Antiemetic and Prokinetic drugs

– Vomiting or emesis occurs due to stimulation of vomiting centre in the lateral medullary reticular formation.
– It receives input from GI mucosa, CTZ & vestibular apparatus.

• Antiemetics are the drugs used to prevent or suppress vomiting.

Classification :-
Awesome People Had Antiemetic Drugs Successfully.

1. Anticholinergics
2. Prokinetic drugs
3. H1 antihistamines
4. Adjuvant drugs
5. D2 blockers (neuroleptics)
6. 5-HT3 antagonists (serotonin )
7. NK1 receptor antagonists


1. Anticholinergics

Hyoscine & Dicyclomine are used.
– Action is exerted by blocking conduction of nerve impulses across a cholinergic link in the pathway leading from vestibular apparatus to vomiting centre.
– Effective in motion sickness.


2. H1 antihistamines :-

– Useful mainly in motion sickness & to a lesser extent in morning sickness.
– Antiemetic action is based on anticholinergic, antihistamines, weak antidopaminergic & sedative properties.
Promethazine, diphenhydramine, dimenhydrinate – effective in motion sickness
Doxylamine – in combination with pyridoxine used for motion sickness in India.
– Meclozine – used in sea sickness.
Cinnarizine – antivertigo drug with antimotion sickness property.


3. Neuroleptics :-

Act by blocking D2 receptors in the CTZ.
– Used in drug induced & postoperative nausea vomiting, disease induced vomiting, chemotherapy induced vomiting, radiation sickness vomiting, morning sickness.
– Cause sedation .
Prochlorperazine is a highly effective drug.


4. Prokinetic drugs :-

These are an important class of drugs which promote gastrointestinal transit & speed gastric emptying by enhancing propulsive motility.

Metoclopramide :

ACTIONS

GIT :- has more prominent effect on GIT. Increases gastric peristalsis, relaxes the pylorus & first part of duodenum – speeds gastric emptying. Lower esophageal sphincter tone is increased & gastroesophageal reflux is opposed.
CNS :- is an effective antiemetic. Acts on CTZ. Blocks apomorphine induced vomiting.

MECHANISM OF ACTION-

– D2 receptor antagonism
– 5-HT4 antagonism
– 5-HT3 antagonism

IMPORTANT DRUG INTERACTIONS-

– Hastens the absorption of drugs like aspirin, diazepam.
– Absorption of digoxin is reduced.
– By acting on D2 receptor, it blocks the action of Levodopa.

ADVERSE EFFECTS-
– Long term use causes parkinsonism, galatorrhea & gynaecomastia.
– Sedation, dizziness, loose stools, muscle dystonias are common.

USES-
Antiemetic : effective in postoperative, drug induced, disease associated, radiation induced nausea vomiting.
Less effective in motion sickness.
Promethazine, diphenhydramine, diazepam injected IV along with metoclopramide supplement it’s action & reduce side effects.
Gastrokinetic action : to accelerate gastric emptying when emergency general anaesthesia is to be given, for postvagotomy associated gastric stasis.
Dyspepsia & other functional GI disorders.
GERD.

Domperidone :
– D2 receptor antagonist.
– Crosses blood brain barrier poorly – less extrapyramidal side effects.
– Antiemetic action is on CTZ (not protected by BBB)

Cisapride
– Lacks D2 receptor antagonism
– Effects of GIT similar to metoclopramide.
At high concentrations, cisapride blocks delayed rectifying K+ channels in heart – prolongation of QT interval.

Mosapride
– Actions similar to cisapride
– Major 5- HT4 agonistic action & minor 5-HT3 antagonistic action.
– Prolongs QT interval.
– Indications : nonulcer dyspepsia, diabetic gastroparesis, GERD.

Itopride


 

5. 5-HT3 antagonists :-

Ondansetron :-
– Controls chemotherapy & radiotherapy induced vomiting, highly effective in post operative nausea, vomiting.
Cytotoxic drugs /radiation – cellular damage – release of mediators like 5-HT3 from intestinal mucosa – activation of vagal afferents in gut – emetogenic impulses to CTZ & NTS – nausea vomiting.
– Odansetron blocks the action of 5-HT3 through 5-HT3 receptors.
– Odansetron alone is less effective in delayed vomiting than in acute vomiting which occurs within 24 hours of cisplastin dose.
– Ondansetron may be combined with dexamethasone, promethazine, etc.
– Is well tolerated
– Common s/e – headache & dizziness.

Palonosetron :-
– Longest acting & has high affinity for 5-HT3 receptor.
– More effective in suppressing delayed vomiting occurring between 2-5 days of cisplastin dose. ( Because of long half life)
– Only drug of its class approved by US-FDA for delayed CINV.
– Rapid IV injection may cause blurring of vision.

Granisetron
Ramosetron


6. NK1 receptor antagonists :-

Release of substance P by emetogenic chemotherapy & other stimuli cause activation of neurokinin receptor NK1 in CTZ & NTS. This causes vomiting.
Aprepitant :-
– Is a high affinity NK1 receptor antagonist
– blocks the action of substance P, with little effect on 5HT3 or D2 receptors.
– Aprepitant + ondansetron + dexamethasone (125 mg + 80 mg + 80 mg over 3 days) is a standard regimen for CINV.


7. Adjuvant drugs :-

Drugs like corticosteroids, benzodiazepines & cannabinoids are also used in pharmacotherapy of nausea & vomiting.

 


– Contributed by Soumya Khot, Jay Shah, Chaitanya Inge.

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