ابو فيصل99
27/08/03, 09 :55 09:55:38 PM
Introduction and Epidemiology
Introduction
Migraine is a recurrent headache of moderate to severe intensity that is associated with gastrointestinal, neurologic, and autonomic symptoms.[1] Medications used for the prophylaxis and the treatment of migraine have both favorable and detrimental cardiovascular (CV) effects. Thus, clinicians responsible for the care of patients with CV disorders should possess a familiarity of the desirable and undesirable CV effects of these medications. To ensure the optimal safety and efficacy of delivering care to such patients, a knowledge of the pharmacological properties of these medications and the underlying CV co-morbidities of the patient is needed when initiating or modifying migraine therapy. The objective of this review is to provide an overview of the CV effects of migraine therapy to empower clinicians with the ability to initiate or modify migraine therapy in a patient with CV disease in a safe and effective manner.
Epidemiology
The American Migraine Study (AMS) II reported that 28 million people in the United States live with migraine.[2] The overall prevalence was found to be 18.2% among females and 6.5% among males. These numbers were similar to those seen in the first AMS, conducted in 1989. At that time, it was shown that 18% of females and 6% of males suffered from migraine.[3] The results of these two studies, as well as others, show that when using standardized diagnostic criteria, the prevalence of migraine in the United States has been stable over the past decade. Interestingly, half of the population in AMS II reported that the headaches were severe enough to affect their school and work productivity. The direct costs associated with migraine appears to be in excess of $1 billion per year, while the indirect costs to employers approaches $13 billion per year.[4]
Pathophysiology
The pathophysiology of migraine was originally explained using the vascular hypothesis. This theory suggests that the aura of migraine is caused by vasoconstriction and reduction in cerebral blood flow, while the migraine itself is the result of a compensatory vasodilation of these same intracerebral arteries.[1,5] Although it has been shown that during the aura of migraine there is decreased cerebral blood flow, other studies do not support this hypothesis.[6] Currently it is believed that migraine involves dysfunction of brain-stem pathways that normally affect input of sensory information.[7] Positron-emission tomography studies have shown that there is activation of the brainstem at the onset of migraine.[8,9] It has also been shown that specific serotonin (5-HT) receptor subtypes (5-HT1B and 5-HT1D) may be involved in the pathophysiology of migraine. These receptors are also the targets of medications used in the treatment of acute migraine.
Diagnosis/Clinical Presentation
The International Headache Society classifies migraine as an idiopathic, recurring headache disorder manifesting in attacks lasting 4-72 hours.[10] For a diagnosis of migraine, at least two of the following characteristics must exist: unilateral location, pulsating quality, moderate or severe intensity, and aggravation by routine physical activity. In addition, an association with nausea, photo- or phonophobia must exist. Migraine headaches can also be subclassified according to the presence or absence of aura ).
Management
Both pharmacologic and nonpharmacologic methods can be used for the treatment and prevention of migraine headaches. Nonpharmacologic measures include disease education for the patient, including its mechanism, treatment options, lifestyle changes, and possible triggers for migraine.[11] Lifestyle changes can include regular sleep, diet, and exercise. The goal for patients should be to maintain a regular schedule and diet rather than producing a long list of foods and activities to avoid. With this type of regularity, the patient may be able to better identify and prevent their personal triggers for migraine. The patients should be encouraged to take an active role in their treatment. This may be accomplished by using diary cards, flow charts, and headache calendars.
Pharmacologic treatment consists of both preventative and abortive therapy. The American Academy of Neurology has published evidence-based guidelines for the treatment of migraine.[12] Drugs for the treatment of migraine (i.e., abortive therapy) can be divided into nonspecific (i.e., antiemetics, nonsteroidal anti-inflammatory drugs [NSAIDs], acetaminophen, opiates, and combination analgesics) and migraine-specific (i.e., triptans and ergot alkaloids). Drug classes used for the prophylaxis of migraine include: -antagonists, calcium channel antagonists, angiotensin-II antagonists, tricyclic antidepressants, and -2 agonists. The following sections will review the CV effects of medications that are used as abortive therapy and prophylaxis ( respectively, in the management of migraine.
