What is the difference between apixaban, dabigatran, edoxaban and rivaroxaban?❓❓❓

For a long period of time in the past, warfarin was the only oral anticoagulant drug until the emergence of novel oral anticoagulant drugs. Although they are called "novel" oral anticoagulants, they are only relative to warfarin. New oral anticoagulants include factor Xa inhibitors (apixaban, edoxaban, and rivaroxaban) and direct thrombin factor IIa inhibitors (dabigatran). Learn more about these four new oral anticoagulants below.

1. Mechanism of action.

The anticoagulant effect of warfarin is produced through multiple targets. It exerts an anticoagulant effect by inhibiting the hepatic synthesis of vitamin K-dependent coagulation factors II, VII, IX, and X.

Since new oral anticoagulants are anticoagulant drugs that act on a single target, their anticoagulant effects are easier to control. Apixaban, edoxaban, and rivaroxaban exert their anticoagulant effects by inhibiting coagulation factor Xa. Dabigatran exerts its anticoagulant effect by inhibiting coagulation factor IIa.

2. Risk of bleeding.

All of the novel oral anticoagulants were associated with a lower risk of intracranial hemorrhage than warfarin. Additionally, they do not increase the risk of fatal bleeding. Apixaban and edoxaban did not increase the risk of gastrointestinal bleeding compared with warfarin. However, dabigatran and rivaroxaban were associated with an increased risk of gastrointestinal bleeding compared with warfarin.

3. Indications.

a.) The difference between novel oral anticoagulants and warfarin: Atrial fibrillation can be divided into non-valvular atrial fibrillation and valvular atrial fibrillation (moderate to severe mitral stenosis, mechanical valve replacement surgery). Warfarin is recommended for valvular atrial fibrillation. Novel oral anticoagulants are recommended for nonvalvular atrial fibrillation.

b.) Differences between the novel oral anticoagulants:

• Apixaban is generally only used for anticoagulation after hip and knee surgery.
• Edoxaban and dabigatran can be used to prevent stroke in non-valvular atrial fibrillation. They can also be used to prevent deep vein thrombosis.
• Rivaroxaban can be used for more indications. It can be used to prevent non-valvular atrial fibrillation stroke, treat and prevent deep vein thrombosis and pulmonary embolism, anticoagulant therapy after hip and knee replacement, prevent coronary artery disease and peripheral artery disease.

4. Pharmacodynamics and pharmacokinetics.

The difference between novel oral anticoagulants and warfarin:

1. Novel oral anticoagulants reach peak blood concentrations more quickly after taking them, making them more effective. Their short half-life causes patients to lose their anticoagulant effect sooner after discontinuing the drug. It makes novel oral anticoagulants have good dose-response relationships. Activated coagulation factors II, VII, IX, and X are not affected by warfarin. Since the half-life of coagulation factor II is as long as 60 to 72 hours, it takes 2 to 7 days for warfarin to achieve its maximum effect.
2. Novel oral anticoagulants have few drug and food interactions.
3. Novel oral anticoagulants are rarely affected by disease or genetic factors. Patients have good medication compliance with them.
4. Andexanet is the specific reversal agent for apixaban, edoxaban and rivaroxaban. Idarucizumab is the specific reversal agent for dabigatran. If warfarin is overdose, vitamin K can be given intravenously.

5. Dosage of novel oral anticoagulants.

1. Apixaban: It is recommended to be taken at 2.5 mg twice daily. It is not affected by eating.
2. Edoxaban: It is recommended to take 60 mg once daily.
3. Dabigatran: It is recommended to be taken at 150 mg twice daily with meals. Dabigatran may damage the esophagus, so it is generally recommended to take it during or immediately after a meal and drink enough water (more than 100ml). Patients should remain in an upright or sitting position for more than 30 minutes after taking dabigatran.
4. Rivaroxaban: It is recommended to take 10mg once daily with or without food. However, rivaroxaban 15 mg or 20 mg tablets should be taken with food.

