DEFENITIONCLASSIFICATIONINDIVIDUAL DRUGSANTIEMETIC THERAPY IN SPECIAL CASESCLINICAL USESSUMMARY

DRUGS THAT PREVENTS NAUSEA AND VOMITNG ARE CALLED ANTIEMETICS.VARIOUS DRUGS INCLUDING SOME ANTIHISTAMINE AND ANTICHOLINERGICS HAVE THIS EFFECT. THEY ARE USED FOR CONDITIONS LIKE MOTION SICKNESS, RADIATION OR CHEMOTHERAPY INDUCED VOMITING, MIGRAINE AND VERTIGO.

Afferent inputs to VC are through CTZ located in area postrema

Emetogenic signals reach VC through CTZ which is rich in dopamine D2 seratonin 5HT3, muscarinic and histamine receptors which causes vomitting

Drugs blocking these receptors are the potential targets

A. Muscarinic receptor antagonists/ antimuscarinic agents.

Hyoscine(scopolamine)Dicyclomine

PromethazineCyclizineCinnarizineDimenhydrinateDiphenhydramine ……………………….3DDoxylamine

These H1 receptor antagonists may act by virtue of significant anticholinergic activity.

Non selective D1 & D2 antagonists1. Phenothiazines : Chlorpromazine, Prochlorperazine. 2. Butyrophenone : Haloperidol & Droperidol.

Selective D2 antagonistsMetoclorpramide & Domperidone

OndansetronGranisetronPalanoseteron- most potentTropisetron

Oral & Parental preparation are available for use.

For CIE – administer drug 30 mins prior to chemotherapy I.V

Cannabinoids Benzodiazipines Pyridoxine (Vit B6) serves as

cofactor for the enzyme glutamate decarboxylase which in turn increases synthesis of GABA

GlucocorticoidsProkinetic drugs are Metoclopramide,

Domperidone, Cisapride Mozapride& Tegaserod.

MECHANISM OF ACTIONMECHANISM OF ACTION

Most effective drug for motion sickness.Action: Probably by blocking conduction of nerve impulses across a cholinergic link in the pathway leading from vestibular apparatus to vomiting center & is not effective in vomiting of other etiologies.Suitable for short brisk journeys & has a brief duration of action.Side effects :Produces sedation & other Anticholinergic side effects.

Treatment: Transedermal patches containing Hyoscine , to be delivered over 3 days has been developed, applied behind the pinna. It suppreses motion sickness whiele producing only mild side effects.Dose: 0.2-0.4 mg oral, i.m.

Uses: For prophylaxis of motion sickness and for morning sickness.It has been cleared of teratogenic potential.Dose: 10-20mg oral.

Action: Affords protection of motion sickness for 4-6hrs, but produce sedation & dryness of mouth.Uses: By their central anticholinergic action, they block the extrapyramidal side effects of Metoclopramide while supplementing its antiemetic action.Their combination is used in chemotherapy induced vomiting.

Promethazine is the first generation of H1 receptor antagonist used as antihistamine antiemetic.Drugs: Phenargan, Promethagan.Indications: Sedative, Antiallergic, Adjunct in Motion sickness, Morning sickness.Side effects: Respiratory depression, Seizures, Neuroleptic malignant syndromes, Paresthesia, tremors, Drowziness, Euphoria, Chest discomfort, & Confusion in elderly.

Action: It is a sedative antihistaminic with prominent anticholinergic activity.Uses: Morning sickness.Side effects: Drowsiness, dry mouth, vertigo & abdominal upsets.Drugs: Doxinate – 10mg with Pyridoxine 10mg tab.Dose: 10-20mg at bed time; if needed additional doses may be given in morning & afternoon.

Cyclizine is a Antihistamine used to treat nausea, vomitting, motion sickness & vertigo.Action: These are less sedative & less anticholinergic.Contraindications: Glaucoma, Prostatic hypertrophy, strong Psychoactive effects.Side effects: Drowsiness, Xerostomia.Drugs & Dosage: Cyclizine HCl 50mg tab (for adults) & 25mg tab (for kids).

It is an antihistamine drugMeclizine is long-acting ; protects against sea sickness for nearly 24hrs.Use: prevents nausea, vomiting, motion sickness and also to relieve allergic reaction.

