Pharmacology - Headache and Migraine Flashcards
What is the recommended pharmacological management in acute migraines?
Migraine specific:
Established efficacy -Triptans, Ergotamine derivatives, Gepants, Lasmidutan
Probably effective - Ergotamine
Non-migraine specific:
Established efficacy -NSAIDs (aspirin, ibuprofen, diclofenac, naproxen, celecoxib), combi analgesics (acetominophen, aspirin, caffeine)
Probably effective -
NSAIDs (ketoprofen, flurbiprogen, IV or IM ketorolac), IV Mg, isometheptene containing cmpds, metoclopramide, promethazine, prochlorperazine, chlorpromazine, droperidol
What is the recommended pharmacological management in migraine prophylaxis?
Established efficacy:
- Candesartan
- BB: Metoprolol, Propranolol, Timolol
- Valproate, Topiramate
- Frovatriptan (good for menstrual assoc migraine)
- Erenumab
Probably effective:
- TCA e.g. amitriptyline
- Lisinopril
- Aspirin
- BB: Atenolol, Nadalol
- Memantine, Venlafaxine
What is the indication of cafergot?
Acute migraine management
What is the MOA of cafergot?
Caffergot is a combination pdt of caffeine and ergotamine
Ergotamine is a 5HT rece agonist causes the vasocostriction of intracranial extracerebral blood vessels without altering blood flow to the brain. This reverses the vasodilation implicated in migraine pathophysiology
Inhib norepinephrine uptake and alpha adrenorece –> prolonged vasoconstriction
Caffeine is an adenosine A1, A2A, A2B rece antagonist which leads to vasoconstriction of cerebral vasculature. It also increases the absorption of ergotamine
Describe the PK of caffergot.
A:
- Rapidly but erratically absorbed
- F: 2%
- Tmax reached within 1.5-2h
D:
- Highly plasma protein bound
M:
- High 1st pass meta
- Hepatic CYP3A
E:
-t1/2: 2-2.5h
- 90% by faeces
What are the S/E assoc w caffergot?
NV
Hypersensitivity
MI
Ergotisms (vascular ischemia)
Insomnia
Transient lower limb muscle pain
Vasoconstriction
Transient increase in BP
Flushing
What are the DDI assoc w caffergot?
Triptans: enhance vasoconstriction
- Avoid taking ergotamine preparations within 6h of triptans
- Avoid taking triptans within 24h of ergotamine
CYP3A inhib
- Erythomycin, clarithyromycin, protease inhib
What are the CI w caffergot?
Stroke/TIA
MI
Uncontrolled HTN
Peripheral vascular disease
IHD
Coronary artery vasospasm
GI ischemia
Concomitant use of triptans (within 24h)
Hx of hemiplegic or basilar migraine
What are the indications of triptans?
Acute migraine, NOT to be used for migraine prophylaxis
Exception - menstrual pain assoc migraine prophylaxis (frovatriptan)
What is the MOA of triptans?
Selective 5HT1B/D rece agonists on trigeminal nerve and intracranial extracerebral blood vessels
Binding to rece on trigeminal nerve inhib the release of vasoactive neuropeptides VIP, sub P and CGRP. Less release of CGRP, less vasodilation, less activation of nociceptor and less neurogenic inflamm and
On intracranial extracerebral blood vessels cause direct vasoconstriction (migraine relief)
Describe the PK of triptans.
A:
- Onset: 30min (PO), 10min (SC)
- Tmax: 2.5h (PO), 12min (SC)
- F: 15% (PO), 97% (SC)
If hepatic impairment PO F increases
- Food intake increases Cmax and AUC by 15% and 12% respectively
D:
- Low plasma protein binding: 14-21%
- Vd: 2.4-2.7L/kg
- Crosses placenta & enters breastmilk
M:
- Xtensive hepatic meta by MAO-A
- Metabolite: indole acetic acid (inactive) undergoes phase II glucuronidation
E:
- PO: 60% renal (mostly as inactive metabolite), 40% faecal
- SC: 38% renal as metabolite, 22% unchanged
- t1/2: 2h
- CL: 1160mL/min
What are the S/E assoc w triptans?
Transient increase in BP
Flushing
Cold sensation
Distal parathesia
NV
Dizziness, unsteadiness
Fatigue
Serotonin syndrome
- Agitation, restlessness
- Hallucinations
- Tachycardia, arrhythmia
- Rigid or twitching movement
Chest pain, P, tightness, pain or tightness in throat or jaw
Minor LFT disturbances
What are the DDI assoc w triptans?
Ergotamines: enhance vasoconstriction effects
- Avoid taking triptans within 24h of these
- Avoid taking ergotamine preparations within 6h of triptans
MAO-A inhib: increase risk of serotonin syndrome
- E.g. isocarboxazid, transdermal selegiline, moclobemide, phenelzine, tranylcypromine
Other triptans (avoid for 24h)
What are the CI assoc w triptans?
Ergotamine or triptan usage (space 1d)
MAO-Ai (space 2 weeks)
Stroke/TIA
MI
Peripheral vascular disease
Ischemic heart disease
Uncontrolled HTN
GI ischemia
Hx or hemiplegic or basilar migraine
Severe hepatic impairment
What are the special considerations assoc w triptans
Take early in course of an attack when pain intensity is mild
Lack of response to one triptan does not predict resp to other
Abt 20-50% of pts xp recurrence of migraine within 48h after 1st dose of triptan. 2nd dose may be admin
If no resp to first dose, do not take 2nd dose for same attack, use for subseq attack
If responsive to 1st dose but sx recur, repeat after >=1h (cluster headache), 2h (migraine)