The frequency of administration is generally determined based on the half-life of drug efficacy and the half-life of plasma clearance. Patients should fix the time they take their medication every day. Novel oral anticoagulants generally do not require dose adjustment. However, in special circumstances (such as combined medication, the patient is underweight, old, or has liver and kidney problems), the dose may need to be reduced. 

6. How should novel oral anticoagulants replace other anticoagulants? 

Replacement of warfarin with novel oral anticoagulants: Check INR after discontinuing warfarin. Novel oral anticoagulants can be used when INR <2.0.

Substitution between novel oral anticoagulants: Patients should take the new novel oral anticoagulant directly with their next dose. Delayed dosing may be required in patients with renal impairment. 

Replacement of heparins with novel oral anticoagulants: The patient takes novel oral anticoagulants with the next injection of LMWH. The patient can take novel oral anticoagulant directly after stopping UFH.

Replacement of novel oral anticoagulants with injectable anticoagulants: The patient can switch to injectable anticoagulants when taking the next medication. Delayed dosing may be required in patients with renal impairment.

Replacing antiplatelet drugs with novel oral anticoagulants: Patients can take novel oral anticoagulants after they stop taking aspirin or clopidogrel.

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What antihypertensive drugs should be used in patients with diastolic hypertension?💓💓💓

Isolated diastolic hypertension (IDH) refers to patients with systolic blood
pressure < 140 mmHg and diastolic blood pressure ≥ 90 mmHg. Isolated diastolic hypertension is common in people younger than 65 and is often accompanied by a rapid heart rate.

What is arterial compliance? What is Peripheral Resistance?

Arterial compliance is arterial elasticity. When the heart contracts, blood rushes into the aorta putting pressure on it, known as systolic pressure. If the arterial elasticity of the patient is poor, the degree of dilation of the large arteries decreases and the volume of the blood vessels decreases, resulting in an increase in systolic blood pressure.

Peripheral resistance refers to resistance to blood flow by arterioles. when the heart is in diastole, the large arteries elastically recoil as they expand, pushing blood into the arterioles. When the heart is at the end of diastole, there will still be a certain amount of blood remaining in the aorta, which will exert pressure on it and that is the diastolic pressure. If the patient's arteriolar resistance increases, blood will flow into the arteriole less. As a result, more blood will remain in the aorta and diastolic blood pressure will increase. In addition, the increased heart rate of the patient will shorten the diastolic period of the heart. Blood flow into arterioles will also be reduced. The aorta will also retain more blood and increase the diastolic pressure. There is usually no obvious abnormality in the elasticity of the large arteries in young and middle-aged people. However, a significant increase in peripheral resistance is often accompanied by an increase in heart rate. Therefore, they are prone to isolated elevated diastolic blood pressure.

What is the mechanism of action of commonly used antihypertensive drugs?

Antihypertensive drugs commonly used in clinical practice include angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), β-blockers, dihydropyridine calcium channel blockers and thiazides diuretics.

1. Angiotensin-converting enzyme inhibitor (ACEI): It inhibits angiotensin-converting enzyme and blocks the production of the renin angiotensin II. It has no effect on heart rate but increases blood potassium levels. It can inhibit the synthesis of angiotensin II and reduce the level of angiotensin II. 
2. Angiotensin Receptor Blocker (ARB): It inhibits the angiotensin II receptor (AT1 type). It does not affect the patient's heart rate but increases his potassium levels. It inhibits the action of angiotensin II.
3. β-blockers: It suppresses sympathetic nerve activity and cardiac contractility and slows the heart rate. It also raises the level of blood potassium. It reduces renin secretion and lowers the level of angiotensin II.
4. Calcium channel blockers: It dilates blood vessels by inhibiting calcium channels on vascular smooth muscle cells. It reflexively activates the sympathetic nerves to increase the heart rate.
5. Diuretics: These decrease volume overload by increasing urination. It does not affect the patient's heart rate but lowers blood potassium levels. It decreases the secretion of renin and the level of angiotensin II.

