How should Ivabradine be used?💔💔💔

The end stages of various cardiovascular diseases lead to heart failure. Patients with heart failure are characterized by high mortality and poor prognosis. One of the important predictors of death from heart failure is heart rate. Therefore, how to effectively control the heart rate of the patient is extremely critical. The guidelines for the diagnosis and treatment of heart failure set the resting heart rate down to about 60 beats per minute as the goal of heart rate management in patients with chronic stable heart failure. β-blockers and ivabradine are clinically mainly used to lower heart rate. 

What is the difference between β-blockers and ivabradine?

β-blockers reduce sympathetic activity and resting heart rate. It will benefit patients with heart failure by reducing myocardial oxygen consumption, reducing cardiac work, delaying and improving ventricular structural remodeling. The guidelines for the treatment of heart failure state that all symptomatic patients with chronic heart failure need long-term use of β-blockers unless the patient is intolerable or contraindicated. At present, it is clinically recommended that the dose for patients with heart failure to reduce the heart rate to 60 beats/min is the target dose or maximum tolerated dose of β-blockers. When treating patients with heart failure, the tolerable target dose should be reached as soon as possible to reduce the resting heart rate. It will result in the greatest benefit to the patient. During the treatment of patients, attention should be paid to whether they may develop worsening heart failure, bradycardia, atrioventricular block, etc., especially at the beginning of treatment and when the dose is increased. β receptors are also distributed in blood vessels. Therefore, peripheral vasculature, coronary resistance and blood pressure are all affected by beta-blockers. Due to the decline of the patient's heart function, too fast increase of the dose of β-blockers can induce or aggravate the risk of heart failure. The dose of β-receptor blockers can reduce the work of myocardial cells and oxygen consumption rate by controlling the heart rate, but it is also necessary to avoid excessive inhibition of myocardial contractility by β-receptor blockers to affect cardiac output and blood pressure. 

Ivabradine is a pure sinoatrial node If-channel blocker. It generally only acts on the ion channel of the sinoatrial node, but in large doses it will also act on the Ih-channel of the retina, resulting in phosphenes. Ivabradine reduces sinus node excitability. It has the characteristic that the faster the base heart rate, the more obvious the effect. No negative inotropic and negative conduction effects are its important features and it will not affect blood pressure.

What is the usual usage of ivabradine?

Many treatment guidelines recommend the use of ivabradine for heart failure with reduced ejection fraction (HFrEF). For patients with sinus rhythm failure of New York heart function class II to IV and left ventricular ejection fraction (LVEF) ≤ 35%, ivabradine can be added with one of the following conditions:

1. The patient has been treated with angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers/angiotensin receptor neprilysin inhibitors, aldosterone receptor antagonists, and β-blockers. The patient has used the target dose or the maximum tolerated dose of β-blockers but the heart rate is still ≥70 beats/min.
2. Heart rate ≥ 70 beats/min in patients who are contraindicated or intolerant of β-blockers.

The guidelines for the use of ivabradine in patients with heart failure are as follows:

1. Patients with chronic HFrEF on ACE inhibitors/ARBs, β-blockers, and spironolactone who have significantly increased resting heart rate (≥80 beats/min) and who cannot increase the dose of β-blockers, the dose of β-blockers can be considered as the maximum tolerated dose in the current state. Early combined use of ivabradine can improve cardiac function and control heart rate. It is also beneficial for patients to subsequently increase the dose of β-blockers.
2. When β-blockers are used in the treatment of patients in the vulnerable stage of heart failure, the dose should not be increased too rapidly. Patients achieved target heart rate more quickly when ivabradine was used in combination. Patients will also more quickly enter into compensation and stabilization.
3. When patients with acute heart failure enter the pre-discharge stage (the patient's hemodynamic status is stable, after orthopnea is relieved, and vasoactive drugs and vasoactive drugs are stopped), ACEI/ARB,  β-blockers and spironolactone therapy can be started on the patient. If the patient has previously used ACEI/ARB, β-blockers and spironolactone, the dose can be increased. However, if the patient has tachycardia, the dose of beta-blockers should not be increased too rapidly. Combined use of ivabradine is beneficial to control the heart rate of patients with tachycardia and further improve cardiac function.
4. Some studies have pointed out that when patients with heart failure and chronic obstructive pulmonary disease are intolerant to β-blockers or can no longer increase the dose, ivabradine can be used in combination or switched. It can control patients' heart rate, improve symptoms and benefit their prognosis.

