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Pharmacology of Migraines - Coggle Diagram
Pharmacology of Migraines
Cephalagia/Analgesic Rebound headaches
Management Principles and Treatments
Lifestyle Control
Avoid changes in sleep, keep regular meals, stress levels
Avoiding Triggers
Stress, Food (Chocolate, aged cheese, red wine, nuts, avocados)
Unavoidable Triggers
Menstruation, barometric pressure, family/job stressors
Abortive Medications
NSAIDs
Bottom Line
For mild, OTC is ok
For Moderately severe: Diclofenac soluble (Cambia), High dose effervescent soluble ASA
Triptans
Mechanisms
Peripheral vasoconstriction, and CGRP antagonism offers very significant migraine relief, and does not vasoconstrict
Inhibition of neurogenic inflammation peripherally
Inhibition of nociceptive inputs to the central pain system
Pharmacologic Control
Serotonin inhibits release of excitatory neurotransmitters
Postsynaptic 5HT blocker decreases effect of excitatory neurotransmitter
Presynaptic 5HT agonist inhibits release of excitatory neurotransmitter
5HT1 receptors are inhibitory
5-HT2-7 receptors are excitatory
Characteristics
First line therapy for moderate to severe migraine
Best taken at beginning of Migraine pain
Types
1st generation
Sumatriptan
2nd Generation
Rizatriptan, zolmitriptan, eletriptan, almotriptan, naratriptan, frovatriptan
Main Principles
Taken as soon as possible after start of migraine pain
May be repeated x1 after waiting 2+ hours with exception of forvatriptan and naratriptan - 4 hrs
Sumatriptan injection or Zomig nasal spray in order to allow for very fast onset to treat rapidly or sudden onset migraine
Never more than 2 triptans in a day, or more than 1 dose at once (except when need fast and long onset)
Onset
About 30 minutes
Sumatriptan tabs a bit shorter at 15-20 min, zomig tabs take longer (30-45 min)
Use slow onset triptans (Naratriptan/frovatriptan) which have longer half lives which can be helpful with headache recurrences
Need fast onset and long duration
take 2 triptans (Sumatriptan/Zomig + Naratriptan/Frovatriptan)
SIde Effects
Chest pain but not usually cardiac, vascular spasm
Contraindications
CAD, Stroke, PVD, Uncontrolled hypertension, raynaud's abnormalities
Drug Interactions
SSRI -> Increase risk of serotonin syndrome
CGRP
CGRP can trigger a migraine
Important downstream from triptan effect (5HT1B/1D)
Gepants
Group of chemically unrelated compounds that have shared modes of action
Ubrogepant - Abortive agent
Atogepant: Prophylactic
Ergots
No longer first line medication
Dirty drug that can be used in paitents refractory to triptans, more side effects than triptans
Examples
Ergotamine, DHE
Contraindications
Use of triptan in previous 24 hrs, atherosclerotic heart disease, uncontrolled hypertension/asthma, severe renal disease
Stacking/Combination Therapies
Combo drugs should be limited to 10 days per month
Rescue Medications
Examples: Neuroleptics, Strong NSAIDs, Steroids, Opioids
Neuroleptic
Side Effects
Sedation, acute dystonia
NSAIDS
Side Effects
GI Distress, gastritis, bleeding
Steroids
Hypertension, gatritis, marked mood changes, exacerbate hyperglycemia
Iseometheptene derivates
Opioids
Last ditch
Medication Overuse Headache
Treatment
Withdrawal of overused medication
Best results in medication withdrawal if prophylactic medication is used: Propranolol, timolol, divalproe
Prophylactic Agents
Indications
When migrain frequency exceeds 1x/week, abortive agents ineffective/not tolerated
Approach
Drug that can do target multiple other conditions
Start at low dosage and slowly increase to allow patient to acclimate
Contraindications to increasing Dosage
Headaches are well-controlled/gone, intolerable side effects, max dose achieved
Nutriceutical Treatment
Use of Coenzyme Q10/Ribofalvin which are cofactors in mitochondria may be helpful
Magnesium: Stabilizing role in sodium pump
Melatonin: Improves sleep, help migraine which has diurnal component
Beta Blockers
MOA
Extert some therapeutic effects in migraine through beta 1 adrenoceptor antagonist, decrease blood vessel dilatation, make nervous system less excitable
Examples
Propranolol, metoprolol, timolo, nadolol, atenolol, beta blcokers with intrinsic symapthetic activity don't work
Contraindications
Poorly controlled diabetes, asthma, hypotension, bradycardia
Interactions
Other hypotensive agents/rizatriptan
Side Effects
Depression, fatigue, hypotension/dizziness,palpitations
Considerations
Propranolol is effective but requires 3 doses per day, higher rate of depression/nightmares, exacerbates dyslipidemia
Nadolol:Once per day, less lipophylic, exacerbates dyslipidemia
Atenolol: Given once per day, does not exacerbate dyslipidemia
TCA
MAO
Blocks noradernaline and other neurotransmitters
Side Effects
Sedation, dry mouth, constipation, weight gain
Examples
Amitriptyline: Sedation and useful with insomnia
Nortriptyline: LEss sedation
Desipramine: Fewer anticholinergic side effects such as dry mouth
ACE and ARBs
MOA
Unknwon action, but positive association between ACE gene and migraine, and ACE activity in migrainw tih aura is higher than in migraine without aura
Examples
ACE: Lisonopril, Enalapril
ARB: Candesartan
Side Effects
Hypotension, Dizziness, increased creatine
Valproate
Side effects
Tremor, somnolence, weight gain, hypertrichosis, teratogenic, Liver abnormalities
MOA
Inhibits glutamade release and blocks NMDA
Topiramate
MOA
Decrease excitability, inhibition of voltage-activated calcium channels, weak inhibition of isozymes of carbonic anhydrase
Side Effects
Acral paresthesia, glaucoma, weight loss, memory and cognitive issues
Lamotrigine
MOA
Blocks voltage sensitive sodium channels -> Inhibits neural release of clutamate
Botox
Initially used consmeticlaly but physician noted improvement of migraines
MOA
Botox inhibits release of neurotransmitters, and certain pain peptides
Criteria for treatment
Fail to respond to 2 or 3 prophylactic agents, >15 days of headache per month
CGRP
Jugular CGRP elevated in migraineurs during attacks
Antibodies
Aimovig/Antibodies against CGRP (Vyepti, Ajovy, Emgality)
Long term risk is unknown, and is potennt vasodilator
Rimegepant, Atogepant, Ubrogepant (abortive)