Migraine can usually be distinguished clinically from the two other common types of headaches—cluster headache and tension-type headache—by its characteristics

Types of migraineTypes of migraine

There are two main types

1.1.Common migraine Common migraine Migraine without aura Approximately 85 percent of patients a severe, unilateral, pulsating headache typically lasts from 2 to 72 hours. often aggravated by physical activity accompanied by nausea, vomiting,

photophobia (hypersensitivity to light), and phonophobia (hypersensitivity to sound).

2. Migraine with aura (classic migraine)

preceded by neurologic symptoms called auras, which can be visual, sensory, and/or cause speech or motor disturbances.

these prodromal symptoms are visual, occurring approximately 20 to 40 minutes before headache pain begins.

In the 15 percent of migraine patients whose headache is preceded by an aura, the aura itself allows diagnosis.

The headache itself in migraines with or without auras is similar.

For both types of migraines, women are three-fold more likely than men to experience either type of migraine.

Symptomatic treatment of acute migraine

Acute treatments can be classified as A.Nonspecific treatment includes:

Analgesics, such as nonsteroidal anti-inflammatory drugs

Antiemetics, such as prochlorperazine, to control vomiting.

Opioids are reserved as rescue medication when other treatments of a severe migraine attack are not successful.

B.Specific migraine therapy includes: Triptans Dihydroergotamine

both are 5-HT1D receptor agonists. It has been proposed that activation of 5-

HT1D receptors by these agents leads either to vasoconstriction or to inhibition of the release of proinflammatory neuropeptides.

Despite their high cost, most patients prefer triptans triptans over ergot derivatives.

Triptans:Triptans:

sumatriptansumatriptan rizatriptanrizatriptan eletriptaneletriptan zolmitriptanzolmitriptan almotriptanalmotriptan frovatriptanfrovatriptan naratriptannaratriptan

Dihydroergotamine:

a derivative of ergotamine administered intravenously has an efficacy similar to that of

sumatriptan nausea is a common adverse effect.

Prophylaxis of migraine headacheProphylaxis of migraine headache Therapy to prevent migraine is indicated if:

the attacks occur two or more times a month

if the headaches are severe or complicated by serious neurologic signs.

Propranolol is the drug of choice, but other β-blockers, particularly nadolol, have been shown to be effective.

Structure Ergots include a wide variety

of compounds sharing the tetracyclic ergoline nucleus that are produced by the fungus Claviceps purpurea.

These agents have a strong structural similarity to the neurotransmitters norepinephrine, dopamine, and serotonin.

Amine ergot alkaloids include: ergonovine methysergide lysergic acid (LSD) methylergonovine

Peptide ergot alkaloids include ergotamine [Ergomar] dihydroergotamine

[Migranol] ergocristine bromocriptine [Parlodel] pergolide [Permax]

Mechanism of action

Ergots display varying degrees of agonist or antagonist activity in three receptor types:

1. α-adrenoceptors2. dopamine receptors3. serotonin receptors

The pharmacologic application of ergots is determined by the relative affinity and efficacy of the individual agents for these receptor systems.

Many agents exhibit partial agonist activities and thus can cause either stimulatory or inhibitory effects.

Pharmacologic properties

Administration: parenterally, rectally, sublingually, as inhalants, or orally and

vary widely in their absorption. Amine alkaloids are slowly and

relatively poorly absorbed; Peptide alkaloids are completely

absorbed.

Ergots are extensively metabolized to compounds of varying activity and half-life.

Therapeutic uses

Postpartum hemorrhage Ergonovine [Ergotrate] methylergonovine [Methergine] the most uterine-selective agents,

cause prolonged and forceful contraction of uterine smooth muscle.

Uterine sensitivity varies with hormonal status; the uterus at term is most sensitive.

Migraine

Ergotamine is most effective if administered in the early stages of attack to reverse rebound vasodilation.

Ergotamine is frequently combined with caffeine, which probably increases absorption.

Ergotamine produces long-lasting and cumulative effects; weekly dosage must be strictly limited.

2. Methysergide [Sansert] is used for prophylaxis of migraine. Methysergide acts as a serotonin-receptor (5-HT2A,C) antagonist,

and it inhibits initial vasoconstriction in the early stages of a migraine.

Methysergide is effective in 60% of patients for the prophylaxis of migraine

it is ineffective after the onset of an attack.

The cumulative toxicity of methysergide requires drug-free periods of 3—4 weeks every 6 months.

Hyperprolactinemia

Bromocriptine mesylate [ParlodelPergolide [Permax]dopaminergic agonists, cause specific inhibition of prolactin secretion (elevated prolactin secretion can induce infertility and amenorrhea (abnormal absence or

suppression of menstruation) in women and galactorrhea (a spontaneous flow of milk) in men and women).

These agents are used to treat prolactin-secreting tumors of the pituitary, to counteract central dopaminergic antagonists, and to suppress normal lactation.

Bromocriptine mesylate and pergolide are used as adjuncts to agents such as levodopa in the management of Parkinson's disease (not a prolactin-lowering effect).

These agents reduce growth hormone secretion.

Diagnosis of variant angina

Ergonovine produces a diagnostic vasoconstriction of coronary arteries that are prone to vasospasm, as in variant angina.

Ergonovine is administered intravenously (IV) during angiography.

Adverse effects The most serious adverse effect is prolonged

vasospasm; this can lead to gangrene and is most frequently caused by ergotamine and ergonovine.

The most common side effect is gastrointestinal disturbance.

Methysergide toxicity includes retroperitoneal fibroplasia coronary and endocardial fibrosis CNS stimulation and hallucinations.

DrugReceptorTarget Tissueand ResponseTherapeutic UsesToxicity

Ergonovineα-Adrenoceptor agonist

Uterine smooth muscle contraction

Postpartum hemorrhage

Hypertension, nausea

Ergotamineα-Adrenoceptor agonist, 5-HT receptor agonist

Vascular smooth muscle; vasoconstriction

Acute migraine attacks

Nausea, diarrhea

Methysergide5-HT receptor antagonist

Vascular smooth muscle;prevent initial vasoconstriction

Migraine prophylaxis

Fibroblastic changes

Bromocriptine, pergolide

Dopamine agonists

Breast, uterus, pituitary; suppress lactation and decrease growth hormone levels

Hyperprolactine-mia, amenorrhea, acromegaly

Dose-related effects, ranging from nausea to parkinsonian-like symptoms

Kinins

Biosynthesis Kinins are found in the circulation and

tissues as kininogens of high molecular weight or low molecular weight (about 80% of total kininogens).

Specific serine proteases called kallikreins convert kininogens to the active kinins.

Kallikreins are activated by Hageman factor, trypsin, and kinins.

The major kinins are a group of related peptides with potent actions as vasodilators.Bradykinin has the following amino acid sequence: Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg.

Lysyl-bradykinin (kallidin) has additional lysine residue on the N-terminus of bradykinin.

Therapeutic uses Aprotinin [Trasylol] Aprotinin [Trasylol] inhibits kallikreins and thus the

formation of kinins it also inhibits other proteases,

including plasmin.

Aprotinin is approved for use during cardiac bypass surgery on the basis of its anticoagulation properties that reduce the amount of blood needed for transfusion during extracorporeal procedures, and in surgery in which the patient is at high risk for excessive bleeding.