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Clinically often encounter many patients have difficulty falling asleep, early awakening, dreams and other symptoms, how to correctly choose insomnia drugs to become the basic ability of clinicians, the author consulted the insomnia drugs related literature, summarized as follows, hope to bring certain help
is the classification of "insomnia drugs"? Drugs that help with sleep include several categories:
the first is sedative sleeping pills, including benzodiazepines such as diazepam, esozolam, clonazepam, alprazolam, etc.
; Non-benzodiazepine new sleeping pills such as zolpidem, zopiclone, dexzopiclone
The second type is a chinese proprietary medicine that calms the spirit and promotes sleep, and is commonly used for jujube anshen capsules, sweet dream capsules or oral liquid, sleep relief capsules and so on
The third category is more special, because most sleep disorders are associated with emotional abnormalities, so patients with chronic insomnia and mood disorders often use drugs to regulate mood and promote sleep, such as mirtazapine, haloperidolamine melirlitracine tablets, citalopram, paroxetine, sertraline, agomelatine and the like
Due to the large individual differences and different sensitivities to drugs, the effect of combination drugs will be more significant
in many cases.
Next, some common insomnia drugs are analyzed from their indications and pharmacokinetics
Commonly used drug inventory ■ eszolam tablets
indications: mainly used for anxiolysis, insomnia
Also used for nervousness, fear, and anti-epileptic and anticonvulsant
The hypnotic effect is relatively strong, and it can fall asleep 0.
5-1 hours after oral administration, and the maintenance time is about
Toxic side effects are mainly dependent, and long-term use has a certain degree of drug resistance
If taken in large quantities at a time, poisoning will occur, and respiratory depression or blood pressure reduction is life-threatening
Clinically, it belongs to the second class of psychotropic drugs and requires a doctor's prescription
■ Indications for oxazepam tablets
: mainly used for short-term relief of anxiety, tension, agitation, can also be used for hypnosis, anxiety accompanied by mental depression of auxiliary drugs, and can alleviate acute alcohol withdrawal symptoms
Muscle relaxation is stronger
than other benzodiazepines.
Oral absorption is slow, 45 to 90 minutes of oral effectiveness, 2 to 4 hours, blood drug concentration peak, blood drug concentration in several days to steady state, plasma protein binding rate of 86% to 89%, T1/2 is generally 5 to 12 hours
Inactivated in combination with glucuronic acid in the body, all excreted by the kidneys, and the amount accumulated in the body is extremely small
▎ Small class
T1/2 refers to the half-life of the drug and refers to the time
required for the drug to metabolize half.
Clinically, it is necessary to decide the frequency of taking drugs according to the half-life of the drug, if the half-life is relatively long, it can be taken once a day or once every other day, if the half-life is relatively short, it needs to be taken three to four times a day, so the half-life is a very important indicator to determine the speed of
■ Alprazolam tablets
indications: mainly used for anxiety, nervousness, agitation, can also be used for hypnosis or anxiety adjuvant medication, can also be used as an anti-panic drug, and can alleviate acute alcohol withdrawal symptoms
It should be used
with caution in patients with mental disorders such as depression.
Oral absorption is fast and complete, and the plasma protein binding rate is about 80%.
Blood concentrations peak
within 1 to 2 hours after oral administration.
The blood concentration reaches a steady state
within 2 to 3 days.
T1/2 is generally 12 to 15 hours, and the elderly are 19 hours
Metabolized by the liver, the metabolite α-hydroxylprazolam, which also has certain pharmacological activity
Excreted by the kidneys
The amount of accumulation in the body is very small, and it is quickly
cleared after stopping the drug.
■ Zalepron dispersible tablets
indications: This product is suitable for short-term treatment
of insomnia with difficulty falling asleep.
Clinical studies have shown that Zalepron can shorten the time to sleep, but it has not been shown to increase sleep time and reduce the number of awakenings
Zalepron is absorbed quickly and completely
after oral administration.
Peak plasma concentration
is reached in about 1 hour.
