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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Repeated damage to cells can cause cancer, so do muscle cells?💪💪💪

Chronic injury and inflammation are major risk factors for cancer. Carcinogenic factors such as eating hot food, drinking hot tea, smoking, and air pollution are all due to their repeated damage to human tissues. But why does repeated tissue damage lead to cancer? Although the mechanism of this carcinogenesis is complex, one of the more easily understood reasons is that the repair of damaged tissue requires cell division. Every time a cell divides, a gene may mutate. Repeated tissue damage increases the number of cell divisions, which increases the probability of mutation into an oncogene. At this time, fitness enthusiasts may think that muscle fibers are constantly damaged and repaired during muscle exercise. Will it also increase the risk of cancer?

Does muscle building increase the chance of a genetic mutation?

Its answer is of course not. Muscle building does not increase your risk of cancer. The main reason is that with or without exercise, muscle tissue rarely develops tumors. Lung cancer, breast cancer, liver cancer, etc. are all common, but muscle cancer is rare. It is because the muscle tissue rarely develops tumors. Although this does not mean that muscle tissue is completely tumor-free, for example, rhabdomyosarcoma is a tumor with muscle tissue characteristics. However, it is not caused by muscle building. Rhabdomyosarcoma is a common childhood tumor. Congenital or early developmental genetic mutations are its main cause. Adults over the age of 30 generally do not have rhabdomyosarcoma. 

Why do muscles rarely get cancer?

Long-term muscle building can lead to repeated muscle growth and injury, but why do muscles rarely get cancer? Because of the special structure of skeletal muscle, it has its own anti-cancer function. 

The structure of muscle.

As it can be seen from the above figure, a skeletal muscle cell is also called a muscle fiber. It has two main features:

1. Most cells in the human body generally have only one nucleus. However, a myofibroblast will have many nuclei. It belongs to multinucleated cells.
2. Muscle cells, which are multinucleated cells, do not divide and proliferate by themselves. They do not go from one muscle fiber directly to two muscle fibers.

So how does muscle training make muscles stronger without splitting muscle fibers? This makes muscles stronger both by making the muscle cells bigger and by fusing more muscle cells. Muscles tend to get bigger because each muscle fiber cell gets bigger, not because there are more of them. Myofibroblasts use nutrients in the body to synthesize more protein when stimulated by exercise. It makes muscle cells larger, but does not proliferate. 

Muscle building

How do muscles repair after muscle damage?

Muscle stem cells are responsible for muscle repair. Although myofibroblasts cannot divide and proliferate, muscle stem cells can. Muscle stem cells usually only attach to the surface of muscle fibers and do not proliferate. Muscle stem cells are activated if the muscle is growing or repairing damage. They divide and proliferate to create new muscle cells. Most stem cell divisions produce new cells that fuse with old myofibroblasts and repair damaged muscle fibers. The rest retain the properties of muscle stem cells and attach to the surface of muscle fibers.

Muscle Repair.

Why doesn't the division and proliferation of muscle stem cells increase cancer risk?

One of the main reasons is that most muscle stem cells fuse into muscle fibers after they divide and proliferate. When these stem cells fuse into muscle fibers, they lose their ability to divide and proliferate. They do not accumulate mutations. Although a single muscle stem cell division may lead to cancer-causing mutations, one mutation is not enough to generate cancer cells. Adults generally need to accumulate multiple mutations to form cancer cells. And in many cases, specific mutation types and sequences are required to cause cancer. The process is also relatively long. And when a muscle stem cell has an oncogene mutation, it is quickly fused into the muscle fiber. Even if the muscle is damaged by the next exercise, it will not divide and grow again. Normally, it does not accumulate into cancer cells and cause cancer. This biological feature is the anticancer function of skeletal muscle. In addition, a number of studies have shown that regular muscle training does not increase cancer risk but significantly reduces cancer incidence.

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Drinking water like this is bad for your body.😖😖😖

Many people know that drinking more water is good for the body. Many people know that drinking more water is good for the body. However, drinking water indiscriminately can be harmful to the body's organs and the damage is not immediately reflected. It can cause long-term damage to your body without even noticing it. Therefore, here are some bad drinking habits, so that you can change your drinking habits in time.

Too cold water is bad for the stomach and intestines.

With summer approaching, many people like to drink cold water. Drinking it can refresh you when you are sleepy, and it can cool down quickly after exercising. This is very refreshing. However, if a person suddenly drinks too cold water, the smooth muscles of the stomach and intestines will spasm, and the blood vessels will suddenly contract. It may cause stomach and intestinal dysfunction, indigestion, constipation and other problems. Especially during or after exercise, these problems are more likely to be caused. 

When a person is exercising, the functions of various organs in the human body will be adjusted due to the exercise. The functions of exercise-related tissues and organs such as the heart, lungs and muscles will be enhanced. Organs involved in metabolism or energy storage, such as the gastrointestinal tract, are also weakened. The rate of gastric emptying is also reduced. In addition, a person's body temperature rises during and after exercise. At this time, if you drink too much or drink too cold water quickly, it will not only easily cause gastrointestinal disorders, but also cause water retention in the stomach. It can cause nausea, stomach pain, bloating, indigestion and constipation.

Drinking water too fast is bad for the heart.

The heart pumps blood throughout the body through the contraction of the myocardium, and returns the blood to the heart through the relaxation of the myocardium. However, as people age, the function of the heart also declines. After the function of the heart declines, its ability to withstand sudden stimuli will also decrease. Even small stimuli, such as drinking water quickly, can damage the heart due to the increased burden. Especially with a lot of people who are thirsty after a bath, they drink water instantly and quickly. It is very dangerous. Heart rate generally rises right after taking a shower. If you drink water quickly at this time, too much water will enter the blood vessels. This water can make the heart more burdened. People with poor heart function, patients with cardiovascular disease and the elderly may experience symptoms such as palpitation and sweating.

Drinking too little water is bad for your kidneys and bladder.

Drinking too little water can reduce urination. Decreased urination can cause the following:

Decreased urine output and increased urine concentration can saturate or supersaturate calcium phosphate, calcium oxalate, and uric acid in urine. They can precipitate as crystalline particles in the urine. These crystals continue to accumulate and eventually form kidney stones or bladder stones.

Decreased urination prevents bacteria from being excreted in time. It can easily cause acute cystitis, urinary tract infection, etc., especially in women. Because the female urethra is relatively short. External bacteria can easily pass through the infected urethra to the bladder.

If the weather is hot, people sweat more and drink too little water, which increases the risk of infection and urinary tract stones.

In addition, if you don't drink enough water for a long time, your body will be dehydrated. It also increases the risk of urinary system cancers.

Drinking too hot water is bad for the esophagus.

Many people drink some hot water to relieve discomfort when they feel uncomfortable. However, too hot water can actually harm our esophagus. The mucosal epithelial layer on the esophagus is very soft and thin. When hot water directly touches the mucosal epithelial layers, it is easy to burn them and cause breakage, ulceration, and bleeding. The mucosal epithelium generally repairs damaged tissue quickly. However, if the mucosal epithelium is often badly stimulated, it will easily appear some cells with abnormal functions and morphology due to frequent repair and proliferation, and then evolve into tumor cells. Although the maximum temperature that the mouth and esophagus can tolerate is 50 to 60 ^oC, the optimal temperature for food to be eaten by the human body is 10 to 40 ^oC. Therefore, food or water that is too hot should be ingested after it has cooled slightly. 

