Injection (prolonged) drugs. Long-acting contraceptives (injection, subcutaneous implants, intrauterine devices)

Injection contraception (IR) is used by more than 18 million women worldwide. The composition of IR includes prolonged-acting progestogens, devoid of estrogenic and androgenic activity:

Depot-Medroxyprogesterone Acetate ("Chain-Provera") ..

- norethisterone enanthate ("EET-EY"). IR contraceptive mechanism:

- suppression of ovulation (inhibitory effect on the hypothalamic-pituitary system),

Changes in the physicochemical properties of the mucus of the cervical canal (its viscosity and fibrousness increase), preventing sperm penetration,

Violation of the level of enzymes that are "responsible" for the fertilization process,

Transformations in the endometrium that prevent implantation.

Contraceptive efficacy IR -   0.5-1.5 pregnancies per 100 women / years.

IR usage mode:

"Depo-Provera-] 50" - the first dose of the drug (150 mg / 1 ampoule) is administered in the first 5 days of the menstrual cycle: subsequent injections are made every 12 weeks (3 months + 5 days);

Yaeg-eya - injections of the drug are performed 1 time in 8 weeks (200 mg / 1 ampoule).

Shake the vial before administering IR. The drug is injected deep into the gluteal muscle. The injection area is not massaged. Fertility recovery occurs within 4-24 months after the last injection.

Indications:

- the impossibility of regular daily intake of other

hormonal drugs if you want to increase the interval between births.

Late reproductive age (over 35 years old),

Contraindications to the appointment of estrogen (a number of extragenital diseases or the presence of estrogen-dependent complications in the anamnesis),

Lactation (6 weeks after birth)

Use as a “postabortion” contraception.

Contraindications:

Pregnancy

Pathological uterine bleeding of unclear genesis,

Pregnancy planning in the near future (especially in patients aged 30 to 40 years),

Malignant diseases of the reproductive organs-n "." And systems (with the exception of endometrial cancer). And mammary glands,

NET-EN is not acceptable during lactation. Side effects:

- menstrual irregularities (especially in the first months of contraception),

Galactorrhea,

Dizziness, headache,

Fatigue,

Irritability,

Depression,

Weight gain.

Decreased libido. Method Limitations:

- menstrual irregularities, especially in the first months of contraception (dysmenorrhea, acyclic uterine bleeding, oligomenorrhea, amenorrhea),

The need for regular injections.

Advantages of the method:

- high contraceptive effect,

Simplicity and privacy of use,

Low metabolic rate (due to lack of estrogen component),

Therapeutic effect in endometriosis. premenstrual and menopausal syndromes, dysfunctional uterine bleeding, algomenorrhea. "hyper-polymenorrhea. hyperplastic processes in the endometrium. recurrent inflammatory diseases of the internal genital organs.

- use additional contraception within two weeks after the first injection of the drug,

Injections of the drug should be carried out every 3 months (+5 days) in a medical institution,

If any complaints appear (profuse uterine bleeding, headaches, depression, weight gain, frequent urination deserve special attention) consult a doctor.

Stop administering the drug a few months before the planned pregnancy (it should be borne in mind that fertility is restored after 4-24 months after discontinuation of injection),

With prolonged amenorrhea, consult a doctor to exclude pregnancy.

Interest in long-acting contraceptives is growing, as they are convenient, solve the problems of adherence, and thus increase their effectiveness. Most long-acting contraceptives are combination drugs, but there are also drugs based on progestins only. The effect of the active components is prolonged, mainly due to special systems that provide a gradual release of active substances. Administration options include injections, transdermal patches, subcutaneous rods, vaginal rings, and intrauterine devices. Various options for long-acting contraceptives are described below.

Injectable contraceptives

Pure Progestins
Injectable progestins containing medroxyprogesterone acetate (Depo-Provera) are indicated in cases where a woman has contraindications to the use of estrogen, receives anticonvulsants, suffers from dementia, or cannot comply with the conditions for taking oral contraceptives. Moreover, it is known that their use is safe for atherosclerotic lesions of the coronary arteries, congestive heart failure, diabetes, smoking, or a history of thromboembolism. Medroxyprogesterone acetate is also used in the treatment of metastases of endometrial carcinoma or kidney.
Although most long-acting contraceptives are based on maintaining the concentration of the substance, Depo-Provera (150 mg of medroxyprogesterone acetate) was created as a water-soluble microcrystalline suspension with a gradually decreasing concentration of the active component over the cycle. A pharmacological dose (\u003e 0.5 ng / ml) is reached after 24 hours, and a peak (2 ng / dl) is observed during the first week after injection. Serum concentrations are maintained at 1 ng / ml for approximately 3 months. Interestingly, for 4 months after injection, estrogen concentrations remain at the level of the early or middle follicular phase (below 100 pg / ml). Over the next 5-6 months, serum concentrations of medroxyprogesterone acetate are reduced to 0.2 ng / ml (ovulation occurs when its content< 0,1 нг/мл). Тем не менее в одном из исследований был отмечен подъем концентрации прогестерона через 3,5 месяца.
The mechanism of action is mainly due to the suppression of pulsation of LH (and, therefore, ovulation) peak concentration of the hormone. Like other progestins, medroxyprogesterone acetate increases the viscosity of cervical mucus, damages endometrial cells and reduces contractility of the fallopian tubes and uterus. The content of FSH when using Depo-Provera is reduced to a minimum.
According to the main recommendations, the drug is administered every 3 months, for 1 week from 5 days after the onset of menstruation. The drug is injected deep into the upper outer quadrant of the buttock or into the deltoid muscle and does not massage the area of \u200b\u200badministration to ensure slow release. If the break lasts more than 1 week, it is necessary to conduct a test before the injection to exclude pregnancy. In non-breastfeeding mothers, Depo-Provera injection is given 3 weeks after delivery, and when breastfeeding, after 6 weeks.
Since it is easy enough to comply with the conditions for administering the drug, the degree of inefficiency is minimal: 0-0.7 per 100 women per year (0.3 per 100 women receiving the drug). Body weight, concomitant use of drugs do not affect effectiveness. However, due to the presence of side effects, only 50-60% of patients continue taking it. The main problem leading to unwillingness to continue taking the drug is bleeding, which occurs in 50-70% of patients in the first year of administration. Other side effects include weight gain (2.1 kg per year), dizziness, abdominal pain, tearfulness, and possibly depression. Another negative point of Depo-Provera administration is the delayed restoration of fertility after cessation of intake. Ovulation occurs when the level of the hormone in the blood drops to 0.1 ng / ml, and it takes a long time from the moment you stop taking it until ovulation occurs. Only in 50% of patients ovulation occurs 6 months after the drug is discontinued, and although the use of medroxyprogesterone acetate does not cause infertility, the onset of a desired pregnancy can be delayed by more than 1 year. (The duration of the release of the drug from the injection site is unpredictable.) After the first year of use, menstruation stops in 60% of women, and after 5 years of taking amenorrhea in 80% of women, which can be regarded as an additional positive effect. Other benefits of using medroxyprogesterone acetate are the prevention of iron deficiency anemia, ectopic pregnancy, pelvic inflammatory disease, and endometrial cancer. In addition, Depo-Provera is recommended for contraception in women with sickle cell anemia (reduces the number of crises) and epilepsy (lowers the threshold for convulsive sensitivity). The drug is used in the treatment of dysmenorrhea and hyperplasia or endometrial cancer.
An important problem with Depo-Provera is the development of osteopenia with possible subsequent progression to osteoporosis. In some studies, a possible negative effect of the drug on bone tissue was noted. In a prospective study, it was found that patients taking the drug after 12 months showed a decrease in bone density of 2.74%. Nevertheless, after examination after 30 months of patients who stopped taking the drug, it was found that the mineral density of bone tissue in them does not differ from that of women who did not take the drug, which indicates the restoration of bone loss and the minimal clinical significance of these losses. A multicenter study currently underway to evaluate BMD in both women receiving and not receiving a drug will clarify the effect of Depo-Provera on bone tissue. IPC was also studied in adolescents, since this age accounts for the main period of bone mineralization. A small prospective study revealed a decrease in BMD of 1.5-3.1% against the background of 1 and 2 years of taking Norplant, compared with an increase in BMD of 9.3% and 9.5% in the control group. Perhaps the same side effect is observed with the use of other progestins, and this should be studied in a prospective multicenter study on the use of Depo-Provera in adolescents. Although one of the possible reasons for the decrease in BMD is a lower estrogen content, another no less probable hypothesis is the theory of medroxyprogesterone-dependent glucocorticoid activity, which leads to a violation of the differentiation of osteoblasts. Other potential side effects include changes in the lipid profile (increased LDL and lower HDL) and a slight increase in the risk of developing breast cancer. The relationship between the incidence of breast cancer and Depo-Provera is minimal in the first 4 years of use, there is no risk after 5 years of use. Paradoxically, medroxyprogesterone acetate has been used to treat breast cancer metastases.

Combined
In order to avoid breakthrough irregular bleeding when using Depo-Provera, monthly injectable combination injections were created (Lunelle1). The effect on the menstrual cycle is the same as when using combined oral contraceptives. Monthly bleeding comes 2 weeks after the injection. The main contingent for the use of drugs are adolescents and women who find it difficult to comply with more precise conditions for taking drugs. Lunelle is an aqueous solution containing 25 mg of medroxyprogesterone acetate and 5 mg of estradiol cypionate in 0.5 ml. In women who regularly receive Lunelle, estradiol peaks on the 2nd day after the third injection and is 247 pg / ml (similar to the ovulatory peak). The content of estradiol returns to its original level 14 days after the last injection (100 pg / ml); a decrease in estradiol concentrations leads to menstrual bleeding (2-3 weeks after the last injection). The peak concentration of medroxyprogesterone acetate (2.17 ng / ml) occurs on 3/2 day after the third injection. The average concentration of medroxyprogesterone acetate is 1.25 ng / ml, and by the 28th day of the cycle its content decreases to 0.44-0.47 ng / ml (the level necessary for the contraceptive effect is 0.1-0.2 ng / ml ) In women who received injections for a long time, the earliest restoration of ovulation is observed 60 days after the last injection. The mechanism of action is the same as that of combined oral contraceptives.
Lunelle is injected intramuscularly into the buttock or deltoid muscle every month. The first injection should be done on the 5th day of the menstrual cycle. Even though a pharmacokinetic analysis indicates a delay in ovulation, a 5-day break is recommended. The degree of inefficiency is 0.1 per 100 women per year. Neither body weight nor concomitant use of drugs affects effectiveness. These contraceptives have the same advantages as oral contraceptives and do not require observance of the exact conditions of admission, however only 55% of women continue taking them. This may be due to side effects similar to those of combined oral contraceptives, and the monthly need to make injections.
A small number of studies have been conducted to study the potential risk of drug use. This risk is probably similar to that of combined oral contraceptives, with a potentially lower frequency of deep vein thrombosis due to the lack of the effect of the first passage through the liver. If you stop taking Lunelle, your desired pregnancy may be delayed 3-10 months after the last injection.

