New findings on metformin.👀👀👀

Every once in a while, new benefits of metformin are discovered. Earlier this
year, a large cohort study conducted by researchers from the University of Southern Denmark in Denmark and Stanford University in the United States also found new findings on metformin. The study noted that men took metformin in the three months before conception (during sperm development). His male offspring will be more prone to reproductive organ defects at birth. The incidence of severe defects of the genitals or urinary tract was 3.39 times that of the control group. They also found that a man taking metformin for a year before or after the 90 days window period for sperm production did not affect his male offspring. However, it is worth noting that the findings of this study are only preliminary and observational and require further confirmation. Men who are taking metformin do not need to stop taking metformin before trying to conceive. In fact, many reasons for miscarriage are due to problems with men's sperm. It takes about 90 days for sperm to develop, form and finally mature in the epididymis. Therefore, men should also prepare for pregnancy three months in advance to improve the quantity and quality of sperm.

Mechanism of action of metformin.

Metformin reduces postprandial blood glucose levels by delaying intestinal absorption of glucose, increasing GLP-1 levels, reducing peripheral insulin resistance, and increasing muscle tissue uptake and utilization of glucose. It also reduces fasting blood glucose levels by reducing hepatic insulin resistance and reducing hepatic glucose output. The reduction in postprandial blood glucose and fasting blood glucose results in a reduction in HbA1c.

Common adverse reactions of metformin.

Common adverse reactions to metformin are headache, nausea, vomiting, bloating, indigestion, abdominal discomfort, diarrhea and fatigue. Most patients experience adverse reactions within the first 10 weeks of treatment. These adverse reactions generally will be gradually tolerated or disappear with the extension of treatment time. 

Therapeutic dose of metformin.

The minimum recommended dose of metformin is 500 mg per day and the optimal effective dose is 2000 mg per day. The maximum dose for adults in ordinary tablets is 2550 mg per day and the maximum recommended dose in extended-release formulations is 2000 mg per day. Switching to metformin sustained-release preparations, starting with small doses and gradually increasing the dose are all effective ways to reduce the occurrence of adverse reactions. In addition, long-term use of metformin may affect the absorption of vitamin B12, resulting in a decrease in vitamin B12 levels in the patient's body.

Other effects of metformin.

Cardiovascular protection.

Insulin resistance in diabetic and non-diabetic patients is improved by metformin. This reduces basal and post-load insulin levels, which directly and indirectly protects the cardiovascular system.

Improve blood lipid levels.

Fat synthesis and metabolism are improved by metformin. Studies have shown that metformin can significantly reduce triglyceride, LDL-cholesterol and total cholesterol levels in patients with type 2 diabetes, but it did not significantly alter the effect of HDL-cholesterol.

Improve the effect of non-alcoholic fatty liver.

Generally, patients with nonalcoholic fatty liver disease can safely take metformin. Unless the patient has significant hepatic impairment (such as serum transaminases greater than three times the upper limit of normal), hepatic insufficiency, or decompensated cirrhosis.

Treatment of polycystic ovary syndrome.

Polycystic ovary syndrome is a heterogeneous disorder characterized by polycystic ovary morphology, ovarian dysfunction, and hyperandrogenism. Its pathogenesis is unclear. Patients usually have varying degrees of hyperinsulinemia. There is medical evidence that metformin reduces androgen levels, plasma insulin levels and increases estradiol levels. It can improve menstrual regularity, improve hirsutism and induce ovulation in polycystic ovary syndrome patients.

Antitumor effect.

Diabetes may be a risk factor for a variety of tumors, including breast, pancreatic, colorectal, and endometrial cancers. Several studies have shown that metformin inhibits tumor initiation and progression. It reduces the risk of breast, lung, rectal, prostate and other cancers.

Other potential effects of metformin.

Alter gut flora.

A study found that the gut microbiome of patients with type 2 diabetes was favorably changed by metformin.

Reduce the risk of Parkinson's disease in patients with type 2 diabetes.

Metformin promotes the growth of new neurons and repairs damage to the nervous system.

Reversal of left ventricular hypertrophy in non-diabetic patients.

Studies have shown that metformin can improve vascular endothelial cell function, delay myocardial cell apoptosis, inhibit ventricular remodeling, and reduce patient weight. These effects may reverse left ventricular hypertrophy in non-diabetic patients.

Prevent age-related macular degeneration.

A study found that people with type 2 diabetes who took metformin had a significantly lower incidence of age-related macular degeneration. This may be related to the antioxidant and anti-inflammatory functions of metformin.

Reversal of pulmonary fibrosis.

Studies have shown that the use of metformin can re-sensitize myofibroblasts to apoptosis. And in mouse models, metformin can speed up the ablation of already fibrotic tissue.

Promote hair growth.

Studies have found that metformin can stimulate telogen hair follicles to enter the growth phase and promote hair growth in mice.

Reduce the risk of blood clots caused by haze.

There are animal studies showing that inflammation caused by smog is prevented by metformin. It inhibits the formation of arterial blood clots, thereby reducing the risk of cardiovascular disease.

Reduce adverse effects of glucocorticoid therapy.

Some studies have shown that patients treated with glucocorticoids and metformin have the possibility of reversing the adverse effects of glucocorticoids.

Finally, metformin can cause fatal lactic acidosis. Therefore, metformin should be used under the guidance of a doctor or pharmacist. Although new effects of metformin are frequently discovered recently, few of them are certified by medical guidelines.

Read More

What should patients pay attention to when taking aspirin for a long time?📝📝📝

Aspirin is a classic and commonly used antithrombotic drug. In clinical, its application is very extensive. It can be used to prevent and treat cerebral thrombosis, cardiopulmonary infarction, angina pectoris, ischemic heart disease, etc. It plays an important role in the prevention of primary and secondary cardiovascular disease. Therefore, aspirin needs to be taken by many patients for a long time. The best results for these patients can only be achieved by taking aspirin correctly. The following will tell about the correct way to take aspirin.

When is it better to take aspirin?

Is it better for patients to take aspirin in the morning, noon, or evening? Some experts pointed out that there is controversy about the time of taking aspirin in the current research. Studies have shown that platelet activity increases in the morning. Therefore, from six o'clock to twelve o'clock in the morning is the high incidence time of cardiovascular events, so patients are advised to take aspirin in the morning. However, other studies have suggested that patients take aspirin at night to lower their blood pressure better, so they are advised to take it at night. In fact, the mechanism of action of aspirin is that the peak blood levels of the drug are not reached until several hours after taking the drug. Its antiplatelet effect can also last for several days after repeated administration. Therefore, whether aspirin is taken in the morning or in the evening, its antiplatelet effect persists after repeated doses. Therefore, it is generally more important to recommend that patients take aspirin regularly for a long time.

Different dosage forms of aspirin have different doses.

Different dosage forms of aspirin have different effects when taken before or after meals. If a patient is taking aspirin as a regular tablet, this dosage form causes it to be broken down in the stomach. Therefore, this form of aspirin should be taken after meals to reduce its damage to the gastric mucosa. If a patient is taking aspirin as an enteric-coated tablet, it will only dissolve in alkaline intestinal fluids and not in acidic gastric fluids. Taking this form of aspirin after meals can delay its absorption. Moreover, the alkaline content of food may cause the enteric-coated tablet to dissolve in the stomach and cause damage to the gastric mucosa. Therefore, it recommends that enteric-coated tablets should be taken 30 to 60 minutes before meals.

Patients should avoid missing to take aspirin.

Missed doses occasionally occur in patients taking long-term medication. What are the effects of missing an aspirin? Although the activity of existing platelets can be effectively inhibited by a single low-dose aspirin, the human body generates 10-15% of platelets every day. Therefore, patients need to take regular daily aspirin to keep these new platelets suppressed. If the patient occasionally misses an aspirin, it has little effect on the antithrombotic effect. However, frequent missed doses increase the risk of blood clots. It is recommended to take the medicine at a fixed time each day to avoid missed doses. If the patient misses a dose and is close to the next dose, there is no need to make up the dose and do not double the dose to avoid increasing adverse reactions. If the patient misses a dose and it is long before the next dose, make up the dose immediately.

Do not drink alcohol while taking aspirin.

First, the activity of an alcohol metabolizing enzyme (alcohol dehydrogenase) is inhibited by aspirin. It slows the metabolism of alcohol and causes more alcohol to accumulate in the body. Alcohol intoxication can become more likely. In addition, alcohol also increases the risk of gastric mucosa and liver damage. Therefore, alcohol should be avoided while taking aspirin. If the patient must drink alcohol, the patient should separate the medication time and alcohol consumption to reduce the interaction between the two.

Who is more likely to experience gastrointestinal adverse reactions when taking aspirin?

The patient's medication compliance is often affected by the adverse reactions of the medication. If a patient develops stomach pain after taking aspirin, it is easy for them to stop taking the drug. Digestive tract adverse reactions are more likely to occur in patients with a history of smoking and drinking, taking high-dose aspirin, taking anticoagulants at the same time, age > 65 years, or previous history of gastrointestinal diseases. These patients may need to take stomach-protecting drugs to reduce the occurrence of gastrointestinal adverse reactions.

Patients who develop aspirin resistance should be reassessed and adjusted their medication.

Aspirin resistance refers to the inability of patients to prevent blood clots after taking aspirin. When this occurs, the patient needs to be reassessed and assessed for factors that affect the efficacy of aspirin. Such as blood pressure, blood sugar, blood lipids are not effectively controlled. Does the patient take medication regularly? Are there any interactions between other drugs (such as NSAIDs) and aspirin? If the patient does not have the above factors, consider increasing the aspirin dose or switching to other antiplatelet drugs.

Read More

What is the difference between alogliptin, linagliptin, saxagliptin, sitagliptin and vildagliptin?📊📊📊

Dipeptidyl peptidase-4 (DPP-4) inhibitor is a new type of oral hypoglycemic drug with the fastest growing clinical use recently. Alogliptin, linagliptin, saxagliptin, sitagliptin and vildagliptin all belong to this class of drugs, but what exactly is the difference between them?

What is the mechanism of action of DPP-4 inhibitors?

Intestinal cells are stimulated by food (especially carbohydrates) to secrete hormones (such as GIP and GLP-1) that increase insulin secretion. And 70 to 80% of the incretin activity is produced by GLP-1.

DPP-4 in the human body can easily degrade GLP-1. It results in a half-life of GLP-1 in plasma of less than two minutes. Concentrations of endogenous GLP-1 are elevated two to threefold by the efficacy of DPP-4 inhibitors in inhibiting DPP-4. The effects of promoting insulin secretion and inhibiting glucagon secretion of GLP-1 are glucose concentration-dependent. Therefore, DPP-4 inhibitors do not increase the risk of hypoglycemia and are therefore suitable for use in the elderly.

What is the difference in chemical structure between DPP-4 inhibitors?

Alogliptin

Linagliptin

Saxagliptin

Sitagliptin

Vildagliptin

What is the difference between the dosage of DPP-4 inhibitors?

1. Alogliptin: It is a DPP-4 competitive inhibitor. It binds non-covalently to the active site of DPP-4. Therefore, its half-life is relatively long, up to 21 hours. Alogliptin is taken once a day, 25 mg each time.
2. Linagliptin: It is a DPP-4 competitive inhibitor. It binds non-covalently to the active site of DPP-4. Therefore, its half-life is 12 hours. Linagliptin is taken once a day, 5 mg each time.
3. Saxagliptin: It binds covalently to the active site of DPP-4. Therefore, its dissociation and association will be slower. This makes its half-life only 2.5 hours, but its hypoglycemic effect lasts longer. Saxagliptin is taken once a day, 5 mg each time.
4. Sitagliptin: It is a DPP-4 competitive inhibitor. It binds non-covalently to the active site of DPP-4. Therefore, its half-life is about 12 hours. Sitagliptin is taken once a day, 100 mg each time.
5. Vildagliptin: It is also covalently bound to the active site of DPP-4. Its half-life is 3 hours. Vildagliptin is taken twice a day, 50 mg each time.

Food does not affect the absorption of the above DPP-4 inhibitors.

Precautions for use in patients with renal insufficiency.

1. Alogliptin: It is rarely metabolized in the body and its metabolites are also active. Its bioavailability can reach 100%. It rarely interacts with other medicines. About 76% of alogliptin is excreted through the kidneys. Therefore, its dosage should be adjusted when it is used in patients with renal insufficiency.
2. Linagliptin: It is rarely metabolized in the body. Its metabolites are inactive. Its bioavailability is about 30%. It rarely interacts with other medicines. Less than 5% of the administered dose of linagliptin is excreted by the kidneys. Therefore, it does not require dose adjustment when used in patients with renal insufficiency.
3. Saxagliptin: It is metabolized by CYP3A4/5. Its metabolites are active. Its bioavailability is about 67%. It rarely interacts with other medicines. Its usual dose is 5 mg once a day. However, when it is co-administered with potent CYP3A4/5 drugs such as itraconazole, clarithromycin and atazanavir, the dose of saxagliptin should not exceed 2.5 mg per day. About 75% of saxagliptin is excreted through the kidneys. Therefore, its dosage should be adjusted when it is used in patients with renal insufficiency.
4. Sitagliptin: It is rarely metabolized in the body. Its metabolites are inactive. Its bioavailability is about 87%. It rarely interacts with other medicines. About 79% of sitagliptin is excreted by the kidneys. Therefore, its dosage should be adjusted when it is used in patients with renal insufficiency.
5. Vildagliptin: It is not metabolized by CYP enzymes, but inactivated by hydrolysis. Its bioavailability is about 85%. It is less likely to interact with other drugs. About 85% of vildagliptin is excreted through the kidneys. Therefore, its dosage should be adjusted when it is used in patients with renal insufficiency.

What are the common adverse reactions of DPP-4 inhibitors?

It is possible that DPP-4 inhibitors increase GLP-1 levels. This can be associated with delayed gastric emptying and appetite suppression. Therefore, DPP-4 inhibitors can cause stomach upset. Their main adverse reactions are upper respiratory tract infection, nasopharyngitis and headache. Less common adverse reactions are hypersensitivity reactions and angioedema. 

In addition, alogliptin and saxagliptin have the potential to increase the risk of heart failure hospitalization events. Therefore, when a patient has risk factors for heart failure, the patient should be observed for symptoms and signs of heart failure during treatment.

Read More

What is the difference between insulin degludec, insulin detemir and insulin glargine?👌👌👌

Among the hypoglycemic drugs, insulin is the most effective one. When the pancreatic function of diabetic patients is severely deteriorated, oral hypoglycemic drugs are contraindicated or the treatment effect is not good, insulin will become a very important therapeutic drug. Among the long-acting insulins, insulin degludec, insulin detemir and insulin glargine are the most commonly used clinically. What is the difference between them?

What types of insulin are commonly used?

Commonly used insulin can generally be divided into recombinant human insulin and human insulin analogs.

• Recombinant human insulin: Protamine recombinant human insulin. It is an intermediate-acting insulin.
• Human insulin analogs: Short-acting human insulin analogs include insulin aspart, insulin lispro, and insulin glulisine. Long-acting human insulin analogs are insulin degludec, insulin detemir and insulin glargine. 

Recombinant human insulin, insulin degludec and insulin detemir formulations are generally valid for 30 months. Insulin glargine preparations are generally valid for 36 months. This is because the A chain of human insulin contains 21 amino acid residues and the B chain contains 30 amino acid residues. Insulin glargine replaces the acid-sensitive asparagine with glycine at position 21 of the A chain. Glycine has a neutral charge. It will be more stable in an acidic environment. Insulin should be sealed and refrigerated at 2 to 8°C before first use. It is sufficient to store insulin at room temperature and it can be stored for up to 8 weeks after first use.

What is the difference in the duration of their action?

In the body, the half-life of insulin is only about a few minutes. The subcutaneous absorption rate is the main factor affecting the duration of insulin action.

	A chain	B chain
Human insulin	Aspartic acid. (21st)	Lysine. (29th) Threonine. (30th)
Insulin degludec	Aspartic acid. (21st)	Lysine. (29th) Glutamate. (30th) 16 carbon fatty diacids.
Insulin detemir	Aspartic acid. (21st)	Lysine. (29th) 14 carbon fatty diacids. (30th)
Insulin glargine	Glycine. (21st)	Lysine. (29th) Threonine. (30th) Arginine. Arginine.

Insulin degludec: The threonine at the end of its B chain has been removed. Instead, a glutamate is attached to the lysine at 29th and a 16-carbon fatty diacid is linked to glutamate. When insulin degludec is injected subcutaneously, it forms stable polyhexamers and continuously releases insulin monomers over an extended period of time. Insulin degludec reversibly binds to albumin after entering the blood. Its protein binding rate is greater than 99%. This can further extend the time to reach the target tissue. The duration of action of insulin degludec is greater than 42 hours.

Insulin detemir: The threonine at the end of its B chain has been removed and a 14-carbon fatty diacid is attached to the lysine at 29th. Insulin detemir formed double hexamers after subcutaneous injection and sustained the release of insulin monomers over an extended period of time. Its duration of action is approximately 16 to 24 hours.

Insulin glargine: It is the addition of two arginines to the end of the B chain of insulin. It changes the isoelectric point of insulin from pH 5.4 to pH 6.7. They form fine precipitates when injected subcutaneously (pH about 7.4). These microprecipitates can sustain the release of insulin monomers for about 30 hours.

What is the difference in the frequency of their use?

The absorption of insulin degludec, insulin detemir, and insulin glargine is smooth and slow. Therefore, they can only be used as basal insulin drugs to lower fasting blood sugar.

	Insulin degludec	Insulin detemir	Insulin glargine
Recommended usage	Administer 1 time a day. It can be administered at any time throughout the day. However, it is best to maintain the same dosing time each day.	Administer 1 to 2 times a day. If administered twice daily, the second dose can be optionally given at dinner, before bedtime or 12 hours after the morning injection.	Administer 1 time a day. It can be administered at any time throughout the day. However, it must maintain the same dosing time each day.
Protein binding rate	>99%	>90%	Unknown
Duration of action	>42 hours	16 to 24 hours	30 hours

What is the difference in their indications?

Their indications will vary slightly.

	Type 1 diabetes	Type 2 diabetes	Gestational diabetes	Diabetes in children
Neutral protamine zinc insulin	✓	✓	✓	✓
Insulin degludec	✓	✓	-	≥6 years old
Insulin detemir	✓	✓	It can be considered for use.	≥6 years old
Insulin glargine	-	✓	-	-

What is the difference between their adverse reactions?

All insulin drugs can cause fatal hypoglycemia. However, insulin degludec has a longer duration of action (>42 hours) and tends to have no peaks, so it has a lower risk of overall hypoglycemia and nocturnal hypoglycemia.

Because insulin increases fat and protein synthesis, it can cause weight gain. However, some studies have pointed out that although insulin detemir has a similar hypoglycemic effect as insulin glargine, it is less likely to cause weight gain.

Read More

What is heat apoplexy and its medical treatment?🌞🌞🌞

Summer is coming, and there have been hot weather in many places around the world recently. Some people even died of heat. In fact, hot weather has caused far more deaths around the world than many other natural disasters. With the recent hot weather, there have been news reports of people diagnosed with heat apoplexy and deaths. So what exactly is heat apoplexy? How should it be treated and what treatments are available?

What is heat apoplexy?

Heat apoplexy is a very severe form of heat stroke. It is caused by the body's thermoregulatory function being impaired by the high temperature and high humidity environment. The human body dissipates heat less than it produces heat. Its core temperature can quickly rise above 40oC. It will be accompanied by severe acute heat-induced diseases such as disturbance of consciousness, burning skin, disturbance of multiple organ functions (such as cardiovascular function, coagulation function, respiratory function, etc.) and even failure. The most dangerous type of heatstroke is heat apoplexy. Its fatality rate can be as high as 21 to 63%.

What are the types of heat apoplexy?

Classic heat apoplexy is more common in the following groups of people:

• Children, infants, elderly people over 70 years old and other people with poor thermoregulation function.
• Mental disorders, physical disabilities and other reasons make it impossible to leave the high temperature environment, replenish water or cool down in time.
• People with neurological diseases, anhidrosis, obesity, cardiovascular diseases and other diseases.
• Traffic police, sanitation workers and other people who need to work in a high temperature and high humidity environment for a long time.

Exertional heat apoplexy is more common in healthy young people who engage in high-intensity activities when the temperature and humidity are high.

How is heat apoplexy treated?

The treatment of heat apoplexy should take the following measures as early as possible:

1. Cool down.
2. Expand blood volume.
3. Blood purification.
4. Calm down.
5. Tracheal intubation.
6. Anticoagulation.
7. Anti-inflammatory.
8. Enteral nutrition.
9. Dehydration prevents edema.
10. Immunomodulatory.

In addition, patients are prohibited from surgery during the coagulation disorder.

The main treatment for heat apoplexy patients is rapid, effective and sustained cooling. Common cooling methods can use ice water bath, hypothermic blanket, ice water therapy and so on. Cold water immersion therapy is an efficient, non-invasive and rapid cooling method. It is often used in younger patients. However, it affects venous circulation and increases mortality in elderly patients, so elderly patients generally do not use this therapy.

Patients with heat apoplexy should not use large amounts of alcohol rubbing their body to cool down. Because when a patient has heat apoplexy, the blood vessels in their skin dilate. At this time, if a large amount of alcohol is used on the epidermis to cool down, the alcohol will be absorbed into the blood through the skin blood vessels and become toxic. Therefore, patients with heat apoplexy are prohibited from using large amounts of alcohol to cool down.

What are the medicines for heat apoplexy treatment?

Infusion: It is commonly used for intravenous infusion of Ringer's injection or 0.9% saline. However, the patient's urine output, cardiorespiratory function, and blood volume status should be assessed before fluid infusion, followed by rapid fluid resuscitation. Patients should avoid fluid overload conditions. In addition, patients should avoid large infusion of glucose injection in the early stage. It can cause a patient's blood sodium to drop rapidly over a short period of time. It can make nerve damage worse.

α-receptor agonists: Vasopressors such as epinephrine or norepinephrine may be infused in shock patients who are poorly resuscitated by infusion. However, α-receptor agonists also constrict the blood vessels of the skin and make external cooling measures less effective. Therefore, patients should try to avoid using them.

Sedatives: Cooling measures may cause shiver in the patient. The shivering process can exacerbate the condition by increasing the patient's endogenous heat production. Therefore, short-acting benzodiazepines such as lorazepam and midazolam may be recommended for intravenous administration during cooling measures to prevent or control shiver. The patient's core body cooling process can also be improved by benzodiazepines. Chlorpromazine may be considered if benzodiazepines are ineffective. However, the anticholinergic effects of chlorpromazine may induce or exacerbate the hypotensive complications of heat apoplexy.

Treatment of complications of heat apoplexy: Patients with heat apoplexy may develop respiratory dysfunction, hypotension, cerebral edema, cardiac insufficiency, electrolyte abnormalities and other related complications. Patients with these symptoms should be treated with corresponding drugs or other treatment methods.

Antipyretic and analgesic drugs are contraindicated: Drugs such as aspirin, acetaminophen, and ibuprofen have no effect on the hyperthermic state of patients with heat apoplexy. The cooling mechanism of antipyretic analgesics is by inhibiting the production of prostaglandins in the hypothalamus, so that the set point that regulates the central body temperature is down-regulated. However, the thermoset point in heat apoplexy patients did not change, so there was no efficacy. In addition, the common adverse reactions of antipyretic analgesics are the same as the common complications of heat stroke (such as disseminated intravascular coagulation, liver injury, acute kidney injury and gastrointestinal bleeding, etc.). These symptoms may be induced or exacerbated by use. 

Read More

What are the precautions for osteoporosis treatment drugs?🦴🦴🦴

Osteoporosis is a systemic metabolic bone disease in which bone mass and
bone density decrease due to different reasons. Osteoporosis is common in postmenopausal women and older men. It is a very common bone disease. It is characterized by increased bone fragility and increased susceptibility to fractures. Osteoporosis can be divided into primary osteoporosis and secondary osteoporosis according to different etiologies.

What is primary osteoporosis?

Primary osteoporosis includes postmenopausal osteoporosis (type I), senile osteoporosis (type II) and idiopathic osteoporosis. Postmenopausal osteoporosis generally occurs within 5 to 10 years after menopause in women. Senile osteoporosis usually occurs after age 70. Idiopathic osteoporosis occurs mainly in adolescents.

What is secondary osteoporosis?

Secondary osteoporosis refers to osteoporosis caused by drugs (such as proton pump inhibitors, antiviral drugs, glucocorticoids, etc.) and/or diseases affecting bone metabolism and other causes.

What medicines are available for the treatment of osteoporosis?

Osteoporosis treatment drugs mainly include basic supplements for bone health, bone resorption inhibitors, bone formation promoters, active vitamin D and its analogs.

Basic supplements for bone health.

The basic supplements for osteoporosis prevention and treatment are calcium and vitamin D.

Calcium: 

• Commonly used are calcium citrate and calcium carbonate. Although calcium citrate has a lower calcium content, its better water solubility can reduce the occurrence of kidney stones. It is suitable for patients who are at risk of kidney stones or who are achlorhydric. Calcium carbonate has a higher calcium content. It is easily soluble in gastric acid and has a high absorption rate by the human body. 
• Epigastric discomfort and constipation are their common adverse effects. Calcium citrate has relatively few gastrointestinal adverse effects. Calcium should be avoided in patients with hypercalcemia and hypercalciuria. High-dose calcium may increase the risk of cardiovascular disease and kidney stones. Fluoroquinolones will complex with calcium ions in calcium. This hinders the absorption of the drug and can easily lead to the failure of anti-infective therapy.

Vitamin D:

• The combination of vitamin D and calcium reduces the risk of osteoporotic fractures. In addition, the efficacy of other anti-osteoporosis drugs can be enhanced by adequate vitamin D supplementation. Elderly osteoporosis patients who are obviously deficient in vitamin D should use vitamin D supplementation, and at the same time, they can use active vitamin D to treat osteoporosis under the guidance of doctors.
• Urinary and serum calcium concentrations should be monitored regularly when taking vitamin D to prevent hypercalcemia and hyperphosphatemia. In addition, taking active vitamin D to correct basal vitamin D deficiency is generally not recommended. Supplemental therapy with larger doses of vitamin D is not recommended for multiple doses within a year.

Bone resorption inhibitors.

Such drugs mainly include bisphosphonates, calcitonins and selective estrogen receptor modulators.

Bisphosphonates:

• Broad-spectrum anti-fracture drugs such as alendronate, risedronate, and zoledronic acid are the preferred drugs. Oral bisphosphonates such as alendronate and risedronate should be the first choice for people with low bone mineral density but no history of fractures and people with low or moderate fracture risk. Injectable forms such as zoledronic acid may be considered in elderly patients with multiple vertebral or hip fractures, as well as in people with high fracture risk, very low bone mineral density, contraindications, or oral intolerance. Lumbar spine and hip bone mineral density in people with osteoporosis can be improved with zoledronic acid. It reduces the risk of vertebral, nonvertebral and hip fractures.
• Their adverse reactions include renal toxicity, osteonecrosis of the jaw, atypical femoral fractures, transient flu-like symptoms, and gastrointestinal reactions. Bisphosphonates should be used with caution in patients with reflux esophagitis, active gastric and duodenal ulcers, and functional esophageal dysfunction. Bisphosphonates are not recommended for patients with severe oral disease or in need of dental surgery. They should also be contraindicated in patients with creatinine clearance <35ml/min. After 3 years of intravenous bisphosphonate use or 5 years of oral bisphosphonates, patients should be reassessed to determine whether continued use of the drug is required.

Calcitonin drugs:

• The biological activity of osteoclasts can be inhibited by calcitonin drugs. They reduce the number of osteoclasts and the loss of bone mass. They also relieve bone pain and increase bone mass. In particular, it can significantly relieve bone pain caused by osteoporosis and fractures.
• Their main adverse reactions are nausea, facial flushing, etc., and occasionally allergic phenomena occur. Because calcitonins have the potential to increase the risk of developing tumors, they should generally not be used continuously for more than 3 months.

Selective estrogen receptor modulators:

• A commonly used selective estrogen receptor modulator is raloxifene. It is indicated for the treatment of postmenopausal osteoporosis and for reducing the risk of vertebral fractures.
• Raloxifene may cause pulmonary embolism and deep vein thrombosis. Therefore, it is contraindicated in those with a history of venous thrombosis and those with thrombophilia (such as those who are sedentary or bedridden for a long time). In addition, the risk of thromboembolism in patients should be strictly assessed before administration.

Bone formation promoter.

Parathyroid hormone analog:

• Teriparatide is a parathyroid hormone analog. It stimulates osteoblast activity by intermittently administering small doses. It increases bone density and promotes bone formation. It also reduces the risk of non-vertebral and vertebral fractures.
• Dizziness, headache, nausea and limb pain are its common adverse effects. Because of the risk of osteosarcoma formation after two years of teriparatide use, it should not be given for more than two years. Patients should also be treated with anti-resorptive drugs sequentially after drug discontinuation to maintain or increase the patient's bone density. This continuously reduces the risk of fractures.

Active vitamin D and its analogs.

These drugs are suitable for patients with impaired renal function, reduction or deficiency of 1-alpha-hydroxylase, and the elderly.

Alpha-calcidol, calcitriol:

• Although α-calcidol does not need to be activated by renal metabolism, it needs to be activated by 25-hydroxylase in the liver to have biological activity. Calcitriol itself has biological activity. In addition, the effect of calcitriol to increase blood calcium will be stronger than that of α-calcidol. However, it has a shorter half-life than alpha-calcidol and loses its efficacy about 2 to 3 days after stopping the drug. After you stop taking alpha-calcidol, it takes about 1 week for it to stop working.
• Active vitamin D and its analogs have a significantly higher risk of hypercalciuria relative to vitamin D. The risk of hypercalcemia increases with higher doses, especially when combined with calcium supplements. Therefore, patients' urinary calcium and serum calcium should be monitored during treatment, especially when combined with calcium supplements. Active vitamin D and its analogs are used with caution in patients with kidney stones and are contraindicated in patients with hypercalcemia. It also increases the risk of hypercalcemia when combined with thiazide diuretics. It may cause hypermagnesemia when used with magnesium-containing drugs, especially in patients with chronic renal failure. It can induce cardiac arrhythmias when combined with digitalis.

Read More

How to use statins correctly?(Part 2: Statin therapy.)✅✅✅

Here is part 2. It is about how to use statins correctly.

What are statins and how should they be used?

There are 7 kinds of statins that are more commonly used in clinical practice. There are 7 kinds of statins that are more commonly used in clinical practice. The seven statins are atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin and simvastatin.

Their characteristics are as follows:

• Atorvastatin is a potent and long-acting statin. It can be taken at any time. It is mainly metabolized via the hepatic enzyme CYP3A4. Therefore, it has more interactions with other drugs, and it is necessary to pay attention to drug interactions when taking it in combination.
• Pitavastatin is a moderate-strength, long-acting statin. It can be taken at any time. Its dose is the smallest among statins. It is mainly excreted through feces. It has fewer interactions with other drugs. It has few side effects and it has minimal effect on blood sugar.
• Pravastatin is a moderate-strength statin. Since it is not metabolized by liver enzymes, it has fewer interactions with other drugs. It has few side effects and it has less effect on blood sugar. However, it has a shorter potency and needs to be taken at bedtime.
• Rosuvastatin is a potent and long-acting statin. It can be taken at any time. It is excreted mainly in the feces and partly in the kidneys. Since only a small amount is metabolized by the liver, it has fewer interactions with other drugs. Combination medication has higher safety.
• Simvastatin is metabolized by the liver enzyme CYP3A4. Many drugs are metabolized through this pathway, so it has more interactions with other drugs. The drug-drug interactions should be paid attention to in combination therapy. It also has a shorter duration of action. Therefore, it needs to be taken at bedtime for the best lipid-lowering effect.

The initial drug should be a moderate-intensity statin, and then the dose should be adjusted according to the patient's lipid-lowering efficacy and tolerance. If the patient's cholesterol level fails to reach the target, it should be combined with other lipid-lowering drugs. The lipid-lowering intensities and doses of statins are as follows:

• Low-intensity (daily dose lowers LDL-C < 30%): Fluvastatin 20-40mg, Lovastatin 20mg, Pitavastatin 1mg, Pravastatin 10-20mg, Simvastatin 10mg.
• Moderate-intensity (daily dose lowers LDL-C 30 to 50%): Atorvastatin 10-20mg, Fluvastatin 80mg, Lovastatin 40mg, Pitavastatin 2-4mg, Pravastatin 40-80mg, Rosuvastatin 5-10mg, Simvastatin 20-40mg.
• High intensity (daily dose lowers LDL-C ≥50%): Atorvastatin 40-80mg, Rosuvastatin 20mg.

The lipid-lowering treatment options.

The usual doses of statins are: atorvastatin 10-20mg, fluvastatin 80mg, pitavastatin 2-4mg or rosuvastatin 5-10mg. If blood lipids still do not reach the target after 3 to 4 weeks of treatment, 10 mg of ezetimibe daily is combined with treatment for 4 weeks.

If the blood lipids still do not reach the target after treatment, there are generally two options. The first option is to increase the dose of the statin. The advantage of this approach is lower cost but an increased risk of side effects (despite doubling the statin dose, the LDL-C reduction is only 6%). The second option is to use a combination of PCSK-9 inhibitors (eg, evolocumab). This regimen will be more effective, but more expensive. Higher-dose statin, ezetimibe and PCSK-9 inhibitor combined use of the three drugs will further enhance the cholesterol-lowering effect. However, it is necessary to strengthen the monitoring of adverse reactions in patients when combined.

However, in patients with homozygous familial hypercholesterolemia, their LDL-C is usually significantly elevated. Even if they are treated with the above-mentioned combination drugs, it is still difficult to have reasonable blood lipid control. Plasma exchange therapy every 1 to 2 weeks may be considered for this type of patient. If the patient's triglycerides are only borderline high (between 1.7 and 2.26 mmol/L), no medical treatment is required. These patients can control their blood lipids by controlling their diet, eating more vegetables, reducing calorie intake, increasing exercise, losing weight and not drinking alcohol.

Patients with moderately elevated triglycerides (between 2.26 and 5.6 mmol/L), especially those with comorbidities such as diabetes or ASCVD, may consider statin therapy. When patients have severely elevated triglycerides above 5.6 mmol/L, they are at high risk for acute pancreatitis. Therefore, they should immediately lower triglycerides to relatively safe levels with drugs such as fibrates, niacin extended-release.

Which patients need to take statins for lipid-lowering therapy?

The following groups of people need oral statins for lipid-lowering therapy:

People with LDL-C>4.9mmol/L.

The patient has been diagnosed with ASCVD. In addition, patients with stable or unstable angina, acute coronary syndrome, peripheral vascular disease, coronary or other revascularization, myocardial infarction, transient ischemic attack, ischemic stroke, or confirmed coronary and Large and medium arteries such as the carotid artery have more than 50% stenosis.

Patients with diabetes or LDL-C (>3.4mmol/L) combined with hypertension.

Low HDL-C (<1.0mmol/L), obesity, smoking, hypertension of grade two or above and other three or more non-diabetic risk factors combined with hypertension.

Diabetic patients with LDL-C>1.8mmol/L or total cholesterol (TC)>3.1mmol/L and age>40 years old.

Some patients with carotid plaque.

Read More

How to use statins correctly?(Part 1: Blood lipids and related diseases.)✅✅✅

Statins are effective and safe in lowering cholesterol and reversing plaque. Clinically they have become fundamental drugs for reducing the risk of cardiovascular disease and treating atherosclerosis. Due to the widespread use of statins, incorrect use of statins can cause adverse reactions in patients.

What are blood lipids?