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What is the difference between the antiprotozoal drugs ornidazole, levornidazole and levornidazole disodium phosphate❓❓❓

Ornidazole is a third-generation nitroimidazole. It has an antagonistic effect on protozoa such as amoeba, trichomoniasis, and giardiasis. In addition, it also has a good anti-anaerobic effect. So, what is the difference between ornidazole, levornidazole and levornidazole disodium phosphate?

Antiprotozoal effect and anti-anaerobic bacteria effect.

For the treatment of anaerobic and protozoal infections, metronidazole, tinidazole, ornidazole, and levornidazole can be used. Secnidazole can only be used for the treatment of protozoal infections. Tinidazole and ornidazole are more resistant to anaerobic bacteria than metronidazole. These drugs have smaller molecular weight, better lipid solubility and poor water solubility. They can enter the placenta and cerebrospinal fluid.

Indications and dosage.

Ornidazole is a racemic compound. It is converted in the body to dexornidazole and levornidazole. Both of them have similar antiprotozoal and antianaerobic abilities. However, dexornidazole is more toxic than levornidazole. The half-lives of ornidazole and levornidazole are 12 to 14 hours and they have the same indications and dosages. The indications and dosage of ornidazole and levornidazole are as follows:

To treat anaerobic infections: 

• After dinner, take 1.5g orally, and take the medicine continuously for 1 to 3 days according to the condition.
• Take 0.5 to 1 g orally each time, once every 12 hours, and take the medicine continuously for 3 to 10 days according to the condition.
• The starting dose by intravenous infusion is 0.5 to 1 g every 12 hours for 5 to 10 days.

To treat trichomoniasis:

• After dinner, take 1.5g orally, and take the medicine continuously for 1 to 2 days according to the condition.

For the treatment of vaginal trichomoniasis, it is recommended that a single dose of metronidazole 2g or a single dose of tinidazole 2g is recommended.

Adverse reactions.

Common adverse reactions of nitroimidazoles are as follows:

• Oral gastrointestinal adverse reactions such as metallic taste, stomach pain, and nausea.
• Nervous system side effects such as numbness, spasms, tremors, dizziness, headache, and confusion in the limbs.

The incidence of gastrointestinal adverse reactions was similar between ornidazole and levornidazole. Taking ornidazole and levornidazole after meals can reduce gastrointestinal adverse effects. However, ornidazole has a higher incidence of neurological adverse effects than levornidazole. 

Nitroimidazoles can cause disulfiram-like reactions. They inhibit acetaldehyde dehydrogenase and prevent hepatic oxidative metabolism of acetaldehyde. It causes acetaldehyde to build up. Nitroimidazoles may also inhibit dopamine beta-hydroxylase activity and reduce dopamine metabolism. It increases dopamine levels in the brain leading to serotonin toxicity syndrome. Compared with other nitroimidazoles, ornidazole has less inhibitory effect on acetaldehyde dehydrogenase. However, it has also been reported that ornidazole can cause a disulfiram-like reaction. Therefore, it recommends that alcoholic beverages or medications should not be taken while taking ornidazole.

Difference between levornidazole and levornidazole phosphate disodium.

Levornidazole has poor water solubility. In order to enhance its water solubility, it is generally added with hydrochloric acid. This lowers the pH of the injection to 3.2 to 4.5. Injections with low pH are more likely to cause phlebitis.

The water solubility of levornidazole disodium phosphate will be higher than that of levornidazole. Its injectable dosage form has a pH of about 5.5. Some studies have pointed out that levornidazole phosphate disodium injection does not cause phlebitis.

When ornidazole and levornidazole are administered intravenously to patients, the injection should be diluted to a solution of ≤5 mg/ml. In addition, each intravenous infusion of 100ml of solution, the infusion time is not less than 30 minutes. Ornidazole and levornidazole injections should be stored in a shaded, airtight and cool place (temperature not exceeding 20°C).

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How to use eye drops correctly?👀

Nowadays, people often use electronic products such as mobile phones and computers. Watching the screen for a long time can easily cause eye discomfort. Whenever the eyes feel uncomfortable and dry, many people use eye drops to relieve the discomfort. However, not everyone knows the correct way to use eye drops and what to pay attention to when using them. The following will explain the correct use of eye drops.

1. Check the eye drops for any abnormality.

First of all, be sure to confirm whether the drug is an ophthalmic preparation. The pharmaceutical requirements for ophthalmic preparations are not the same as for general dosage forms. The resistance of the eyes is lower than that of the skin or the stomach. Ophthalmic preparations are used directly on the eyes, so their pharmaceutical requirements are much higher than those of general dosage forms. Medication in normal dosage form should not be used in the eyes. In addition, you should also check that the expiration date on the packaging has not expired when you use it. Not only eye drops, but all medicines should not be used after they have expired. All ophthalmic preparations should not continue to be used and should be thrown away if particles appear or if the color of the solution changes.

2. The correct procedure for eye drops.

You should wash your hands before applying eye drops or ointment. Then you can lie down or sit with your head thrown back. Use your index finger and thumb to gently pull the lower eyelid down to form a sac. Turn your eye upward so that your inferior fornix conjunctiva is fully exposed. Put the eye drops close to your eyelid. But do not touch the eyedrops on the eyelids, as this may contaminate the eyedrops. You dispense the eye drops as prescribed and close your eyes gently. Try not to blink immediately after instilling the eye drops. Gently press with one finger on the corner of the eye near the side of the nose for 1 to 2 minutes. If you don't do this, the eye drops may flow from the surface of the eye through the nasolacrimal duct into the nose and mouth. After 1 to 2 minutes you wipe off the excess eye drops with a clean tissue. 

When using eye ointment, squeeze a certain amount of eye ointment into the lower eyelid. Eye ointment should be squeezed into a thread. However, do not touch your eyelids or eyes when squeezing the ointment. Then close your eyes and roll them a few times. This allows the ointment to spread evenly.

3. How to store eye drops.

Eye drops bottles do not need to be wiped or rinsed after use, as this will contaminate the drops. Just screw the cap tightly and store it in a suitable environment. In addition, because the eye drops are sterile preparations, it is easy to breed bacteria after opening. Unless there are special regulations for eye drops, they should be used up within 1 month after opening. After opening, eye drops should be stored in a dry, cool place away from direct sunlight. Some eye drops will need to be refrigerated, but not frozen.

4. Precautions for combined use of eye drops.

Sometimes a patient may need to use several eye drops. However, these eye drops cannot be used together at the same time. Under normal circumstances, one eye drop is instilled first, and then another eye drop is applied 10 to 15 minutes later. If eye drops are used at the same time, the first eye drop is not fully absorbed and washed away by another eye drop. This can cause the first eye drop to be ineffective. 

In addition, in order to avoid eye drops that are too irritating to the eyes, it recommends that patients use less irritating eye drops first. For example, patients need to use levofloxacin eye drops and sodium hyaluronate eye drops in combination. It recommends that patients use sodium hyaluronate eye drops first, and then levofloxacin eye drops after 10 to 15 minutes. 