Subcutaneous implants

The Norplant package contains 6 capsules (34 mm long, 2.4 mm in diameter), each of which contains 36 mg of levonorgestrel (216 mg in total). The main contingent for its use are women who have contraindications or side effects from exposure to estrogen, women in the postpartum period or nursing mothers, teenage mothers. This method provides long-term (up to 5 years), but quickly reversible contraception. The benefits, side effects, risks and contraindications are similar to those of oral progestin-based contraceptives. The main disadvantage absent in oral progestins is the surgical installation and removal of the rods. The new drug, Norplant II, consists of 2 rods (4 cm long, 3.4 cm in diameter) and contains 50 μg / dl norgesterl (released over 3 years). The two-core system has a similar mechanism of action and side effects, like its predecessor. However, rods are much easier to insert and remove than capsules.
During the first 24 hours, serum concentrations of levonorgestrel are 0.4-0.5 ng / ml. During the first year, 85 mcg of levonorgestrel is released from the capsule per day (equivalent to the daily dose of progestin-based oral drugs), and then for 5 years - 50 mcg daily. The average progestin content after 6 months is 0.25-0.6 ng / ml and gradually decreases to 0.17-0.35 ng / ml. A content of levonorgestrel below 0.2 ng / ml leads to an increase in pregnancy. The implantation site (leg, forearm, or shoulder) does not affect the concentration of progestins in the blood. Although a sufficient level of progestins is achieved to suppress ovulation in the first 24 hours, it is recommended to use an additional method of contraception within 3 days after the drug is established. When the implant is removed, the progestin content rapidly decreases and is not determined after 96 hours. As a result, 1 month after the removal of the implant, most women experience ovulation.
The contraceptive effect of Norplant is achieved through several mechanisms. In the first 2 years, the concentration of levonorgestrel is high enough to suppress the increase in LH concentration - most likely the inhibition occurs at the hypothalamic level - and thus ovulation is suppressed. Nevertheless, the resulting low doses of progestins are not enough to affect FSH. The estradiol content corresponds to that in women with a normal ovulatory cycle. In addition, there are uncontrolled rises (often long) and a decrease in serum estrogen concentrations that can trigger bleeding. After 5 years, more than 50% of the cycles are ovulatory. However, ovulatory cycles during the use of Norplant are often accompanied by luteal phase insufficiency. Other mechanisms to achieve a contraceptive effect are similar to those of oral progestin contraceptives and include changes in the viscosity of cervical mucus, damage to the endometrium, changes in contractility of the fallopian tubes and uterus.

(module direct4)

Inefficiency is 0.2-2.1 cases per 100 women per year (0.9 per 100 who received the drug). As in the case of oral progestins, body weight affects the content of active substances in the blood and can lead to increased inefficiency at the 4-5th year of use. As with the use of oral progestin drugs, the frequency of ectopic pregnancy with drug inefficiency increases to 20% (total prevalence of 0.28-1.3 cases per 1000 women per year). 33-78% of women continue to use the drug, and this indicator depends on age, approximately 10-15% of women per year stop taking it. The most common side effect is a violation of the regularity of the menstrual cycle, which is observed in 40-80% of patients, especially in the first 2 years of admission. The frequency of irregular menstruation with the use of Norplant is similar to that with Depo-Provera. However, Norplant is significantly different in that in the first 5 years amenorrhea develops only in 10% of cases. Other side effects include: headaches (30% of the reasons for discontinuation), weight gain, mood instability, tearfulness and depression, as well as the formation of ovarian cysts (an increase of 8 times), breast engorgement, acne, galactorrhea (if the drug established before the cessation of lactation), excessive hair growth, pain and other adverse reactions at the implantation site (0.8% refusal to continue using the drug).

Transdermal patches

Transdermal patch (Evra) is another option for contraception. A strip of patch 20 cm 2 in size consists of a protective layer, a middle (drug) layer and a strip that is removed before use. The system daily releases 150 μg of norelgestromine (an active metabolite of norgestimate) and 20 μg of ethinyl estradiol into the systemic circulation. The main patient population is similar to that for Lunelle. One of the advantages of this system compared to Lunelle is the lack of intramuscular injection and, as a result, greater patient autonomy. The patch is attached once a week for 3 weeks, followed by a week free of the patch, during which menstrual bleeding occurs. The patch should be changed on the same day of each week. The mechanism of action, contraindications and side effects are similar to oral contraceptives.
When using a transdermal patch, the peak concentrations of ethinyl estradiol and norelgestromine are 50-60 pg / ml and 0.7-0.8 ng / ml, respectively. The uniqueness of the releasing system allows you to maintain constant concentrations of hormones throughout the cycle. On the seventh day after application, hormone concentrations are sufficient to suppress ovulation for another two days. With prolonged use, the minimum cumulative effect of norelgestromine and ethinyl estradiol is noted. The concentration of hormones released by the system is not affected by the environment, physical activity, or where the patch is attached (stomach, buttocks, arms, trunk). Attachment is usually very reliable in all conditions, including exercise, swimming, sauna, bathroom. A complete separation is observed in 1.8% of cases, partial in 2.9%.
Inefficiency is observed in 0.7 per 100 women per year under ideal conditions of use. Body weight does not affect efficiency. Understanding and observing the conditions for ideal use is observed in 88.1-91% of patients, which significantly differs from the results when using oral contraceptives (67-85%), especially among women under 20 years of age. Side effects when using patches are similar to those when using oral contraceptives, with the exception of a slightly more frequent bleeding in the first 1-2 months (12.2% vs 8.1%) and a smaller number of cases of engorgement of the mammary glands (6.1% vs 18 ,8%). The frequency of occurrence of allergic skin manifestations is 17.4%, a mild reaction is noted in 92% of cases, and entails cessation of use in 2% of patients.

Vaginal rings

Since the 90s, it was known that steroids are rapidly absorbed from the vagina and enter the systemic circulation. In a 1960 study, it was found that from silicone uterine rings containing sex steroids, active substances are released slowly and continuously. These studies have contributed to the creation of contraceptive vaginal rings.
As with oral contraceptives, there are combination drugs and systems based on progestins only. Progestin-based vaginal rings have been produced since the 1970s. However, their use was associated with the occurrence of serious menstrual irregularities. Combined drugs were later created. The last (2002) FDA-approved combination vaginal ring is NovaRing.
NovaRing consists of ethylene vinyl acetate and releases 0.015 mg of ethinyl estradiol and 0.12 mg of ethonogestrel daily. Maximum serum hormone concentrations are reached 1 week after ring establishment. The ring provides for 21 days of use, then is removed for 1 week for the onset of menstrual bleeding. This tool is able to inhibit ovulation within 3 days after insertion, ovulation occurs 19 days after ring removal. The mechanism of action, contraindications and risks are similar to those of oral contraceptives. However, when evaluating the systemic effect, it is seen that when using vaginal rings, the dose of estrogen is only 50% of the total ethinyl estradiol content when taken orally (15 μg in the ring compared to 30 μg of ethinyl estradiol in oral contraceptives).
The degree of inefficiency is similar to that of oral contraceptives. Use continues to 85.6-90% of patients. Acyclic bleeding occurs rarely (5.5%), in addition, the drug is well tolerated, so cases of discontinuation of use are only 2.5%. Although the side effects are similar to those for oral contraceptives, the regulation of the cycle improves. The frequency of vaginal discharge is 23% compared with 14.5% when using oral contraceptives. The ring does not affect intercourse (1-2% of patients feel discomfort), however, it can be removed for 2-3 hours of sexual contact without changing the effectiveness.

Intrauterine device

Intrauterine devices (IUDs) are another contraceptive option that has been used in the clinic since the 1960s. Previously, these products were made of plastic (polyethylene) impregnated with barium sulfate to create radiopaque. Other tools were later created, such as the IUD, called Dalkon Shield, introduced by Dalkon Corporation. After the beginning of the use of this spiral, the frequency of inflammatory processes in the pelvic region increased, associated with the features of the thread for removing the spiral1. Moreover, after the use of this IUD, a large number of cases of uterine infertility and septic abortion were observed, as a result, many lawsuits were conducted. As a result, despite the safety and effectiveness of modern intrauterine devices, their use in the United States is minimal - less than 1% among married women.
Currently, the United States uses two types of intrauterine devices: copper and hormone-containing spirals. The latest FDA-approved intrauterine system developed contains levonorgestrel (Mirena) and is designed for 5 years of use. In some studies, it has been demonstrated that this tool, unlike Dalkon Shield, is absolutely safe and effective. These remedies are indicated for women who need highly effective and long-lasting, but quickly reversible contraception.
Copper-containing IUDs (TSi-380A) are T-shaped. The mechanism of action is based on a spermicidal effect arising from a sterile inflammatory reaction that occurs due to the presence of a foreign body in the uterine cavity. In the presence of many white blood cells and phagocytes, spermatozoa die due to phagocytosis. The amount of copper entering the body due to its release from the spiral is less than its content in the daily diet. Nevertheless, when it is released in sufficient quantities, salts are formed that damage the endometrium and cervical mucosa. Sperm transport is significantly reduced, limiting their access to the fallopian tubes.
There are intrauterine devices that release two types of hormones: progesterone (Progestasert) or levonorgestrel (Mirena). Progestasert contains progesterone released at a dose of 65 mg / day (dose for 1 year). The drug is introduced into the uterine cavity, provokes decidualization and atrophy of the endometrium. When using Progestasert, the serum content of progesterone does not change. The main mechanism of action is the exclusion of the possibility of implantation. Mirena contains 52 mg of levonorgestrel, which is gradually released at a dose of 20 mcg / day (over 5 years). Unlike Progestasert, in this case, the systemic effect of levonorgestrel inhibits ovulation for half the duration of use. Although women can continue to menstruate, follicular growth is suppressed in about 40%, and luteinization of neovulating follicles develops in more than 23%. Other mechanisms of action of Mirena are similar to those for Progestasert and oral progestin contraceptives. Mirena has an additional advantage, significantly reducing the number of menstrual bleeding, and is used to treat menometrorrhagia.
Intrauterine devices should be injected into the uterine cavity on the 7th day of the menstrual cycle or on any day of the postpartum period. The contraceptive effect occurs immediately after the establishment of the drug. Inefficiency for 1 year of use is 0.5-0.8% for TSi-380A, 1.3-1.6% for Progestasert and 0.1-0.2% for Mirena. Spontaneous prolapse of the IUD occurs in about 10% of cases.
In the case of pregnancy in the presence of an intrauterine device, the frequency of an ectopic pregnancy is 4.5-25%. The frequency of an ectopic pregnancy varies depending on the type of IUD. For Progestasert, this number is significantly higher (6.8 per 1000 women per year), which is most likely due to the limitation of the mechanism of action of this IUD only by the suppression of implantation in the endometrium; for copper- or levonorgestrel-containing IUDs, this indicator is lower (0.2-0.4 per 1000 women per year), since these drugs additionally suppress ovulation.
The desire to continue using intrauterine devices is noted in 40-66.2% of patients (Mirena). Side effects of copper-containing intrauterine devices include dysmenorrhea and menorrhagia. The most common side effect of hormone-containing products is irregular, albeit mild, menstruation. Amenorrhea is observed in 40% of women in the first 6 months of use, and in 50% of women in the first 12 months. The incidence of spotting in the first 6 months is 25% and decreases to 11% after 2 years of use. Other possible side effects of levonorgestrel include depression, headaches, and acne. There is a tendency to the formation of ovarian cysts in the near future after the establishment of levonorgestrel-containing agents, which usually pass after 4 months of use.
The use of intrauterine devices is associated with a slight risk of developing an inflammatory process in the pelvic region (within 1 month of use), loss of IUD (i.e., perforation of the uterus and exit of the IUD into the abdominal cavity; 1: 3000) and miscarriage. There was no association between the use of intrauterine devices and the development of cancer of the body or cervix.
Contraindications to the use of intrauterine devices are ongoing genital infections and unexplained bleeding.

