Drugs used in migraine Flashcards
what other symptoms are sometimes reported with migraines?
muscle pains
cognitive disruptions
autonomic symptoms - relatively rare
what is a migraine ?
headache accompanied by nausea, vomiting, photophobia and phonophobia
headache: idiopathic, paroxysmal, recurring, moderate to severe attacks, unilateral, throbbing, exacerbated by physical activity
what do most people have to do if they are suffering from a migraine ?
most people have to go and lie down until it passes, often in a dark and silent room
what can induce the onset of a migraine ?
often the onset is unclear but sometimes stress can induce them
how many people are affected by migraines ?
10-15% of worlds adult population
it is the 19th most common debilitating condition according to WHO
which gender suffers more from migraines ?
18% females and 6% males
when do migraines usually start ?
they begin around puberty and this increases to peak around 40s and the disappears
what are the 2 types of migraine?
classical= 20% pain with aura common= 80% pain without aura
what is aura ?
it is a focal neurological symptom
for diagnosis:
2 attacks with aura symptoms
3 of the following - transient, develop over 4+ minutes, aura lasts
what is 99% of aura made up of ?
visual disturbances
- zig zag lines
- shimmering lights
- spreading to whole field of vision
what are the other disturbances caused by aura ?
SENSORY DISTURBANCES- numbness, spreading numbness that starts at the fingers and spreads to arms and then shoulder
APHASIC- difficulty speaking
BASILAR- loss of balance, double vision and fainting- this is in extreme cases
alternating body sites are affected with different attacks
what re the 5 distinct stages of migraines?
prodromal (30-40%)- awareness that you are likely to develop a migraine
aura (20%)- this is only present in classical migraines
headache- moderate to severe
resolution
postdromal- you dont feel 100% still you can sometimes feel nauseous
how long can attacks last for ?
last between 4-72 hours
what is the average number of attacks per year which migraine sufferers suffer from ?
12
what are the percentage of sufferers which have a family member that also suffers from them ?
80%
what is a thunderclap migraine?
this is when a headache starts all of a sudden
what are the causes of familial hemiplegic migraine ?
P/Q calcium channel chromosome 19- this accounts for about 50% of cases- it affects ion channels or proteins involved in maintaining ionic bases
Na+/K+ pump - chromosome 1
this form is relatively rare
what are the 2 main theories for sporadic migraines ?
vascular theory
neurovascular theory
what is the vascular theory ?
traditional theory
states that auras are caused by vasoconstriction of cerebral blood vessels followed by vasodilation which causes the headache- thought that this causes the visual and cognitive disturbances
why is the vascular theory too simple ?
most patients dont experience aura therefore it doesnt explain what happens in the patients not suffering from aura
doesnt explain the premonitory features- the prodromal phase
recent blood flow studies do not support vascular theory because it appears that constriction is not followed by dilation
what is the neurovascular theory ?
dilation of blood vessels and pain is triggered by neural rather than vascular signals
serotonin, nitric oxide, CGRP, substance P are all thought to be involved- serotonin and substance P are involved in pain and inflammation
in some patients cortical spreading depression is involved- ongoing reduction in nervous activity that spreads from 1 region of the brain to the next
what are 2 methods of treatment ?
prophylaxis - ongoing treatment to prevent attacks
acute attacks- take treatment when you start to have an attack
what are some simple analgesics used as acute treatment of migraines and what are the side effects ?
aspirin, ibuprofen, diclofenac and paracetamol - these are the most common ways to deal with migraines
side effects- GIT discomfort (due to inhibition of prostaglandin production), peptic ulceration and GIT bleeding
what compound analgesics/antiemetics are used for acute treatment of migraines ?
