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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What are the classifications and differences of commonly used antifungal drugs?👀

More patients develop deep fungal infections (invasive fungal infections) due to the increased use of immunosuppressive drugs, antibiotics, organ transplants, and medically invasive procedures. Therefore, the use of antifungal drugs is also increasing and the rational use of antifungal drugs has become important.

What are the antifungal drugs for invasive fungal infections?

Antifungal drugs commonly used for invasive fungal infections are systemic antifungal drugs. Among them are:

Echinocandins : Anidulafungin, caspofungin and micafungin.

Polyenes : Amphotericin B and nystatin. Nystatin is mainly used in the treatment of Candida infections of the gastrointestinal tract and its oral absorption is poor.

Triazoles : fluconazole, isavuconazole, itraconazole, posaconazole and voriconazole.

Squalene epoxidase inhibitor : Oral terbinafine is mainly used for superficial fungal infections (such as hair, skin and nails).

Pyrimidines : Flucytosine.

Others : Oral griseofulvin is also mainly used for superficial fungal infections (such as hair, skin and nails).

What is the mechanism of action of antifungal drugs?

1. Fungal cell wall synthesis inhibitor : The main component of fungal cell wall is 1,3-β-gluean. Echinocandin drugs exert antifungal effects mainly by inhibiting the synthesis of 1,3-β-gluean. In addition, since human cells do not have cell walls, the toxicity of echinocandin drugs is relatively low.

2. Membrane Stability Inhibitors : Polyenes bind to ergosterol on fungal cell membranes. It acts as an antifungal agent by causing impaired cell membrane permeability. Damage to the cell membrane is also responsible for the toxicity of amphotericin B. However, it binds to human cell membranes much weaker than to fungal cell membranes.

3. Ergosterol Synthesis Inhibitors : 14-α-sterol demethylase is a microsomal enzyme. It will be inhibited by triazoles to reduce the synthesis of ergosterol and play an antifungal effect. Squalene cyclooxygenase will be inhibited by squalene epoxidase inhibitor to reduce the synthesis of lanosterol (the precursor of ergosterol) and play an antifungal effect.

4. Fungal Nucleic Acid Synthesis Inhibitors : Fungal cells convert pyrimidine antifungals to 5-fluorouracil. It inhibits the nucleic acid synthesis of fungi and thus acts as an antifungal agent.

Which fungal infections can they treat?

Flucytosine has strong antagonism against Candida and Cryptococcus. However, since fungi will rapidly develop drug resistance to flucytosine, flucytosine is mainly used in combination with amphotericin B in the clinical treatment of severe fungal infections.

The following table shows the antibacterial spectrum of commonly used antifungal drugs:

How to choose antifungal drugs?

The clinical selection of antifungal drugs is mainly based on the antifungal drug spectrum, pharmacokinetic characteristics, and the severity of the patient's infection. Fluconazole, flucytosine, and voriconazole cross the blood-brain barrier in patients. More than 80% of the dose of fluconazole and flucytosine will be excreted through the kidneys in their original form. Caspofungin, isavuconazole, itraconazole, micafungin, posaconazole, voriconazole, less than 2% of the dose will be excreted unchanged through the kidneys. 

1. Invasive pulmonary aspergillosis : For patients with invasive pulmonary aspergillosis, voriconazole is the first choice for clinical treatment. Isavuconazole will be used as an alternative drug.

2. Candidal disease : Caspofungin or micafungin are the first choice for the treatment of blood infection candidiasis. Since most of the fluconazole taken will be excreted through the kidneys in its original form, fluconazole is the first choice for the treatment of patients with urinary tract infection candidiasis. Amphotericin B can be used as an alternative treatment drug.

3. Cryptococcal disease : For patients with nonmeningitis infections, fluconazole is the first choice for the treatment. In severe cases, amphotericin B can be used for treatment. However, if the patient has meningitis, a combination of amphotericin B and flucytosine is required. When the patient enters the treatment maintenance period, fluconazole can be used. This is due to the fact that both fluconazole and flucytosine can enter the cerebrospinal fluid.