Antipsychotic drugs prolongs new possibilities in helping people with schizophrenia. These are ampoule forms of antipsychotics for intramuscular injection. The introduction into the muscle of an antipsychotic dissolved in oil (for example, olive), allows to achieve its long-term stable concentration in the blood. Absorbing into the blood gradually, the drug exerts its effect within 2-4 weeks.

Currently, there is a fairly wide selection of long-acting antipsychotics. These are moditen – depot, haloperidol – decanoate, clopixol – depot (and prolong of clopixol, but 3-day duration of action, clopixol – acuphase), fluanxol – depot, risplept – konsta.

Conducting antipsychotic therapy with long-acting drugs is convenient because the patient does not need to constantly remember the need to take them. Only some patients are forced to take correctors of side extrapyramidal effects. The undoubted advantages of such antipsychotics in the treatment of patients in whom, upon discontinuation of drugs or a decrease in the concentration of the drug necessary for them in the blood, they quickly lose their understanding of the painfulness of their condition and refuse treatment. Such situations often lead to a sharp exacerbation of the disease and hospitalization.

Noting the possibility of prolonged-acting antipsychotics, one cannot fail to say about the increased risk of extrapyramidal side effects with their use. This is due, firstly, to the large amplitude of fluctuations in the concentration of the drug in the blood during the period between injections compared to taking tablet antipsychotics, and secondly, to the inability to “cancel” the drug already injected into the body with individual hypersensitivity to its side effects in a particular patient. In the latter case, you have to wait until the drug-prolong is gradually, within a few weeks, removed from the body. It is important to keep in mind that of the aforementioned prolonged-acting antipsychotics, only risplept-const is atypical.

Small antipsychotics.

Medium (small) antipsychotics include drugs with moderate antipsychotic and sedative properties that do not cause significant side effects. Polyvalent antipsychotics combine a powerful antipsychotic effect with a sedative or disinfectant. The group of disinhibiting antipsychotics has an activating effect mainly when administered in small doses.

The use of prolonged forms of antipsychotics significantly facilitates the implementation of long-term outpatient therapy. The slow, or retarded, effect of these compounds is associated with various mechanisms. When the active molecule is combined with carboxylic acids, esters are formed, which, due to delayed hydrolysis, gradually release the active substance from the depot. The duration of the drug is determined by the type of carboxylic acid. So, when combined with enanthic acid, the complete release of the antipsychotic occurs within 10-14 days, with unicycline within 15-21 days, with decane within 16-25 days, and with palmitic within 25-28 days. A more rare introduction of such an antipsychotic leads to an exacerbation of productive symptoms, and with more frequent administration, cumulation is possible.

Long-acting antipsychotic drugs have a number of undeniable advantages over conventional ones. They allow to ensure maximum continuity of therapeutic effect, reliable control over the administration of antipsychotics in case the patient does not have the proper understanding of the need for long-term therapy; a more stable and lower concentration of antipsychotic in the blood, which is probably associated with a lower severity of side effects; lower total dose, which also reduces the risk of late side effects.

The medicine for hypertension is prescribed if the patient is at risk. It includes people whose blood pressure constantly exceeds 160/100 mm RT. Art. Persons who are classified as low risk, experts primarily advise lifestyle correction and moderate physical activity.

If these measures do not help, doctors prescribe special drugs. What are the most effective hypertension medications?

1. Vascular tone. The greater the spasm of the vessels, the higher the pressure. This indicator depends on the condition of small arteries - arterioles.
2. Circulating blood volume. The higher this indicator, the higher the pressure.
3. Heart function. The harder it beats, the more blood is pumped. This also provokes an increase in pressure.

To choose the best medicine for hypertension, you need to see a doctor. Similar drugs are prescribed in the following situations:

• With an increase in pressure to 160-90 mm RT. st .;
• With an increase in the indicator to 130/85 mm RT. Art. - This is important for people with heart or kidney failure, as well as diabetes.

It is recommended that preference be given to medicines that need to be drunk 1 time per day, or to medicines that have an effect of 12 hours. However, in most cases, doctors prescribe combination therapy, which includes two drugs at once. This allows you to reduce the dosage and minimize the risk of side effects.

The main groups of drugs for hypertension

There are a number of tools to help relieve pressure. To get the desired result and choose the most effective medicine for hypertension, you should consult a doctor.

Beta blockers

These funds can be used for monotherapy or complex therapy. They give results in the development of a resistant form of the disease. They can be used in the presence of a history of heart attack and angina pectoris. Also, these drugs are allowed in the chronic form of heart failure and atrial fibrillation.

The mechanism of action of these funds is based on stopping the production of renin and angiotensin, which lead to vasoconstriction. These drugs block beta receptors. Beta blocker isolated therapy lasts 2-4 weeks. The doctor may then prescribe a combination with a diuretic or calcium channel blocker.

Non-selective drugs include the following:

• Carvedilol;
• Propranolol;
• Sotalol;
• Oxprenolol.

• Atenolol;
• Bisoprolol;
• Nebivolol;
• Betaxolol.

Alpha blockers

These drugs block alpha-adrenergic receptors, which provides the irritating effect of norepinephrine. This leads to a decrease in blood pressure.

An effective remedy in this category is doxazosin. It is used to eliminate bouts of high blood pressure or prolonged therapy. However, many other funds from this group are discontinued today.

Calcium antagonists

These drugs are usually divided into several categories:

• Dihydropyridines - this group includes amlodipine, nifedipine;
• Benzodiazepines - they include diltiazem;
• Phenylalkylamines - Verapamil belongs to this category.

These agents increase load tolerance. They can be used in combination with ACE inhibitors. Due to this, it is possible to avoid the use of diuretics.

Calcium antagonists are often prescribed to older people with cerebral atherosclerosis. They are used in combination with hypertension with angina pectoris or arrhythmia.

Angiotensin 2 Antagonists

These are relatively new drugs for hypertension that successfully lower blood pressure throughout the day. They can be used once a day - in the morning or before bedtime.

Candesartan has a maximum duration of action - it is up to 2 days. Also in this group there are drugs for hypertension that lower blood pressure by 24 hours.

These drugs rarely provoke a dry cough. They do not cause a rapid drop in pressure and do not lead to the development of withdrawal syndrome. A lasting effect can be achieved 4-6 weeks after the start of therapy.

These modern drugs for hypertension can be used with the renal form of the disease, since they can eliminate spasm of the vessel wall. Also, these drugs can be part of combination therapy with a stable form of the disease.

Diuretics

Thiazide diuretics and sulfonamides, which are included in the category of saluretics, help to improve the synthesis and excretion of urine. This ensures a decrease in edema of the vessel wall, which leads to an increase in their clearance. Thanks to this, it is possible to reduce the pressure.

This category includes hydrochlorothiazide, hypothiazide. These substances prevent the reverse absorption of chlorine and sodium ions by the renal tubules, which provokes their elimination. Medicines from this group have no effect on normal pressure.

Sulfonamides include indapamide, arifon, indal. These funds are used for complex forms of hypertension. They can also be part of a combination treatment for the development of resistant hypertension.

Indapamide is included in the approved medications for hypertension in type 2 diabetes, because it does not affect blood glucose.

Angiotensin Converting Enzyme Inhibitors

These funds lead to the blocking of the enzyme, leading to the conversion of angiotensin to renin. Thanks to their use, it is possible to reduce the flow of blood to the heart muscle. Drugs from this group become a reliable prevention of cardiac muscle hypertrophy and restore it in the presence of this problem.

ACE inhibitors with sulfhydryl category are used to eliminate hypertensive crises. These include captopril, benazepril.

ACE inhibitors with a carboxyl group include

enalapril

Lisinopril

perindopril

So, enalapril has a positive effect on the life expectancy of patients. However, it provokes an undesirable side effect in the form of a dry cough.

How to choose a medicine for hypertension

To choose the safest medicine for hypertension, you need to see a doctor. A specialist in prescribing medications takes into account a number of criteria. These include the following:

• Patient age;
• Pathology of the cardiovascular system;
• Complications that are present in other organs.

The doctor will choose a combination treatment that includes a number of drugs. This will provide a comprehensive effect on the mechanism of the appearance of hypertension. The use of several drugs at once reduces the volume of each of them. This will reduce the risk of side effects.

List of the best drugs for new generation hypertension

Each medicine for new generation hypertension has many advantages. They include excellent effectiveness of therapy and a minimum of side effects. Today there are two categories of such drugs. These include:

• ACE inhibitors - from this group you can choose a new medicine for hypertension, such as lisinopril, monopril or prestarium;
• Calcium channel blockers - this category includes lacidipine, nimodipine, felodipine.

Effective drugs for hypertension have a gentle effect on the body. They do not lead to impaired potency or mental abnormalities. Thanks to their application, it is possible to improve the quality of life. However, such funds can not be used without a doctor's prescription.

Rapid Action High Pressure Tablets

Such drugs are required to eliminate the symptoms of a hypertensive crisis. They must be present in the medicine cabinet of every person who has arterial hypertension. First aid products include the following:

• Captopril;
• Nifedipine;
• Clonidine.

Side effects and contraindications

Contraindications directly depend on the category of the drug. However, many drugs are forbidden to use in such situations:

• Pregnancy;
• Lactation;
• Bile duct obstruction;
• Complicated diseases of the kidneys and liver;
• Bronchial asthma;
• Hypersensitivity to the components of the product;
• Decompensated heart failure;
• Age less than 18 years.

Choosing a cure for hypertension without side effects is quite problematic. Each drug can lead to undesirable health effects. The most common side effects include the following:

• Allergic reactions;
• Pain in the digestive system;
• Nausea and vomiting;
• Violation of the stool;
• Sharp drop in pressure;
• Depressive states;
• Feeling of dryness in the oral cavity;
• Sleep disturbances.

If such symptoms appear, the drug should be immediately withdrawn and consult a doctor. The specialist will be able to choose a more suitable analogue. Sometimes symptomatic therapy is required.

The safest cure for hypertension

So far, there are no cures for hypertension without side effects. Scientists have not been able to develop a substance that will bring the desired result without harm to health.

However, if we consider new drugs, they have many advantages compared with drugs of previous generations. These include the following:

• High efficiency;
• Prolonged action - this makes it possible to minimize the dosage of the drug and minimize the risk of side effects;
• Comprehensive action - this list of drugs for hypertension includes drugs that perform several functions at once.

The category of third-generation drugs includes physiotens. It almost does not provoke side effects in the form of dry mouth or increased drowsiness. This drug is allowed to use in patients with bronchial asthma and diabetes.

New agents that are successfully used to eliminate hypertension include selective imidazoline receptor agonists. They reduce pressure, have a minimum of contraindications and very rarely provoke side effects. This group includes rilmenidine and monoxidine.

New generation beta-blockers, which are actively used to combat hypertension, include nebivolol, labetalol. They rarely provoke side effects and almost do not harm human health. Using such means, it is possible to prevent the occurrence of complications of hypertension.

