Tag: Prokinetic Drugs

Prokinetic Drugs

PROKINETIC DRUGS

Q. 1

Drug not used in H. pylori :

 A

Metronidazole

 B

Omeprezole

 C

Mosapride

 D

Amoxicillin

Q. 1

Drug not used in H. pylori :

 A

Metronidazole

 B

Omeprezole

 C

Mosapride

 D

Amoxicillin

Ans. C

Explanation:

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

RECOMMENDED TREATMENT REGIMEN FOR HELICOBACTER PYLORI :

Regimen duration

Drug 1

Drug 2

Drug 3

Drug 4

1st line treatment

 

 

 

 

Regimen 1

OCA (7 days)

Omeprazole

Clarithromycin

Amoxicillin

 

Regimen 2

OCM (2 days)

Omeprazole

Clarithromycin

Metronidazole

 

2nd line treatment

 

 

 

 

Regimen 3

OBTM (14 days)

Omeprazole

Bismuth

Tetracycline

Metronidazole

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



Q. 2

All the following statements regarding interactions of levodopa are correct except –

 A

In Parkinsonism, phenothiazines reduce its efficacy

 B

It is a prodrug

 C

Pyridoxine reduces effect of levodopa in parkinsonism

 D

Domperidone blocks levodopa induced emesis and its therapeutic potential

Q. 2

All the following statements regarding interactions of levodopa are correct except –

 A

In Parkinsonism, phenothiazines reduce its efficacy

 B

It is a prodrug

 C

Pyridoxine reduces effect of levodopa in parkinsonism

 D

Domperidone blocks levodopa induced emesis and its therapeutic potential

Ans. D

Explanation:

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.


Q. 3

Metoclopramide is useful for all except –

 A

Motion sickness

 B

Chemotherapy induced vomiting

 C

Antiemetic

 D

All

Q. 3

Metoclopramide is useful for all except –

 A

Motion sickness

 B

Chemotherapy induced vomiting

 C

Antiemetic

 D

All

Ans. A

Explanation:

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.

Quiz In Between


Q. 4

Prokinetic drug with extrapyramidal side effect is?

 A

Cisapride

 B

Domperidone

 C

Ondansetron

 D

Metoclopramide

Q. 4

Prokinetic drug with extrapyramidal side effect is?

 A

Cisapride

 B

Domperidone

 C

Ondansetron

 D

Metoclopramide

Ans. D

Explanation:

Ans. is ‘d’ i.e., Metoclopramide

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


Q. 5

A prokinetic drug which lacks D2 receptor antagonistic action is which one of the following‑

 A

Metoclopramide

 B

Domperidone

 C

Cisapride

 D

Chlorpromazine

Q. 5

A prokinetic drug which lacks D2 receptor antagonistic action is which one of the following‑

 A

Metoclopramide

 B

Domperidone

 C

Cisapride

 D

Chlorpromazine

Ans. C

Explanation:

Ans. is ‘c’ i.e., Cisapride

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


Q. 6

The commonest side-effect of Cisapride is –

 A

Abdominal cramps

 B

Diarrhea

 C

Headache

 D

Convulsions

Q. 6

The commonest side-effect of Cisapride is –

 A

Abdominal cramps

 B

Diarrhea

 C

Headache

 D

Convulsions

Ans. B

Explanation:

Ans. is ‘b’ i.e., Diarrhea

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

Quiz In Between


Q. 7

Drug implicated for prolongation of QT interval in a premature baby is –

 A

Domperidone

 B

Metoclopramide

 C

Cisapride

 D

Omeprazole

Q. 7

Drug implicated for prolongation of QT interval in a premature baby is –

 A

Domperidone

 B

Metoclopramide

 C

Cisapride

 D

Omeprazole

Ans. C

Explanation:

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


Q. 8

Patient is on Cisapride for gastroesophageal reflux develops upper respiratory tract infection, and physician prescribes erythromycin. What pharma­logical interaction would be expected –