It is an Anti vertigo or Antihistaminic drug, & also protective for motion sickness causing nausea & vomiting.Action: Probably by inhibiting influx of Ca2+ from endolymph into the vestibular sensory cells which mediates labyrinthine reflexes.Contraindications: acute & chronic parkinsonism, drowsiness & blurred vision. Drug & Dose: Stugeron tab 25mg, 75mg

It is a dopamine receptor antagonist used for treatment of nausea & vertigo.It is also a highly potent typical antipsychotic & more potent than chlorpromazine.Uses: Treat Migrane headaches, as an Anti-psychotic & alleviates labrynthitis.Side Effects: Hypersensitivity Dyskinesia, Seizures, Neuroleptic malignancy syndrome.

It is a prokinetic drug that promotes g.i. transit & gastric emptying.

Action: on the GIT & CNS through D2 & 5-HT antagonism & 5-HT4 agonism.

Adverse Effects: Sedation ,Dizziness, Loose stool, Muscle dystonia, Galactorrhoea & Gynacomastia.

Uses: Antiemetic, Gastrokinetic, Dyspepsia & Gastoesophageal reflux disease.

It is a D2 antagonist, related chemically to Haloperidol & pharmacologically to Metoclopramide.It crosses BBB very poorly, hence does not affect the CTZ.Its prokinetic action is based on D2 antagonism in the upper g.i.t.Side Effects: Dry mouth, Loose stool, Headache, Rashes, Galactorrhoea.Drug & Dose: Domstal tab, 10mg, liq. 1mg/ml

It is a gastro prokinetic drug, which increases motility in upper g.i.t. Action: promotes Ach release through 5-HT4 agonists so there is increased G.I motility Side Effects: mainly Antidopaminergic side effects also Dizziness & increased serum transaminase. Drug & Dose: Ciza 20mg tab, Syspride 10mg tab.

Newer congener of cizapride with similar gastro kinetic actions. Side Effects : Diarrhoea, Dizziness, abdominal cramps & Antidopaminergic side effects. Drug & Dosage: Moza 5mg TDS, Normagut 2.5mg.

It is a prototype developed to control cancer chemotherapy or radiotherapy induced vomiting.Action: Reduces the activity of vagus nerve which deactivates the vomiting center & also blocks the action of 5-HT3.Uses: prevents Chemotherapy, Post operative nausea & vomiting , Cyclic vomiting syndrome.

Side Effects: Constipation, Dizziness, Headache.Clinical Use: CIV, Parkinson’s disease, AlcoholismDrug & Dosage: Emeset, tab. 4mg, 8mg, inj. 2mg/ml.

Vomiting associated with pregnancy: Antiemetic drug therapy may not be required for early pregnancy vomiting (morning sickness). If excessive Promethazine is used, Pyridoxine supplement is not required. However, in hyperemesis gravidum, Pyridoxine supplement along with doxylamine may be required.

Motion sickness: Antihistamines (Meclizine, Cyclizine) Hyoscine, Promethazine.Vertigo & other Labyrinthine disorders: Hyoscine Antihistamines, Phenothiazines.Emesis due to Cytotoxic agents: Odansetron, Metoclopramide. In refractory cases Nabilone, Dexamethasone are used.

SUMMARYSUMMARY

Histamine H1 – receptor antagonist-Cyclizine: motion sickness Hyoscine: motion sickness-Cinnarizine: vestibular disorders (eg. Menieres disease) & motion sickness-Promethazine : severe morning sickness of pregnancy (but if only absolutely essential)

Muscarinic receptor antagonists - Dopamine D2-receptor antagonists -Phenothiazines(eg. Prochlorperazine) : vomiting caused by uraemia , radiation, viral gastroenteritis: severe morning sickness of pregnancy( but if only absolutely essential)

-Metaclopramide: vomiting uremia , radiation, gastrointestinal disorders , cytotoxic drugs.

5- Hydroxytryptamine 5HT3- receptor antagonists (eg. Odansetron): vomiting caused by cytotoxic anticancer drugs ; postoperative vomiting , radiation induced vomiting.Cannabinoids(eg. Nabilone) for vomiting caused by anticancer drugs.

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