The recommended starting dose for patients with chronic HFrEF is 5 mg twice daily with meals. The starting dose for elderly patients ≥75 years is 2.5 mg twice daily. Patients were evaluated and dose adjusted two weeks after treatment. The patient's resting heart rate should be controlled at about 60 beats per minute. The maximum dose of ivabradine is 7.5 mg twice daily. Ivabradine is only metabolized by CYP3A4. Ivabradine is only metabolized by CYP3A4. It interacts with inhibitors and inducers of CYP3A4. CYP3A4 inducers decrease the plasma concentration of ivabradine whereas CYP3A4 inhibitors increase its plasma concentration. Elevated plasma concentrations of ivabradine may cause bradycardia in patients.

What other cardiovascular diseases can ivabradine be used for?

The general indication of ivabradine is for sinus rhythm and heart rate ≥ 75 beats/min, accompanied by New York Heart Function Class II to IV chronic heart failure patients with systolic dysfunction. In order to control the patient's condition early or improve the patient's prognosis, there are several practical clinical applications as follows:

1. Stable coronary artery disease: ivabradine or nicorandil can be used for patients who have contraindications to the use of β-blockers, poor treatment effect or adverse reactions. Ivabradine can reduce the heart rate of patients with coronary heart disease to reduce oxygen consumption, increase coronary blood flow, improve coronary microcirculation, prevent ischemia and improve exercise tolerance.
2. After the symptoms of acute heart failure are relieved: when the heart rate of a patient with acute heart failure is still fast after systemic treatment, the treatment guidelines require that the patient should use β-blockers as soon as possible. In patients with acute heart failure who are hemodynamically stable after hospitalization, if the patient cannot tolerate β-blockers, low-dose ivabradine (2.5 mg twice a day) may be considered initially . Ivabradine can be adjusted according to the blood pressure and heart rate of the patient. At the same time, the β-blockers used by patients should be evaluated in time, so that the two can be used in combination reasonably. It can further improve the symptoms of heart failure decompensation and reduce the risk of rehospitalization.
3. Focal atrial tachycardia, inappropriate sinus tachycardia, and orthostatic tachycardia syndrome: Guidelines recommend ivabradine alone or in combination with beta-blockers in patients with symptomatic inappropriate sinus tachycardia. Guidelines recommend ivabradine alone or in combination with beta-blockers in patients with symptomatic inappropriate sinus tachycardia. Ivabradine may be considered in patients with postural tachycardia syndrome. Patients with chronic focal atrial tachycardia may consider using ivabradine combined with β-blockers.
4. Heart rate preconditioning before coronary CT angiography: Excessive heart rate will affect coronary CT angiography. Therefore, metoprolol and propranolol are general pretreatment drugs. Ivabradine safely, rapidly and consistently lowers the patient's heart rate. The regimen of using ivabradine alone or in combination may be a better choice.

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What is the difference between the new hypolipidemic agents alirocumab and evolocumab?😵😵😵

A new type of hypolipidemic agent that is a PCSK9 inhibitor developed in
recent years. It is effective in lowering low-density lipoprotein cholesterol (LDL-C) levels alone or in combination with statins. Alirocumab and evolocumab (both are injections) are two commonly used PCSK9 inhibitors in clinical practice.

How does the body clear LDL-C?