4. Mucormycosis : Clinically, amphotericin B is the first choice for the treatment of patients with mucormycosis. Isavuconazole can be used as an alternative treatment drug.

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What is the difference between the new hypolipidemic agents alirocumab and evolocumab?😵😵😵

A new type of hypolipidemic agent that is a PCSK9 inhibitor developed in
recent years. It is effective in lowering low-density lipoprotein cholesterol (LDL-C) levels alone or in combination with statins. Alirocumab and evolocumab (both are injections) are two commonly used PCSK9 inhibitors in clinical practice.

How does the body clear LDL-C?

LDL-C is transported from surrounding tissues to the liver by high-density lipoprotein cholesterol (HDL-C). After they reach the liver, they will bind to the LDL receptors on the liver cells and be transported into the liver cells. LDL-C is degraded and metabolized in liver cells.

What is PCSK9?

Proprotein Convertase Subtilisin/Kexin Type 9 is the full name of PCSK9. It degrades LDL receptors by binding to LDL receptors on the surface of liver cells. It reduces the number of LDL receptors on the surface of liver cells and prevents the removal of LDL-C from the blood.

How do PCSK9 inhibitors lower blood lipids?

PCSK9 is specifically bound by PCSK9 inhibitors so that it cannot bind to LDL receptors. Thus, the degradation of LDL receptor caused by PCSK9 is inhibited. This can increase the number of LDL receptors on the surface of liver cells and enhance the effect of clearing LDL-C in the blood.

What is the approximate strength of lipid-lowering effect of PCSK9 inhibitors?

PCSK9 inhibitors such as alirocumab and evolocumab have strong cholesterol-lowering effects. LDL-C can be lowered by about 50 to 70% by them. Several commonly used lipid-lowering regimens and their magnitude of lowering LDL-C:

• Ezetimibe: It lowers LDL-C by about 20% on average.
• Moderate-strength statins (such as simvastatin and pravastatin): They lower LDL-C by about 30% on average.
• High-intensity statins (such as atorvastatin and rosuvastatin): They lower LDL-C by about 50% on average.
• Monotherapy with PCSK9 inhibitors: They reduce LDL-C by about 60% on average.
• High-intensity statin + Ezetimibe: They reduce LDL-C by about 65% on average.
• High-intensity statin + PCSK9 inhibitor: They reduce LDL-C by about 75% on average.
• High-intensity statin + PCSK9 inhibitor + Ezetimibe: They reduce LDL-C by about 85% on average.

Usage and dosage of PCSK9 inhibitors.

Both alirocumab and evolocumab are given subcutaneously. Alirocumab is injected every 2 weeks and evolocumab is injected monthly. 

	Alirocumab	Evolocumab
Common dosage forms	Single-dose prefilled injection pen
	75mg/1ml/pen 150mg/1ml/pen	140mg/1ml/pen
Dosage	Subcutaneous injection: Upper arms, abdomen or thighs.
	1 time every 2 weeks, 75 to 150mg each time.	1 time per month, 420mg each time.
Storage	Store away from light at 2 to 8oC. They should not be refrigerated and shaken. Return to room temperature for at least 30 minutes before use. It can be stored at room temperature (25 oC) for up to 30 days when the patient travels.

What are their side effects?

1. Common adverse reactions of PCSK9 inhibitors include: 

Influenza, nasopharyngitis, upper respiratory infection, back pain. In addition, there may be pain, erythema and bruising at the injection site.

2. Specific adverse reactions of PCSK9 inhibitors are:

PCSK9 inhibitors, like other therapeutic protein drugs, may cause immune reactions. Clinical studies have pointed out that in patients with neutralizing antibodies, the long-term lipid-lowering effect of the drug will not be affected. However, they have an increased incidence of local injection reactions.

What is the difference between the adverse effects of PCSK9 inhibitors and statins?

