuronal M1 receptor whose activation by pilocarpine causes an increse in acetylcholine release. Dicyclomine has low affinity for both the prejunctional M2 receptor mediating inhibition of electrically evoked acetylcholine release and the post junctional M2 receptor. (15)
  • Dicyclomine hydrochloride is used in the treatment of infantile colic. (16)
  • Fixed dose combination of dexketoprofen and dicyclomine (DXD) has superior efficacy and tolerability than diclofenac and dicyclomine combination (DLD) in patients clinically diagnosed to be suffering from acute renal colic. (17)
  • Dicyclomine causes increase in heart rate variability indexes in uncontrolled normal breathing test, increase in vagal ratio and decrease in sympathetic ratio in squatting test. In muscular administration with 20 mg dose, dicyclomine shows cholinergic effects. (18)
  • A rare case of dicyclomine abuse has been reported having anticholinergic toxicity. (19)
  • Dicyclomine reduces biomarker levels but neuronal degeneration in fluid percussion brain injury. (20)
  • Dicyclomine hydrochloride (Merbentyl) syrup is effective in the treatment of infant colic. (21)
H1 Antihistaminics
  • Promethazine, Diphenhydamine, Dimenhydrinate
  • They are useful mainly in motion sickness and to lesser extent in morning sickness, postoperative and some other forms of vomiting.
  • Their antiemetic effect appears to be based on anticholinergic, antihistaminic, weak antidopaminergic and sedative properties.
  • Afford protection from motion sickness for 4-6 hours, but produce sedation and dryness of mouth.
  • By their central anticholinergic action they suppress the extrapyramidal side effects of metaclopramide while supplementing its antiemetic action.
  • Promethazine, is a phenothiazine; has weak antidopaminergic action as well. Their combination has been used in chemotherapy induced nausea and vomiting (CINV).
  • Promethazine is not recommended as a first line agent in the treatment of post operative nausea and vomiting, but can be considered for use as a rescue antiemetic. (22)
  • Promethazine potentiates the action of 6 different narcotics (morphine, pethidine, hydromorphone, fentanyl and pentazocine). (23)
  • Topical promethazine allergy is becoming a common clinical problem. Assessment by a dermatologist or an allergist is important for appropriate diagnosis and management of the condition. (24)
  • Promethazine should not be given to patients with a history or evidence of preeclampsia, epilepsy, convulsions, intracranial trauma and severe hypertension. (25)
  • Promethazine along with haloperidol is effective for psychosis induced aggression. (26)
  • Intramuscular haloperidol plus promethazine is more effective and safer than haloperidol alone for rapid tranquillisation of agitated mentally ill patients. (27)
  • Physiostigmine is used in patients with promethazine poisoning. (28)
  • Geriatric status is a significant risk factor for promethazine ADEs. Concomitant use of sedating drugs may further increase the risk for ADEs. (29)
  • Promethazine hydrochloride is effective in the treatment of psychiatric disorders. (30)
  • Pretreatment with promethazine significantly decreases mivacurium induced histamine release in children and provides stable hemodynamics during administration of anesthesia. (31)
  • Intravenous injection of promethazine hydrochloride is used y young injection heroin users as a substitute for heroin or to augment the effects of an inadequate heroin dosing. (32)
  • Promethazine treatment is ineffective and unpleasant in children with attention deficit disorder with hyperactivity. (33)
  • Promethazine can interact with cardiac histamine receptors but the interaction is either noncompetitive or competitive non-equilibrium in nature. (34)
  • Acetaminophen and diphenhydramine are effective therapies for fever and allergy respectively. But they have potential toxicity particularly in ill patients. They have failed to prevent transfusion reactions. (35)
  • Injectable 1% diphenhydramine is a safe, inexpensive and effective local anesthetic for simple dermatologic procedures in patients who report “caine” allergies. (36)
  • Diphenhydramine may not be an effective sedative/ hypnotic in elderly women. (37)
  • Diphenhydramine and dextromethorphan are not superior in providing nocturnal symptoms relief for children with cough and sleep difficulty as a result of an upper respiratory infection. (38)
  • Diphenhydramine is effective in the management of patients with nocturnal leg cramps. (39)
  • Diphenhydramine is effective in the treatment of haloperidol abuse. (40)
  • Opsoclonus occurs in patients with diphenhydramine poisoning. (41)
  • Diphenhydramine is an antihistamine with anticholinergic properties which may be used as a palliative treatment for patients dying with Parkinson’s disease and tremors. (42)
  • Although not a replacement of lidocaine, diphenhydramine is a viable alternative for anesthesia in the repair of minor lacerations. (43)
  • Routine coadministered 20 mg diphenhydramine does not prevent metoclopramide induced akathisia. (44)
  • Metoclopramide administered with diphenhydramine (MAD) regimen is effective for the treatment of headaches in pregnant women when acetaminophen alone is ineffective. (45)
  • Dimenhydrinate is considered to be safe to use in children with vomiting. (46)
  • There is no teratogenicity with dimenhydrinate. A lower rate of obstructive uropathy is found in infants born to mothers treated with dimenhydrinate during the first trimester of pregnancy. (47)
  • Overdose of dimenhydrinate and diphenhydramine can result in rapid central nervous system stimulation including status epilepticus. Death can occur within two hours. (48)
