New drugs for the treatment of migraine in recent years have greatly improved the prognosis of patients, the most revolutionary of which are triptans.
(1) Mechanism of action of triptans:
triptans can selectively stimulate 5HT1B/1D receptors, and 5HT1 receptors target the bias through the following pathways: It has a therapeutic effect on headaches: ① Stimulating 5-HT1B receptors has only a slight constriction effect on blood vessels in physiological conditions, but can strongly contract dilated cerebral and meningeal blood vessels; ② By stimulating presynaptic 5-HT1D receptors on the trigeminal nerve Inhibiting the neurogenic inflammatory response of the dura mater and plasma extravasation can reduce the CGRP (calcitonin gene-related peptide) content in the blood during migraine; ③ Inhibit the trigeminal peptide by stimulating the 5-HT1B or 5-HT1D receptors in the brain stem Excitation of nerve nuclei.
(2) The first-generation triptan drug—sumatriptan:
Before the first triptan drug, sumatriptan, was launched in 1992, doctors were There is usually no good solution for migraine. Patients can only take painkillers, ergot alkaloids, diazepam and other drugs, with an effective rate of about 50%. Drugs such as ergot alkaloids have very toxic side effects and are contraindicated in patients with severe cardiovascular, liver, and kidney diseases; some powerful analgesics may cause terrible rebound headaches and even lead to drug addiction.
The effectiveness of sumatriptan oral tablets, whether 25mg or 50mg, reaches 60-80% within 2 hours, which is better than the combination of ergotamine and caffeine, and is especially suitable for patients with autonomic nervous system symptoms. Some studies suggest that oral administration of more than 100 mg is not more effective, but the rate of side effects is greatly increased.
After 20 mg of sumatriptan nasal spray (1 to 2 mg/kg for children), headaches can be significantly reduced in 15 minutes. After 2 hours, patients over 70 can return to normal life and work. Subcutaneous injection has a faster onset of action, and symptoms such as headache, blurred vision, and blind spots can be relieved within 10 minutes. This rapid drug absorption is very critical for alleviating migraines, because the faster the therapeutic blood concentration of the drug is reached and the plasma peak The higher the concentration, the better the overall migraine relief effect. But about 40% of patients with a longer history of migraines will relapse and require a second injection or other treatment.
(3) Second-generation triptans:
There are currently six second-generation triptans on the market. Compared with sumatriptan, they It has stronger effects and smaller side effects, and can also relieve the accompanying symptoms of migraines such as photophobia, phonophobia, and nausea. Like antidepressants and antibiotics, different individuals have different sensitivities to different triptans. So more choices mean more hope for patients.
1． Zolmitriptan:
Launched in 1996, it has dual effects on both the periphery and the center, and acts on the brainstem trigeminal nucleus, which is considered the "pain generator" in the brain.
The oral bioavailability of zolmitriptan is about 40, which is higher than sumatriptan (14). Data from a study of 2,000 patients showed that after taking 25 mg, it took effect 30 minutes; 65 to 81 patients were effective within 2 hours of treatment, while 15 to 34 patients with placebo; 47 patients in the treatment group had their migraines disappear completely; but 24 hours after administration The recurrence rate of internal headaches in the treatment group ranged from 21 to 37.
2． Rizatriptan:
Launched in 1998, it is characterized by ① rapid onset of action. The headache relief rate within 30 minutes of taking the medicine is 13-28; ② The efficacy is good, the relief rate after 2 hours of oral administration is 70, the symptoms disappear is 33, and it is still effective after the headache recurs; ③ The dose is low, and the headache relief rate of its 5 mg dose is higher than that of sumatriptan 100 mg is high; ④ has little side effects; ⑤ has a wide range of applications and can be used to treat migraine in patients with hypertension and mild liver insufficiency. It can be combined with the antidepressant paroxetine and is still effective in the treatment of menstrual migraine.
3. Naratriptan:
The recommended dosage is 25 mg. The peak blood plasma level is 3 to 5 hours after taking the medicine. The average time required for headache relief is about 4 hours.
4. Iritriptan:
The effective rate is 84, and the 24-hour relief rate is higher than other triptans. The incidence of side effects is slightly higher than that of sumatriptan, but they are all mild and there are no serious side effects. Researchers at the Headache Institute in New York, USA, examined the pharmacokinetics of eletriptan during menstruation and lactation in women. It was found that the menstrual cycle did not significantly change the effectiveness of the drug. During lactation, the drug in breast milk is very small, accounting for only 0.02 of the 80 mg taken by the mother. Moreover, the nursing mother tolerated iritriptan very well, with no abnormalities in blood pressure, pulse or electrocardiogram, and no serious side effects. The drug is also well tolerated by women taking birth control pills or hormone replacement therapy.
5. Fluvatriptan (Fluvatriptan):
Migraine attacks generally last 4 to 72 hours. Fluvatriptan 2.5 mg tablets have a relatively short time to reach maximum concentration (2-3 hours) and a half-life of 26 hours. This is an important breakthrough given that the current half-lives of other triptan drugs are less than 6 hours. In addition, there is almost no interaction between drugs and the recurrence rate is low. Long-term patients or patients with a high recurrence rate of headaches should consider using it.
