Avery L. Spunt, R.Ph., M.Ed.
Spring 1998
Headaches: Considerations in Drug Treatment
Avery L. Spunt, R.Ph., M.Ed.
Spring 1998
Headaches: Considerations in
Drug Treatment
Learning Objectives:
1. Describe the clinical presentation of the various types of headaches.
2. Explain the pathophysiology of each type of headache.
3. Differentiate between the clinical presentation of a patient with tension headache, vascular headache of migraine type, non-migraine vascular, and cluster.
4. Explain the mechanism of action, administration, side effects, adverse effects, and toxicities of the various therapeutic agents used in the treatment of headaches.
5. Formulate and monitor a rational treatment plan for patients with tension, vascular of the migraine type, and cluster.
6. Explain the pharmacist=s role in the identification and management of headache patients.
I. DIAGNOSIS AND CLINICAL FINDINGS
A. Medical and Neuro Exam
B. History
- Baseline Description
- Quality ( constricting, dull, aching, boring, burning, pulsating, steady shape, intermittent )
- Duration ( time, cyclic)
- Intensity
- Location
- What factors produce H.A.
- What makes it worse
- What makes it better ( previous therapies)
II. Migraine a familial disorder characterized by recurrent attacks of headache widely variable in intensity, frequency, and duration. Attacks unilateral and usually associated with anorexia, nausea, and vomiting. In some cases preceded by, or associated with, neurological and mood disturbances.
OR
A paroxysmal neurological disorder with the most prominent feature being a unilateral headache.
III. THE MIGRAINE ATTACK
(Refer:http://www.achenet.org/headdef2.htm)
A. Prodrome may occur hours to days before the headache
1. Psychological
- Depression
- Irritability
- Drowsiness
- Euphoria
- Restlessness
2. Neurological
3. Systemic
B. Aura: ( classic migraine ) transient neurological deficit
1. Scotomas
2. Numbness
3. Dysphagia
4. Aphasia
5. Paresthesia
C. Headache phase unilateral, throbbing, increasing escalation of pain form mild to severe
1. G.I. Disturbance N & V
2. Photophobia
3. Phonophobia
4. Impaired concentration and memory
IV. POTENTIAL TRIGGERS OF MIGRAINE
(Refer:http://www.achenet.org/pretre.htm)
A. Nonpharmacologic strategies
1. Avoid triggering factors
2. Stress management
B. Symptomatic therapy
1. Analgesics
2. Antiemetic
3. Sedatives
C. Abortive therapy
(Refer:http://www.ama-assn.org/special/migraine/treatment/drug.htm)
1. Ergot preparations
a. Serotonin antagonist, vasoconstriction, decrease neurogenic inflammation
b. Efficacy 50-90 % , failures usually due to poor absorption
c. Efficacy varies with route:
IM>rectal>inhaled>sublingual>oral
d. Effects on arterial bed last for > 24 hrs.
e. Adverse effects: nausea, vomiting, diarrhea, cramping, transient paresthesia, stroke, hypertensin, myocardial infarct/ischemia, peripheral vasospasm, gangrene, tachycardia, bradycardia, rebound headache, ergotism.
f. Contraindications: A complicated migraine@ , PVD, Raynaud=s, renal or liver disease, pregnancy, active sepsis, thyrotoxicosis, uncontrolled hypertension.
g. New product
Dihydro ergotamine(RDHE) Nasal spray Migranal Novartis
2. Isometheptene mucate
a. Alpha-adrenergic agonist
b. Use in patients refractory to above agents
c. Dose administration
Available as combination product ( Midrin) 65 mg isometheptene, 100 mg dichloralphenazone and 325 mg APAP. Dose is 2 capsules at onset, then 1 capsule Q1h until relief or 5 caps/12 hr.
