What should be paid attention to when taking levothyroxine for a long time to treat hypothyroidism?😮😮😮

Levothyroxine is a thyroid hormone drug. It is generally used clinically for the treatment of hypothyroidism, non-toxic goiter, thyroid hormone supplementation after surgical resection of thyroid cancer, and adjuvant treatment of hyperthyroidism with antithyroid drugs. The following will introduce the precautions about the use of levothyroxine.

The basic knowledge of levothyroxine.

In clinical practice, the most commonly used dosage form of levothyroxine is levothyroxine sodium tablets. It is most commonly used as a replacement for patients with hypothyroidism and as an adjunctive treatment for patients with hyperthyroidism.

What are the pharmacological effects of levothyroxine?

One of the main indications for levothyroxine is as an alternative treatment for hypothyroidism. Insufficient synthesis and secretion of thyroid hormone in the body is the main cause of hypothyroidism. Levothyroxine is a synthetic form of tetraiodothyronine (T4). It is converted in the body to the more active triiodothyronine (T3). Thus it will exert the same effect as the thyroxine secreted by the body itself and treat hypothyroidism.

Who are the suitable and contraindicated groups of levothyroxine?

It is generally used in patients with thyroid-related diseases. However, it should be prescribed by a doctor and should not be used by patients on their own. It should be contraindicated in patients with untreated adrenal or pituitary insufficiency, thyrotoxicosis, acute myocardial infarction, acute myocarditis, and acute pancarditis. In addition, it should be used with caution in pregnant and lactating women.

What are the common precautions for levothyroxine?

1. Will long-term use of levothyroxine cause adverse reactions?

Current studies have pointed out that when patients take levothyroxine for a long time, as long as they take it in the correct way and in the right dose, they will not cause adverse reactions. Within certain limits, the human body is able to metabolize thyroxine on its own. This keeps thyroxine from causing adverse reactions. However, if the patient takes levothyroxine in large doses for a long time or takes it by mistake, the patient may experience symptoms of hyperthyroidism such as sweating, insomnia, tremors (especially hand tremors), palpitation, and increased appetite.

2. Why is it not recommended to take soy products together with levothyroxine?

Although it is not recommended to eat soy products while patients are taking levothyroxine, it does not mean that patients cannot eat soy products. Under normal circumstances, patients are not recommended to eat soy products, eggs or milk and other related foods within four hours after taking the medicine. Because they reduce the intestinal absorption of levothyroxine, they affect how well it works. Because these foods reduce the amount of levothyroxine absorbed in the intestine, the dose of levothyroxine may need to be adjusted if the patient starts or stops taking soy products for nutritional supplementation.

3. When is the best time to take levothyroxine?

It is generally recommended that patients take one day's dose of levothyroxine with water half an hour before breakfast every day. It can avoid that when food and levothyroxine are taken at the same time, oily substances or other substances in food will affect the absorption of drugs in the gastrointestinal tract. If patients are unable or have difficulty taking levothyroxine in the morning, they may take it four hours after dinner or at bedtime. However, patients are generally not advised to take levothyroxine at night. It is because levothyroxine is an excitatory hormone. Patients taking levothyroxine at night may affect sleep quality. They may experience adverse effects of poor sleep quality or insomnia.

What are the other precautions for levothyroxine?

In addition to the above precautions, the foods and diseases described below can also affect the body's absorption of levothyroxine. 

• Food: soy foods or their products, grapefruit, iron or calcium-containing foods, milk or their products, tea, coffee, foods that can cause thyroid swelling (such as walnuts, cassava, cabbage, cabbage, rapeseed, etc.), cholesterol unhealthy foods (such as animal offal and butter), high-fat foods (such as cooking oil, walnut kernels, almonds, ham, etc.). Patients should avoid or reduce consumption of these foods. The consumption of these foods should also be separated from the time of taking levothyroxine.
• Diseases: malabsorption syndrome (such as achlorhydria), liver cirrhosis, celiac disease, etc.
• Drug Interactions: Antidiabetic drugs, coumarin derivatives, protease inhibitors (eg, ritonavir, lopinavir), phenytoin, cholestyramine, colestipol, drugs containing aluminum, iron, or calcium ( such as antacids), salicylic acid drugs, dicoumarol, furosemide, clofibrate, orlistat, sevelamer, tyrosine kinase inhibitors (such as imatinib), propylthiouracil, Glucocorticoids, amiodarone, iodine-containing contrast media, beta-sympathomimetics, sertraline, chloroquine, hepatic enzyme inducers (eg, barbiturates, carbamazepine), estrogens.

