ANTIEMETICS

ANTIEMETICS

Regulation of vomitingRegulation of vomiting

• medulla oblongatamedulla oblongata

– the vomiting centre– chemoreceptor trigger zone (area postrema)

• emetogenic substances, apomorphine, morphine, chemotherapy, motion sickness

– Ach, histamine, 5-HT, Dop

Clinical use of anti-emetic drugs:H1-receptor antagonists: cylizine - motion sickness

cinnarizine - motion sickness, vestibular disorders (e.g. Meniére´s disease)

promethazine - severe morning sickness of pregnancy (only if absolutely essential)

D2-receptor antagonists:phenothiazines (e.g. thiethylperazine) - vomiting causedby uraemia, radiation, viral gastroenteritis (drugs of choice);severe morning sickness of pregnancy (if absolutely essential)

metoclopramide - vomiting caused by uraemia, radiation, gastrointestinal disorders, cytotoxic drugs

Muscarinic-receptor antagonists:hyoscine - motion sickness (drug of choice)

5-HT3receptor antagonists:ondansetron - vomiting caused by cytotoxic anticancerdrugs (drug of choice), postoperative vomiting; radiation-induced vomiting

Cannabinoids:nabilone - for vomiting caused by cytotoxic anticancer drugs

laxatives

antidiarhoeal drugs

LAXATIVESLAXATIVES• bulk laxativesbulk laxatives

– =increasing the volume, not absorbed– methylcelulose, agar, psyllium seeds– no serious unwanted effects

• osmotic l.osmotic l.– not absorbed, osmosis - distension of colon– magnesium sulphate, magnesium hydroxide, lactulose– ADR: flatulence, cramps, diarhoea, electrolyte dist.,

tolerance

• stimulant l.stimulant l.– stimulation of enteric nerves - secretion, motility– bisacodyl, senna preparations– ! only for short-term use - nerve reduction

antidiarrhoeal agents Iantidiarrhoeal agents I

• secretion, motility, decreased absorption• ! fluid and electrolyte balance - rehydration

• antiinfective agents…gastroenteritis– sever cases of Campylobacter - erythromycin,

ciprofloxacin

• antidiarrhoeal agents

antidiarrhoeal agents IIantidiarrhoeal agents II• antimotility agentsantimotility agents

– opiates, morphine - constipation, sphincter contraction– codeine, diphenoxylate, loperamide– ! drowsiness, dizziness, paralytic ileus

• adsorbentsadsorbents– adsorbing microorganisms and toxins– kaolin, pectin, charcoal

motility stimulantsmotility stimulants• = prokinetic drug

• domperidone (Motilium) - D2 antagonist, also antiemetic oesophageal sphincter pressure…GERD

– ! hyperprolactinemia

• metoclopramide (Paspertin) - DA antagonist and Ach agonist– increases gastric emptying - GERD

– ! extrapyramidal side effects

• cisapride (Prepulsid) - 5-HT4 rec. agonist….Ach release

gut motility, no antiemetic action

– withdrawn due to QT prolongation