What are the pathophysiological characteristics of hypertensive patients in young and middle-aged patients?

Activation of the sympathetic nervous system: The biological marker of sympathetic nervous activation is increased heart rate, hypertensive patients in young and middle-aged are often accompanied by increased heart rate.

Activation of the renin-angiotensin system: hypertensive patients in young and middle-aged , especially those with risk factors such as abdominal obesity, dyslipidemia, and smoking, have higher plasma renin activity and angiotensin II levels than the elderly.

What antihypertensive drug should be preferred in patients with isolated elevated diastolic blood pressure?

ACEI and ARB inhibit the renin-angiotensin system. β-blockers inhibit the sympathetic nervous system. 

If the patient's heart rate is >80 beats/min, β-blockers such as bisoprolol, carvedilol, and metoprolol are preferred.

If the heart rate of the patient is ≤80 beats/min, ACEIs (such as enalapril, perindopril) or ARBs (such as losartan, valsartan) are preferred.

Calcium channel blockers reflexively activate the sympathetic nerves. Diuretics can increase renin secretion and thereby promote the synthesis of angiotensin I and II. They are ineffective in the treatment of isolated diastolic hypertension.

In addition, studies have pointed out that about 200 patients who use β-blockers for 1 year will suffer from erectile dysfunction. ACEIs and ARBs are generally considered to have no adverse effects on sexual function, and some studies even suggest that they can improve.

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What are the normal values of blood pressure, blood sugar, blood lipids and uric acid for people of different ages?👀👀👀

Blood pressure, blood sugar, blood lipids and uric acid are the four basic
indicators for evaluating the health of the human body. However, the values of these indicators are not fixed and it will change with age. Therefore, some people will mistakenly think that they are unhealthy when they find that the value of the index is different from the standard value after the physical examination.

What is the normal blood pressure value?

A person's blood pressure should neither be too high nor too low. Excessive blood pressure can damage organs or tissues such as the cardiovascular system and kidneys. It also increases the risk of stroke. Low blood pressure prevents sufficient delivery of oxygen and blood to all parts of the body. It can cause fatigue, weakness, dizziness, and even fainting. Low blood pressure also increases the risk of stroke. However, in fact, people's blood pressure is not always stable. A person's blood pressure can vary at different times of the day and in different physical conditions. The following is the reference value of normal blood pressure for people of various ages:

Age	Systolic blood pressure (Male)	Diastolic blood pressure (Male)	Systolic blood pressure (Female)	Diastolic blood pressure (Female)
16-20 y/o	115	73	110	70
21-25 y/o	115	73	110	71
26-30 y/o	115	75	112	73
31-35 y/o	117	76	114	74
36-40 y/o	120	80	116	77
41-45 y/o	124	81	122	78
46-50 y/o	128	82	128	79
51-55 y/o	134	84	134	80
56-60 y/o	137	84	139	82
61-65 y/o	148	86	145	83

The following table will indicate the blood pressure status represented by each blood pressure range:

Type	Systolic blood pressure	Diastolic blood pressure
Hypotension	Below 90	Below 60
Ideal blood pressure	About 120	About 80
Normal blood pressure	Below 130	Below 85
Normal hypertension	130-139	85-89
Borderline hypertension	140-149	90-94
Mild hypertension	140-159	90-99
Simple systolic hypertension	Over140	Below 90
Moderately hypertension	160-179	100-109
Highly hypertension	Over 180	Over110

However, many factors such as mood, exercise and temperature can affect blood pressure values. Therefore, a single blood pressure measurement cannot be used as a diagnostic result.

What is the normal blood glucose value?

