Physiology and Pharmacology of nausea and vomiting Flashcards
What is nausea?
The unpleasant urge to vomit- not the actual act of vomiting
What is vomiting/emesis?
The forceful expulsion of stomach contents through the mouth/nose by contraction of the abdominal muscles and diaphragm
What is retching?
repetitive reverse peristalsis of the stomach and oesophagus without vomiting. (usually follows vomiting)
What is regurgitation?
is the effortless movement of swallowed food contents/ stomach acid back into the mouth (not associated with nausea or retching, no vomiting).
Effortless reflux of the gastric contents
Patients - might label it as vomiting
What is vomiting co-ordianted by?
The vommitting centre in the medulla oblongata of the brain stem
The contraction of what muscles cause vomiting?
Contraction of the abdominal muscles and diaphragm
Is vomiting due to stomach contraction?
No both the stomach and oesophagus and associated sphincters are relaxed
What is vomiting frequently preceded by?
Profuse salivation, sweating (cold), elevated HR and sensation of nausea
What are some of the consequences of severe (repeated) vomiting?
Dehydration
Loss of gastric protons and chloride - causes hypochloraemic metabolic alkalosis
Hypokalaemia (reflux potassium excretion by kidneys)
Mallory-Weiss tear (due to profuse committing that tears the inner mucosal walls of the oesophagus
Aspiration of the vomitus into the air passage and lungs (sometimes glottis closure is incomplete)
Describe the different places in the brain that help to control vomiting?
Chemoreceptor trigger zone (CTZ) - drugs (chemoradiation), opioids
Nucleus tractus solitarius (NTS)
Vomiting centre (VC) - smell, thought, sight
Vestibular nuclei - motion sickness
What are the different types of drug types that can be used to target nausea and vomiting?
D2 receptor antagonists
H1 receptor antagonists
5-HT3 receptor antagonists
Muscarinic Ach receptor antagonists
What is the vomiting centre?
Main sight of neural control of vomiting
What is the CTZ?
The chemoreceptor trigger zone
Senses blood borne chemical stimuli that induces vomiting like morphine
Also stimulates the VC to induce vomiting
What is the vestibulocochlear/vestibular nuclei?
It plays a role in motion sickness and diseases of the ear, it sends signals to the VC to induce vomiting
Why do heart rate, sweating and salivation increase when you vomit?
Because the autonomic centres regulating those things are close to the VC and they are stimulated in the surge of neuronal activity that company vomiting
What can prolonged or profuse vomiting deplete?
Fluid and electrolytes - leading to dehydration and changes in the blood chemistry
What is the mechanism of muscarinic ACh receptor antagonists? (Anticholinergics)
Block muscarinic receptors in the vestibular nuclei, NTS and VC
What are muscarinic ACh receptor antagonists used in?
Motion sickness mostly
What are the side effects of muscarinic ACh receptor antagonists?
Blurred vision
Urinary retention
Dry mouth
All due to blockage of the parasympathetic ANS
How might you administer muscarinic ACh receptor antagonists?
Transdermal patch, Oral, IM
What are adjuvant antiemetics?
They are given with standard emetics to enhance their effect
What are some examples of adjuvant antiemetics?
Corticosteroids
Benzodiazepines - can cause a sedative affect preventing vomiting etc
Cannabinoids
NK1 receptor antagonists
Describe the treatment of chemotherapy-induced Nausea and vomiting (CINV)
Triple drug therapy
- 5HT3 receptor antagonist
- dexamethasone - corticosteroid
- aprepitant - NK1 receptor antagonists
Describe the mechanism of Histamine H1 receptor antagonists?
blockade of H1 receptors in vestibular nuclei and NTS
Some may also block muscarinic receptors - contributing to their effectiveness
What are H1 receptor antagonists used for?