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What are the differences between the 7 angiotensin II receptor antagonists?😵😵😵

Angiotensin II receptor antagonists are one of the commonly used antihypertensive drugs in clinic. They bind to angiotensin II receptors and inhibit the release of active substances that increase blood pressure. It will have the effect of lowering blood pressure. Allisartan, candesartan, irbesartan, losartan, olmesartan, telmisartan and valsartan are seven commonly used angiotensin II receptor antagonists. Their efficacy is different. However, patients with hypertension and chronic kidney disease, coronary heart disease or diabetes are suitable for angiotensin II receptor antagonists. They have the advantage of a longer duration of action and fewer adverse reactions.

What is the antihypertensive mechanism of angiotensin II receptor antagonists?

Angiotensin II receptor antagonists can selectively inhibit angiotensin II receptors (especially AT1 type) to dilate blood vessels, lower blood pressure, reduce aldosterone secretion, drain sodium, and inhibit sympathetic nerves. AT1 receptors are mainly distributed in the human brain, heart, vascular smooth muscle cells, blood vessels, kidneys, adrenal cortex and placenta. When angiotensin II activates it, it will synthesize and release aldosterone, constrict blood vessels, reduce renal blood flow, increase renal tubular reabsorption of sodium, and stimulate sympathetic nerve activity. These are closely related to blood pressure levels.

The indications and dosage of allisartan.

Pharmacokinetics:

Allisartan is hydrolyzed by enzymes in the gastrointestinal tract and not metabolized by the liver. Therefore, it can significantly reduce the burden on the liver in patients with hypertension. It is well absorbed orally and its half-life is about 10 hours.

Dosage:

The initial and maintenance doses of allisartan are generally 240 mg once daily. Increasing the dose of allisartan did not significantly improve its efficacy. The maximum blood pressure lowering effect can be achieved after taking the medicine for 4 weeks. Since the absorption of allisartan is reduced by food, it is not recommended to take it with food.

Indications:

1. Allisartan is effective in the treatment of mild to moderate primary hypertension. Its efficacy is similar to that of valsartan. Mild-moderate primary hypertension patients who take allisartan for a long time have high safety. 
2. Allisartan can improve carotid atherosclerosis. It improves intima media thickness better than valsartan.
3. For patients with hypertension and stable angina, the antihypertensive effect of allisartan is more significant. In addition, it can also significantly reduce the number of angina attacks in patients.

The indications and dosage of candesartan.

Pharmacokinetics:

The efficacy of candesartan peaks 4 to 6 hours after taking the drug and then slowly declines.

Dosage:

Adults generally take candesartan 4 to 8 mg orally once a day after breakfast. Its dose can be increased to 12mg if it is necessary.

Indications:

There is clear experimental evidence that candesartan can be used in hypertensive patients with heart failure.

The indications and dosage of irbesartan.

Pharmacokinetics:

Oral administration of irbesartan is well absorbed. Its absolute bioavailability is about 60 to 80%. Its bioavailability is not significantly affected by food. Its plasma peak time is 1 to 1.5 hours. It generally has a half-life of 11 to 15 hours and reaches steady state within three days.

Dosage:

The initial and maintenance doses of irbesartan are generally recommended to be 150 mg once a day. For some special patients (such as patients undergoing hemodialysis or patients over 75 years old), the initial dose can be considered as 75 mg once a day. If the patient takes irbesartan 150mg daily and still fails to effectively control his blood pressure, it may consider increasing the dose to 300mg or adding a diuretic (such as hydrochlorothiazide). For hypertensive patients with type 2 diabetes, their initial dose was 150 mg once daily and increased to 300 mg once daily as a maintenance dose.

Indications:

Irbesartan is indicated for the treatment of hypertensive patients with type 2 diabetes mellitus or patients with primary hypertension.

The indications and dosage of losartan.

Pharmacokinetics:

Losartan is rapidly absorbed orally. It takes approximately 0.5 to 1 hour for peak plasma concentrations. It has a more obvious liver first-pass effect. Its bioavailability is about 33 to 37% and its plasma protein binding is about 98.7%. Losartan has difficulty crossing the blood-brain barrier. It has a half-life of about 1.5 to 2 hours. Losartan is metabolized to more active substances in the liver. Its metabolites have a half-life of about 6 to 9 hours. Its metabolites will enhance and prolong its antihypertensive effect.