Similarly, too high or too low blood sugar will also have adverse effects on the human body. Excessive blood glucose can cause disease in the patient's large blood vessels. These lesions include atherosclerosis in the basilar arteries, coronary arteries, aorta, renal arteries, and peripheral arteries. These patients tend to have severe atherosclerosis and high mortality. About 70 to 80% of diabetic patients die of diabetic macrovascular disease. In addition, hypoglycemia will also damage the patient's health. Hypoglycemia may lead to memory loss, slow reaction time, dementia, coma, and even death. Hypoglycemia may also induce arrhythmia and myocardial infarction in patients. People's blood glucose levels change as they eat, digest and absorb food. Therefore, fasting blood glucose and postprandial blood glucose are generally used as reference values. 

	Venous (whole blood)	Capillary	Venous (plasma)
Normal value - fasting	3.9 – 6.1
Normal values – 2hrs after meals	Below 7.8
Diabetics - fasting	Over 6.1	Over 6.1	Over 7.0
Diabetics - 2hrs after meals	Over 10	Over 11.1	Over 11.1
Impaired glucose tolerance - fasting	Below 6.1	Below 6.1	Below 7.0
Impaired glucose tolerance - 2hrs after meals	6.7 – 10.0	7.8 – 11.1	7.8 – 11.1
Impaired fasting glucose - fasting	5.6 – 6.1	5.6 – 6.1	6.1 – 7.0
Impaired fasting glucose - 2hrs after meals	Below 6.7	Below 7.8	Below 7.8

What is the normal blood lipid value?

Patients with hyperlipidemia will make the blood thicken. Blood becomes prone to deposits on the walls of blood vessels, gradually forming plaques. These plaques can gradually build up and grow and clog blood vessels. It slows or even blocks blood flow. However, blood lipid levels are not as low as possible. Some studies have pointed out that when the cholesterol level of the elderly over 70 years old is lower than 4.16mmol/L, their risk of acute cardiovascular and cerebrovascular events is similar to that of the elderly whose cholesterol level is higher than 6.24 mmol/L. The normal reference values of blood lipids are as follows:

Types	Normal values
Total Cholesterol	2.8 – 5.17 mmol/L
Triglycerides	0.56 – 1.7 mmol/L
High Density Lipoprotein (Male)	0.96 – 1.15 mmol/L
High Density Lipoprotein (Female)	0.90 – 1.55 mmol/L
Low Density Lipoprotein	0 – 3.1 mmol/L

What is the normal uric acid value?

Under a normal diet, hyperuricemia is clinically diagnosed when the blood uric acid value of males exceeds 420 μmol/L and that of females exceeds 360 μmol/L in two tests on different days. 

	The range of normal blood uric acid level
Male	237.9 – 420 μmol/L
Female	178.4 – 360 μmol/L

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How should patients take Ambroxol?😷😷😷

Ambroxol is a very commonly used expectorant in clinical practice. Recently, more and more people pay attention to other pharmacological effects of ambroxol. The following relevant knowledge can help us use ambroxol rationally.

1. Chemical structure of Ambroxol.

Ambroxol is the active product produced by the metabolism of bromhexine. Due to its local anesthetic properties, it is given as a lozenge to soothe sore throats. Ambroxol is broken down by light, so it needs to be stored away from light. Its granule form needs to be dissolved in room temperature water. The injection form of ambroxol will produce free base precipitation of ambroxol due to the increase of the pH value of the solution, so it should not be mixed with an alkaline solution with a pH>6.3.

2. The expectorant effect of ambroxol.

The main components of sputum secreted by humans are a small amount of acidic glycoprotein and a large amount of water. When inflammation occurs in the respiratory tract, there will also be a small amount of residual DNA from damaged inflammatory cells in the sputum. There are disulfide bonds (-S-S-) in the acid glycoprotein molecular structure, so the sputum has a certain viscosity. It is also the main component in white sputum. Ambroxol can reduce the production of acidic mucopolysaccharides in the trachea, bronchial glands and goblet cells to reduce the viscosity of sputum. In addition, it can also promote the movement of cilia on the trachea and increase the expectoration of sputum. Ambroxol is suitable for patients with white and sticky sputum that is not easy to cough up.

