Antiemetics Flashcards
What is emesis?
Involuntary,forceful expulsion of gastric contents through the mouth
Process of vomiting
- coordinated by vomiting centre in medulla
- take a deep breath
- glottis closes
- abdominal muscles contract
- lower oesophageal sphincter relaxes
- retrograde peristalsis of small bowels
What is vomiting coordinated by?
Vomiting centre in medulla
Neurological pathway of vomiting
- When the vomiting centre in the medulla is stimulated the vomiting reflex occurs
- motion + morning sickness trigger the vestibular centre > CTZ > vomiting centre
- cytotoxic agents trigger the CTZ > vomiting centre
- high cortical centre in brain can be triggered by pain, emotion or repulsive sights/smells > vomiting centre
What receptors are found in the vomiting centre
- NK1
- Muscarinic Ach
- H1 - histamine
- 5HT2 - serotonin receptor
Stimuli for the higher cortical centre of nausea
- Pain
- Repulsive sights + smells
- Emotional factors e.g. stress
Management of nausea due to stimuli from higher cortical centre
Conservative management - avoid stimulus
What portion of the brain is involved in motion sickness?
Vestibular nuclei
Due to inputs from the labyrinth centre
Act on NK1, Muscarinic Ach, H1 + 5HT2
What receptors are in the vestibular nuceli?
Muscarinic Ach
H1
What receptor is in the higher cortical centres?
GABA
Example of Muscarinic antagonists
Hyoscine hydrobromide
What is the mechanism of action of Muscarinic antagonists?
Competitive blockage of Muscarinic acetylcholine receptors - act on vestibular nuclei
What are adverse drug reactions of muscarinic antagonists?
Sedation
Consiptiaon
Dizziness
Dry mouth
Visual problems
Confusion
What are contraindications of muscarinic antagonists?
Elderly patients
Glaucoma
What are important drug drug interactions of Muscarinic antagonists?
Anti-psychotic meds
Examples of H1 antagonists
Cycilzine
Levomepromazine
Prochlorperazine
Promethazine
What are uses of H1 antagonist?
Motion sickness
Promethazine - morning sickness in pregnancy
What is the mechanism of action of H1 antagonists in treatment of vomiting?
- Works centrally
- Acts on vomiting centre + vestibular nuclei
- inhibits histaminergic signals from vestibular system to CTZ in medulla
What are adverse drug reactions of H1 antagonists?
Sedation
Dry mouth
Constipation
Urinary retention
Blurred vision
What are contraindications of H1 antagonists?
Epilepsy
Urinary retention
Children + elderly
Glaucoma
Who is motion sickness more common?
Women
Children
People who have migraines
Prevention of motion sickness
Hydration
Position in vehicle
Distraction
What 2 classes of drugs are used in the treatment of motion sickness?/
Examples of each
- Anti muscarinics e.g. hyoscine hydrobromide
- anti histamines e.g. cyclizine, propchlorperazine
What affects the chemotherapy trigger zone?
- inputs from vestibular centre
- cytotoxic agents e.g. chemotherapy
- vagal afferents
What are the receptors of the chemotherapy trigger zone?
NK1
D2 - dopamine
5HT3 - serotonin
Examples of dopamine D2 receptor antagonist
Metoclopramide
Domperidone
Haloperidol
Prochlorperazine
What class of drug is metoclopramide?
D2 dopamine receptor antagonist
5HT3 antagonist
What are the uses of metoclopramide?
GORD
Anti-emetic for chemotherapy patients
Ileus
What is the mechanism of action of metoclopramide?
- Blocks D2 dopamine receptors +5HT3 serotonin receptors
- acts on visceral afferent in gut > increases Ach in gut > promotes gastric emptying + peristalsis
What are adverse drug reactions of metoclopramide?
Depression
Diarrhoea
Drowsiness
Hypotension
Galatorrhoea
Parkinsonism
Dsytonia
What class of drug is domperidone?
D2 dopamine antagonists
What is a use of domperidone?