Abortive Therapy
Nonopiate Analgesics
NSAIDs are effective agents in the treatment of mild to moderate migraine attacks .The NSAIDs with proven efficacy include aspirin, diclofenac potassium, ibuprofen, ketoprofen, and naproxen sodium.[1,5,7] It appears that via the inhibition of prostaglandin synthesis, the NSAIDs prevent neurogenically mediated inflammation in the trigeminovascular system.[13] Along with preventing inflammation and relieving pain, the inhibition of prostaglandin in the kidneys can decrease renal blood flow and glomerular filtration rate, thereby promoting the retention of sodium and water. Clinically, this could lead to the development of edema and possibly loss of blood pressure control.[14] Patients with heart failure (HF), hepatic cirrhosis with ascites, or those with chronic renal disease are at greatest risk for the development of NSAID-induced acute renal failure, due to the effects of NSAIDs on renal hemodynamics. This places these individuals at an even greater risk for the development of NSAID-induced edema. It is also important to note that chronic NSAID use has been associated with loss of blood pressure control in patients receiving blood pressure-lowering medications for the management of hypertension. This risk is still present even when using cyclooxygenase-2 selective NSAIDs. For these reasons, NSAID use could be considered as a relative contraindication in patients with HF, hepatic cirrhosis with ascites, chronic renal failure, and hypertension. It is also important to remember that NSAIDs have antiplatelet effects that may increase the risk of bleeding when used in conjunction with other antiplatelet agents such as aspirin. Since aspirin is used for the prevention of coronary events in patient who are at an increased risk for coronary artery disease (CAD) or who have established CAD, the relative benefits vs. risks of using NSAIDs need to be carefully considered in such patients.
Serotonin Receptor Agonists (Triptans)
Triptans are a family of medications with proven efficacy that represent a major advancement in the treatment of migrain. There are three possible mechanisms of action that may be additive in the overall relief of migraine.[15] These include constricting cerebral blood vessels, reducing inflammation around these vessels, and inhibiting sensory nerve activation within the trigeminovascular system.[15,16] It has also been shown that the triptans constrict human coronary arteries via the same 5-HT activity.[17] However, the effect on normal vs. diseased coronary arteries appears to be different.
Some common complaints include tightness, pressure, and/or pain in the chest, neck, and/or throat. These symptoms can be especially worrisome in that they can mimic those of angina pectoris. There have been case reports of increases in blood pressure, serious cardiac events, including acute myocardial infarction, life-threatening disturbances of cardiac rhythm, and even death in patients taking triptans.[18] The incidence of these adverse effects seems to be relatively infrequent based on the extensive usage of these medications.
It may seem intuitive to contraindicate the use of these medications in patients at highest risk for these events. In fact, the prescribing information for sumatriptan indicates that the drug should not be given to patients with history, symptoms, or signs of ischemic, cardiac, cerebrovascular, or peripheral vascular syndromes.[19] It also seems reasonable to avoid using triptans in patients with significant risk factors for CAD (i.e., hypertension, hypercholesterolemia, smoking, diabetes, family history of premature CV disease) unless a CV evaluation provides clear evidence that they are free of disease. MaasenVanDenBrink et al.[17] found that in otherwise healthy patients treated with triptan therapy, there was no increase in the risk of myocardial ischemia at therapeutic doses. However, the authors still recommend that the triptans remain contraindicated in all patients with CAD. This evidence further strengthens the argument for risk stratification of migraine patients before initiating therapy with a triptan in that some patients with subclinical or undiagnosed CAD may be at elevated risk for these unwanted CV effects. Once therapy is started, it is important to monitor the patient for signs and symptoms of angina. If there appears to be a temporal relationship between the administration of the triptan and the onset of angina, then triptan therapy should be discontinued and nitrates should be administered.
