Knowledge about streptococcal infection.📜📜📜

Streptococcus has a wide variety of bacteria and is widely distributed. Some streptococci are normal human flora, while others are pathogenic bacteria of humans. 

1. What is streptococcus?

Streptococcus is a gram-positive cocci and the bacteria are purple after Gram staining. According to whether hemolysis occurs on blood agar, Streptococcus bacteria are divided into three categories: α-hemolytic streptococcus, β-hemolytic streptococcus and γ-streptococcus.

Medically important streptococci:

1. α-hemolytic streptococcus: Streptococcus pneumoniae, Streptococcus viridans.
2. β-hemolytic streptococcus: Group A Streptococcus (also call streptococcus pyogenes), group B, group C, group D and group G streptococcus.
3. γ-streptococcus: They are generally not causing disease.

2. Common streptococcus infections:

• Streptococcus pneumoniae: Streptococcus pneumoniae is distributed in the nasopharynx of 5-10% of adults and 20-40% of children. Most of the strains are not pathogenic and only a few strains are pathogenic. It is the main pathogen of bacterial pneumonia. It causes diseases such as acute bacterial otitis media, acute bacterial sinusitis, community-acquired pneumonia and lung abscess.
• Streptococcus viridans: It is mainly distributed in the oropharynx and gastrointestinal tract. It1 is a common pathogen causing dental caries, infective endocarditis and bacteremia.
• Streptococcus pyogenes: It is mainly distributed in the throat and is the most pathogenic bacteria among streptococci. It accounts for about 90% of streptococcal infections. It is the main pathogen of acute bacterial pharyngitis and tonsillitis. It can also cause lymphangitis, acute cellulitis, acute rheumatic fever, and glomerulonephritis.

3. Commonly used antibacterial drugs for streptococcal infections.

• Penicillin is the first choice for streptococcal infections. The antibacterial activity of the first and second generation cephalosporins against Streptococcus pneumoniae is less than penicillin. The drug resistance of streptococcus is caused by genetic mutations. Streptococcus pneumoniae is also less resistant to them. Streptococcus is not sensitive to penicillin. Amoxicillin, ceftriaxone and cefotaxime will have good antibacterial activity. 
• Penicillin-resistant Streptococcus pneumoniae is highly sensitive to vancomycin, linezolid and carbapenems.
• The resistance rate of macrolides and clindamycin is high.
• Aminoglycosides have no antibacterial activity against streptococci, but have synergistic effects with β-lactam antibiotics.

Acute bacterial pharyngitis and tonsillitis:

The common pathogen is group A hemolytic streptococcus. Penicillin is the first choice. Optional amoxicillin. Amoxicillin/clavulanic acid should not be used. This is mainly because hemolytic streptococcus does not produce β-lactamase, and clavulanic acid is useless at all. Since non-suppurative complications (acute rheumatic fever and glomerulonephritis) can occur after infection of group A hemolytic streptococcus, antibacterial treatment is aimed at removing bacteria and the course of treatment takes 10 days.

Acute bacterial otitis media and acute bacterial sinusitis:

The common pathogens are Streptococcus pneumoniae, Moraxella catarrhalis and Haemophilus influenzae. The first choice is amoxicillin or amoxicillin/clavulanic acid. 

Mainly reasons:

• Anti-Gram-positive bacteria activity (group A hemolytic streptococcus, streptococcus pneumoniae): amoxicillin ≈ penicillin.
• Anti-Gram-negative bacteria activity (Moraxella catarrhalis, Haemophilus influenzae): amoxicillin/clavulanic acid> amoxicillin> penicillin.

	Common pathogens	Antibacterial drugs
Acute bacterial pharyngitis and tonsillitis	Group A hemolytic streptococcus	l   Penicillin, amoxicillin. l   Patients who are allergic to penicillin can choose tetracyclines or fluoroquinolones that are sensitive to hemolytic streptococci (such as levofloxacin, moxifloxacin).
Acute cellulitis and lymphangitis.	Group A hemolytic streptococcus	l   Penicillin, amoxicillin. l   Amoxicillin/clavulanic acid, ceftriaxone.
Acute bacterial otitis media.	Streptococcus pneumoniae, Moraxella catarrhalis and Haemophilus influenzae.	l   Amoxicillin. l   If Moraxella catarrhalis and Haemophilus influenzae which producing β-lactamase strains are common in the local area, amoxicillin/clavulanic acid should be used. l   If the patient has no effect after taking the medicine for 3 days, it should be considered as possible penicillin-resistant Streptococcus pneumoniae infection. Ceftriaxone should be used.
Acute bacterial sinusitis.	Streptococcus pneumoniae, Moraxella catarrhalis and Haemophilus influenzae.	l   Amoxicillin/clavulanic acid.
Infective endocarditis	Streptococcus viridans.	l   Penicillin is used in combination with gentamicin. l   Combine ceftriaxone or cefotaxime with gentamicin.
Purulent meningitis (age < 1 month)	Group B hemolytic streptococcus, Escherichia coli, Listeria and Klebsiella pneumoniae.	l   Combine ceftriaxone or cefotaxime with ampicillin. l   Gentamicin is combined with ampicillin.

