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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What are the differences between the 7 angiotensin II receptor antagonists?😵😵😵

Angiotensin II receptor antagonists are one of the commonly used antihypertensive drugs in clinic. They bind to angiotensin II receptors and inhibit the release of active substances that increase blood pressure. It will have the effect of lowering blood pressure. Allisartan, candesartan, irbesartan, losartan, olmesartan, telmisartan and valsartan are seven commonly used angiotensin II receptor antagonists. Their efficacy is different. However, patients with hypertension and chronic kidney disease, coronary heart disease or diabetes are suitable for angiotensin II receptor antagonists. They have the advantage of a longer duration of action and fewer adverse reactions.

What is the antihypertensive mechanism of angiotensin II receptor antagonists?

Angiotensin II receptor antagonists can selectively inhibit angiotensin II receptors (especially AT1 type) to dilate blood vessels, lower blood pressure, reduce aldosterone secretion, drain sodium, and inhibit sympathetic nerves. AT1 receptors are mainly distributed in the human brain, heart, vascular smooth muscle cells, blood vessels, kidneys, adrenal cortex and placenta. When angiotensin II activates it, it will synthesize and release aldosterone, constrict blood vessels, reduce renal blood flow, increase renal tubular reabsorption of sodium, and stimulate sympathetic nerve activity. These are closely related to blood pressure levels.

The indications and dosage of allisartan.

Pharmacokinetics:

Allisartan is hydrolyzed by enzymes in the gastrointestinal tract and not metabolized by the liver. Therefore, it can significantly reduce the burden on the liver in patients with hypertension. It is well absorbed orally and its half-life is about 10 hours.

Dosage:

The initial and maintenance doses of allisartan are generally 240 mg once daily. Increasing the dose of allisartan did not significantly improve its efficacy. The maximum blood pressure lowering effect can be achieved after taking the medicine for 4 weeks. Since the absorption of allisartan is reduced by food, it is not recommended to take it with food.

Indications:

1. Allisartan is effective in the treatment of mild to moderate primary hypertension. Its efficacy is similar to that of valsartan. Mild-moderate primary hypertension patients who take allisartan for a long time have high safety. 
2. Allisartan can improve carotid atherosclerosis. It improves intima media thickness better than valsartan.
3. For patients with hypertension and stable angina, the antihypertensive effect of allisartan is more significant. In addition, it can also significantly reduce the number of angina attacks in patients.

The indications and dosage of candesartan.

Pharmacokinetics:

The efficacy of candesartan peaks 4 to 6 hours after taking the drug and then slowly declines.

Dosage:

Adults generally take candesartan 4 to 8 mg orally once a day after breakfast. Its dose can be increased to 12mg if it is necessary.

Indications:

There is clear experimental evidence that candesartan can be used in hypertensive patients with heart failure.

The indications and dosage of irbesartan.

Pharmacokinetics:

Oral administration of irbesartan is well absorbed. Its absolute bioavailability is about 60 to 80%. Its bioavailability is not significantly affected by food. Its plasma peak time is 1 to 1.5 hours. It generally has a half-life of 11 to 15 hours and reaches steady state within three days.

Dosage:

The initial and maintenance doses of irbesartan are generally recommended to be 150 mg once a day. For some special patients (such as patients undergoing hemodialysis or patients over 75 years old), the initial dose can be considered as 75 mg once a day. If the patient takes irbesartan 150mg daily and still fails to effectively control his blood pressure, it may consider increasing the dose to 300mg or adding a diuretic (such as hydrochlorothiazide). For hypertensive patients with type 2 diabetes, their initial dose was 150 mg once daily and increased to 300 mg once daily as a maintenance dose.

Indications:

Irbesartan is indicated for the treatment of hypertensive patients with type 2 diabetes mellitus or patients with primary hypertension.

The indications and dosage of losartan.

Pharmacokinetics:

Losartan is rapidly absorbed orally. It takes approximately 0.5 to 1 hour for peak plasma concentrations. It has a more obvious liver first-pass effect. Its bioavailability is about 33 to 37% and its plasma protein binding is about 98.7%. Losartan has difficulty crossing the blood-brain barrier. It has a half-life of about 1.5 to 2 hours. Losartan is metabolized to more active substances in the liver. Its metabolites have a half-life of about 6 to 9 hours. Its metabolites will enhance and prolong its antihypertensive effect.

Dosage:

The initial dose and maintenance dose are generally 50 mg once a day. The maximum antihypertensive effect will be achieved after 3 to 6 weeks after taking the medicine. For some patients, the dose can be increased to 100 mg once a day to produce a further antihypertensive effect. If the patient's blood vessel volume is insufficient (for example, the patient has taken a large dose of diuretics), the initial dose can be considered to take 25 mg once a day.

