PH3113 - Pain and Analgesia 2 Flashcards
What are the risk factors for nausea and vomiting during chemotherapy?
Age
- under 50
Female
Non-smokers
Motion sickness
Previous history
How are 5-HT3 receptor antagonists used to treat acute symptoms of nausea and vomiting?
Examples
- ondansetron
- granisetron
- palonosetron
Formulations
- oral
- might not keep tablets down
- IV injection
- IV infusion
- IM injection
- rectal
- transdermal patches
Side effects
- headache
- dizziness
- diarrhoea
- constipation
- insomnia
5-HT3 receptors found on nerves in the
- GI tract
- CTZ
- vomiting centre
Not known which receptors which need to be blocked
Often used in combination with dexamethasone
How are 5-HT3 receptor antagonists used to treat acute and delayed symptoms of nausea and vomiting?
Metoclopromide
- delayed
Neurokinin 1 receptor antagonists
WITH
5-HT3 receptor antagonists
AND
Dexamethasone
Many side effects limit use
What percentage of migraine sufferers get a warning that an attack is going to happen?
25%
What is migraine with aura?
Set of neurological symptoms
- visual field disturbance
- brightly coloured or blinking lights in a pattern that move across the field of vision
- numbness
- blind spots
- weakness on one side of the body
- slurred speech
What are the symptoms of migraine with aura?
Throbbing headache starts about 30 - 60 minutes after aura
Unilateral in ~ 60% of migraine sufferers
Often associated with
- photophobia
- heightened sensitivity to sound
- nausea and/or vomiting
How long do migraines last?
Several hours up to 3 days
- very debilitating
Migraines usually occasional
- sometimes 1 or 2 a week
- NEVER DAILY
How common are migraines?
Affects
- 33% of women
- 13 % of men
75% of sufferers are female
Evidence for genetic link involving various ion channels
Give examples of migraine triggers?
Diet
Hormones
Sensory stimuli
Stress
Change of environment or habits
What causes a migraine?
Spreading cortical depression
- 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
- 5th cranial nerve
Terminals of the trigeminal nerve in the meninges release calcitonin gene-related peptide (CGRP)
Extra-cerebral vasodilation of cranial arteries and arterio-venous anastosomes causes the pain
Nerve becomes inflamed releasing more peptides (antidromic stimulation) and the vasodilatation continues
What is the involvement of 5-HT in migraines?
5-HIAA levels increase during an attack
- metabolite of 5-HT
Platelet concentrations of 5-HT fall during the onset of an attack
- released from platelets
Intravenous injection of 5-HT aborts headaches induced by reserpine and spontaneous headache
5-HT(1B) receptor agonists are the best drugs for treating migraine
What is the role of 5-HT(1B) receptors in migraines?
Receptors are found on blood vessels in the meninges and large cranial arteries
Receptors on smooth muscle cells of large intracranial arteries
- vasoconstriction
- reduce nerve activation and CGRP release
Receptors on peripheral trigeminal nerve terminals
- switch off CGRP release reducing vasodilatation
Receptors may inhibit central trigeminal nerve firing
- area of brainstem which trigger attacks
What is the treatment for acute migraines?
Analgesics
Triptans
Anti-emetics
Ergotamine tartrate
What is migraine prophylaxis?
Treatment before a migraine happens
- beta blockers
-
antidepressants
- amitriptyline
- Venlafaxine
Anticonvulsants
- Topiramate
- Valproic acid
What is the main effect of 5-HT?
Increase motility and contractility
- direct contractile effect on smooth muscle cells
- 5-HT(2A)
- 5-HT(5A)
- indirect effect on enteric nerves leading to the release of acetylcholine and contraction
- 5-HT(3)
- indirect effect on enteric nerves leading to relaxation
- 5-HT(1A)
- direct relaxant effect on smooth muscle cells
- 5-HT(7)