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Have you ever used corticosteroids ointments❓❓❓

Topical glucocorticoid is a very commonly used topical drug. Some people think that it is a panacea that can cure skin diseases such as itching, redness and swelling. However, some people refuse to use it because it contains steroids. The following are some practical knowledge about topical glucocorticoids.

1. Classification and intensity.

According to the different types and concentrations of glucocorticoids, topical glucocorticoids can be divided into 4 categories: super strong, strong, medium and weak. The same glucocorticoid has different strengths at different concentrations.

Commonly used topical glucocorticoids
Super strong	Clobetasol propionate	0.02%	1.    It is suitable for severe and hypertrophic skin lesions. 2.      Not for use in children <12 years old. 3.    Do not use on soft skin area. 4.    Long-term use in a small area. 5.    Do not exceed 50g per week. 6.    Continuous medication should not exceed 2-3 weeks. 7.    * They can be used with caution in children.
	Betamethasone valerate	0.1%
	Halometasone	0.05%
	Halcinonide	0.1%
	Fluocinolone	0.2%
Strong	Beclomethasone dipropionate	0.025%
	Betamethasone valerate	0.05%
	Fluocinolone	0.025%
	*Fluticasone propionate	0.05%
	*Mometasone furoate	0.1%
Medium	Prednisolone acetate	0.5%	1.    Suitable for mild to moderate skin lesions. 2.    It should not be used for a long time in a large area. 3.    It can be applied continuously for 4-6 weeks. 4.    Children <12 years old try not to use it continuously for more than 2 weeks.
	Dexamethasone acetate	0.05%
	Clobetasone butyrate	0.05%
	Hydrocortisone butyrate	1%
	Triamcinolone acetonide	0.025%
	Fludrocortisone acetate	0.025%
	Fluocinolone acetonide	0.01%
Weak	Hydrocortisone acetate	1%	1.    Suitable for mild to moderate skin lesions. 2.    Apply to the soft skin areas. 3.    Suitable for children <12 years old. 4.    It can be used in a larger area in a short time. 5.    It can be used for a long time if necessary.
	Methylprednisolone acetate	0.025%
	Desonide	0.05%
	Fluocinolone acetonide	0.0025%

Although fluticasone propionate and mometasone furoate are both strong glucocorticoids, they are less absorbed throughout the body when used externally. They are suitable for use by the elderly, infants and in a large areas.

2. The choice of topical glucocorticoids in various populations.

Children and the elderly: It is advisable to choose weak glucocorticoids, and use strong and super strong types with caution.

Pregnant women: Glucocorticoids should be used with caution in pregnant women. Weak or medium types can be selected when they must be used.

Soft skin areas: The face, neck, armpits, groin, inner thighs, perineum and other soft skin areas have a high drug absorption rate, so strong glucocorticoids should not be used. When it must be used, desonide, mometasone furoate and hydrocortisone can be used.

Ointment: The ointment dosage form has an encapsulating effect, which enhances the drug penetration ability. Ointment is suitable for keratinized, hypertrophic and desquamative skin, especially palms and soles. It is not recommended for non-hypertrophic, keratinized skin lesions on soft skin areas such as the face. Ointment should not be used in skin areas where babies wear diapers.

Creams, gels and solutions: They are suitable for all kinds of skin lesions and are also suitable for thick hair areas.

3. Indications.

Dermatitis, eczema, papular urticaria, erythema scaly skin disease, autoimmune skin disease, etc.

4. Contraindications.

Impetigo (bacterial infection), tinea hand and foot (fungal infection), shingles (viral infection), rosacea, acne, skin ulcers, etc. It is also not suitable for acute urticaria. The redness and itching caused by acute urticaria should be relieved with appropriate antihistamines (such as cetirizine, loratadine).

5. Dosage:

The most commonly used method for estimating the amount is the "fingertip unit"(FTU).

FTU: It refers to the amount of ointment squeezed from the ointment tube (with a diameter of 5mm) to an adult's fingertip (from the end of the index finger to the horizontal line of the first knuckle joint). A fingertip unit is about 0.5g ointment.

Estimate the skin area with the palm of your hand, and then calculate the FTU based on the area. Use about 0.5 FTU per palm area.

6. Adverse reactions.

The correct use of topical glucocorticoids is relatively safe. Long-term or large amounts of topical glucocorticoids may induce or aggravate local infections, leading to skin atrophy, telangiectasia, hirsutism, pigment changes, hormone dependence and other adverse reactions.

Patients should actively monitor for adverse reactions: The strong and super strong types are once every 2 weeks, the medium types are once every 3-4 weeks, and the weak types are once every 4-6 weeks.

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Some learning points about levothyroxine.📝📝📝

The manual for levothyroxine.

Indications:

1. Treatment of non-toxic goiter with normal thyroid function.
2. After goiter resection, prevent the recurrence of goiter.
3. Adjuvant treatment of hyperthyroidism with antithyroid drugs.
4. Suppressive treatment after thyroid cancer surgery.
5. Alternative treatment of hypothyroidism caused by various reasons.
6. Thyroid suppression test (used in diagnosis and treatment of diseases).