Improving lactation in breastfeeding mothers
Anti-emetic
What is the mechanism of action of domperidone?
- blocks D2 receptors
What are adverse drug reactions of domperidone?
- Dry mouth
- sudden cardiac death (long QT + VT)
- galactorrhea
- loss of libido
Examples of D2 receptors antagonists which work as anti-psychotics
Haloperidol
Chloropromazine
Prochlorperazine
What are the uses of haloperidol?
Post op N+V
Anti-psychotic
What is the mechanism of action of haloperidol?
Post synaptic D2 receptors antagonism
What are adverse drug reactions of haloperidol?
Parkinsonism
Arrhythmia
Constipation
Dry mouth
What receptors do the ‘zines’ work on?
Block H1, D2 + muscarinics receptors
Examples of neurokinin-1 receptor antagonists
What is the suffix?
Aprepitant
Fosaprepitant
Netupitant
-pitant
What are the uses of neurokinin-1 receptor antagonists
- Chemotherapy - delayed emesis
- anxiolytics
- antidepressants - boost 5HT3 receptor antagonists effects
What are adverse drug reactions of NK-1 receptor antagonists
Constipation
Headache
Asthenia
What is asthenia?
a condition in which the body lacks strength or has lost strength, either as a whole or in any of its parts
Examples of corticosteroids used as antiemetics
Dexamethasone
Methylprednisolone
What are the uses of dexamethasone + methylprednisolone as antiemetics?
Perioperative N+V
Chemotherapy N+V
Palliation N+V
Where do corticosteroids act on when working as antiemetics?
Chemoreceptor trigger zone
What are adverse effect of corticosteroids?
- Insomnia
- osteoporosis
- weight gain
- increased appetite
- increased blood sugar
- Cushing’s syndrome
Example of canabinoids
Nabilone
Where do canabinoids act when working as antiemetics?
Chemoreceptor trigger zone
What are adverse drug reactions of cannabinoids?
Confusion
Depression
Drowsiness + dizziness
Movement disorders
Psychosis
Tremor
Management of pregnancy induced vomiting
- fluid replacement
- antihistamines e.g. Promethazine/cyclizine
- odanestron
- Prochlorperazine
- thiamine replacement
What class do drugs are effective for delayed nausea in chemotherapy?
Dopamine antagonists e.g. metoclopramide
What class do drug is given to cover acute emetic stimulus of chemotherapy?
5-HT3 antagonists e.g. ondansetron
Examples of 5HT3 antagonists
Ondansetron
Granisetron
Palonestron
What are the uses of 5HT3 antagonists?
Antiemetics in chemotherapy patietns
Post op N+V
What is the mechanism of action of 5-HT3 antagonists?
- blocks serotonin receptors
- Centrally: inhibit chemoreceptor trigger zone
- Peripherally: reduce GI motility + secretions
What are adverse drug reactions of 5-HT3 antagonists?
- Uncommon
- constipation
- headache
- elevated liver enzymes
- long QT syndrome
- Parkinsonism
- dsytonia
Outline serotonin production in the GI system
Enterochromaffin cells in response to parasympathetic stimulation
Action of serotonin on the GI system
- regulates appetite
- increases gut secretions
- smooth muscle contraction increases motility
What drug is first line for bowel obstruction?
What class is it?
Cyclizine
H1 receptor antagonist
What are extra pyramidal side effects?
- hyperprolactinaemia side effects
- dystonia
- Parkinsonianism
What are anticholinergic side effects?
Alice in Wonderland:
- bind as a bat: mydriasis
- mad as a hater: confusion
- red as a beet: flushed skin
- hot as a desert: hyperthermia
- dry as a bone: urinary retention + dry mouth
- tachycardia
- absent bowel sounds
What is the mechanism of action of NK-1 receptor antagonists?
- prevents action of substance P at CTZ and in peripheral nerves
- boosts effect of 5HT3 receptor antagonists
- anxiolytic + antidepressant properties
