Nausea & Vomiting Flashcards
What is nausea?
Feeling of wanting to vomit accompanied by gastric dilation and upper intestinal contractions propelling the intestinal contents by reverse peristalsis into the stomach.
What is retching?
Involuntary contractions of diaphragm and abdominal muscles leading to the cardiac portion of the stomach being forced into the thorax.
What is vomiting?
Rapids inspiration followed by reflex closure of the glottis & elevation of the soft palate to prevent vomit entering lungs and nasal cavity.
- Contractions of diaphragm and abdominal muscle compress the stomach and expel gastric contents into oesophagus and mouth through relaxed lower and upper oesophageal sphincters.
What are the causes of N & V?
therapeutic agents
pregnancy
CNS - motion sickness
alimentary canal - alcohol
metabolic disorders
Describe chemo induced N & V
Acute post treatment - occurs within 24 hours after treatment and may last 120 hours.
- Late response from poorly controlled nausea and vomiting associated with pervious chemo.
- Occurs during following treatment cycle when prophylaxis and/or resue has failed in pervious cycle.
What are the effects of N & V?
- Physical: drugs, toxins, chemo, gag reflex
- Psychological: smell, sight
- Emotional: fear, anxiety, panic
What are the emesis trigger zones?
CNS
Vestibular nuclei
Vomiting center
Chemoreceptor tigger zone (CTZ)
GI system
What ligand is the H1-R attached to and what is its role?
Histamine - neurotransmitter
What ligand is the muscarinic receptor attached to and what is its role?
Acetyl choline - is a major neurotransmitter found in synapses neuromuscular junction.
What ligand is the 5-HT3-R attached to and what is its role?
Serotonin - monoamine neurotransmitter found in the found the CNS and GI tract.
What ligand is the D2 receptor attached to and what is its role?
Dopamine - catecholamine found in the brain which serves as a neurotransmitter for pleasure and pain
What ligand is the Neurokinin-1-R attached to and what is its role?
Substance P - Neurotransmitter involved in inflammation, pain and vomiting
What ligand is the Mu-R attached to and what is its role?
Opioids - neurotransmitter involved in pain/mood - activated by endorphins and opioids.
Describe the chemoreceptor trigger zone (CTZ)
- Outside BBB - accessible to emetogenic stimuli in blood/CBF
- CTZ sense increased blood levels of potentially toxic substances, which initiates nausea and triggers vomit reflex
Describe vestibular nuclei
Sense motion
- motion sickness: car/sea sickness, meniere’s disease
- H1 & M1-R mediate stimulus of vestibular apparatus
- Alcohol can trigger stimulation
Describe the GI and N
GI is a primary source of toxin absorption
- Stimulation of gut chemoreceptors and stretch-R triggers N & V via vagal nerve afferents and afferent fibres associated with SNS.
- Enterochromaffin cells in GIT respond to chemo by releasing serotonin
- Stomach irritation/ distention can trigger
Describe the Cerebal cortex and emesis
- Modulates taste, sight, smell, memory, emotion/ anxiety
- Cortical effects stimulate/suppress N & V
What drugs are associated with high incidence of N & V?
- levodopa
- opioid analgesics
What is the emesis reflex?
- Afferent impulses from the chemoreceptor trigger zone stimulate the vomiting centre - initiating emesis
- The vomiting centre consists of an intertwined neural network in the nucleus tractus soitartius that controls patterns of motor activity.
List the antiemetics used for treatment.
- H1-R antagonists - cinnarizine
- Muscarinic antagonists - hyoscine
- 5-HT3-R antagonists - ondansetron
- D2-R antagonists - metoclopromide HCL, domperidone
- Neurokinin-1- antagonist - aprepitant, fosaprepitant
- Adjuvant antirmetics e.g. dexamethasone, benzodiazepines
Antihistamines
- H1RA that prevents/ treat vomiting
- weakly effective
SE: dizziness, sedation, dry mouth
EX: Cinnarizine - 20 hour half life, Promethazine - pregnancy 7-14 hour half life
Anticholinergics
Muscarinic antagonist
- Does not cross BBB - not sedative
- Poorly absorbed and not very effective
Hyoscine hydro-bromide: motion sickness, nausea, post operative vomiting - short duration
Hyoscine butyl-bromide: relaxes GI SM
Dopamine antagonists
Block CTZ
- Effectively treat severe N/V associated with cancer, radiation, therapy, cytotoxic drugs, opioids, anaesthetic.
- In children severe dystonic (movement) reactions can occur
Examples; prochlorperazine, trifluoperazine
D2 antagonists
Domperidone - Acts at the CTZ and does not cross BBB and less likely to cause central effects than metaclopromide not indicated in under 12s.
Metaclopromide HCL- Acts on gastric SM stimulating gastric emptying. Antagonises 5HT3-R being phased out by more effective 5HT3-As
5HT3-RAs
The antiemetic action is restricted to emesis caused by vagal stimulation.
- Emetic stimuli - motion sickness are poorly controlled
- No effect on GI motility but may slow colonic transit
Explain - ondansetron
NK1-RAs
I.V. substance P causes vomiting
- aprepitant- highly selective NK1-RA that crosses the BBB and occupies brain NK1-R
- fosaprepitant IV is converted to aprepitant in 30mins after infusion
