Headache

Classification: Prevalence of migraine and tension headaches is 3 times higher in females than males; cluster headaches are 4-10 times more prevalent in males.

Migraines and cluster headaches are referred to as vascular headaches while tension headaches are known as muscle-contraction headaches.

• Classical migraine: Preceded by prodromal aura. Pain is throbbing or dull ache, frontotemporal, usually one-sided, and accompanied by nasusea and vomiting. Digital-lingual syndrome ipsilateral to headache. Duration is hrs to 1-2 days.

• Common migraine: No aura.

• Cluster headaches: Horton’s syndrome. Constant, unilateral orbital (sometimes temporal) pain with onset 2-3 hrs after falling asleep (REM sleep). Very intense and steady pain with autonomic symptoms. Most severe type of headache. Duration of 1-2 hrs recurring nightly for several weeks or mos. Episodic is 2 attacks per day for 4-12 wks with remissions of months or years. Chronic is attacks occurring for a year or longer and diminished periods of remission. Associated with heritable factors and lifestyle (smoking and drinking).

• Tension headaches: Common everyday headache responding to NSAIDs or chronic recurrent or long-duration headache not responsive to NSAIDs. Pain is usually bilateral, often diffuse and may consist of various sensations. Chronic tension headache is often associated with depression and anxiety.

Mechanisms: Pain sensitive structures in head. Anterior pain is mediated by CN5, while posterior pain is mediated by CN9, 10, and C1-C3. Serotonin is definitely involved in migraine, tension, and cluster headaches. Noxious event causes vasoconstriction and then vasodilation.

Acute drugs – vasoconstrictors used for migraines and clusters

• Ergotamine tartate & dihydroergotamine – Most effective treatment; oral, IV, sublingual, rectal; to avoid rebound 48 hrs should elapse between doses; DHE used IV for emergency termination.

MOA: Agonist activity at 5-HT1B and 5-HT1D; marked vasoconstrictor effects at aa. and vv.

Pharmacokinetics: Caffeine increases absorption; high first-pass effect; low oral bioavailability

Side effects: Nausea and vomiting (controlled by metaclopramide or phenothiazine); can cause severe vasoconstriction of extremeties (gangrene); dependency

Contraindications: Pregnancy, peptic ulcer disease, hepatic or renal disease, CVD.

• Sumatriptan – 5HT1 agonist; used in treatment of acute migraine; fewer side effects than ergots; rebound headache may be more likely than with ergots.

MOA: Selective for 5HT-1 receptors (most potent at 1B and 1D). Results in vasoconstriction and inhibition of release of proinflammatory molecules.

Side effects: Coronary vasospasm when given IV; DO NOT use concurrently with ergots.

Contraindications: Angina, MI, severe hypertension.

• Isometheptene – Sympathomimetic vasoconstrictor used in combination with acetominophen and dichloralphenazone for oral administration.

Acute drugs – analgesics used for acute migraines, clusters, and tension headaches

• NSAIDS

• Opioids

Prophylactic drugs

• Methysergide – Migraines and cluster prophylaxis

MOA: Ergot alkaloid that is a mixed agonist/antagonist. Prophylactic actions presumed due to 5-HT1 antagonist activity, which causes vasodilation and prevention of noxious event.

Side effects: Fibrosis

Contraindications: Same as ergots

• Propanolol – Preferred agent for migraine prophylaxis; agents with sympathomimetic activity (pindolol, acebutolol) are NOT effective. Inhibition of prostaglandin synthesis.

• Ca2+ channel blockers – Migraine prophylaxis; 6-8 wks for therapeutic effect.

• alpha 2 Adenoreceptor agonists – Migraine prophylaxis in Europe (clonidine & gunabenz).

• NSAIDs – Migraine and cluster prophylaxis; inhibition of prostaglandin synthesis.

• Sedatives & antianxiety agents – Prophylaxis of tension headaches (diazepam)

• Antidepressants – Prophylaxis of migraine and tension headaches (DOC). Mostly TCAs (amitriptyline).

• Cyproheptadine – Migraine prophylaxis. Antihistamine, antiserotonin. Useful in children.

• Lithium – DOC for prophylaxis of clusters.

• Corticosteroids – Useful for cluster headaches. Short course helpful in termination and preventing chronic episodes.

• Other treatments – Oxygen therapy, dietary and lifestyle changes, menstrual cycle (associated with migraines but not clusters).

Category: Pharmacology Notes