LDL-C is transported from surrounding tissues to the liver by high-density lipoprotein cholesterol (HDL-C). After they reach the liver, they will bind to the LDL receptors on the liver cells and be transported into the liver cells. LDL-C is degraded and metabolized in liver cells.

What is PCSK9?

Proprotein Convertase Subtilisin/Kexin Type 9 is the full name of PCSK9. It degrades LDL receptors by binding to LDL receptors on the surface of liver cells. It reduces the number of LDL receptors on the surface of liver cells and prevents the removal of LDL-C from the blood.

How do PCSK9 inhibitors lower blood lipids?

PCSK9 is specifically bound by PCSK9 inhibitors so that it cannot bind to LDL receptors. Thus, the degradation of LDL receptor caused by PCSK9 is inhibited. This can increase the number of LDL receptors on the surface of liver cells and enhance the effect of clearing LDL-C in the blood.

What is the approximate strength of lipid-lowering effect of PCSK9 inhibitors?

PCSK9 inhibitors such as alirocumab and evolocumab have strong cholesterol-lowering effects. LDL-C can be lowered by about 50 to 70% by them. Several commonly used lipid-lowering regimens and their magnitude of lowering LDL-C:

• Ezetimibe: It lowers LDL-C by about 20% on average.
• Moderate-strength statins (such as simvastatin and pravastatin): They lower LDL-C by about 30% on average.
• High-intensity statins (such as atorvastatin and rosuvastatin): They lower LDL-C by about 50% on average.
• Monotherapy with PCSK9 inhibitors: They reduce LDL-C by about 60% on average.
• High-intensity statin + Ezetimibe: They reduce LDL-C by about 65% on average.
• High-intensity statin + PCSK9 inhibitor: They reduce LDL-C by about 75% on average.
• High-intensity statin + PCSK9 inhibitor + Ezetimibe: They reduce LDL-C by about 85% on average.

Usage and dosage of PCSK9 inhibitors.

Both alirocumab and evolocumab are given subcutaneously. Alirocumab is injected every 2 weeks and evolocumab is injected monthly. 

	Alirocumab	Evolocumab
Common dosage forms	Single-dose prefilled injection pen
	75mg/1ml/pen 150mg/1ml/pen	140mg/1ml/pen
Dosage	Subcutaneous injection: Upper arms, abdomen or thighs.
	1 time every 2 weeks, 75 to 150mg each time.	1 time per month, 420mg each time.
Storage	Store away from light at 2 to 8oC. They should not be refrigerated and shaken. Return to room temperature for at least 30 minutes before use. It can be stored at room temperature (25 oC) for up to 30 days when the patient travels.

What are their side effects?

1. Common adverse reactions of PCSK9 inhibitors include: 

Influenza, nasopharyngitis, upper respiratory infection, back pain. In addition, there may be pain, erythema and bruising at the injection site.

2. Specific adverse reactions of PCSK9 inhibitors are:

PCSK9 inhibitors, like other therapeutic protein drugs, may cause immune reactions. Clinical studies have pointed out that in patients with neutralizing antibodies, the long-term lipid-lowering effect of the drug will not be affected. However, they have an increased incidence of local injection reactions.

What is the difference between the adverse effects of PCSK9 inhibitors and statins?

Muscle toxicity: PCSK9 inhibitors did not increase the incidence of muscle-related adverse reactions in the current clinical research performance. They have the opportunity to become a new option for lipid-lowering therapy in patients with muscle-related adverse events on statins.

Hepatotoxicity: PCSK9 inhibitors did not significantly increase liver function damage compared with placebo in the current clinical research performance. Therefore, no dosage adjustment is required for their use in patients with mild or moderate hepatic impairment.

Blood glucose changes in patients: PCSK9 inhibitors did not accelerate the transformation of prediabetic patients to diabetes in current clinical studies. They also did not affect fasting blood glucose and glycated hemoglobin levels in non-diabetic patients. The incidence of dysglycemic events was not increased by the use of PCSK9 inhibitors.

