What is the difference between azivudine, monogravir and nematvir/ritonavir?💫💫💫

Azivudine, monogravir and nematvir/ritonavir are all clinical drugs used to treat the new coronavirus. What's the difference between them? 

What is the anti-coronavirus mechanism?

The new coronavirus is composed of RNA and protein. The raw material for RNA synthesis is cytosine nucleoside. Azivudine and monogravir are cytosine nucleoside analogs. They will synthesize poor RNA with the new coronavirus and inhibit the replication of the virus. Nematvir is a peptidomimetic substance. It will prevent the virus from synthesizing functional proteins by inhibiting 3C-like protease, and the replication of the virus will be inhibited. Although ritonavir has no effect against the new coronavirus, it will inhibit the elimination of nematvir and enhance its effect.

What are the properties of azivudine, monogravir and nematvir/ritonavir?

Due to their different chemical structures, they have different adverse reactions and metabolic processes in the body. 

Bone and Cartilage Toxicity: In trials, rats were repeatedly dosed with monogravir, which caused toxicity to the bones and cartilage of rats. Therefore, monogravir may affect bone and cartilage development in children.

Dosage in Patients with Hepatic or Renal Impairment: Monolavir is not eliminated primarily through the liver or kidneys, so no dose adjustment is required in patients with hepatic or renal impairment.

Drug interactions:

• Azivudine: Caution is required when combined with amiodarone, colchicine, dabigatran, digoxin, dronedarone, voriconazole, grapefruit juice, etc.
• Monolavir: Due to limited available data, no drug interactions have been found.
• Nematvir/ritonavir: These interact with many medicines.

What are the treatment differences between azivudine, monogravir, and nematvir/ritonavir?

Azivudine: It is mainly used to treat adult patients with characteristic pneumonia manifestations of new coronavirus infection visible on imaging (moderate infection). It is not intended for use in pregnant or breastfeeding women. If Azivudine is used, breastfeeding should be discontinued during treatment and for 4 days after treatment.

Monolavir: It is indicated for the treatment of adult patients with mild or moderate infections within five days of onset and who are at high risk for progression to severe disease. It has fetal toxicity similar to that of azivudine. If monogravir is used, breastfeeding should be discontinued during treatment and for 4 days after the end of treatment.

Nematrevir/ritonavir: Same indications as monogravir. However, it may still be used when the potential benefit to the mother outweighs the potential risk to the fetus. If nematvir/ritonavir is used, breastfeeding should be discontinued during treatment and for 7 days after the end of treatment.

What are the dosages of azivudine, monogravir, and nematvir/ritonavir?

Azivudine: If taken after meals, its absorption rate and total amount will be increased. Changes in drug concentration in the blood will also increase, thereby increasing the risk of adverse reactions. Its recommended usage is to take it orally once on an empty stomach before going to bed, 5mg each time (generally each tablet is 1mg, 5 pills taken orally each time), and the course of treatment should not exceed 14 days.

Monolavir: Take on an empty stomach or with food, once every 12 hours, 0.8g each time (usually 0.2g per tablet, 4 tablets taken orally each time) for 5 consecutive days.

Nematrevir/ritonavir: Take on an empty stomach or with food, once every 12 hours, 300 mg of nematvir (each tablet is 150 mg, 2 tablets taken orally each time) and 100 mg of ritonavir ( Each tablet is 100mg, 1 tablet taken orally at a time), taken continuously for 5 days.

What are the adverse reactions of azivudine, monogravir, and nematvir/ritonavir?

Azivudine: Common adverse reactions include diarrhea, increased transaminases, increased breathing, and occasionally increased the level of blood glucose. It may cause moderate to severe damage to the liver, so patients with moderate to severe liver damage should use it with caution.

Monolavir: Common adverse reactions include diarrhea, nausea, dizziness, and occasionally rash and urticaria.