Its absolute bioavailability is about 30%, with a clear first-pass effect
Zalepron is a fat-soluble compound that, when administered intravenously, is evenly distributed throughout the bloodstream without being widely distributed in
red blood cells.
After oral administration, zalepron is widely metabolized, in the urine, only no more than 1% of the dose is the original drug
■ Indications for dexzopiclone tablets
: for the treatment of insomnia
were conducted on healthy volunteers (adults and the elderly) and patients with liver and kidney disease.
In healthy subjects, the maximum dose of a single dose reached 7.
5 mg, and a 7-day continuous dosing trial was performed at doses of 1 mg, 3 mg and 6 mg
This product can be absorbed quickly, reaching a peak (tmax) in about 1 hour, and the elimination half-life is about 6 hours
Healthy adults take this product continuously without accumulation, at 1-6mg, and the distribution is linear with
■ Indications for clonazepam tablets
• Mainly used for the treatment of epilepsy and convulsions, it is effective for all types of epilepsy, especially for small seizures and myoclonus seizures
Intravenous injection for status epilepticus
• Can be used to treat anxiety states and insomnia
• Also effective
It also has a certain effect
on drug-induced ADHD, chronic multiple convulsions, zombie syndrome, and various types of neuralgia.
Oral absorption is good, and the blood concentration reaches a peak
in 2 to 4 hours.
The plasma half-life is 20 to 40 hours
It is highly fat-soluble and easily passes through the blood-brain barrier
It takes effect after 30 to 60 minutes of oral administration, and the effect can last for 6 to 8 hours
Almost all is metabolized in the liver, mainly by the CYP3A enzyme
Metabolites are excreted in free or bound form through the urine, and only a very small amount is excreted
in the form of the original drug.
■ Indications for lorazepam tablets
: suitable for the treatment of anxiety disorders or for short-term treatment to relieve anxiety symptoms and anxiety associated with depressive
Anxiety or nervousness associated with stress in everyday life usually does not require treatment
The effect of long-term application of lorazepam, that is, the effect of more than 4 months of application has not been evaluated by systematic clinical studies
Physicians should periodically re-evaluate the effectiveness
of the drug in individual patients.
Oral larazepam is rapidly absorbed with an absolute bioavailability of 90%.
Peak blood concentrations occur about 2 hours
after taking the drug.
The peak concentration of the plasma drug after oral administration of 2 mg of lorazepam is about 20 ng / ml
The average elimination half-life of free lorazepam in human plasma is about 12 hours, and the main metabolite, lorazepam glucuronate, is about 18 hours
At clinically relevant blood concentration levels, the plasma protein binding rate of lorazepam is about 85%.
■ Indications for zolpidem tartrate tablets
: treatment of severe sleep disorders, such as occasional insomnia and temporary insomnia
The bioavailability of oral zolpidem is about 70%, and the peak time for plasma drug concentrations is between
5 and 3 hours.
At therapeutic dose, the pharmacokinetics is linear
Plasma protein binding rate is about 92%.
The volume of distribution in adults is 0.
Zolpidem is metabolized by the liver and excreted
mainly in the form of inactive metabolites by urine (about 60%) and feces (about 40%).
It has no inducing effect on liver enzymes
The plasma elimination half-life is approximately 2.
4 hours (0.
In the risk group: a decrease
in the clearance of the liver can be observed in elderly patients.
The peak concentration increased by about 50%, while the half-life (averaged 3 hours) did not increase
The volume of distribution is reduced to 0.
In patients with renal insufficiency, a moderate reduction
in clearance can be observed, regardless of whether dialysis is performed or not.
Other kinetic parameters remain unchanged
Zolpidem cannot be removed
In patients with hepatic insufficiency, the bioavailability of zolpidem increases
Its clearance is reduced and the elimination half-life is prolonged (about 10 hours).
do I need to take insomnia pills?