If the patient needs to use eye ointment and eye drops at the same time, it recommends using eye drops in the morning and eye ointment at night before going to bed. After applying eye ointment, the ointment spreads into a film on the cornea. This can affect vision. It recommends using eye ointment at bedtime.

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Some dietary habits may cause liver cancer.👿👿👿

More and more attention is now paid to protecting the liver. Many people
know that staying up late and drinking alcohol can be harmful to the liver, but many people do not know that some eating habits are also harmful to the liver, even more damaging than staying up late. Here are some dietary habits that can damage the liver.

Eating this flavor is more damaging to the liver than staying up late.

Many people know that staying up late hurts the liver, but there is a taste that will make the liver more and more hurt. Eating this flavor for a long time is even worse than staying up late and that taste is sweet. Many people know that eating too many sweets can cause obesity, increase the risk of cardiovascular and cerebrovascular diseases and diabetes. However, eating too many sweets can actually damage the liver, and the damage of fructose is more serious. Fructose is one of these sugars. It is widely found in natural foods such as fruits and honey. Recent studies have identified excessive fructose intake as a risk factor for nonalcoholic fatty liver disease. The main risk factors for this type of fatty liver are obesity, insulin resistance, and excessive fructose intake. If the patient does not control the development of nonalcoholic fatty liver disease, it can develop into more serious diseases such as liver fibrosis, liver cirrhosis, liver cancer, and even lead to death.

But how does fructose damage the liver? This is because fructose is mainly metabolized by the liver. There are no rate-limiting enzymes during the process of hepatic metabolism of fructose. This results in the continuous production of intermediate products of fructose metabolism, which are then converted into fat and accumulated in the liver. Eventually, it develops into fatty liver and other metabolic diseases. In addition, the barrier function of the gut is also compromised by excessive fructose intake. This increases the enzymes in the liver to synthesize fat, causing the liver to accumulate more fat. Large amounts of fructose can also cause fatty denaturation of the liver. When these denatured fats combine with other risk factors, steatohepatitis can result. Fructose also doesn't make you feel full, like staying up late can cause drowsiness, and it won't cause discomfort like drinking too much alcohol. Therefore, many people do not feel that the fructose intake is excessive and the liver is continuously damaged unintentionally.

Does eating fruit also damage the liver?

As mentioned above, since fructose will damage the liver, and fruits also contain fructose, will eating fruit also damage the liver? In fact, only excessive intake of fructose can damage the liver. Therefore, it is safe and healthy to eat fruit within the normal range. 

Eat 200 to 350g of fruit per day.

Although fruits contain fructose, they also contain a lot of dietary fiber. Dietary fiber slows the rate at which fructose enters the bloodstream, making it less damaging to the liver. It is recommended to eat 200 to 350g of fruit per day.

Fruit should not be juiced.

Fruit juice is a high-sugar food. Although freshly squeezed juice still contains many minerals and vitamins, many people filter the juice after juicing. This removes substances rich in minerals and vitamins. The dietary fiber in the fruit is also removed. The absorption of fructose is accelerated. And after filtering out these nutrients, only a lot of fructose is left in the juice. For example, 500g of orange contains about 11g of fructose. Eating an orange directly not only does not consume too much fructose, but also absorbs nutrients such as vitamin C and fills the stomach. However, the orange juice drinks sold on the market generally contain about 20g of fructose in a 500ml bottle. Drinking fruit juice instead of eating fruit will not only consume more fructose, but also lack different nutrients and will not make you feel full.

Foods contain other sugars.

Processed foods such as packaged breads, snacks, biscuits, energy drinks, carbonated drinks, and seasonings all have high amounts of added sugar. Different added sugars such as fructose, glucose, and sucrose are added to these foods. When sucrose is digested, it will produce fructose and increase the burden on the liver. If you do not pay attention to the intake of sugar when eating, it is easy to lead to excessive intake of sugar. Therefore, in addition to paying attention to the intake of fructose, excessive intake of other sugars should also be avoided.

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Antihypertensive drug usage and common side effects.👀

What differences in characteristics, indications and adverse reactions of five commonly used antihypertensive drugs angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists, β-blockers, dihydropyridine calcium channel blockers and thiazide diuretics?

Angiotensin-converting enzyme inhibitors.

Commonly used drugs include benazepril, enalapril, perindopril, etc.

Pharmacological effects: Their antihypertensive effects are achieved by inhibiting angiotensin-converting enzyme resulting in the blocking of renin-angiotensin II production and preventing the degradation of kininase.

Strong indications: prevention of atrial fibrillation, cardiac insufficiency after myocardial infarction, heart failure, metabolic syndrome, proteinuria, microalbuminuria, diabetic nephropathy or non-diabetic nephropathy in patients with hypertension.

Dosage of the drug: 

• Benazepril: 5 to 40 mg once a day. It peaks in about 2 to 4 hours. Its half-life is 11 hours.
• Captopril: 12.5 to 75 mg 3 times a day. It peaks in about 1 to 1.5 hours. Its half-life is 2 hours.
• Enalapril: 5 to 40 mg once a day. It peaks in about 1 hour. Its half-life is 11 hours.
• Fosinopril: 10 to 40 mg once a day. It peaks in about 3 hours. Its half-life is 12 hours.
• Imidapril: 2.5 to 10 mg once daily. It peaks in about 2 hours. Its half-life is 8 hours.
• Lisinopril: 5 to 40 mg once a day. It peaks in about 6 to 8 hours. Its half-life is 12 hours.
• Perindopril: 4 to 8 mg once a day. It peaks in about 2 to 4 hours. Its half-life is 30 to 120 hours.
• Ramipril: 2.5 to 10 mg once a day. It peaks in about 1 hour. Its half-life is 13 to 17 hours.
• Trandolapril: 1 to 4 mg once daily. It peaks in about 1 hour. Its half-life is 16 to 24 hours.

Side effects: A dry cough is a common side effect of these drugs. About 30% of patients develop a persistent dry cough that usually worsens when lying down. Female patients are more likely to have a dry cough than male patients. If the patient cannot tolerate a dry cough, an angiotensin II receptor inhibitor can be used instead.

Angiotensin II receptor inhibitors.

Commonly used drugs include irbesartan, losartan, valsartan, etc.

Pharmacological effects: Their antihypertensive effect is through the inhibition of angiotensin II receptors.

Strong indications: Angiotensin II receptor inhibitors can be used in patients who cannot tolerate angiotensin-converting enzyme inhibitors.

Dosage of the drug: 

• Candesartan: 4 to 16 mg once daily. It takes 3 to 4 hours to peak. Its half-life is 9 hours.
• Irbesartan: 150 to 300 mg once a day. It takes 1 to 1.5 hours to peak. Its half-life is 11 to 15 hours.
• Losartan: 50 to 100 mg once a day. It takes 3 to 4 hours to peak. Its half-life is 6 to 9 hours.
• Olmesartan: 20 to 40 mg once a day. It takes 1 to 2 hours to peak. Its half-life is 13 hours.
• Telmisartan: 40 to 80 mg once a day. It takes 0.5 to 1 hour to peak. Its half-life is more than 20 hours.
• Valsartan: 80 to 160 mg once a day. It takes 2 hours to peak. Its half-life is 9 hours.