In addition, levothyroxine is not used for weight loss. It is because inappropriate long-term use of levothyroxine can cause various complications of hyperthyroidism and even life-threatening.

Some moderate to severe obesity patients may have subclinical hypothyroidism. Thyroid stimulating hormone is compensatory elevated, but thyroid hormone levels are normal. Consider taking a small dose of levothyroxine sodium tablets (such as 25ug/day) within a certain period of time. It can reduce the level of thyroid-stimulating hormone and increase the basal metabolic rate, which may help weight loss, but also should pay attention to adverse reactions and strengthen thyroid function.

Medicine interactions:

For drugs that affect the absorption of levothyroxine, you can increase the interval or increase the dose:

1. Cholesterol-lowering drugs: such as cholestyramine and colestipol.
2. Drugs containing aluminum, iron and calcium. Such as gastric mucosal protective agent (sucralfate), antacids (aluminum hydroxide, ferrous sulfate, calcium carbonate tablets).
3. Acid inhibitors and stomach drugs: H2 receptor blockers and proton pump inhibitors (such as ranitidine, omeprazole).
4. Anti-epileptic drugs: such as phenobarbital, phenytoin sodium, carbamazepine.
5. Anti-tuberculosis drugs: such as rifampicin.

Drugs affected by levothyroxine:

1. Anti-diabetic drugs: Levothyroxine can reduce the effect of hypoglycemic. Therefore, patients with diabetes should increase blood glucose monitoring and adjust the dosage in time.
2. Anticoagulant: Levothyroxine can enhance the anticoagulant effect of coumarin derivatives (such as warfarin). Patients should pay attention to adjusting the dosage to prevent the risk of bleeding.

Others:

Propylthiouracil, amiodarone, iodine-containing contrast agents and β-sympathomimetic drugs, glucocorticoids, estrogen, sertraline, etc. can reduce the efficacy of the drug. Salicylate, dicoumarin, high-dose furosemide (250mg), oxytocin, phenytoin, etc. can increase the efficacy of the drug. Need to adjust the dose of levothyroxine sodium tablets as appropriate.

Foods:

Animal offal, spinach, cherries, grapes, peaches, grapefruit, soybeans, high-fiber foods, coffee, milk, yogurt, soy milk, etc.

Medication time:

Since food can affect the absorption of levothyroxine sodium tablets, it is recommended to take the dose with water every morning on an empty stomach. It can be taken immediately after getting up in the morning, but do not eat breakfast within half an hour.

If the dose of the drug is large, it is still not necessary to take it in divided doses. Try not to take the medicine before going to bed, otherwise it may increase the excitability of the body and affect the quality of sleep.

Dosage:

The blood level of thyroid stimulating hormone is a reliable basis for determining the dosage of treatment. If the child has no obvious contraindications, the full dose should be used at the beginning of treatment or the optimal dose can be reached quickly in a short period of time. However, adults should start with a small dose and gradually increase to the optimal dose every 2 to 4 weeks. Elderly patients should increase the dose more slowly.

1. Goiter (normal thyroid function): 75-200ug/day for adults, 50-150ug/day for teenagers.
2. Prevention of goiter recurrence after thyroidectomy: 75-200ug/day for adults.
3. Hypothyroidism in adults: initial dose 25-50ug/day, increase 25-50ug every 2-4 weeks, maintenance dose 125-250ug/day.
4. Hypothyroidism in children: the initial dose is 12.5-50ug/day/m² body surface area, and the maintenance dose is 100-150ug/day/m² body surface area.
5. Adjuvant treatment of anti-hyperthyroidism: 50-100ug/day. After total thyroidectomy: 150-300ug/day.
6. Thyroid suppression test: 200ug/day.

Monitor:

At the beginning of treatment and every time the dosage is adjusted, thyroid function needs to be measured every 4 to 6 weeks. Adjust the dose according to the inspection results. After the treatment reaches the standard, check again every 6 to 12 months. If the treatment is not up to standard, you should carefully look for the reasons, such as clinical compliance and medication time.

Adverse reactions:

Levothyroxine is generally well tolerated. Patients who increase the dose too quickly in the early stage of treatment or overdose may have symptoms of hyperthyroidism, such as palpitations, tremor, sweating, skin flushing, diarrhea, weight loss, menstrual disorders, insomnia and irritability.

When the patient has any adverse reactions, appropriate treatment should be given. If necessary, reduce the dose or discontinue the drug until the adverse reaction disappears and then start the treatment from a small dose.

Long-term use of levothyroxine can accelerate the bone transformation process. Elderly and postmenopausal patients with osteoporosis should pay attention to calcium and vitamin D supplementation. They should monitor the bone density regularly.

Missed medication:

The half-life of levothyroxine is 7 days and its effect is slow and lasting. The effect is significant and stable after taking the medicine one month. 

In the early treatment of hypothyroidism, if there is a missed dose, it may be considered supplementing the dose on the same day or doubling the dose the next day. If the thyroid function is relatively stable after taking the medicine regularly for a long time, it may be considered that there is no need to take supplements, and it can be maintained at the current dose.

