Anti-Emetics

Question 1

What anti-emetics are used for cancer patients?

Answer 1

• Histamine H1-Receptor Antagonists - Cyclizine, Cinnarizine, Promethazine.
• Histamine H3-Receptor Antagonists - Betahistine, Hydrochloride
• 5-HT3 Receptor Antagonists - Ondansetron, Granisetron, Palonosetron
• Muscarinic (mACh) Receptor Antagonists - Hyoscine, Scopolamine.
• D2-Receptor Antagonists - Phenothiazines, Prochloropromazine, Perphenazine
• Cannabinoids - Nabilone
• Dexamethasone
• Corticosteroids
• Neurokinin-1 Antagonist - Aprepitant

Question 2

What is the physiology of emesis?

Answer 2

• Controlled by CNS (medulla)
• There are 3 major inputs to the dorsal vagal complex: 1) the chemoreceptor trigger zone 2) The vagal pathway (GIT, pharynx, senses) 3) the vestibular pathway (in ear).
• Need to block the neurotransmitters (and the receptors they come from) involved in the triggering of emesis response:
• Serotonin - 5HT3 Receptor
• ACh - Muscarinic Receptor
• Dopamine - D2 Receptor
• Substance ‘P’ - NK1 Receptor
• Histamine - H1 Receptor
• Enkephalin - Delta-Receptor

Question 3

How do Histamine-1 Receptor Antagonists Work?

Answer 3

• Cyclizine - motion sickness
• Cinnarizine - motion sickness, vestibular disorders (vertigo)
• Promethazine - morning sickness
• Side Effects - Drowsiness and sedation.

Question 4

How do Histamine-3 Receptor Antagonists work?

Answer 4

• Betahistine, Hydrochloride
• Anti-vertigo drugs
• Activates H-Receptors on blood vessels in inner ear - local vasodilation, increased permeability, reverses underlying problem of endolympathic hydrops.
• Side Effects - GI disturbance, headache, rashes, pruritus,

Question 5

How do Muscarinic Receptor Antagonists work?

Answer 5

• Hyoscine, Scopolaimine
• Non-selective antagonists (ACh)
• Motion sickness - oral treatment
• Side effects - dry mouth, blurred vision, less sedative actions than antihistamines.

Question 6

How do Dopamine Receptor Antagonist work?

Answer 6

• Have a strong representation in the chemoreceptor trigger zone.
• Powerful anti-emetic action and will antagonise muscarinic and histamine receptors too.
• Phenothiazines - severe morning sickness (oral, IV, suppository)
• Prochlorpromazine oral, IM
• Perphenazine oral
• Side Effects - sedative, hypotension, dystonia, dyskinesia.
• Metaclopramide - penetrates BBB, acts on GIT (increased motility)
• Side effects - movement disorders (children), fatigue, motor restlessness, spasmodic torticollis, occulogyric crisis, mestruation disorders.
• Domperidone - does not penetrate BBB - decreases central effectiveness. Fewer side effects - oral, IV, suppository. Used for migraine and cytotoxic therapy.

Question 7

How do Serotonin Receptor Antagonists work?

Answer 7

• Ondansetron - Drug of choice for cheo-induced N+V and post-op N+V.
• Vagal pathway, chemoreceptor zone and vomiting centre.
• Oral, suppositories, IV and IM.
• Side Effects - GI disturbances, headache.
• Others - Granisetron, Palonosetron, Tropisetron.

Question 8

How do Neurokinin-1 Antagonists work?

Answer 8

• Active in late phase emesis with cytotoxic drugs
• Aprepitant - substance-P antagonist for chemo-induced N+V and post-op N+V.
• Side effects - fatigue, listlessness, constipation/diarrhoea, anorexia.
• Others - Fosaprepitant** (pro drug) and **Casopitant, Maropitant(Motion sickness).

Question 9

How do Cannabinoids work?

Answer 9

• Mimics chemical component of cannabis (HTC)
• For the treatment of chemo-induced N+V.
• Act via opioid receptors in chemo-trigger zone.
• Agonise CB receptors (in brainstem).
• Nabilone, Marinol (oral)
• Side effects - drowsiness, dizziness, dry mouth, mood changes, postural hypotension.

Question 10

How do corticosteroids work?

Answer 10

• Dexamethasone
• Vomiting caused by cytotoxics
• Mechanisms not fully understood.
• Used in combnation with D2 or 5HT3 antagonists.

Question 11

Why would emetics be used to induce vomitting?

Answer 11

• Poisonous substance ingested, drug overdose, alcohol intoxication.
• NOT FOR - ingestion of corrosive substances, CNS simulant (morphine overdose), kerosene poisoning.
• Syrup of Ipecac - 2 alkaloids (emetine and cepheline) (oral-works in 15 mins) irritates gastic mucosa and activates chemotrigger zone directly.
• Apomorphine - directly stimulates chemotrigger zone and vomiting centre.
• IM or SC -acts within 5-10 mins.
• Activated Charcoals - Most commonly used to absorb toxins.