3. Common dosage forms and dosages of ambroxol.

Ambroxol is generally administered 2 to 3 times a day. Its half-life is about 10 hours. If ambroxol is in the form of injection, its dosage is about half that of oral administration. Inhaled dosage forms will have smaller doses. 

1. Ambroxol Hydrochloride Tablets: Adults take orally three times a day, 30 to 60 mg each time, after meals.
2. Ambroxol hydrochloride oral solution: 1 to 2 years old, twice a day, 15mg each time. From 2 to 6 years old, three times a day, 15mg each time. 6 to 12 years old, two to three times a day, 30mg each time. Over 12 years old and adults, twice a day, 60mg each time.
3. Ambroxol Hydrochloride Injection: Children under 2 years old twice a day, 7.5mg each time. From 2 to 6 years old, three times a day, 7.5mg each time. 6 to 12 years old, two to three times a day, 15mg each time. Over 12 years old and adults, two to three times a day, 15 to 30mg each time.
4. Ambroxol hydrochloride solution for inhalation: children from 6 months to 2 years old inhale once or twice a day, 7.5mg each time. From 2 to 12 years old, inhale once or twice a day, 15mg each time. Over 12 years old and adults inhale once or twice a day, 15 to 22.5mg each time.

4. What is Neonatal Respiratory Distress Syndrome?

The site of gas exchange in the lungs is the alveoli. Oxygen in the alveoli will diffuse into the blood through the liquid membrane on the inner surface of the alveoli, the epithelial cells of the alveoli, the interstitium between the epithelium of the alveoli and the endothelium of the pulmonary capillaries, the endothelial cells of the capillaries, and then enter the blood. Alveolar epithelial cells are classified into type I and type II. Type II alveolar epithelial cells are inlaid between type I alveolar epithelial cells. It can synthesize and secrete alveolar surfactant. The main component of this surface active substance is phospholipid protein. It reduces the surface tension of the alveoli, preventing the alveoli from collapsing or overinflating. Neonatal respiratory distress syndrome refers to symptoms such as progressive dyspnea and respiratory failure in newborns. Its main cause is a series of symptoms caused by alveolar atrophy due to the lack of alveolar surfactant. Because ambroxol can increase the synthesis and secretion of alveolar surfactant, it has been approved for the treatment of respiratory distress syndrome in premature infants and neonatal infants. The dosage is 30mg/kg as the total daily dosage, divided into 4 doses. It should be administered with a syringe pump and administered intravenously over at least 5 minutes. In addition, when amoxicillin, cefuroxime, erythromycin, doxycycline and other antibiotics are taken together with ambroxol, the concentration of antibiotics in lung tissue can be increased.

5. Off-label use of ambroxol.

Taking large doses of ambroxol has the effects of anti-inflammation, anti-oxidation and scavenging free radicals in the body. It also increases alveolar surfactant. This has a protective and therapeutic effect on lung damage. It is used off-label to prevent postoperative atelectasis in patients with chronic obstructive airway disease. It is used continuously for six days from the third day before the patient's lung surgery to the second day after the operation, with a daily dose of 1000mg. Ambroxol can cause adverse reactions such as nausea, stomach discomfort, and loss of appetite, so it is recommended to take ambroxol oral preparations after meals. Ambroxol may also cause severe skin reactions such as toxic epidermal necrolysis. If patient develops symptoms of progressive rash, discontinue use ambroxol and seek medical attention immediately.

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What are the precautions for using hypnotics?😴😴😴

In today's society, many people suffer from insomnia. Insomnia is the most common sleep disorder clinically. About 10 to 15% of adults meet the criteria for a diagnosis of insomnia. Generally recommended for the treatment of insomnia psychotherapy and drug therapy. For patients with insomnia, medication is generally used on the basis of psychotherapy. Hypnotic drugs are given according to the patient's condition to relieve insomnia symptoms, improve sleep quality and improve the patient's quality of life.