  • Erythema multiforme can occur due to dimenhydrinate with pamabron cross-sensitivity. Therefore a comprehensive medication history should be taken for all drug allergy patients to ensure greater informed decision making when choosing medications to use for that patient in the future. (49)
  • Antimotion sickness property of diphenhydramine and dimenhydrinate may be due to diminished excitability of the vestibular nuclear complex. (50)
  • Clozapine helps in reducing cravings for dimenhydrinate in patients with the drug abuse. (51)
  • Prophylactic dimenhydrinate in a dose of 50 mg effectively decreases the incidence of emesis without any increase in side effects following cesarean section with intrathecal morphine. (52)
  • The fixed dose combination of cinnarizine 20 mg + dimenhydrinate 40 mg is effective, clinically beneficial and well tolerated in patients with vestibular vertigo of central and/or peripheral origin. (53)
  • Dimenhydrinate augments heart rate responses to baroreceptor unloading, but does not alter resting muscle sympathetic nerve activity (MSNA), the sympathetic baroreflexes or the vestibulosympathetic reflex. (54)
  • It is a sedative H1 antihistaminic with prominent anticholinergic activity.
  • Marketed in combination with pyridoxine, for morning sickness.
  • Oral absorption is slow and its t1/2 is 10 hr.
  • The side effects are drowsiness, dry mouth, vertigo and abdominal upset.
  • Dose: 10-20 mg at bed time: if needed additional doses may be given in morning and afternoon.
  • Although combined doxylamine-pyridoxine treatment is already the single most studied pharmacologic therapy for use for vomiting in pregnancy, the FDA will continue to carelfully monitor the post marketing data related to Diclegis use. (55)
  • The first line treatment recommendations for nausea and vomiting during pregnancy as per the Americab College of Obstetricians and Gynecologists (ACOG) include pyridoxine or pyridoxine plus doxylamine. (56)
  • Rhabdomyolysis can occur with doxylamine overdose. (57)
  • Diclectin delayed release formulation of doxylamine succinate and pyridoxine hydrochloride is efefctive and well tolerated in treating nausea and vomiting of pregnancy. (58)
  • Ondansteron is superior to the combination of pyridoxine and doxylamine for the reduction of nausea and vomiting occuring in the first trimester of pregnancy. (59)
  • Doxylamine increases the activity of those hepatic enzymes involved in T4 metabolism. (60)
  • The single doses of doxylamine are well tolerated in children. Somnolence is the most common adverse effect, with no apparent differences in incidence noted with age. An age/ weight dosing nomogramutilizing a fourfold range of doses achieves similar Cmax, whereas AUC increases only 60%. (61)
  • Doxylamine produces liver lesions in male mice including hepatocellular hypertrophy, atypical hepatocytes, clear cell and mixed cell foci and necrosis. In females, it produces liver fatty change, hepatocellular hypertrophy and necrosis. It produces a significant increase in hepatocellular adenoma in mid and high dosage groups of males and high dosage group of females. Thyroid follicular cell hyperplasia and thyroid follicular cell adenoma is also increased. A treatment related increase in cytoplasmic alteration of the parotid salivary gland in males and an increased incidence in hyperplasia of the pituitary gland in females is observed. (62)
  • Syndrome of inappropriate antidiuresis (SIAD) may be considered as a potential serious adverse reaction of doxylamine overdose. (63)
  • Doxylamine and pheniramine possess the most potent infiltrative analgesic ability among the screened H1 blocking antihistamines. The potencies are weaker than bupivacaine but similar to lidocaine. In addition, doxylamine had the longest duration of drug effect. (64)
  • In case of doxylamine intoxicated patients, there is a close relationship between seizure and ingested amount. (65)
  • Doxylamine toxicity can cause seizure, rhabdomyolysis and a flase positive urine drug screen for methadone. (66)
  • HIgh fat, high calorie food intake does not affect the kinetics of doxylamine in healthy subjects. (67)
  • It is less sedative and longer acting
  • It protect against sea sickness for nearly 24 hrs.
  • Meclizine is effecive for preventing nausea and vomiting associated with the Yuzpe regimen of emrgency contraceptive pills. WOmen using this drug should be cautioned to anticipate drowsiness. (68)
  • Meclizine attenuates mitochondrial respiration by directly inhibiting the kennedy pathway of phosphatidylethanolamine biosynthesis. (69)
  • Meclizine is an approved drug that crosses the blood brain barrier and hold a therpeutic potential in the treatment of polyQ toxicity disorders like Huntington's disease. (70)
  • Meclizine reduces the severity and frequency of attacks, as well as signs and symptoms associated with vertigo. These include nausea, positional and positioning nystagmus and postural instability. (71)
  • Norchlorcyclizine penetrates the placental barrier and is responsible for the congenital malformations observed in meclizine hydrochloride treatment of rats. (72)
  • Meclizine is effective for prevention and treatment of motion sickness, particularly during mild civilian travel. It is well tolerated with few adverse effects and its oral dosage form is convenient for patients to take prior to exposure to motion as a preventive measure. (73)
  • Pregnane X receptor (PXR) is a receptor that regulates the transcription of genes involved in various functions, including drug metabolism and transport. Meclizine is an agonist of human pregnane X receptor. (74)
  • Withdrawal symptoms experienced after removal of transdermal scopolamine can be successfully treated with oral meclizine. (75)
  • Auditory hallucinations is elicited by combined meclizine and metaxalone use at bedtime. (76)
  • Meclizine hydrochloride- Niacin combination (Antivert) is very useful for treatment of ambulatory patients with vestibular disease. (77)