Patients after thyroid cancer surgery should ensure that they do not miss a dose as much as possible. If a missed dose is taken, it should be refilled in time to ensure that the dose is sufficient for at least the entire week.

Special population:

At the recommended dose, levothyroxine is not teratogenic to the fetus, nor will it interfere with fetal thyroid function. Therefore, women during pregnancy and lactation cannot stop levothyroxine treatment. The dose may need to increase during pregnancy. Hypothyroidism caused by drug withdrawal has a great impact on maternal and fetal development. Levothyroxine cannot be used as an adjuvant treatment for hyperthyroidism during pregnancy, as this will increase the dose of antithyroid drugs and increase the risk of suppressing fetal thyroid function.

Patients with coronary heart disease, elderly, severe or long-term hypothyroidism must be very cautious about the dose of levothyroxine. It must be started with a small dose, the interval between dose increases should be lengthened, and the monitoring of thyroid function should be strengthened.

Patients with after thyroid cancer surgery take levothyroxine on the one hand to supplement thyroid hormones to prevent hypothyroidism, and on the other to inhibit thyroid stimulating hormone to prevent cancer recurrence.

Contraindications:

1. Allergy.
2. Untreated adrenal insufficiency, pituitary insufficiency, hyperthyroidism, coronary heart disease, angina pectoris, arteriosclerosis and high blood pressure.
3. Acute myocardial infarction, acute myocarditis.

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Vitamin D may be good for heart health.💖💖💖

After the human body is irradiated by ultraviolet rays in the sun, the skin cansynthesize an essential vitamin-vitamin D. Many people know that vitamin D is good for bones. However, recent studies have pointed out that when vitamin D is deficient, not only bone health may be affected, but also heart health. Researchers at the University of South Australia discovered genetic evidence for the first time. It proves that vitamin D deficiency can cause cardiovascular disease. People with vitamin D deficiency are more likely to develop heart disease and high blood pressure than those with normal levels of vitamin D. Cardiovascular diseases are one of the leading causes of human deaths worldwide. It is estimated to cause more than 15 million deaths each year. At the same time, cardiovascular diseases also cause huge economic losses to countries around the world. Understanding the causes of cardiovascular disease can effectively prevent it and reduce economic losses. 

For people who do not often do outdoor activities, it is easy to cause vitamin D deficiency.

Vitamin D deficiency is actually very common. Data from the United Kingdom showed that 55% of the participants had low levels of vitamin D (<50nmol/L), and 13% had severe vitamin D deficiency (<25nmol/L). Statistics show that 37% of Canadians, 23% of Australians and 24% of Americans have had low vitamin D levels. Especially for the elderly, since they may take less outdoor activities, they do not have enough time to be exposed to the sun. This prevents them from getting enough vitamin D. Although food also contains vitamin D, such as oily fish and eggs, the content of vitamin D in food is relatively low. Therefore, even through a balanced diet, there is generally not enough vitamin D. If we cannot get enough vitamin D through sunlight, we need to take supplements every day to achieve the demand. 

Vitamin D can affects cardiovascular health.

The results of the study show that if they can increase the level of vitamin D within the normal range, it should also affect the incidence of cardiovascular disease. Among the population participating in the study, individuals with vitamin D deficiency increased their vitamin D levels to at least 50 nmol/L, which is estimated to prevent 4.4% of cardiovascular disease cases. Researchers evaluated how increasing the levels of vitamin D affect cardiovascular disease risk based on how high the participants' actual the levels of vitamin D were. The study used data from nearly 300,000 people. This allows the study to provide strong statistical evidence for the link between vitamin D deficiency and cardiovascular disease. People with vitamin D deficiency are more likely to develop heart disease and high blood pressure than those with normal levels of vitamin D. For participants with the lowest levels of vitamin D, the risk of heart disease was more than twice that of those with sufficient vitamin D. The research leader thinks, "It is unethical to recruit patients with vitamin D deficiency to participate in randomized controlled trials and keep them from receiving treatment for a long time. But it is this method that can show how increasing the concentration can affect the risk of those who need it most, and don't let participants suffer any harm." Non-linear Mendelian randomization analysis supports the L-type association between serum 25-hydroxyvitamin D concentration and cardiovascular disease risk. This shows that the cardiovascular health benefits of improving vitamin D status are the strongest for those in the vitamin D deficiency range. Vitamin D supplementation may have the strongest effect on those with the lowest levels of vitamin D. The methods to eliminate vitamin D deficiency within the population can reduce the global burden of cardiovascular disease. 

Non-linear Mendelian randomization analyses support a role for vitamin D deficiency in cardiovascular disease risk.

If you want to know more detail, you can read this article.👇

Ang Zhou, Joseph B Selvanayagam, Elina Hyppönen, Non-linear Mendelian randomization analyses support a role for vitamin D deficiency in cardiovascular disease risk, European Heart Journal, 2021;, ehab809, https://doi.org/10.1093/eurheartj/ehab809

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Be careful when drinking alcohol outdoors in winter.🍺🍺🍺

In the news, people sometimes get drunk in the winter, fall asleep on the road, and then freeze to death. Some people who are still young and strong will freeze to death on the side of the road. What is going on here? Can people be frozen to death so easily? In fact, this situation is not uncommon. There will be similar news all over the world every winter, but many people may not know it.