What are the clinical applications of PCSK9 inhibitors?

For patients who are intolerant to statins or have contraindications, PCSK9 inhibitors can be used alone or in combination with other lipid-lowering drugs.

PCSK9 inhibitors combined with maximally tolerated doses of statins can further reduce the risk of cardiovascular events in patients with atherosclerotic cardiovascular disease.

If after four to six weeks of treatment with statins combined with ezetimibe in patients with ultra-high-risk atherosclerotic cardiovascular disease, the patient's LDL-C does not reach the treatment target (LDL-C<1.4mmol/L), it is recommended to add PCSK9 Inhibitors.

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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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How to use statins correctly?(Part 2: Statin therapy.)✅✅✅

Here is part 2. It is about how to use statins correctly.

What are statins and how should they be used?

There are 7 kinds of statins that are more commonly used in clinical practice. There are 7 kinds of statins that are more commonly used in clinical practice. The seven statins are atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin and simvastatin.

Their characteristics are as follows:

• Atorvastatin is a potent and long-acting statin. It can be taken at any time. It is mainly metabolized via the hepatic enzyme CYP3A4. Therefore, it has more interactions with other drugs, and it is necessary to pay attention to drug interactions when taking it in combination.
• Pitavastatin is a moderate-strength, long-acting statin. It can be taken at any time. Its dose is the smallest among statins. It is mainly excreted through feces. It has fewer interactions with other drugs. It has few side effects and it has minimal effect on blood sugar.
• Pravastatin is a moderate-strength statin. Since it is not metabolized by liver enzymes, it has fewer interactions with other drugs. It has few side effects and it has less effect on blood sugar. However, it has a shorter potency and needs to be taken at bedtime.
• Rosuvastatin is a potent and long-acting statin. It can be taken at any time. It is excreted mainly in the feces and partly in the kidneys. Since only a small amount is metabolized by the liver, it has fewer interactions with other drugs. Combination medication has higher safety.
• Simvastatin is metabolized by the liver enzyme CYP3A4. Many drugs are metabolized through this pathway, so it has more interactions with other drugs. The drug-drug interactions should be paid attention to in combination therapy. It also has a shorter duration of action. Therefore, it needs to be taken at bedtime for the best lipid-lowering effect.

The initial drug should be a moderate-intensity statin, and then the dose should be adjusted according to the patient's lipid-lowering efficacy and tolerance. If the patient's cholesterol level fails to reach the target, it should be combined with other lipid-lowering drugs. The lipid-lowering intensities and doses of statins are as follows:

• Low-intensity (daily dose lowers LDL-C < 30%): Fluvastatin 20-40mg, Lovastatin 20mg, Pitavastatin 1mg, Pravastatin 10-20mg, Simvastatin 10mg.
• Moderate-intensity (daily dose lowers LDL-C 30 to 50%): Atorvastatin 10-20mg, Fluvastatin 80mg, Lovastatin 40mg, Pitavastatin 2-4mg, Pravastatin 40-80mg, Rosuvastatin 5-10mg, Simvastatin 20-40mg.
• High intensity (daily dose lowers LDL-C ≥50%): Atorvastatin 40-80mg, Rosuvastatin 20mg.

The lipid-lowering treatment options.

The usual doses of statins are: atorvastatin 10-20mg, fluvastatin 80mg, pitavastatin 2-4mg or rosuvastatin 5-10mg. If blood lipids still do not reach the target after 3 to 4 weeks of treatment, 10 mg of ezetimibe daily is combined with treatment for 4 weeks.

If the blood lipids still do not reach the target after treatment, there are generally two options. The first option is to increase the dose of the statin. The advantage of this approach is lower cost but an increased risk of side effects (despite doubling the statin dose, the LDL-C reduction is only 6%). The second option is to use a combination of PCSK-9 inhibitors (eg, evolocumab). This regimen will be more effective, but more expensive. Higher-dose statin, ezetimibe and PCSK-9 inhibitor combined use of the three drugs will further enhance the cholesterol-lowering effect. However, it is necessary to strengthen the monitoring of adverse reactions in patients when combined.