Dosage:

The initial dose and maintenance dose are generally 50 mg once a day. The maximum antihypertensive effect will be achieved after 3 to 6 weeks after taking the medicine. For some patients, the dose can be increased to 100 mg once a day to produce a further antihypertensive effect. If the patient's blood vessel volume is insufficient (for example, the patient has taken a large dose of diuretics), the initial dose can be considered to take 25 mg once a day.

Indications:

There are treatment guidelines that losartan can be used in patients with hypertension and heart failure. In addition, there are clinical studies that losartan has the effect of increasing the excretion of uric acid. A reduction in blood uric acid levels in patients was associated with a 13 to 29% reduction in cardiovascular events.

The indications and dosage of olmesartan.

Pharmacokinetics:

Olmesartan does not affect hepatic cytochrome P450 enzymes because it is not metabolized by hepatic cytochrome P450. Its bioavailability is about 26%. Its peak plasma concentration is reached approximately 1 to 2 hours after taking the drug. Food does not affect the absorption of olmesartan.

Dosage:

The dose of olmesartan should be individualized. When it is used as a monotherapy for patients with normal blood volume, the initial dose is generally recommended to be 20 mg once a day. The dose of olmesartan can be increased to 40mg once a day for patients who still need to further lower blood pressure after taking the drug for two weeks.

Indications:

Studies have shown that olmesartan can improve cardiac function in patients with chronic heart failure. Olmesartan may be considered for the treatment of patients with chronic heart failure and hypertension.

The indications and dosage of telmisartan.

Pharmacokinetics:

Oral telmisartan is rapidly absorbed by the body. Its absolute bioavailability is approximately 50%. Food does not affect its absorption. Its half-life is greater than 20 hours.

Dosage:

The initial dose of telmisartan is 40 mg once daily. When the dose of telmisartan is 20 to 80 mg, its antihypertensive effect is dose-related. Its maximum dose is 80 mg once daily.

Indications:

Telmisartan is used to treat adults with primary hypertension. It reduces the risk of cardiovascular events.

The indications and dosage of valsartan.

Pharmacokinetics:

Valsartan generally produces its hypotensive effect within 2 hours of oral administration and reaches its maximum effect in 4 to 6 hours. The blood pressure lowering effect can last more than 24 hours. The maximum antihypertensive effect will be achieved after 2 to 4 weeks after taking the drug.

Dosage:

The recommended dose of valsartan is 80mg once a day. Food does not affect its absorption. It is recommended to take the medicine at a fixed time every day. For patients with unsatisfactory blood pressure control, the dose of valsartan can be increased to 160 mg per day or diuretics can be added.

Indications:

There is clear experimental evidence that valsartan can be used in the treatment of hypertensive patients with heart failure.

The drug interactions with angiotensin II receptor antagonists.

Irbesartan and losartan are metabolized by CYP2C9 enzymes, therefore drugs metabolized by this enzyme should not be taken together. Fluconazole and rifampin should not be used in combination with losartan. Digoxin concentrations are elevated by valsartan, so the two should not be used together. Lithium, non-steroidal anti-inflammatory drugs, potassium-sparing diuretics, etc. should be avoided in combination with all angiotensin II receptor antagonists.

What are the adverse reactions of angiotensin II receptor antagonists?

There is no significant difference in the adverse reactions of the above seven angiotensin II receptor antagonists. Common adverse reactions include hypotension, aggravation of renal artery stenosis, and elevated serum potassium. Angiotensin II receptor antagonists are contraindicated in pregnant women.

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What are the indications, dosage and precautions of warfarin?💊💊💊

More and more new oral anticoagulants are being developed. As an older oral anticoagulant, warfarin has disadvantages such as large individual dose variability, narrow therapeutic window, interactions with many drugs and foods, and the need for drug monitoring in patients when used. Warfarin has so many disadvantages. Should it be eliminated from anticoagulation? Although there are many new anticoagulant drugs, it does not mean that warfarin can be completely replaced. Warfarin still plays an important role in anticoagulation therapy. 

What kind of medicine is warfarin?

Warfarin is an anticoagulant drug derived from dicoumarin. Vitamin K epoxide reductase is inhibited by warfarin. This will limit the synthesis of coagulation factors II, VII, IX, and X to produce anticoagulant effects. In addition, some anticoagulant proteins are also inhibited by warfarin. Therefore, patients may experience transient procoagulant effects during the initial period of treatment with warfarin. Its clinical manifestations are gangrene of the limbs and skin necrosis. They generally appear on the third to eighth day after dosing.

What are the indications for warfarin?