 A

Dereased level of erythromycin and exacerbation of URTI

 B

Decreased effect of cisapride due to enzyme inductor of erythromycin

 C

Fatal ventricular arrhythmia

 D

Hemorrhagic cystitis

Q. 8

Patient is on Cisapride for gastroesophageal reflux develops upper respiratory tract infection, and physician prescribes erythromycin. What pharma­logical interaction would be expected –

 A

Dereased level of erythromycin and exacerbation of URTI

 B

Decreased effect of cisapride due to enzyme inductor of erythromycin

 C

Fatal ventricular arrhythmia

 D

Hemorrhagic cystitis

Ans. C

Explanation:

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


Q. 9

All of the following drug may be used for motion sickness except –

 A

Hyoscine

 B

Dicyclomine

 C

Domperidone

 D

Scopolmine

Q. 9

All of the following drug may be used for motion sickness except –

 A

Hyoscine

 B

Dicyclomine

 C

Domperidone

 D

Scopolmine

Ans. C

Explanation:

Ans. is ‘c’ i.e., Domperidone

o Drugs used are :

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

b)      Hl-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.

Quiz In Between


Q. 10

Which of the following is a prokinetic drug with no dopamine antagonism:         

March 2005

 A

Chlorpromazine

 B

Metaclopramide

 C

Domperidone

 D

Mosapride

Q. 10

Which of the following is a prokinetic drug with no dopamine antagonism:         

March 2005

 A

Chlorpromazine

 B

Metaclopramide

 C

Domperidone

 D

Mosapride

Ans. D

Explanation:

Ans. D: Mosapride

Metoclopramide is a dopaminergic antagonist and peripheral serotonin receptor antagonist with GI and CNS effects Cisapride is chemically related to metoclopramide, but unlike metoclopramide, it does not cross the blood-brain barrier or doesn’t have antidopaminergic effects. Therefore, it does not have antiemetic action or cause extrapyramidal effects (extreme CNS stimulation).

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


Q. 11

Commonest side effect of cisapride

 A

Abdominal cramps

 B

Headache

 C

Diarrhea

 D

Convulsions

Q. 11

Commonest side effect of cisapride

 A

Abdominal cramps

 B

Headache

 C

Diarrhea

 D

Convulsions

Ans. C

Explanation:

Ans. is ‘c’ i.e., Diarrhoea


Q. 12

Which of the following is a prokinetic drug‑

 A

Domperidone

 B

Cimetidine

 C

Ondansetron

 D

Hyoscine

Q. 12

Which of the following is a prokinetic drug‑

 A

Domperidone

 B

Cimetidine

 C

Ondansetron

 D

Hyoscine

Ans. A

Explanation:

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.

Quiz In Between



Prokinetic Drugs

PROKINETIC DRUGS


PROKINETIC DRUGS

Introduction:

  • Are drugs used for increasing GI motility.
  • Mainly used for treatment of gastroparesis, postoperative paralytic ileus & constipation.

MOA:

    • ACh – Main excitatory neurotransmitter in GIT.
  • Presynaptic receptors in cholinergic neurons:
    • Excitatory (5-HT4) & Inhibitory (5HT 3, D).
    • Hence, D2 & 5HT3 antagonists and 5 HT4 agonists – Increases ACh release & stimulates GI motility.

Drugs included:

  • Metoclopramide, domperidone, cisapride, mosapride, renzapride, prucalopride & tegaserod.

Important drugs:

1. Metoclopramide:

  • MOA:
    • Blocks both central & peripheral D2.
    • Central D2 blocking action – Mainly antiemetic effects
  • Prokinetic properties:
    • Due to 5HT4 receptor agonism (main mechanism) & 5HT4 receptor antagonism –> ACh release.
  • Other uses:
    • Antiemetic agent.
    • In GERD.
    • Gastroparesis treatment (in diabetic patients).
    • During emergency general anesthesia – Enhances gastric emptying, if patient has taken food within 4 hrs.
  • Side effects:
    • Extrapyramidal side effects (muscle dystonia, parkinsonism) – Due to D2 blocking action.
    • Hyperprolactinemia –> leading to galactorrhoea.
  • Treating overdose effects:
    • Antagonized by atropine.
    • It increases gastric peristalsis –> Enhances gastric emptying & LES tone.
    • No effect on colonic motility.