Side effects: Angiotensin II receptor inhibitors can cause back pain as a side effect. Studies have shown that the incidence of back pain caused by valsartan is about 1.6%, and the incidence of joint pain is 1.0%.

β-blockers.

Commonly used drugs include bisoprolol, metoprolol, etc.

Pharmacological effects: Their antihypertensive effect is exerted by slowing heart rate, inhibiting myocardial contractility, and inhibiting excessive activation of sympathetic nerve activity.

Strong indications: They are suitable for patients with hypertension complicated with chronic heart failure, coronary heart disease and tachyarrhythmia.

Dosage of the drug: 

• Arotinolol: 10 to 20 mg twice a day. It has a peak time of 2 hours and a half-life of 10 to 12 hours.
• Bisoprolol: 2.5 to 10 mg once daily. It has a peak time of 3 to 4 hours and a half-life of 10 to 12 hours.
• Carvedilol: 12.5 to 50 mg twice daily. It has a peak time of 1 hour and a half-life of 6 to 7 hours.
• Metoprolol tartrate: 50 to 100 mg twice daily. It has a peak time of 1 to 2 hours and a half-life of 3 to 4 hours.
• Metoprolol tartrate extended-release tablets: 47.5 to 190 mg once a day. It has a peak time of 3 to 7 hours and a half-life of 12 to 24 hours.

Side effects: β-blockers slow down the heartbeat and pulse, and they vary widely from person to person. The patient's heart rate should be monitored. Control of blood pressure in patients with hypertension and coronary heart disease should also reduce their resting heart rate to 50 to 60 beats per minute. Sudden withdrawal of the drug can cause severe angina and even sudden death. Therefore, the dose must be gradually reduced under the guidance of a doctor when the drug is discontinued, and the discontinuation process will take at least 2 weeks.

Dihydropyridine calcium channel blockers.

Commonly used drugs include amlodipine, felodipine, nifedipine, etc.

Pharmacological effects: Their blood pressure-lowering effect is caused by blocking calcium channels on vascular smooth muscle cells to dilate blood vessels.

Strong indications: They are indicated for patients with isolated systolic hypertension or elderly hypertension with coronary or carotid atherosclerosis, stable angina and peripheral vascular disease.

Dosage of the drug: 

• Amlodipine: 2.5 to 10 mg once daily. It has a peak time of 6 to 12 hours and a half-life of 35 to 50 hours.
• Felodipine extended-release tablets: 5 to 10 mg once a day. It has a peak time of 2.5 to 5 hours and a half-life of 11 to 16 hours.
• Nifedipine controlled-release tablets: 30 to 60 mg once a day. Its peak time is 6 to 12 hours.
• Nitrendipine: 10 to 20 mg 1 to 2 times a day. It has a peak time of 1 to 2 hours and a half-life of 10 to 22 hours.

Side effects: Common side effects of dihydropyridine calcium channel blockers are ankle edema, gingival hyperplasia, and constipation. Ankle edema is dose-related. Elevating the patient's foot can reduce edema symptoms. In addition, combined with angiotensin-converting enzyme inhibitors or angiotensin II receptor inhibitors can reduce the symptoms of edema. To reduce the incidence of gingival hyperplasia, patients should maintain oral hygiene during medication.

Thiazide diuretics.

Commonly used drugs include hydrochlorothiazide, indapamide, etc.

Pharmacological effects: They lower blood pressure by increasing the excretion of sodium and urine to lower blood volume.

Strong indications: They are suitable for isolated systolic hypertension, salt-sensitive hypertension, elderly hypertension, refractory hypertension, etc.

Dosage of the drug: 

• Hydrochlorothiazide: 12.5 to 25 mg once daily. It has a peak time of 4 hours and a half-life of 9 to 10 hours.
• Indapamide: 1.25 to 2.5 mg once daily. It has a peak time of 1 to 2 hours and a half-life of 14 to 18 hours.

Side effects: Their common side effects are hypokalemia, hyperuricemia, and photosensitivity.

• Hypokalemia: Its clinical symptoms include weakness, fatigue, confusion, nausea, anorexia, etc. Hypokalemia can be relieved by reducing sodium intake.
• Hyperuricemia: Severe cases can cause gout in patients. If the patient's serum uric acid level is ≥480 μmol/L, it is recommended to use other antihypertensive drugs.
• Photosensitivity: Patients may develop a rash. Patients should avoid direct sunlight while taking thiazide diuretics.

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What are the treatments for Pseudomonas aeruginosa?💊💊💊

Pseudomonas aeruginosa is a non-fermenting gram-negative bacillus and is a common opportunistic pathogen. It is widely distributed in the daily environment. Its main source is domestic sewage. It can cause lung infections, bloodstream infections, skin infections (often in people with burns), among others. In addition, Pseudomonas aeruginosa often causes nosocomial infections in patients. Studies have pointed out that patients with low immunity, skin and mucous membrane damage (such as mechanical ventilation, tracheal intubation, indwelling central venous catheter, etc.), structural lung disease (such as cystic fibrosis, bronchiectasis, chronic obstructive pulmonary disease, etc.), as well as patients who are using broad-spectrum antibiotics and have been hospitalized for a long time have a higher risk of infection with Pseudomonas aeruginosa. In addition, in patients with cystic fibrosis, respiratory infections caused by Pseudomonas aeruginosa may develop into chronic infections that are more difficult to treat.

Commonly used drugs against Pseudomonas aeruginosa.

β-lactam antibiotics:

• Penicillin: Piperacillin 9 to 16g intravenously daily, divided into 3 to 4 times.
• Penicillin/β-lactamase inhibitor: Piperacillin/tazobactam 4.5g intravenously every 6 to 8 hours.
• Cephalosporins: Ceftazidime 2g intravenously every 8 hours. Cefoperazone 2g intravenously every 8 hours. Cefepime 2g intravenously every 8 to 12 hours.
• Third generation cephalosporins/β-lactamase inhibitor: Cefoperazone/sulbactam 3g intravenously every 8 hours.
• Monobactams: Aztreonam 2g intravenously every 6 to 8 hours.
• Carbapenems: Imipenem/cilastatin 0.5 g intravenously every 6 hours or 1 g intravenously every 6 to 8 hours. Meropenem is administered intravenously at 1 g every 6 to 8 hours.

Aminoglycosides:

• Gentamicin: The dose is 7mg/(kg x d).
• Tobramycin: The dose is 7mg/(kg x d).
• Amikacin: The dose is 15mg/(kg x d).

Quinolones:

• Ciprofloxacin: The dose is 0.4g every 8 to 12 hours.
• Levofloxacin: The dose is 0.5 to 0.75 g daily.

Other:

• Polymyxin B: The dose is 2.5 to 5 mg/(kg x d) by intravenous infusion, divided into 3 to 4 times.
• Polymyxin E: The dose is 2.5 to 5 mg/(kg x d) by intravenous infusion, divided into 3 to 4 times.
• Fosfomycin: The dose is 300mg/(kg x d) by intravenous infusion, divided into 2 to 3 times.