  • It is an antivertigo drug having antimotion sickness property.
  • It probably acts by inhibiting influx of Ca2+ from endolymph into the vestibular sensory cells which mediates labyrinthine reflexes. 
  • The mean plasma elimination half-life of cinnarizine is 3.24 h. (78)
  • Cinnarizine is an efficacious and well tolerated prophylactic antimigraine medication, which has early onset effectiveness. (79)
  • The fixed dose combination of cinnarizine 20 mg + dimenhydrinate 40 mg was effective, clinically beneficial and well tolerated in patients with vestibular vertigo of central and/or peripheral origin. (80)
  • Cinnarizine should be added to the list of drugs capable of aggravating Parkinson's disease. (81)
  • Flunarizine and cinnarizine induced parkinsonism (FCIP) is a recognized condition with specific clinical features and is the second most common cause of parkinsonism in many counteries. (82)
  • Cinnarizine has an atypical antipsychotic profile in animal models of psychosis. (83)
  • Cinnarizine is safe and effective in reducing both headache and vertigo aspects of migraine plus vertigo among the patients who suffer from either vestibular migraine or migraine with brainstem aura associated with vertigo. (84)
  • Cinnarizine can induce cholestasis in patients. (85)
  • The mild sedation produced by cinnarizine is counteracted by the doses of the phenylpropanolamine used. A potential therapeutic interaction is likely. (86)
  • A significant difference is seen in the duration of nystagmus during initial acceleration and in average eye speed following the sudden stop after treatment with cinnarizine in induced vestibular nystagmus. (87)
  • Cinnarizine improves the haloperidol induced brain oxidative stress and impeirment of learning and memory in the water maze test in mice. (88)
  • There is a potential benefit of adding calcium channel blockers (CCBs) cinnarizine and nifedipine to sodium valproate in treatment of maximal electroshock (MES) induced and pentylenetetrazole (PTZ) induced convulsions. (89)
  • There is a direct relationship between time of use of cinnarizine and flunarizine, the age and the prevalence of Parkinsonism and other movement disorders. These drugs also increase the incidence of depression. (90)