3. NSAID=s
4. Sumariptan ( Imitrex) injection
indicated for the acute treatment of migraine attacks with or without aura. Sumatriptan should bot b administered to patients with basilar or hemiplegic migraine
a. Begins to relieve pain within 10 minutes
b. Highly effective - any time during the attack
c. Treats the total symptom complex: pain nausea, vomiting, and light and sound sensitivity
d. Nonsedating
e. Restores patients= ability to work
f. 6 mag sub q injection
g. Adverse events
h. For migraine attacks that require accelerated relief or that are accompanied by vomiting/nausea.
5. Sumatriptan ( Imitrex) tablets
a. Effective taken early or late in attack .Early administration is recommended
b. For the migraine patients who prefer oral medications and can benefit from the efficacy, ease , and convenience of a tablet dosage form
c. Available in blister packs ( of 9) 25 or 50 mg tablets
d. Dosing
The recommended dose is a single 25mg tablet taken whole; maximum single dose recommended is 100 mg.
If patient needs a greater degree of relief at 2 hours: A second dose of up to 100 mg may be used.
If headache returns after initial relief: Use additional doses ... at least 2 hours between doses
300mg maximum 24-hour dosage.
If any given migraine attack is first treated with Imitrex (Sumatriptan succinate) Injection
Single doses up to 100mg of Imitrex Tablets may be given if headache returns
At least 2 hours between tablet doses ... maximum 200 mg of tablets in 24 hours.
6. Sumatriptan (Imitrex) Nasal Spray
a. Faster onset than tablets-more effective
b. Onset of action 15 minutes
c. Nasal Spray available in two strengths 5mg and 20mg
d. No more than 40 mg in 24 hours
e. May cause bad taste or nausea
f. Unit of use- Do not Aprime@ spray
7. Future Drugs
a. Naratriptan (AmergeR, Glaxo)
b. Rizatriptan (MaxaltR, Merk)
c. Zolmitriptan(Zomig, Zeneca)
These are similar to sumatriptan . They may prove to last longer and prevent the headache from Acoming back@.
D. Migraine Prophylaxis
1. Nonsteroidal anti-inflammatory agents
a. Very effective for migraine associated with menses
b. Dose and administration
Naproxen base -----500-1250 mg/day
Naproxen Na -------550-1325 mg/day
Ibuprofen -----------1200-1600 mg/day THATCHED
Indomethacin --------75-200 mg/day T.I.D.
Ketoprofen ----------100-225 mg/day/BID,TID
c.Adverse effects
2. Beta adrenergic blockers
a. Prevent arterial dilation, serotonin antagonist, inhibit catecholamines
b. First line therapy, efficacy 55-80 %
c. Will not alleviate migraine prodrome
d. Continued improvement may occur during therapy
e. Dose and administration, **individual titration
Propranolol -------80-320 mg/day
Nadolol -----------40-160 mg/day
Atenolol------------50-100 mg/day
Timolol ------------20-40 mg/day
Metoprolol --------100-200 mg/day
f. Adverse affects: fatigue, diarrhea, abdominal pain, nausea, nightmares, insomnia, hypotension, cold extremities, decreased libido
g. Contraindications: asthma, COPD, CHF, PVD, diabetes, heart block
3. Calcium channel blockers
a. Inhibits platelet aggregation, serotonin release and uptake, vasoconstriction during prodrome
b. Useful in complicated and classic migraine
c. Efficacy 46%
Prodrome relief may take 10-14 days
Reduction in frequency may take 2-4 weeks
d. Dose and administration
Verapamil ---------240-480 mg/day**
Nifedipine ---------30 - 60 mg/day*
Diltiazem ----------90-360 mg/day*
Nimodipine --------60-120 mg/day BID to QID
*T.I.D. to QID unless sustained release form, then QD to BID
e. Adverse effects:
Verapamil, diltiazem - constipation, edema, rash, hypotension, conduction abnormalities, lightheadedness
Nifedipine - edema, flushing, lightheadedness, headache, fatigue, tachycardia
Nimodipine - muscle pain, menstrual cramping, nausea, abdominal discomfort, irritability, fatigue
f. Contraindications: CHF, hypotension, sick sinus syndrome, second or third degree AV block
