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The gender difference in drugs is an objective fact. The statin lipid-lowering drug simvastatin, the gastrointestinal motility drug cisapride and the antihistamine terfenadine were all withdrawn from the market because they were found to cause lethal rhabdomyolysis or severe arrhythmias in women shortly after the market. So, what other drugs should pay attention to gender differences when applied? Below we summarize several types of drugs that should be focused on.

I. Antipsychotics

Commonly used atypical antipsychotics, such as clozapine, olanzapine, quetiapine, aripiprazole, risperidone, and ziprasidone, can induce ECG abnormalities and extrapyramidal symptoms, and women are significantly higher In men; risperidone can cause elevated levels of prolactin in women, leading to a higher incidence of osteoporosis and sexual dysfunction than men.

Clozapine and olanzapine are primarily metabolized by CYP1A2. Studies have shown that the activity of female liver drug enzyme CYP1A2 is lower than that of males. In the case of the same dose and weight, the serum drug concentration of female patients is significantly higher than that of male patients.

Oral contraceptives can inhibit the activity of CYP1A2 and increase the blood concentration of clozapine and olanzapine. When determining the dose to be administered, women must be asked if they are taking a contraceptive or a hormone replacement.

Clozapine can cause fatal neutropenia with an incidence of about 0.8%, most of which occurs within 3 months of starting treatment. The incidence of neutropenia in women is higher than in men. Before the drug administration, the first 3 months of administration, and at least 1 month after administration, the white blood cell differential count should be checked every week.

II. Sedative hypnotics

Zolpidem (Sinus, Jun Le Ning, Shu Sleeping Morning), fast onset and short duration, can be used as a hypnotic for short-term treatment of insomnia. The usual dosage for domestic drug instructions is: 10 mg orally immediately before bedtime.

Taking zolpidem can cause some strange behavior. Such as sleep sickness, dream drive, or other potentially dangerous behaviors during apparent sleep, including preparing food, eating, making phone calls, and having sex. The patient has no memory of the occurrence of these behaviors.

Due to differences in body fat and liver drug enzymes, the clearance rate of zolpidem in women is significantly slower than that of men, and is more sensitive to the side effects of zolpidem. In 2013, based on the results of simulation studies, the FDA reduced the dose of a single dose from 10 mg to 5 mg for women to reduce adverse drug reactions.

III. Statins lipid-lowering drugs

The drug-metabolizing enzyme CYP3A4 is the most abundant CYP450 enzyme in the human body and participates in the metabolism of more than 50% of drugs on the market. In vitro and in vivo experiments showed that the activity of female CYP3A4 was 30%~50% higher than that of males.

A meta-analysis included a total of 79,494 patients in 10 studies. The results showed that statins reduced the relative risk of severe coronary events in 27% of men and 23% of women, and women often benefited less than men.

Further analysis found that the above results may be related to the use of statins metabolized by CYP3A4, while pravastatin, rosuvastatin and fluvastatin are not metabolized by CYP3A4, and no gender differences are found in clinical trials.

IV. Cardiac glycosides

Digoxin is a commonly used drug for the treatment of heart failure. Although long-term treatment with Gaoxin can not improve the prognosis of patients with chronic heart failure, it can improve exercise endurance, reduce the rate of re-hospitalization related to heart failure, and improve the quality of life.

Clinical studies have found that there is a gender difference in digoxin. Compared with men, the mortality rate of digoxin in women was higher than that in placebo (33.1% vs 28.9%).

The possible reasons are that the relative dose of the female digoxin is too large, and the second is that the activity of the sodium pump on the female cardiomyocyte membrane is decreased.

The usual dose of digoxin is 0.125 ~ 0.5mg once a day. Because digoxin is hardly distributed to adipose tissue, women use a low-dose (0.125 mg/d) regimen that usually reaches the desired therapeutic concentration (0.5 to 1.0 ng/ml).

The Na+ level and sodium pump activity of female red blood cells were lower than that of males. The number of sodium pumps in female skeletal muscle cells with heart failure was also less. It was speculated that the activity of sodium pump on myocardial cell membrane was decreased, which may cause fatal arrhythmia with women. More relevant.

V. β-receptor antagonist

According to statistics, 70% to 80% of the oral dose of metoprolol is metabolized by CYP2D6. Therefore, CYP2D6 enzyme activity is a major factor affecting the metabolism of metoprolol.

The results of the study showed that the activity of female CYP2D6 was lower than that of males. Using the same dose of metoprolol, the plasma concentration of women was significantly higher than that of men, and heart rate and blood pressure were more pronounced.

There are three large-scale clinical trials on the treatment of heart failure with β-blockers (8900 females), indicating that female drug mortality is significantly lower than that of males, which may be related to female CYP2D6 enzyme activity and estrogen levels.

Metoprolol can vary in blood concentration by 20 times in different individuals and must be administered from a small dose. As a patient, especially a female patient, the resting heart rate should be monitored. If the heart rate is not lowered, the dose is insufficient; if the heart rate is too low (less than 55 beats / min), the dose is too large.

In summary, there are gender differences in the efficacy and adverse reactions of some drugs. Therefore, whether it is a clinician or a patient, when applying the above drugs, attention should be paid to the similarities and differences between the efficacy and adverse reactions caused by gender differences, and jointly promote the drug. Reasonable application.

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