Reviews

Reviews of the best medicines for hypertension confirm the high effectiveness of these funds:

Marina: For the treatment of hypertension I use a new generation of drug - lisinopril. An effective remedy that helps relieve pressure. During use, there have never been any side effects, so I am very pleased with the result.

Anna: With pressure drops, I went to the doctor who diagnosed me with arterial hypertension. As a result, he appointed a whole complex of beta blockers and other drugs. After that, my condition improved significantly. Therefore, I advise everyone not to pull, but to consult a doctor in a timely manner.

Now you know how to find a cure for hypertension. In order to minimize the risk of side effects and not cause harm to health, it is very important to consult a doctor on time. Thanks to adequate and comprehensive therapy, it will be possible to improve your condition.

Popular drugs

Among the most commonly used in medical practice antihypertensive drugs in recent years:

CAPTOPRIL (capoten, tenziomin) - inhibits the formation of angiotensin-2 described in the section on the mechanism of development of hypertension and eliminates its vasoconstrictor effect on arterioles; lowers the formation of aldosterone in the adrenal glands. Indications: arterial hypertension, chronic heart failure. It has a side effect and has contraindications. With simultaneous use with potassium-sparing diuretics, hyperkalemia is possible.

CAPOSID contains captopril and a diuretic, hydrochlorothiazide (hypothiazide). Antihypertensive drug of prolonged action. It has a number of side effects and has contraindications.

ENALAPRIL (enam, enap, renitene) refers, along with capoten, to drugs that inhibit the formation of angiotensin-P and eliminate the vasoconstrictor effect of the latter. Reduces total peripheral vascular resistance, lowers blood pressure. Indications - as for capoten. It is used, like all other antihypertensive drugs, strictly as prescribed by the doctor.

ENAP-N (contains enapril and hydrochlorothiazide (hypothiazide) - a diuretic drug, which leads to a decrease in the sodium content in the vascular wall and helps to lower blood pressure.

PRESTARIUM (perindopril) reduces blood pressure due to impaired formation of angiotensin P and the elimination of its constricting effect on blood vessels (see "secondary link in the pathogenesis of hypertension"). Indications: arterial hypertension and chronic heart failure. Reduces myocardial hypertrophy. The treatment is under the supervision of a physician.

ATENOLOL (synonyms - tenolol, tenor-min, norton, Falitonsin, etc.) - cardioselective beta-blocker. It has a hypotensive effect, which stabilizes by the end of the second week of drug administration. It has significant advantages over non-selective beta-blockers, such as propronalol (obzidan, inderal). Indications: arterial hypertension, prevention of angina attacks, tachycardia. Exercise caution while taking clonidine, reserpine, alpha-methyldopa.

TENORIC (tenoretic) contains atenolol and diuretic - chlortalidone. Indications are the same as for atenolol - arterial hypertension.

METAPROLOL (betalok, corvitol, metolol, spesicor, etc.) is a selective beta-adrenergic blocking effect mainly on beta-1 receptors of the heart. Indications: arterial hypertension, prevention of angina attacks, cardiac arrhythmias, secondary prevention after myocardial infarction.

KARDURA (active ingredient - dex-zosin) exerts a vasodilating effect by selective blocking of the alpha-1-adrenergic receptors of the heart. Causes a clinically significant decrease in blood pressure as a result of a decrease in total peripheral vascular resistance. Indications: arterial hypertension.

Blood pressure regulating agents

See also amiloride, brinaldix, veroshpiron, hypothiazide, dalargin, diltiazem, oxodoline, triamteren, furosemide, cyclomethiazide, etc.

Beta-blockers

ATENOLOL (Atenolol)

Synonyms:  Apo-Atenol, Atenobene, Atkardil, Betakard, Dignobeta, Catenol, Tenolol, Tenormin, Falitonzin, Ormidol, Atenol, Blockium, Catenolol, Hypoten, Myocord, Normiten, Prenormin, Telvodin, Tenoblock, Tenzrenen, Atorinen, Velorinor, Velorinor, Velorinor, Velorinor, Velorinor, Velorinor, Velorinor, Velorinor, Velorin Atenosan, Blockotenol, Vazkoten, NovoAtenol, Pantanol, Prikorm, Sinar, Unilok, etc.

Pharmachologic effect.  Atenolol is a selective (cardioselective) beta! Adrenoblocker.

Differs in duration of action. The half-life (time for which ‘/ 2 doses of the drug is excreted) is 6–9 hours.

Indications for use.

It can be prescribed to patients with a tendency to bronchospasm (narrowing of the lumen of the bronchi) and spasm of peripheral vessels with a lower risk than non-selective beta-blockers.

Dosage and administration.  Assign inside in a single dose of 0.05-0.1 g (50-100 mg \u003d 1 / 2-1 tablet). Take a long time.

Side effect and contraindications.

Release form.  Coated 0.1 g tablets.

Storage conditions.

ATEGEXAL COMPOSITUM (Atehexal compositum)

Pharmachologic effect.

Indications for use.

Dosage and administration.

Side effect.

Contraindications

Release form.

Storage conditions.  List B.

Athehexal compositum

Pharmachologic effect.  Combined antihypertensive drug. Atenolol, which is part of it, is a cardioselective beta-blocker (selectively blocking heart beta-adrenergic receptors), reduces the heart rate, reduces stroke and minute volumes of the heart, and reduces the activity of renin (an enzyme involved in the regulation of blood pressure) in blood plasma. Oxodolin is a diuretic (diuretic) and natriuretic (excreting sodium ions in the urine) long-acting drug that inhibits the reabsorption (reabsorption) of sodium mainly in the distal

ny (located on the periphery of the kidney) tubules of the kidneys.

Indications for use.  Arterial hypertension (persistent rise in blood pressure) in the absence of a sufficient effect from the separate use of each of the active substances that make up the drug.

Dosage and administration. The dose of the drug is set individually. The drug is taken 1 time per day before breakfast, without chewing. Drink plenty of fluids. The daily dose is 1 tablet containing 100 mg of atenolol and 25 mg of oxodoline, or 50 mg of atenolol and 12.5 mg of oxodoline.

During treatment, periodic monitoring of liver function indicators, as well as electrolyte (ionic) blood composition (especially potassium levels), glucose, uric acid, lipids (fats), and plasma creatinine is necessary.

With the simultaneous administration of insulin or oral antidiabetic agents, blood glucose levels should be regularly monitored.

If, after prolonged treatment, there is a need to cancel the drug, this should be done as slowly as possible, since a sudden withdrawal can lead to a decrease in blood supply to the myocardium (heart muscle) and a rapid increase in blood pressure.

Side effect.  Arterial hypotension (lowering blood pressure), bradycardia (rare pulse), fainting, atrioventricular conduction disturbances (conduction of excitation along the cardiac conduction system), heart failure. In rare cases - Raynaud's syndrome (narrowing of the lumen of the vessels of the limbs). Hypokalemia, hyponatremia, hypomagnesemia, hypochloremia (decrease in blood levels of potassium, sodium, magnesium, chlorine ions), rarely - hyperkalemia (increase in blood potassium). Feeling of fatigue, dizziness, feeling of stupor, headache, nightmares, hallucinations (delirium, visions acquiring the character of reality), depression (state of depression). Nausea, vomiting, constipation, or diarrhea. Bronchospasm (a sharp narrowing of the lumen of the bronchi) in predisposed patients. Rarely - anemia (a decrease in hemoglobin in the blood), leukopenia (a decrease in the level of white blood cells in the blood), thrombocytopenia (a decrease in the number of platelets in the blood), skin

rash. In some cases, acute nephritis (inflammation of the kidney), vasculitis (inflammation of the walls of blood vessels), impaired liver function.

Contraindications Heart failure; acute myocardial infarction; violations of atrioventricular and / or sinoatrial conduction (conducting excitation along the conduction system of the heart); sinus node weakness syndrome (heart disease, accompanied by rhythm disturbance); bradycardia (with a resting heart rate of less than 50 beats / min); predisposition to bronchospasm; severe peripheral circulatory disorders; pronounced renal dysfunction (creatinine clearance / rate of blood plasma purification from the final product of nitrogen metabolism of β-creatinine / less than 50 ml / min); glomerulonephritis (kidney disease); severe impaired liver function, accompanied by impaired consciousness; hypokalemia; acidosis (acidification of the blood); gout; concomitant use of MAO inhibitors; pregnancy; lactation; hypersensitivity to atenolol and other beta-blockers, oxodoline and other thiazide and loop diuretics.

The drug in some cases may impair the patient's ability to drive a car or other mechanisms. This effect is enhanced by alcohol.

Release form.  Tablets in a package of 30, 50 and 100 pieces. 1 tablet contains 50 mg of atenolol and 12.5 mg of oxodoline or 100 mg of atenolol and 25 mg of oxodoline.

Storage conditions.  List B.

CALBETA (Calbeta)

Pharmachologic effect.  The combined drug, which includes selective (selective) beta-blocker atenolol and calcium channel blocker nifedipine. It has a pronounced hypotensive (lowering blood pressure) effect. It also has antianginal (anti-ischemic) and antiarrhythmic activity. With prolonged course use, it causes a regression of hypertrophy (a decrease in hypertrophy / a sharp increase in size /) of the left ventricle of the heart, which developed as a result of a prolonged rise in blood pressure.

Indications for use.  Arterial hypertension (persistent rise in blood pressure), angina pectoris, especially in the case of combination with hypertension (increase in blood pressure) or extrasystole (disturbance of the heart rhythm).

Dosage and administration.  Assign 1 capsule 1 or 2 times a day.

Treatment with the drug should be carried out under the control of water-electrolyte (water-ion) balance.

Side effect. Fatigue, headache, hyperemia (redness) of the face, feeling of heat (these side effects are usually noted at the beginning of treatment and disappear on their own after 1-2 weeks of course). Perhaps the development of hyponatremia, hypokalemia and hypochloremia (lowering blood levels of sodium, potassium and chlorine), alkalosis (alkalization). Rarely, dyspeptic symptoms (digestive disorders). Perhaps a violation of conduction (conduction of excitation along the heart muscle).

Contraindications  Sinus bradycardia (rare rhythmic pulse), myocardial conduction disturbances, severe heart failure, hypersensitivity to the drug.

Release form.  Capsules containing 0.05 g of atenolol and 0.02 g of nifedipine, in a package of 10 pieces.

Storage conditions.  List B. In the dark place.

LABETALOL (Labetalol)

Synonyms:  Abetol, Albetol, Amipress, Ipolab, Labetol, Labrokol, Lamitol. Operkol, Presolol, Trandat, Trandol, etc.

Pharmachologic effect.  Belongs to the "hybrid" adrenergic blocking, blocking both beta and alpha adrenergic receptors.

The combination of beta-adrenergic blocking and peripheral vasodilator (vasodilator) action provides a reliable antihypertensive (lowering blood pressure) effect. The drug does not significantly affect the amount of cardiac output and heart rate.

Indications for use.  Labetalol is used to lower blood pressure in hypertension (a rise in blood pressure) of varying degrees. Unlike conventional beta-blockers, it has a quick antihypertensive effect.

Dosage and administration.  Inside, it is prescribed in the form of tablets (with food) 0.1 g (100 mg) 2-3 times a day. In severe forms of hypertension, the dose is increased. The average daily dose of 600-1000 mg in 2-4 doses. For maintenance therapy, use 1 tablet (100 mg) 2 times a day.