Nematrevir/ritonavir: Common adverse reactions include diarrhea and taste problems, and occasionally elevated transaminases. It may cause severe liver damage and is therefore contraindicated in patients with severe hepatic impairment.

Additionally, they can affect fertility. Therefore, it recommends the use of effective contraception during and for 4 days after treatment with azivudine and monogravir, and the use of effective contraception during and for 7 days after treatment with nematvir/ritonavir.

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What is the difference between acetaminophen and ibuprofen?👀👀👀

Acetaminophen and ibuprofen are very commonly used antipyretic and
analgesic drugs in clinical practice. However, their chemical structure, intensity of action and adverse reactions will differ. Will there be any difference in clinical use?

Difference in effectiveness of acetaminophen and ibuprofen.

The analgesic and antipyretic effect of ibuprofen is slightly stronger than that of acetaminophen, and its duration is also longer (ibuprofen <183 minutes, acetaminophen <134 minutes). However, ibuprofen takes a slightly slower onset of action. Patients will experience a more significant decrease in body temperature within 30 minutes of taking acetaminophen than ibuprofen. Both of them can be used to treat headaches, migraines, toothaches, muscle pain, dysmenorrhea (ibuprofen is more effective), and osteoarthritis (ibuprofen is more effective). However, acute attacks of gout and rheumatoid arthritis can only be treated with ibuprofen. Neither of them can be used to treat abdominal pain. In terms of effectiveness alone, ibuprofen is superior to acetaminophen.

Comparison of the safety of acetaminophen and ibuprofen.

Acetaminophen: Excessive doses of acetaminophen can cause life-threatening liver failure. Patients who are dehydrated or malnourished also have an increased risk of liver damage. It is less damaging to the gastrointestinal tract. It is contraindicated in patients with viral hepatitis and favismia. It should be used with caution in patients with renal insufficiency, active peptic ulcer, or aspirin allergy. Acetaminophen may also be used during pregnancy and in patients with severe heart failure.

Ibuprofen: It can cause irreversible damage to the kidneys. Overdose or use while dehydrated may increase a patient's risk of kidney damage. It also increases the risk of myocardial infarction and cerebral infarction. Although it can also cause gastrointestinal bleeding, ulceration, and perforation, the risk is lower than other NSAIDs. Ibuprofen is contraindicated in patients with renal insufficiency, active peptic ulcer, severe heart failure, pregnancy, and aspirin allergy. However, it can be used in patients with viral hepatitis and favismia.

Precautions when using acetaminophen and ibuprofen.

Acetaminophen: It can be used in children older than 3 months and can be taken before meals. The maximum daily dose for children is 15 mg/kg and for adults it is 2 g/day, once every 4 to 6 hours, and should not be taken more than 4 times a day. Alcohol and other hepatotoxic drugs can worsen liver damage when combined with acetaminophen. Acetaminophen is occasionally used concomitantly with coumarin anticoagulants without significant effects.

Ibuprofen: It can be used in children older than 6 months, with or after meals. The maximum daily dose for children is 10mg/kg and for adults it is 1.2g/day, once every 6 to 8 hours, and should not be taken more than 4 times a day. When ibuprofen is combined with alcohol, it can aggravate gastrointestinal damage. When used together with antihypertensive drugs, it will also reduce the antihypertensive effect. It may also reduce the effectiveness of low-dose aspirin in preventing cardiovascular disease and stroke. Other nephrotoxic drugs may worsen kidney damage when used with ibuprofen. When anticoagulant drugs such as heparin and dicoumarol are used together with it, it will prolong the prothrombin time and increase the risk of bleeding.

Conclusion.

For children, the elderly over 60 years old, and patients with multiple underlying diseases (except those with liver dysfunction), it is recommended to use acetaminophen first.

For patients who require long-term medication and those with arthritis, it is recommended to give priority to ibuprofen (because acetaminophen has no anti-inflammatory effect).

