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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Seven drugs should not be used in combination with omeprazole.🈲🈲🈲

Omeprazole is a proton pump inhibitor. It is also the most commonly used gastric acid suppressant drug. It is a fat-soluble weakly basic drug. After oral administration by patients, it will be specifically distributed in the secretory tubules of the parietal cells of the gastric mucosa. A high acid environment will convert it into the active ingredient of sulfenamide. It inhibits the activity of hydrogen-potassium ATPase on the gastric parietal cells to block the secretion of gastric acid and increase the pH of gastric juice. Therefore, its inhibitory effect on gastric acid secretion caused by various reasons is long-lasting and potent. Omeprazole is suitable for stomach diseases such as gastric ulcer and duodenal ulcer.

What diseases can omeprazole be used to treat?

1. Gastroesophageal reflux: These patients experience symptoms such as acid reflux and heartburn. Omeprazole can inhibit the secretion of gastric acid to control the symptoms and promote the recovery of esophagitis.
2. Peptic ulcer: abnormal secretion of gastric acid and pepsin can be treated with omeprazole. It can effectively suppress stomach acid and promote the healing of peptic ulcer. At the same time, it can also relieve various related symptoms and reduce complications.
3. Upper gastrointestinal bleeding: Omeprazole can increase the pH of the stomach and reduce the redissolution of blood clots in the stomach. Therefore, upper gastrointestinal bleeding in patients caused by various diseases can be treated with omeprazole.

Which drugs should not be used in combination with omeprazole?

Acidic drugs: Omeprazole is a weakly basic drug. It decomposes rapidly in an acidic environment. Therefore, omeprazole is often made into enteric-coated tablets or capsules. When acidic drugs and omeprazole are used in combination, a neutralization reaction may occur and affect the efficacy of the drug. Acidic drugs such as ambroxol hydrochloride, ornidazole and vitamin B6 should not be used in combination with omeprazole.

Clopidogrel: It is an anti-platelet aggregation drug. Most proton pump inhibitors reduce the production of the active metabolite of clopidogrel, thereby reducing the efficacy of clopidogrel. Among the proton pump inhibitors, omeprazole has a significant effect on clopidogrel. If clopidogrel needs to be used in combination with a proton pump inhibitor, a proton pump inhibitor with less effect such as rabeprazole or pantoprazole should be used.

Digoxin: It is a commonly used cardiac glycoside drug in clinical practice. Its hydrolysis needs to be carried out in an acidic environment. Therefore, omeprazole inhibits gastric acid secretion, which will increase the pH value in the stomach and reduce the hydrolysis of digoxin. The combination of the two will reduce or eliminate the activity of digoxin.

Iron supplements: Growing children or pregnant women sometimes need to take iron supplements to supplement the iron in the body in order to avoid iron deficiency anemia. However, the stomach needs an acidic environment to absorb iron properly. Because omeprazole inhibits gastric acid secretion, the body cannot absorb iron normally.

Nifedipine: It is a commonly used antihypertensive drug in clinical practice. Omeprazole inhibits the enzymes that metabolize nifedipine, thereby increasing the body's absorption of nifedipine. There is an increased risk of hypotension and the risk of adverse effects.

Ketoconazole: It is an antifungal medicine. The release of its drug effect needs to rely on the secretion of gastric acid. The secretion of gastric acid is inhibited by omeprazole to increase the pH value of the stomach. The release of ketoconazole is thus reduced and the bioavailability is reduced, which in turn weakens the antifungal effect.

Probiotics such as Bifidobacterium and Lactobacillus: They can regulate intestinal flora and improve symptoms such as constipation and diarrhea. These probiotics require an acidic environment to remain active. Therefore, they should not be used in combination with antacids.

Precautions for Omeprazole.