In case of hypertensive crises (fast and sharp rise in blood pressure), labetalol is administered intravenously slowly at a dose of 20 mg (2 ml of a 1% solution). If necessary, repeat the injection at intervals of 10 minutes It is preferable to administer labetalol as an infusion. For this, a 1% injection solution in ampoules is diluted with an isotonic solution of sodium chloride or glucose to a concentration of 1 mg / ml. Enter at a rate of 2 ml (2 mg) per minute. Usually the required dose is 50-200 mg.

Intravenous administration is carried out in a hospital (hospital) with the patient lying down (due to a rapid and significant decrease in blood pressure).

Side effect.  When using labetalol, dizziness, headache, nausea, constipation or diarrhea, a feeling of fatigue, and itching are possible.

Contraindications Labetalol is contraindicated in patients with severe heart failure, atrioventricular block (impaired conduction of excitation in the heart).

The drug usually does not cause bronchospasm (a sharp narrowing of the lumen of the bronchi), but caution should be exercised in patients with bronchial asthma.

Release form.  Tablets of 0.1 and 0.2 g (100 and 200 mg) of 30 and 100 pieces per pack; 5% solution for injection in ampoules of 5 ml (50 mg per ampoule).

Storage conditions.  List B. In the dark place.

METIPRANOLOL (Metipranolol)

Synonyms:  Trimepranol.

Pharmachologic effect.  Non-selective (non-selective) beta-blocker. In its action, it resembles propranolol. By beta-adrenergic blocking action is more active than propranolol. According to the negative inotropic effect (decrease in heart rate) is much weaker than propranolol. The onset of hypotensive (lowering blood pressure) action 1-2 hours after taking the drug inside. The negative chronotropic effect (decrease in heart rate) of metipranolola lasts 10 hours.

Indications for use.  Hypertension (persistent rise in blood pressure).

Dosage and administration.  As a hypotensive (lowering blood pressure) funds are prescribed 10 mg 2-3 times a day. After a weekly interval, the dose can be increased. The maximum daily dose is usually 80 mg.

Side effect and contraindications. See Propranolol.

Release form.  Tablets of 10 and 40 mg.

Storage conditions.  List B. In the dark place.

METOPROLOL (Metoprolol)

Synonyms:  Betalok, Bloksan, Spesikor, Protein, Lopresor, Neoblok, Desresol, Selopral, Vazokardin, Corvitol, Metohexal, Metolol, etc.

Pharmachologic effect.  It is a selective (cardioselective) beta! Adrenoblocker (selectively blocking cardiac beta-adrenergic receptors).

Indications for use.  Applied with hypertension (persistent increase in blood pressure).

Dosage and administration.  Applied orally and intravenously. Inside appoint a dose of 100-200 mg per day - 2-3 doses. If necessary, increase the dose. The maximum daily dose -: 400 mg. Sustained-release tablets (long-acting) are prescribed 1 tablet 1 time per day. In the morning after a meal.

When using a daily dose of more than 200 mg, the cardioselective effect of the drug decreases, that is, it blocks beta and beta2-adrenergic receptors.

If necessary, the daily dose can be prescribed in 1 dose in the morning. The drug is taken before or during meals, washed down with water.

In case of insufficient effectiveness, other antihypertensive (blood pressure lowering) drugs are additionally prescribed.

Side effects and contraindications are the same as with atenolol. Metoprolol should not be administered intravenously if the systolic ("upper") blood pressure is less than 110 mm Hg. Art. In patients with bronchospastic phenomena (narrowing of the lumen of the bronchi), the simultaneous administration of beta-adrenostimulating drugs is recommended.

Release form.  50 and 100 mg tablets in a package of 30; 100 and 200 pieces; 200 mg retard tablets in a package of 14 pieces; 1% solution in ampoules of 5 ml in a package of 10 pieces.

Storage conditions.  List B. At a temperature not higher than +25 "C.

NADOLOL (Nadolol)

Synonyms:  Korgard, Anabet, Betadol, Nadik, Solgol.

Pharmachologic effect.  Non-selective beta-blocker (blocks beta and beta2-adrenergic receptors). It does not have a negative inotropic effect (does not reduce the strength of heart contractions). It has a long duration of action.

Indications for use.  Hypertension (persistent rise in blood pressure) in various stages.

Dosage and administration.  Assign inside (in the form of tablets) regardless of food intake. Due to the long-term effect, it can be used 1 time (sometimes 2 times) per day. The dose is adjusted depending on the effect. With hypertension (a rise in blood pressure), 40-80 mg is prescribed once a day, gradually (at weekly intervals) the dose is increased to 160 mg per day, rarely to 240 mg (in 1-2 doses) per day. Can

use diuretics (diuretics) or vasodilators (vasodilators) at the same time.

Side effect.  When applying nadolol, in some cases, the phenomena of fatigue, insomnia, paresthesia (a feeling of numbness in the limbs), dry mouth, bradycardia (rare pulse), and gastrointestinal disturbances are possible.

Contraindications  The drug is contraindicated in bronchial asthma and a tendency to bronchospasm (narrowing of the lumen of the bronchi), sinus bradycardia (rare pulse) and heart block (violation of the excitation of the conduction system of the heart) II-III degree, cardiogenic shock, with pulmonary hypertension (increased pressure in the vessels of the lungs ), "Congestive" heart disease. It should not be prescribed to women during pregnancy and lactation. Caution is needed in renal and hepatic insufficiency, diabetes.

Release form.  Tablets of 20; 40; 80; 120 and 160 mg (0.02; 0.04; 0.08; 0.12 and 0.16 g) in bottles of 100 and 1000 pieces.

Storage conditions.  List B. At room temperature, in a dark place.

CORZID

Pharmachologic effect.  A combined drug containing nadolol and a diuretic, bendroflumethiazide.

Indications for use.  It is used to treat arterial hypertension (raising blood pressure).

Dosage and administration. Assign 1-2 tablets depending on the condition of the patient. In the future, the regimen is determined according to the instructions of the attending physician.

Side effects and contraindications are the same as with nadolol.

Release form.  Combination tablets containing 40 mg of nadolol and 5 mg of bendroflumethiazide and tablets containing 80 mg of nadolol and 5 mg of bendroflumethiazide.

Storage conditions.  List B. In a dry, dark place.

PENBUTOLOL (Penbutolol)

Synonyms:  Betapressin.

Pharmachologic effect.  Non-selective beta-blocker with moderately pronounced intrinsic sympathomimetic activity (prevents heart rate reduction, which develops as a result of blockade of beta-adrenergic receptors of the heart). Antihypertensive (lowering blood pressure) effect begins within 2 weeks of treatment, the full effect after 6-8 weeks.

Indications for use.

Dosage and administration.  Inside, 40 mg 1 time per day in the morning. After 3-6 weeks. the dose can be increased to 80 mg once a day. The maintenance dose is 20 mg per day.

The antihypertensive effect can be enhanced by a combination of: with diuretics, peripheral vasodilators, methyldopa and alpha-blockers.

Side effect.

Contraindications  Atrioventricular block (violation of the excitation of the conduction system of the heart) I-III degree; bradycardia (rare pulse - less than 50 in 1 min); heart failure; hypotension (low blood pressure), cardiogenic shock, bronchial asthma, chronic bronchitis, emphy

lung zema (increased airiness and decreased lung tissue tone).

Release form.  Tablets and dragees of 20 and 40 mg.

Storage conditions.  List B. In the dark place.

Pindolol (Pindololum)

Synonyms:  Wisken, Bloklin, Karvisken, Durapindol, Pentoblock, Pinadol, Pinbetol, Pindomeks, Pinlock, Prindolol, etc.

Pharmachologic effect.  It is a non-cardioselective beta-blocker (non-selectively blocking beta-adrenergic receptors). It has a hypotensive (lowering blood pressure) effect. Indications for use. Hypertension (persistent rise in blood pressure), hypertension crisis (fast and sharp rise in blood pressure).

Dosage and administration.  With hypertension, it is prescribed starting with 5 mg (1 tablet) 2-3 times a day; if necessary, the dose is gradually increased to 45 mg per day (in 3 divided doses). The antihypertensive effect is slightly less pronounced than with propranolol. You can combine the use of pindolol with saluretics (diuretics that enhance the excretion of sodium and chlorine) and other antihypertensive (lowering blood pressure) drugs (in reduced doses).

0.4 mg (2 ml of a 0.02% solution) is slowly injected intravenously under the control of blood pressure. If necessary, you can re-enter 1 ml (0.2 mg) after 15-20 minutes.

In case of hypertensive crises (a quick and sharp rise in blood pressure) in patients with stage I and stage II hypertension, 1 mg in 20 ml of 5% glucose solution is administered.

Side effect and contraindications. Possible side effects and contraindications are the same as when using other non-selective beta-blockers (see Propranolol).

Release form.  5, 10 and 15 mg tablets; 20 mg delayed-release tablets; oral solution with a content of 5 mg in 1 ml (0.5%) - 20 drops in 1 ml; 0.004% solution for injection in ampoules of 2 ml (0.8 mg in ampoule).

Storage conditions.  List B. In the dark place.

VISKALDIX (Viskaldix)

Pharmachologic effect.  A combined drug containing pindolol and the diuretic Brinaldix, which has a prolonged (prolonged) hypotensive (lowering blood pressure) effect.

Indications for use.  Arterial hypertension (persistent rise in blood pressure).

Dosage and administration.  Assign in an initial dose of ‘/ 2 tablet 1 time per day during breakfast. If after 2-3 weeks. there is not a sufficient decrease in blood pressure, the dose should be increased to 2-3 tablets per day in 2 divided doses (morning and afternoon).

Side effect.  Dizziness, feeling tired, dyspeptic symptoms (digestive upsets), sleep disturbances. These effects are temporary and do not require discontinuation of the drug. In rare cases, skin reactions, depression, hallucinations (delusions, visions that acquire the character of reality), thrombocytopenia (a decrease in the number of platelets in the blood), leukocytopenia (a decrease in the number of white blood cells in the blood).

Contraindications  Same as for propranolol.

Release form.  Tablets containing 10 mg pindolol and 5 mg brindaldix.

Storage conditions.  List B. In the dark place.

Propranolol (Propranololum)

Synonyms:  Inderal, Obzidan, Stobetin, Anaprilin, Propranolol hydrochloride, Alindol, Angilol, Antarol, Avlokardil, Bedranol, Betadren, Brikoran, Cardinol, Caridorol, Dederal, Deralin, Dociton, Elanol, Elib-lok, Inderex, Naproline, Naprilin, Naprilin, Naprilin, Naprilin, Napril , Propral, Pilapron, Sloprolol, Tenomal, Tiperal, Novo Prolol, Propra ratiopharm, Proprabene, Apopropranolol, etc.

Pharmachologic effect. By weakening the effect of sympathetic impulse on cardiac beta-adrenoreceptors, propranolol reduces the strength and heart rate, blocks the positive chrono- and inotropic effect of catecholamines (prevents the increase in strength and heart rate under the action of catecholamines). It reduces the contractility of the myocardium (heart muscle) and the value of cardiac output. Myocardial oxygen demand is reduced.

Blood pressure decreases under the influence of propranolol. The tone of the bronchi in connection with the blockade of beta2-adrenergic receptors increases.

