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Antacids, anti-emetics &GI motility drugs

Dr Ally DuncanEducation Fellow & SpR in AnaestheticsManchester Royal Infirmary

April 2012

Applied Sciences LectureCourse

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Aims and objectives

Categorise drugs acting on the gut

Discuss relevant pharmacologicalaspects

Discuss common clinical uses

Categorise antiemetics

Discuss relevant pharmacologicalaspects

Discuss common clinical uses

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Drugs acting on the gut

Antacids

Drugs influencing gastric secretion

Drugs influencing gastric motility

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Antacids

Drug action based on physicalproperties

Weak bases that neutralise gastricacid

Traditionally compounds containingaluminium or magnesium

Liquid more effective than tablet

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Antacids

Clinical uses:

symptomatic relief of dyspepsia

some promotion of ulcer healing but

less effective than drugs that inhibitacid secretion

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Antacids

Magnesium containing

Laxative

Aluminium containing Constipating

Interactions May affect absorption of other drugs.

Avoid giving at same time

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Antacids

Examples Aluminium hydroxide

Magnesium trisilicate

Over the counter Gaviscon

Sodium alginate, sodium bicarbonate, calcium chloride

Peptac Sodium alginate, calcium carbonate

Rennie Duo Calcium carbonate, magnesium carbonate

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Drugs influencing gastricsecretion

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Mechanism of gastric acidsecretion

Gastrin AcetylcholinePGE2Histamin

H+

K+

ATP-ase

Ca2

+

Ca2

+

Gs Ac Gi

Protein Kinases

ATPCyclicAMP

ParietalCell

Apical Cellsurface

H2

receptor

Muscarinicreceptor

Proton pump

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Drugs influencing gastricsecretion

H2 receptor antagonists

Proton pump inhibitors

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Reduce basal and food stimulatedgastric acid by 90%

Heal gastric and duodenal ulcers

Provide symptomatic relief indyspepsia

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Which of the following is notan H2 antagonist?

1 2 3 4 5

0%

17%

0%

50%

33%

1. Ranitidine

2. Zantac

3. Gavilast4. Losec

5. Cimetidine

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Rantidine

Zantac, gavilast

Oral / IV preparations

Available over the counter

Side effects (rare)

Cardiac arrhythmias during rapid IV

administrationThrombocytopenia, leucopenia, liver

dysfunction

Anaphylaxis

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Cimetidine

Hepatic enzyme inhibitor (AODEVICES)

Inhibits cytochrome P450 system

Can reduce metabolism of other drugscausing a rise in serum levels e.g.warfarin

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Enzyme INHIBITORS

A Allopurinol

O Omeprazole

D Disulfiram

E Erythromycin V Valproate

I Isoniazid

C Cimetidine & ciprofloxacin E Ethanol (acute intoxication)

S Sulphonamides

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Enzyme INDUCERS

P Phenytoin

C Carbamazepine

B Barbiturates R Rifampicin

A Alcohol

S Sulphonylureas

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Cause irreversible inhibition of proton pump Final common pathway of gastric acid production

Examples Esomeprazole

Nexium Lanzoprazole

Zoton

Omeprazole Losec

Pantoprazole Protium

Rabeprazole pariet

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Uses

Dyspepsia & GORD

Treatment of gastric & duodenal ulcers

H. pylori eradication

In combination with antibacterials

Bleeding peptic ulcers (IV)

To reduce further bleeding & need forsurgery

Zollinger-Ellison syndrome

Gastrin producing tumour

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Side effects

Inhibition of cytochrome p450 system

Limited. Rarely substantial effect

Rarely rashes & GI disturbances

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Drugs influencing gastricmotility

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Drugs influencing gastricmotility

Reduce motility Antispasmodics Antimotility drugs

Codeine

Loperamide

Increase motility Prokinetics

Laxatives Bowel cleansing solutions

Picolax Klean-prep

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Antispasmodics

Antimuscarinics

Hyoscine butlybromide

Buscopan

Uses

Symptomatic relief of gastro-intestinal orgenito-urinary disorders characterised bysmooth muscle spasm

IBS

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Antispasmodics

Other

Mebeverine

Peppermint oil

Thought to be direct relaxants of intestinalsmooth muscle

May relieve pain & diverticular disease

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Prokinetics

Drugs which stimulategastrointestinal motility

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Which of the following is notconsidered a prokinetic?

1 2 3 4

30%

0%

70%

0%

1. Loperamide

2. Metoclopramide

3. Erythromycin4. Domperidone

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Prokinetics

Dopamine antagonists

Stimulate gastric emptying and small intestinaltransit

Examples Metoclopramide

Domperidone

Uses

Functional dyspepsia GORD

Gastroparesis in diabetes

Aid speed of transit of barium in follow through test

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Prokinetics

Erythromycin

Increases gastric & small bowel activity

Thought to act on motilin receptor

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Laxatives

Bulk-forming Isaghula Husk

Fybogel

Stimulant Docusate sodium

Senna

Glycerol suppositories

Osmotic Lactulose

Movicol

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Anti-emetics

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Vomiting

Afferent pathway

Control centre

Efferent pathway

Vagus nerve Phrenic nerve

Spinal motor neurones supplying abdo muscles

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Vomiting

Chemoreceptor Trigger Zone(Area Postrema, floor of 4th ventricle)

Outside BBB

5HT

3D

2

Dopamine Drugs Gut

Gut

Vestibular apparatus& cerebellar nuclei

Peripheral painpathways

Chemoreceptors &baroreceptors

VomitingCentremedulla

H

1

ACh

5HT

3

Limbic cortex

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Which group IS NOT used as anantiemetic?

1 2 3 4 5

9%4%

87%

0%0%

1. Antihistamine

2. Antimuscarinics

3. Dopaminergicantagonists

4. 5-HT3 receptor

antagonists5. Opioids

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Antiemetics

Dopamine Antagonists

Antihistaminines

Antimuscarinics

5HT3 receptor antagonists

miscellaneous

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Metoclopramide

Phenothiazines

Prochlorperazine (Stemetil)

Chlorpromazine

Thoridazine

Domperidone

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Side effects

Extrapyramidal side effects

Acute dytonias, ocular gyric crises

Commoner in young women

Can trigger neuroleptic malignant syndrome

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Antihistamines

Cyclizine

Also has anticholinergic properties

Side effects

Pain on injection

Tachycardia (IV bolus)

Antimuscarinic effects

Dry mouth, blurred vision

Restlessness, excitation, nervousness

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Antimuscarinics

Hyoscine hydrobromide

Particularly effective in motion sickness

Atropine

Glycopyrrolate

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5HT3 Antagonists

Ondansetron

Dolasetron

Granisetron

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Miscellaneous

Corticosteroids

Dexamethasone

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Vomiting

Chemoreceptor Trigger Zone(Area Postrema, floor of 4th ventricle)

Outside BBB

5HT

3D

2

Dopamine Drugs Gut

Gut

Vestibular apparatus& cerebellar nuclei

Peripheral painpathways

Chemoreceptors &baroreceptors

VomitingCentremedulla

H

1

ACh

5HT

3

Limbic cortex

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Commonest Antiemetics used inHospital

Prochlorperazine (stemetil)

12.5mg IM

3mg Buccal (Buccastem)

Cyclizine

50mg PO/IM/IV

Metoclopramide

10mg PO/IM/IV

Ondansetron

4-8mg PO/IM/IV

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Summary

Discussed Drugs affecting the GItract

Antacids

Drugs inhibiting acid secretion

Antispasmodics

Prokinetics

Laxatives

Discussed antiemetics

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Any questions?

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