anti-emetics Flashcards
State the 5 major classes of anti-emetic drugs.
Mixed receptor antagonists Dopamine (D2) receptor antagonists Muscarinic receptor antagonists Serotonin (5-HT3) receptor antagonists Cannabinoids
What is nausea and vomiting often preceded by?
Sweating, salivation and an increase in heart rate
Describe the process of vomiting.
Stomach, oesophagus and associated sphincters are relaxed
Contraction of upper small intestine, pyloric sphincter and pyloric region of stomach
Contents of upper jejunum, duodenum and pyloric region of stomach move to the body and fundus of the stomach
Lower and upper oesophageal sphincters and oesophagus relaxes
Retching/vomiting may occur
What are the consequences of severe vomiting?
Dehydration
Hypochloraemic metabolic alkalosis
Contributes to reduction in bicarbonate excretion and increase in bicarbonate reabsorption
Increase in sodium reabsorption and increase in potassium excretion (hypokalaemia)
What types of receptors in the stomach transmit signals to the vomiting centre and chemoreceptor trigger zone?
Chemoreceptors and Mechanoreceptors
What is special about the location of the CTZ and vomiting centre?
It is located in a part of the brain that has a very porous blood brain barrier
So the CTZ and vomiting centre act as an early warning system to protect the brain from toxin damage
Give an example of a mixed receptor antagonist.
Promethazine
What is this drug a derivative of?
Phenothiazine (other phenothiazines are used as neuroleptics)
Describe the mode of action of this drug.
It is a competitive antagonist for the following receptors:
• Histaminergic
• Muscarinic
• Dopaminergic
Order of potency of antagonist activity: H > M > D
What are the uses of promethazine?
Motion sickness Disorders of the labyrinth Hyperemesis gravidarium Pre and post-operatively Relief of allergic symptoms, anaphylactic emergency, night sedation; insomnia
Describe the pharmacokinetics of promethazine
Administer orally
Onset of action – 1-2 hours
Peak action – 4 hours
Duration of action – 24 hours
What are the unwanted effects of promethazine?
Dizziness Tinnitus Fatigue Sedation Convulsions
Give 2 examples of dopamine receptor antagonists.
Metoclopramide
Domperidone
Describe the order of agonist potency of these drugs.
D > H > M
What effect do these drugs have on the GI tract?
They have PROKINETIC effects on the GI tract:
• Increase smooth muscle motility
• Accelerate gastric emptying
• Accelerate the transit time of intestinal contents
Why are these drugs poor at treating motion sickness?
The vestibular system has connections to the CTZ and it has direct connections to the vomiting centre
The dopamine antagonists block dopamine receptors in the CTZ but they are not blocking the rest of the signals that are going directly from the vestibular system to the vomiting centre
State some uses of metoclopramide and domperidone.
Uraemia (severe renal failure)
Radiation sickness
GI disorders
Cancer chemotherapy
(Metoclopramide crosses the BBB)
Why must care be given over the bioavailability of co-administered drugs when patients are on dopamine receptor antagonists?
These drugs have prokinetic effects on the GI tract hence they accelerate the transit through the GI tract – this may mean that some drugs are not sufficiently absorbed in the GI tract e.g. digoxin
What are some unwanted effects of metoclopramide and domperidone?
CNS side effects only with metoclopramide:
• Drowsiness
• Dizziness
• Anxiety
• Extrapyramidal reactions (Parkinsonian like syndrome – children more susceptible)
Endocrine side effects:
• Hyperprolactinaemia
• Galactorrhoea
• Disorders of menstruation
Give an example of an anti-emetic muscarinic receptor antagonist.
Hyoscine - Used to treat motion sickness
sometimes used pre-operatively
What is the mode of action of muscarinic receptor antagonists?
Act centrally on the CTZ, vestibular nuclei and vomiting centre to block the activation of the vomiting centre
Describe the pharmacokinetics of hyoscine.
Administered orally (peak effect 1-2 hours) Could also be administered via a transdermal skin patch
What are the unwanted effects of hyoscine?
Drowsiness Dry mouth Cycloplegia Mydriasis Constipation
Give an example of a serotonin receptor antagonist.
Ondansetron
What is the mode of action of serotonin receptor antagonists?
Act to block transmission in visceral afferents and CTZ
What is the main use of serotonin receptor antagonists as an anti-emetic?
MAIN USE: preventing anti-cancer drug induced vomiting (especially cisplatin)
Also used for radiotherapy induced sickness and post-operative nausea and vomiting