Indications:

There are treatment guidelines that losartan can be used in patients with hypertension and heart failure. In addition, there are clinical studies that losartan has the effect of increasing the excretion of uric acid. A reduction in blood uric acid levels in patients was associated with a 13 to 29% reduction in cardiovascular events.

The indications and dosage of olmesartan.

Pharmacokinetics:

Olmesartan does not affect hepatic cytochrome P450 enzymes because it is not metabolized by hepatic cytochrome P450. Its bioavailability is about 26%. Its peak plasma concentration is reached approximately 1 to 2 hours after taking the drug. Food does not affect the absorption of olmesartan.

Dosage:

The dose of olmesartan should be individualized. When it is used as a monotherapy for patients with normal blood volume, the initial dose is generally recommended to be 20 mg once a day. The dose of olmesartan can be increased to 40mg once a day for patients who still need to further lower blood pressure after taking the drug for two weeks.

Indications:

Studies have shown that olmesartan can improve cardiac function in patients with chronic heart failure. Olmesartan may be considered for the treatment of patients with chronic heart failure and hypertension.

The indications and dosage of telmisartan.

Pharmacokinetics:

Oral telmisartan is rapidly absorbed by the body. Its absolute bioavailability is approximately 50%. Food does not affect its absorption. Its half-life is greater than 20 hours.

Dosage:

The initial dose of telmisartan is 40 mg once daily. When the dose of telmisartan is 20 to 80 mg, its antihypertensive effect is dose-related. Its maximum dose is 80 mg once daily.

Indications:

Telmisartan is used to treat adults with primary hypertension. It reduces the risk of cardiovascular events.

The indications and dosage of valsartan.

Pharmacokinetics:

Valsartan generally produces its hypotensive effect within 2 hours of oral administration and reaches its maximum effect in 4 to 6 hours. The blood pressure lowering effect can last more than 24 hours. The maximum antihypertensive effect will be achieved after 2 to 4 weeks after taking the drug.

Dosage:

The recommended dose of valsartan is 80mg once a day. Food does not affect its absorption. It is recommended to take the medicine at a fixed time every day. For patients with unsatisfactory blood pressure control, the dose of valsartan can be increased to 160 mg per day or diuretics can be added.

Indications:

There is clear experimental evidence that valsartan can be used in the treatment of hypertensive patients with heart failure.

The drug interactions with angiotensin II receptor antagonists.

Irbesartan and losartan are metabolized by CYP2C9 enzymes, therefore drugs metabolized by this enzyme should not be taken together. Fluconazole and rifampin should not be used in combination with losartan. Digoxin concentrations are elevated by valsartan, so the two should not be used together. Lithium, non-steroidal anti-inflammatory drugs, potassium-sparing diuretics, etc. should be avoided in combination with all angiotensin II receptor antagonists.

What are the adverse reactions of angiotensin II receptor antagonists?

There is no significant difference in the adverse reactions of the above seven angiotensin II receptor antagonists. Common adverse reactions include hypotension, aggravation of renal artery stenosis, and elevated serum potassium. Angiotensin II receptor antagonists are contraindicated in pregnant women.

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What are the indications, dosage and precautions of warfarin?💊💊💊

More and more new oral anticoagulants are being developed. As an older oral anticoagulant, warfarin has disadvantages such as large individual dose variability, narrow therapeutic window, interactions with many drugs and foods, and the need for drug monitoring in patients when used. Warfarin has so many disadvantages. Should it be eliminated from anticoagulation? Although there are many new anticoagulant drugs, it does not mean that warfarin can be completely replaced. Warfarin still plays an important role in anticoagulation therapy. 

What kind of medicine is warfarin?

Warfarin is an anticoagulant drug derived from dicoumarin. Vitamin K epoxide reductase is inhibited by warfarin. This will limit the synthesis of coagulation factors II, VII, IX, and X to produce anticoagulant effects. In addition, some anticoagulant proteins are also inhibited by warfarin. Therefore, patients may experience transient procoagulant effects during the initial period of treatment with warfarin. Its clinical manifestations are gangrene of the limbs and skin necrosis. They generally appear on the third to eighth day after dosing.

What are the indications for warfarin?

It can be used to prevent and treat pulmonary embolism and deep vein thrombosis. It also prevents thromboembolic complications following myocardial infarction, atrial fibrillation, heart valve disease, or prosthetic valve replacement. For patients with mechanical valve replacement, moderate to severe mitral stenosis, or bioprosthetic valve replacement in the first 3 months, warfarin is an irreplaceable alternative to other novel oral anticoagulants.

Dosage of warfarin.