When omeprazole is used for peptic ulcer, 1 to 2 times a day, 20 mg each time, the patient swallows once in the morning or once in the morning and evening. The course of gastric ulcer treatment is generally 4 to 8 weeks. The course of treatment for duodenal ulcer is generally 2 to 4 weeks. When omeprazole is used for gastrinoma, the patient should take 60 mg once a day. The total daily dose is adjusted to 20 to 120 mg according to the patient's condition. If the total daily dose exceeds 80 mg, patients should take it in two divided doses. In order to prevent omeprazole from dissolving in the acidic stomach, it is generally made into enteric-coated tablets or capsules. Enteric-coated preparations are generally recommended to be taken on an empty stomach or before meals. It will ensure that the pH value of the stomach will not be affected by food, which will cause the drug to dissolve and release in the stomach in advance, resulting in ineffectiveness.

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How to treat postherpetic neuralgia?🔨🔨🔨

Herpes zoster is an infectious disease caused by a virus. The varicella-zoster virus can remain latent in the human body for a long time. They can be reactivated to cause infectious skin disease. Postherpetic neuralgia is one of the complications of shingles. Pain that persists for 1 month or more after clinical healing of the shingles rash is considered postherpetic neuralgia. Its prevalence ranges from approximately 9% to 34%. Patients with postherpetic neuralgia suffer from severe pain for a long time, which can easily lead to depression and their quality of life will be seriously reduced.

What are the clinical manifestations of postherpetic neuralgia?

1. Clinical manifestations of pain:

The clinical presentation of postherpetic neuralgia is complex and varied. It can be continuous or discontinuous. It has the following characteristics:

• Pain location: common in trigeminal nerve (mainly ophthalmic branch), neck or unilateral chest. About 50% of the patients occurred in the chest. Occurrence in the head and face, neck and waist accounted for 10% to 20% respectively. Occurs in the sacrum about 2% to 8%. Other parts are less than 1%. The painful area of postherpetic neuralgia is usually larger than the area of herpes zoster. Bilateral herpes is rarely seen in patients.
• The feeling of pain: Different patients experience different pain sensations. It can be like burning, knife cutting, needle sticking, shocking or tearing. Patients may experience one type of pain or possibly multiple pains at the same time.

2. Features of Pain:

• Spontaneous pain: Pain occurs in the rash distribution area and the surrounding area without any stimulation.
• Hyperalgesia: The patient's response to a noxious stimulus is prolonged or intensified.
• Allodynia: Nonnoxious stimuli cause pain in the patient. Such as small changes in temperature, clothing rubbing against the body, etc. will cause pain to the patient.
• Paresthesia: The patient will have some paresthesias such as numbness, itching and tightness in the painful area. Patients may also experience objective sensory abnormalities such as hypoesthesia, abnormal temperature and vibration sensations. 

3. Course of disease:

Postherpetic neuralgia persists for more than a year in 30% to 50% of patients. In some patients, the course of the disease can even reach ten years or more.

4. Other clinical manifestations:

Patients with postherpetic neuralgia are often accompanied by decreased mood, sleep and quality of life. Anxiety, depression, inability to concentrate, etc. are manifestations of moderate to severe disturbance of their emotions. Studies have pointed out that about 60% of patients have had or often have suicidal thoughts. More than 40% of patients have moderate to severe disturbance of daily life and sleep disturbance. Various systemic symptoms such as chronic fatigue, anorexia, weight loss and lack of activity may also appear in patients. 

Drug therapy for postherpetic neuralgia.

Gabapentin: It is a first generation calcium channel modulator. Its pharmacokinetic profile is non-linear and its bioavailability decreases with increasing dose. Its initial oral dose is 300 mg daily and patients need about several weeks to slowly titrate to the effective dose. Its effective dose is generally 900 to 1800 mg daily. The dose of gabapentin should be reduced in patients with renal insufficiency. In order to avoid adverse reactions of dizziness and drowsiness in patients, the dose should be started, slowly increased or gradually decreased at night.

Pregabalin: It is a second-generation calcium channel modulator. It can relieve postherpetic neuralgia. It can also improve sleep and mood disorders. Its pharmacokinetic profile is linear and has a rapid onset of action. Its oral initial dose is 150 mg daily. Its dose can be increased to 300 mg daily within a week and its maximum dose is 600 mg daily.