Introduction
Migraine is a recurrent headache of moderate to severe intensity that is associated with gastrointestinal, neurologic, and autonomic symptoms.[1] Medications used for the prophylaxis and the treatment of migraine have both favorable and detrimental cardiovascular (CV) effects. Thus, clinicians responsible for the care of patients with CV disorders should possess a familiarity of the desirable and undesirable CV effects of these medications. To ensure the optimal safety and efficacy of delivering care to such patients, a knowledge of the pharmacological properties of these medications and the underlying CV co-morbidities of the patient is needed when initiating or modifying migraine therapy. The objective of this review is to provide an overview of the CV effects of migraine therapy to empower clinicians with the ability to initiate or modify migraine therapy in a patient with CV disease in a safe and effective manner.
Epidemiology
The American Migraine Study (AMS) II reported that 28 million people in the United States live with migraine.[2] The overall prevalence was found to be 18.2% among females and 6.5% among males. These numbers were similar to those seen in the first AMS, conducted in 1989. At that time, it was shown that 18% of females and 6% of males suffered from migraine.[3] The results of these two studies, as well as others, show that when using standardized diagnostic criteria, the prevalence of migraine in the United States has been stable over the past decade. Interestingly, half of the population in AMS II reported that the headaches were severe enough to affect their school and work productivity. The direct costs associated with migraine appears to be in excess of $1 billion per year, while the indirect costs to employers approaches $13 billion per year.[4]
Pathophysiology
The pathophysiology of migraine was originally explained using the vascular hypothesis. This theory suggests that the aura of migraine is caused by vasoconstriction and reduction in cerebral blood flow, while the migraine itself is the result of a compensatory vasodilation of these same intracerebral arteries.[1,5] Although it has been shown that during the aura of migraine there is decreased cerebral blood flow, other studies do not support this hypothesis.[6] Currently it is believed that migraine involves dysfunction of brain-stem pathways that normally affect input of sensory information.[7] Positron-emission tomography studies have shown that there is activation of the brainstem at the onset of migraine.[8,9] It has also been shown that specific serotonin (5-HT) receptor subtypes (5-HT1B and 5-HT1D) may be involved in the pathophysiology of migraine. These receptors are also the targets of medications used in the treatment of acute migraine.
Diagnosis/Clinical Presentation
The International Headache Society classifies migraine as an idiopathic, recurring headache disorder manifesting in attacks lasting 4-72 hours.[10] For a diagnosis of migraine, at least two of the following characteristics must exist: unilateral location, pulsating quality, moderate or severe intensity, and aggravation by routine physical activity. In addition, an association with nausea, photo- or phonophobia must exist. Migraine headaches can also be subclassified according to the presence or absence of aura ).
Management
Both pharmacologic and nonpharmacologic methods can be used for the treatment and prevention of migraine headaches. Nonpharmacologic measures include disease education for the patient, including its mechanism, treatment options, lifestyle changes, and possible triggers for migraine.[11] Lifestyle changes can include regular sleep, diet, and exercise. The goal for patients should be to maintain a regular schedule and diet rather than producing a long list of foods and activities to avoid. With this type of regularity, the patient may be able to better identify and prevent their personal triggers for migraine. The patients should be encouraged to take an active role in their treatment. This may be accomplished by using diary cards, flow charts, and headache calendars.
Pharmacologic treatment consists of both preventative and abortive therapy. The American Academy of Neurology has published evidence-based guidelines for the treatment of migraine.[12] Drugs for the treatment of migraine (i.e., abortive therapy) can be divided into nonspecific (i.e., antiemetics, nonsteroidal anti-inflammatory drugs [NSAIDs], acetaminophen, opiates, and combination analgesics) and migraine-specific (i.e., triptans and ergot alkaloids). Drug classes used for the prophylaxis of migraine include: -antagonists, calcium channel antagonists, angiotensin-II antagonists, tricyclic antidepressants, and -2 agonists. The following sections will review the CV effects of medications that are used as abortive therapy and prophylaxis ( respectively, in the management of migraine.