- gastric stasis is reduction in gastric contractions which will reduce the ability to absorb drugs - this occurs in migraines
antiemetics are used to reduce nausea to also improve drug absorption - metaclopramide (D2 antagonist)/aspirin
- metaclopramie/paracetamol
- domperidone/paracetamol
- lysine/aspirin/metaclopramide- the lysine increases aspirin absorption
what is ergotamine ?
acute treatment for migraines
- vasoconstrictor of blood vessels
- serotonin and dopamine receptor agonist
- used for 50 years but no longer really used due to its adverse effects
what are the adverse effects of ergotamine ?
nausea, vomiting, abdominal pain, muscular cramps
overuse headache- body will adapt to ergotamine so you have to take more and more to overcome the headache
peripheral vasospasm
cold extremities, gangrene - as blood supply to extremities gets cut off
high first pass metabolism
what are the contraindications associated with ergotamine?
pregnancy, CHD, peripheral vascular disease
what are triptans ?
serotonin 1B/D agonists such as sumatriptan
highly specific for receptors in cranial blood vessels therefore very few peripheral side effects
cause vasoconstriction
activates serotonin receptors in trigeminal nuclei of brainstem- some of the pain associated with migraines appears to be caused by these nuclei
inhibits dural neurogenic inflammation
sumatriptan is effective in 60% of patients
what are the side effects associated with triptans?
they are often frequent, and short lived
tingling/heat in head, neck, chest and limbs
other side effects of sumatriptan
- chest related symptoms- 40% of patient, pressure in chest and arms, shortness of breath, mimic angina
- nausea
- dizziness,
- flushing
- fatigue
some of these effects can be avoided by taken it as a nasal spray
what are the contraindications associated with sumatriptan ?
angina/mi uncontrolled hypertension pregnancy/lactation children and >65 also drug interactions with SSRIs, MAOIs and lithium
what does it mean by triptan wars ?
the triptans were a major breakthrough and therefore many variations of them were produced
- enable less headache recurrence
- faster acting
- it meant that if one was not effective another one could be tried
what are examples of other triptans than sumatriptan ?
naratriptan- most common because it has less interactions, fewer side effects zolmitriptan rizatriptan almotriptan eletriptan frovatriptan
when is prophylactic treatment used for migraines ?
2-4 attacks per month
interfering with patients lifestyle
why do patients need to be fully informed when taking medication propylactically ?
daily medication for potentially 30 years
may have unpleasant side effects
also have to allow it time to work- 2 months
how much does prophylactic treatment ususally reduce migraines?
usually by about 50% but it may just be a short term solution
what beta blockers can be used and prophylactic treatment and what are their effects ?
propranolol, metaprolol, timolol and nadolol
propranolol causes more than an 50% reducton in migraine attacks in 35-60% of patients
has no effect on reducing severity of duration of attacks
what are the side effects of beta blockers ?
drowsiness fatigue, lethargy sleep disorders, nightmares depression memory disturbances hallucinations bronchoconstriction cardiac failure cold extremities hypotension exacerbation of heart failure renal failure
what are the contraindications associated with beta blockers ?
asthma and hypertensio
what anticonvulsants are used as prophylactic treatment and what do they do ?
topiramate and sodium valporate
- only topiramate is licensed in UK
block voltage gated calcium cahnnels, increase GABA action at GABAa receptors and AMPA/KA antagonists
what are the side effects of topiramate ?
paraesthesia fatigue anorexia nausea taste disturbance diarrhoea
what are the side effects of sodium valporate ?
mild to moderate nausea vomiting gastrointestinal distrss infection alopecia tremor asthenia dizziness somnolence
what tricyclic antidepressants are used as prophylactic treatment ?
amitriptyline
not licensed in UK
need much lower doses compared to depression treatment
what are the side effects of amitriptyline ?
sedation drowsiness dry mouth weight gain constipation mania dizziness tachycardia blurred vision tremor confusion arterial hypotension urinary retention akathesia
what serotonin antagonists are used inn prophylactic treatment ?
methysergide and pizotifen - have antihistamine and sertonin antagonistic effects - some have anticholinergic effects block serotonin 1, 2a and 2c 2nd line of medication
what are the side effects of pizotifen ?
increased appetite- weight gain drowsiness antimuscarinic activity- dry mouth constipation blurred vision
what are the contrainidcations of pizotifen ?
pregnancy breast feeding glaucoma urinary retention renal impairment
what are the side effects of methysergide?
rarely used now - only in hospitals very dangerous side effects - retroperitoneal fibrosis - fibrosis of heart valves - behavioural disturbances - arterial spasm can only be taken for 4 months before you have to have a month off