With hypertension (persistent increase in blood pressure) propranolol is prescribed mainly in the initial stages of the disease. The drug is most effective in patients of a young age (up to 40 years) with hyperdynamic type of blood circulation and with an increased content of renin. A decrease in blood pressure is accompanied by a decrease in cardiac output due to a decrease in heart rate and a decrease in stroke volume of the heart. Peripheral resistance is moderately increased. The drug does not cause orthostatic hypotension (a drop in blood pressure when moving from horizontal to vertical). There is evidence of the effectiveness of the drug also in renal hypertension (persistent rise in blood pressure due to kidney disease).

Indications for use.  Hypertonic disease.

Dosage and administration.  Assign propranolol inside (regardless of the time of administration write). Usually begin in adults with a dose of 20 mg (0.02 g) 3-4 times a day. With insufficient effect and good tolerance, the dose is gradually increased by 40-80 mg per day (with intervals of 3-4 days) to a total dose of 320-480 mg per day (in some cases, up to 640 mg) with the appointment of equal doses in 3-4 doses . The drug is withdrawn gradually.

Propranolol is usually used for a long time (under close medical supervision).

In patients with pheochromocytoma (adrenal tumor), alpha-adrenergic blocking agents should be used previously and simultaneously with propranolol

The hypotensive (lowering blood pressure) action of propranolol is enhanced when it is combined with hypothiazide, reserpine, apressin and other antihypertensive drugs.

There is evidence of the use of propranolol in combination with alpha-adrenergic blocking agent phentolamine in case of hypertension (moderate and severe)

In case of an overdose of propranolol (and other beta-blockers) and persistent bradycardia is administered inside

venous (slow) solution of atropine 1-2 mg and beta-adrenostimulator isadrine 25 mg or orciprenaline 0.5 mg.

Side effect.  When using, side effects are possible in the form of nausea, vomiting, diarrhea (diarrhea), bradycardia (rare pulse), general weakness, dizziness; allergic reactions (itchy skin), bronchospasm (narrowing of the lumen. bronchus) are sometimes observed. Possible phenomena of depression (depression).

In connection with the blockade of beta2-adrenergic receptors of peripheral vessels, Raynaud's syndrome (narrowing of the lumen of the vessels of the limbs) is possible.

Contraindications  The drug is contraindicated in patients with sinus bradycardia, incomplete or complete atrioventricular block (impaired conduction of excitation along the cardiac conduction system), with severe right- and left ventricular heart failure

accuracy, with bronchial asthma and a tendency to bronchospasm, diabetes with ketoacidosis (acidification due to the excess content of ketone bodies in the blood), pregnancy, and peripheral arterial blood flow disorders. It is undesirable to prescribe propranolol for spastic colitis (inflammation of the colon, characterized by its sharp contractions). Caution is needed with the simultaneous use of hypoglycemic (lowering blood sugar) agents (danger of hypoglycemia / lowering blood sugar below normal /). In patients with diabetes, treatment should be carried out under the control of blood glucose.

Release form.  Tablets of 0.01 and 0.04 g (10 and 40 mg); 0.25% solution in ampoules of 1 ml.

Storage conditions.  List B. In the dark place

Long-acting calcium antagonists in the treatment of arterial hypertension

Martsevich S.Yu. Kutishenko N.P.

State Research Center for Preventive Medicine of the Ministry of Health of the Russian Federation, Moscow

Introduction

Antagonists calcium  - a large group of drugs whose main property is the ability to reversibly inhibit current calcium  through the so-called slow calcium  channels. These drugs have been used in cardiology since the late 70s and have now become so popular that in most developed countries occupy one of the first places in the frequency of administration among the drugs used for treatment  cardiovascular disease   . This is due, on the one hand, to high clinical efficacy. antagonists calcium. on the other hand, a relatively small number of contraindications to their purpose and a relatively small number of side effects caused by them.

Buy Sharing Antagonists calcium - A large group of drugs whose main property is the ability to reversibly inhibit the flow of calcium through the so-called slow calcium channels. These drugs have been used in cardiology since the late 70s and have so far gained so much popularity as in most developed countries. This is due, on the one hand, to high clinical efficacy. antagonists  calcium, on the other hand, with a relatively small number of contraindications to their prescription and a relatively small number of side effects caused by them.

Recently, dosage forms have been increasingly used. antagonists  calcium prolonged actions. Such dosage forms have been created for almost all currently used groups antagonists  calcium.

Classification antagonists  calcium

There are various classifications of calcium antagonists. Chemical structure   distinguish between dihydropyridine calcium antagonists (nifedipine, nicardipine, felodipine, lacidipine, amlodipine, etc.), benzodiazepine derivatives (diltiazem) and phenylalkylamines (verapamil). Calcium antagonists also distinguish by duration actions   . Short duration calcium antagonists actions  (first-generation calcium antagonists) include regular tablets of nifedipine, verapamil, diltiazem, to maintain a constant effect, they must be prescribed 3 or even 4 times a day. To calcium antagonists prolonged actions  (second-generation calcium antagonists) include either special dosage forms of nifedipine, verapamil, diltiazem, which ensure uniform release of the drug for a long time (IIa generation drugs), or drugs of a different chemical structure that have the ability to circulate longer in the body (generation IIb drugs: felodipine , amlodipine, lacidipine).

Second generation calcium antagonists are prescribed 1 or 2 times a day. The most lasting effect of all calcium antagonists has amlodipine   . its half-life reaches 35–45 hours

The main pharmacological properties

Despite a single mechanism actions  calcium antagonists at the cellular level, the pharmacological properties of various drugs in this group are quite different. The most significant differences are observed between dihydropyridine calcium antagonists (nifedipine), on the one hand, and phenylalkylamine derivatives (verapamil) and benzodiazepine derivatives (diltiazem), on the other hand.

Dihydropyridine calcium antagonists primarily act on the smooth muscles of peripheral arteries, i.e. are typical peripheral vasodilators. Due to this, they reduce arterial  pressure (BP) and reflex can increase the heart rate (HR), for which they are also called pulse-increasing calcium antagonists. Dihydropyridine calcium antagonists in therapeutic doses do not affect the sinus node and the cardiac conduction system, so they do not have antiarrhythmic properties. They also do not affect myocardial contractility.

The selectivity of action on peripheral vessels varies among different dihydropyridine calcium antagonists. Nifedipine is the least selective in this respect; amlodipine and lacidipine are the most selective. Due to the gradual onset of action and a long half-life amlodipine does not cause reflex tachycardia   or its manifestations are negligible.

Verapamil and diltiazem have a significantly less pronounced peripheral vasodilating effect than dihydropyridine calcium antagonists. In their action, a negative effect on the automatism of the sinus node predominates (due to this they are able to reduce heart rate and are called pulse-reducing calcium antagonists), the ability to slow down atrioventricular conduction, have a negative inotropic effect due to the effect on myocardial contractility. These properties bring verapamil and diltiazem closer to b-blockers.

Indications and contraindications for the appointment of calcium antagonists

All calcium antagonists have been successfully used for treatment arterial hypertension. stable angina pectoris, vasospastic angina pectoris. Pulse-reducing calcium antagonists - verapamil and diltiazem are quite widely used as antiarrhythmic drugs (for treatment supraventricular arrhythmias). These drugs, however, are contraindicated in patients with sinus syndrome, patients with impaired atrioventricular conduction. In these last two conditions (quite common in elderly patients), only dihydropyridine calcium antagonists can be used. If we recall that the use of dihydropyridine calcium antagonists is also possible in a number of situations where the use of b-blockers (peripheral circulatory disorders, obstructive pulmonary diseases, bronchial asthma) is contraindicated or undesirable, it becomes clear why calcium dihydropyridine antagonists are often the drugs of choice.

The use of pulse-reducing calcium antagonists is undesirable in patients with impaired left ventricular function, as it can cause its even worse. The use of dihydropyridine calcium antagonists in such patients is safer, however, in such cases, preference should be given to more selective dihydropyridine calcium antagonists, primarily amlodipine. In a special study PRAISE   (Prospective Randomized Amlodipine Survival Evaluation), it was demonstrated that the administration of amlodipine to patients with chronic heart failure and a significantly reduced left ventricular ejection fraction was not only completely safe, but also significantly improved life prognosis   in such patients.

Calcium antagonists in treatment arterial hypertension

All calcium antagonists have the ability to lower blood pressure in patients arterial hypertension  and are successfully used as antihypertensive drugs. It is noteworthy that the ability to lower blood pressure in these drugs is more pronounced when they are prescribed to patients with arterial hypertension  and less pronounced when they are assigned to people with normal blood pressure. High efficacy and good tolerance of calcium antagonists in arterial hypertension  made them very popular among doctors and patients. In most countries calcium antagonists continue to occupy one of the first places in the frequency of administration among drugs used for treatment  arterial hypertension .

Most researchers believe that different calcium antagonists have approximately the same hypotensive effect. Nevertheless, the impression is that the actual antihypertensive effect of dihydropyridine calcium antagonists is slightly more pronounced than pulse-decreasing calcium antagonists. According to various researchers, the number of patients who have a significant hypotensive effect (a decrease in diastolic blood pressure to 90 mm Hg or 10 mm Hg or more), when prescribing calcium antagonists, ranges from 55 to 80%, which is not differs from the results obtained with other antihypertensive drugs.

For antihypertensive drugs prolonged  It is very important that the effect completely covers the 24-hour interval and persists until the next dose. Since antihypertensive drugs are usually taken in the morning, the therapeutic effect should overlap the morning hours, since it is this period of the day that is the most vulnerable in terms of the development of serious cardiovascular complications. Modern calcium antagonists prolonged  actions (amlodipine, lacidipine) when prescribed for the treatment of hypertension clearly provide the required value of the ratio of the final effect / peak effect\u003e \u003d 0.5   . The calculation of this indicator allows to a certain extent to give a comprehensive assessment of both the magnitude and duration of the hypotensive effect of the drug. According to a number of studies, for diastolic blood pressure, the ratio of the final effect / peak effect is 0.5–1.0 for amlodipine, prescribed in a dose of 5-10 mg.

Left ventricular hypertrophy, which is a compensatory response to an increase in blood pressure over a long period of time, is now recognized as one of the serious risk factors for the development of cardiovascular complications. Available data suggest that treatment with calcium antagonists can reduce the severity of myocardial hypertrophy and thereby reduce the risk of serious cardiovascular complications. Ismail F. Islim et al. in their study showed that amlodipine after 20 weeks of therapy in an effective dose of 5-10 mg leads to a significant decrease in left ventricular myocardial mass   . a significant decrease in the thickness of the interventricular septum and the posterior wall of the left ventricle, a significant and statistically significant decrease in peripheral resistance. There were no significant changes in the size of the left ventricular cavities, ejection fraction, stroke volume and cardiac output.

As you know, there is still no consensus on which drugs should begin the treatment of arterial hypertension. As first-line drugs, diuretics and b-blockers are often called. It should be noted, however, that calcium antagonists have significantly fewer contraindications to prescription than many other antihypertensive drugs, and do not cause a number of side effects characteristic of other antihypertensive drugs.

So, calcium antagonists, unlike diuretics, do not cause adverse metabolic changes (do not affect the level of electrolytes, lipids, uric acid, blood glucose). The advantages of calcium antagonists over b-blockers in patients with obstructive pulmonary disease and peripheral arterial disease were mentioned above. Calcium antagonists never cause an angiotensin converting enzyme (ACE) inhibitor, which is so common in prescribing inhibitors, as a cough.