Amitriptyline: It is a tricyclic antidepressant. It inhibits the reuptake of serotonin and norepinephrine by the presynaptic membrane. It also blocks alpha adrenoceptors and sodium channels. The descending pathway of pain conduction will be regulated by the above mechanism to play an analgesic effect. However, its onset is slow. Its first dose should be taken at bedtime. Take two to three times a day, 12.5 to 25mg each time. The dose can be gradually increased according to the patient's response to amitriptyline. It recommends a maximum daily dose of 150mg, but in some patients up to 300mg is available. Amitriptyline should be avoided in patients with ischemic heart disease or at risk of sudden cardiac death. Patients with high risk of glaucoma, urinary retention and suicide should also use amitriptyline with caution.

5% lidocaine patch: It inhibits voltage-gated sodium channels and reduces ectopic impulses of primary afferent nerves after injury. This reduces pain perception in people with postherpetic neuralgia. Its onset of efficacy is ≤4 hours. Patients can apply 1 to 3 patches to the painful area. Each patch can be used for up to 12 hours.

Tramadol: It acts on μ-opioid receptors, serotonin receptors, and norepinephrine receptors to achieve analgesic effects. It can relieve burning pain, pin prick pain and allodynia caused by postherpetic neuralgia. However, it has no obvious analgesic effect on lightning-like and knife-like pain. Its initial dose is 25 to 50 mg once or twice daily. The maximum daily dose is 400mg. Nausea, vomiting, dizziness, constipation and other adverse reactions are dose-related.

Opioid analgesics such as morphine, oxycodone, and fentanyl are effective in the treatment of postherpetic neuralgia, but their addiction and tolerance limit them to second-line treatment. In addition, neurotrophic drugs can help relieve nerve pain and neuroinflammation. Commonly used drugs are methylcobalamin, vitamin B1 and vitamin B12. They can be given orally or injected intramuscularly.

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How should cough medicine be chosen?😷😷😷

Cough is one of the body's important defense mechanisms against pathogens. It clears respiratory secretions and substances that are harmful to the respiratory tract. However, severe and frequent cough can seriously affect the patient's life and work. According to the course of the disease, cough can be divided into chronic cough (>8 weeks), subacute cough (3 to 8 weeks) and acute cough (<3 weeks). According to the volume of sputum, it can also be divided into dry cough and wet cough (sputum volume > 10 ml per day). There are different treatment options for different types of coughs. Therefore, the following will introduce the different types of cough medicines.

1. The patient had frequent and severe cough, less or no sputum volume, no itchy throat, nasal congestion, runny nose, belching, acid reflux and other symptoms.

For this type of patients, it is recommended to use only single-ingredient antitussives. Antitussives can be divided into peripheral antitussives and central antitussives. Commonly used in clinical are dextromethorphan, pentoxyverine and phenproperine.

1. Dextromethorphan is a commonly used antitussive drug in clinical practice. Its effects are similar to codeine, but without the hypnotic and analgesic effects. Therapeutic doses generally have no inhibitory effect on the respiratory center and are not addictive. Adults are orally administered three times a day, 15 to 30 mg each time.
2. Pentoxyverine also has antispasmodic and anticonvulsant properties. It should be used with caution in patients with cardiac insufficiency and glaucoma. Adults are orally administered three times a day, 25 mg each time.
3. Phenproperine is a non-narcotic antitussive that inhibits peripheral afferent nerves. It also has some central cough-relieving effects. Adults are orally administered three times a day, 20 to 40 mg each time.

Phenproperine is the first choice for patients with severe cough, followed by dextromethorphan. Phenproperine or pentoxyverine is recommended for patients with an irritating dry cough. Phenproperine is indicated for patients with a cough that occurs mainly during the day. Dextromethorphan is used for patients who cough mainly at night. Studies have pointed out that the same dose of codeine and dextromethorphan have similar effects in reducing the frequency of chronic cough, but the antitussive effect of codeine is not as strong as dextromethorphan. In addition, dextromethorphan had no significant effect on treating nocturnal cough in children.