However, in patients with homozygous familial hypercholesterolemia, their LDL-C is usually significantly elevated. Even if they are treated with the above-mentioned combination drugs, it is still difficult to have reasonable blood lipid control. Plasma exchange therapy every 1 to 2 weeks may be considered for this type of patient. If the patient's triglycerides are only borderline high (between 1.7 and 2.26 mmol/L), no medical treatment is required. These patients can control their blood lipids by controlling their diet, eating more vegetables, reducing calorie intake, increasing exercise, losing weight and not drinking alcohol.

Patients with moderately elevated triglycerides (between 2.26 and 5.6 mmol/L), especially those with comorbidities such as diabetes or ASCVD, may consider statin therapy. When patients have severely elevated triglycerides above 5.6 mmol/L, they are at high risk for acute pancreatitis. Therefore, they should immediately lower triglycerides to relatively safe levels with drugs such as fibrates, niacin extended-release.

Which patients need to take statins for lipid-lowering therapy?

The following groups of people need oral statins for lipid-lowering therapy:

People with LDL-C>4.9mmol/L.

The patient has been diagnosed with ASCVD. In addition, patients with stable or unstable angina, acute coronary syndrome, peripheral vascular disease, coronary or other revascularization, myocardial infarction, transient ischemic attack, ischemic stroke, or confirmed coronary and Large and medium arteries such as the carotid artery have more than 50% stenosis.

Patients with diabetes or LDL-C (>3.4mmol/L) combined with hypertension.

Low HDL-C (<1.0mmol/L), obesity, smoking, hypertension of grade two or above and other three or more non-diabetic risk factors combined with hypertension.

Diabetic patients with LDL-C>1.8mmol/L or total cholesterol (TC)>3.1mmol/L and age>40 years old.

Some patients with carotid plaque.

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How to use statins correctly?(Part 1: Blood lipids and related diseases.)✅✅✅

Statins are effective and safe in lowering cholesterol and reversing plaque. Clinically they have become fundamental drugs for reducing the risk of cardiovascular disease and treating atherosclerosis. Due to the widespread use of statins, incorrect use of statins can cause adverse reactions in patients.

What are blood lipids?

Cholesterol in the human body is mainly present in the body in the form of cholesterol esters and free cholesterol. Although lipids are insoluble in water, lipids in plasma are mainly combined with apolipoproteins to form soluble lipoproteins, so that plasma is normally clear and transparent. Lipoproteins are classified into high density lipoprotein (HDL), intermediate density lipoprotein (IDL), low density lipoprotein (LDL), very low density lipoprotein (VLDL) and chylomicrons (CM). In addition, there is a lipoprotein called lipoprotein a (LPa). Lipoproteins are the major transport form of blood lipids in the human body. Clinically, the level of LDL in the blood can be reflected by the level of low-density lipoprotein cholesterol (LDL-C). In addition, there are triglycerides in the blood, which are also commonly known as fats. Clinically, the two main indicators of concern are LDL-C and cholesterol. Because only cholesterol is the basis pathophysiology of atherosclerosis.

What is atherosclerotic cardiovascular disease?

Atherosclerotic cardiovascular disease (ASCVD) includes ischemic stroke, myocardial infarction (MI), stable and unstable angina, transient ischemic attack, and peripheral vascular disease (PAD).

What is the source of cholesterol in blood?