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When should lipid-lowering drugs be taken?⌚⌚⌚

Dyslipidemia generally refers to elevated levels of cholesterol and/or
triglycerides (TG) in the blood. It is also called hyperlipidemia. At the same time, it also includes various dyslipidemias including low high-density lipoprotein cholesterol (HDL-C). The main clinical lipid-lowering drugs currently include cholesterol absorption inhibitors, HMG-CoA inhibitors (statins), fibrates, anti-lipid peroxidation drugs (probucol), niacin drugs, and PCSK9 inhibitors. , bile acid chelators, high-purity fish oil preparations and other lipid-lowering drugs, etc.

Lipid-lowering drugs can generally be divided into three categories.

1. Drugs that mainly lower cholesterol: Such drugs include statins, cholesterol absorption inhibitors, probucol, bile acid chelators. They reduce cholesterol levels by inhibiting cholesterol synthesis in liver cells, accelerating low-density lipoprotein cholesterol (LDL-C) catabolism, or reducing intestinal cholesterol absorption.
2. Drugs mainly aimed at lowering triglycerides: These drugs include fibrates, niacin and high-purity fish oil preparations. They can lower blood levels of triglycerides in patients.
3. PCSK9-inhibitors: such as evolocumab. It prevents the degradation of LDL-receptors by inhibiting PCSK9, thereby promoting the body's clearance of LDL-C. It reduces blood levels of LDL-C and has a powerful cholesterol-lowering effect.
4. Microsomal triglyceride transfer protein inhibitors: such as lomitapide. It lowers blood levels of LDL-C.
5. Apolipoprotein B-100 synthesis inhibitors: such as mipomexan. It reduces the production and secretion of VLDL. At the same time, it will also reduce the blood level of LDL-C.

The timing of taking lipid-lowering medications.

Drugs that mainly lower cholesterol:

1. Statins: Lovastatin, simvastatin, pravastatin, fluvastatin (tablets) and other statins with short half-lives are recommended to be taken before going to bed. While cholesterol will reach its synthesis peak at night, these drugs will also reach their concentration peak. Statins with long half-lives such as fluvastatin (sustained-release preparation), atorvastatin, rosuvastatin, and pitavastatin can be taken at any time, but it is recommended that patients take them at the same time every day to avoid missing doses. 
2. Cholesterol absorption inhibitors: such as ezetimibe. It inhibits the intestinal absorption of cholesterol. Statins will have a good synergistic effect when combined with it. At the same time, it will not affect the absorption of other drugs and fat-soluble vitamins. Food will not affect its absorption. Therefore, it is generally taken once daily, with or without food.
3. Probucol: It is mainly suitable for hypercholesterolemia. It will enter the core of LDL and affect lipoprotein metabolism. LDL becomes easily eliminated through non-receptor pathways. It can also reduce xanthomas on the skin. Food increases its absorption, so patients are advised to take it with a meal. Generally, it needs to be taken twice a day, with breakfast and dinner.

Drugs mainly aimed at lowering triglycerides: 

1. Fibrates: such as bezafibrate, fenofibrate, gemfibrozil. Bezafibrate generally needs to be taken with or after meals. To reduce stomach upset caused by fenofibrate, it is recommended to take it with food. Gemfibrozil is generally taken twice daily, and it is recommended to take it 30 minutes before breakfast and dinner. Additionally, when they are combined with statins, it is recommended to take fibrates in the morning and statins at bedtime. This reduces the occurrence of drug interactions.
2. Niacin drugs: This type of drugs includes acipimox and niacin extended-release tablets. The usual dose of acipimox is two or three times a day, taken with or after meals. Acipimox dispersible tablets need to be taken after meals. The usual dose of niacin extended-release tablets is once daily, taken before bed.

