Pharmacology Of Headaches Flashcards
Pathophysiology of migraines
ExactOrigin is unknown
Involves sensitization of trigemniovascular pathways and brainstem
Results in vasodilation, and release of the following neuropeptides
- CGRP
- substance P
- Neurokinin A
CN 5 trigeminal pathways are activated via these release of neuropeptides and transmits pain signals
Four stages of migraines
Prodromal
- 2hrs- 3 days
Aura
- 5-60 minutes
Migraine headache
- 4-72 hrs
Post dromal
- 24-48 hrs
Propionic acid derivatives
Profens and naproxen
MOA: reversible inhibitor of COX 1/2 enzymes
- works at the same site as aspirin (except it reversible)
- inhibits prostaglandin synthesis
Pregnancy B in 1st/2nd trimester, D in 3rd trimester
dont use naproxen for a mother who is breastfeeding
ADRs:
- GI distress, tinnitus
- CHF, MIs and GI ulcers are serious but rare
- naproxen has lowest cardiovascular risk*
Triptians
MOA: selective serotonin receptor agonists (5-HT)
Causes constriction of the cranial blood vessels in the CN5 nerve tract
all are eliminated hepatically
rizatriptan, sumatriptan, zolmitirptain and naratriptan all also go under monoamine oxidase metabolism as well
Pregnancy C: use sumatriptan
ADRs:
- nausea/dizziness/vomiting
- can cause MI, strokes, angioedema and serotonin syndrome in rare cases
- CONTRAINDICATED in patients with CAD or uncontrolled HTN
Don’t administer within 24 hrs of a ergo and vise versa
Don’t administer with a MAO-A inhibitor
Ergot alkaloids
“Ergots”
MOA: stimulates vasoconstriction by stimulating serotonin 5-HT and alpha adrenergic receptors
CONTRAINDICATED IN PREGNANCY, CAD, previous history of stokes or uncontrollable HTN
ADRs:
- nausea/vomiting
- leg cramps
- MI, stroke are rare
- life-threatening peripheral ischemia if co administered with a potent CYP3A4 inhibitor
Can cause rebound effects and has increased risk of abuse due to developing tolerance
Don’t administer within 24 hrs of a Triptan
Calcitonin genre-related peptide (CGRP) antibodies
Erenumab/Fremanezumab/Galcanezumab/Eptinezumab
MOA: binds to CGRP receptors or CGRP itself and antagonizes them
- CGRP causes intensive pain in migraine patients
Super new, super expensive and requires monthly subcutaneous doses.
- because of this is usually only restricted to patients who cant handle anything else.
Calcitonin gene related peptide antagonist
Rimegepant
MOA: essentially a stronger CGRP antibody that almost completely inhibits receptors
fast acting oral tablet, but almost as expensive as the antibodies
CONTRAINDICATED IN PREGNANCY
ADRs:
- nausea
- Hypersensitivity
*dont give with CYP3A4 inhibtors
Botulinum neurotoxins (BoNTs)
Inhibits Exocytosis is of ACh by cleaving snare proteins
- is reversible and decreases substance P and CGRPs
Pregnancy category C
CONTRAINDICATED in patients with muscle weakness conditions
- makes them worse and can result in total paralysis
Antimetics
Phenothiazines, Butyrophenone
MOA: antagonizes D2, H1 and M1 receptors (dopamine, histamine and muscarinic respectively)
- Note: butyrophenones really only works on dopamine (D2)
Bualbital combination
Butalbital w/ acetaminophen or aspirin and with/without codeine
MOA: A GABAa agonist which acts on the CNS as a depressant.
- increases CL- currents and channels which prolongs repolarization
Pregnancy category C
ADRs:
- nausea/vomiting
- lightheadness
- Hepatic failure is rare
serious concerns with withdrawal and overuse, also no controlled studies have been done to establish efficacy
What populations are BBs contraindicated in?
Asthmatics
Raynaud’s disease
Pregnancy or lactating women
What patient population in tricyclic antidepressants contraindicated in?
(Amitryptillne)
Patients with glaucoma
Treatment for tension headaches
NSAIDs alone or w/ caffeine
Combination therapy of aspirin/acetaminophen w/ butalbital or codeine
Tricyclic antidepressants (prophylaxis only)
Treatment for cluster headaches
1) 100% oxygen with on-rebreather for 15 minutes
- dont repeat often since this cause them to get worse instead eliminating
2) triptans or ergots
Prophylaxis
1) verapamil
2) Lithium (pretty bad thyroid and renal complications are possible)
3) glucocorticoids