Among these anti-Pseudomonas aeruginosa drugs, aztreonam, aminoglycosides, polymyxin and fosfomycin generally need to be used in combination with other antibiotics, and are not used alone. Clinically, the course of treatment will be determined according to the patient's condition. If the patient's condition is stable within 3 days after taking the drug, the recommended treatment course is 8 days. If the patient's efficacy is poor after treatment, the course of treatment can be extended to 10 to 14 days.

The drug resistance mechanism of Pseudomonas aeruginosa and its recommended medication.

Pseudomonas aeruginosa develops drug resistance by expressing efflux pumps, forming biofilms, changing target sites and outer membrane proteins, and producing β-lactamases. Some studies have pointed out that the resistance rate of Pseudomonas aeruginosa to polymyxin and amikacin is low, but the resistance rate to carbapenem can be as high as 23%. Drug-resistant Pseudomonas aeruginosa can be divided into:

• Multi-drug resistance: Pseudomonas aeruginosa is not susceptible to 3 or more antibacterial drugs against Pseudomonas aeruginosa.
• Extensive drug resistance: generally refers to that Pseudomonas aeruginosa is not sensitive to other antibiotics and only sensitive to polymyxins.
• Pandrug resistant: Pseudomonas aeruginosa is not sensitive to existing antibiotics.

Dual therapy regimens for extensively drug-resistant Pseudomonas aeruginosa:

1. Combined use of two β-lactam antibiotics: Ceftazidime + Piperacillin/tazobactam, Aztreonam + Piperacillin/tazobactam, Ceftazidime + Aztreonam, Ceftazidime + Cefoperazone/sulbactam.
2. Ciprofloxacin-based: Combine a β-lactam antibiotic or aminoglycoside.
3. Polymyxin-based: Combine a β-lactam antibiotic, ciprofloxacin, fosfomycin or rifampicin.
4. Based on β-lactam antibiotics: combined with ciprofloxacin, aminoglycoside or fosfomycin.

Triple therapy for extensively drug-resistant Pseudomonas aeruginosa:

1. Polymyxin + β-lactams + Ciprofloxacin.
2. Polymyxin + β-lactams + Fosfomycin.
3. Polymyxin (intravenous) + Polymyxin (aerosol inhalation) + Carbapenems.
4. Aztreonam + Ceftazidime + Amikacin.

Due to the increased risk of side effects (eg, increased nephrotoxicity with polymyxin and aminoglycosides, immune-mediated thrombocytopenia with rifampicin and piperacillin), rational drug selection and monitoring The patient's drug response.

Inhaled antimicrobials are believed to be the mainstay of treatment for Pseudomonas aeruginosa-related lung infections.

The goal of treatment for pulmonary infections caused by Pseudomonas aeruginosa is to reduce bacterial counts in the respiratory tract and improve patient outcomes. Antibiotics for inhalation have the advantage of a dosage form that allows the drug to accumulate in the respiratory tract to increase local drug concentration. This is believed to significantly improve the patient's respiratory symptoms and improve the patient's quality of life. There are now many inhaled formulations of antibiotic drugs into the field of research.

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What medications are available to treat peripheral neuropathy caused by diabetes?💊💊💊

Diabetes can lead to many complications. Common complications include retinopathy (the leading cause of blindness in adults), stroke (two to four times as common in people with diabetes as in non-diabetic patients), cardiovascular disease (about 80% of patients die from cardiovascular events), diabetes Nephropathy (one of the leading causes of end-stage renal disease), diabetic foot (which is characterized by high amputation rates and high mortality), diabetic neuropathy (the leading cause of non-traumatic amputations). The most common chronic complication is diabetic peripheral neuropathy. Its prevalence is over 50%. The following will introduce the common symptoms of peripheral neuropathy and what treatments are available.

Common symptoms of diabetic peripheral neuropathy.

Diabetic peripheral neuropathy can occur even in prediabetes. It recommends that patients be screened for diabetic peripheral neuropathy when they are diagnosed with type 2 diabetes. Then patients should also receive relevant screening at least once a year. Common clinical symptoms are as follows:

Distal symmetric polyneuropathy: This lesion begins distally (finger or toe) and progresses proximally (wrist or ankle). Its clinical manifestations are acupuncture, numbness, burning, and ant line feeling in bilateral extremities. Some patients have hypoesthesia, the limbs seem to be wearing gloves or socks, and they are not sensitive to stimuli such as heat, cold, and touch. There are also patients with spontaneous skin acupuncture, burning, and even knife-like pain symptoms.

Autonomic neuropathy:

• Cardiovascular autonomic neuropathy: orthostatic hypotension, resting tachycardia, syncope, etc.
• Gastrointestinal autonomic neuropathy: hiccups, dysphagia, gastroparesis, diarrhea, constipation, etc.
• Urogenital autonomic neuropathy: urinary incontinence, urinary retention, voiding disorders, urinary tract infections, etc.
• Other autonomic neuropathy: Decreased or no sweating. Hands and feet will become dry and cracked, making them prone to infection.

Pathogenesis of diabetic peripheral neuropathy.

Its pathogenesis has not yet been fully elucidated. It is mainly considered to be related to the accumulation of sorbitol, dyslipidemia, hyperglycemia, oxidative stress, and microcirculation disorders.

The accumulation of sorbitol:

Most of the glucose is generally metabolized by the glycolysis and pentose phosphate pathways. Less than 3% of glucose is metabolized via the sorbitol bypass pathway. 

When blood sugar rises uncontrollably, the level of glucose in nerve tissue and blood vessels also increases significantly. This condition causes more aldose reductase to be activated, resulting in a marked enhancement of the sorbitol pathway. Sorbitol accumulates in nerve tissue and blood vessels. The accumulation of sorbitol in nerve tissue can damage peripheral nerves.

What medications are commonly used to treat diabetic peripheral neuropathy?

Apart from improving glycemic control in patients, there is currently no effective treatment for the underlying nerve damage. Because some drugs are off-label use, doctors should use with caution.

Methylcobalamin: It is an active vitamin B12 preparation. It can enter nerve cells more easily than inactive vitamin B12 (cyanocobalamin). It promotes nerve myelination and axon regeneration. It is a drug that nourishes the nerves. Oral mecobalamin 3 times a day, 500 μg each time, for at least 3 months. If there is no effect after taking it for more than three months, there is no need to continue taking it.

α-lipoic acid: It is an antioxidant factor and acts as an anti-oxidative stress. It inhibits aldose reductase and reduces lipid oxidation in nerve tissue. Oral lipoic acid 3 times a day, 0.2g each time. Or take it orally once a day, 0.6g each time, half an hour before breakfast. The absorption of lipoic acid is affected by food, so it should not be taken with food.

Epalrestat: It is a drug that inhibits aldose reductase activity. It prevents sorbitol from building up in the nerves, improving nerve conduction velocity and symptoms caused by diabetic neuropathy. Epalrestat is taken orally three times a day, 50 mg each time, before meals. If epalrestat is not effective for more than 3 months, it is not necessary to continue taking it. In addition, the patient's urine may appear brownish-red after taking it, which is normal.