It can be used to prevent and treat pulmonary embolism and deep vein thrombosis. It also prevents thromboembolic complications following myocardial infarction, atrial fibrillation, heart valve disease, or prosthetic valve replacement. For patients with mechanical valve replacement, moderate to severe mitral stenosis, or bioprosthetic valve replacement in the first 3 months, warfarin is an irreplaceable alternative to other novel oral anticoagulants.

Dosage of warfarin.

The starting dose of warfarin is generally recommended to be 1 to 3 mg once daily. Certain patients with congestive heart failure, high risk of bleeding, impaired hepatic function, or the elderly require individual dose adjustment. Their starting dose can be reduced as appropriate. Rapid anticoagulation is required for diseases such as venous thromboembolism. Patients need to use unfractionated heparin or low molecular weight heparin overlapping with warfarin for 5 to 7 days. Patients were given warfarin immediately on day 1 or day 2 of heparin. Adjust the drug dose until the INR reaches the target value for more than 2 days before discontinuing parenteral anticoagulants. 

Indications	INR target range	Course of treatment
Venous embolism	2.5 (Range 2 to 3)	Patients secondary to transient risk factors require 3 months of use. Patients with unprovoked venous embolism need to use it for at least 3 months. After 3 months, the risk-benefit ratio of the patient's treatment was evaluated before deciding whether to extend the course of treatment. Long-term treatment is required for patients with two unprovoked venous embolisms, and the risk-benefit ratio of treatment is regularly assessed.
Myocardial infarction prognosis	2 to 3	For patients at high risk of myocardial infarction, combined use of low-dose aspirin is recommended for at least 3 months. (Daily take ≤100mg aspirin)
Atrial fibrillation (non-valvular and valvular)	2 to 3	It recommends long-term anticoagulation in patients at intermediate and high risk of stroke. Nonvalvular atrial fibrillation: Warfarin is not the drug of choice for these patients. The treatment plan needs to be determined based on the evaluation. Valvular atrial fibrillation: Warfarin is the drug of choice for these patients. Most new oral anticoagulants are contraindicated in patients with atrial fibrillation complicated by moderate-to-severe mitral stenosis, mechanical valve replacement, or bioprosthetic replacement (the first 3 months).
Mechanical valve replacement	The INR range needs to be adjusted appropriately according to the valve type and location, and it is generally 2 to 3.	Lifelong treatment.
Bioprosthetic replacement	2 to 3	It is generally 3 to 6 months. After 3 months of treatment, patients can be switched to new oral anticoagulant drugs or discontinued according to the situation.

Pharmaceutical monitoring of warfarin.

Efficacy monitoring:

INR (International Normalized Ratio) and PT (Prothrombin Time) are its main monitoring items. INR can evaluate its anticoagulation strength, and the general target range of INR is 2 to 3. 

Adverse reaction monitoring:

The main adverse reaction of warfarin is bleeding. Although a patient's risk of embolism increases with increased bleeding risk, the benefit of anticoagulation is generally greater. Therefore, bleeding should not be considered a contraindication to anticoagulation. Reversible factors that increase their bleeding risk should be screened for and corrected for in patients who require anticoagulation but are at greater risk of bleeding. They should also strengthen their monitoring and conduct regular evaluations. 

Compliance Monitoring:

Compliance monitoring is mainly to monitor whether the patient takes the medicine on time and according to the dose, and whether there is any self-adjustment of the dose.

Instructions for dosing warfarin.

Dosing time: Warfarin is recommended to be taken at a fixed time in the evening. It is mainly due to the fact that pharmaceutical monitoring is generally performed during the day. When patients take warfarin at night, the dose can be adjusted immediately based on monitoring results.

Dosage: After the patient's INR reaches the target and is stable, frequent dose adjustments are not required. However, the patient should record each dose adjustment and the next monitoring time.

Precautions while taking the medicine:

1. Missed dose: The patient should make up the dose immediately unless it is close to the next dose. A single dose should not be doubled in the event of a missed dose.
2. Diet: In the past, patients were told to avoid foods containing vitamin K as much as possible. However, more and more studies have pointed out that as long as the daily diet structure is relatively stable and do not suddenly consume large amounts of foods containing vitamin K, the efficacy of warfarin will not cause much impact.
3. Self-monitoring: Patients should monitor themselves for signs of bleeding or embolism.
4. Pregnancy and lactation: Warin is generally not recommended for patients during pregnancy. Low molecular weight heparin is preferred for pregnant patients. Patients can continue to use warfarin while breastfeeding because it does not pass into breast milk.

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