Emesis (Vomiting) Flashcards
Role of GI Tract
- digestion and absorption of food
- important endocrine organ
- gastric acid secretion
- gut motility and defecation
- formation and excretion of bile
- vomiting and nausea
True or False?
GI Tract contains its own neuronal network?
True.
The GI Tract contains its own neuronal network (enteric nervous system) that contains as many neurons as there are in the spinal cord
Vomiting
- defensive response to rid the host of toxic/irritating material
How is vomiting regulated?
Regulated via the vomiting center in the medulla and communicates with chemoreceptor trigger zone (CTZ)
Acute chemotherapy drug-induced vomiting
- vomiting within the first 24 hours of chemotherapy
- Involves 5HT/5HT3 receptor signaling
Delayed chemotherapy drug-induced vomiting
- vomiting after 24 hours of chemotherapy
- involves substance P (SP/NK1) receptor
5-HT3 receptor antagonists
- ondansetron
- granisetron
- alosetron - original 5HT3 but removed from market and now used to treat IBS in women
- palonosetron
5-HT3 receptor
- ligand-gated cation channels that mediates Na+/K+ ions
- primary site of action is the CTZ
- 5-HT3 receptors induce vagal signaling of nausea and mediate contraction of the GI tract
5-HT receptors
- 7 families
- all are G-protein coupled, except 5-HT3
5-HT3 receptor antagonists action
- inhibits vagal signaling to vomiting (emetic) center in the brainstem to prevent vomiting from occurring.
- also slows intestinal transit
Adverse Effects of 5-HT3 receptor antagonists
- Headache and GI upset (constipation)
- Ischemic colitis (alosetron)
5-HT3 Receptor Antagonists Pharmacokinetics
- prolonged half-life that persists even when the drug is removed from the systemic circulation
- drug can be given orally or through IV/IM
Dopamine Receptor 2 (D2) Antagonists - antipsychotic phenothiazines
- chlorpromazine
- perphenazine
- prochlorperazine
- trifluoperazine
- work by inhibiting dopamine signaling
Dopamine Receptor 2 (D2) receptor antagonists
- D2 receptor is Gi-protein coupled and inhibits adenylyl cyclase thereby lowering cAMP formation
- D2 receptor antagonists would reverse the action of D2 receptor and increase cAMP formation and activation of protein kinase A (PKA)
D2 receptor antagonists Pharmacokinetics
- highly lipophilic
- half-lives range from 12-24 hours
- available orally and in parenteral formulations
D2 receptor antagonists adverse effects
- extrapyramidal syndrome like dystonias and tardive dyskinesia (involuntary repetitive movements of the face and body)
- hyperprolactinemia
D2 receptor antagonist is contraindicated in patients with?
CNS depression
Metoclopramide
- D2 antagonist
- may also block histamine and muscarinic receptors
- acts centrally on the CTZ, also has peripheral actions (increased GI motility)
- also blocks D2 receptors in other areas of the CNS
- primarily given orally
Adverse effects of metoclopramide
- spasmodic torticollis
- oculogyric crises
- stimulates prolactin release
Domperidone
- D2 receptor antagonist (specific for D2 receptor)
- does not penetrate the blood brain barrier (less CNS side effects)
- small increased risk for serious cardiac adverse effects
- primarily given orally
D2 receptor antagonists used for acute chemotherapy-induced emesis
- metoclopramide
- domperidone
- haloperidole
- droperidol
- levomepromazine
Histamine (H1) receptor antagonists
- cinnarizine
- cyclizine
- promethazine
- inhibit Gq protein coupled receptor
- effective against nausea and vomiting due to motion sickness
H1 receptors
- G-protein coupled receptors linked to Gq proteins (phospholipase C)
- activates protein kinase C, and increases Ca2+
Promethazine
- H1 receptor antagonist
- can also be used to treat pregnancy-associated morning sickness
Muscarinic Receptor Antagonists
- hyoscine (scopolamine)
- used for the prophylaxis and treatment of motion sickness
- given orally or via transdermal patches
Muscarinic Receptor Antagonists adverse effects
- includes dry mouth and blurred vision
- may also cause drowsiness
Aprepitant/Fosaprepitant
- antaognists of substance P receptors (NK1 receptors) in the CTZ
- antiemetic drug
- fosaprepitant is a prodrug of aprepitant
Nabilone
- antiemetic drug
- synthetic cannabinol
- antagonised via naloxone
Dexamethasone
- antiemetic drug
- high doses can prevent vomiting caused by sytotoxic drugs (MOA unknown)
