ANTIEMITICS

& ANTACID
Presented by Dr.Khaleel Nassar.
Supervised by Dr.Asma’ Zyoud.
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 PHYSIOLOGY

 The vomiting centre (VC) It has no discrete anatomical site but may be considered as a collection of effector
neurones situated in the medulla.
 The treatment of nausea and vomiting is aimed at reducing the afferent supply to the VC.
 Causes that induce nausea & vomiting includes:
1. Drugs.
2. Motion sickness.
3. Fear.
4. Pregnancy.
5. Vestibular disease and migraine.
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 Types of antiemitics
Receptor antagonists: agents:

Ach (acetylcholine) Anticholinergics.

D (dopamine) Dopamine antagonists.
H1 (histamine) Antihistamines.
5-HT3 (serotonin) 5-HT3 antagonists.
NK-1 (neurokinin) Miscellaneous.

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 A. ANTICHOLINERGICS

1) Hyoscine (Scopolamine): (Central & peripheral Antimuscarinic effects).

 Used as a sedative and amnesic agent.
 Given with an intramuscular opioid as premedication, and in this setting has been shown to reduce PONV.
 It may precipitate a central anticholinergic syndrome?!! which is characterized by: excitement, ataxia,
hallucinations, behavioural abnormalities and drowsiness.

2) Atropine !!
 Used to treat bradycardia, It is also used to antagonize the muscarinic side effects of anticholinesterases, It is not
used to treat PONV because of its cardiovascular effects.

3) Glycopyrrolate !! (ideal reverse)

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 B. DOPAMINE ANTAGONISTS

1) Phenothiazines: one of the main group of anti-psychotic drugs (neuroleptics) and have a limited
role in the treatment of vomiting.

2) Chlorpromazine:
 MOA antagonizes the following receptor types: dopaminergic (D2), muscarinic, noradrenergic (α1
and α2), histaminergic (H1) and serotinergic (5-HT).
 Used in schizophrenia, used to control vomiting or pain in terminal care. It has also been shown to
be effective in preventing PONV.
 Effects: Central nervous system – extrapyramidal effects are due to central dopamine antagonism.
Cardiovascular – it antagonizes α-adrenoceptors resulting in peripheral vasodilation, hypotension
and increased heat loss.
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 Miscellaneous Cholestatic jaundice, agranulocytosis, leucopenia, leucocytosis and haemolytic
anaemia are all recognized.
3) Prochloroperazine:
 Uses Prochloroperazine is effective in the prevention and treatment of PONV and vertigo, as well as in
schizophrenia and other psychoses.
 Effects: Central nervous system – extrapyramidal effects are common & it produces only mild sedation
and may prolong the recovery time.
 Side effects: cause cholestatic jaundice, haematological abnormalities, skin sensitization,
hyperprolactinaemia.

4) Butyrophenones:
I. Droperidol: shown to be effective in the prevention and treatment of PONV,
MOA Droperidol antagonizes central dopamine (D2) receptors at the CTZ, Dose 0.625 to 1.25 mg, one of
the main side effect QT prolongation.

II. Domperidone: D2 antagonist it does not cross the blood–brain barrier.

 Used in children to prevent & limits the nausea and vomiting following chemotherapy or 01/05/2021
radiotherapy. 7
 Side effect is increase the prolactin levels and may cause galactorrhoea and gynaecomastia. The
5) Benzamides:
I. Metoclopramide: (0.25 mg/kg) upto (1-2 mg/kg).
 Uses as a prokinetic (enhance rapid gastric emptying) and an antiemetic.
 Mechanism of action Its prokinetic actions are mediated by antagonism of peripheral dopaminergic (D2)
receptors and selective stimulation of gastric muscarinic receptors (which can be blocked by atropine).
 Acts peripherally as a cholinomimetics & centrally as a dopamine receptor antagonist in the CTZ, and
cause increase the intestinal smooth muscle tone & increase the lower esophageal sphincter tone & it
dose not affect the secretions of gastric acid or the PH of gastric fluids.
 Effects: Central nervous system – it crosses the blood brain barrier and may precipitate extrapyramidal
effects up to 72 hours after administration, Cardiovascular – hypotension, tachy- and bradycardia, the
dose should be adjusted in renal dysfunction patients.
 Interactions with the antimuscarenics (atropine & glycopyrrolate).

