Transcript Cluster headaches

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 .
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Slide 1
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 ( 5HT) are involved. The role of (CBRP) is to promote
migraine whereas the role of 5-HT is to suppress
migraine.
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Slide 2
Treatment :
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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 .
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Slide 3
• . 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.
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Slide 4
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 ).
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Slide 5
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.
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Slide 6
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.
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Slide 7
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.
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Slide 8
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.
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Slide 9
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.
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Slide 10
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 ).
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Slide 11
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.
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Slide 12
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
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Slide 13
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Dihydroergotamine
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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.
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Slide 14
Pharmacokinetic
• May be administered parenterally (SC.IM. IV)or
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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.
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Slide 15
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.
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Slide 16
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 .
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Slide 17
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 .
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Slide 18
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.
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Slide 19
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.
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Slide 20
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
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Slide 21
Adverse effects
• Chest symptoms
• 50% of patients experience heavy arms or chest
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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.
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Slide 22
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 .
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Slide 23
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
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Slide 24
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 .
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Slide 25
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.
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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.
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Slide 27
Tension headache.
• Is the most common headache. Is characterized
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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.
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Slide 28