6. Almotriptan:
It is the latest and most effective type of triptan drugs. It is characterized by ① high oral bioavailability (70-80) and fast onset of action (lt; 30 minutes) , high efficacy (12.5mg is effective, effective rate gt; 75), long maintenance time (gt; 24 hours); ② low recurrence rate (24 hours recurrence rate 18-27); ③ effect and age, gender, stomach content ④ No cross-reaction with other drugs; ⑤ The incidence of side effects is extremely low (lt; 1). Therefore, almotriptan is expected to become the first-line anti-migraine drug in the near future.
(4) Dosage forms of triptans
1. Subcutaneous injection: Quick and effective method for migraine sufferers. Subcutaneous injection is suitable for patients with nausea symptoms, difficulty in taking oral medication, acute onset, strong pain, and ineffective treatment with other triptan oral medications.
2． Intravenous administration: Zolmitriptan can be administered intravenously. After intravenous administration of 3.5 mg, the average values ??of cmax and auc were 79 and 77 respectively. The t1/2 of intravenous and oral administration is 2.30h and 2.94h respectively.
3. Oral tablets: Oral tablets are easy to use, have good patient compliance and tolerance, and are low-cost. However, they are slow-acting and difficult to take for patients with nausea symptoms. A meta-analysis by Ferrari et al. showed that within 2 hours, rizatriptan and iritriptan had the highest headache response rate; rizatriptan, almotriptan and iritriptan had the best effect in terms of sustained pain-free symptoms; Zatriptan and almotriptan have a rapid onset of action; naratriptan and almotriptan are the best tolerated drugs.
4. Nasal Spray: Nasal spray is a fast and effective option for patients who experience nausea and vomiting and have difficulty tolerating oral formulations. Compared with subcutaneous administration, its advantages are convenient administration and quick onset of headache relief (as early as 15 minutes). However, it has an irritating effect on the nasal cavity, a bitter taste in the mouth, and unsatisfactory drug absorption when used improperly. Currently available in this dosage form are sumatriptan and zolmitriptan.
5. Orally disintegrating tablets: It is a new dosage form developed in the past ten years, including rizatriptan and zolmitriptan orally disintegrating tablets. Its main feature is that after oral administration or sublingual administration, no water is required. The tablets can generally disintegrate within 40 seconds under the action of a small amount of saliva. Freeze-dried orally disintegrating tablets can disintegrate within 15 seconds. It is especially suitable for situations where water cannot be obtained, such as in the wild, difficulty swallowing, or other situations where rapid administration is required.
6. Rectal suppositories: an alternative route of administration for migraine patients with significant nausea/vomiting symptoms. Rectal administration avoids part of the hepatic first-pass effect, has good efficacy, good local and systemic tolerance, and rapid absorption. Disadvantages include inconvenient medication, patient discomfort, rectal mucosal irritation, interruption of drug absorption due to defecation, and unstable absorption. Sumatriptan rectal suppository was approved for marketing in September 2002, mainly for use in Europe.
(5) Problems with side effects:
Generally speaking, the incidence and severity of side effects of triptan drugs are lower than those of traditional anti-migraine drugs, mainly systemic side effects. Fever, dry mouth, dizziness, dizziness, malaise, fatigue, drowsiness, abnormal sensation and temporary increase in blood pressure, etc., the incidence rate is not more than 15; temporary chest pressure, restraint and chest pain can also be seen (incidence rate 1-4 ). Severe cases may induce coronary artery spasm or pulmonary hypertension. The best way to avoid serious side effects is to comprehensively assess the patient, master the indications, and use the medication as early as possible (to avoid having to increase the dose later).
Patients generally tolerate second-generation triptans well, with mild and short-lived adverse reactions that often resolve spontaneously without treatment. Nonetheless, clinical use should be contraindicated in patients with coronary artery disease or any other significant cardiovascular disease, as well as in patients with uncontrolled hypertension, hemiplegia, or underlying migraine. There are also reports suggesting that patients with two or more cardiovascular risk factors, renal dialysis patients, or patients with moderate hepatic impairment should be warned when using triptans.
Almotriptan has the least side effects of all triptans. However, for patients with severe renal insufficiency, the dosage of almotriptan in 24 hours should not exceed 12.5 mg.
(6) Development prospects of triptan drugs:
Since 1999, 4 of the international triptan migraine treatment drugs have become the best-selling prescription drugs in the world. Top 500 companies, accounting for 95% of the entire migraine treatment drug market. But in our country, most migraine patients still stay in the stage of resting and simply taking painkillers, or do not see a doctor at all; primary doctors give patients too many addictive, short-term relief painkillers instead of more effective ones. Triptans; my country’s own development of triptans is limited, and imported drugs are expensive (sumatriptan is about 60 yuan per tablet). These are issues that need to be addressed urgently. It is believed that with the emergence of cheaper triptans, increased awareness among primary-care doctors, and enhanced publicity to patients, migraine will no longer be a headache for both patients and doctors.