What medications can be used to treat insomnia?

The principles of drug therapy should be individualized, on demand, intermittent and sufficient. The drug treatment guidelines for insomnia are generally recommended as follows: non-benzodiazepine drugs are the first choice. Short and medium-acting benzodiazepines or melatonin receptor agonists are the second choice. Antidepressants with sedative effects are optional only when necessary, but they are especially indicated for insomniacs with depression and/or anxiety. Treatment guidelines do not recommend the use of antipsychotics and antiepileptics as first-line drugs, and they are only applicable to certain special situations and special populations. 

Non-benzodiazepines: These drugs selectively activate the α subunit of the γ-aminobutyric acid receptor A (GABA_A). Their hypnotic effects are similar to those of benzodiazepines. Due to the short half-life of these drugs, their next-day residual effects are greatly reduced. They generally do not cause daytime drowsiness in patients and have a lower risk of dependence than benzodiazepines. Therefore, non-benzodiazepines can be safe and effective in the treatment of insomnia, and their long-term use has no significant adverse drug effects. Sudden discontinuation of the drug may cause transient insomnia rebound in patients. Because non-benzodiazepines are less muscle relaxant, they cause a lower risk of falls than benzodiazepines. Therefore, non-benzodiazepines are especially suitable for elderly patients with insomnia. CYP3A4 metabolizes non-benzodiazepines such as eszopiclone, zopiclone and zaleplon. Therefore, CYP3A4 inhibitors such as clarithromycin will inhibit their metabolism. It can increase blood levels of non-benzodiazepine drugs and increase the occurrence of adverse reactions. Inducers of CYP3A4, such as rifampin, lower their blood levels and reduce their efficacy. Co-administration of alcohol or other central depressants with non-benzodiazepines increases the central depressant effect. 

1. Eszopiclone: This is indicated for the treatment of trouble falling asleep or maintaining sleep. It has a peak time of 1 to 1.5 hours and a half-life of 6 hours. Adults take 1 to 3 mg orally before going to bed. Its common adverse reaction is abnormal taste. Eszopiclone was better tolerated than zopiclone.
2. Zaleplon: It is indicated for the treatment of difficulty falling asleep. It has a peak time of ≤1 hour and a half-life of 0.7 to 1.4 hours. Adults take 5 to 20 mg orally before going to bed. Its common adverse reactions are dizziness and ataxia.
3. Zopiclone: It is indicated for the treatment of trouble falling asleep or maintaining sleep. It has a peak time of 1.5 to 2 hours and a half-life of 5 hours. Adults take 3.75 to 7.5 mg orally at bedtime. Its common adverse reaction is bitter taste in mouth. 
4. Zolpidem: This is indicated for the treatment of trouble falling asleep or maintaining sleep. It has a peak time of 0.5 to 3 hours and a half-life of 0.7 to 3.5 hours. Adults take 1.75 to 10 mg orally or 6.25 to 12.5 mg sustained-release tablets before going to bed. Its common adverse effects are headache, dizziness and forgetfulness.

Benzodiazepines: These drugs bind nonselectively to GABA_A receptors. They have anxiolytic, sedative, muscle relaxant and anticonvulsant properties. Therefore, this class of drugs has a better effect on patients with anxiety insomnia. Benzodiazepines commonly used in clinical practice include estazolam, flurazepam, quazepam, temazepam and triazolam. Among them, triazolam and temazepam are relatively recommended for the treatment of insomnia. Other commonly used benzodiazepines are alprazolam, diazepam, and lorazepam. These drugs are dependent. Therefore, after long-term use, patients may experience withdrawal symptoms after stopping the drug. Most benzodiazepines are contraindicated in pregnant or lactating women, patients with impaired liver and kidney function, patients with obstructive sleep apnea syndrome, and patients with severe ventilatory impairment. In addition to lorazepam and temazepam, CYP3A4 has a certain ability to metabolize benzodiazepines. Therefore, both CYP3A4 inducers and inhibitors affect their plasma concentrations. CNS depressants and alcohol also enhance the CNS depressant properties of benzodiazepines.

