Posted by Steve H. in Germany on June 07, 1999 at 15:42:31:
In Reply to: Re: OK...if they are shadows... posted by Barbara D. on June 07, 1999 at 08:00:08:
I'm experiencing rebound headaches with the Sumatriptan (Imitrex) that I am taking. I am also taking Naratriptan (Amerge) with better results.
Below is an excerpt from Clinical Pharmacology Online dealing with "the Triptans". Note that Sumatriptan is known to cause recurrent headaches. There is also a comparison of DHE with Sumatriptan concerning recurrence.
After that I have included a copy of a document dealing with medication induced headaches.
Sumatriptan ( USA: Imitrex®, Germany: Imigran® )
Description: Sumatriptan is an antimigraine drug that is structurally similar to serotonin. Sumatriptan is very specific for one subtype of serotonin receptors. It is approved for the treatment of migraine with or without aura, but not for long-term migraine prophylaxis or for the management of hemiplegic or basilar migraine. Although the efficacy of subcutaneous sumatriptan as an abortive agent in the treatment of migraine has been demonstrated,[134] headache recurrence is a frequent problem.[1273] Compared to dihydroergotamine, sumatriptan has a faster onset of relief but headache recurs less often with dihydroergotamine.[1274] Sumatriptan also has been used to treat cluster headaches, but the safety and efficacy for this indication have yet to be established. Subcutaneous sumatriptan was approved by the FDA in December 1992 for self-administration. Oral sumatriptan was cleared for marketing June 2, 1995. The nasal spray formulation was approved by the FDA August 30, 1997. The manufacturer is also developing suppository forms of sumatriptan.
Mechanism of Action: Sumatriptan represents a new development in the treatment of migraine. It is not an analgesic. The search for a new approach to therapy was instigated by the observation that changes in serotonin levels parallel migraine attacks. Platelet serotonin levels have been shown to increase before a migraine attack and decrease during an attack. In addition, artificially depleted serotonin levels produce typical headaches.
Many receptors have been identified for serotonin, also known as 5-hydroxytryptamine (5-HT). Sumatriptan stimulates 5-HT receptors of the 1-D subtype. The drug's therapeutic effect is a result of selective vasoconstriction of inflamed and dilated cranial blood vessels in the carotid circulation. Type 1-D 5-HT receptors have been identified on the cranial arteries in the dog and primate, on basal arteries in humans, and in the vasculature of the dura mater in humans. Animal studies have shown that sumatriptan decreases carotid arterial blood flow but only slightly affects blood pressure; it has little effect on diastolic blood pressure or total peripheral resistance. In dogs, sumatriptan selectively reduces carotid arterial blood flow without affecting arterial blood pressure or total peripheral resistance.
It is likely that the 5-HT 1-D receptors affected by sumatriptan are presynaptic receptors. In general, agonism at presynaptic receptors (i.e., autoreceptors) stimulates negative feedback, thereby shutting down further release of the neurotransmitter controlled by that receptor. Sumatriptan has been shown to block the release of vasoactive neuropeptides from perivascular trigeminal axons in the dura mater during migraine.[936] Fluoxetine, a drug that potentiates synaptic concentrations of serotonin, has been reported to worsen the clinical efficacy of sumatriptan.[1248] These findings suggest that sumatriptan ultimately decreases synaptic concentrations of serotonin.
Migraine also may be caused by stimulation of the trigeminal nerve, which leads to distention of the large, intracranial blood vessels. Sumatriptan may inhibit the release of inflammatory mediators from the trigeminal nerve. Sumatriptan has no pharmacologic activity at dopaminergic, muscarinic, or sympathetic receptors and does not possess intrinsic analgesic properties.
Naratriptan ( USA: Amerge®, Germany: Naramig® )
Description: Naratriptan is an antimigraine agent similar to sumatriptan but with a longer half life and a corresponding longer duration of action. In clinical trials, naratriptan had a slower onset and was slightly less effective than sumatriptan, but naratriptan was better tolerated. In addition, migraine recurrence was lower with naratriptan. Naratriptan is only approved for the acute treatment of migraine attacks with or without aura in adults. Naratriptan oral tablets were approved for marketing on February 10, 1998.
Mechanism of Action: Naratriptan is a potent agonist at serotonin 5-HT1 type B and type D receptors. Current theories regarding the etiology of migraines suggest that symptoms are the result of local cranial vasodilation and/or the release of pro-inflammatory neuropeptides through nerve endings in the trigeminal system. Naratriptan's antimigraine effects arise from its agonist activities at the 5-HT receptors on intracranial blood vessels, resulting in selective vasoconstriction of dilated vessels in the carotid circulation. Naratriptan also binds to pre-synaptic 5-HT receptors of trigeminal nerves, therefore inhibiting the release of pro-inflammatory neuropeptides from the terminals. Unlike sumatriptan, naratriptan also appears to act centrally at the trigeminal nucleus, but the clinical significance of this action is unknown. Naratriptan has no significant affinity for other serotonin receptors or for adrenergic, dopaminergic, muscarinic, or benzodiazepine receptors.
Zolmitriptan ( USA: Zomig® )
Description: Zolmitriptan (311C90) is an oral antimigraine agent. Zolmitriptan has actions similar to those of sumatriptan, but unlike sumatriptan, zolmitriptan can penetrate the blood-brain barrier to act centrally within the trigeminovascular system. In preclinical trials, zolmitriptan had response rates as high as 81% within two hours of dosing. Zolmitriptan is approved for the treatment of migraine with or without aura, but not for migraine prophylaxis or for the management of hemiplegic or basilar migraine. Final FDA approval was granted November 26, 1997. Zolmitriptan was also approved in 1997 in the United Kingdom and in Sweden for the treatment of migraine.