What happened to make people drunk?

When people drink too much alcohol, they are easily paralyzed by feeling good about themselves at first. People are usually in a more excited state when they are just drunk. They will feel that they are not drunk and that all their states are normal. This is because the human body absorbs only a small dose of ethanol at this time. Small doses of ethanol can inhibit the cerebral cortex and cause the "disinhibitory excitement" of the subcortical center. Therefore, people who drink alcohol often exhibit high mood, excessive excitement and decreased control ability. 

However, as the absorbed dose of ethanol increases, the inhibitory effect will spread to the subcortical center. At this time, people turn from an excited state to a restrained state. At this time, in addition to the above symptoms will aggravate. The body will also experience symptoms such as impaired motor control ability and decreased clarity of consciousness, such as instability, confusion, lethargy and so on. 

If ethanol intake continues to increase, then it will inhibit the medulla oblongata life center. It can cause coma and even death. 

Why is it easy to freeze to death when sleeping outdoors after drinking?

In fact, This is usually caused by people underestimating the power of alcohol and lead to happen the accidents. In addition to the above, when drinking alcohol and for a short period of time after drinking, the human body will temporarily feel warm due to the effect of acetaldehyde. But in fact, the body is actually losing heat continuously at this time. As the body's heat continues to be lost, drunk people will feel colder and colder. In this case, if a person sleeps outside in the cold winter because of being drunk, it is easy to have an accident due to hypothermia.

Therefore, we must not underestimate the effects of alcohol on the human body. Never walk alone outside after excessive drinking, especially on cold winter nights.

What is alcohol dependence?

Alcohol dependence refers to the mental and physical dependence of people who drink alcohol for a long time. Mental dependence means that as long as you don't drink, you will feel restless, anxious, irritable, listless and will try everything to drink. Physical dependence refers to people who drink for a long time. Once they start to give up, the body will have a lot of discomfort, such as palpitation, headache, fatigue. Once they resume drinking, the symptoms will naturally disappear. Another feature of alcohol dependence is the continuous increase in alcohol consumption and increased tolerance. It generally takes several years to decades to reach alcohol dependence. Many people know that drinking too much is harmful to the body, but they are unable to control themselves. Occasionally reducing the amount or not drinking will cause discomfort and must drink alcohol to relieve their discomfort.

Some ways to Quit Drinking:

1. Reduce the amount of alcohol: If you drink too much, you must take it slowly to avoid withdrawal symptoms. You can choose a specific weekday to never drink and reduce the amount of alcohol you drink each time.
2. Reduce participation in drinking activities: Reduce contact with friends who drink with you and participate in their drinking activities.
3. Eat something before drinking: Eating before drinking can reduce your desire to drink, and it will also make it more difficult to get drunk.
4. Drink more water: This keeps you hydrated, and also helps your body expel toxins.
5. Self-feelings: Face your own feelings well. Explore your own inner thoughts, emotions and behaviors.
6. Refusal to drink: Bravely refuse people who invite you to drink.
7. Learn how to eliminate worries: try to understand your worries. Drinking is just an escape from the problem, and there are actually many ways to get rid of worries.
8. Consult a doctor: You should not start quitting alcohol alone. The process of quitting alcohol can be fatal. If you have withdrawal symptoms (panic, anxiety, trembling, rapid heartbeat), you should seek medical help immediately. This condition may worsen into delirium tremens, which can be fatal if not treated. 

In fact, as long as your will to quit drinking is strong enough, there are many ways to help you quit drinking. There are also some drugs that can reduce your desire for alcohol. Those drugs can make you feel discomfort when you drink alcohol.

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What is the difference between zopiclone and eszopiclone?💤💤💤

Insomnia is one of the most common types of sleep disorders in clinical practice. Almost all psychiatric patients may be accompanied by insomnia. The main manifestations of insomnia are: difficulty falling asleep (falling asleep for more than 30 minutes), difficulty maintaining sleep (the number of awakenings throughout the night ≥ 2 times), total sleep time reduction (total sleep time ≤ 6 h), sleep quality reduction and early awakening. At present, the clinical treatment of insomnia drugs is mainly divided into three categories: benzodiazepine receptor agonists (that is, traditional benzodiazepine drugs and new non-benzodiazepine drugs), melatonin receptors agonists and antidepressants with hypnotic effects. Previously used traditional benzodiazepines, such as alprazolam, lorazepam. They can also shorten the patient's sleep latency and increase the total sleep time. However, due to continuous use will produce dependence and obvious adverse reactions,  it is now gradually withdrawing from the clinical stage. The new non-benzodiazepine drugs, such as zolpidem, zopiclone and zaleplon. These drugs have short half-life and the residual effect of the next day is minimized. Therefore, they generally do not produce daytime drowsiness. The dependence caused by long-term use is also greatly reduced compared with traditional benzodiazepine drugs. In addition, these drugs are safe and effective in the treatment of insomnia. Among non-benzodiazepine drugs, zopiclone and eszopiclone are commonly used clinical sedatives and hypnotics. What is the difference between them?