Muscle toxicity: PCSK9 inhibitors did not increase the incidence of muscle-related adverse reactions in the current clinical research performance. They have the opportunity to become a new option for lipid-lowering therapy in patients with muscle-related adverse events on statins.

Hepatotoxicity: PCSK9 inhibitors did not significantly increase liver function damage compared with placebo in the current clinical research performance. Therefore, no dosage adjustment is required for their use in patients with mild or moderate hepatic impairment.

Blood glucose changes in patients: PCSK9 inhibitors did not accelerate the transformation of prediabetic patients to diabetes in current clinical studies. They also did not affect fasting blood glucose and glycated hemoglobin levels in non-diabetic patients. The incidence of dysglycemic events was not increased by the use of PCSK9 inhibitors.

What are the clinical applications of PCSK9 inhibitors?

For patients who are intolerant to statins or have contraindications, PCSK9 inhibitors can be used alone or in combination with other lipid-lowering drugs.

PCSK9 inhibitors combined with maximally tolerated doses of statins can further reduce the risk of cardiovascular events in patients with atherosclerotic cardiovascular disease.

If after four to six weeks of treatment with statins combined with ezetimibe in patients with ultra-high-risk atherosclerotic cardiovascular disease, the patient's LDL-C does not reach the treatment target (LDL-C<1.4mmol/L), it is recommended to add PCSK9 Inhibitors.

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What medicines should not be taken with milk?🥛🥛🥛

Milk is a great natural nutritional supplement. It is also a drink that many people drink every day. Although drinking milk has many benefits for people, it will affect the absorption of drugs when it is taken with many drugs at the same time. It may even interact with those drugs and make them less effective. One of the main reasons is that milk can form a thin film on the surface of gastric mucosa and drugs. When the film is digested and absorbed, the drug may miss its optimal absorption period. As a result, drug absorption and efficacy are reduced. In addition, milk can also produce physical or chemical reactions with some drugs. It may adversely affect medicines. Milk contains substances such as iron, calcium, phosphorus, protein, fat and multivitamins. They react chemically with some drugs and form insoluble salts or stable chromium compounds. This can make it difficult for the body to absorb the medicine and can even lead to gallstones or kidney stones. Some drugs are listed below for specific explanation:

1. Preparations containing iron, zinc or calcium.

Calcium, zinc, or iron preparations such as calcium lactate, calcium gluconate, zinc gluconate, ferrous gluconate, ferrous fumarate, and ferrous succinate can form clots with the protein in milk. In addition to reducing the absorption of drugs and reducing the peak plasma concentration of drugs, this clot will also increase the burden on the gastrointestinal tract. Iron can also be precipitated by phosphorus in milk and affect its absorption. Iron is absorbed mainly in the duodenum and proximal jejunum in the form of ferrous ions. Calcium ions in milk compete with iron for absorption in the duodenum. It reduces iron absorption and effectiveness. Therefore, when patients take calcium, zinc or iron preparations, they should be separated from milk for 1 to 2 hours.

2. Antacids and gastric mucosal protective agents.

Aluminum hydroxide, bismuth potassium citrate, calcium carbonate, magnesium hydroxide, sodium bicarbonate, etc. are clinically commonly used antacids and gastric mucosal protective agents containing metal ions. The above-mentioned drugs containing metal ions also form clots with proteins in milk. It will reduce the efficacy of drugs and increase the burden on the gastrointestinal tract, but also affect the body's absorption of nutrients in milk. In addition, when sodium bicarbonate is taken together with milk, milk-alkali syndrome can occur.

3. Most antibacterial drugs.

Almost all quinolones such as ciprofloxacin, levofloxacin, and norfloxacin will be combined into insoluble chelates by metal ions in milk. These chelates will affect the absorption of antibacterial drugs, reduce their antibacterial effect, and make the drug less effective or even completely ineffective. Therefore, most antibacterial drugs should not be taken together with milk.