4. Tricyclic antidepressants
a. Inhibit serotonin reuptake
b. Efficacy 50-60 %, onset of effect takes 10-14 days
c. Dose administration: amitriptyline - titrate up to 100-200 mg hs doxepin 25-100 mg/day
d. Adverse effects: anticholinergic effects, sedation, orthostatic hypotension
e. Contraindications: urinary retention, narrow angle glaucoma, cardiac conduction disturbances
5. Methylsergide
a. Central serotonin agonist, inhibits serotonin release from platelet
b. Efficacy 60-75%
c. Dose and administration: 2 mg/day increased in 2 mg increments over 3-4 days until reach 4-8mg/day in divided doses (BID)
d. Unlikely to see effect if none in 3 weeks
e. Need drug holiday every 4-6 months
f. Adverse effects: nausea, vomiting, ataxia, paresthesias, edema, weight gain, hair loss, fibroproliferative changes
g. Contraindications: similar to ergotamine
6. Cyproheptadine
a. Serotonin antagonist
b. 4-16mg/day T.I.D. to QID
c. Sedation and weight gain
7. Non Specific Agentsl
Phenytoin, valproic acid, fluoxetine
Pharmacist's Work Up of Headache Therapy
(This is not a complete assessment of a headache patient but a guide to use when evaluating therapy.)
Family History
Patients with common and/or classic migraine will have a positive family history in 60-90% of cases.
Gender
Cluster headaches are more likely to occur in males than females; a 6:1 ratio, whereas migraine is more likely to occur in females.
Diagnosis
Concurrent disease states can have an important effect on drug selection. Asthma patients and/or aspirin sensitive individuals may not tolerate NSAIDs, pregnant females should not receive ergotamine or sumatriptan preparations, beta-blockers may also be contraindicated in asthmatics.
Medication
A thorough, complete medication history is essential to determining therapy. Both OTC and RX preparations need to be reviewed in addition to the impact of foods eg: caffeine, chocolate. It is also important to assess the patient for drug-seeking behavior since many of the combination preparations use codeine. In addition, certain medications may exacerbate/induce headaches eg: OCP, nitrates, vasodilators, reserpine, nifedipine.
Allergies
Cross sensitivity among NSAIDs and aspirin has been reported.
Smoking/Alcohol History
Smoking is often a trigger for migraine development.
Alcohol may alter hepatic metabolism which may alter therapy with agents such as calcium channel blockers, propranolol, etc.
Compliance
-Patient
Lack of compliance with regimen may cause headaches to occur more frequently or cause severe adverse effects.
-Drug Delivery System
Patient must be well instructed in the use of sumatriptan injection, ergotamine inhalers, suppositories and/or sublingual tablets to acheive full benefit from therapy.
System Functions
-Vital Signs
Heart rate, blood pressure and respiration, may all be altered with some of the prophylactic therapies used. Additionally, ergotamine preparations may cause tachycardia/bradycardia. Sumatriptan may increase blood pressure.
-Renal
Doses of NSAIDs may need to be altered in renal-insufficiency. Choice of therapy may be altered if the patient receives dialysis.
Prolonged use of methylsergide may cause fibrosis, blocking the ureters and causing hydronephrosis.
-Cardiovascular
Hypertensive patients may benefit from the use of calcium channel or beta block therapy for migraine prophylaxis.
Patients with a history of MI. TIA and/or stroke should not receive sumatriptan or ergotamine therapy due to its vasoconstrictive properties.
-Pulmonary
Asthmatic patients max. receive calcium channel blockers or amitriptyline as prophylactic therapy.
-GI
Many of the analgesic agents may cause nause/vomiting which needs to be distinguished from the occurence of migraine symptoms. In addition, codeine and/or verapamil may also cause constipation.