  • The older neuroleptics (Chlorpromazine, Triflupromazine, Prochlorperazine, Haloperidol) are potent antiemetics.
  • Act by blocking D2 receptors in the CTZ.
  • They antagonize apomorphine induced vomiting and have additional anticholinergic and H1 antihistaminic property as well.
  • They are less effective in motion sickness.
  • The antiemetic dose is much lower than antipsychotic doses.
  • These agents should not be administered until the cause of vomiting has been diagnosed otherwise treatment may be delayed due to symptomatic relief.
  • They can cause extrapyramidal side effects and sedation.
  • They have broad spectrum antiemetic action effective in:-

a) Drug induced and postoperative nausea and vomiting (PONV).

b) Disease induced vomiting: gastroenteritis, uremia, liver disease, migraine etc.

c) Mailgnancy associated and cancer chemotherapy (mildly emetogenic) induced vomiting.

d) Radiation sickness vomiting (less effective).

e) Morning sickness: should not be used except in hyperemesis gravidarum.


  • This D2 blocking phenothiazine is a labyrinthine suppressant, has selective antivertigo and antiemetic actions.
  • Dose: 5-10 mg BD/TDS oral, 12.5-25 mg by deep i.m. injection.
  • Acute dystonic reaction occurs with small doses of prochlorperazine. (91)
  • Prochlorperazine is used for the prevention of nausea and vomiting after adenotonsillectomy. (92)
  • 2.5 mg of intravenous prochlorperazine given over one minute is an effective, safe treatment for the control of vomiting in the emergency department, until the etiology of the nausea and vomiting is determined and treated specifically. (93)
  • Prochlorperazine for the prevention of nausea and vomiting in patients undergoing fractionated radiotherapy. (94)
  • Prochlorperazine was statistically superior to octreotide in clinical success rate and decrease in pain in migraine patients but caused more restlessness and sedation. (95)
  • A combination of prochlorperazine and dipyridamole may enhance cellular doxorubicin retention by blocking efflux while reducing normal tissue toxicity and unwanted side effects in vivo. (96)
  • IV high dose metoclopramide and prochlorperazine is similar and effective in the management of cisplatin induced emesis. IV prochlorperazine at 20 mg dosage is surprisingly effective. (97)
  • Intravenous diphenhydramine rapidly reduces signs and symptoms of acute akathisia induced by prochlorperazine. (98)
  • Peculiar neuromuscular reaction of dystonic type is a infrequent side effect of prochlorperazine therapy. (99)
  • Prochlorperazine can potentiate chloroquine action against resistant parasites found in natural conditions. (100)
  • Of the various CYP450s that contribute to prochlorperazine metabolism, CYP2D6 and CYP2C19 are the most efficient. N-desmethyl prochlorperazine is the major metabolite formed by CYP2D6 and CYP2C19. (101)
  • Droperidol iv provides a similar reduction of headache as as achieved with prochlorperazine iv with a similar incidence of akathisia. (102)
  • Neuroleptic Malignant Syndrome is rare complication with the use of prochlorpreazine in patient with a recent history of antipsychotic induced neuroleptic malignant syndrome. (103)
Prokinetic Drugs
  • They promote gastrointestinal transit and speed gastric emptying by enhancing coordinated propulsive motility.
  • GIT: it has more prominent effect on upper g.i.t.; increases gastric peristalsis while relaxing the pylorus and the first part of duodenum → speeds gastric emptying, especially if it was slow. Lower esophageal sphincter (LES) tone is increased and gastroesophageal reflux is opposed.
  • CNS: it is an effective antiemetic acting on the CTZ, blocks apomorphine induced vomiting. The gastrokinetic action may contribute to the antiemetic effect. It has no antipsychotic property but share the extrapyramidal and prolactin secretion augmenting action of antipsychotics.
  • Mechanism of action: it act through both dopaminergic and serotonergic receptor.
  • a) D2 antagonism: In GIT (augmenting ACh release) and CNS
  • b) 5-HT4 agonism: In GIT (myenteric motor neurons→augmenting ACh release)
  • c) 5-HT3 antagonism: At high concentration it block 5-HT3 receptors present on inhibitory myenteric interneurones and in NTS/CTZ.
  • Pharmacokinetics: it is rapidly absorbed orally. It is partly conjugated in liver and excreted in urine within 24 hours; t1/2 is 3-6 hrs.
  • Interactions: it hasten the absorption of many drugs, e.g. asprin, diazepam, etc. by facilitating gastric emptying. The extent of absorption of digoxin is reduced by allowing less time for it. It also abolishes the effect of levodopa by blocking D2 receptors in basal ganglia.
  • Adverse effect: it is well tolerated; sedation, dizziness, loose stools, muscle dystonias (especially in children) are the main side effects. Long term use can cause extrapyramidal side effects and hyperprolactinaemia.
  • Metoclopramide can induce tardive dyskinesia in patients. (104)
  • Metoclopramide is effective in the treatment of postoperative nausea and vomiting. In adult, the best documented regimen is 10 mg iv. In children, the best documented regimen is 0.25 mg/kg iv. Minor adverse effects (sedation, dizziness, drowsiness) are not significantly associated with metoclopramide. (105)
  • Metoclopramide is safe for the fetus when drug is given to women to relieve nausea and vomiting during pregnancy. (106)
  • Metoclopramide not generally need to be used for control of vomiting in acute porphyria if a safe alternative is available like chlorpromazine or prochlorperazine. (107)
  • Metoclopramide produces an overall improvement in acute schizophrenic symptoms. (108)
  • Increased daily milk production is seen with metoclopramide treatment due to increase in the basal prolactin level. Metoclopramide treatment can permit a successful breast-ffeding experience in women who deliver prematurely and have difficulty in maintainning lactation. (109)
  • Metoclopramide has a direct effect on the heart, block presynaptic autoreceptors and enhance catecholamine release, enhance cholinergic neurotransmission and cause 5-HT3 receptor blockade and 5-HT4 receptor antagonism. It can cause cardiac arrest, bradycardia, total heart block, acute hypotension, supraventricular tachycardia, circulatory collapse, QT prolongation, Torsades de Pointes, ST depression and congestive heart failure. (110)
  • Metoclopramide is efficacious in the treatment of both the pain and nausea of migraine headache. Tjis is a direct action that is not dependent on the concomitant administration of another agent. (111)
  • The black box warning for metoclopramide has decreased its usage and increased its rate of adverse events reporting. Lawyer initiated reports of tardive dyskinesia pharmacovigilance. (112)
  • Metoclopramide and haloperidol are both excellent antiemetics when given in sufficient dosage by an effective route. Metoclopramide does show a mild advantage. (113)
  • Prophylactic administration of metoclopramide for patients receiving pain relief may reduce the incidence of nausea and vomiting in the ambulance. (114)
  • Dose: 10 mg (children 0.2-0.5 mg/kg) TDS oral or i.m. For CINV 0.3-2 mg/kg slow i.v./i.m.
  • Uses :
  • Antiemetic:

• Postoperative, drug induced, disease associated (especially migraine), radiation sickness, etc, but it is less effective in motion sickness.

• Though ondansetron is preferred, it continues to be used for prophylaxis and treatment of vomiting induced by anticancer drugs.

• A higher dose is often needed, but is effective when other drugs fails.

• Promethazine, diphenhydramine, diazepam or lorazepam injected i.v. along with it to supplement its antiemetic action and reduce the attending dystonic reactions.

• Dexamethasone i.v. also augments its efficacy.

• It should be used for morning sickness only when other measures do not work.