2. Patients with cough and phlegm or phlegm that is difficult to cough up.

The use of antitussives alone is not suitable for this type of patients, especially strong antitussives such as codeine. They reduce the secretion of the bronchial glands. It makes mucus thick and difficult to cough up. Not only can it worsen the infection, it can even increase the risk of choking. Therefore, mucolytics or expectorants (eg, acetylcysteine, ambroxol, ammonium chloride, bromhexine) should be the mainstay of treatment for this type of patient. Expectorant therapy enhances the clearing effect of cough on airway secretions. They increase phlegm discharge and enhance the antitussive effect. 

Ambroxol and bromhexine are mucolytics. Bromhexine is metabolized into ambroxol in the human body. It reduces the viscosity of secretions and promotes ciliary movement in the airways. In addition, it can increase the concentration of antibacterial drugs in the respiratory tract. 

• Ambroxol: Adults take 30-60 mg orally three times a day. 
• Bromhexine: Adults take 8-16 mg orally three times a day.

Acetylcysteine can reduce the viscosity of the patient's sputum. Adults take 600 mg orally once or twice a day, or 200 mg (granules) three times a day.

3. Patients with dry cough or low sputum production and nasal symptoms such as runny nose and/or nasal congestion and sneezing.

This cough is usually caused by a cold or rhinitis. Antihistamines or decongestants can significantly relieve cough symptoms in these patients. However, caution should be exercised when prescribing these medications for children. Central or peripheral antitussives can be used in patients with severe cough. First-generation antihistamines (chlorpheniramine), decongestants (ephedrine, pseudoephedrine), and antitussives (codeine, dextromethorphan, pholcodine) are used to treat the common cold with cough. Medications containing codeine are contraindicated for children under 18 years of age. Drugs containing ephedrine and pseudoephedrine should be used with caution in patients with hypertension and heart disease.

4. Patients cough with shortness of breath or wheezing but no nasal symptoms.

It is recommended to treat this type of patient with drugs that suppress bronchospasm and relieve cough during asthma attacks, such as aminophylline and methoxyphenamine. When patients use aminophylline, lincosamides (clindamycin, lincomycin), macrolides (clarithromycin, erythromycin, roxithromycin), quinolones (ciprofloxacin, norfloxacin, ofloxacin), tetracyclines (doxycycline, minocycline). They inhibit the excretion of aminophylline and cause aminophylline poisoning. Azithromycin and moxifloxacin can be used in combination with aminophylline because they have no obvious interaction.

5. Patients with cough accompanied by one or more symptoms of typical acid reflux, such as acid reflux, belching, burning sensation behind the breastbone, and epigastric fullness.

This cough is due to gastroesophageal reflux. Patients are generally treated for the cause and do not require antitussive therapy.

6. Cough caused by cough variant asthma, eosinophilic bronchitis, allergic cough, pharyngitis, drug-induced cough, and psychogenic cough.

Antitussive therapy is generally not required for these patients. Treatment should be directed at the cause of the patient's cough.

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How should Ivabradine be used?💔💔💔

The end stages of various cardiovascular diseases lead to heart failure. Patients with heart failure are characterized by high mortality and poor prognosis. One of the important predictors of death from heart failure is heart rate. Therefore, how to effectively control the heart rate of the patient is extremely critical. The guidelines for the diagnosis and treatment of heart failure set the resting heart rate down to about 60 beats per minute as the goal of heart rate management in patients with chronic stable heart failure. β-blockers and ivabradine are clinically mainly used to lower heart rate. 

What is the difference between β-blockers and ivabradine?

