17 - Migraines Flashcards
Higher prevalence among ______
females
_____ predisposition to migraines
genetic
List 3 migraine triggers (more on slide 4)
- emotional stress
- smoke
- not eating
Describe a typical migraine headache
- Unilarteral (most often) - but not always on the same side
- Throbbing, pulsating (recall the trigeminal influence on the arteries of the dura
- Attack progressively worsens over hours
- Often N & V (vomiting less common)
- Photophobia/Phonophobia very common (sensitive to light and sounds) - often migraine sufferer will need to rest in dark, quiet room because of this
- Osmophobia and cutaneous allodynia
What are some red flag symptoms?
- Age > 50
- severe and abrupt onset
- worsening over days/weeks
- stiff neck, focal signs, reduced consciousness
- abnormal speech, motor reflex, cognitive impairment
- fever, rash, n,v
- new onset of cancer, lyme disease or HIV
What are some differential diagnoses for migraines?
- Mass/lesion, CVE, meningitis
- Hemorrhage
- Subdural hematoma
- Encephalitis, meningitis
- Metastasis, opportunistic infection, etc.
What is acute drug treatment?
Abortive medications “relievers”
-Taken prn for headache symptom relief (ex. sumatriptan, ibuprofen, ergotamine)
What is preventative drug treatment?
aim to decrease migraine frequency, taken on a regular basis (ex. amitriptyline, topiramate, metoprolol)
When do you consider migraine prophylaxis?
- Frequent and/or long-lasting and/or severely debilitating migraines
- CI to acute therapies
- Failure of acute therapy (either poor efficacy &/or intolerable SEs)
- > 2 attacks per week (risk of MOH) - medication overuse headache
Goals of migraine prophylaxis
reduce attack frequency by > 50% and severity, reduce associated disability, prevent transition from acute > chronic migraine
List 5 NHPs for migraine
- butterbur
- feverfew
- riboflavin
- coenzyme Q10
- magnesium
Butterbur:
Scientific name of butterbur
Petasites hybridius
Butterbur:
Lots of extracts of butterbur have been used, but in migraine the ______ extract has been primarily evaluated
rhizome
Butterbur:
Is butterbur for prevention or treatment of migraines?
prevention
Butterbur:
List a few other things that people use butterbur for
pain, stomach upset, gastric ulcers, headache, etc.
Butterbur:
What is butterbur most possibly effective for?
migraines, allergic rhinitis and somatoform disorders
Butterbur:
Dosage for migraine management of butterbur?
migraine prophylaxis in adults: 50-75 mg BID for 4 months
Butterbur:
Safe?
possibly safe
Butterbur:
Butterbur products should be labeled “PA Free” which means what?
They are free of pyrrolizidine alkaloids, which is a hepatotoxic agent. Repeated use can cause veno-occlusive disease, can be carcinogenic.. effects can be systemic if used on broken skin.
Butterbur:
Can butterbur be used in pregnancy or lactation?
likely unsafe
-may be teratogenic
Butterbur:
Adverse effects ?
GI symptoms, including nausea, flatulence and belching
Butterbur:
Is it deemed effective ?
yes - for migraine prevention
“possibly effective”
Butterbur:
What does turcotte think after reviewing the evidence?
- seems to reduce frequency of migraines when used over a period of 16 weeks in adults
- can reduce frequency, intensity and duration of migraines
Butterbur:
What does it interact with?
CYP 3A4 if it contains the hepatic pyrrolizidine alkaloid and could cause even more hepatotoxicity
Butterbur:
What are potential cross allergies ?
Asteraceaea/ composite family - ragweed, chrysanthemums, marigolds, daisies and other herbs
Butterbur:
Due to potential “PA” contamination, patients with _____ dysfunction may want to avoid butterbur
liver
Butterbur:
MOA of anti-inflammatory action of butterbur ?
might have an effect by inhibiting leukotriene synthesis
Butterbur:
MOA of smooth muscle relaxant/VD effect ?
anti-spasm effects of smooth muscle and vascular wall
Butterbur:
Should we recommend ?
Yes as long as no significant interactions and they are monitoring for adverse effects
Scientific name of CoEnzyme Q10 ?
Mitoquinone Ubidecarenone
CoEnzyme Q10:
Produced _____ in the body and plays multiple vital roles
endogenously
CoEnzyme Q10:
Levels decline with ?
age and chronic illnesses including CV disease, muscular dystrophies, parkinson’s, cancers, diabetes, HIV/AIDS
CoEnzyme Q10:
For prevention or treatment of migraines
prevention
CoEnzyme Q10:
What has been shown to deplete body stores ?
smoking cigarettes
CoEnzyme Q10:
What do people use it for?
migraines, male fertility, neurological disorders, diabetes, Prader-Willi syndrome, CV disease
CoEnzyme Q10:
Dose?
300mg daily split up in 100mg TID
(A dose of 1200 mg/day) showed promise in patients with end-stage renal disease at high cardiac risk.
CoEnzyme Q10:
Safe ?
Likely lmao
CoEnzyme Q10:
What does Canadian headache society say?
strong recommended based on low quality evidence for migraine prophylaxis
CoEnzyme Q10:
What does American headache society say?
Level C recommendation - possibly effective, ineffective or harmful
CoEnzyme Q10:
What does European Federation of Neurological Societies say ?
Level C recommendation - possibly effective, ineffective or harmful
CoEnzyme Q10:
Side effects?
stomach upset, loss of appetite, nausea, vomiting and diarrhea
CoEnzyme Q10:
Effective ?
possibly
CoEnzyme Q10:
Important drug interactions ?