Pancreatic kininogenase enteric-coated tablet: Plasmin is activated by it and reduces blood viscosity. It also activates phospholipase A2, preventing thrombosis and platelet aggregation. It can improve the microcirculation of the body. Pancreatic kininogenase enteric-coated tablet is to be taken 120 to 240 units 3 times daily on an empty stomach. Since it is an enteric-coated tablet, it needs to be swallowed whole to prevent it from being destroyed in the stomach.

Pregabalin: It binds to calcium channels in the central nervous system. It reduces the release of calcium channels in the central nervous system, thereby inhibiting central sensitization and hyperalgesia. This can reduce pain. The initial dose of pregabalin is 150 mg daily in 2 to 3 divided doses, with subsequent dose adjustments to 300 to 600 mg daily. Its common side effects are drowsiness and dizziness. In addition, it can cause weight gain and the patient's dosage of antidiabetic drugs may need to be adjusted.

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These habits before bed can help lower uric acid.👍👍👍

As more and more people suffer from hyperuricemia, more and more people
are concerned about how to reduce uric acid in the body. The increase in uric acid in humans is mainly due to insufficient uric acid excretion and excessive uric acid production. The human body generally has about 1200mg of uric acid, and the human body produces about 700mg of uric acid every day. Under normal circumstances, About 500mg of uric acid is excreted through the kidneys, and the remaining 200mg of uric acid is excreted through the intestines. The body's daily excretion of uric acid and the production of uric acid should maintain a balance. Clinically, normal values for uric acid are 149 to 416 μmol/L in men and 89 to 357 μmol/L in women. When the blood uric acid concentration is higher than the normal value, it can be diagnosed as hyperuricemia clinically. Excessive uric acid in patients with hyperuricemia can form urate crystals. The crystals deposit in the patient's joint synovium, bursa, cartilage, and other tissues, causing a recurring inflammatory disease called gout. Gout attacks can cause gouty nephropathy, gouty acute arthritis, chronic arthritis, tophi and joint deformities.

Why does uric acid in the body increase?

Elevated uric acid is caused by an imbalance between the excretion and production of uric acid. However, only about 10% of patients with elevated uric acid are caused by excessive uric acid production, and most (more than 90%) patients are caused by decreased uric acid excretion.

Causes of decreased uric acid excretion:

• Innate factors: Inherited genes cause a patient's decreased uric acid clearance and decreased excretion.
• Acquired factors: Obesity, hypertension, metabolic diseases (eg, hypothyroidism, hyperthyroidism, lactic acidosis, diabetic ketosis), drugs (eg, aspirin, thiazide diuretics, cyclosporine).

Causes of increased uric acid production:

• Innate factors: Genetically related enzyme deficiencies lead to metabolic abnormalities.
• Acquired factors: Blood disorders (eg, myelodysplasia), strenuous exercise, diet (eg, excessive alcohol consumption, foods and beverages high in fructose, frequent consumption of foods high in purines), taking cytotoxic drugs (eg, chemotherapy drugs).

These habits before bed can help lower uric acid.

Try not to eat late night supper:

It is well known that diet plays an important role in the prevention and treatment of hyperuricemia. In daily life, many foods contain purines, especially animal offal, seafood, mushrooms and soybeans. These purines absorbed from food are called exogenous purines. It makes up about 20% of purines in the body. The human liver metabolizes purines into uric acid, so excessive intake of high-purine foods will increase blood uric acid. Eating late night supper is not only bad for your health. It has a more severe effect on patients with hyperuricemia, especially late night supper that are high in purines. Therefore, it is recommended that patients with hyperuricemia try not to eat late night supper. Even if you have a late night supper, eat foods that are low in purines and light.

Drink some water before bed:

In addition to taking uric acid-lowering drugs to reduce blood uric acid, drinking more water can also effectively reduce uric acid. Clinicians recommend that patients with hyperuricemia should drink plenty of water. Drinking plenty of water is a simple, inexpensive, and side-effect-free way to lower uric acid. Clinicians recommend that you should drink more than 1500ml of water per day. If the patient has urinary uric acid stones, the daily drinking water should be more than 2 liters. This promotes the excretion of more uric acid in the urine. In addition, since most gout attacks occur at night, drinking some water before going to bed can prevent the increase of blood uric acid during long sleep. During sleep, with the loss of blood water, blood uric acid will be concentrated, which will increase the concentration of uric acid. Therefore, hyperuricemia patients and gout patients are especially advised to drink some water before going to bed. In addition to drinking plain water, soda water can also help patients reduce uric acid. Because it alkalizes the urine, this increases the solubility of urate in the urine and promotes the excretion of more uric acid from the body.

Finally, although strenuous exercise may lead to increased uric acid production, moderate exercise can still be beneficial in patients with hyperuricemia (Appropriate stretching exercises can be done before going to bed.). Clinically, it is recommended that patients with hyperuricemia actively engage in aerobic exercise, and at the same time cooperate with muscle resistance training. For patients with gouty arthritis, activities should be reduced during an acute attack, but with the relief of symptoms, reasonable exercise can be performed under the guidance of experts. This is more helpful for the long-term management of uric acid.

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How to choose a treatment for knee osteoarthritis❓❓❓

Knee osteoarthritis can be painful and inconvenient for patients. The first symptom of knee osteoarthritis is pain. Pain initially occurs when going up and down stairs, squatting down, or sitting and then standing up. Later, the movement of the knee joint is further restricted, and eventually the patient may not be able to walk a single step. Knee osteoarthritis patients with mild initial symptoms can generally be relieved by non-drug treatment. However, patients with mid-stage knee osteoarthritis generally experience pain. They need medication to relieve the pain. This article will describe how to choose a drug to treat knee osteoarthritis.

Systemic analgesics.

Analgesics for knee osteoarthritis are not just for pain relief, they also have anti-inflammatory effects. Knee pain is caused by inflammation. Inflammation must be eliminated in order to eliminate pain in patients. The inflammatory cause of knee osteoarthritis is not caused by a bacterial or viral infection, so antibiotics or antiviral drugs are not used to treat it. Analgesic and anti-inflammatory drugs can eliminate the inflammation of knee osteoarthritis. Pain relief for knee osteoarthritis can be divided into three levels. Different levels of pain medication are used to treat different levels of pain. In clinical practice, drugs should be selected according to the individual situation of patients and the efficacy of drugs, so as to achieve the purpose of individualized medication.

First-level: Acetaminophen.

Acetaminophen is a drug that has been used for many years. It can be used short-term for mild pain and it has relatively low damage to the gastrointestinal tract, liver and kidneys. However, its anti-inflammatory effect is relatively weak, so it can only be used for mild pain. The total daily dose of acetaminophen should not exceed 4 g. Although its damage to the liver is relatively low, liver damage is still its main side effect, especially when taking the drug, patients should avoid drinking alcohol.

Second-level: Non-steroidal anti-inflammatory analgesics (NSAIDs).

For moderate pain, the most commonly used analgesics are NSAIDs. It can be divided into the following categories: acetic acid derivatives (such as diclofenac, indomethacin), propionic acid derivatives (such as ibuprofen, naproxen, ketobufen), fenamic acid esters (such as methyl chloride sulfonate), enolic acid derivatives (eg, piroxicam), and selective cyclooxygenase-2 inhibitors (eg, celecoxib). The most common side effects of these drugs are increased cardiovascular adverse events, gastrointestinal bleeding, liver and kidney damage.

