Physiology and Pharmacology of Nausea and Vomiting Flashcards
what is emesis
vomiting
what is nausea
highly unpleasant subjective urge to vomit. Felt in stomach and throat as a sinking feeling, doesn’t necessarily lead to vomiting
what is vomiting
the forceful expulsion of stomach contents through the mouth/nose by contraction of the abdominal muscles and diaphragm
what autonomic influences are seen in nausea
paleness, sweating, excessive salivation, elevation of heart rate, relaxation of smooth muscle of stomach and oesophagus, upper intestinal contractions with reverse peristalsis
what is retching
repetitive reverse peristalsis of the stomach and oesophagus without vomiting
what is regurgitation
effortless movement of swallowed food contents/ stomach acid back into the mouth (not associated with nausea or vomiting)
why is there excessive salivation in nausea
reduces acidic content entering the oesophagus helps reduce damage
why do you stop breathing when you vomit
to close the glottis and elevate the soft palate which helps seal off the nasal passage
does vomiting involve the active contraction of the stomach- why
no- smooth muscle of stomach relaxed so it can receive contents from the small intestine
what muscle contract to allow vomiting
skeletal muscles and diaphragm- increases intra-abdominal pressure
what state are the sphincters of the oesophagus in during vomiting
relaxed
what are the different pathways that stimulate vomiting
vestibular (motion sickness, labyrinth), central (brainstem), CNS, mechanical
what do all pathways stimulate
the vomiting centre in the medulla
how do absorbed toxins stimulate the vomiting centre
via CTZ within the AP of the brainstem
how do mechanical stimuli or pathologies within the GI tract stimulate the vomiting centre
via vagal afferents to brain stem
how does the vestibular system stimulate the vomiting centre
vestibular nuclei, CTZ
how do stimuli within the CNS stimulate the vomiting centre (pain, repulsive sights, odours, fear, anticipation, psychological factors
cerebral cortex, limbic system,
what do enterochromaffin cells in the mucosa release which causes the stimulation of vagal nerve fibres to the brainstem
5-HT and substance P
what are CTZ IMPORTANT
chemoreceptor trigger zone
where do vagal fibres from the gut terminate IMPORTANT
in CTZand NTS, both in the brain stem
what are NTS IMPORTANT
nucleus tractus solitarius
what prevents harmful toxins entering the CNS
blood brain barrier- CTZ lack this
what is the medullas proper name
the medulla oblongata
where can you eject GI contents from
ileocecal valve
what effect do the vagal afferents have to the GI organs during vomiting
oesophagus shortens,
proximal relaxation of the stomach, retrograde contraction of the small intestine
what effect do the somatic motor neurones have during vomiting
contraction of abdo muscles and diaphragm
what are the prodromal signs that precede vomiting
increase HR and force, increased salivation, pallor of skin and cold sweating
what nerves cause the constriction of the sphincters of the bladder and anus
autonomic/ somatic afferents
what are the consequences of severe vomiting
dehydration,
loss of gastric proton and chloride= hypochloraemic metabolic alkalosis,
proton loss is accompanied by potassium excretion= hypokalaemia,
mallory-weiss tear,
aspiration
when can severe vomiting cause metabolic acidosis (rare)
loss of duodenal bicarbonate
why does chemotherapy and radiotherapy cause nausea and vomiting
releases 5-HT and substance P
what is PONV
post operative N&V occurs with administration of general anaesthetic
why do dopamine agonists cause N&V
as dopamine receptors prevalent in CTZ
name a cardiac drug that causes N&V
cardiac glycosides e.g. digoxin
what are setron drugs and how do they work
5-HT3 receptor antagonists- competitive block the receptors at peripheral and central terminal
when are setrons used
to suppress chemo and radio therapy N&V and PONV
what are setrons not effective against
motion sickness, agents increasing dopaminergic transmission
what are the SE of setrons
constipation and headaches
what is the main use of muscarinic acetylcholine receptor antagonists
prophylaxis and treatment of motion sickness
how do muscarinic acetylcholine receptor antagonists relieve N&V
inhibit GI movements and relax GI tract
what are the SEs of muscarinic acetylcholine receptor antagonists
blockade of para system causes blurred vision, urinary retention, dry mouth
and centrally mediated sedation
how do histamine H1 receptor antagonists work to prevent N&V and what are they used for
motion sickness and acute labyrinthisitis N&V caused by irritants of the stomach
block receptors
what are the SEs of histamine H1 receptor antagonists
depression and sedation
what are dopamine receptor antagonists sued for
drug induced vomiting and GI disorders- not effective against motion sickness
what dopamine receptor antagonist is safer and why
domperidone as does not cross the blood brain barrier so produces less side effects
when are NK1 receptor agonists used
in combo with 5-HT3 receptor antagonists in chemotherapy
when is cannabinoid (CB1) receptor agonists used and what are the SEs
in cytotoxin chemo thats unresponsive to other anti emetic drugs
drowsiness, dizziness, dry mouth, mood swings
what is metaclopramide used to treate
antiemetic, GORD, migraine
what does an NK1 receptor block
substance P
what causes pregnancy N&V
placenta produces HCG
when does morning sickness happen
begins weeks 4-8, peaks 7-12, subsides 16
what are the non pharmcological treatments for morning sickness
changes in diet, ginger/ pyridoxine, wrist acupressure
what is hyperemesis gravidarum
Fluid and electrolyte disturbances or nutritional deficiency develops from intractable vomiting in pregnancy
what is the treatment for hyperemesis gravidarum
First line recommended treatment is an antihistamine such as promethazine or cyclizine.
Second line treatments are prochlorperazine and metoclopramide.