β-blockers reduce sympathetic activity and resting heart rate. It will benefit patients with heart failure by reducing myocardial oxygen consumption, reducing cardiac work, delaying and improving ventricular structural remodeling. The guidelines for the treatment of heart failure state that all symptomatic patients with chronic heart failure need long-term use of β-blockers unless the patient is intolerable or contraindicated. At present, it is clinically recommended that the dose for patients with heart failure to reduce the heart rate to 60 beats/min is the target dose or maximum tolerated dose of β-blockers. When treating patients with heart failure, the tolerable target dose should be reached as soon as possible to reduce the resting heart rate. It will result in the greatest benefit to the patient. During the treatment of patients, attention should be paid to whether they may develop worsening heart failure, bradycardia, atrioventricular block, etc., especially at the beginning of treatment and when the dose is increased. β receptors are also distributed in blood vessels. Therefore, peripheral vasculature, coronary resistance and blood pressure are all affected by beta-blockers. Due to the decline of the patient's heart function, too fast increase of the dose of β-blockers can induce or aggravate the risk of heart failure. The dose of β-receptor blockers can reduce the work of myocardial cells and oxygen consumption rate by controlling the heart rate, but it is also necessary to avoid excessive inhibition of myocardial contractility by β-receptor blockers to affect cardiac output and blood pressure. 

Ivabradine is a pure sinoatrial node If-channel blocker. It generally only acts on the ion channel of the sinoatrial node, but in large doses it will also act on the Ih-channel of the retina, resulting in phosphenes. Ivabradine reduces sinus node excitability. It has the characteristic that the faster the base heart rate, the more obvious the effect. No negative inotropic and negative conduction effects are its important features and it will not affect blood pressure.

What is the usual usage of ivabradine?

Many treatment guidelines recommend the use of ivabradine for heart failure with reduced ejection fraction (HFrEF). For patients with sinus rhythm failure of New York heart function class II to IV and left ventricular ejection fraction (LVEF) ≤ 35%, ivabradine can be added with one of the following conditions:

1. The patient has been treated with angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers/angiotensin receptor neprilysin inhibitors, aldosterone receptor antagonists, and β-blockers. The patient has used the target dose or the maximum tolerated dose of β-blockers but the heart rate is still ≥70 beats/min.
2. Heart rate ≥ 70 beats/min in patients who are contraindicated or intolerant of β-blockers.

The guidelines for the use of ivabradine in patients with heart failure are as follows:

1. Patients with chronic HFrEF on ACE inhibitors/ARBs, β-blockers, and spironolactone who have significantly increased resting heart rate (≥80 beats/min) and who cannot increase the dose of β-blockers, the dose of β-blockers can be considered as the maximum tolerated dose in the current state. Early combined use of ivabradine can improve cardiac function and control heart rate. It is also beneficial for patients to subsequently increase the dose of β-blockers.
2. When β-blockers are used in the treatment of patients in the vulnerable stage of heart failure, the dose should not be increased too rapidly. Patients achieved target heart rate more quickly when ivabradine was used in combination. Patients will also more quickly enter into compensation and stabilization.
3. When patients with acute heart failure enter the pre-discharge stage (the patient's hemodynamic status is stable, after orthopnea is relieved, and vasoactive drugs and vasoactive drugs are stopped), ACEI/ARB,  β-blockers and spironolactone therapy can be started on the patient. If the patient has previously used ACEI/ARB, β-blockers and spironolactone, the dose can be increased. However, if the patient has tachycardia, the dose of beta-blockers should not be increased too rapidly. Combined use of ivabradine is beneficial to control the heart rate of patients with tachycardia and further improve cardiac function.
4. Some studies have pointed out that when patients with heart failure and chronic obstructive pulmonary disease are intolerant to β-blockers or can no longer increase the dose, ivabradine can be used in combination or switched. It can control patients' heart rate, improve symptoms and benefit their prognosis.

The recommended starting dose for patients with chronic HFrEF is 5 mg twice daily with meals. The starting dose for elderly patients ≥75 years is 2.5 mg twice daily. Patients were evaluated and dose adjusted two weeks after treatment. The patient's resting heart rate should be controlled at about 60 beats per minute. The maximum dose of ivabradine is 7.5 mg twice daily. Ivabradine is only metabolized by CYP3A4. Ivabradine is only metabolized by CYP3A4. It interacts with inhibitors and inducers of CYP3A4. CYP3A4 inducers decrease the plasma concentration of ivabradine whereas CYP3A4 inhibitors increase its plasma concentration. Elevated plasma concentrations of ivabradine may cause bradycardia in patients.