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 C. ANTIHISTAMINES
1) Cyclizine:
 Used as an antiemetic in motion sickness, radiotherapy, PONV and emesis induced by opioids, It is also
used to control the symptoms of Meni´ere’s disease.
 Mechanism of action it is a histamine (H1) antagonist, but also has anticholinergic properties that may
contribute significantly to its antiemetic actions.
 Effects:

a. Gut–it increases lower oesophageal sphincter tone.

b. Anticholinergic -- these are mild although it may cause an increase in heart rate following
intravenous injection.
2) Promethazine:
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 Used in combination with pethidine for intramuscular premedication.


 D. 5-HT3 ANTAGONISTS
1) Ondansetron (serotonin):
 Act by antagonize 5-HT3 both peripherally and centrally & Its half-life is about 3 hours.
 Uses for the treatment of Nausea and vomiting associated with chemo- or radiotherapy and in the
peri-operative period, due to The activation of 5-HT3 receptors peripherally and centrally, then
activate and stimulate the vagal afferent neurones that connect to the VC.
 It is licensed for children above 2 years of age.
 Side effects of ondansetron limited to headache, flushing, constipation and bradycardia following
rapid intravenous administration.
 Prolongation of QT interval !!!
 The dose should be adjusted in hepatic impairment patients.
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2) Granisetron:
 E. MISCELLANEOUS

1) Steroids: the dose of 2.5–10 mg used to prevent post-operative nausea and vomiting, but Its mode of action in this area
is unknown !!

2) Acupuncture: The acupuncture point lies between the tendons of flexor carpi radialis and palmaris longus about 4 cm
from the distal wrist skin crease, It should be performed on the awake patient.

3) Canabinoids: Acts at the VC and has been used as an antiemetic.

4) Benzodiazepines:
 Lorazepam is used as an antiemetic during chemotherapy. It has amnesic and sedative properties. Its mode of action as an
antiemetic is unknown, but it may prevent the anticipatory nausea that is seen with repeated doses of chemotherapy.

5) Neurokinin-1 Receptor Antagonist: NK-1 antagonists centrally on (CTZ) and peripherally on (vagal afferents in GI tract).

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 ANTACIDS

 Antacids neutralize gastric acidity.

 Particulate vs nonparticulate !!! (particulate – most potent, more dangerous)
 Aluminium and magnesium containing antacids low water solubility so they are long-acting providing that they remain
in the stomach.
 Aluminium containing; produce constipation.
 magnesium containing; produce diarrhoea.
 Sodium bicarbonate and sodium citrate These antacids are water soluble and their onset of action is faster than the
aluminium and magnesium antacids.
 Sodium citrate is often used with ranitidine to reduce gastric acidity before caesarean section & LGS, it should be given
in less than 10 minutes before the start of surgery, Why?!!

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 A. DRUGS INFLUENCING GASTRIC
SECRETION
• Physiology: Gastrin and ACh stimulate parietal cells (via gastrin and muscarinic receptors) to secrete H+ into the
gastric lumen.
1) H2 receptor antagonists:
 Cimetidine
 Ranitidine & Famotidine

2) Proton pump inhibitors:

 Omeprazole
3) Antimuscarinics:
 Pirenzipine
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 H2 RECEPTOR ANTAGONISTS
A. CIMETIDINE

 Cimetidine is the only H2 receptor antagonist with an imidazole structure.

 Uses It is used in peptic ulcer disease, reflux oesophagitis, Zollinger–Ellison syndrome and pre-operatively in
those at risk of aspiration.
 Mechanism of action Cimetidine is a competitive and specific antagonist of H2 receptors at parietal cells.