1. Estazolam: It is indicated for the treatment of difficulty falling asleep or maintaining sleep. The adult dosage is 1 to 2 mg orally at bedtime. It has a peak time of 3 hours and a half-life of 10 to 24 hours. Its common adverse effects include dry mouth, hangover and weakness.
2. Flurazepam: It is indicated for the treatment of trouble falling asleep or sleep maintenance. The adult dosage is 15 to 30 mg orally at bedtime. It has a peak time of 1.5 to 4.5 hours and a half-life of 48 to 120 hours. Its common adverse effects include ataxia, dizziness and hangover.
3. Quazepam: It is indicated for the treatment of difficulties falling asleep or maintaining sleep. The adult dose is 7.5 to 15 mg orally at bedtime. It has a peak time of 2 to 3 hours and a half-life of 48 to 120 hours. Its common adverse effects include dizziness, drowsiness, dry mouth, headache and unsteadiness on standing.
4. Temazepam: It is indicated for the treatment of difficulty falling asleep or maintaining sleep. The dosage for adults is 7.5 to 30 mg orally at bedtime. It has a peak time of 1.2 to 1.6 hours and a half-life of 3.5 to 18.4 hours. Its common adverse effects include ataxia and dizziness.
5. Triazolam: It is indicated for the treatment of difficulty falling asleep. The dosage for adults is 0.125 to 0.25 mg orally at bedtime. It has a peak time of 0.2 to 0.5 hours and a half-life of 1.5 to 5.5 hours. Its common adverse effects include amnesia, euphoria, upset stomach and skin tingling.

Melatonin receptor agonists: The sleep-wake cycle is regulated by melatonin. Melatonin can effectively improve symptoms caused by jet lag, delayed sleep phase syndrome, and circadian rhythm sleep disorders. Melatonin receptor agonists can be used as an alternative treatment for patients who cannot tolerate benzodiazepines or who have developed drug dependence. Melatonin and ramelteon tablets are commonly used melatonin receptor agonists.

1. Melatonin: It is indicated for patients who have difficulty falling asleep or maintaining sleep. Adults take 2 mg orally before going to bed. It has a peak time of 0.75 to 3 hours and a half-life of 6 hours. Its common side effects are dizziness, drowsiness and fatigue.
2. Ramelteon: It is indicated for patients who have trouble falling asleep. Adults take 8 mg orally before going to bed. It has a peak time of 0.75 to 1 hour and a half-life of 1 to 2.6 hours. Its common adverse reactions are dizziness, drowsiness and fatigue. It is especially effective and safe for insomniacs with sleep-disordered breathing. CYP1A2 is the main metabolic enzyme of ramelteon. CYP2C and CYP3A4 also metabolize a small amount of it. Therefore, CYP1A2 inhibitors such as ciprofloxacin will increase its plasma concentration and should not be used in combination.

Antidepressants: Serotonin and norepinephrine reuptake inhibitors (SNRIs), selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants and other antidepressants are also used to treat insomnia.

Serotonin and norepinephrine reuptake inhibitors (SNRIs): Venlafaxine and duloxetine can be used to treat depression and anxiety to improve insomnia.

Selective serotonin reuptake inhibitors (SSRIs): Fluoxetine, fluvoxamine, paroxetine, sertraline, etc. are commonly used clinical SSRIs. They improve insomnia symptoms in patients by treating depression and anxiety disorders. Among them, fluvoxamine has a sedative effect and is a better choice for insomnia patients.

