Characteristics of Cardiovascular Drugs for Women
With the growth of knowledge about gender differences in cardiovascular diseases, in recent years, diagnostic methods and treatments adapted to gender have attracted widespread attention from cardiovascular doctors. It is common for men and women to have different responses to cardiovascular drugs. This is because of gender differences in physiology, pharmacokinetics, and pharmacodynamics.
Physiological gender differences include: women have a lower body mass index and smaller organ volume, which leads to a smaller volume of distribution in women; women have a higher proportion of fat, which increases the volume of distribution of fat-soluble drugs; in women During the menstrual cycle, higher levels of estrogen promote the retention of sodium and water, resulting in greater fluctuations in the proportion of tissue fluid; women’s glomerular filtration rate and creatinine clearance rate are lower than men’s. In addition, there are also gender differences in the cardiovascular system. Including: the size of the female heart is small; the average heart rate of women at rest is 3~5 beats/min faster than that of men; the length of the female heartbeat cycle changes throughout the menstrual cycle and prolongs during the menstrual period. This cyclical fluctuation is completely blocking autonomy. The nerves no longer appear; women have a longer corrected QT interval (QTc) and a shorter sinus node recovery time.
Pharmacokinetic studies have confirmed that most drugs have gender differences, and gender differences in drug-metabolizing enzyme activities may have clinical significance. Many cardiovascular drugs are metabolized by the enzymes of the cytochrome P450 system, and endogenous hormones including estrogen and progesterone are also metabolized by these enzymes. Human liver biopsy found that female CYP3A4 messenger RNA expression was high, CYP3A4 level was about twice that of male, CYP3A4 was involved in more than 50% of the first pass effect of the drug. The substrates of this enzyme include: atorvastatin, diltiazem, verapamil, estradiol, nimodipine, quinidine, etc. There are few reports on whether the activities of CYP2C19 and CYP2C9 (substrates including fluvastatin, torasemide, losartan and irbesartan, etc.), which are partly involved in the metabolism of propranolol, are different between men and women. The activity of CYP2D6 (substrates including: encarney, flecainide, mexiletine, propafenone, metoprolol, etc.) is not different between men and women. There is little information about sex differences in drug delivery vehicles, and their expression and activity are regulated by genetic components and sex hormones. CYP3A4 isoenzymes and multiple drug export carriers P-glycoprotein have multiple substrate crossover phenomena, suggesting that the gender difference in CYP3A4 clearance may be due to the low expression of female liver P-glycoprotein. However, recent studies have not found that the expression of this vector in the liver is different between men and women. Most drug metabolizing enzymes and drug carriers have genetic variability. This variation can lead to weakened enzyme activity, such as CYP2D6, CYP2C19, CYP2C9, etc., or may lead to increased enzyme activity, such as CYP2D6. The decrease in enzyme activity leads to an "overdose" of the relative drug, which plays a key role in increasing adverse drug reactions, but there is no evidence to show that the frequency of this gene mutation differs between men and women.
Physiological gender differences include: women have a lower body mass index and smaller organ volume, which leads to a smaller volume of distribution in women; women have a higher proportion of fat, which increases the volume of distribution of fat-soluble drugs; in women During the menstrual cycle, higher levels of estrogen promote the retention of sodium and water, resulting in greater fluctuations in the proportion of tissue fluid; women’s glomerular filtration rate and creatinine clearance rate are lower than men’s. In addition, there are also gender differences in the cardiovascular system. Including: the size of the female heart is small; the average heart rate of women at rest is 3~5 beats/min faster than that of men; the length of the female heartbeat cycle changes throughout the menstrual cycle and prolongs during the menstrual period. This cyclical fluctuation is completely blocking autonomy. The nerves no longer appear; women have a longer corrected QT interval (QTc) and a shorter sinus node recovery time.
Pharmacokinetic studies have confirmed that most drugs have gender differences, and gender differences in drug-metabolizing enzyme activities may have clinical significance. Many cardiovascular drugs are metabolized by the enzymes of the cytochrome P450 system, and endogenous hormones including estrogen and progesterone are also metabolized by these enzymes. Human liver biopsy found that female CYP3A4 messenger RNA expression was high, CYP3A4 level was about twice that of male, CYP3A4 was involved in more than 50% of the first pass effect of the drug. The substrates of this enzyme include: atorvastatin, diltiazem, verapamil, estradiol, nimodipine, quinidine, etc. There are few reports on whether the activities of CYP2C19 and CYP2C9 (substrates including fluvastatin, torasemide, losartan and irbesartan, etc.), which are partly involved in the metabolism of propranolol, are different between men and women. The activity of CYP2D6 (substrates including: encarney, flecainide, mexiletine, propafenone, metoprolol, etc.) is not different between men and women. There is little information about sex differences in drug delivery vehicles, and their expression and activity are regulated by genetic components and sex hormones. CYP3A4 isoenzymes and multiple drug export carriers P-glycoprotein have multiple substrate crossover phenomena, suggesting that the gender difference in CYP3A4 clearance may be due to the low expression of female liver P-glycoprotein. However, recent studies have not found that the expression of this vector in the liver is different between men and women. Most drug metabolizing enzymes and drug carriers have genetic variability. This variation can lead to weakened enzyme activity, such as CYP2D6, CYP2C19, CYP2C9, etc., or may lead to increased enzyme activity, such as CYP2D6. The decrease in enzyme activity leads to an "overdose" of the relative drug, which plays a key role in increasing adverse drug reactions, but there is no evidence to show that the frequency of this gene mutation differs between men and women.