What other cardiovascular diseases can ivabradine be used for?

The general indication of ivabradine is for sinus rhythm and heart rate ≥ 75 beats/min, accompanied by New York Heart Function Class II to IV chronic heart failure patients with systolic dysfunction. In order to control the patient's condition early or improve the patient's prognosis, there are several practical clinical applications as follows:

1. Stable coronary artery disease: ivabradine or nicorandil can be used for patients who have contraindications to the use of β-blockers, poor treatment effect or adverse reactions. Ivabradine can reduce the heart rate of patients with coronary heart disease to reduce oxygen consumption, increase coronary blood flow, improve coronary microcirculation, prevent ischemia and improve exercise tolerance.
2. After the symptoms of acute heart failure are relieved: when the heart rate of a patient with acute heart failure is still fast after systemic treatment, the treatment guidelines require that the patient should use β-blockers as soon as possible. In patients with acute heart failure who are hemodynamically stable after hospitalization, if the patient cannot tolerate β-blockers, low-dose ivabradine (2.5 mg twice a day) may be considered initially . Ivabradine can be adjusted according to the blood pressure and heart rate of the patient. At the same time, the β-blockers used by patients should be evaluated in time, so that the two can be used in combination reasonably. It can further improve the symptoms of heart failure decompensation and reduce the risk of rehospitalization.
3. Focal atrial tachycardia, inappropriate sinus tachycardia, and orthostatic tachycardia syndrome: Guidelines recommend ivabradine alone or in combination with beta-blockers in patients with symptomatic inappropriate sinus tachycardia. Guidelines recommend ivabradine alone or in combination with beta-blockers in patients with symptomatic inappropriate sinus tachycardia. Ivabradine may be considered in patients with postural tachycardia syndrome. Patients with chronic focal atrial tachycardia may consider using ivabradine combined with β-blockers.
4. Heart rate preconditioning before coronary CT angiography: Excessive heart rate will affect coronary CT angiography. Therefore, metoprolol and propranolol are general pretreatment drugs. Ivabradine safely, rapidly and consistently lowers the patient's heart rate. The regimen of using ivabradine alone or in combination may be a better choice.

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How should doctors choose eye drops?👀👀👀

Today's people's work patterns and lifestyles have changed. These changes place an increasing burden on the eyes. Therefore, more and more people have some problems with their eyes nowadays. Eyes can feel uncomfortable for various reasons in everyday life. Dryness, fatigue, bloodshot eyes, itching, etc. are mild symptoms of the eyes. Tears, redness, inflammation, excess eye mucus, and even blurred vision are serious eye discomforts. The following will explain what eye drops should be used when the above symptoms appear.

1. Symptoms: Dry, tired, bloodshot eyes.

People who often use their eyes, such as students and clerks, are more prone to these symptoms. Excessive use of their eyes reduces their tear production. It can cause dryness, discomfort, fatigue and bloodshot eyes. These are relatively mild symptoms. Generally, preservative-free artificial tear eye drops such as sodium hyaluronate eye drops and polyvinyl alcohol eye drops are sufficient. These drugs can effectively relieve the above symptoms. Sodium hyaluronate eye drops are generally used at a concentration of 0.1%. However, 0.3% sodium hyaluronate eye drops should be used when the treatment is not obvious or in severe cases.