1. Fluvoxamine: It prevents the degradation of melatonin and increases the concentration of endogenous melatonin. It is the only sedating drug among the SSRIs. The combination of doxepin and it will increase the blood concentration of the two drugs, so the dose should be reduced when used in combination. Its starting dose is 50mg or 100mg taken daily at bedtime. The commonly used effective dose is 100 mg per day.

Tricyclic antidepressants: Amitriptyline and doxepin are commonly used tricyclic antidepressants. However, because of its anticholinergic effects, amitriptyline can cause adverse reactions such as dry mouth and increased heart rate in patients, so it will not be used as the drug of choice for the treatment of insomnia.

1. Amitriptyline: It can treat anxiety and depression patients with insomnia. It has a peak time of 2 to 5 hours and a half-life of 10 to 100 hours. Adults take 10 to 25 mg orally before going to bed. Its common adverse reactions are anticholinergic effects, cardiac damage, excessive sedation, and orthostatic hypotension.
2. Doxepin: Doxepin in small doses (3 to 6 mg orally at bedtime) has a specific antihistamine mechanism. It improves insomnia symptoms in adults and elderly patients with chronic insomnia. It also can treat sleep maintenance disorders. It was clinically well tolerated and had no withdrawal effects. It has become one of the recommended drugs for the treatment of insomnia in recent years. It has a peak time of 1.5 to 4 hours and a half-life of 10 to 50 hours. Its common adverse reactions are drowsiness and headache.

Other antidepressants: Small doses of mirtazapine and trazodone can calm the patient and relieve insomnia symptoms. They are used to treat both insomnia and rebound insomnia after hypnotic drug withdrawal.

1. Mirtazapine: It can relieve symptoms of sleep disorders in depressed patients and treat anxiety and depression with insomnia. It has a peak time of 0.25 to 2 hours and a half-life of 20 to 40 hours. Adults take 3.75 to 15 mg orally at bedtime. Its common adverse effects are anticholinergic effects, appetite and weight gain, and excessive sedation.
2. Trazodone: Although its antidepressant effect is weak, it has strong hypnotic power. It can be used in patients with anxiety and depression with insomnia, sleep disturbance or severe sleep apnea syndrome. It may also be used to treat rebound insomnia after the hypnotic drug is discontinued. It has a peak time of 1 to 2 hours and a half-life of 3 to 14 hours. Adults take 25 to 150 mg orally at bedtime. Its common adverse reactions are dizziness, orthostatic hypotension, and priapism.

Orexin receptor antagonist: Orexin has a refreshing effect, also known as hypocretin.

1. Suvoresan: It is an orexin receptor antagonist. It has been approved in some countries for adults with trouble falling asleep or sleep maintenance disorders. It has a different target than other sleeping pills. Studies have shown that it has good clinical efficacy and tolerability. It has a peak time of 0.5 to 6 hours and a half-life of 9 to 13 hours. Adults take 5 to 20 mg orally before going to bed. Its common adverse reaction is residual sedation.

Non-benzodiazepines such as zolpidem and eszopiclone are generally the first choice for clinical treatment of insomnia. If the first-line drug is ineffective, melatonin receptor agonists, short- to medium-acting benzodiazepines, or orexin receptor antagonists can be replaced. Antidepressants may be added to patients with insomnia who are anxious or depressed.

When should patients use hypnotics?

1. Hypnotics may be taken 5-10 minutes before bedtime when the patient anticipates difficulty falling asleep.
2. If the patient fails to fall asleep 30 minutes after going to bed, hypnotics can be taken immediately.
3. Hypnotics can be taken immediately if the patient cannot fall asleep again after waking up at night and is more than 5 hours away from the expected time of waking up. It recommends using hypnotics with a short half-life.
4. Patients with chronic insomnia were treated intermittently with non-benzodiazepines. It will generally take the hypnotics on selected nights per week rather than on consecutive nights.

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