1. Medicinal effect.

Zopiclone is a racemate. It is consisting of S-Zopiclone (Eszopiclone) and R-Zopiclone (L-zopiclone). It is a non-benzodiazepine sedative and hypnotic, which mainly exerts sedative and hypnotic effects by selectively activating the α1 subunit on the γ-aminobutyric acid receptor.

The affinity of eszopiclone to the γ-aminobutyric acid receptor is 50 times that of L-zopiclone. The hypnotic effect of 3mg eszopiclone is equivalent to that of 7.5mg Zopiclone.

2. Toxicity.

The results of animal experiments showed that the LD50 of eszopiclone was 1500mg/kg, the LD50 of L-zopiclone was 300mg/kg and the LD50 of racemate was 850mg/kg.

3. Pharmacokinetics.

Eszopiclone is absorbed faster and has a longer half-life than L-zopiclone. However, zopiclone contains 50% of eszopiclone, so there is not much difference between the onset time and maintenance time of zopiclone and eszopiclone. 

It takes about 1 hour for eszopiclone to reach its peak value. Taking it with food can delay the peak time by 1 hour. The half-life in adults is 6 hours, and the half-life in the elderly is 9 hours. It is metabolized by the liver, and CYP3A4 is the main metabolic enzyme. 10% is excreted in urine in its original form.

• For adult patients: The recommended dose is 1-3 mg before going to bed. 
• For elderly patients who have difficulty falling asleep (It takes more than 30 minutes to fall asleep): The recommended starting dose is 1 mg, and can be increased to 2 mg if necessary. 
• For elderly patients with sleep maintenance disorders (The number of awakenings throughout the night ≥ 2 times): the recommended dose is 2 mg before going to bed.

Zopiclone takes about 1.5-2 hours to reach its peak, and food does not affect its peak time. The half-life in adults is 5 hours, and the half-life in the elderly is 7 hours. It is also metabolized by the liver, and CYP3A4 is also its main metabolic enzyme. 4-5% is excreted in urine in its original form.

• For adult patients: the recommended dose is 3.75-7.5 mg before going to bed. 
• For elderly patients: the recommended dose is 3.75 mg.

The total absorption of the two drugs in the elderly (≥65 years) is 41% higher than that in adults, and the half-life is longer. Therefore, elderly patients should start with a low dose.

4. Adverse effects.

The most common adverse effect of zopiclone and eszopiclone is abnormal taste (bitter mouth, metallic taste), which is dose-related and can disappear after stopping the drug. There are also stomach burning and sedation, dizziness, and dose-related amnesia. Some patients also experience symptoms such as dry mouth, headache, and nervousness. Some long-term studies believe that they will not show obvious dependence.

Non-benzodiazepine drugs may cause sleepwalking, sleepwalking and driving. Although it is rare, it can cause serious injury or death. If the above sleep behavior occurs, please seek medical attention immediately and stop such drugs under the guidance of a doctor.

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Some habits of getting up may be harmful to your health.👿👿👿

Studies have shown that about 40% of myocardial infarction and 29% of sudden cardiac death occur in the early morning. This is because blood pressure rises rapidly in the early morning hours. From 6 to 10 in the morning, the blood pressure of most people will reach the highest level in a day, and the occurrence of cardiovascular and cerebrovascular diseases is directly related to the increase in blood pressure in the morning. Therefore, some habits of waking up may induce these risks.

1. Alarm clock is too loud.

Most people wake up by an alarm clock. The sound of the alarm clock will stimulate the nerves and physiology of the human body, thereby interrupting normal sleep and awakening people. However, if this sound is too loud, it will cause the body's protective conditioned reflex and increase the body's adrenaline level. If things go on like this, it may lead to a series of problems such as high blood pressure and mental depression. Especially middle-aged and elderly people with heart disease and high blood pressure, if they wake up suddenly in their sleep, they are prone to nervousness, vasoconstriction and increased blood pressure. In severe cases, they may even lead to heart attack or cerebral infarction.

Therefore, the sound of the alarm clock should be as soft as possible or music, which is less irritating. Older people sleep more lightly, so they don't need an alarm clock. If there are special circumstances, they need to get up early to go out, so that their family members can wake them up quietly.

2. Get up too rapid.

As soon as the alarm sounds, get up quickly to go to the toilet or wash to catch up with work. This practice is bad for the body. When a person is sleeping, the cerebral cortex is in a dormant, inhibited state. Various physiological functions maintain low-speed operation, lower metabolic level, slower heartbeat, lower blood pressure, etc. 

When you wake up, if you get up immediately, the body's various functions have not been functioning normally. For example, the blood flow is relatively slow, and oxygen cannot be delivered to the brain in time. This is prone to dizziness, vertigo and other discomforts. If you are middle-aged and elderly people, you are also prone to cardiovascular and cerebrovascular risks. In addition, the neck muscles are in a relaxed state after a night of rest. If you get up hard, it is easy to damage the neck muscles, fascia and ligaments.

Getting up should be slow and soft.