2. Domperidone:

  • D2 receptor antagonist.
  • Doesn’t cross blood-brain barrier.
  • Mainly as an antiemetic (less efficacious than metoclopramide).
  • Decreases l-dopa induced vomiting without interfering with its efficacy.
  • Devoid of extrapyramidal & hyperprolactinemic adverse effects.

3. 5HT4 agonists:

  • Drugs: Cisapride, mosapride, renzapride, prucalopride & tegaserod.
  • MOA: 
    • 5-HT4 agonistic activity.
    • No action on D2 receptors – Hence, no antiemetic property.
    • Increases whole GI motility including colon.

Individual drug description:

  • Cisapride:
    • Previously used for GERD treatment.
    • Withdrawn in some countries – Due to QT-prolonging action.
    • Metabolized by CYP 3A4 – Hence, should not be administered with microsomal enzyme inhibitors like ketoconazole & erythromycin.
    • Increased chances of torsades de pointes (arrhythmia with QT prolongation).
  • Mosapride & renzapride:
    • Does not prolong QT interval.
  • Tegaserod: 
    • Used for constipation dominant irritable bowel syndrome.
    • Recently withdrawn from India – Due to increased incidence of myocardial infarction & stroke.

4. Other prokinetic drugs:

  • Levosulpiride:
    • l-isomer of sulpiride.
    • Newer D2 blocker with prokinetic activity.
    • Also an antipsychotic drug.
  • Loxiglumide:
    • CCK1 receptor antagonist.
    • Indicated for constipation dominant IBS.
  • Macrolides (mainly erythromycin):
    • Acts as motilin agonists.
    • Indicated in diabetic gastroparesis.
    • Rapid tolerance development limits this use.

Exam Important

  • Prokinetic drugs are drugs used for increasing GI motility.
  • 5-HT4 receptors are excitatory & 5HT3, Dare inhibitory are in nature among presynaptic receptors in cholinergic neurons.
  • Prokinetic drugs include Metoclopramide, domperidone, cisapride, mosapride, renzapride, prucalopride & tegaserod.
  • Prokinetic properties of metoclopramide are mainly due to 5HT4 receptor agonism (main mechanism) & 5HT4 receptor antagonism resulting in ACh release.
  • Metoclopramide is also an antiemetic drug, useful in gastroparesis treatment (in diabetic patients) & also during emergency general anesthesia by enhancing gastric emptying, if patient has taken food within 4 hrs.
  • Prokinetic drug with extrapyramidal side effect is Metoclopramide.
  • Extrapyramidal side effects (muscle dystonia, parkinsonism) – Due to D2 blocking action.
  • Metoclopramide can cause hyperprolactinemia, leading to galactorrhoea.
  • Domperidone is a D2 receptor antagonist which doesn’t cross blood-brain barrier.
  • Domperidone is less efficacious than metoclopramide & mainly as an antiemetic.
  • Domperidone decreases l-dopa induced vomiting without interfering with its efficacy.
  • Domperidone is devoid of extrapyramidal & hyperprolactinemic adverse effects.
  • 5HT4 agonists like Cisapride, mosapride, renzapride, prucalopride & tegaserod have no action on D2 receptors, hence, no antiemetic property.
  • Cisapride is withdrawn in some countries, due to QT-prolonging action.
  • Cisapride is metabolized by CYP 3A4 not administered with microsomal enzyme inhibitors like ketoconazole & erythromycin.
  • Cisapride has increased chances of torsades de pointes (arrhythmia with QT prolongation).
  • Mosapride & renzapride does not prolong QT interval.
  • Tegaserod used for constipation dominant irritable bowel syndrome.
  • Tegaserod has recently withdrawn from India, due to increased incidence of myocardial infarction & stroke.
  • Levosulpiride is a newer D2 blocker with prokinetic activity.
  • Loxiglumide is a CCK1 receptor antagonist, indicated for constipation dominant IBS.
  • Macrolides (mainly erythromycin)acts as motilin agonists, indicated in diabetic gastroparesis.
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