1. Migraine headache
is characterized by unilateral , throbbing or non throbbing headache , associated with nausea, vomiting ,photophobia and phonophobia .pain increase gradually and persist for hours or days .
Mosby items and derived items © 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc.

2. Pathphysiology
Migraine headache result from inflammation and dilatation of intracranial blood vessels , the underlying cause is not completely understood. Available data suggest that 2 compounds—calcitonin gene –related peptide (CGRP) and serotonin 5-hydroxytryptamin ( 5-HT) are involved. The role of (CBRP) is to promote migraine whereas the role of 5-HT is to suppress migraine.
Mosby items and derived items © 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc.

3. Treatment : Drugs for migraine are employed in 2 ways :
1-To abort an ongoing attack , and
2-To prevent attacks from occurring (prophylaxis )
Abortive therapy:
Drug selection depend on intensity of the attack:
-For mild to moderate symptoms , an aspirin-like drug (e,g asperin , ibuprofen, acetaminophen ) may be sufficient.
-If these are inadequate, aspirin combined with codeine may be tried .
Mosby items and derived items © 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc.

4. . If these analgesic prove insufficient, the second attack should be treated with sumatriptan or an ergot alkaloid ( ergotamine or dihydroergotamine).
If these agents fail to relief pain , an opioid analgesic may be needed.
Mosby items and derived items © 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc.

5. Aspirin-like drugs
Aspirin , acetaminophen , ibuprofen and other can provide adequate relief of mild to moderate migraine attack .
when combined with metoclopramide , aspirin can be effective as sumatriptan , and costs less than sumatriptan and causes fewer side effects . Acetaminophen may be used alone or in combination with other drugs. A popular combination consist of acetaminophen and isomethepten(a sympathomimitic drug) and dichloralphenazone (a sedative ).
Mosby items and derived items © 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc.

6. Metoclopramide
Metoclopramide may be used as an adjunct to other agents for treating an acute migraine attack , this drug suppress nausea and vomiting cased by the attack itself and by the therapy with ergot alkaloid . In addition metoclopamide reverse the gastric stasis caused by the attack, thereby facilitate the absorption of oral medication.
Mosby items and derived items © 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc.

7. Ergot alkaloids :( Ergotamine)
Ergotamine is a drug of choice for stopping an ongoing attack. It is used also for cluster headache.
Mechanism of antimigraine action .
The actions are complex, and precise mechanism by which the drug aborts migraine attack is unknown.
Mosby items and derived items © 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc.

8. Cont. Relief related to vascular effect.
By acting directly to promote vasoconstriction of cranial vessel , and reduce the amplitude of pulsations. In addition, the drug can affect blood flow by depressing the vasomotor center and contribute to reduction of migraine pain.
Mosby items and derived items © 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc.

9. Pharmacokinetics ;
Administration may be oral, sublingual, rectal, or by inhalation. Bioavailability with rectal and inhalation is higher than oral and sublingual. Half life is only 2 hours but effects can still observed for 24 hrs. Metabolized by the liver and excreted in the bile.
Mosby items and derived items © 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc.

10. Adverse effects
Adverse effects: is well tolerated at usual therapeutic dosed. The drug stimulates the chemoreceptor trigger zone to cause nausea and vomiting.
Other side effects includes weakness in the legs myalgia , numbness and tingling in fingers and toes, angina-like pain.
Overdose.
Can cause serious toxicity ( ergotism) :symptoms include the adverse effects seen at therapeutic doses plus sign and symptoms of ischemia caused by constriction of peripheral arteries and arterioles : cold and pale extremities , numb , muscle pain and gangrene may result.
Mosby items and derived items © 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc.

11. ( i.e withdrawal resembles a migraine attack ).
Physical dependence .
Daily use of ergotamine can cause physical dependence. The withdrawal symptom is characterized by headache, nausea, vomiting, and restless
( i.e withdrawal resembles a migraine attack ).
Mosby items and derived items © 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc.

12. Contraindications.
Ergotamine is C.I for patients with hepatic and or renal impairment., coronary artery disease , should not taken during pregnancy , since it can promote uterine contraction .
Should not combined with selective serotonin-receptor agonist because a prolonged vasospastic reaction may occur.
Mosby items and derived items © 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc.

13. Preparations, dosage and administration;
Is available as tablet for sublingual and in aerosol for inhalation .
Ergotamine is dispensed in combination with other drugs for oral and rectal administration
Mosby items and derived items © 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc.

14. .
Dihydroergotamine .
The actions of dihydroergotamine are similar to those of ergotamine , alters transmission at serotonergic , dopaminergic and alpfa-adrenergic
It causes minimal peripheral vasoconstriction , little nausea and vomiting and no physical dependence . However diarrhea is prominent.
Mosby items and derived items © 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc.

15. Pharmacokinetic
May be administered parenterally (SC.IM. IV)or intranasal . Because of extensive first-pass metabolism , it is not active orally.
Elimination is by hepatic metabolism .
Parenteral administration :
Intramuscular and subcutaneous
The initial dose is 1mg. after onset of symptoms . additional 1mg. may be given hourly up to3mg. per attack.
Intravenous : one mg. is given initially , followed by 1mg. in 1hour if needed.
Mosby items and derived items © 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc.