3. Do not eat breakfast.

After one night, the stomach is emptied. If there is no food to supplement in time, stomach acid and various digestive enzymes will digest the gastric mucosa. If this happens, you will be prone to gastritis, gastric ulcer and other diseases. In addition, skipping breakfast for a long time will also cause low-density lipoproteins to deposit on the inner walls of blood vessels. This can lead to arteriosclerosis. A large number of studies believe that skipping breakfast is related to obesity, diabetes, and gallstones.

Every day after waking up, you should have breakfast.

4. Forced bowel movements.

Get up in the morning and want to go to the toilet to defecate. But you are about to be late for work, so you have to repeatedly forced bowel movements, try hard and try to finish quickly and leave home quickly. This is not good for your health. Because of forced defecation, the intestinal tract's ability to actively contract during defecation will be weakened. This can cause or aggravate constipation, hemorrhoids, and even cause anal prolapse. In addition, when people defecate, their blood pressure tends to rise. Excessive force can easily cause abdominal pressure to increase sharply, and blood pressure will increase, heartbeat will increase, and myocardial oxygen consumption will increase, which may induce severe acute ischemia and even myocardial infarction. Therefore, when you wake up in the morning to defecate, you must relax. If you have difficulty defecation, try abdominal breathing.

Abdominal breathing: When you breathe in, you bulge your belly, and when you breathe out, your belly dents. Inhale and exhale, pay attention to the slow rhythm, which can activate the spleen and stomach in the abdomen, promote intestinal peristalsis, and smooth defecation.

5. Strenuous exercise.

Many people like to go for a run in the nearby park after getting up, get some fresh air, and then come back to take a shower and eat breakfast. It looks good, but it is not recommended. According to statistics, among the sudden deaths from exercise in the elderly, the number one is the sudden death from exercise in the morning. This is because the blood viscosity of the human body in the morning is relatively large, the flow is not smooth, and too vigorous exercise can easily induce cardiovascular attacks.

It is recommended not to do such strenuous exercise in the morning exercise, especially for middle-aged and elderly people. Just take a walk and practice yoga after getting up.

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Vitamin B12 deficiency may increase the risk of depression.😣😣😣

Depression is the most common type of mental illness. It is characterized by continuous and long-term depression and is the most important type of mental illness in modern people. Recently, a longitudinal study in the Ireland found that vitamin B12 deficiency can increase the risk of depression. The study investigated the relationship between the levels of folic acid and vitamin B1 levels in the elderly and depression. Research results show that the low levels of vitamin B12 are related to depression symptoms, but the levels of folic acid are not significantly related to depression. The research results provide relevant information for the elderly and public health to better understand how to identify risks and take protective measures to improve health outcomes for people 50 years and older.

The levels of participant's vitamin B.

Low levels or deficiencies of vitamin B such as folic acid and vitamin B12 are common in the elderly. Studies have pointed out that one-eighth of the local elderly have low levels of vitamin B12. People of all ages have also reported that the dietary intake and blood concentration of vitamin B12 are low. Some of the negative consequences of low vitamin B12 levels may include impaired cognitive function, megaloblastic anemia or damage to the protective layer (myelin sheath) that surrounds the nerve fibers of the brain. It is important to understand the relationship between the low levels of folic acid or vitamin B12 and depression in later life. It is because depression is a risk factor for cognitive decline, hospitalization, and premature death. The study surveyed participants aged 50 years and older. The plasma folic acid and plasma vitamin B12 levels were measured and screened for depression. Researchers have observed that those with low levels of vitamin B12 are 51% more likely to develop depressive symptoms within 4 years.

Research result.

1. The study found that over a four-year period, low levels of vitamin B12 were associated with a significant increase in the risk of depressive symptoms, but no such association was observed with folic acid.
2. Researchers have observed that those with low levels of vitamin B12 are 51% more likely to develop depressive symptoms within 4 years.
3. These findings are still valid even after controlling for related adjustment factors such as physical activity, vitamin D levels, burden of chronic disease, cardiovascular disease and use of antidepressants.
4. Other factors that affect the nutritional status of the elderly include smoking, drug use, obesity, gender, financial ability and place of residence.
5. With age, the risk of depression decreases.
6. In the surveyed elderly population, the incidence of sudden depression is very high, and their level of vitamin B12 is very low.
7. These findings show that the level of these vitamins can be increased by improving the diet and may have potential benefits for preventing depression.

In view of the high incidence of depression among the elderly living in Ireland, especially after there is evidence that one in eight elderly people report a high level of vitamin B12 deficiency, this study is highly relevant. In Europe and the United Kingdom, there is a growing trend for governments to implement food policies to increase vitamin B intake. In particular, the practice of increasing folic acid in food in the United States has shown a positive effect. Among people aged 60 and above, the low levels or deficient folic acid is only 1.2%. Research results indicate that food fortification policies can provide a potential way to help prevent depression in the elderly and benefit overall health through foods such as breakfast cereals rich in vitamin B12 and folic acid. The main advantage of this study is that it is based on a large amount and representative sample of elderly people observed for more than four years. In addition, the researchers examined a group of well-characterized patients and incorporated a series of confounding factors, including lifestyle, chronic diseases, medications, and other nutritional blood biomarkers to reveal strong research results. In view of the increase in loneliness and depression in the elderly since the beginning of COVID-19 restrictions. The study emphasizes the importance of increasing vitamin B12 intake or supplement to help reduce potential risk factors for depression in the elderly.