The starting dose of warfarin is generally recommended to be 1 to 3 mg once daily. Certain patients with congestive heart failure, high risk of bleeding, impaired hepatic function, or the elderly require individual dose adjustment. Their starting dose can be reduced as appropriate. Rapid anticoagulation is required for diseases such as venous thromboembolism. Patients need to use unfractionated heparin or low molecular weight heparin overlapping with warfarin for 5 to 7 days. Patients were given warfarin immediately on day 1 or day 2 of heparin. Adjust the drug dose until the INR reaches the target value for more than 2 days before discontinuing parenteral anticoagulants. 

Indications	INR target range	Course of treatment
Venous embolism	2.5 (Range 2 to 3)	Patients secondary to transient risk factors require 3 months of use. Patients with unprovoked venous embolism need to use it for at least 3 months. After 3 months, the risk-benefit ratio of the patient's treatment was evaluated before deciding whether to extend the course of treatment. Long-term treatment is required for patients with two unprovoked venous embolisms, and the risk-benefit ratio of treatment is regularly assessed.
Myocardial infarction prognosis	2 to 3	For patients at high risk of myocardial infarction, combined use of low-dose aspirin is recommended for at least 3 months. (Daily take ≤100mg aspirin)
Atrial fibrillation (non-valvular and valvular)	2 to 3	It recommends long-term anticoagulation in patients at intermediate and high risk of stroke. Nonvalvular atrial fibrillation: Warfarin is not the drug of choice for these patients. The treatment plan needs to be determined based on the evaluation. Valvular atrial fibrillation: Warfarin is the drug of choice for these patients. Most new oral anticoagulants are contraindicated in patients with atrial fibrillation complicated by moderate-to-severe mitral stenosis, mechanical valve replacement, or bioprosthetic replacement (the first 3 months).
Mechanical valve replacement	The INR range needs to be adjusted appropriately according to the valve type and location, and it is generally 2 to 3.	Lifelong treatment.
Bioprosthetic replacement	2 to 3	It is generally 3 to 6 months. After 3 months of treatment, patients can be switched to new oral anticoagulant drugs or discontinued according to the situation.

Pharmaceutical monitoring of warfarin.

Efficacy monitoring:

INR (International Normalized Ratio) and PT (Prothrombin Time) are its main monitoring items. INR can evaluate its anticoagulation strength, and the general target range of INR is 2 to 3. 

Adverse reaction monitoring:

The main adverse reaction of warfarin is bleeding. Although a patient's risk of embolism increases with increased bleeding risk, the benefit of anticoagulation is generally greater. Therefore, bleeding should not be considered a contraindication to anticoagulation. Reversible factors that increase their bleeding risk should be screened for and corrected for in patients who require anticoagulation but are at greater risk of bleeding. They should also strengthen their monitoring and conduct regular evaluations. 

Compliance Monitoring:

Compliance monitoring is mainly to monitor whether the patient takes the medicine on time and according to the dose, and whether there is any self-adjustment of the dose.

Instructions for dosing warfarin.

Dosing time: Warfarin is recommended to be taken at a fixed time in the evening. It is mainly due to the fact that pharmaceutical monitoring is generally performed during the day. When patients take warfarin at night, the dose can be adjusted immediately based on monitoring results.

Dosage: After the patient's INR reaches the target and is stable, frequent dose adjustments are not required. However, the patient should record each dose adjustment and the next monitoring time.

Precautions while taking the medicine:

1. Missed dose: The patient should make up the dose immediately unless it is close to the next dose. A single dose should not be doubled in the event of a missed dose.
2. Diet: In the past, patients were told to avoid foods containing vitamin K as much as possible. However, more and more studies have pointed out that as long as the daily diet structure is relatively stable and do not suddenly consume large amounts of foods containing vitamin K, the efficacy of warfarin will not cause much impact.
3. Self-monitoring: Patients should monitor themselves for signs of bleeding or embolism.
4. Pregnancy and lactation: Warin is generally not recommended for patients during pregnancy. Low molecular weight heparin is preferred for pregnant patients. Patients can continue to use warfarin while breastfeeding because it does not pass into breast milk.

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What diseases can vitamin B6 be used for?😵😵😵

In 1926, it was discovered that a lack of a vitamin in mice's diet caused them to induce pellagra. In 1934, a doctor discovered an ingredient that had therapeutic effects on dermatitis in mice and named it vitamin B6. It wasn't until around 1938-1939 that vitamin B6 could be isolated and synthesized. It is a water-soluble vitamin. Pyridoxamine, pyridoxal, and pyridoxine are the three forms of vitamin B6 found in food. The three of them can be transformed into each other. Since pyridoxine is photosensitizing, it gradually breaks down when exposed to light. There are many foods that contain vitamin B6. Meat, whole grain products (especially wheat), nuts and vegetables are rich in vitamin B6.

Pharmacological mechanism of action of vitamin B6.

