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MIGRAINE
BY
PROF, AZZA EL-MEDANY
MIGRAINE
Recurrent attacks of headache.Unilateral, associated with migraine aura ( anorexia, nausea, vomiting, visual or auditory disturbances ).Common in young female.Pulsating or throbbing in character.Sustain for more than 2 hours.Affect about 10-20% of population
RISK FACTORS
PHYSICAL
Fatigue, Fasting ,Exercise
PSYCHOLOGICAL
Stress , Anxiety , Depression
DISEASES
Hypertension ,Fever
CONTINUE
HORMONAL
Menstruation, Menopause ,Oral contraceptive pills.
DIET
Cheese , Chocolate ,Alcohol
CLIMATIC FACTORS
Temperature changes
VASCULAR THEORY
PHASE ( 1) :: V.C. of intra& extracranial b.v. may be due to release of 5HT from platelet or mast cells.
Migraine aura occurs in this phase.PHASE (2): V.D. of intra & extracranial b.v. may be due to release of neurotransmitters as substance P ,or neurokinins.PHASE (3) : Inflammatory reactions due to liberation of inflammatory mediators
Cassification Of MigraineMild
Moderate
Severe
(Cont.)
MILD
One attack /month
Normal daily activities continue.
MODERATE
One or two attacks / month
Normal daily activities may or not continue.
CONTINUE
SEVERE
More than 3 attacks / month
Normal activities cannot continue.
Patients treated with both acute & prophylactic medications.
Drugs used in acute attack
NSAIDS
ANTIEMETICS
ERGOT ALKALOIDS
TRIPTAN CLASS
NSAID,s
Inhibits prostaglandins synthesis centrally.
Antiemetic drugs are usually added to increase their absorption.
No withdrawal symptoms on sudden withdrawal.
Main adverse effects Gastric Upset.
ANTIEMETICS
e.g. Metoclopramide , DomperidoneThey are dopamine receptors antagonist.
Given at the onset of the attack as adjunctive therapy to reduce gastric symptoms ( N.& V.).
To improve oral absorption of analgesics
ERGOT ALKALOIDS
Ergotamine
Dihydroergotamine
They act as partial agonists ( Agonist & Antagonist) at adrenergic , dopaminergic & serotonergic (5-HT1B/1D)receptors.
N.B.
Patients advised to take ergot preparations at the earliest sign of a migrain attack for the maximal benefit.
Their main pharmacological effect is V.C. either centrally or peripherally.
PHRMACOKINETICS
Ergotamine can be given by all routes.Orally undergoes extensive 1st pass metabolism.Sublingual has a bioavailability less than 1%Rectal route best method of absorption Nasal sprayI.M. , SC, I.V.
CONTINUE
Usually given in combination with caffeine to facilitate its absorption.Long acting drug Cumulative drug.High tissue binding90% of metabolites are excreted in the bileIts effect persist up to 24 hours.
CLINICAL USES
Acute attack of migraine ( Moderate & Severe ).
ADVERSE EFFECTS
Nausea , vomiting( direct effect on CNS emetic centre), diarrhea, abdominal pain.
Coldness, numbness of fingers & toes.
Prolonged use causes paresthesias , gangrene .
Coronary vasospasm .
Rebound headache ( V.D after V.C)
CNS (hallucination)
CONTRAINDICATIONS
Pregnancy
Peripheral & coronary vascular diseases.
Hypertension
Impaired hepatic or renal diseases
CONTINUE
In concurrent use with :
TRIPTANS
β- BLOCKERS
In prophylaxis of migraine
TRIPTAN CLASS
Triptans have selective agonist activity at 5-HT1D &1B subtype receptors.
Unlike ergotamine , triptans are effective when given 4 hours or longer after the onset of the attack.
They are more expensive than ergot.
MECHANISM OF ACTION
Reducing the excitability of neurons in the trigeminovascular system via stimulation of brain stem 5-HT1B/1D receptors.
Attenuating the release of neuropeptides with inflammatory & vasodilating effect as substance P via 5-HT1D receptors.
Continue
Vasoconstriction of cerebral & extracerebral vessels by stimulation of vascular 5HT1B receptors.
N.B.
Coronary artery contains 5-HT1B
receptors so they cause coronary vasoconstriction.
SUMATRIPTAN
Selective agonist at 5-HT1D&1B receptors.
PHRMACOKINETICS
Orally undergoes 1st pass hepatic metabolism.( bioavailability 14-17%S.C ( rapid absorption, peak in 12 min). Bioavailability 97%.I.V. Not given ( risky ).Nasal sprayHALF-life 2 hrs.
ZOLMITRIPTAN
Oral bioavailability (40%) .
Metabolized in liver to active metabolites which have a higher affinity to 5HT1B & 1D receptors than the parent drug.
Half- life for both 2-3hrs.
Plasma protein binding 14%.
NARATRIPTAN
Oral bioavailability 70%.
Half-life 6 hrs ( longest).
50% excreted unchanged in urine.
Plasma protein binding 30%.
CLINICAL USES
Acute attack of migraine ( moderate & severe ).
Acute cluster headache.
ADVERSE EFFECTS
Mild pain & burning sensation at the site of injection.Paresthesia, warmth, heaviness in head or other parts of the body.DizzinessHypertensionCoronary artery vasospasm (anginal pain), MI, Ventricular arrhythmias.Bitter taste ( nasal spray)
CONTRAINDICATIONS
Coronary vascular disease. Ischemic heart disease . HypertensionConcurrent use with ergotamine Concurrent use with β- blockers.
Naratriptan is contraindicated in patients with severe renal or hepatic impairment.
PROPHYLAXIS OF MIGRAINE
INDICATIONS
Two or more attacks / month
Acute symptomatic treatment is required more than 2-3 times/ week.
Drugs used in acute attack are ineffective, intolerable or contraindicated.
CONTINUE
Headache is severe and associated with neurological symptoms.Drugs used in prophylactic treatment need several weeks to manifest their effects.Treatment should continue for 6 months & can be repeated after a rest period .
DRUGS USED IN PROPHYLAXIS
Methysergide
Cyproheptadine & Pizotifen
β- blockers
Calcium channel blockers
Antidepressant drugs
Ondansetron
METHYSERGID
5HT2A&C receptor antagonist .Anti-inflammatory effect.Mild V.C. effect.Given orally.Used only for prophylaxis treatment.Not used for more than 6 months , repeated after a holiday of one month.
SIDE EFFECTS
Retroperitoneal , pericardial , pleural or valvular fibrosis ( mainly after prolonged use).
Nausea,Vomiting, Diarrhea.
Peripheral edema.
CNS manifestations
CONTRAINDICATIONS
With β- blockers.
With ergot alkaloids.
Valvular diseases
Pregnancy
CYPROHEPTADINE & PIZOTIFEN
Antiserotonergic ( 5HT2A) receptors.
Antihistaminic ( H1) receptors.
Anticholinergic
SIDE EFFECTS
Vertigo, Drowsiness
Increase body weight.
ONDANSETRON
5-HT3 antagonist.
Effective for prophylaxis of migraine.
Effective in the treatment of chemotherapy induced nausea.
β- BLOCKERS
Act through β- blocking effect on intra or extracranial blood vessels.
Antiserotonergic effect.
CONTRAINDICATIONS
Old age
Bronchial asthma
A-V block
CHF
ANTIDEPRESSANTS
TCA & SSRIs prevent the release of 5HT from brain mast cells.
Prevent V.C. which trigger 1st phase.
CALCIUM CHANNEL BLOCKERS
Decrease severity & frequency of migraine through blocking the influx of calcium.
Recommended