Third-level: Weak opioids.

Weak opioids such as codeine or tramadol may be considered for patients with severe pain and poor response to first- and second-level drugs. The initial dose of these drugs should be low and then slowly and gradually increased to reduce side effects.

Joint topical medication.

Emulsions, ointments and patches of topical pain relievers such as NSAIDs or capsaicin. They can be used outside the body for pain relief. Topical topical analgesics are simply and directly applied to or rubbed on the painful area. Their active ingredients penetrate quickly into the skin and effectively relieve pain. Topical application avoids their irritation of the gastrointestinal tract, reduces side effects and is convenient to use. The following points should be paid attention to when using:

• Adequate amount of use: The dosage of topical drugs must be sufficient to achieve the best pain relief and anti-inflammatory effect.
• The location of the medication should be correct: Anti-inflammatory and analgesic external medicines are used in the acute inflammatory attack period, and the skin will appear red, swollen, hot and painful. Infrared hyperthermia topical medicine is used for chronic injury. There was no redness, swelling and pain at this time. In addition, opioid patches are absorbed through the skin and can be applied to any painful area. Therefore, they should be attached to the shoulders, the upper edge of the chest and the outside of the forearm, and try not to attach to other places.
• Use for less than 12 hours: Most topical analgesics should be used for less than 12 hours. If they are used for more than 12 hours, they may cause adverse effects on the skin.

Intra-articular injection of drugs.

Glucocorticoids: It provides temporary pain relief for patients. However, if high-dose glucocorticoids are used for a long time, patients will experience many adverse reactions such as hypertension, renal impairment, and lower extremity edema. Although the dose of intra-articular glucocorticoid injection is small and generally does not cause the above-mentioned adverse reactions, long-term application will still cause damage to the bones and joints. The bone and cartilage of the joints are damaged by prolonged use of glucocorticoids. This in turn worsens the patient's condition. Therefore, it is recommended that it should not be applied more than 4 times a year.

Sodium Hyaluronate: It is a component of the joint fluid in the joint cavity, which can repair the joints. In patients with knee osteoarthritis, the synovial fluid contains less sodium hyaluronate and becomes thinner. Intra-articular injection of sodium hyaluronate can supplement the lack of sodium hyaluronate in synovial fluid. This increases joint fluid viscosity and reduces joint friction. This can help relieve symptoms and slow the progression of the disease. It is effective in relieving mild to moderate knee osteoarthritis, but it is not very effective in severe advanced knee osteoarthritis. It is generally recommended to use it once a week, with 4 to 6 weeks as a course of treatment.

Disease-modifying drugs and chondroprotective agents.

In patients with knee osteoarthritis, the articular surface cartilage is damaged. These drugs can protect the cartilage and improve the condition. Commonly used drugs are glucosamine and chondroitin sulfate. They are the two major nutrients for articular cartilage.

• Glucosamine: Although it has been widely used in the prevention and treatment of osteoarthritis, its efficacy has been controversial. Osteoarthritis patients with mild or moderate abrasion of articular cartilage are best candidates for glucosamine therapy. It does not work well for people with osteoarthritis who have severely abrasion of articular cartilage. Glucosamine needs to be continuously taken at 1500mg daily for more than 8 weeks to have a certain effect. Taking it for more than one year will have a more stable effect.
• Chondroitin Sulfate: It provides nutrients to cartilage, absorbs and retains water in cartilage. This can help repair articular cartilage. 

Studies have pointed out that the simultaneous application of glucosamine and chondroitin sulfate can obtain a more precise effect.

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Knowledge about antiplatelet drugs - ticagrelor.🩸🩸🩸

Ticagrelor is an antiplatelet drug. It is a potent P2Y12 receptor antagonist. For patients with acute coronary syndromes, ticagrelor is recommended as first-line treatment in the treatment guidelines of many countries. The following will introduce the knowledge about its use.

The mechanism of ticagrelor.

Platelet aggregation refers to the adhesion of platelets to platelets. Normally, glycoprotein IIb/IIIa (GP IIb/IIIa) receptor on the platelet membrane is not activated. It does not bind to fibrinogen. Early thrombus formation is because after GP IIb/IIIa receptor is activated and it binds to fibrinogen. Fibrinogen makes it be able to connect to adjacent platelets and causing platelets aggregation. 

GP IIb/IIIa receptor is directly inhibited by tirofiban and eptifibatide, so that fibrinogen cannot bind to it. 

Adenosine diphosphate (ADP) enters platelet through platelet P2Y12 receptor and then activating GP IIb/IIIa receptor. Ticagrelor reversibly inhibits P2Y12 receptor and the active metabolite of clopidogrel irreversibly inhibits P2Y12 receptor. These drugs prevent the P2Y12 receptor from binding to ADP. GP IIb/IIIa receptors are unable to activate and prevent platelet aggregation.

Adverse reactions to ticagrelor.

The most common side effect of ticagrelor is the risk of bleeding. It prolongs the bleeding and has no antidote. It is contraindicated in patients with active pathological bleeding or a history of intracranial hemorrhage. It should also not be enabled when a patient is undergoing emergency coronary artery bypass surgery.

In addition, it increases the concentration of adenosine in the blood. Elevated adenosine concentrations can cause other adverse effects of ticagrelor such as bradycardia and dyspnea. In addition, adenosine also promotes the synthesis of uric acid, which can lead to hyperuricemia or gout.

Difference between ticagrelor and clopidogrel.

Studies have shown that ticagrelor is more effective than clopidogrel in the first 12 months of acute coronary syndrome. However, ticagrelor has a higher incidence of side effects such as bradycardia, dyspnea, bleeding, and increased uric acid levels than clopidogrel.

Rapid antiplatelet therapy for acute coronary syndromes.

All patients without contraindications should be given aspirin immediately. The loading dose is 300 mg, followed by a long-term maintenance dose of 75 to 100 mg daily. All patients should receive a P2Y12 receptor antagonist for more than 12 months in addition to aspirin unless the patient has a high risk of bleeding or other contraindications. Among P2Y12 receptor antagonists, ticagrelor is the drug of choice. Its loading dose is 180 mg, followed by 90 mg twice a day. In patients with contraindications to ticagrelor, clopidogrel should be used. Its loading dose is 300 to 600 mg, followed by 75 mg once daily.

Oral antiplatelet therapy in stable coronary heart disease.

In patients with stable coronary heart disease without contraindications to aspirin, daily 75 to 100 mg of aspirin should be used as a long-term treatment. If the patient is intolerant to aspirin, it recommends taking a P2Y12 receptor antagonist. Ticagrelor 60 to 90 mg twice daily or clopidogrel 75 mg once daily. Aspirin combined with ticagrelor (60 mg twice a day) can be considered as a long-term treatment if the bleeding risk is not high in patients at high risk of thrombosis.

Precautions while using ticagrelor.

Food has only a small effect on ticagrelor, so it can be taken before or after meal.

If the patient cannot swallow whole ticagrelor tablet, it can be crushed and taken or given by nasogastric tube.

Since the half-life of ticagrelor is approximately 7 hours and the half-life of its active metabolite is approximately 9 hours, if a patient misses a dose, another dose is not required. One missed dose has limited effect on the antiplatelet effect.