  • Gastrokinetic
  • Dyspepesia
  • Gastroesophageal reflux disease (GERD)
  • It is D2 receptor antagonist chemically related to haloperidol, but pharmacologically related to metaclopramide.
  • The antiemetic and prokinetic actions have a lower ceiling.
  • Unlike metaclopramide, its prokinetic action is not attenuated by atropine and is based only on D2 receptor blockade in upper g.i.t.
  • It crosses blood-brain barrier poorly. Accordingly extrapyramidal side effects are rare, but hyperprolactinaemia can occur.
  • The antiemetic action is exerted mainly through CTZ which is not protected by blood-brain barrier.
  • Because of their poor entry into CNS, it does not block the therapeutic effect of levodopa and bromocriptine in parkinsonism, but counteracts their dose-limiting emetic action.
  • It is absorbed orally, but bioavailability is only ~15% due to first pass metabolism. It is completely biotransformed and metabolites are excreted in urine. Plasma t1/2 is 7.5 hr.
  • Side effects: Mild-dry mouth, loose stools, headache, rashes, galactorrhoea. Cardiac arrhythmia have developed on rapid i.v. injection.
  • Its indications are similar to that of metaclopramide, but it is less efficacious gastrokinetic and not useful against highly emetogenic chemotherapy.
  • Dose: 10-40 mg (children 0.3-0.6 mg/kg) TDS.
  • Domperidone acts as both antiemetic and an upper gastrointestinal tract prokinetic agent. It is approved for use for symptomatic managemnt of upper gastrointestinal tract motility disorders and to prevent gastrointestinal symptoms associated with the use of dopamine agonist agents in Parkinson's disease. (115)
  • Domperidone provides an excellent safety profile for long term administration orally in the recommended doses. It is widely used for the treatment of gastroparesis and any condition causing chronic nausea and vomiting. (116)
  • Domperidone produces a greater increase in breast milk supply. (117)
  • Domperidone increases the volume of breast milk of preterm mothers experiencing lactation failure, without substantially altering the nutrient composition. (118)
  • The use of domperidone is not recommended in the management of irritable bowel syndrome. (119)
  • For alzheimer's disease patients with higher FSSG scores (Frequency scale for symptoms of gastroesophageal reflux disease) at baseline, domperidone is effective in preventing rivastigmine related gastrointestinal disturbances. (120)
  • Domperidone is considered safe in controlling levodopa and dopamine agonist induced gastric upset in patients wit Parkinson's disease. Its protective effect is on the chemoreceptor trigger zone of the area prostema which lies outside the blood brain barrier. Domperidone is effective in metoclopramide induced parkinsonism. (121)
  • Domperidone can induce galactorrhea in treated patient. (122)
  • Domperidone possesses cardiac electrophysiological effects similar to those of cisapride and class III antiarrhythmic drugs. It should not be considered a no risk alternative to cisapride in the treatment of gastrointestinal motility disorders. (123)
  • Ondansteron plus domperidone exert more pronounced antiemetic effect in patients with breast cancer receiving moderately emetogenic chemotherapy (FAC regimen) with good appetite status and less adverse effect. (124)
  • Domperidone and metoclopramide effectively reduce the symptoms of diabetic gastroparesis; CNs side effects are more pronounced with metoclopramide. (125)
  • Domperidone at doses up to 80 mg/day does not cause clinically relevant QTc interval prolongation. (126)
Cisapride, Mosapride
  • The benzamide derivative is a prokinetic with little antiemetic property, because it lacks D2 receptor antagonism.
  • The prokinetic action is exerted mainly through 5-HT 4 agonism aided by weak 5-HT3 antagonism in the myentric plexus in g.i.t.
  • It is inactivated by CYP3A4 and not safe in patients who take CYP3A4 inhibitors like azole antifungals, macrolides, etc. concurrently. As it can cause serious ventricular arrhythmias in them. At high concentration it prolongs Q-Tc interval and predisposes to torsades de pointes/ventricular fibrillation.  
  • Cisapride is associated with a doubling to tripling of the risk of hospitalization for ventricular arrhythmia and nearly eightfold risk in the initial prescription period. (127)
  • US FDA warns doctors to use cisapride as last resort only. (128)
  • Cisapride accumulates in less mature neonates and cause increase in QTc interval. (129)
  • Cisapride is useful in children with chronic intestinal pseudo-obstruction with those having migrating motor complexes responding best, especially if there is postprandial duodenal hypomotility. It can be given at dose of 0.6-0.8 mg/kg/day measuring Qtc before and after starting treatment. It should not be used when QTc is > 450 or with contraindicated drugs. (130)
  • Cisapride is safe medicine in GERD in children considering appropriate cautions. Its efficacy is comparable to metoclopramide in short period, but it is much better with continuing treatment. (131)
  • Cisapride is associated with QT prolongation and torsades de pointes. The risk of fatal arrhythmia is believed to outweigh the benefit for the approved indication, treatment of nocturnal heartburn due to gastroesophageal reflux disease, leading to the drug's discontinuation in the United States. (132)
  • Cisapride is effective in the treatment of chronic intestinal pseudo-obstruction in a complex pediatric patient. (133)
  • Concomitant administration of cisapride accelerates the absorption and increases the peak concentration of sparfloxacin without having a significant effect on the extent of bioavailability. Coadministration of sucralfate leads to a 44% decrease in the bioavailability of sparfloxacin. (134)
  • Concomitant use of cisapride and clarithromycin may cause torsades de pointes arrhythmia. (135)
  • Treatment with cisapride increase colonic motility and reduce urinary retention in paraplegic patient who suffered traumatic spinal cord injury. (136)
  • Preanesthetic administration of cisapride and esomeprazole decreases the number of reflux in anesthetized dogs, but administration of esomeprazole alone is associated with nonacid and weakly acidic reflux in all but 1 dog. (137)
  • Cisapride enhances gastric emptying in critically ill patients. (138)
  • The age difference does not have an impact on cisapride induced QTc prolongation. (139)
