Prokinetic Drugs

Mosapride[Ref. Harrison 16^th/e p 888]

Mosapride is a 5-HT4 agonist used for GERD. Stimulation of 5-HT4 receptors on the presynaptic terminal of submucosal intrinsic primary afferent nerves enhances the release of their neurotransmitters, including calcitonin gene-related peptide, which stimulate second-order enteric neurons to promote the peristaltic reflex. These enteric neurons stimulate proximal bowel contraction (via acetylcholine and substance P) and distal bowel relaxation.

Drugs useful for H. Pylori infection

o Amoxicillin                                                    o Tetracycline

o Tinidazole/metronidazole                               o Bismuth

o Omeprazole                                                 o Clarithromycin

o Ranitidine

Ans. is ‘d’ i.e., Domperidone blocks levodopa induced emesis and it’s therapeutic potential

`When domperidone is administered with levodopa or bromocriptine, it counteracts their dose limiting emetic action, without affecting the therapeutic effect in Parkinsonism’                                    

Levodopa is a prodrug, inactive by itself but is the immediate precursor of the transmitter dopamine.

Ans. is ‘a’ i.e., Motion sickness

o Metoclopramide can be used as an antiemetic in postoperative, drug induced, disease associated, radiation sickness,

but is less effective in motion sickness.

o It should not be used to augment lactation. Though the amount secreted in milk is small, but suckling infant may develop loose motions, dystonia, myoclonus.

Ans. is ‘d’ i.e., Metoclopramide

o Metaclopramide can prodce extrapyramidal side effects due to D₂ blockade action.

Ans. is ‘c’ i.e., Cisapride

o Cisapride has 5-HT₄ agonistic activity (without any D₂ blocking activity).

Ans. is ‘b’ i.e., Diarrhea

Cisapride is a prokinetic agent and often produces loose stools (diarrhea is thus the commonest side effect)

Ans. is ‘c’ i.e., Cisapride

Cisapride is a non-selective serotonin 5HT4 agonist and partial 5HT3 antagonist.

This drug accelerates gastric emptying, so it is used in patients with Gastro Esophageal Reflex Disease (GERD).

One of the rare complications includes QT prolongation in ECG, ventricular dysarrthymias and sudden death.

Cisapride inhibits the delayed rectifying IC- channels in heart and can cause prolongation of QT interval. o Drugs inhibiting CYP3A4 enzyme can precipitate Torsaes DePointes, Caused by cisapride eg; clarithromycin, erythromycin, cyclosporine, fluconazole, itraconazole, ketoconazole, Nefazodone, Ritonavir, Fluvoxamine.

The drug has been withdrawn from most countries.

Ref: Henry P. Parkman, Richard W. McCallum (2012)  Chapter 22, “Prokinetic Agents for Gastroparesis”, In the  book, “Gastroparesis: Pathophysiology, Presentation and Treatment”, Springer Publications, Newyork, Page 267 ; Katzung, 9th Edition, Page 1046

Ans. is ‘c’ i.e., Fatal ventricular arrythmia

Ans. is ‘c’ i.e., Domperidone

o Drugs used are :

a)         Anticholinergics —> Hyoscine (Scopolamine), Dicyclomine.

b)      H_l-antihistaminic —> Promethazine, cyclizine, meclizine, cinnarizine, etc.

o Hyoscine (scopolamine) is the most effective drug for motion sickness.

About option ‘c’

o Domperidone is a prokinetic drug and acts by D₂ blockade. It is ineffective in motion sickness as vestibular pathway does not involve dopaminergic link.

Ans. D: Mosapride

Mosapride is a new congener of cisapride with similar gastrokinetic and LES tonic action due to 5-HT4 agonistic (major) and 5-HT3 antagonistic (minor) action in the myenteric plexus, but has not caused Q-Tc prolongation or arrhythmias. Like cisapride, it has no clinically useful antiemetic action and does not produce extrapyramidal/hyperprolactinemic side effects due to absence of D2 blocking property.

Domperidone is a peripheral dopamine receptor antagonist

Ans. is ‘c’ i.e., Diarrhoea

Ans. is ‘a’ i.e., Domperidone

Gastrokinetic (prokinetic drugs)

• These are the drugs which promote gastrointestinal transit and speed gastric emptying by enhancing coordinated propulsive motility.
• Prokinetic drugs are → Metoclopramide, Domperidone, Cisapride, Mosapride, Tegaserod, renzapride, prucalopride.

Pathophysiology of gastrokinetic drugs :

• Acetylcholine is the major neurotransmitter in the GIT which is responsible for the peristaltic movement.
• Its secretion is affected by other neurotransmitter also ‑

1. Activation of prejunctional excitatory 5-HT, receptors increases the release of Ach.
2. Activation of prejunctional inhibitory D2 and 5-HT, receptors inhibits the release of Ach.

• So, prokinetic drugs can act by ‑

1. 5HT4 agonistic activity
2. D2 and 5-HT3 antagonistic activity

• Both these action will increase the release of Ach and there by motility of GIT.