The clinical efficacy of ticagrelor is reduced by high doses (greater than 100 mg) of aspirin. In addition, ticagrelor can cause severe and even fatal bleeding when used in combination with maintenance doses of aspirin greater than 100 mg/day. Therefore, the maintenance dose of aspirin should not exceed 100 mg, typically 75 to 100 mg per day.

The metabolism of ticagrelor is via CYP3A4. Therefore, strong CYP3A4 inducers (such as carbamazepine, phenobarbital, phenytoin, dexamethasone, rifampin, etc.) and strong CYP3A4 inhibitors (such as voriconazole, itraconazole, clarithromycin, etc.) should be avoided taking with ticagrelor. Additionally, because ticagrelor metabolism requires depletion of CYP3A4, it is a CYP3A4 inhibitor. When simvastatin or lovastatin is used in combination with ticagrelor, the dose of simvastatin and lovastatin should not exceed 40 mg.

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Herpes zoster virus infection and treatment.👿👿👿

Herpes zoster is an infectious skin disease caused by the varicella-zoster virus that is latent in the human body and then activated. It is a clinically common viral skin disease. This article will introduce the knowledge about the pathology, prevention and treatment of herpes zoster.

How can you get herpes zoster?

Varicella-zoster virus causes chickenpox in people who are first infected. When a chickenpox patient is cured, the virus is not completely cleared from his body. The rest of the virus lurks in the ganglia along the sensory nerves. When his immunity declines, these latent viruses reactivate. The viruses do a lot of replication, and then they spread along the sensory nerve fibers to the areas of the skin that these nerves control. It can cause herpes zoster. When the body's immunity is good, although herpes zoster will not be caused, the virus can remain dormant in the ganglia waiting to be activated. 

What kind of disease is herpes zoster?

The varicella-zoster virus is a DNA-like virus. It is characterized by being close to the skin and close to the nerves. It always spreads along the nerve and is distributed in strips. It generally occurs only on one side of the patient's body and does not go beyond the midline. Herpes zoster consists of dense clusters of blisters. Its course is usually 2 to 4 weeks. Postherpetic neuralgia is a common complication of herpes zoster. This can last for months or even years. The older the patient, the more severe the symptoms of neuralgia. In addition, the risk of developing herpes zoster is greater for women than for men.

What is the treatment for herpes zoster?

Goals of treatment: Relief of acute pain in patients, limitation of spread of skin lesions, promotion of repair of skin lesions, prevention or alleviation of postherpetic neuralgia.

Medications for herpes zoster:

Antiviral: It can promote the healing of herpes, effectively shorten the course of the disease, reduce the formation of new herpes and prevent the spread of the virus to the internal organs. Antiviral medication should be started within 24 to 72 hours of the blisters. This allows the drug to reach the effective concentration quickly and obtain the best therapeutic effect. Commonly used drugs are as follows:

• Acyclovir: It is indicated for patients with severe and immunocompromised herpes. The usual dose is 5 to 10 mg intravenously per kg, 3 times a day for 7 consecutive days. Crystals may form in the kidneys at high doses. Therefore, patients should drink plenty of water during the medication. In addition, it is neurotoxic. Clinical manifestations include epileptic seizure, paresthesia and neurological confusion.
• Valacyclovir: It is a precursor to acyclovir. The same applies to patients with severe and immunocompromised herpes. Its bioavailability is 3 to 5 times that of acyclovir. The usual dose is 0.3g orally three times a day for 7 consecutive days. Also crystals may form in the kidneys at high doses. Patients should drink plenty of fluids during the medication. It is also neurotoxic. Clinical manifestations include epileptic seizure, paresthesia and neurological confusion.
• Famciclovir: It is present in higher concentrations in infected cells and has a longer half-life. Its efficacy is similar to that of valacyclovir. The usual dose is 0.25g 3 times a day for 7 consecutive days. Its common side effects are headache, nausea and diarrhea. It can also cause hives, hallucinations and confusion, especially in the elderly.
• Foscarnet: It is indicated for patients with herpes who are resistant to nucleoside analogs. The usual dose is 100 mg intravenously per kg, twice a day. It is nephrotoxic and neurotoxic. Serum creatinine is elevated in more than half of patients and headache in about 25%. In addition, it has the side effects of hypocalcemia, hypokalemia, and hypomagnesemia.

Analgesics: Calcium channel modulators (eg, gabapentin or pregabalin) and tricyclic antidepressants (eg, amitriptyline) are first-line therapy. Opioids and tramadol are second-line treatments. Aspirin and acetaminophen have limited effects. 

• Gabapentin: It is a 1st generation calcium channel blocker. Its pharmacokinetic profile is nonlinear. The starting dose is 300 mg orally per day, and the usual effective dose is 900 to 1800 mg per day. Common side effects include drowsiness, dizziness, blurred vision, edema, dry mouth, weight gain, and abnormal thinking.
• Pregabalin: It is a second generation calcium channel blocker. Hyperalgesia and central sensitization will be inhibited by it to achieve analgesic effect. The starting dose is 150 mg orally per day, which can be increased to 300 mg per day within 1 week, with a maximum dose of 600 mg per day. Common side effects are the same as gabapentin.
• Amitriptyline: It inhibits the reuptake of norepinephrine and serotonin and blocks various ion channels. The descending pathway of pain conduction is where it primarily works. The starting dose is 25 mg orally per day and the maximum dose is 150 mg per day. Common side effects include blurred vision, dizziness, tremor, drowsiness, sweating, dry mouth, constipation, dysuria, and orthostatic hypotension.

Anti-inflammatory drugs: Oral corticosteroids can suppress the inflammatory process in the early stages of an acute herpes zoster attack. It reduces the healing time of skin lesions and the duration of acute pain. However, it has no effect on postherpetic neuralgia that has already occurred. In addition, patients should not use topical corticosteroids. It does not recommend the use of glucocorticoids alone in the absence of systemic antiviral therapy.

• Prednisone: Start with a daily dose of 30 to 40 mg and then gradually reduce the dose. Its course of treatment is 1 to 2 weeks.

Neurotrophic: It is helpful for nerve pain and link neuroinflammation, but its therapeutic effect is limited. Commonly used drugs are vitamin B1, methylcobalamin and vitamin B12, which can be injected intramuscularly or orally.

Topical medicines: Its main purpose is to reduce inflammation and dryness.

• Acyclovir cream, penciclovir cream and calamine lotion: These can be used topically when the herpes is not broken.
• 3% boric acid solution or 1:5000 nitrofurazone solution (wet compress), 2% mupirocin ointment and 0.5% neomycin ointment: After the herpes has ruptured, these drugs may be used as appropriate.
• 5% lidocaine patch: It can be used for postherpetic pain. Place 1 to 3 patches on the painful area, each patch for up to 12 hours.

How to prevent herpes zoster?

The herpes zoster vaccine is effective in preventing the occurrence of herpes zoster, shortening its duration, and reducing the incidence of postherpetic neuralgia. Generally, herpes zoster recurs only once in a lifetime. However, very few patients can relapse several times. Adults ≥50 years of age should get the herpes zoster vaccine even if they have ever had herpes zoster.

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