2. Symptoms: Itchy eyes.

Symptoms of itchy eyes are common in allergic diseases. For example, allergic rhinitis can easily cause itchy eyes, and even lead to allergic conjunctivitis in severe cases. When patients only have mild eye itching, anti-allergic eye drops such as olopatadine hydrochloride eye drops can be used to treat these patients. Oral allergy medications such as loratadine can be used as a temporary alternative when antiallergy eye drops are not available. If a patient has severe itchy eyes, this is allergic conjunctivitis. Antiallergic eye drops can usually treat this symptom. If the therapeutic effect of these anti-allergic eye drops is not satisfactory, after measuring the intraocular pressure of the patient, hormone eye drops (such as fluorometholone) can be used in combination for auxiliary treatment. Benzalkonium chloride is a preservative commonly used in ophthalmic products. There are clinical reports that benzalkonium chloride can cause toxic ulcerative keratopathy and punctate keratopathy. Therefore, patients with dry eye who require long-term or frequent use of these eye drops or who have corneal damage should be closely monitored while using these eye drops.

3. Symptoms: Watery eyes, red, swollen, inflamed eyes, excessive eye mucus.

These symptoms are usually due to conjunctivitis. If the patient's eye mucus increases, this symptom generally belongs to bacterial conjunctivitis. For people with bacterial conjunctivitis, antibiotic eye drops can be used to treat them. Among the most commonly used are levofloxacin eye drops and tobramycin eye drops. In order to avoid bacterial resistance, the time of medication should be controlled within the minimum time required to treat the disease. In women of potential pregnancy or pregnant women, these drugs are prescribed only if the therapeutic benefits outweigh the possible risks. In addition, for patients with concurrent viral infections, antiviral eye drops need to be used in combination. Clinically common antiviral eye drops include acyclovir and ganciclovir.

4. Symptom: Blurred vision.

Older adults experience blurred vision. The eyes seem to be blocked by something and cannot see clearly. At this time, patients should seek medical treatment as soon as possible to check whether they have cataracts.

What is the correct usage of eye drops?

The correct usage of eye drops:

1. Wash hands before using eye drops. Check to see if it is the eye drops you want to use. After opening the eye drops, the bottle cap should be placed flat without allowing the cap mouth to directly touch the table.
2. The opening of the eye drops should not touch the patient's eyelids or eyelashes. It will contaminate the eye drops and make the eye drops lose their efficacy.
3. Patients should gently close their eyes for about 3 minutes after using the eye drops.
4. If a patient needs to use several ophthalmic drugs in different dosage forms at the same time, the patient should use the thinner drug and then the thicker drug. For example, patients should use eye drops first, then eye gel, and then eye ointment. This practice ensures adequate absorption of various medications.

Precautions for eye drops.

The preservatives in the eye drops have certain toxicity to the patient's cornea and conjunctiva and cause different adverse reactions. Therefore, patients should not overuse eye drops to relieve eye fatigue. Patients should rest with eyes closed or look into the distance instead of using eye drops. Patients should not use eye drops more than 6 times per day for no more than 7 consecutive days unless directed by a physician. In addition, it is not recommended to continue using the eye drops 1 month after opening.

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What is the difference between acarbose, miglitol and voglibose?📏📏📏

Acarbose, miglitol and voglibose are commonly used clinical α-glucosidase inhibitors. Although they all belong to the same type of hypoglycemic drugs, there are some differences between them and the choice of drugs is also different.

What is the mechanism of action of α-glucosidase inhibitors?

α-glucosidase inhibitors reversibly inhibit α-glucosidase. They inhibit the degradation of disaccharides, oligosaccharides and polysaccharides to glucose and other monosaccharides. As a result, the absorption and decomposition of carbohydrates will be delayed, which will lower the patient's postprandial blood sugar.

It can be seen from the figure above that the structures of glucose and miglitol are very similar. Therefore, α-glucosidase inhibitors have good inhibitory effects on various α-glucosidases.

	Acarbose	Miglitol	Voglibose
Maltase	+	+	++
Isomaltase	+	+	+
Sucrase	+	+	++
Glucoamylase	+	+	-
α-amylase	+	+	-
Trehalase	-	+	-
Lactase	-	+	-

Since acarbose, miglitol and voglibose all have strong inhibitory effects on sucrase, sucrose or starch should not be used in hypoglycemic conditions in patients taking α-glucosidase inhibitors to correct blood sugar in patients. These foods are less effective at correcting blood sugar levels for this condition. Glucose or honey should be consumed to correct blood sugar in these patients.

