Nausea, Vomiting and Pain (DONE) Flashcards
5-HT distribution
~89% of the total body content of 5-HT is found in entero-chromaffin cells in the intestine, some is also found in the nerve cells of the myenteric plexus
About 10% is found in platelets which take 5-HT up from the plasma
About 1% of the 5-HT is in the CNS where it has a very important role despite the relatively small amounts found there
Physiological actions of 5-HT in the GI tract
Main effect is to increase motility and contractility
Direct contractile effect on smooth muscle cells
Indirect effect on enteric nerves leading to the release of ACh and contraction
Indirect effect on enteric nerves leading to relaxation
Physiological actions of 5-HT in the nervous system
Peripheral nervous system- involved in the sensation of pain by sensory nerve endings
Cardiovascular effects of 5-HT
Receptors on sensory vagal nerves produce reflex bradycardia and hypotension
In the heart causes tachycardia
Many complex cardiovascular CNS effects leading to increased or decreased BP and HR
Platelet aggregation effects of 5-HT
Causes platelets to aggregate and adhere to the vessel wall
Platelets release more 5-HT causing further aggregation
Released 5-HT also causes vasodilatation in intact endothelium by stimulating the production of NO, causing vasoconstriction if endothelium damaged
Effects of 5-HT on platelet aggregation most important in vascular disease when the endothelium is damaged
Blood vessel effects of 5-HT
Direct vasoconstriction of smooth muscle in arteries and veins, leading to increased BP, vasoconstriction in cranial vessels
Indirect vasodilator action (fall in BP) either by stimulating nitric oxide production from endothelial cells or by inhibiting noradrenaline release from sympathetic nerves
Direct vasodilator effect on smooth muscle, usually only seen when vasoconstrictor responses blocked, more marked in vessels in skeletal muscle and the heart
Microcirculation 5-HT effects
In the microcirculation, 5-HT produces vasodilatation in arterioles and vasoconstriction in venules, increasing capillary pressure so fluid escapes from the capillaries
5-HT also increases microvascular permeability, increasing tissue volume
Nausea and vomiting
Different types of stimuli can induce nausea and vomiting (emesis):
Gastric irritation and peritonitis- gets rid of the irritant
Inner ear dysfunction
Pregnancy
Drugs- digitalis, cancer chemotherapeutics, general anaesthetics, radiotherapy
Brain regions and receptors involved in nausea and vomiting
Different areas of the brain involved: cerebellum- motion sickness, solitary tract nucleus- irritants, CTZ- drugs or chemicals in the blood, higher centres (cortex, hypothalamus)- psychological influences
Vomiting centre in the medulla controls the series of events which precede vomiting
Different receptors- muscarinic, dopamine, histamine, serotonin, neurokinin, cannabinoid, opioid
Motion or travel sickness
Inner ear dysfunction
Conflict of messages to the brain
Involves dopamine D2 receptors in the vestibular nucleus
Pharmacological and non-pharmacological treatments e.g. antihistamines, antimuscarinics
Nausea and vomiting in pregnancy
Morning sickness but can occur at any time of the day
Causes unknown but thought to be due to hormonal changes
Symptoms often disappear by the end of the third month, 1 in 10 women still feel sick after week 20
About 50% of pregnant women vomit, more than 80% fell nauseous
Generally not treated with drugs
Hyperemesis gravidarum
Prolonged, severe vomiting, affects about 1 in 100 women
Associated with dehydration, ketosis, weight loss and postural hypotension
May need hospitalisation for IV fluids and drugs
Treated with anti-emetics, steroids, vitamins B6 and B12
Anti-emetics in pregnancy
Anti-histamines (H1 receptors)- cyclizine, promethazine
D2 receptor antagonist- prochlorperazine
D2 receptor antagonist/5-HT receptor antagonist- metoclopramide
D2/D3 receptor antagonist- Domperidone
5-HT3 receptor antagonist- ondansetron
Steroid- prednisolone
D2 receptor antagonist prochlorperazine
Severe nausea and vomiting (treatment and prevention)
Caution in various patient groups including cardiovascular disease and elderly
Many side effects including dystonia, esp in children
Oral, IM, buccal tablets e.g. Buccastem
Can be used in combination with dexamethasone, although the mechanism for its anti-emetic action is unknown
D2 receptor antagonist/5-HT3 receptor antagonist metoclopramide
Migraine, chemotherapy, radiotherapy and general anaesthetics
Caution in elderly and 15-19 year olds
Many side effects including adverse neurological effects
Restrictions on indications, dose and duraction
Oral, IM, IV
Also used with dexamethasone
D2/D3 receptor antagonist domperidone
Periphery only, blocks D2 receptors in the CTZ, less central side effects
Nausea and vomiting
Caution in children and those over 60
Many side effects including serious cardiac effects
Restrictions on indication, dose and duration
Oral
Nausea and vomiting with chemotherapy, radiotherapy and general anaesthetics
N+V produced by drugs such as cisplatin, drugs affect all dividing cells including hair follicles, bone marrow and the GI epithelium
Enterochromaffin cells in the gut release 5-HT
3 types of N+V: acute (within 24 hours of treatment), delayed (more than 24 hours after treatment), anticipatory (before the next dose)
General anaesthetics depends on anaesthetic, type and duration of surgery
Range of risk factors: female, non-smoker, history of N+V, motion sickness, opioid use
5-HT3 receptor antagonists for treatment of acute symptoms
Ondansetron, granisetron, palonosetron
Oral, IV, IM, rectal, transdermal
Side effects: headache, dizziness, diarrhoea, constipation, insomnia
Receptors found on nerves in the GI tract, CTZ and vomiting centre but it is not known which receptors need to be blocked
Often used in combination with dexamthasone
5-HT3 receptor antagonists for treatment of acute and delayed symptoms
Metoclopramide
Neurokinin 1 receptor antagonist, can use with dexamethasone
Given orally, aprepitant, or by IV infusion, fosaprepitant
Many side effects limit use
Droperidol
D2 receptor antagonist
Post-operative nausea and vomiting/acute symptoms
Caution in various patient groups including cardiovasulcar disease and elderly
Many side effects including adverse neurological effects e.g. anti-pyramidal
In injection
Perphenazine, trifluouoperazine
D2 receptor antgonists
Severe nausea and vomiting unresponsive to other anti-emetics
Caution in various patient groups including cardiovascular disease, elderly
Many side effects including adverse neurological effects e.g. anti-pyramidal
Oral
Nabilone
Cannabinoid
Only for nausea and vomiting caused by cytotoxic drugs unresponsive to other anti-emetics
Many CNS side effects including drowsiness and dizziness
Oral, used under hospital supervision
Migraine
About 25% of sufferers get an aura that an attack is going to happen- visual field disturbance, numbness, blind spots, weakness on one side of the body or slurred speech
Symptoms: throbbing headache starts 30-60 minutes after the aura, unilateral in ~60%, often associated with photophobia and n+v
Attacks can last from several hours to three days
Usually occasional, sometimes 1-2 a week, never daily
Evidence for a genetic link involving various ion channels
75% of sufferers are female
How is a migraine caused?
Spreading cortical depression due to a wave of decreased neuronal activity spreading across the brain probably accounts for the aura, could be related to stress
Increased neuronal activity from the brainstem activates the trigeminal nerve innervating the face and forehead
Terminals of the trigeminal nerve in the meninges release calcitonin gene related peptide
Extra-cerebral vasodilation of cranial arteries and arterio-venous anastsosomes causes the pain
The nerve becomes inflamed releasing more peptides and the vasodilation continues