Vitamin B6 is converted to pyridoxal phosphate in red blood cells. It is a coenzyme and plays a role in the synthesis or metabolism of some neuromediators, nucleic acids, DNA, vitamin B2, vitamin B12, lipids and proteins. In addition, it is also involved in the conversion of homocysteine to methionine. It also plays a role in the metabolism of sphingomyelin, steroids and glycogen.

Clinical application of vitamin B6.

1. Dermatology.

In dermatology, the clinical application of vitamin B6 is very extensive. When the human body lacks vitamin B6, seborrheic-like damage will appear in the eyes, nose and corners of the mouth. Patients also have stomatitis, glossitis, eczema or acne. Therefore, vitamin B6 is often used in the treatment of alopecia areata, androgenetic alopecia, acne, cheilitis, stomatitis, folliculitis, seborrheic dermatitis, and the like. Vitamin B6 is also used as adjunctive therapy for lupus erythematosus and vitiligo.

2. Neurology.

Peripheral neuritis is the clinical manifestation of vitamin B6 deficiency in the nervous system. It is accompanied by tenderness and swelling of synovial fluid (especially in the wrist). Convulsions, restlessness, excitement and vomiting are also clinical manifestations of vitamin B6 deficiency. Therefore, vitamin B6 is used in the adjuvant treatment of autism, epilepsy, drug-induced neuritis, peripheral neuritis, facial neuritis, cognitive impairment, tic disorder, tardive dyskinesia, hand-foot syndrome, and limb numbness. In addition, studies have pointed out that increasing the intake of vitamin B6 in the daily diet can help reduce the incidence of Parkinson's disease. This is because brain cells can be protected from damage by harmful substances such as free radicals by vitamin B6.

3. Gynecology.

For vomiting of pregnancy, vitamin B6 can play a role in reducing. The FDA approved the combined use of 75mg of vitamin B6, 12ug of vitamin B12, 1mg of folic acid, and 200mg of calcium to treat nausea and vomiting during pregnancy. Although efficacy is unclear, 50 to 100 mg of vitamin B6 daily can be used for premenstrual syndrome. However, daily use of more than 100 mg of vitamin B6 has not been shown to provide additional benefits and may also increase the risk of adverse effects. In addition, because vitamin B6 can pass through the placenta of pregnant women, if a woman takes a large amount of vitamin B6 during pregnancy, it can cause vitamin B6 dependence syndrome in newborns.

4. Cardiology.

Patients are at increased risk of dementia and stroke due to hyperhomocysteinemia. The use of 50 to 200 mg of vitamin B6 daily alone or in combination with 100 mg of vitamin B6, 1 mg of folic acid, and 1500 μg of vitamin B12 daily can reduce the level of hyperhomocysteinemia. However, long-term daily use of more than 1 mg of folic acid may increase the risk of cancers such as prostate and colorectal cancer.

5. Urology.

The most common type of urinary stones are calcium oxalate stones. Because vitamin B6 can reduce the production of oxalic acid, it can be used clinically for the prevention and treatment of urinary calculi.

6. Oncology.

Studies have pointed out that a lack of vitamin B6 may increase the risk of cancer. Although not confirmed by research, some experts believe that increasing the intake of vitamin B6 in the daily diet can reduce the risk of cancers such as esophageal, breast, stomach, pancreatic and colorectal cancers. In addition, high-dose vitamin B6 is also commonly used clinically to prevent hand-foot syndrome caused by capecitabine (an antineoplastic drug).

7. Other.

Neonatal hereditary vitamin B6-dependent syndrome, hereditary sideroblastic anemia, leukopenia, vascular restenosis, primary urinary hyperoxalate, metabolic disorders (eg, homocystinuria and cystathione) etheruria), anti-tremor paralysis, cerebral dysfunction syndrome, etc. can also use vitamin B6 as adjuvant therapy.

Adverse effects of vitamin B6.

Peripheral neuropathy such as limb numbness is the main adverse reaction of long-term or high-dose vitamin B6. It is manifested by an unsteady gait. Patients first experience numbness in the feet, then numbness in the hands, followed by severe impairment of vibration and distal position sensation in the extremities. It generally has less effect on pain, touch and temperature. Symptoms generally disappear when vitamin B6 is stopped. However, some patients on high doses of vitamin B6 experience irreversible symptoms. The patient's own disease and the adverse reactions of vitamin B6 are easily confused. Clinical use of vitamin B6 (especially when used in high doses) should closely monitor patients. Drowsiness, headache, nausea, and paresthesia are also common adverse effects of vitamin B6. In severe cases, it can also damage the function of organs. Anaphylactic shock may also occur in patients with intravenous use. In general, regular doses of vitamin B6 are relatively safe. However, long-term or high-dose use should pay attention to the occurrence of adverse reactions.

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