Canonical Question
GIT Pharm – Gastric fluid
Master answer
Physiology of Vomiting
Vomiting
- Involuntary, forceful and rapid expulsion of gastric contents through the mouth
Triggers
- Excessive GI tract distension
- Stimulation of CTZ
- Directly by certain drugs eg apomorphine, morphin
- Rhythmic motion of the body stimulating the vestibular labyrinth of the inner ear
- Cerebral excitation secondary to odours, pain, stress
Central control of vomiting
- Vomiting center (5HT3, NK1, Muscarinic and Histamine), near NTS
- Inputs
- Chemoreceptor trigger zone (NK1, 5HT3, Dopamine), area postrema outside BBB
- Vestibular system (Histamine and Muscarinic) via CNVIII
- GI Tract (5HT3, stretch and chemoreceptors) via vagal
- Higher centres
- Efferent arc
- via CN V,VII,IX,X,XII and spinal nerves to abdominal wall musles and diaphragm
- Inputs
| Afferent signal | Sensor | Efferent signal | Effect |
|---|---|---|---|
| Chemo/ baroreceptor input Drugs Stim from NTS Stim from GIT (5HT3) | CTZ (area postrema) | 5HT3, D2 and Opioid neurons | Direct stimulation of vomit centre in lateral reticular formation |
| Surgery/ Rhythmic motions | Labyrinths | ACh and H1 neurons | |
| Memory/ Emotions Sensory (sight, smell, taste) | Cortex | ||
| Severe painful stimuli | Pain | H1 neurones | |
| Irritation Manipulation during surgery Distension | GIT | NK1, NAdr, ACh neurons | |
| Via CNX, to NTS | Stimulation of CTZ then Vomit centre | ||
| Via 5HT3 to CTZ | CTZ to vomit centre | ||
| Manipulation of pharynx via CN9 to.. | NTS | Direct to CTZ | To vomit centre |
Vomiting act
- Antiperistalsis as the prelude to vomiting
- At the onset of vomiting, strong intrinsic contractions occur in both the duodenum and the stomach
- Partial relaxation of the lower oesophageal sphincter (LOS)
- Deep inspiration
- Raising of the hyoid bone and larynx to open the upper oesophageal sphincter
- Glottic closure
- Lifting of the soft palate to close the posterior nares
- Strong down ward contraction of diaphragm and simultaneous contraction of all the abdominal wall muscles
- Complete relaxation of the LOS
Gladwin / Sakurai 2016
Anti-emetic Agents
| CLASS | EXAMPLES | MECHANISM OF ACTION |
|---|---|---|
| Anticholinergics | Hyoscine Atropine | – M1-Ach-R antagonism (NTS, CTZ, VC) – Small antihistamine and D2 antagonist effects |
| Antihistamines (H1) | Cyclizine Promethazine | – H1 antagonism- VC, vestibular nucleus and CTZ – Anti-muscarinic effects- NTS, CTZ, vomit center – D2 antagonism (GIT, CTZ) |
| 5-HT3 Antagonists | Ondansetron | – Peripheral in GIT – Central at VC and CTZ |
| Dopamine Antagonists | 1. Phenothiazines – Prochlorperazine (stemetil) 2. Butyrophenones – Droperidol, domperidone 3. Benzamides – Metoclopramide | – Decreased sensitivity of visceral afferents to vomit center – Central D2 blockade increased threshold at CTZ Other effects: – Inhibition of 5-HT3 – Anti-H1 effects |
| Steroids | Dexamethasone | – Proposed to act centrally to inhibit prostaglandin synthesis and inhibit endorphin receptors |
| Miscellaneous | 1. Propofol 2. Benzos 3. Cannabinoids 4. NK1- Receptor antagonists (aprepitant) | – Propofol and BZD- GABAergic inhibition of VC – Cannabinoids- Direct CTZ and VC inhibition – NK1 antagonists inhibit VC |
Exam appearances
| Exam | Exact wording | Relationship | Success |
|---|---|---|---|
| 2022A Q14 | Describe the neural integration of vomiting, highlighting the site and mechanism of action of antiemetics. | historical_member | — |