Since calcium antagonists prolonged  actions are part of the main drugs for the treatment of coronary heart disease, their purpose is especially indicated for patients with arterial hypertension and concomitant coronary heart disease, especially in cases where the appointment of b-blockers is contraindicated for any reason.

Benefits of Long-acting Calcium Antagonists

Sustained-release drugs were created in order to simplify the regimen of the drug up to once a day and thereby improve the patient's adherence to treatment. It is known that adherence to drugs is especially poorly performed by patients with arterial hypertension, since the disease is usually asymptomatic. Given that the treatment of arterial hypertension has been carried out for a long time, for many years, and that the success of this therapy, in particular, its effect on the prognosis of the disease, significantly depends on the regularity of treatment, it becomes clear that this property may be decisive.

The advantage of long-acting calcium antagonists is that they significantly less often than short-acting calcium antagonists give side effects (This pattern is characteristic primarily for dihydropyridine calcium antagonists). This is due to the fact that short-acting calcium antagonists quickly create a high concentration of the drug in the blood, which causes significant, sometimes excessive vasodilation and significantly increases the tone of the sympathetic nervous system. That is why the side effects of dihydropyridine calcium antagonists associated with peripheral vasodilation (tachycardia, redness of the skin, dizziness, feeling of heat) are much more common when using short-acting drugs.

In addition, long-acting calcium antagonists are drugs that can provide an adequate therapeutic effect in patients who do not always take therapy regularly, when the interval between doses of the drug can be 48 hours. It was shown that a single pass in the administration of amlodipine leads only to a small decrease in the antihypertensive effect of therapy. In a comparative study that examined the possibility of developing withdrawal syndrome with amlodipine and perindopril by Zannad F. et al. it was shown that 48 hours after the last dose of amlodipine, only a slight increase in blood pressure was observed and the systolic and diastolic blood pressure were lower in patients receiving amlodipine than in patients receiving perindopril. The absence of a sharp increase in blood pressure with an unintentional omission of the drug indicates a low likelihood of developing withdrawal syndrome while taking amlodipine and increases the safety of therapy with this drug.

The possibility and feasibility of combination therapy with calcium antagonists and other drugs

Combination therapy of arterial hypertension can be used both to achieve a more pronounced decrease in blood pressure, and to reduce the dose of the drug and reduce the likelihood of side effects.

The possibility and feasibility of combination therapy in relation to calcium antagonists should be considered differentially for different subgroups of these drugs. So, verapamil and diltiazem go well with most other groups of antihypertensive drugs, with the exception of b-blockers. In the latter case, the likelihood of side effects of each of the drugs is significantly increased. Dihydropyridine calcium antagonists, in contrast, are well combined with b-blockers. This combination not only significantly enhances the severity of the hypotensive effect, but also significantly reduces the likelihood of side effects. In particular, tachycardia, which can nevertheless occur when prescribing prolonged-acting calcium dihydropyridine antagonists, is completely eliminated when b-adrenoblocker is added to therapy.

Dihydropyridine calcium antagonists, in addition, are well combined with ACE inhibitors, diuretics. Such combinations have been successfully used in a number of large international studies.

Do calcium antagonists affect the prognosis of patients?

Since the mid-90s, there has been ongoing discussion about whether long-term use of calcium antagonists is safe. The reason for them was the data obtained back in the 80s, demonstrating the ability of short-acting calcium dihydropyridine antagonists prescribed without b-blockers to adversely affect the outcome of the disease in patients with unstable angina and acute myocardial infarction. There are no special studies proving the possibility of a negative effect of prolonged-acting calcium antagonists in patients with coronary heart disease or in patients with arterial hypertension. In 2000, a special analysis was published in Lancet magazine, which proved that prolonged use of calcium antagonists with prolonged action in patients with arterial hypertension is not only safe, but also leads to a significant decrease in the likelihood of developing a stroke and the likelihood of developing coronary heart disease   and its complications. According to this analysis, the effectiveness and safety of calcium antagonists was not inferior to those of ACE inhibitors.

The safety of long-term treatment of arterial hypertension with long-acting calcium antagonists from the dihydropyridine group confirms the safety of recently completed studies of NOT and INSIGHT. In study HOT (Hypertension Optimal Treatment) has been shown that a significant decrease in diastolic blood pressure (on average up to 82.6 mm Hg) under the influence of drug therapy with felodipine, both in the form of monotherapy and in combination with other antihypertensive drugs, leads to a significant decrease in the likelihood of cardio –Vascular complications and increase the life expectancy of patients.

In study Insight   (International Nifedipine GITS Study Intervention as a Goal in Hepertension Treatment) it was demonstrated that prolonged administration of a special dosage form of nifedipine, nifedipine-GITS (gastrointestinal therapeutic system), to patients with arterial hypertension is no less effective and safe than treatment with diuretics. An additional analysis conducted as part of this study showed that nifedipine has a positive effect on the prognosis of patients' lives, and the severity of this action of nifedipine is not inferior to that of diuretics.

Conclusion

Thus, the data available to date convincingly indicate the effectiveness and safety of treatment with calcium long-acting antagonists   patients with arterial hypertension. In some cases, when other antihypertensive drugs are contraindicated, these drugs may be the drugs of choice. The ability to prescribe these drugs once a day makes them very convenient with prolonged regular treatment.

Literature:

1. Abernethy DR. The pharmacokinetic profile of amlodipine. Burges RA, Dodd MG, Gardiner DG Pharmacologic profile of amlodipine Am J Cardiol 1989; 64: 101–201 Am Heart J 1989; 118: 1100-1103.

2. Burges RA, Dodd MG, Gardiner DG. Pharmacologic profile of amlodipine. Am J Cardiol 1989; 64: 101–201.

3. Packer M. O’Connor C. Ghali J. et. al. Effect of amlodipine on morbidity and mortality in severe chronic heart failure. New. Engl. J. Med. 1996; 335: 1107–1114.

4. Halperin A.K. Icenogle M.V. Kapsner C.O. et al. A comparison of the effects of nifedipine and verapamil on exercise performance in patients with mild to moderate hypertension. Am. J. Hypertens. 1993; 6: 1025-1032.

5. Zannad F, Matzinger A, Laeche J. Through / peak ratios of once daily angiotensin converting enzyme inhibitors and calcium antagonists. Am. J. Hypertens 1996; 9: 633–643.

6. Levy D, Garrison RJ, Kannel WB, Castelli WP: Prognostic implications of echocardiographically determined left ventricular mass in Framingham Heart Study. New Engl J Med 1990; 322: 1561-1566.

7. Dahlof B, Pennert K, Hansson L: Reversal of left ventricular hypertrophy in hypertensive patients. A meta analysis of 109 treatment studies. Am J Hypertens 1992; 5: 95–110.

8. Islim IF, Watson RD, Ihenacho HNC, Ebanks M, Singh SP: Amlodipine: Effective for treatment of Mild to Moderate Essential Hypertension and Left Ventricular Hypertrophy. Cardiology 2001; 96: 10–18.

9. Leenen FHH, Fourney A, Notman G, Tanner J. Persistence of antihypertensive effect after missed doses of calcium antagonist with long (amlodipine) vs short (diltiazem) harf – life. Br.J. Clin. Pharmacol. 1996; 41: 83–88.

10. Zannad F, Bernaud C.M. Fay R. Double – blind, randomized, multicentre comparison of the effects of amlodipine and perindopril on 24h therapeutic coverage and beyond in patients with mild to moderate hypertension. Journal of Hypertension 1999; 17: 137–146

11. Zannad F. Boivin J.M. Lorraine General Physician Investigators Group. Ambulatory 24 – h blood pressure assessment of the felodipine – metoprolol combination versus amlodipine in mild to moderate hypertension. J. Hypertens. 1999; 17: 1023-1032.

12. Hansson L. Zanchetti A. Carruthers S.G. et al. Effects of intensive blood – pressure lowering and low dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomized trial. Lancet 1998; 351: 1755-1762.

13. Brown M.J. Palmer C.R. Castaigne A. et al. Morbidity and mortality in patients randomized to double – blind treatment with a long – acting calcium – channel blocker or diuretic in the International Nifedipine GITS study: Intervention as a Goal in Hypertension Treatment (INSIGHT). Lancet 2000; 356: 366–372.

ISPOLIN - WMD prolonged action

• The most effective drugs for high blood pressure
• Quick effect pressure pills
• Long-acting Pressure Pills
• Rating of drugs (in tablets) with their description
• Combination drugs
• The combined use of several drugs
• Summary

Almost every person after 45–55 years suffers from an increase in blood pressure (abbreviated A / D). Unfortunately, hypertension cannot be completely cured, so hypertensive patients have to take pressure pills constantly to the end of their lives to prevent hypertensive crises (attacks of increased pressure - or hypertension), which are fraught with a host of consequences: from severe headache to heart attack or stroke.

Monotherapy (taking one drug) gives a positive result only at the initial stage of the disease. A greater effect is achieved with the combined use of two or three drugs from various pharmacological groups, which must be taken regularly. It is worth considering that the body gets used to any antihypertensive tablets over time and their effect weakens. Therefore, for stable stabilization of the normal level of A / D, periodic replacement is necessary, which is carried out only by a doctor.

Hypertonic should know that drugs that lower blood pressure are quick and prolonged (long) action. Preparations from different pharmaceutical groups have different mechanisms of action, i.e. to achieve an antihypertensive effect, they affect various processes in the body.  Therefore, the doctor may prescribe different drugs to different patients with arterial hypertension, for example, atenolol is better for one to normalize the pressure, and its administration is undesirable to the other because, together with the hypotensive effect, it reduces the heart rate.

In addition to directly reducing the pressure (symptomatic), it is important to influence the cause of its increase: for example, treat atherosclerosis (if there is such a disease), prevent secondary diseases - heart attack, cerebrovascular accident, etc.

The table provides a general list of drugs from different pharmaceutical groups prescribed for hypertension:

Drugs prescribed for hypertension

These drugs are indicated for the treatment of hypertension (persistent increase in pressure) of any degree. The stage of the disease, age, the presence of concomitant diseases, the individual characteristics of the body are taken into account when choosing a remedy, dosage selection, frequency of administration and combination of drugs.

Tablets from the sartans group are today considered the most promising and effective in the treatment of hypertension. Their therapeutic effect is due to the blocking of receptors for angiotensin II, a powerful vasoconstrictor that causes a steady and rapid increase in A / D in the body. Pills with long-term use give a good therapeutic effect without the development of any undesirable consequences and withdrawal syndrome.

Important: prescribe drugs for high blood pressure should only be a cardiologist or a local therapist, as well as monitor the patient's condition during therapy. An independent decision to start taking some hypertensive drug that helps a friend, neighbor or relative can lead to disastrous consequences.

Further in the article we will talk about which drugs are most often prescribed for high blood pressure, about their effectiveness, possible side effects, as well as about the schemes of combined use. You will find a description of the most effective and popular drugs - Losartan, Lisinopril, Renipril GT, Captopril, Arifon-retard and Veroshpiron.

The list of the most effective drugs for high blood pressure

Hypertension pills with quick effect

List of quick-acting antihypertensive drugs:

• Furosemide
• Anaprilin
• Captopril
• Adelfan
• Enalapril.