16. Cont. Intranasal administration:
The nasal spray device delivers 0.5mg. per spray . the dosage is 1 spray in each nostril repeated in 15 min. , for a total of 2mg.pain is relieved in 60% of patients.
Mosby items and derived items © 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc.

17. Cont. Therapeutic uses:
parenteral dihydroergotamine is the drug of choice in terminating migraine and cluster headaches. Administration is by injection and nasal spray .
Contraindications;
Are the same as for ergotamine, and should not be administered within 24hrs. of serotonin agonist .
Mosby items and derived items © 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc.

18. Selective serotonin 1-receptor agonists ( Triptans):
Selective serotonin 1-receptor agonists also known as triptans , are first line drugs for terminating a migraine attack . they relief pain by constricting intracranial blood vessels and suppressing the release of inflammatory neuropeptides .
Mosby items and derived items © 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc.

19. Sumatriptan
Is a prototype for the group, can be administered by mouth, nasal inhalation, and subcutaneous
Mech . of action .
Sumitriptan is an analog of 5-HT, cause selective stimulation of 5-HT1.
-Binding to 5-HT1receptor on intracranial blood vessels causes vasoconstriction.
Mosby items and derived items © 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc.

20. Cont.
-Binding to 5-HT1 receptors on sensory nerves of the trigeminal vascular system suppresses release of CGRT, a compound that promote the release of inflammatory neuropeptides and thereby diminishes perivascular inflammation. Both actions –help relieve migraine attack.
Mosby items and derived items © 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc.

21. Therapeutic uses
Is used to abort ongoing attacks. Both headache and associated symptoms are relieved. Beneficial effects begin 15 min. after SC or intranasal admin. And 30 min. after oral administration ..
In addition is approved for cluster headache .
Mosby items and derived items © 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc.

22. Adverse effects Chest symptoms
50% of patients experience heavy arms or chest pressure rather than pain . These symptoms not related to ischemic heart disease. The cause is pulmonary vasoconstriction , esophageal spasm , and bronchoconstriction
Coronary vasospasm .
Sumatriptan cause angina secondary to coronary vasospasm .
Teratogenesis .
Sumatriptan should be avoided in pregnancy, may produce embriolethal effects.
Mosby items and derived items © 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc.

23. Prophylactic therapy;
Beta adrenergic blocking agents.
Not all beta adrenergic blockers are active against migraine , agents that demonstrated efficacy are , propanolol ,atenolol , metoprolol , and timolol. Agents shown to be infective include oxprenolol and pindolol. Because only some beta blockers are effective, whereas all of them block beta adrenergic receptors , it would appear that a mechanism other than beta blockade is responsible for the beneficial effects .
Propanolol : Is the drug of choice for migraine prophylaxis , this agent can reduce the number and intensity of attack in 70% of patients .
Mosby items and derived items © 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc.

24. Cont.treat Tricyclic Antidepressants .
Tricyclic antidepressants can prevent migraine in some patients, the mechanism is unknown. Amitripyline is the most employed.
Calcium Channel blokers ;
These include verapamil, nifedipine , beneficial effects develop slowly ( 1 to 2 months ).
Although all of these drugs can relieve vasospasm , it is not clear that vasodilatation explain explain antimigraine effects. A direct effect on neuron is possible
Mosby items and derived items © 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc.

25. Methysergide
Is an ergot alkaloid, is more effective than propanolol, but is more dangerous , therefore prophylaxis with propanolol is preferred .
The mechanism by which provides prophylaxis is not clear. The drug is able to activate serotonin receptor in the central nervous system.
Side effects
Cause a serious adverse effects , retroperitoneal, pleuropulmonary, and cardiac fibrosis .
Mosby items and derived items © 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc.

26. Cluster headaches
Cluster headaches occur in a series or (cluster) of attacks , each attack lasts 15 min. to 2 hrs. and is characterized by severe , nonthrobbing , unilateral pain located in or around the eye . A cluster consist of one or more such attacks every day for 4 to 12 weeks .An attack-free interval of months to years separate each cluster.
Mosby items and derived items © 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc.

27. Treatment of cluster headch
Methysergide was the drug of choice in preventing attacks , other include calcium channel blocker agents (verapamil ), lithium, and glucocorticoids.
Abortive treatment by sumatriptan or an ergot preparation .
An attack may also terminated by inhalation of 100% oxygen for 10 min. is effective in 90% of patients. The mechanism is unknown.
Mosby items and derived items © 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc.

28. Tension headache.
Is the most common headache. Is characterized by moderate non throbbing pain located in -hat band – distribution around the head, with sense of tightness or pressure in the head and neck.
Treatment :
Mild to moderate intensity can be relieved with acetaminophen or nonsteroidal antiinflammatory drugs ( aspirin, ibuprofen, naproxen ).
An analgesic –sedative combination may be used.
For prophylaxis , amitriptiline is the drug of choice.
Mosby items and derived items © 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc.