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.

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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. 

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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.

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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.

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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.

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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/

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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.

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Learning about ezetimibe.📜📜📜

Ezetimibe was the first drug to inhibit cholesterol absorption in the gut. It can be combined with statins to enhance the ability to lower cholesterol levels. It is widely used clinically. The following will introduce the relevant knowledge about ezetimibe.

1. The mechanism of ezetimibe.

Ezetimibe is converted to ezetimibe-glucuronide in the intestinal tract. Ezetimibe-glucuronide acts at the brush border of intestinal epithelial cells. It inhibits the activity of the sterol carrier transporter NPC1L1, thereby reducing intestinal absorption of cholesterol.

Dosage: Once a day, 10mg ezetimibe each time. Ezetimibe can be taken any time of the day. It can also be taken on an empty stomach or with food.

2. The enterohepatic circulation of ezetimibe.

First, ezetimibe is converted to ezetimibe-glucuronide in the intestine. It then travels from the portal vein to the liver and from the liver to the bile. Finally it goes back into the intestines. Enterohepatic circulation maintains ezetimibe-glucuronide in the brush border of intestinal epithelial cells. It can inhibit the intestinal absorption of cholesterol. In addition, enterohepatic circulation can also slow the elimination of ezetimibe-glucuronide. Its half-life is 22 hours.

3. The lipid-lowering intensity of ezetimibe.

Cholesterol in the human body can be divided into endogenous synthesis by the body and exogenous absorption in the diet. About 2/3 of cholesterol is synthesized endogenously and 1/3 of cholesterol is absorbed exogenously. 

Ezetimibe alone can reduce low-density lipoprotein cholesterol (LDL-C) by about 20%. 

	Total cholesterol (TC)	Low-density lipoprotein cholesterol (LDL-C)	High-density lipoprotein cholesterol (HDL-C)	Triglycerides (TG)
Ezetimibe	13%↓	18%↓	8%↓	1%↑
Pravastatin	17%↓	25%↓	8%↓	7%↑
Simvastatin	26%↓	36%↓	17%↓	7%↑
Atorvastatin	32%↓	44%↓	25%↓	4%↑

From the above table, it can be seen that statins have stronger lipid-lowering intensity than ezetimibe. Therefore, ezetimibe is often used in combination with statins to further reduce LDL-C.

	Lipid-lowering treatment plan	Reduced levels of LDL-C
Monotherapy	Ezetimibe	20%
	Moderate-intensity statins (eg, simvastatin, pravastatin)	30%
	High-intensity statins (eg, atorvastatin, rosuvastatin)	50%
	PCSK9 inhibitors (eg, evolocumab, alirocumab)	60%
Combination therapy	High-intensity statin + Ezetimibe	65%
	High-intensity statin + PCSK9 inhibitor	75%
	High-intensity statin + PCSK9 inhibitors + Ezetimibe	85%

4. Adverse reactions.

Because ezetimibe is not metabolized by CYP450 enzymes, it is less likely to have drug interactions. Ezetimibe was well tolerated and safe. Its adverse effects are mild and mostly transient. Its main adverse reactions are gastrointestinal discomfort and headache. In addition, side effects such as muscle pain and increased transaminases can occur when it is used in combination with statins.

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