Occasional, short-term insomnia does not necessarily require medication
They are often able to find relevant precipitating factors, such as environmental changes, physiological changes, jet lag, stimulant food, or drug effects
After removing the trigger or relieving it by self-regulation, some patients can sleep back to normal and do not need drug treatment
However, if insomnia persists and has an impact on the body, mind, life, work and study, and neither removing triggers nor establishing good sleep habits can improve sleep, medication is needed
to choose insomnia medication? Drugs should be selected based on the different causes of insomnia, symptom characteristics and age, whether there are other diseases, and whether other drugs are taken
For different patients, choose drugs for their characteristics, such as: people who are not easy to fall asleep, suitable for drugs that have a fast onset of action and a short duration of action, and can fall asleep quickly after taking, and there is no hangover the next day; People with persistent sleep difficulties and more nightmares are suitable for short- or moderate-acting drugs, which can deepen slow-wave sleep and shorten the time
to fall asleep.
The 2017 China Insomnia Diagnosis and Treatment Guidelines recommend that the treatment of insomnia include psychotherapy and medication
In terms of drug therapy, it is recommended to give hypnotic drugs as appropriate on the basis of psychotherapy, so as to achieve the goals
of relieving symptoms, improving sleep quality, prolonging effective sleep time, and improving the quality of life of patients.
Pharmacotherapy should follow the principles of individualization, on-demand, intermittent, and adequate amounts
The guidelines recommend the order of choice of drug types: short and moderate-acting benzodiazepine receptor agonists (including non-benzodiazepines and benzodiazepines) or melatonin receptor agonists (e.
, ramemetamide), antidepressants with a sedative effect (trazodone, mirtazapine, fluvoxamine, and doxepine), the latter are particularly indicated in patients
with insomnia with depression and/or anxiety.
Guidelines do not recommend antiepileptic drugs and antipsychotics as the drug of choice and are only suitable for certain special cases and populations
Precautions for insomnia pills • During the medication, do not drink coffee, tea and other exciting and refreshing drinks
• Do not drink alcohol
Small amounts of alcohol will quickly excite the brain, anti-drug sedative hypnotic effects
Excessive alcohol has an inhibitory effect, and together with "insomnia drugs", it has a double inhibition of the cardiovascular system and respiratory system, resulting in slower breathing, decreased blood pressure, and even respiratory arrest and death
• Elderly people should be cautious when
Many elderly people have problems with poor sleep and even take their own medication
However, the elderly are weak, the function of organs is declining, most people also suffer from other diseases, and if the dose of the drug is large, it will cause many risks
At the same time, the elderly often take other drugs or health care products, without the guidance of doctors or pharmacists, take "insomnia drugs" on their own, if there is an interaction between drugs, it may affect the efficacy or damage health
In addition, the elderly should pay special attention to the dizziness that may cause dizziness after taking the drug and then cause falls and fractures
•Patients with depression or anxiety disorders should be used as directed by a physician in combination with antidepressant or anti-anxiety medications
Because depression and anxiety can also cause sleep disturbances, sleep will also improve
after depression and anxiety are relieved.
• Increase or decrease the dosage or change the dose under the guidance of the doctor, do not arbitrarily change the dose, use it for a long time or stop the drug suddenly, and avoid tolerance and dependence
•Long-term users are advised to check liver and kidney function and blood routine every 3 months
Finally, regarding what medicine is best to take for sleep disorders, it is necessary to combine the patient's different causes of insomnia, symptom characteristics and age, whether there are other diseases, whether to take other drugs to choose insomnia drugs, and sleep well, which is the best medicine
to cure life.
Liu Aobo,Tang Yonghong.
Research progress in the treatment of chronic insomnia in the elderly[J].
World Journal of Sleep Medicine.
 Gao He, Mei Jianqiang, founded.
Professor Mei Jianqiang's experience in the treatment of drug-dependent insomnia[J].
Modern Journal of Integrative Medicine.
Chinese Sleep Research Society.
Chinese Insomnia Diagnosis and Treatment Guidelines[J].
Chinese Medical Journal,2017,97(24):1844-1856.
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The source of this article Medical Neurology Channel Author | Wang Lulu reviewed this article | Li Tuming Deputy Chief Physician
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