4. Drugs for the treatment of cardiovascular diseases.

Drink a lot of milk while taking digoxin, digitoxin and other drugs for the treatment of chronic heart failure. The toxicity of these drugs will be increased by the calcium ions in the milk. When patients with severe hypertension take antihypertensive drugs, if they take milk or milk products at the same time, their blood pressure may rise sharply. In severe cases, the patient's blood pressure will continue to rise, and even hypertensive crisis will occur.

5. Anti-Parkinson's disease drugs.

Milk should not be taken together with anti-Parkinson's disease drugs such as carbidopa and levodopa. These drugs need a carrier to help them move in the body when they are absorbed in the small intestine. The aromatic amino acids contained in protein in milk will compete with them for the same carrier system and affect their absorption.

6. Antidepressants.

Monoamine oxidase inhibitors in antidepressants should not be taken with milk. When monoamine oxidase is inhibited, tyramine, which is rich in milk, will accumulate in the body in large quantities. It can cause cardiac arrhythmia, sudden increase in blood pressure, and severe cases can lead to cerebral hemorrhage and even death.

7. Constipation medicine.

The stimulant laxative bisacodyl is used to treat acute, chronic, and habitual constipation. The enteric coating of bisacodyl is prematurely dissolved by the milk, making it irritating to the stomach and duodenum. Therefore, milk should not be consumed for 2 hours before or after taking this medicine.

8. Other drugs.

Calcium and bone metabolism regulators such as alendronate sodium, ibandronate sodium, anticancer drugs such as estramustine, etc. should not be taken together with milk.

Unless instructed by a doctor, it is best to take the medicine with water, not milk, tea, etc.

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How to choose external medicine for skin disease?🙌🙌🙌

Whenever the seasons change, many people will have some skin problems
(such as skin allergies, eczema, tinea manuum, tinea pedis, etc.). There are many different types of ointments available at community pharmacies for skin inflammation. Many patients don't know what are the uses and differences of these ointments? This article will introduce the relevant knowledge of topical ointments commonly found in community pharmacies.

What are the common skin diseases?

1. Infectious skin diseases:

Infectious skin diseases: When patients are infected by fungi and suffer from skin diseases, then patients should choose ointments containing antifungal drug ingredients. Econazole, ketoconazole, and miconazole are commonly used antifungal ingredients in ointments. If the patient has pustules on the skin, it is likely due to a bacterial infection. Therefore, patients should choose ointments containing antibacterial ingredients, such as mupirocin ointment, chlortetracycline ointment and erythromycin ointment.

2. Allergic skin diseases:

The vast majority of dermatitis and eczema are allergic skin diseases. This type of skin disorder generally responds well to steroid therapy. Weak- or moderate-acting steroid creams are used on areas of tender or wrinkled skin such as the face, armpits, groin or vulva. Strong-acting steroid creams can be used to treat areas of thicker skin, but stronger steroid creams are usually only used for about a week. When the patient's symptoms improve, they are switched to a weaker steroid cream. Because of the thin skin in babies and children, they usually only get weak steroid creams and they should not be used for too long.

An introduction of the strength of steroid creams for topical use.

Weak-acting steroid creams:

Hydrocortisone Acetate 1.0%: Apply to the affected area 2 to 4 times a day and massage gently for a while. It can be used to treat non-infectious skin diseases, allergic skin diseases and some proliferative skin diseases, such as eczema, pruritus, dermatitis, seborrheic dermatitis, neurodermatitis. Long-term use can cause pigmentation, telangiectasia, skin atrophy and secondary infection. Occasionally, patients have allergic reactions. It is contraindicated in infectious skin diseases such as tinea corporis, jock itch, impetigo, etc.

Medium-acting steroid ointment:

Prednisolone Acetate 0.5%: Apply an appropriate amount of ointment to the affected area 2 to 3 times a day. It is suitable for allergic eczema, lichenoid pruritus, seborrheic dermatitis and contact dermatitis, etc. Long-term use can cause pigmentation, telangiectasia, skin atrophy and secondary infection. Occasionally, patients have allergic reactions. It is contraindicated in infectious skin diseases. 

