Antacids, anti-emetics & GI motility drugs

Dr Ally Duncan
Education Fellow & SpR in Anaesthetics
Manchester Royal Infirmary

Applied Sciences Lecture Course

April 2012

Aims and objectives

Categorise drugs acting on the gut
Discuss relevant pharmacological aspects Discuss common clinical uses

Categorise antiemetics
Discuss relevant pharmacological aspects Discuss common clinical uses

Drugs acting on the gut

Antacids Drugs influencing gastric secretion Drugs influencing gastric motility

Antacids
Drug action based on physical properties Weak bases that neutralise gastric acid Traditionally compounds containing aluminium or magnesium Liquid more effective than tablet

Antacids
Clinical uses: symptomatic relief of dyspepsia some promotion of ulcer healing but less effective than drugs that inhibit acid secretion

Antacids
Magnesium containing
Laxative

Aluminium containing
Constipating

Interactions
May affect absorption of other drugs. Avoid giving at same time

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

Drugs influencing gastric secretion

Mechanism of gastric acid secretion

H+
Apical Cell surface Proton pump

ATPase K+ Protein Kinases Parietal Cell Ca2

+

ATP
Gs H2 receptor Ac

Cyclic AMP
Gi

Ca2
+

Muscarin ic receptor

Histamin

PGE2

Gastrin Acetylcholine

Drugs influencing gastric secretion

H2 receptor antagonists

Proton pump inhibitors

H2 receptor antagonists
Reduce basal and food stimulated gastric acid by 90% Heal gastric and duodenal ulcers Provide symptomatic relief in dyspepsia

Which of the following is not an H2 antagonist?

1. 2. 3. 4. 5. Ranitidine Zantac Gavilast Losec Cimetidine
50%

33%

17%

0%
1 2 3 4

0%
5

H2 receptor antagonists
Rantidine
Zantac, gavilast Oral / IV preparations Available over the counter Side effects (rare)
Cardiac arrhythmias during rapid IV administration Thrombocytopenia, leucopenia, liver dysfunction Anaphylaxis

H2 receptor antagonists
Cimetidine
Hepatic enzyme inhibitor (AODEVICES)
Inhibits cytochrome P450 system Can reduce metabolism of other drugs causing a rise in serum levels e.g.warfarin

Enzyme INHIBITORS
A Allopurinol O Omeprazole D Disulfiram E Erythromycin V Valproate I Isoniazid C Cimetidine & ciprofloxacin E Ethanol (acute intoxication) S Sulphonamides

Enzyme INDUCERS
P Phenytoin C Carbamazepine B Barbiturates R Rifampicin A Alcohol S Sulphonylureas

Proton pump inhibitors

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

Examples
Esomeprazole
Nexium

Lanzoprazole
Zoton

Omeprazole
Losec

Pantoprazole
Protium

Rabeprazole
pariet

Proton pump inhibitors

Uses
Dyspepsia & GORD Treatment of gastric & duodenal ulcers H. pylori eradication
In combination with antibacterials

Bleeding peptic ulcers (IV)

To reduce further bleeding & need for surgery

Zollinger-Ellison syndrome
Gastrin producing tumour

Proton pump inhibitors

Side effects
Inhibition of cytochrome p450 system
Limited.
Rarely substantial effect

Rarely rashes & GI disturbances

Drugs influencing gastric motility

Drugs influencing gastric motility

Reduce motility
Antispasmodics Antimotility drugs
Codeine Loperamide

Increase motility
Prokinetics Laxatives Bowel cleansing solutions
Picolax Klean-prep

Antispasmodics
Antimuscarinics
Hyoscine butlybromide
Buscopan

Uses
Symptomatic relief of gastro-intestinal or genito-urinary disorders characterised by smooth muscle spasm
IBS

Antispasmodics
Other
Mebeverine Peppermint oil
Thought to be direct relaxants of intestinal smooth muscle May relieve pain & diverticular disease

Prokinetics
Drugs which stimulate gastrointestinal motility

Which of the following is not considered a prokinetic?

1. 2. 3. 4. Loperamide Metoclopramide Erythromycin Domperidone
70%

30%

0%
1 2 3

0%
4

Prokinetics
Dopamine antagonists
Stimulate gastric emptying and small intestinal transit Examples
Metoclopramide Domperidone

Uses
Functional dyspepsia GORD Gastroparesis in diabetes Aid speed of transit of barium in follow through test

Prokinetics
Erythromycin
Increases gastric & small bowel activity Thought to act on motilin receptor

Laxatives
Bulk-forming
Isaghula Husk
Fybogel

Stimulant
Docusate sodium Senna Glycerol suppositories

Osmotic
Lactulose Movicol

Anti-emetics

Vomiting
Afferent pathway Control centre Efferent pathway
Vagus nerve Phrenic nerve Spinal motor neurones supplying abdo muscles

Dopamine

Drugs

Gut

D
2

5HT
3

Chemoreceptor Trigger Zone

(Area Postrema, floor of 4th ventricle) Outside BBB

Peripheral pain pathways Limbic cortex Chemoreceptors & baroreceptors

Vomiting Centre
medulla
3

AC h 5HT

Vestibular apparatus & cerebellar nuclei

Gut

Vomiting

Which group IS NOT used as an antiemetic?

1. Antihistamine 2. Antimuscarinics 3. Dopaminergic antagonists 4. 5-HT3 receptor antagonists 5. Opioids
87%

9%

4%

0%
3

0%
4 5

Antiemetics
Dopamine Antagonists Antihistaminines Antimuscarinics 5HT3 receptor antagonists miscellaneous

Dopamine antagonists
Metoclopramide Phenothiazines
Prochlorperazine (Stemetil) Chlorpromazine Thoridazine

Domperidone

Dopamine antagonists
Side effects
Extrapyramidal side effects
Acute dytonias, ocular gyric crises
Commoner in young women

Can trigger neuroleptic malignant syndrome

Antihistamines
Cyclizine
Also has anticholinergic properties

Side effects
Pain on injection Tachycardia (IV bolus) Antimuscarinic effects
Dry mouth, blurred vision

Restlessness, excitation, nervousness

Antimuscarinics
Hyoscine hydrobromide
Particularly effective in motion sickness

Atropine Glycopyrrolate

5HT3 Antagonists
Ondansetron Dolasetron Granisetron

Miscellaneous
Corticosteroids
Dexamethasone

Dopamine

Drugs

Gut

D
2

5HT
3

Chemoreceptor Trigger Zone

(Area Postrema, floor of 4th ventricle) Outside BBB

Peripheral pain pathways Limbic cortex Chemoreceptors & baroreceptors

Vomiting Centre
medulla
3

AC h 5HT

Vestibular apparatus & cerebellar nuclei

Gut

Vomiting

Commonest Antiemetics used in Hospital

Prochlorperazine (stemetil)
12.5mg IM 3mg Buccal (Buccastem)

Cyclizine
50mg PO/IM/IV

Metoclopramide
10mg PO/IM/IV

Ondansetron
4-8mg PO/IM/IV

Summary
Discussed Drugs affecting the GI tract
Antacids Drugs inhibiting acid secretion Antispasmodics Prokinetics Laxatives

Discussed antiemetics

Any questions?