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Basic knowledge about febuxostat.📃📃📃

Febuxostat is a xanthine oxidase inhibitor. It inhibits the production of uric acid. While allopurinol can only inhibit the reduced form of xanthine oxidase, febuxostat can inhibit both the reduced and oxidized forms of xanthine oxidase. Therefore, febuxostat's ability to lower uric acid is faster and stronger. 80% of blood uric acid is synthesized in the body, and only 20% is absorbed from food. Patients with gout need to control their blood uric acid within the target range (<360 μmol/mL) throughout their lives to reduce the frequency of gout attacks, prevent tophi formation, prevent bone destruction, and reduce the risk of death. Therefore, they may need to take long-term uric acid-lowering medications.

What are the indications for Febuxostat?

Allopurinol, febuxostat, and benzbromarone are recommended for patients with gout. However, febuxostat is not recommended for use in asymptomatic hyperuricemia. In patients with asymptomatic hyperuricemia in stages 3 and 4 chronic kidney disease, the dose of allopurinol needs to be adjusted and severe hypersensitivity reactions may occur. Therefore, febuxostat may be a better treatment. Febuxostat is indicated for the long-term treatment of hyperuricemia in patients with gout. However, it is not recommended for use in patients with asymptomatic hyperuricemia. Febuxostat has little effect on renal function. No dose adjustment is required in patients with renal insufficiency.

When should uric acid-lowering drugs be used?

Some guidelines recommend that patients with gout can start uric acid-lowering drug treatment after the acute gout attack is completely relieved for 2 to 4 weeks. This is because urate-lowering medications can worsen the symptoms of gouty arthritis. However, if gout attacks are frequent, uric acid-lowering medication can be started at the time of the gout attack. Therefore, they should not be used until the symptoms of acute inflammation of gouty arthritis have resolved. In addition, allopurinol is generally recommended as the first-choice uric acid-lowering drug, but HLA-B*5801 genotype monitoring should be performed before use. Allopurinol is contraindicated in patients with positive HLA-B*5801 genotype.

What is the dosage of Febuxostat?

Common tablet doses of febuxostat are 20mg, 40 mg and 80 mg. The recommended starting dose of febuxostat is 20 mg daily. Patients whose serum uric acid levels do not reach the target value after 2 to 4 weeks of treatment can be increased to 40 mg per day, with a maximum dose of 80 mg per day. Febuxostat tablets can usually be taken in split doses without affecting the effectiveness of the medicine. Its uric acid-lowering effect is not affected by food. 

What are the adverse effects of Febuxostat?

Common adverse reactions generally refer to adverse reactions that occur in at least 1% of patients and are at least 0.5% higher than those in the placebo group. Abnormal liver function, arthralgia, nausea, and rash are common adverse reactions of febuxostat. Abnormal liver function is the most common adverse reaction causing patients to discontinue febuxostat treatment. Therefore, patients should undergo a liver function test before doctors prescribe febuxostat. In addition, if patients experience fatigue, loss of appetite, right upper quadrant discomfort, soy sauce-colored urine or jaundice during the medication period, they should seek medical treatment in time.

Side effect	Placebo group	Allopurinol	Febuxostat
			40 mg/day	80 mg/day
Abnormal liver function	0.7%	4.2%	6.6%	4.6%
Arthralgia	0%	0.7%	1.1%	0.7%
Nausea	0.7%	0.8%	1.1%	1.3%
Rash	0.7%	1.6%	0.5%	1.6%

Febuxostat is more likely to increase the risk of cardiovascular death in patients with gout than allopurinol. Therefore, febuxostat should be used with caution in elderly patients with gout and cardiovascular and cerebrovascular diseases. Allopurinol is the first-line treatment for gout patients with severe cardiovascular disease (such as myocardial infarction, history of stroke, unstable angina). During the medication period, patients should seek medical attention immediately if they develop symptoms such as chest pain, shortness of breath, fast or irregular heartbeat, numbness or weakness on one side of the body, dizziness, difficulty speaking, or sudden severe headache.

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