Dexamethasone acetate 0.05%: It is mainly used for autoimmune inflammatory diseases and allergic diseases, such as chronic eczema, contact dermatitis, seborrheic dermatitis, neurodermatitis, localized pruritus, etc. Patients generally take a small amount of ointment and apply it to the affected area two to three times a day and rub it gently for a while.

Clobetasone Butyrate 0.05%: It is used for short-term control and treatment of dermatitis and eczema, such as allergic dermatitis, primary irritant dermatitis, atopic eczema, etc. Children over 12 years old or adults can apply an appropriate amount of the ointment to the affected area twice a day. It can be used for up to seven days.

Triamcinolone acetonide 0.025 to 0.1%: It can be used in the treatment of eczema, pruritus, seborrheic dermatitis, allergic dermatitis, neurodermatitis. Apply to the affected area 2 to 3 times a day and massage gently for a while.

Hydrocortisone Butyrate 1.0%: It can be used to treat lichenoid pruritus, seborrheic dermatitis, allergic dermatitis, allergic eczema, etc. Apply an appropriate amount of ointment to the affected area twice a day.

Fludrocortisone acetate 0.025%: It is mainly used to treat skin pruritus, eczema, psoriasis, seborrheic dermatitis, contact dermatitis, neurodermatitis, allergic dermatitis, atopic dermatitis and other skin diseases. Apply ointment topically to affected area twice daily. Long-term use may cause acne, folliculitis, perioral dermatitis, telangiectasia, skin atrophy, and possibly increased susceptibility to infection. Occasionally, patients develop allergic contact dermatitis.

Fluocinolone 0.01%: It can be used to treat psoriasis, pruritus, eczema, seborrheic dermatitis, neurodermatitis, atopic dermatitis, allergic dermatitis, contact dermatitis, etc. Apply to affected areas twice daily. Infants or children should not be given medication for too long and the amount of medication should be kept to a minimum. Long-term or large-scale use of ointment by patients can cause telangiectasia, perioral dermatitis, and skin atrophy. Patients may also have increased skin susceptibility to infection. Occasionally, patients develop reactive contact dermatitis.

Strong-acting steroid ointment:

Beclomethasone Dipropionate 0.025%: It treats inflammatory and allergic skin diseases and related conditions, including pruritus, discoid lupus erythematosus, lichen planus, psoriasis, palmar impetigo, eczema, neurodermatitis, allergies Dermatitis, contact dermatitis, etc. Apply topically to affected area two to three times daily. It should be used with caution in infants.

Mometasone furoate 0.1%: It is indicated for the treatment of pruritus, neurodermatitis, atopic dermatitis and eczema. Apply an appropriate amount of ointment to the affected area once a day.

Fluocinolone 0.025%: In addition to the above-mentioned dermatitis, it can also be used for vitiligo, psoriasis, etc. It is generally used 2 to 3 times a day.

Betamethasone 0.05%: It is indicated for the relief of itching and inflammation in children 13 years and older and adults with hormone-sensitive skin disorders. However, it is contraindicated in children 12 years and younger.

Super strong-acting steroid ointment:

Clobetasol Propionate 0.02 to 0.05%: It can be used to treat discoid lupus erythematosus, palmar impetigo, lichen planus, psoriasis, chronic eczema, neurodermatitis and other skin diseases for which topical steroid therapy is effective. It cannot be used for long-term, large-area applications.

Betamethasone 0.1%: Apply to the affected area two to four times a day and massage gently for a while.

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What should be paid attention to when taking levothyroxine for a long time to treat hypothyroidism?😮😮😮

Levothyroxine is a thyroid hormone drug. It is generally used clinically for the treatment of hypothyroidism, non-toxic goiter, thyroid hormone supplementation after surgical resection of thyroid cancer, and adjuvant treatment of hyperthyroidism with antithyroid drugs. The following will introduce the precautions about the use of levothyroxine.

The basic knowledge of levothyroxine.

In clinical practice, the most commonly used dosage form of levothyroxine is levothyroxine sodium tablets. It is most commonly used as a replacement for patients with hypothyroidism and as an adjunctive treatment for patients with hyperthyroidism.