  • CYP3A is the main isoform involved in the overall metabolic clearance of cisapride. Cisapride metabolism is likely to be subject to interindividual variability in CYP3A expression and to drug interactions involving this isoform. (140)
  • A subsequently introduced congener of cisapride with similar gastrokinetic and LES tonic action.
  • Like cisapride, it has no clinically useful antiemetic action.
  • It does not cause prolongation of QT interval and subsequent arrhythmias.
  • Therefore, it was introduced as safe prokinetic.
  • Side effects are diarrhoea,  abdominal pain, headache, dizziness and insomnia.
  • Mosapride combined therapy is not more effective than PPI alone as first line therapy. (141)
  • Mosapride does not provide additional benefit to a standard dose of lansoprazole in patients with reflux esophagitis, except possibly in the subgroup of severely symptomatic patients. (142)
  • There is an improvement in the glycemic control after the treatment with mosapride in patients with diabetic gastropathy. (143)
  • Mosapride citrate has a dose dependent prokinetic effect on the duodenal and cecal contractions in healthy donkeys. (144)
  • Pharmacokinetics of mosapride does not change in the patients operated by distal or total gastrectomy. (145)
  • Combining mosapride with a PPI provides no additional improvement in reflux symptoms compared to PPI alone. (146)
  • Using mosapride citrate for gerontal patients after operation on abdominal region can promote the function recovery of the stomach intestine, decrease the incidence rate of total complication and shorten the length of stays in hospital. (147)
  • Administration of mosapride increased bowel frequency and ameliorated symptoms of reflux and constipation possibly stimulating the lower intestine. It may be a useful prokinetic agent in treating diabetic patients with constipation. (148)
  • Adding mosapride on esomeprazole improved esophageal contractability and lowered intrabolus pressure in patients with GERD. Mosapride and esomeprazole cotherapy tended to yield better response in patients with concomitant dyspepsia. (149)
  • Mosapride is more favorably accepted than teprenone by the patients with functional dyspepsia with sufficient safety and efficacy. (150)
  • Mosapride has beneficial effect on post operative ileus and it is enhanced by low dose ondansteron but interrupted by high dose ondansetron. (151)
  • Mosapride can be used in the treatment of blepharospsm. (152)
  • Mosapride selectively stimulates upper GI motility in vivo and in vitro. (153)
  • Mosapride is effective in preventing delayed gastric emptying and increase in plasma gastrin level induced by PPI treatment but does not show prominent clinical symptom improvements. (154)
5-HT3 Antagonists
  • It is the prototype drug of distinct class of drugs developed to control cancer chemotherapy/radiotherapy induced vomiting.
  • Later they have found to be highly effective in PONV and disease/drug associated vomiting as well.
  • It blocks the depolarizing action of 5-HT exerted through 5-HT3 receptors on vagal afferents in the g.i.t. as well as in NTS and CTZ.
  • It blocks emetogenic impulses both at at their peripheral origin and their central relay.
  • Pharmacokinetics: oral bioavailability is 60-70% due to first pass metabolism. It is hydroxylated by CYP1A2, 2D6 and 3A, followed by glucuronide and sulfate conjugation. It is eliminated in urine and faeces, mostly as metabolites: t1/2 is 3-5 hrs, and duration of action is 8-12 hrs (longer at higher doses).
  • Dose: 4-8 mg oral/i.v.
  • Addition of dexamethasone, promethazine/diazepam or both dexamethasone + NK1 antagonist aprepitant enhances antiemetic efficacy.
  • Further nausea and vomiting could be prevented with ondansetron who had nausea or vomiting. (155)
  • Palanosetron is comparable to ondansetron for post operative nausea and vomiting prophylaxis in elective laparoscopic cholecystectomy when administered as single pre-induction dose. (156)
  • Ondansetron relieves some of the most intrusive symptoms of irritable bowel syndrome with diarrhea namely loose stools, frequency and urgency. (157)
  • Ondansetron 8 mg and granisetron 3 mg, both combined with dexamethasone has similar efficacy and tolerability in the prevention of cisplatin induced emesis. (158)
  • Co-administration of ondansetron neither increases tramadol consumption nor frequency of post opreative nausea and vomiting in postoperative setting. (159)
  • Ondansetron plus dexamethasone is effective antiemetic prophylaxis for high dose cisplatin chemotherapy, has few side effects and is active when given orally. (160)
  • A single dose of oral ondansetron helps in reducing vomiting, the need of iv fluid and hospital admission in pediatric gastroeneteritis. (161)
  • Ondansetron can be used for intractable vertigo complicating acute brainstem disorders. (162)
  • Perioperative use of ondansetron or dolasetron is not associated with extended QT prolongation and this does not vary by diabetic status. (163)
  • Ondansetron is anb effective antiemetic in the treatment of acute chemotherapy- or radiotherapy- induced nausea and vomiting and post operative nausea and vomiting. (164)
  • Ondansetron has a preventive effect on post anesthesia shivering without a paralleled side effect of bradycardia. (165)
  • A concomitant dose of ondansetron at the end of surgery does not block the analgesic effect of acetaminophen. (166)
  • Single dose ondansetron is effective in preventing post operative nausea and vomiting after laparoscopic cholecystectomy with sevoflurane and remifentanil infusion anaesthesia. (167)
  • Ondansetron induces ventricular tachycardia and ectopics in a patient of caeserian section. (168)
  • No adverse outcomes are seen from the use of ondansetron in pregnancy but further research is needed to conclude that ondansetron is safe to use in pregnancy. (169)
  • Pre-treatment with intravenous ondansetron significantly reduces the pain on injection of etomidate. (170)
  • There is a therapeutic potential for ondansetron in obstructive sleep disordered breathing, particularly REM sleep apnea. (171)
  • There is reduction in spinal induced hypotension with ondansetron in parturients undergoing caeserean section. (172)
  • Adjuvant drugs are more often required for delayed phase vomiting that occurs on the second to fifth day of cisplatin therapy, in some, but not all patients.
  • Other types of vomiting:

Used in treatment of PONV. It is administered before surgery (4-8mg i.v.) repeated after 4 hrs has become the first choice antiemetic at many centres.

Effective in disease/drug associated vomiting.

  • Side effects: it is generally well tolerated: the only common side effects are headache and dizziness. 
  • It is 10 times more potent than ondansetron and probably more effective during the repeat cycle of chemotherapy.
  • Its plasma t1/2 is longer (8-12 hrs).
  • Side effects profile is similar.
  • Dose: 1-3 mg orally/i.v. (in dilution)
  • Single dose iv granisetron is used in the prevention of post operative nausea and vomiting. (173)
  • Granisetron is an effective and well tolerated agent for the treatment of nausea and vomiting in the oncology and surgical settings. It is effective and well tolerated in patients refractory to antiemetic treatment, patient with hepatic and renal impairment and children. Its safety profile and minimal potential for drug-drug interactions makes it an antiemetic agent of choice for elderly cancer patients. (174)
  • The administration of granisetron after 24 houts has no benefit in the control of delayed emesis for patients who recieve highly emetogenic chemotherapy. (175)
  • Granisetron has an immediate, short lasting and specific pain reducing effect in temporo-mandibular joint inflammatory arthritis. The 5HT3 receptor may therefore be involved in the mediation of TMJ pain in systemic inflammatory joint disorders. (176)
  • Granisetron is more effective than ondansetron in controlling postoperative nausea and vomiting after laparoscopic gynecological surgery. (177)
  • Granisetron and ondansetron are of similar efficacy within the first 24 hour period but granisetron is less efficacious more than 24 hours after the onset of therapy. (178)
  • INtravenous injection of 8 mg dexamethasone or 3 mg granisetron before anesthesia induction has similar effects in prophylaxis of nausea and vomiting after laparoscopic cholecystectomy. (179)
  • Granisetron might be an effective, safe and well tolerated drug for the treatment of uremic pruritis. (180)
  • GRanisetron combined with dexamethasone is the most effective regimen for the prevention of emesis induced by moderately emetogenic chemotherapy. (181)
  • Granisetron injection used as the primary prophylaxis in low emetogenic chemotherapy demonstrates limited role in chemotherapy induced nausea and vomiting control. (182)
  • Granisetron interacts with agents affecting heme oxygenase/ carbon monoxide pathway both in vitro and in vivo. Hemin and zinc protoporphyrin IX affect granisetron constipating effects in vitro and in vivo. (183)
  • The number of cycles completed with granisetron is significantly higher than the number completed with prednisolone plus metopimazine but the anti emetic efficacy of both treatments declined during multiple cycles of moderately emetogenic chemotherapy. (184)
  • Pre treatment with granisetron or nitroglycerine both are highly effective in attenuation of rocuronium induced pain. (185)
  • It is longest acting. Elimination t1/2 is 40 hrs.
  • It is more effective in suppressing delayed vomiting of CINV occurring between 2nd to 5th days, probably because of its longer duration of action.
  • Side effects are headache, fatigue, abdominal pain and dizziness. Additive Q-T prolongation can occur. Rapid i.v. injection can cause blurring of vesion.
  • Dose: 250 ug slow i.v. before chemotherapy and 75 ug i.v. for PONV.
  • A single iv dose of palonosetron 0.25 mg is significantly superior to iv ondansetron 32 mg in the prevention of acute and delayed chemotherapy induced nausea and vomiting. (186)
  • Palanosetron inhibits substance P mediated responses in vitro and in vivo. It is effective in delayed chemotherapy induced nausea and vomiting in the clinic. (187)
  • Palonosetron is a better drug to prevent post operative nausea and vomiting in patients undergoing day care surgical procedures as compared to ondansetron as it has got a prolonged duration of action and favorable side effects profile. (188)
  • Prophylactic therapy with palonosetron is more effective than granisetron for long term prevention of postoperative nausea and vomiting after laparoscopic cholecystectomy. (189)
  • Owing to its efficacy in controlling both acute and delayed CINV, palonosetron may be very effective in the clinical setting of multiple day chemotherapy and bone marrow transplantation. (190)
  • Palonosetron is more effective than other 5HT3R in preventing acute and delayed CINV in patients receiving moderately or highly emetogenic treatments regardless of the use of concomitant corticosteroids. (191)
  • When administered with dexamethasone before highly emetogenic chemotherapy, palonosetron exerts efficacy against CINV which is non inferior to that of granisetron in the acute phase and better than that of granisetron in the delayed phase. (192)
  • IgE mediated hypersensitivity reaction is seen with ondansetron while palonosetron is safe to use. (193)
  • Palonosetron 0.075 mg is more effective than ondansetron 8 mg in preventing post operative nausea and vomiting. (194)
  • Palonosetron dosed according to patient's weight at 3 and 10 mcg/kg is effective and well tolerated in the pediatric population. (195)
  • Palonosetron is a very active antiemetic drug for the prevention of nausea and vomiting induced by folfox-4 regimen for colorectal cancer patients. (196)
  • Palanosetron is safer and more efficacious than other 5HT3RAs in prevention of chemotherapy induced nausea and vomiting. (197)
  • Palanosetron does not any significant effect on QTc and TpTe intervals. It might be the drug of choice in patients with known cardiotoxic potential or who have a pre existing cardiac disease that predispose them to drug induced arrhythmias. (198)