The main sources of cholesterol in the blood are synthesis in the body and dietary intake. The amount of synthesized in the body is about 2/3 (70%-80%) and the amount of dietary intake is about 1/3 (20%-30%). The main site of cholesterol synthesis in the body is the liver. However, cholesterol cannot enter the blood directly after being synthesized in the liver. It is excreted into the intestines through bile, and then absorbed by the intestines into the blood. This process is called enterohepatic circulation of cholesterol. Both the cholesterol synthesized by the liver and the cholesterol absorbed from the diet must be absorbed by the intestine before entering the blood. Therefore, the ability of the intestines to absorb cholesterol greatly affects the level of cholesterol in the body's blood. Clinically, ezetimibe has a lipid-lowering effect by inhibiting the absorption of cholesterol in the intestines. 

What are the causes of hyperlipidemia?

The causes of hyperlipidemia include the following:

1. Diet can cause hyperlipidemia. Long-term consumption of high-sugar, high-fat and high-energy foods or beverages can easily lead to hyperlipidemia. Lack of physical activity or excessive alcohol consumption can lead to dyslipidemia.
2. The disease causes hyperlipidemia. Some diseases may cause dyslipidemia, such as: thyroid disease, liver disease, pancreatitis, diabetes, obesity, gout, familial hypercholesterolemia, etc. Hypothyroidism can cause hyperlipidemia including cholesterol and triglyceridemia.
3. Drugs can also cause hyperlipidemia. Some drugs can also increase blood lipids, such as glucocorticoids, non-selective β-blockers, and diuretics, which can induce secondary dyslipidemia.

Who needs to be screened for blood lipids?

The following people need to be screened for blood lipids:

Men or women over the age of 40 (or postmenopausal women).

All patients with any of the following conditions, regardless of age, should be screened for lipids.

• Clinical evidence points to the presence of atherosclerotic cardiovascular disease.
• Diabetes.
• Hypertension.
• Hypertension in pregnancy.
• Chronic kidney disease (eGFR≤60ml/min 1.73m2).
• Abdominal aortic aneurysm.
• Chronic Obstructive Pulmonary Disease.
• Signs of dyslipidemia (eg, xanthomas, corneal arches).
• Inflammatory diseases (inflammatory bowel disease, psoriatic arthritis, systemic lupus erythematosus, rheumatoid arthritis, ankylosing spondylitis). 
• Family history of premature cardiovascular disease (age of onset in first-degree relatives: female < 65 years, male < 55 years).
• Obesity (BMI ≥ 30). 
• Still smoking. 

How long is the interval between blood lipid tests?

People between the ages of 20 and 40 should have their blood lipids tested every 5 years.

Men over the age of 40 should have their blood lipids checked once a year.

Postmenopausal women should have their blood lipids checked once a year.

Patients with ASCVD or their high-risk groups should have blood lipids measured every 3 to 6 months. (High-risk groups refer to people with multiple ASCVD risk factors, such as diabetes, hypertension, familial hyperlipidemia, family history of premature cardiovascular disease, obesity, smoking, etc.)

Inpatients with ASCVD should be tested for blood lipids at the time of hospital admission.

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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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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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Knowledge of calcium channel blockers.📓📓📓

Calcium channel blockers are one of the most commonly used
antihypertensive drugs in clinical practice. It has been used for many years. Its efficacy and safety have been proven. It plays an important role in the clinical treatment of cardiovascular disease. Therefore, for calcium channel blockers, you should have the following knowledge.

Mechanism of action of calcium channel blockers.

There are two types of calcium channel blockers: dihydropyridines and non-dihydropyridines. The pharmacological effects of both of them are to inhibit the influx of calcium ions into vascular smooth muscle cells by selectively blocking voltage-dependent calcium ion channels. This relaxes the smooth muscle of the blood vessels, which dilates the blood vessels. Peripheral vascular resistance will therefore decrease, to achieve a blood pressure lowering effect. They mainly dilate the arteries, especially the coronary arteries.

• Dihydropyridine calcium channel blockers have better vascular selectivity. It generally does not affect atrioventricular conduction, sinoatrial node function, and myocardial contractility at therapeutic doses.
• Non-dihydropyridine calcium channel blockers have poor vascular selectivity. It has a negative inotropic effect and negative conduction on the heart. Therefore, it not only lowers blood pressure but also lowers heart rate.