-Muscular-Skeletal
Prolonged therapy with methylsergide has also caused parasthesias and leg cramps. Ergotamine preparations may also cause peripheral vasoconstriction if large doses are use.
-Neuro-Mental
-Skin
-EENT
Patient Case: Migraine Headache
MH is a 25 year old 65 kg white female who c/o a severe, right-sided throbbing headache for the past eight hours. The episode started with blind spots in both eyes, flashing lights, photophobia, nausea, vomiting, and a tingling feeling in the fingers of her left hand. These symptoms gradually subsided as the headache started, although the nausea and vomiting persist. The patient took two extra-strength Tylenol tablets without any relief. She has had only two previous headaches similar to this one, both with in the past three weeks. These headaches responded to extra-strength Tylenol and were shorter than the current episode.
PMH: Asthma x 6 years (1-2 attacks/year), no known allergies.
Meds: Albuterol Inhaler 1-2 puffs prn wheezing; Extra-strength Tylenol 2 tabs q4h x 2 doses; Ortho-Novum 1/50 1 qd x 1 year
FH: Mother with migraines
SH: Married x 1 mo, started new job as cashier 1 wk ago
PE: WDWN/WF in moderate pain, otherwise unremarkable
Neuro: Mild photophobia, otherwise unremarkable
Case (Questions and Answers)
1. What are the signs, symptoms, patient factors, and trigger factors that are suggestive of classic migraine in this patient?
This patient's history and symptomatology are characteristic of classic migraine. First, it is biphasic in nature. The aura phase consists of neurologic symptoms (scintillating scotomata, photophobia, and left hand paresthesias). These symptoms resolved as the headache phase began.
Note: The absence of neurologic deficits on physical confirms the patient's history (she only manifests residual photophobia, without any motor, sensory, or reflex abnormalities) and also speaks against focal CNS lesions that may be secondary causes of headache, such as tumor or hemrrhage. If the transient neurological symptoms persisted through the headache phase, then the headache would be considered a "complicated" migraine.
Secondly, the patient's history provides other information consistent with migraine: recurrence of the headache, young age, female, family history, and unilateral headache.
Note: Migraine headaches usually involve either side of the head, not always the same side. Headaches which always involve only one side are a typical for migraines and suggestive of a secondary cause for the headaches.
Possible trigger factors for the migraines are the use of ora contraceptives, and stress from recently marrying and starting a new job.
2. How would you treat this patient's migraine headache? Specify drug(s) dose, route, and side effects to monitor.
Acute management should be aimed at relieving the nausea and vomiting as well as the headache. A factor to take into consideration is the need for a non-oral route of administration.
Regimen A.
Sumatriptan 6 mg sub Q if headache return repeat dose no sooner than 2 hours after first dose.
Regimen B
Ibuprofen 600 mg po q4-6h prn or Naproxen Na 825 mg po then 275-550 mg q30-60 min up to 1375mg/d (more likely to be successful after nausea/vomiting have been relieved).
3. What would you recommend for the long-term management of migraine in this patient?
For chronic management, several issues need to be considered:
a) Are there any trigger or exacerbating factors which can be eliminated or reduced?
Of this patient's trigger factors, the easiest one to eliminate would be the birth control pills. Alternative contraceptive methods should be discussed with the patient.
b) Does the patient require prophylactic therapy due to the frequency or severity of the attacks?
Although she has had more than two attacks in a month period, it may be too early to have established the pattern of her migraines, since she has had them for only a month and they may be partly dependent on certain trigger factors,whose effect may diminish with time. Long-term prophylactic therapy may be withheld for 1-2 months or until a more definite headache pattern is observed. In the meantime, the patient may use obortive agents to treat any headaches acutely.
 Previous |
 Next |
 Syllabus |
| The College of Pharmacy | UICPHARM@uic.edu | |
| The University of Illinois at Chicago | Last modified: Dec 31, 1997 | |