Anti-Emitic and Prokinetic Drugs
Uploaded by
Dr.Farhana Dutta MajumderAnti-Emitic and Prokinetic Drugs
Uploaded by
Dr.Farhana Dutta MajumderAnti-emetic Dr Farhana Dutta Majumder
Professor, Pharmacology
& Sree Balaji Medical College
Prokinetic drugs and Hospital
Introducti
on
Definition of emesis
Nausea is an unpleasant sensation preceding vomiting
Vomiting is forceful expulsion of gastric contents through the mouth
Emetic
s 1. Apomorphine
• Synthetic derivative of morphine
• Dopaminergic agonist on the CTZ
• Use for induced vomiting in poisoning
2. Ipecacuanha
• The dried root of Cephaelis ipecacuanha
• Acts by irritating gastric mucosa and then
through CTZ.
• Safer than Apomorphine
Contraindication of Emetics
+ Corrosive (acid, alkali) poisoning
+ CNS stimulant drug poisoning
+ Kerosine (petroleum) poisoning
+ Unconscious patient
+ Morphine or phenothiazine poisoning
Anti-emetics classification
Anticholinergics Neuroleptics NK1 receptor Prokinetic drugs
antagonists
Hyoscine Chlorpromazine Metoclopramide
Dicyclomine Triflupromazine Aprepitant Domperidone
Prochlorperazine Fosaprepitant Cisapride
Mosapride
ltopride
Levosulpiride
H1 anti-histaminics 5-HT3 antagonists Cinitapride
Promethazine Ondansetron Adjuvant antiemetics
Diphenhydramine Granisetron
Dimenhydrinate Palonosetron Dexamethasone
Doxylamine Ramosetron Benzodiazepines
Meclozine Dronabinol
ANTICHOLINERGICS
Hyoscine
• Hyoscine inhibits the cholinergic communications between the higher
centers of CNS, the reticular formation in the brainstem, the vestibular
nuclei, the cerebellum, the glossopharyngeal nerve, and the vagus nerve
• Most effective drug for motion sickness
• Adverse effects: dry mouth, dizziness, confusion, agitation, delirium, mydriasis
• Dosage forms: Transdermal patch, 1.5 mg applied behind the pinna of the ear
H1 ANTIHISTAMINICS
Promethazine, Diphenhydramine
• Use for motion sickness
• Dry mouth, sedation
• No advisable for driving after taking the medication
Doxylamine
• Has marked anti-muscarinic activity
• Mainly marketed in India for motion sickness
• T ½ - 10 hours
• Adverse effects: drowsiness, dry mouth, vertigo and abdominal upset
H1 ANTIHISTAMINICS
Meclozine
• Less sedative, less anti-cholinergic and longer acting
• Use for sea sickness for 24 hours
Cinnarizine
• Antivertigo drug
• MOA: inhibits the influx of Ca+2 from endolymph into the vestibular
sensory cells
• First choice drugs for motion sickness. The drug should be taken
½ - 1 hour before the journey
NEUROLEPTICS
Prochlorperazine, Haloperidol
• MOA: blocks D2 receptors in the CTZ
• Antiemetic actions –
Drug induced and postoperative nausea and vomiting
Disease induced vomiting (gastroenteritis, uraemia, liver disease, migraine)
Malignancy and cancer chemotherapy associated vomiting
Radiation sickness vomiting
Morning sickness (hyperemesis gravidarum)
Most common adverse effects: Muscle dystonia and extra-pyramidal side effects
PROKINETIC DRUGS
Metoclopramide
• Discovered in 1970, known as ‘gastric hurrying agent’
• GIT: increases gastric peristalsis while relaxing the pylorus and the
first part of duodenum
• CNS: Metoclopramide acts on CTZ
Metoclopramide
MOA
D2 antagonism
• In the GIT, metoclopramide blocks D2 receptors and increases gastric
emptying and LES tone by releasing ACh.
• In CNS, D2 receptors on CTZ are blocked
5-HT4 agonism
• Metoclopramide acts in the GIT to enhance ACh release from myenteric
motor neurones
• 5-HT4 receptor activation on primary afferent neurones (PA ) of the ENS
– activation of the excitatory neurons – gastric hurrying and LES tonic effect
Metoclopramide
Kinetics: rapidly absorbed orally, enters brain, crosses placenta
T ½ 3-6 hrs
Adverse effects: Sedation, dizziness, loose stools, muscle dystonia
(especially in children) are the main side effects.
Long-term use can cause parkinsonism, galactorrhoea
and gynaecomastia
Metoclopramide
Uses: 1) Anti-emetic
2) Gastrokinetic
(a) Emergency general anaesthesia
(b) To relieve postvagotomy or diabetic gastroparesis
associated gastric stasis
(3) Dyspepsia
(4) Gastroesophageal reflux disease (GERD)
Mosapride
• MOA: 5-HT4 agonistic and 5-HT3 antagonistic action in the myenteric
plexus.
• Does not produce extrapyramidal or hyperprolactinaemic side
• Adverse effects: loose motions, abdominal pain, headache,
dizziness and insomnia
• Uses: Non-ulcer dyspepsia. diabetic gastroparesis, GERD
(as adjuvant to PPIs), and some cases or chronic constipation
5-HT3 ANTAGONISTS
Ondansetron
MOA: Ondansetron blocks the depolarizing action of serotonin exerted
through 5-HT receptors on vagal afferents in the GIT as well as in
NTS (nucleus tractus solitarii) and CTZ (chemoreceptor trigger zone)
Kinetics: Oral bioavailability 60 -70%
Uses: Chemotherapy induced vomiting, Post operative nausea and vomiting
Adverse effects: Common - headache and dizziness, mild constipation.
With IV - Hypotension, bradycardia, chest pain and
allergic reactions
NK1 RECEPTOR ANTAGONISTS
Aprepitant
MOA: Selectively blocks kinin (K1) receptor on NTS and CTZ that inhibits the
emetic action of substance P
Uses: patients against cisplatin based highly emetogenic chemotherapy,
cyclophosphamide based moderately emetogenic chemotherapy
Adverse effects: weakness, fatigue, flatulence and rarely rise in liver
enzymes
ADJUVANT ANTIEMETICS
Corticosteroids
• Augment the efficacy of other primary antiemetic drugs like
metoclopramide and ondansetron against highly emetogenic regimens
• E.g, Dexamethasone 8 mg/day orally from 2- 5th day of chemotherapy
(help to helps delayed vomiting – thought for their anti-inflammatory action)
DIGESTANTS
• These are substances intended to promote digestion of food.
E.g, Pepsin, Papain, Pancreatin, Diastase
Methyl polysiloxane
• It is a silicone polymer
• Reduces surface tension and collapses froth - ' anti-foaming agent'
• Methyl polysiloxane claims to coat and protect ulcer surface, aids
dispersion of antacids in gastric contents, and prevents gastroesophageal
reflux