Warfarin, decreases BP, might lower effectiveness of doxorubicin
Statins lower CoQ10 levels
CoEnzyme Q10:
How does it effect BP ?
thought to lower BP (interacts with antihypertensives)
CoEnzyme Q10:
Safe in pregnancy or lactation ?
evidence is lacking
CoEnzyme Q10:
What is the MOA ?
CoQ10 is the cofactor in the electron transport chain and protects against mitochondrial collapse/degradation during respiratory chain - involved in oxygenated ATP production
Low CoQ10 associated with mitochondrial dysfunction in occipital lobes of patients with migraines
Theory is to supplement the CoQ10 deficiency
Feverfew:
Scientific name ?
Tanacetum parthenium
Feverfew:
The leaves of the plant are generally _____ prior to being used medicinally, though fresh leaf extract is also used.
dried
Feverfew:
Prevention or treatment of migraines?
prevention
Feverfew:
What do people use it for?
Oral: fever, headaches, menstrual irregularities, arthritis, psoriasis, allergies
Topical: insecticide and tooth ache reliever
Feverfew:
Standardized to _____ content
Parthenolide
Feverfew:
Standardization of parthenolide in clinical trials ranges from which percentages?
- 2% - 0.35%
* impact of standardization on efficacy is not clear
Feverfew:
Dose ?
5-15 mg PO of feverfew powder once daily
Feverfew:
Describe the making of a feverfew tincture
2.5 fresh leaves with or after food and the tincture can be used in 5-10 drops of 1:5 parts, 25% ethanol tincture
Feverfew:
Need to taper ?
Yes - to avoid withdrawal symptoms
Feverfew:
Been used in combo with ?
white willow or ginger
Feverfew:
Safe ?
Likely safe for short term basis, studies have only been done for 4 months of use
Feverfew:
Should we advise people to chew raw (unprocessed, fresh) feverfew leaves?
No - can lead to adverse effects such as oral inflammation, ulceration, swelling of the lips and sometimes loss of taste
Feverfew:
Why should it be avoided in pregnancy?
Documented adverse effects (emmenagogue - ejection of placenta and fetal membranes)
Includes uterine contraction
Feverfew:
When is feverfew safe ?
safe when used orally and appropriately short-term
Feverfew:
Side effects ?
Fairly well-tolerated
-contact dermatitis, GI upset, potential CNS allergic reaction
Feverfew:
Effective ?
Possibly
Feverfew:
Helps to decrease ____ of headaches
frequency
Feverfew:
Important drug interactions?
NSAIDs, anti-platelets, anti-coagulants, salicylates and any natural products that affect coagulation
Multiple CYP interactions (3A4, 2C9, 2C19)
Feverfew:
Cross allergies ?
similar to chrysanthemums, chamomile, sunflowers and ragweed
Feverfew:
May ____ platelet aggregation and should therefore be avoided in individuals with clotting disorders.
inhibit
Feverfew:
MOA
cox - 2 inhibitor, inhibits myocardial angiogenesis and inhibits platelet aggregation
parthenolide acts as a partial agonist of TRPAI, which can cause migraines.
Feverfew:
Should we recommend ?
No - lots of side effects and drug interactions and efficacy not proven !!
Magnesium:
What contributes to deficiency?
low dietary intake and impaired absorption
Magnesium:
Prevention or treatment
both
Magnesium:
Deficiency can be linked to various health conditions such as ?
osteoporosis, hypertension, atherosclerotic vascular disease cardiomyopathy, diabetes and stroke
Magnesium:
What is it found in?
legumes, whole grains, veggies, seeds & nuts, hard water
Magnesium:
RDA for female adults
310 mg/day
Magnesium:
RDA for male adults
400 mg/day
Magnesium:
Safe?
likely safe
Magnesium:
Effective?
- insufficient reliable evidence to rate
- “possibly effective” is not extremely compelling
Magnesium:
Side effects?
Oral Mg: loose stool and diarrhea, N, V, GI irritation
IV Mg: flushing sensation, local pain and irritation, dizziness, bradycardia and hypotension
Magnesium:
Aside for pentamidine, what are three drugs that can cause MAJOR depletion, often requiring supplementation
ampho B, tacrolimus, PPIs
Magnesium:
Normal serum Mg levels ?
0.65 - 1.05 mmol/L
Magnesium:
Caution in those with ?
reduced kidney function due to an increased risk of hypermagnesemia
Magnesium:
What can hypermagnesemia cause?
can cause heart block
IV formulations are CI in heart block, bleeding disorders (magnesium increases bleeding risk)
Magnesium:
MOA
- magnesium is a co-factor in enzymatic reactions in body involving protein synthesis and carb metabolism
- suggested that magnesium plays a central role in establishing a threshold for migraine attacks
Magnesium:
Do we recommend it?
Nah - not effective
Riboflavin:
What is it?
water-soluble B vitamin known as vitamin B2
Riboflavin:
Used for prevention or treatment?
prevention
Riboflavin:
What is it found in?
liver, kidneys, dairy products, green vegetables, eggs, whole grain cereals, yeast and shrooms
Riboflavin:
dosage for migraine prophylaxis?
400mg/day for up to 3 months
Riboflavin:
What are 2 PK/PD properties of riboflavin in the body that are thought to limit any potential toxicity include ?
1) limited absorption into the blood stream due to increased GI motility (only 27mg of the 400mg dose would be maximally absorbed)
2) excretion in the urine
Riboflavin:
safe?
likely
Riboflavin:
In the US, it is labelled as GRAS , which stands for ?
generally recognized as safe
Riboflavin:
Can change _____ color
urine
bright yellow orange
Riboflavin:
Adverse effects
- weight gain
- dizziness
- GI discomfort
Riboflavin:
effective ?
possibly effective
Riboflavin:
drug interactions?
if you are on oral contraceptives, it will decrease concentrations of riboflavin