Nk1 receptor antagonists

  • NK1 receptor is present in CTZ and NTS. Their activation by emetogenic chemotherapy release substance P plays a role in causation of vomiting.
  • It is a recently introduced selective, high affinity NK1 receptor antagonist that blocks the emetic action of substance P.
  • Oral aprepitant (125 mg + 80 mg + 80 mg over 3 days) combined with standard i.v. ondansetron + dexamethasone regimen increase antiemetic efficacy  against high emetogenic chemotherapy.
  • Greater additional protection was afforded against delayed than against acute vomiting.
  • Also found to be equally effective as ondansetron in PONV.
  • Pharmacokinetic: it is well absorbed orally. It is metabolized in liver by CYP3A4; t1/2 is 9-13 hrs. Eliminated via bile in faeces and in urine.
  • Tolerability is good. Weakness, fatigue, flatulence and rarely rise in liver enzymes can occur.
  • Fosaprepitant: it is parenterally administered prodrug of aprepitant.
  • In patients with breast cancer treated with anthracycline plus cyclophosphamide chemotherapy, dexamethasone is not superior to aprepitant but instead has similar efficacy and toxicity in preventing delayed emesis. (199)
  • Acute encephalopathy occurs following ifosfamide infusion which is directly triggered by aprepitant. (200)
  • Aprepitant is approved by FDA for the prevention of chemotherapy induced nausea and vomiting. It undergoes extensive metabolism primarily via CYP3A4 mediated oxidation. It is eliminated by metabolism and is not renally excreted. The apparent terminal half life in humans ranged 9-13 hours. (201)
  • Interaction is seen between ifosfamide and aprepitant in patients with gynecologic malignancies precipitating neurotoxicity. (202)
  • Aprepitant has a potential role as an antiemetic for refractory symptoms within palliative care setting. (203)
  • Fosaprepitant and aprepitant are recommended for preventing CINV due to moderately and highly emetogenic chemotherapy. (204)
  • Concomitant administration of aprepitant has no clinically significant effect on the mean pharmacokinetic characteristics of either ondansetron or granisetron in healthy subjects. (205)
  • Aprepitant significantly increases sirolimus levels in patients undergoing allogenic hematopoietic SCT. (206)
  • Aprepitant adds additional antiemetic protection to standard therapy and should be considered in all patients receiving highly emetogenic chemotherapy. (207)
  • Aprepitant appears to be effective for both acute and prophylactic management of pediatric cyclical vomiting syndrome refractory to conventional therapies. (208)
  • Efficacy of aprepitant for the prevention of chemotherapy induced nausea and vomiting in a range of tumor types. (209)
  • Triple antiemetic therapy with aprepitant and dexamethasone improves the control of CINV prevention in patients receiving carboplatin and pemetrexed chemotherapy in patients with advanced non small cell lung cancer. (210)
  • The treatment with pantoprazole and aprepitant significantly inhibits the gastric secretion, total acidity and esophagitis index in gastro esophageal reflux disease in albino rats. (211)
Adjuvant Antiemetics
  • Corticosteroids: (e.g. dexamethasone 8-20 mg i.v.) employed to augment the efficacyof other primary antiemetic drugs like metaclopramide and ondansetron against highly emetogenic regimens. It benefits both acute and delayed vomiting. The basis of their effect appears to be their anti-inflammatory action. They also serve to reduce the certain  side effect of primary antiemetic.
  • Benzodiazepines: the weak antiemetic property is primarily based on the sedative action. Used as adjuvant with other primary antiemetics, Diazepam/lorazepam help by relieving the psychogenic component, anticipatory vomiting and produce amnesia for the unpleasant procedure. They also suppress dystonic side effects of metoclopramide.
  • Cannabinoids: they probably act through the CB1 subtypes of cannabinoid receptors located on neurons in the CTZ and/ or the vomiting centre itself.
  • Dronabinol, Nabilone: used as alternative emetogenic for moderately emetogenic chemotherapy. The hallucinogenic, disorienting and other central sympathomimetic effects limit their use. They are also appetite stimulant.
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