Cholesterol in the human body is mainly present in the body in the form of cholesterol esters and free cholesterol. Although lipids are insoluble in water, lipids in plasma are mainly combined with apolipoproteins to form soluble lipoproteins, so that plasma is normally clear and transparent. Lipoproteins are classified into high density lipoprotein (HDL), intermediate density lipoprotein (IDL), low density lipoprotein (LDL), very low density lipoprotein (VLDL) and chylomicrons (CM). In addition, there is a lipoprotein called lipoprotein a (LPa). Lipoproteins are the major transport form of blood lipids in the human body. Clinically, the level of LDL in the blood can be reflected by the level of low-density lipoprotein cholesterol (LDL-C). In addition, there are triglycerides in the blood, which are also commonly known as fats. Clinically, the two main indicators of concern are LDL-C and cholesterol. Because only cholesterol is the basis pathophysiology of atherosclerosis.

What is atherosclerotic cardiovascular disease?

Atherosclerotic cardiovascular disease (ASCVD) includes ischemic stroke, myocardial infarction (MI), stable and unstable angina, transient ischemic attack, and peripheral vascular disease (PAD).

What is the source of cholesterol in blood?

The main sources of cholesterol in the blood are synthesis in the body and dietary intake. The amount of synthesized in the body is about 2/3 (70%-80%) and the amount of dietary intake is about 1/3 (20%-30%). The main site of cholesterol synthesis in the body is the liver. However, cholesterol cannot enter the blood directly after being synthesized in the liver. It is excreted into the intestines through bile, and then absorbed by the intestines into the blood. This process is called enterohepatic circulation of cholesterol. Both the cholesterol synthesized by the liver and the cholesterol absorbed from the diet must be absorbed by the intestine before entering the blood. Therefore, the ability of the intestines to absorb cholesterol greatly affects the level of cholesterol in the body's blood. Clinically, ezetimibe has a lipid-lowering effect by inhibiting the absorption of cholesterol in the intestines. 

What are the causes of hyperlipidemia?

The causes of hyperlipidemia include the following:

1. Diet can cause hyperlipidemia. Long-term consumption of high-sugar, high-fat and high-energy foods or beverages can easily lead to hyperlipidemia. Lack of physical activity or excessive alcohol consumption can lead to dyslipidemia.
2. The disease causes hyperlipidemia. Some diseases may cause dyslipidemia, such as: thyroid disease, liver disease, pancreatitis, diabetes, obesity, gout, familial hypercholesterolemia, etc. Hypothyroidism can cause hyperlipidemia including cholesterol and triglyceridemia.
3. Drugs can also cause hyperlipidemia. Some drugs can also increase blood lipids, such as glucocorticoids, non-selective β-blockers, and diuretics, which can induce secondary dyslipidemia.

Who needs to be screened for blood lipids?

The following people need to be screened for blood lipids:

Men or women over the age of 40 (or postmenopausal women).

All patients with any of the following conditions, regardless of age, should be screened for lipids.

• Clinical evidence points to the presence of atherosclerotic cardiovascular disease.
• Diabetes.
• Hypertension.
• Hypertension in pregnancy.
• Chronic kidney disease (eGFR≤60ml/min 1.73m2).
• Abdominal aortic aneurysm.
• Chronic Obstructive Pulmonary Disease.
• Signs of dyslipidemia (eg, xanthomas, corneal arches).
• Inflammatory diseases (inflammatory bowel disease, psoriatic arthritis, systemic lupus erythematosus, rheumatoid arthritis, ankylosing spondylitis). 
• Family history of premature cardiovascular disease (age of onset in first-degree relatives: female < 65 years, male < 55 years).
• Obesity (BMI ≥ 30). 
• Still smoking. 

How long is the interval between blood lipid tests?

People between the ages of 20 and 40 should have their blood lipids tested every 5 years.

Men over the age of 40 should have their blood lipids checked once a year.

Postmenopausal women should have their blood lipids checked once a year.

Patients with ASCVD or their high-risk groups should have blood lipids measured every 3 to 6 months. (High-risk groups refer to people with multiple ASCVD risk factors, such as diabetes, hypertension, familial hyperlipidemia, family history of premature cardiovascular disease, obesity, smoking, etc.)

Inpatients with ASCVD should be tested for blood lipids at the time of hospital admission.

Read More

Vitamin B3 may slow the progression of Alzheimer's disease.👴👵

Indiana University School of Medicine (IUSM) researchers have found in
laboratory models that people's intake of vitamin B3 (niacin) can slow the progression of Alzheimer's disease. The findings of this study offer new possibilities for treating Alzheimer's disease. They recently published the results of the study in the journal Science Translational Medicine. They investigated how vitamin B3 alters the response of microglia to amyloid plaques in animal models of Alzheimer's disease. The researchers believe the results of this study could identify a potential new therapeutic target for Alzheimer's disease. In addition, it could adjust the treatment guidelines for Alzheimer's disease. This therapeutic strategy has great potential in clinical treatment.

What are the benefits of niacin?

Niacin is also known as vitamin B3. Niacin can be obtained mainly through specific diets. It can maintain the function of metabolism of the whole body. Clinically, it is also used as a cholesterol-lowering drug or nutritional supplement. It is one of the water-soluble B vitamins. It occurs naturally in some foods, and it is added to foods as a supplement. Niacin and niacinamide are the two most common forms of niacin found in foods and supplements. In addition, an amino acid called tryptophan is also converted into niacinamide by the body. Because niacin is a water-soluble vitamin, the body excretes excess niacin in the urine when ingested in excess. Niacin works in the body as a form of coenzyme. There are more than 400 enzymes in the human body that depend on niacin for various reactions. It also helps convert nutrients into energy in the body, produces fat and cholesterol, generates and repairs DNA, and acts as an antioxidant.

Niacin interacts with highly selected HCAR2 receptors in the brain. HCAR2 receptors are present in immune cells associated with amyloid plaques. The researchers say that when niacin activates the receptor, these immune cells are stimulated by it to have beneficial effects on Alzheimer's disease. 