 Effects:

a. Gut – the gastric pH is raised and the volume of secretions reduced, while there is no change in gastric
emptying time or lower oesophageal sphincter tone.

b. Cardiovascular – bradycardia and hypotension follow rapid intravenous administration.

c. Central nervous system – confusion, hallucinations and seizures are usually only seen when impaired renal
function leads to high plasma level.
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d. Metabolic – it inhibits hepatic cytochrome P450 and will slow the metabolism of the following drugs:
lidocaine, propranolol, diazepam, phenytoin, warfarin and aminophylline.
 B. RANITIDINE & FAMOTIDINE

 Ranitidine is more potent than cimetidine.

 Uses: Ranitidine has similar uses to cimetidine, BUT it does not inhibit hepatic cytochrome P450, so it is often used in
preference to cimetidine. It is also used widely in labour with apparently no effects on the fetus or progress of labour.
 Mechanism of action competitive and specific antagonist of H2 receptors at parietal cells.
 Effects:

a. Gut – similar to that of cimetidine.

b. Cardiovascular – it may produce cardiac arrhythmias during rapid intravenous administration.
c. Miscellaneous – rarely it may cause thrombocytopenia & leucopenia.

 Famotidine are newer H2 antagonists with increased potency.

 Like ranitidine they do not inhibit hepatic cytochrome P450.
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 PROTON PUMP INHIBITORS
A. OMEPRAZOLE

 It is a prodrug, becoming active within the parietal cell, it is a granules that absorped in the small intestine.
 Mechanism of action: A proton pump (K+/H+ ATPase) in the membrane of the parietal cell mediates the
final common pathway of gastric acid secretion. Omeprazole reversibly blocks the proton pump and so
achieves complete achlorhydria.
 Effects: Gut – the acidity and volume of gastric secretions is reduced, while no change is seen in lower
oesophageal sphincter tone or gastric emptying.
 Close monitoring is recommended with patients use of warfarin and phenytoin, because it inhibate the
hepatic cytochrome P450, so their effects are potentiated & The effects of diazepam may be increased via
a similar mechanism.

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 ANTIMUSCARINICS:
A. PIRENZIPINE

 It is a selective antimuscarinic that was used in the treatment of gastric ulcers.

 It is relatively selective on the gut and decreases acid secretion but less effectively than H2
blockers and the proton pump inhibitors.
 Its use has been discontinued !!

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 B. DRUGS INFLUENCING GASTRIC
MOTILITY
1) Metoclopramide (Antivote):
2) Domperidone (Motilium):
 It does not cross the blood–brain barrier. Its use in children to prevents & treats nausea and
vomiting following chemotherapy or radiotherapy.
 It increases prolactin levels so it may cause galactorrhoea and gynaecomastia. The intravenous
preparation was withdrawn due to serious arrhythmias during administration of large doses.
 It is only available as tablets or suppositories.

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 C. MUCOSAL PROTECTORS

1) Sucralfate:
 Sucralfate acts by forming a barrier over the gut lumen. It protects ulcerated regions specifically.
 It does not alter gastric pH, motility or lower oesophageal sphincter tone, although it has been reported
to have bacteriostatic effects.
 Effects: It has no effect on the central nervous or cardiorespiratory systems.

a. Gut – minor gastric disturbances. Enhanced aluminium absorption. It may reduce the absorption of
certain drugs (ciprofloxacin, warfarin, phenytoin and H2 antagonists) by direct binding.

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 D. PROSTAGLANDIN ANALOGUES

1) Misoprostil (Cytotec):
 Misoprostil is a synthetic analogue of prostaglandin E1.
 Uses It is used for the prevention and treatment of non-steroidal anti-inflammatory induced ulcers.
 Mechanism of action It inhibits gastric acid secretion and increases mucous secretion thereby protecting the gastric mucosa.
 Effects

a. Endocrine – It increases uterine tone and may precipitate miscarriage (abortion). Menorrhagia and vaginal bleeding have
been reported.
b. Gut – Severe diarrhoea and other intestinal upset.
c. Cardiovascular – At normal doses it is unlikely to produce hypotension.

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 REFERENCES

 Pharmacology for Anaesthesia Intensive Care/3RDedition/TOM-E-PECK - S. A. HILL.

 Morgan & Mikhails Clinical Anesthesiology/6thedition 2018.
 Armando Hasudungan/ Pharmacology – Antiemetics.

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‫ش ْك َراً‬
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