What are the pharmacological effects of levothyroxine?

One of the main indications for levothyroxine is as an alternative treatment for hypothyroidism. Insufficient synthesis and secretion of thyroid hormone in the body is the main cause of hypothyroidism. Levothyroxine is a synthetic form of tetraiodothyronine (T4). It is converted in the body to the more active triiodothyronine (T3). Thus it will exert the same effect as the thyroxine secreted by the body itself and treat hypothyroidism.

Who are the suitable and contraindicated groups of levothyroxine?

It is generally used in patients with thyroid-related diseases. However, it should be prescribed by a doctor and should not be used by patients on their own. It should be contraindicated in patients with untreated adrenal or pituitary insufficiency, thyrotoxicosis, acute myocardial infarction, acute myocarditis, and acute pancarditis. In addition, it should be used with caution in pregnant and lactating women.

What are the common precautions for levothyroxine?

1. Will long-term use of levothyroxine cause adverse reactions?

Current studies have pointed out that when patients take levothyroxine for a long time, as long as they take it in the correct way and in the right dose, they will not cause adverse reactions. Within certain limits, the human body is able to metabolize thyroxine on its own. This keeps thyroxine from causing adverse reactions. However, if the patient takes levothyroxine in large doses for a long time or takes it by mistake, the patient may experience symptoms of hyperthyroidism such as sweating, insomnia, tremors (especially hand tremors), palpitation, and increased appetite.

2. Why is it not recommended to take soy products together with levothyroxine?

Although it is not recommended to eat soy products while patients are taking levothyroxine, it does not mean that patients cannot eat soy products. Under normal circumstances, patients are not recommended to eat soy products, eggs or milk and other related foods within four hours after taking the medicine. Because they reduce the intestinal absorption of levothyroxine, they affect how well it works. Because these foods reduce the amount of levothyroxine absorbed in the intestine, the dose of levothyroxine may need to be adjusted if the patient starts or stops taking soy products for nutritional supplementation.

3. When is the best time to take levothyroxine?

It is generally recommended that patients take one day's dose of levothyroxine with water half an hour before breakfast every day. It can avoid that when food and levothyroxine are taken at the same time, oily substances or other substances in food will affect the absorption of drugs in the gastrointestinal tract. If patients are unable or have difficulty taking levothyroxine in the morning, they may take it four hours after dinner or at bedtime. However, patients are generally not advised to take levothyroxine at night. It is because levothyroxine is an excitatory hormone. Patients taking levothyroxine at night may affect sleep quality. They may experience adverse effects of poor sleep quality or insomnia.

What are the other precautions for levothyroxine?

In addition to the above precautions, the foods and diseases described below can also affect the body's absorption of levothyroxine. 

• Food: soy foods or their products, grapefruit, iron or calcium-containing foods, milk or their products, tea, coffee, foods that can cause thyroid swelling (such as walnuts, cassava, cabbage, cabbage, rapeseed, etc.), cholesterol unhealthy foods (such as animal offal and butter), high-fat foods (such as cooking oil, walnut kernels, almonds, ham, etc.). Patients should avoid or reduce consumption of these foods. The consumption of these foods should also be separated from the time of taking levothyroxine.
• Diseases: malabsorption syndrome (such as achlorhydria), liver cirrhosis, celiac disease, etc.
• Drug Interactions: Antidiabetic drugs, coumarin derivatives, protease inhibitors (eg, ritonavir, lopinavir), phenytoin, cholestyramine, colestipol, drugs containing aluminum, iron, or calcium ( such as antacids), salicylic acid drugs, dicoumarol, furosemide, clofibrate, orlistat, sevelamer, tyrosine kinase inhibitors (such as imatinib), propylthiouracil, Glucocorticoids, amiodarone, iodine-containing contrast media, beta-sympathomimetics, sertraline, chloroquine, hepatic enzyme inducers (eg, barbiturates, carbamazepine), estrogens.

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