Calcium channel blockers commonly used in clinical practice.

Dihydropyridine calcium channel blockers:

Drug	Drug standard (mg)	Dosage (initial dose to full dose, mg/d)	Times of taking medicine (times/d)
Amlodipine	5、10	5 to 10	1
Barnidipine	5、10、15	5 to 15	1
Benidipine	2	4 to 8	1
Cilnidipine	5、10	5 to 10	1
Felodipine	2.5、5	2.5 to 10	2
Lacidipine	4	4 to 8	1
Lercanidipine	10	10 to 20	1
Levamlodipine	2.5、5	2.5 to 5	1
Manidipine	5	5 to 20	1
Nicardipine	20	40 to 80	2 to 3
Nifedipine	5、10	10 to 30	2 to 3
Nifedipine (Sustained Release)	20、30	10 to 80	2
Nifedipine (Controlled Release)	30	30 to 60	1
Nitrendipine	10	20 to 60	2 to 3

Non-dihydropyridine calcium channel blockers:

Drug	Drug standard (mg)	Dosage (initial dose to full dose, mg/d)	Times of taking medicine (times/d)
Diltiazem	30	90 to 360	1 to 2
Diltiazem (Sustained release)	200	200	1
Verapamil	40	80 to 480	2 to 3
Verapamil (Sustained release)	240	120 to 480	1 to 2

Characteristics of calcium channel blockers.

Their pharmacodynamics are dose-dependent and have a good antihypertensive effect. Single-agent therapy generally achieves the desired effect. Mild to moderate hypertension can generally be controlled by it. They are the first-line treatment in many national hypertension guidelines.

Stroke risk in hypertensive patients is significantly reduced by calcium channel blockers.

Many clinical studies have shown that calcium channel blockers can change the physiological activities related to calcium ions to affect atherosclerosis. They can slow the progression of atherosclerosis

Calcium channel blockers do not alter sugar and lipid metabolism. Therefore, it can be used by patients with diabetes and metabolic syndrome. In addition, levamlodipine besylate can dilate the bulbar arterioles and afferent arterioles. It reduces the resistance of the renal blood vessels without increasing the intra-glomerular pressure. These factors make it beneficial for hypertensive patients with diabetes mellitus and patients with parenchymal renal disease.

Calcium channel blockers have the effect of increasing sodium excretion. If the patient has salt-sensitive hypertension, its antihypertensive effect will be better. Its antihypertensive effect is not affected by a high-salt diet, so it is also suitable for people on a high-salt diet.

Calcium channel blockers have a good effect on volume hypertension such as isolated systolic hypertension and elderly hypertension.

Medium- and long-acting calcium channel blockers have a good safety profile, fewer side effects, and a lower incidence of hypotension. Their effects are gentle and long-lasting. Most only need to take 1 or 2 pills a day. This can improve patient compliance with medication and the efficacy of treatment.

Calcium channel blockers dilate the coronary arteries, thereby reducing coronary resistance and improving the ability of the heart muscle to supply blood. It can treat coronary heart disease, angina pectoris, hypertrophic cardiomyopathy and peripheral vascular disease, especially for variant angina pectoris caused by coronary spasm.

Non-dihydropyridine calcium channel blockers can also slow the heart rate and improve blood supply to the coronary arteries. It can prevent and treat coronary heart disease, arrhythmias such as premature atrial beats, and supraventricular tachycardia.

Indications for calcium channel blockers.

Calcium channel blockers are used for various types of high blood pressure. It is the first-line treatment for high blood pressure.

Dihydropyridine calcium channel blockers:

• Hypertension with atherosclerosis: Peripheral vascular disease, coronary atherosclerosis, carotid atherosclerosis or stable angina with hypertension.
• Volumetric hypertension: Hypertension with low sympathetic or low renin activity, isolated systolic hypertension and elderly hypertension.