Mechanism of Action: Zolmitriptan is an agonist at 5-hydroxytryptamine (5-HT) type 1B and 1D receptors. The drug appears to have both peripheral and central sites of action. Based on current theories, migraines are believed to be caused by serotonin-induced local cranial vasodilatation and/or release of sensory neuropeptides (calcitonin gene-related peptide, substance P, and vasoactive intestinal peptide). 5-hydroxytryptamine type 1B and 1D receptors are present on intracranial blood vessels (including the arterio-venous anastomoses) and on sensory nerves of the trigeminovascular system which consists of bipolar neurons that innervate pain-sensitive intracranial structures. By binding to these receptors, zolmitriptan stimulates negative feedback, thereby shutting down further release of serotonin leading to lower synaptic concentrations of serotonin. Peripherally, zolmitriptan causes selective vasoconstriction of inflamed and dilated cranial blood vessels in the carotid circulation. Centrally, zolmitriptan ultimately inhibits the production of pro-inflammatory neuropeptides in the trigeminovascular system. Zolmitriptan has no pharmacologic activity at dopaminergic, muscarinic, or sympathetic receptors and does not possess intrinsic analgesic properties.
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Medication Induced Headaches
The Migraine Foundation has taken a proactive role in educating Canadian migraine sufferers about the dangers of taking analgesics too often and the all-too-common result -- Medication Induced Headache (MIH).
At a September Migraine Foundation news conference, Dr. Marek Gawel of the Department of Neurology at Sunnybrook Health Science Centre said that "Medication Induced Headache is of particular concern in Canada, since this country has the world's highest per capita consumption of codeine, a common analgesic." In fact, Canadian migraine sufferers take approximately 29 million prescriptive analgesic tablets a year.
Daily headache is the presenting complaint in up to 75 percent of all new referrals to headache diagnostic units and, of these, 77 per cent are using analgesics on a daily basis. Approximately 90 percent of migraineurs who suffer chronic daily or almost-daily headaches, have some form of MIH.
MIH can be caused by prescription medications such as ergotamine, pain medication containing condeine, or barbiturates as will as many over-the-counter pain medications.
The danger of overusing these medications is that the person (specifically migraine sufferers) can become reliant on them in such a way that is becomes necessary to take the medication daily or almost daily to fight constant headache.
Dr. Allan Purdy, Professor of Medicine (Neurology) at Dalhousie University in Halifax, explains: "Think of your brain as a sophisticated computer. When you have a bad headache, you take a headache medicine to 'reset the controls' in your brain for a little while, just to let your system get back in working order. When you take too much of a headache medicine - especially if you take it for many weeks or months - the medicine resets all the switches, and when they come on again, they're set to a different speed. If you keep taking the medicine, the system never has a chance to get back to the speed it's made to work at."
This does not mean you have an addiction. "Medication dependency can be a very different thing from drug addiction," Purdy says. "You're probably taking more medicine than you need. Your brain 'resets' its pain response because of the medication, but eventually this fails to work and it produces more headache instead of pain relief."
These are the common signs that can help identify MIH:
The headache occurs almost every day and is often present first thing in the morning.
The pain is a steady ache. It's different from the throbbing or pounding feeling that comes with a migraine. The pain is usually all over the head, not just on one side.
Daily headaches have been occurring for a least six months.
Daily headaches interfere with your work, family life, or your social life.
You are taking the medication more frequently, or at higher doses, than your doctor recommended.
Medication works only for a short time, or does not completely relieve the pain.
The headache worsens if you skip the usual dosage of medication.
The pain medication is being taken at least three times a week over an extended period of time.
Migraineurs who suspect they are suffering from MIH should make an appointment to discuss their symptoms with their doctor. Based on a thorough history, physical examination, and perhaps some laboratory tests, your physician can advise you on the most appropriate treatment plan.
Usually, the plan will include stopping the medicine right away. Sometimes, a plan will help you to cut down on doses until you stop the medication altogether.
This is not always easy to do, and may require a physician's supervision, sometimes in hospital.
Because it took some time for MIH to develop, treatment will also take time. However, every MIH patient can be helped through appropriate treatment. Most patients feel better within four to six weeks after beginning treatment. It takes your body at least this long to get rid of the effects of the medication you've been taking.
After MIH treatment, your daily headaches will be gone, but your migraine attacks may still occur. It is important to realize that the original problem that started the cycle of overuse still exists. Often, the use of appropriate preventive medications to correct the underlying problem in brain chemistry becomes part of the proper treatment, if you continue to suffer frequent migraine attacks. However, preventive medications will only work once the use of the MIH causing medication is stopped.
There are also new and effective medications for relieving migraine attacks when they occur.
The treatment of MIH, like the prevention and/or relief of migraine, may involve making important lifestyle changes. Regular exercise, for example, is the best way to boost the body's own natural pain killers, endorphins. Other changes may include quitting (or cutting down on) smoking, lowering alcohol intake and maintaining regular eating and sleeping patterns. A treatment plan may also include adopting such techniques as relaxation, meditation, or biofeedback.
The best defense against MIH is to know as much as possible about migraine and how it affects you as an individual. Everybody's migraine is different. Isolating and avoiding known triggers such as food, stress, and flickering lights can help dramatically. The key to preventing MIH is using the appropriate therapy for each migraine attack, depending on the severity, and using medication only as directed by a physician.
By working closely with your doctor, the proper treatment strategy for migraine can be determined based on the symptoms and triggers. Working as a team, you and your physician can determine the best way to manage future migraine attacks. If you want to gain control, you must become an active participant in your own care. Start by seeing your doctor to discuss your situation openly and honestly.