The results of the study showed that niacin treatment reduced amyloid plaques in an animal model of Alzheimer's disease. It also improves cognition in animal models of Alzheimer's disease. These effects are all due to the HCAR2 receptor. The researchers also said that past epidemiological and niacin studies on Alzheimer's disease indicated that people with higher dietary intake of niacin had a lower risk of developing Alzheimer's disease. In clinical trials, niacin has also been used in the treatment of glioblastoma and Parkinson's disease.

What are the main food sources of niacin?

In general, few people develop niacin deficiency. Because it is present in the food of many animals and plants. These foods include pork, poultry, fish, beef, beef liver, beans, nuts, seeds, brown rice, grains, bread, bananas, and more.

For more detail, you can read this article.👇

Miguel Moutinho, Shweta S. Puntambekar, Andy P. Tsai, Israel Coronel, Peter B. Lin, Brad T. Casali, Pablo Martinez, Adrian L. Oblak, Cristian A. Lasagna-Reeves, Bruce T. Lamb, Gary E. Landreth. The niacin receptor HCAR2 modulates microglial response and limits disease progression in a mouse model of Alzheimer’s disease. Science Translational Medicine, 2022; 14 (637) DOI: 10.1126/scitranslmed.abl7634

https://www.hsph.harvard.edu/nutritionsource/niacin-vitamin-b3/

Read More

What common drugs are contraindicated in patients with glucose-6-phosphate dehydrogenase deficiency?📝📝📝

In recent years, broad beans and their products have become a favorite
snack for many people. However, some children will experience physical discomfort such as fever, chills, headache, dizziness, fatigue, abdominal pain or vomiting after eating these foods, and even dark yellow urine or jaundice. If children have the above symptoms after eating broad beans and their products for the first time, they may have glucose-6-phosphate dehydrogenase deficiency. 

What is glucose-6-phosphate dehydrogenase deficiency?

Glucose-6-phosphate dehydrogenase deficiency (G6PD deficiency) is also called favism. Human red blood cell membranes have an enzyme called glucose-6-phosphate dehydrogenase (G6PD). It is involved in the process by which red blood cells metabolize glucose. In the process, it produces a substance that protects red blood cells from being damaged by oxides. If people eat oxidative foods or drugs in the absence of G6PD, red blood cells will be easily destroyed by them and acute hemolysis will occur. Since most patients developed acute hemolysis within 48 hours of eating fresh broad beans or their products, G6PD deficiency is also known as favism.

What are the clinical manifestations of glucose-6-phosphate dehydrogenase deficiency?

In patients with G6PD deficiency, the onset is generally acute. Its incubation period can range from 2 hours to 15 days, but is generally 1 to 2 days. 

1. Prodromal symptoms include fever, dizziness, abdominal pain, nausea, vomiting, fatigue, and general malaise, which generally last for 1 to 2 days.
2. The manifestations of acute intravascular hemolytic anemia include rapid onset of jaundice, pale complexion, and dark yellow urine. Some patients also develop spleen and liver enlargement.
3. Severely ill patients may experience convulsions, lethargy, coma, severe anemia, acute renal failure, shock, and systemic failure.

What are the main causes of Glucose-6-Phosphate Dehydrogenase Deficiency?

1. Eating broad beans and their products, contacting broad bean pollen.
2. Nursing mothers ate fava beans and their products, or were exposed to broad bean pollen.
3. Taking medicines (such as antipyretic analgesics, some antimalarial drugs, or sulfonamides, etc.).
4. Infections: Viral infections (eg, flu, typhoid, mumps, pneumonia, hepatitis, etc.).

G6PD deficiency is most common in children under 5 years of age, and is more common in men than women. It is an inherited blood disorder. Therefore, it cannot be cured, but it can be prevented.

Why does glucose-6-phosphate dehydrogenase deficiency occur mainly in children?

Some studies suggest that it may be due to poor digestion, abnormal intestinal permeability and the easy entry of broad bean protein into children's bodies. In addition, some studies have pointed out that with the growth of children's age, the enzymes, liver, spleen and various physiological functions will gradually improve. At the same time, the human body will neutralize broad beans and some oxidative substances, so it will inhibit the pathogenesis of G6PD deficiency. 

Moreover, people with G6PD deficiency generally stop eating broad beans or other oxidative substances after they develop it in childhood. As a result, the incidence of G6PD deficiency in young and old is reduced.

What foods and drugs are contraindicated in patients with Glucose-6-Phosphate Dehydrogenase Deficiency?

Food: Broad beans and their products. Broad bean products include soy sauce, bean paste and other condiments. In terms of oxidative capacity, fresh fava beans will be stronger than cooked fava beans. In patients with favism, fresh fava beans will almost certainly cause hemolysis. In addition, broad bean pollen will almost certainly cause severe hemolysis in patients. Therefore, they should avoid visiting fava bean fields during the fava bean harvest season.

Mothballs: Naphthalene contained in mothballs can also cause acute hemolysis in patients with favism. Therefore, mothballs are prohibited in the patient's wardrobe. Once the clothes come into contact with mothballs, they must be exposed to the sun before the patient can wear them.

Topical medicines: The external use of salicylic acid and some Chinese herbal oils should also be prohibited by patients.

Traditional Chinese medicines: Patients should avoid using traditional Chinese medicines such as pearl powder, Sichuan lotus, bezoar, winter plum blossom, honeysuckle, and their proprietary Chinese medicines.

Medicines: Patients with favism should avoid self-medication and inform their doctor when seeking medical treatment. Patients with favism should try to avoid the following drugs:

• Antidiabetic drugs: such as glimepiride, gliclazide, glyburide, glipizide, etc.
• Antipyretic analgesics: such as aminopyrine, aspirin, acetaminophen, etc.
• Antimicrobial drugs: chloramphenicol, streptomycin, ciprofloxacin, moxifloxacin, levofloxacin, furazolidone, chloroquine, primaquine, etc.
• Vitamins: such as vitamin C, vitamin K1, vitamin K3, vitamin K4.
• Others: isosorbide nitrate, hydroxychloroquine, sulfasalazine, etc.
• In addition, levodopa, dopamine, phenytoin, diphenhydramine, chlorpheniramine, colchicine, and doxorubicin also have a lower risk.

Read More