For more detail, you can read this article.👇

Laird, E., O’Halloran, A., Molloy, A., Healy, M., Hernandez, B., O’Connor, D., . . . Briggs, R. (2021). Low vitamin B12 but not folate is associated with incident depressive symptoms in community-dwelling older adults: A 4 year longitudinal study. British Journal of Nutrition, 1-22. doi:10.1017/S0007114521004748

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Anti-aging function of vitamin B2.👴👵

Previous studies have shown that the accumulation of aging cells in the body can lead to aging-related diseases and aging. Using supplements or drugs containing vitamin B2 can inhibit cell senescence. This may prevent and improve age-related diseases and extend people's healthy lifespan. Recently, researchers from Kobe University in Japan stated that adding vitamin B2 to cells exposed to the stress of aging will increase the ability of mitochondria to produce energy and prevent cell aging.

1. The mechanism of human aging.

Aging research is becoming more and more important to solve the medical and welfare problems that come with it and to help people live healthier lives. The process of body aging is not fully understood, but the aging of the cells that make up the body has been proven to be a factor. As the cell division cycle repeats, the telomere region at the end of each chromosome becomes shorter, which eventually leads to cell senescence. It is the cell loses the ability to divide. The reduction of telomere area is not the only relevant factor. Various types of stress on cells (such as DNA damage and reactive oxygen bursts) can also cause cell senescence. Aging cells caused by these stresses accumulate in the body with age. Aging cells have the harmful ability to cause the decline of the function of every organ in the body. By preventing the accumulation of senescent cells, age-related diseases such as Alzheimer's disease, cancer, cardiovascular disease and diabetes can be prevented or improved. 

2. The original intention of the research.

Vitamins are micronutrients necessary to maintain the normal functioning of the human body. Since the human body cannot synthesize vitamins, it must be absorbed from food and drinks. Vitamin B2 (also called riboflavin) is widely found in foods such as eggs, meat, and dairy products. It is an important vitamin for energy production and metabolism. Lack of vitamin B2 can cause symptoms such as mouth swelling and anemia. In addition, excessive intake of vitamin B2 generally has no negative effects, because it is a water-soluble vitamin that can be excreted from the body very quickly. Although vitamin B2 is an essential nutrient for maintaining health, its relationship with aging has not been studied. The research team began to study the effect of vitamin B2 on aging, hoping that if daily vitamins can inhibit cell aging, this will help provide low-cost and safe anti-aging drugs.

3. Research methods.

The research team found that by increasing the amount of SLC52A1 produced, the phenomenon of cell aging can be resisted. SLC52A1 is a vitamin B2 transporter. It is responsible for transporting vitamin B2 to the cell. When the production of SLC52A1 increases, even under stress conditions (treatment of human cells with drugs to damage DNA and induce senescence), cellular senescence does not occur immediately. On this basis, the researchers exposed the cells to a stressful environment, and then increased the vitamin B2 content in the culture medium. They found that the ability to resist aging increases with the content of vitamin B2 in the solution. In the cell, vitamin B2 is converted into a substance called flavin adenine dinucleotide (FAD), which is a coenzyme that promotes the chemical reactions necessary for biological activities (such as energy production). In stressed cells, mitochondrial activity temporarily increases and then decreases in activity leading to senescence. By increasing the content of vitamin B2 in the culture medium, maintaining a high level of stress-mediated mitochondrial activity, this also has anti-aging effects. Studies have found the activity of AMPK enzyme, which can detect energy deficiency in cells, and found that AMPK activity is inhibited by mitochondrial activity. On the contrary, using drugs to inhibit mitochondrial activity will cause AMPK to be activated and send a signal to the p53 (inducing cell senescence) protein to prevent cell division, leading to a state of senescence. The above results indicate that vitamin B2 can increase the mitochondrial activity of stressed cells and prevent aging by inhibiting the functions of AMPK and p53.

Summary: Cells under stress will produce SLC52A1 and increase their absorption of extracellular vitamin B2. Once in the cell, vitamin B2 will be converted into FAD, and increase the production of mitochondrial energy by becoming a coenzyme of the mitochondrial respiratory chain complex II. Therefore, AMPK and p53 (inducing cellular senescence) are inactivated, so stress-mediated cellular senescence is suppressed.

👉Vitamin B2 is easily absorbed from food and supplements, and even if it is taken too much, it will be quickly excreted from the body. Therefore, based on the cellular anti-aging properties of vitamin B2, treatment methods for age-related diseases have been developed. This drug is believed to be relatively cheap and safe.

For more detail, you can read this article.👇

Nagano T, Awai Y, Kuwaba S, Osumi T, Mio K, Iwasaki T, Kamada S. Riboflavin transporter SLC52A1, a target of p53, suppresses cellular senescence by activating mitochondrial complex II. Mol Biol Cell. 2021 Nov 1;32(21):br10. doi: 10.1091/mbc.E21-05-0262. Epub 2021 Sep 15. PMID: 34524871.

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