10 - Antiemetics Flashcards
What are the physiological steps of vomiting?
What are the inputs on the chemoreceptor trigger zone that can activate it and therefore cause vomiting?
CTZ is found on the floor of the fourth ventricle on the blood side of the BBB so can interact with toxins and things in the blood
Part of medulla
How can we stop nausea and vomiting?
Avoid the triggers or use drugs to target different triggers
What are the two classes of drug that act on the vestibular nuclei as antiemetics?
- Muscarinic receptor antagonists
- H1 receptor antagonists
How do muscarinic receptor antagonists act as anti-emetics and what are some examples of this class of drug?
Hyoscine Hydrobromide (oral or patch)
- Competitive blockage of muscarinic receptors in the vestibular nuclei and CTZ
- Antispasmodic
- Good for people who cannot take tablets, motion sickness and bowel obstruction
What are the side effects of hyoscine hydrobromide?
- Classic anticholinergic side effects
- Can exploit side effects, e.g long flight motion sickness and sedation for sleep
How do H1 receptor antagonists work as an antiemetic and what are some examples of this type of drug?
- Act centrally on the vestibular nuclei and inhibit histaminergic signals from vestibular system to the CTZ in medulla
- Good for motion sickness on long journeys
- Promethazine used for morning sickness
What are the side effects of the class of antiemetic drugs containing cyclizine?
H1 receptor antagonist!
- Cyclizine is the most common antiemetic but cannot be used in old women and children as they are affected most by excitation side effects
What are some classes of antiemetics that work by blocking visceral aferents in the gut?
- 5HT3 receptor antagonists
- D2 receptor antagonists
What is the normal function of serotonin in the gut?
- Produced by enterochromaffin cells in response to parasympathetic stimulation
- Regulates appetite, causes smooth muscle contraction so increased motility and increased gut secretions
How do 5HT3 receptor antagonists work as antiemetics and what are some examples of this type of drug?
Ondansetron
- Acts on visceral afferents in the gut so peripherally reduces GI motility and GI secretions
- Centrally inhibits the CTZ
- OFTEN FIRST LINE TREATMENT
What are some of the side effects of Ondansetrons and other serotonin receptor antagonists?
How do D2 receptor antagonists work as antiemetics (by targeting visceral afferents of the gut) and what are some examples of this type of drug?
Domperidone and Metoclopramide (also 5HT3 antagonist)
- Increases Ach at muscarinic receptors in the gut
- Promotes gastric emptying by increasing tone of LOS and decreasing tone of pylorus so it opens. Also increased tone of gastric contractions
- Increases peristalsis
Apart from emesis, what are metoclopramide and domperidone used for?
Metoclopramide: GORD and ileus
Domperidone: improving lactation in breastfeeding mothers
What are some side effects of antiemetics from the D2 receptor antagonist class?
Metoclopramide: galactorrhoea due to prolactin release, extra-pyramidal effects (e.g dystonia and parkinsonianism)
Domperidone: sudden cardiac death (long QT and VT) so not used very often, galactorrhea
What are some classes of drugs that act directly on the CTZ to prevent/stop vomiting?
What are some D2 receptor antagonists that act on the CTZ as antiemetics, how do they work and what vomiting situations are they used in?
ANTIPSYCHOTICS: chlorpromazine and haloperidol
What are some side effects of antipsychotics being used as antiemetics?
How do corticosteroids act as antiemetics and what are the side effects of these?
Dexamethasone and Methylprednisolone
Not used long term so don’t get side effects like skin changes and Cushing’s
How do cannabinoids act as antiemetics and what are the side effects of these?
Used for chemotherapy last line when everything else has failed!
How do neurokinin 1 receptor antagonists act as antiemetic, what else can they be used for and what are some examples of this class of drug?
Aprepitant
- Prevent the excitatory action of substance P at CTZ and in peripheral nerves so can be used as pain killers
- Good anxiolytic and antidepressant properties
- Boost effects of serotonin agonists
- Good for chemotherapy delayed emesis
What are some side effects of neurokinin 1 receptor antagonists?
- Headache
- Diarrhoea/Constipation
- Stevens-Johnson syndrome
What drugs are used for motion sickness?
- Trial and error to see what is best and what side effects the patient prefers
- Take before journey
What are some gut problems that can cause nausea and vomiting, and how should we treat this acutely before treating the underlying cause?
- Infective gastroenteritis is supportive treatment as toxin needs to get out
- Consider a nasogastric tube to decompress
- Give antiemetic
What are prokinetic drugs?
- Drugs that increase gut motility, e.g domperidone and metoclopramide (D2 antagonists)
- Useful for ileus and GORD
- Do not use for obstructions as risk of perforation
What are the first line anti-emetics?
If one not working don’t choose another drug in the same class
What is hyperemesis gravidarum and how do we treat it?
- Rapid rise in b-hCG stimulates CTZ so severe N+V
- Higher risk with multiple pregnancies
- Can cause dehydration, weight loss, electrolyte imbalance
- May require admission to replace fluids
What antiemetics are used for nausea caused by chemotherapy?
Patients are risk stratified depending on their chemo drug and dose and then this decides their antiemetic
What are some risk factors that increase your chance of post operative nausea and vomiting?
What antiemetics are used for postoperative nausea?
- Can alter the risk factors, e.g use a different anaesthesia
- If patient is motion sick use drugs that act on vestibular nuclei e.g H1 receptor antagonists
- If patient is having gut surgery use drugs that act on visceral afferents from the gut e.g 5HT3 antagonists and D2 receptor anatagonists
What drugs can we use to treat diarrhoea?
- Antimotility drugs (opioid agonists)
- Loperamide (u) and Codeine Phosphate (u and d)
- Loperamide is 1st line as gut specific
What are the side effects of using u opioid agonists to treat diarrhoea?
- Paralytic ileus
- Nausea and Vomiting
- Sedation
- Addiction (codeine)
What diet can you recommend to someone with long term loose stools, e.g IBS, short bowel, drug side effects?
CONSTIPATING DIET
What lifetsyle changes can you recommend to someone with constipation?
- Drink more water
- Increase fibre intake e.g fruit, veg, nuts
- Regular exercise
- Toilet routine and positioning
What are some different drugs used for constipation?
What are some examples of osmotic laxatives and what is their mechanism of action?
- Lactulose: draws fluid in from outside the gut
- Macrogol (really good - up to 12 sachets a day): retain the fluid they came with
- MOVICOL FIRST LINE: both increasing amount of water in large bowel
What are some examples of stimulant laxatives and how do they work?
- Bisacodyl, Docusate Sodium, Glycerol Suppository, Senna
- Enhance gut motility and increase water and electrolyte transfer into the lower gut
- Given orally or rectally when osmotics haven’t worked
What are some examples of bulk-forming laxatives and how do they work?
- Ispaghula Husk and Methylcellulose
- Stimulation through increase faecal bulk, hydrophillic action causing gut lumen water retention
How do stool softeners work to relieve constipation and what are some examples?
Like washing up liquid changing the surface tension!!!