Motion sickness
Vomiting and nausea - esp related to irritants within the stomach
morning sickness
Post op nausea and vomiting
Less effective against substances that act directly on the CTZ
What are some of the side effects of H1 receptor antagonists
Depression
Drowsiness
Sedation
Describe the mechanism of Dopamine D2 receptor antagonists?
Centrally block dopamine D2 (and D3) receptors in the CTZ
Peripherally exert a pro kinetic (enhances gastric motility) action on the oesophagus, stomach and intestine - some
What are Dopamine D2 receptor antagonists used in?
Drug induced vomiting
Vomiting in GI disorders
Not effective against motion sickness
What are some examples of H1 receptor antagonists?
Cyclizine Cinnarazine Promethazine
What are some examples of D2 receptor antagonists?
domperidone
metoclopramide
Why might domperidone be more beneficial that metoclopramide?
It cannot cross the BBB and thus wont produce the same side effects as metoclopramide such as disorders of movement
Describe the mechanism of action of 5-HT3 receptor antagonists?
Block peripheral and central 5-HT3 receptors (in the GI Tract as well as the CNS)
What are some examples of 5-HT3 receptor antagonists?
Ondansetron
Palonosetron
Granisetron
Describe when you would use 5-HT3 receptor antagonists?
Used to suppress chemotherapy- and radiation-induced emesis and post-operative nausea and vomiting
What is associated with the VC?
Sight, smell and thought
What is associated with the CTZ?
Cancer chemotherapy
Opioids
What is associated with the vestibular nuclei?
Motion sickness
What drugs will work on the CTZ?
Dopamine antagonists
5-HT3 antagonists
What drugs will work on the VC and the vestibular nuclei?
H1 antagonist
Antimuscarinc drugs
What are the side effects of 5HT-3 antagonists?
Generally well tolerated
Constipation and headaches
Describe the mechanism of NK1 receptor antagonists?
antagonism of substance P (which causes vomiting and is released by vagal afferents) is assumed
What are NK1 receptor antagonists used in?
Used in combination with a 5-HT3 receptor antagonist and dexamethasone in the acute phase of highly emetogenic chemotherapy. In combination with dexamethasone in the delayed phase
Give an example of an NK1 receptor antagonist?
aprepitant
What is the mechanism of Cannabinoid (CB1) receptor agonists?
Decreases vomiting induced by agents stimulating the CTZ. Evidence suggests that opiate receptors are involved in drug effect
What are Cannabinoid (CB1) receptor agonists used in?
Used ideally in in-patient setting for treatment of cytotoxic chemotherapy that is unresponsive to other anti-emetics
What are some side effects of cannabinoids?
drowsiness, dizziness, dry mouth, mood changes are common
Give an example of an cannabinoid?
nabilone
What is located in the brainstem?
The major output that coordinates vomiting
Descrive what the vagal efferents do in terms of motor output?
Oesophagus - swallowing
Stomach - proximal relaxation
Small intestine - giant retrograde contraction
Describe what the somatic motor neurones do in terms of motor output?
Diaphragm - contracts
Anterior abdominal muscles - contract
Describe what the autonomic/somatic efferents to in terms of motor output?
Increases HR and force
Increases salivation
Skin - pallor, cold, sweating
Sphincters of bladder and anus - contraction
Describe what causes pregnancy associated nausea and committing?
Caused by human chorionic gonadrotropin (HCG) produced by the placenta
What treatment might you offer for pregnancy associated nausea and vomiting?
Non pharmacological treatments
- changes in diet
- use of ginger or pyridoxine
- wrist (P6) acupressure
What is hyperemesis gravidarum?
Fluid and electrolyte disturbances or nutritional deficiency developing from intractable vomiting in pregnancy
What would you use to treat hyperemesis gravidarum?
First line - antihistamine (promethazine or cyclizine)
Second line - prochlorperazine and metoclopramide
What can metoclopramide do specifically?
Has unique properties of increasing lower esophageal sphincter pressure and increasing the rate of gastric emptying.
Used to treat: antiemetic, migraine, GORD