Abortive Therapy
Nonopiate Analgesics
NSAIDs are effective agents in the treatment of mild to moderate migraine attacks .The NSAIDs with proven efficacy include aspirin, diclofenac potassium, ibuprofen, ketoprofen, and naproxen sodium.[1,5,7] It appears that via the inhibition of prostaglandin synthesis, the NSAIDs prevent neurogenically mediated inflammation in the trigeminovascular system.[13] Along with preventing inflammation and relieving pain, the inhibition of prostaglandin in the kidneys can decrease renal blood flow and glomerular filtration rate, thereby promoting the retention of sodium and water. Clinically, this could lead to the development of edema and possibly loss of blood pressure control.[14] Patients with heart failure (HF), hepatic cirrhosis with ascites, or those with chronic renal disease are at greatest risk for the development of NSAID-induced acute renal failure, due to the effects of NSAIDs on renal hemodynamics. This places these individuals at an even greater risk for the development of NSAID-induced edema. It is also important to note that chronic NSAID use has been associated with loss of blood pressure control in patients receiving blood pressure-lowering medications for the management of hypertension. This risk is still present even when using cyclooxygenase-2 selective NSAIDs. For these reasons, NSAID use could be considered as a relative contraindication in patients with HF, hepatic cirrhosis with ascites, chronic renal failure, and hypertension. It is also important to remember that NSAIDs have antiplatelet effects that may increase the risk of bleeding when used in conjunction with other antiplatelet agents such as aspirin. Since aspirin is used for the prevention of coronary events in patient who are at an increased risk for coronary artery disease (CAD) or who have established CAD, the relative benefits vs. risks of using NSAIDs need to be carefully considered in such patients.
Serotonin Receptor Agonists (Triptans)
Triptans are a family of medications with proven efficacy that represent a major advancement in the treatment of migrain. There are three possible mechanisms of action that may be additive in the overall relief of migraine.[15] These include constricting cerebral blood vessels, reducing inflammation around these vessels, and inhibiting sensory nerve activation within the trigeminovascular system.[15,16] It has also been shown that the triptans constrict human coronary arteries via the same 5-HT activity.[17] However, the effect on normal vs. diseased coronary arteries appears to be different.
Some common complaints include tightness, pressure, and/or pain in the chest, neck, and/or throat. These symptoms can be especially worrisome in that they can mimic those of angina pectoris. There have been case reports of increases in blood pressure, serious cardiac events, including acute myocardial infarction, life-threatening disturbances of cardiac rhythm, and even death in patients taking triptans.[18] The incidence of these adverse effects seems to be relatively infrequent based on the extensive usage of these medications.
It may seem intuitive to contraindicate the use of these medications in patients at highest risk for these events. In fact, the prescribing information for sumatriptan indicates that the drug should not be given to patients with history, symptoms, or signs of ischemic, cardiac, cerebrovascular, or peripheral vascular syndromes.[19] It also seems reasonable to avoid using triptans in patients with significant risk factors for CAD (i.e., hypertension, hypercholesterolemia, smoking, diabetes, family history of premature CV disease) unless a CV evaluation provides clear evidence that they are free of disease. MaasenVanDenBrink et al.[17] found that in otherwise healthy patients treated with triptan therapy, there was no increase in the risk of myocardial ischemia at therapeutic doses. However, the authors still recommend that the triptans remain contraindicated in all patients with CAD. This evidence further strengthens the argument for risk stratification of migraine patients before initiating therapy with a triptan in that some patients with subclinical or undiagnosed CAD may be at elevated risk for these unwanted CV effects. Once therapy is started, it is important to monitor the patient for signs and symptoms of angina. If there appears to be a temporal relationship between the administration of the triptan and the onset of angina, then triptan therapy should be discontinued and nitrates should be administered.