Non-dihydropyridine calcium channel blockers:

• Angina pectoris, supraventricular tachycardia, carotid atherosclerosis with hypertension.

Combination medication.

Diuretics: The risk of stroke in hypertensive patients can be reduced by combining calcium channel blockers with diuretics. However, the hypotensive effect of calcium channel blockers reflexively activates sympathetic nerves. Diuretics also activate sympathetic nerves after reducing blood volume. Their side effects may be aggravated by this.

Angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists: They dilate arteries and veins. Calcium channel blockers can directly dilate the arteries. Therefore, their combined use will have a synergistic effect. Angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists can partially inhibit the side effects of increased heart rate and increased reflex sympathetic tone caused by calcium channel blockers. Ankle edema is a common side effect of dihydropyridine calcium channel blockers, which can be eliminated or alleviated by angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists.

β-blockers: It can inhibit the blood volume mechanism and sympathetic nerve, and achieve a significant antihypertensive effect. The reflex sympathetic excitation caused by vasodilation by calcium channel blockers is inhibited by β-blockers. The increase in peripheral arterial resistance caused by long-term use of β-blockers is also inhibited by calcium channel blockers. They are suitable for patients with angina pectoris, heart failure, tachycardia, myocardial infarction with hypertension.

Side effects of calcium channel blockers.

Edema: It is a common side effect of calcium channel blockers. Edema of the face, lower extremity pretibial, lower extremity pretibial edema may occur. It will improve after stopping the drug. Alternatively, it may try to replace the patient with other calcium channel blockers. The incidence of side effects with levamlodipine is relatively low.

Gingival hyperplasia: It may occur in patients taking calcium channel blockers for a long time. Among them, nifedipine caused the highest incidence of gingival hyperplasia.

Hypotension: Some calcium channel blockers, especially short-acting calcium channel blockers, may lower blood pressure too quickly and cause hypotension. Therefore, it recommends the use of long-acting calcium channel blockers (eg, amlodipine) to lower blood pressure. The patient's blood pressure should also be monitored after taking the drug.

Atrioventricular block: Non-dihydropyridine calcium channel blockers have negative effects on the heart. It inhibits sinus node and myocardial contraction. The main clinical manifestation is atrioventricular block. Therefore, patients with sick sinus syndrome and 2nd degree or higher atrioventricular block are contraindicated.

Heart failure: Calcium channel blockers dilate systemic blood vessels, reduce cardiac load and protect ischemic myocardium. However, the degree of heart failure can be aggravated, so it should be used with caution in patients with heart failure.

Tachycardia: Calcium channel blockers reflexively activate the sympathetic nervous system. It increases the heart rate. When necessary, calcium channel blockers should be combined with β-blockers to alleviate this adverse effect.

Headache and flushing: The dilation of blood vessels caused by calcium channel blockers may cause headaches and flushing. If the patient cannot tolerate it, other antihypertensive drugs should be used.

Constipation: Intestinal smooth muscle calcium transport may also be affected, resulting in constipation. If the constipation is more severe, it may consider changing the dressing or adding a laxative.

Caution with calcium channel blockers.

Short-acting nifedipine: It may drop blood pressure too quickly and cause low blood pressure. It will also increase the heart rate reflex reflex, blood pressure fluctuations and other problems. Therefore, it is mainly used in the clinical treatment of coronary heart disease and angina pectoris, and it can be sucked in the first aid.

Pay attention to the method of administration: Sustained-release or controlled-release tablets should be swallowed whole.

Avoid grapefruit or grapefruit juice: The activity of the CYP3A4 enzyme can be inhibited by grapefruit. In addition to no obvious effect on amlodipine, other metabolic rates will be reduced, thereby enhancing drug efficacy and the occurrence of adverse reactions.

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