What are the clinical applications of α-glucosidase inhibitors?

α-glucosidase inhibitors are indicated for patients with elevated postprandial blood glucose following a carbohydrate-based diet. Some researchers have evaluated clinical studies on patients with type 2 diabetes, and the results show that α-glucosidase inhibitors can reduce the HbA1c of patients by about 0.5% and reduce their weight. Studies have shown that acarbose can reduce the risk of developing diabetes by 25% in patients with impaired glucose tolerance within 3.3 years. Therefore, acarbose can be used to treat patients with type 2 diabetes and reduce postprandial blood glucose in patients with impaired glucose tolerance.

Drug Name	Common dosage forms
Acarbose	Oral regular-release dosage form.
	Chewable tablet.
Miglitol	Oral regular-release dosage form.
Voglibose	Oral regular-release dosage form.
Oral regular-release dosage forms include regular tablets, soft capsules, hard capsules and enteric-coated capsules.

Effects of α-glucosidase inhibitors on the liver.

Acarbose: 1 to 2% of orally administered acarbose is absorbed through the gut. In addition, digestive enzymes and intestinal bacteria will also break down some of the acarbose. These amounts add up to about 35% of the dose. High doses of acarbose may cause asymptomatic liver enzyme elevations. Therefore, monitoring of changes in liver enzymes in patients should be considered during the first 6 to 12 months of treatment. Acarbose is contraindicated in patients with severe liver disease.

Miglitol: Miglitol can be completely absorbed after oral administration of 25 mg. 100mg of miglitol is only about 50 to 70% absorbed. Miglitol is not metabolized in the body. Therefore, there is no mention of hepatotoxicity in its labelling. In addition, the incidence of rash when taking miglitol orally is about 4.3%. This rash is usually temporary.

Voglibose: After oral administration of voglibose, voglibose could not be detected in the patient's plasma and urine. However, less than 0.1% of patients will develop fulminant hepatitis, severe liver dysfunction with elevated ALT and AST, or jaundice after taking voglibose. Voglibose should be used with caution in patients with severe hepatic impairment.

What are the drug interactions of acarbose, miglitol and voglibose?

Common ground: The clinical efficacy of α-glucosidase inhibitors is suppressed by digestive enzyme preparations and intestinal adsorbents.

The difference:

1. Acarbose: The bioavailability of digoxin can be affected by acarbose. Therefore, the dose of digoxin needs to be adjusted when the two are used at the same time.
2. Miglitol: Studies have shown that when healthy people take digoxin and miglitol at the same time, the plasma concentration of miglitol will be reduced by 19 to 28%. However, in diabetic patients taking digoxin, the concentration of digoxin in their blood will not change due to the combination of miglitol. In addition, the bioavailability of ranitidine and propranolol was decreased by about 60% and 40%, respectively, by miglitol.
3. Voglibose: Its instruction manual does not mention the above interaction.

What is the dosage of acarbose, miglitol and voglibose?

Acarbose: The initial dose is 50mg three times a day, and then gradually increased to 100mg three times a day. For individual patients, the dose can be increased to 200 mg three times a day. Acarbose needs to be swallowed whole immediately before a meal or chewed with food at the beginning.

Miglitol: The general recommended initial dose is 25 mg three times a day. The recommended maintenance dose is 50 mg three times a day. Its maximum recommended dose is 100 mg three times daily. Miglitol needs to be taken at the beginning of each meal.

Voglibose: The dosage for adults is generally 0.2 mg three times a day. If the curative effect of the patient is not obvious, the dosage can be increased to 0.3mg each time. Voglibose needs to be taken orally before meals, and meals need to be taken immediately after taking the medicine.

α-glucosidase inhibitors slow the digestion and absorption of carbohydrates in the small intestine. Flatulence is caused by bacteria in the colon that interact with unabsorbed sugars. It may cause bloating, abdominal pain, and diarrhea. Therefore, α-glucosidase inhibitors need to be started with small doses. This can reduce the occurrence of gastrointestinal reactions.

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