Drugs for fast acting hypertension

At high pressure, it is enough to put half or a whole tablet of Captopril or Adelfan under the tongue and dissolve. Pressure drops in 10-30 minutes. But you should know that the effect of taking such funds is short-lived. For example, a captopril patient is forced to take up to 3 times a day, which is not always convenient.

The action of Furosemide, related to loop diuretics, is the rapid onset of severe diuresis. Within an hour after taking 20-40 mg of the drug and in the next 3-6 hours, you will often begin to urinate. Blood pressure will decrease due to the removal of excess fluid, relaxation of the smooth muscles of blood vessels and a decrease in the volume of circulating blood.

Long-acting Hypertension Pills

List of long-acting antihypertensive drugs:

• Metoprolol
• Diroton
• Losartan
• Cordaflex,
• Prestarium
• Bisoprolol
• Propranolol.

Long-acting hypertension medications

They have an extended therapeutic effect, designed for the convenience of treatment. It is enough to take these medications only 1 or 2 times a day, which is very convenient, because hypertensive therapy is indicated continuously until the end of life.

These funds are used for long-term combination therapy for hypertension of the 2nd to 3rd degree. Features of the reception are a long-term cumulative effect. To obtain a lasting result, you need to take these drugs for 3 weeks or more, so you do not need to stop taking it if the pressure has not decreased immediately.

A list of antihypertensive drugs has been compiled, ranging from the most effective with a minimum of undesirable effects to drugs with more frequent side effects. Although in this regard everything is individual, it is not in vain that one has to carefully select and, if necessary, adjust antihypertensive therapy.

Losartan

The drug from the sartans group. The mechanism of action is to prevent the powerful vasoconstrictor action of angiotensin II on the body. This substance with high activity is obtained by transformations from renin produced by the kidneys. The drug blocks the AT1 subtype receptors, thereby preventing vasoconstriction.

Systolic and diastolic A / D decreases after the first oral administration of Losartan, the largest after 6 hours. The effect persists for a day, after which it is required to take the next dose. A stable pressure stabilization should be expected after 3-6 weeks from the start of administration. The drug is suitable for the treatment of hypertension in diabetics with diabetic nephropathy - damage to blood vessels, glomeruli, and tubules of the kidneys due to metabolic disorders provoked by diabetes.

What analogs does it have:

• Blocktran
• Lozap,
• Presartan,
• Xartan
• Losartan Richter,
• Cardomin Sanovel,
• Vasotens,
• Lakea
• Renicard.

Valsartan, Eprosartan, Telmisartan - drugs from the same group, but Losartan and its analogues are more productive. Clinical experience has shown its high efficiency in eliminating elevated A / D, even in patients with a complicated form of arterial hypertension.

Lisinopril

It belongs to the group of ACE inhibitors. The antihypertensive effect is observed already 1 hour after taking the desired dose, increases in the next 6 hours to a maximum and lasts a day. This is a drug with a long cumulative effect. The daily dosage is from 5 to 40 mg, take 1 time per day in the morning. In the treatment of hypertension, patients note a decrease in pressure from the first days of admission.

List of analogues:

• Diroton
• Renipril
• Lipril
• Licked
• Dapril
• Lysacard
• Lysinotone
• Sinopril
• Lysigamma.

Renipril GT

This is an effective combination drug consisting of enalapril maleate and hydrochlorothiazide. In combination, these components have a more pronounced antihypertensive effect than each individually. Pressure decreases gently and without loss of potassium by the body.

What are the analogues of the tool:

• Burlipril Plus,
• Enalapril N,
• Co-Renitec
• Enalapril-Acre
• Enalapril NL,
• Enap-N,
• Enapharm-N.

Captopril

Perhaps the most common drug from the group of ACE inhibitors. Designed for emergency care in order to stop the hypertensive crisis. For long-term treatment is undesirable, especially in older people with cerebral arteriosclerosis, because it can provoke a sharp decrease in pressure with loss of consciousness. It can be prescribed together with other hypertensive and nootropic drugs, but under strict control of A / D.

List of analogues:

• Kopoten
• Kaptopres,
• Alcadil
• Catopil,
• Blockordil
• Captopril AKOS,
• Angiopril
• Rilcapton,
• Kapofarm.

Arifon Retard (Indopamide)

Diuretic and antihypertensive agent from the group of sulfonamide derivatives. In complex therapy for the treatment of arterial hypertension, it is used in minimal doses, which do not have a pronounced diuretic effect, but stabilize the pressure during the day. Therefore, when taking it, you should not wait for an increase in diuresis, it is prescribed in order to lower the pressure.

• Indopamide
• Acripamide
• Perinid
• Indapamide Werth,
• Indap,
• Acripamide Retard.

Veroshpiron

Potassium-sparing diuretic. Take from 1 to 4 times a day in courses. It has a pronounced diuretic effect, but does not remove potassium from the body, which is important for the normal functioning of the heart. Applied only in combination therapy for the treatment of arterial hypertension. Subject to the dose prescribed by the doctor, it does not cause side effects, with rare exceptions. Long-term treatment in large doses (more than 100 mg / day) can lead to hormonal disorders in women and impotence in men.

Combined drugs for high blood pressure

To achieve the maximum antihypertensive effect and ease of administration, combined preparations consisting of several optimally selected components have been developed at once. It:

• Noliprel (indopamide + perindopril arginine).
• Aritel plus (bisoprolol + hydrochlorothiazide).
• Exforge (valsartan + amlodipine).
• Renipril GT (enalapril maleate + hydrochlorothiazide).
• Lorista N or Lozap plus (losartan + hydrochlorothiazide).
• Tonorma (triamteren + hydrochlorothiazide).
• Enap-N (hydrochlorothiazide + enalapril) and others.

Combined intake of several drugs for high blood pressure

Combination therapy is the most effective in the treatment of hypertension.  Achieving persistent positive results helps the simultaneous administration of 2-3 drugs necessarily from different pharmacological groups.

How to take high-pressure tablets in combination:

There are a large number of tablets for high blood pressure. With hypertension of 2 and 3 degrees, patients are forced to take medication constantly to keep their pressure normal. For this purpose, combination therapy is preferred, due to which a persistent antihypertensive effect is achieved without hypertensive crises. Prescribe any drug for pressure should only be a doctor. Before making a choice, he will take into account all the features and nuances (age, the presence of concomitant diseases, the stage of hypertension, etc.) and only then he will select a combination of drugs.

An individual treatment regimen is drawn up for each patient, which he must adhere to and regularly monitor his A / D. If the prescribed treatment is not effective enough, you should again consult a doctor to adjust the dosage or replace the drug with another. Self-medication, based on the reviews of neighbors or acquaintances, most often not only does not help, but also leads to the progression of hypertension and the development of complications.

Modern drugs for the treatment of hypertension should not only and not so much lower high blood pressure. Their task is to prevent irreversible damage to target organs, to keep target numbers of blood pressure, to prevent hypertensive crises and complications of hypertension. When prescribing a particular medicine, the doctor takes into account possible risks, tries to minimize the list of side effects. Consider the general principles of choice, a list of antihypertensive drugs of the latest generation.

On the principles of the choice of antihypertensive drugs

The initial stage of hypertension in 90% of cases is due to psychoemotional factors. The problem is exacerbated by an improper lifestyle and diet. Isolated cases of increased blood pressure develop into a disease.

Based on the nature of the disease, medications are prescribed in extreme cases. Antihypertensive drugs have an impressive list of side effects. It is recommended to influence the high pressure numbers with the help of tablets only when the patient has minimized risk factors:

• gave up alcohol and smoking;
• lost weight;
• reduced the amount of salt in the diet, diversified it with fresh vegetables and fruits;
• went in for sports.

If the lifestyle has changed, and hypertension does not recede, prescribe pills for hypertension. Principles of drug selection:

1. You need to start with half the dose. We drank - we controlled the pressure in half an hour. If there is no effect, increase the dosage.
2. It is impossible to exceed the recommended dose. The cure for pressure does not help - you need to find another drug. And start again in half dosage.
3. If the remedy does not fit due to side effects, stop taking it and consult a doctor for another prescription.
4. It is more convenient to take one medicine for pressure, and not 2-3 tablets. New drugs are combined drugs, which contain several active substances.
5. It is advisable to find a drug that must be taken once a day. Many modern drugs have a prolonged effect.
6. It is important to take high-pressure drugs daily, continuously. Even when the state of health is normal and the numbers on the tonometer are not elevated. Unauthorized breaks are unacceptable.

Hypertension can be called a purely individual disease. The same remedies well help some patients, but are absolutely ineffective in relation to the high pressure of others.

Hypertension Medication Classes

1. Diuretics. Diuretics aimed at removing excess fluid from the body. They have a number of side effects: dry mouth, tachycardia / bradycardia, dizziness, nausea, leg cramps, lethargy, and frequent mood swings.
2. ACE inhibitors. Reduce the secretion of the hormone, which causes the vessels to narrow. Of the undesirable effects - a rapid decrease in blood pressure, allergies, dry cough.
3. Beta blockers. Reduce the heart rate, as a result of which the pressure normalizes. Side effects - a strong pulse reduction, lethargy, rashes on the skin.
4. Calcium antagonists. Affect the tone of blood vessels, relaxing their walls. As a result, the pressure normalizes. Of the negative effects, we note the increase in heart rate, dizziness, strong flushing.
5. Angiotensin-2 Antagonists. They are prescribed if ACE inhibitors do not help. Drugs of this class protect the vasculature from angiotensin-2. Negative reactions of the body - nausea, allergies, dizziness.

New generation drugs directly inhibit renin activity. This is a hormone produced by the kidneys in response to a dysfunction in the body (oxygen starvation of the body). Due to increased secretion, pressure rises. Today, new tools are available for practical use.

Researchers are constantly looking for the most effective drugs that should not only alleviate the symptoms, but also reduce the risk of heart attacks, strokes, renal failure, and similar complications. The list of new generation tools is constantly growing.

In hypertension resistant to multicomponent drug therapy, selective endothelin receptor antagonists may be effective. The most effective are new tablets, including five main classes.

General principles of purpose and combination

The list of remedies for hypertension is larger. So far, blood tests have prescribed medications that have been tested for decades (a well-known composition is a new name). There are a lot of new things in this list (modern combinations, special mechanisms of action).

As a rule, doctors are guided by the following recommendations for prescribing drugs:

Concomitant diseases / complications	Hypertension medications
	Diuretics	ACE inhibitors	Beta blockers	Calcium antagonists	Angiotensin-2 blockers
Diabetes	+	+	+	+	+
A history of myocardial infarction		+	+
Heart failure	+	+	+		+
Prevention of Recurrent Stroke	+	+
Chronic kidney disease		+			+

Possible combinations of drugs of various classes:

Blood pressure class	Indications for use
Diuretics
Thiazides	Chronic heart failure, advanced age, ischemia; african race
Loop diuretics	Chronic heart failure, kidney disease
Aldosterone receptor antagonists	Chronic heart failure, a history of myocardial infarction
Beta blockers	A history of myocardial infarction, angina pectoris, tachycardia, arrhythmia; as drugs of choice - with congestive heart failure
Calcium antagonists
Dihydropyridines	Elderly, ischemia, pathology of the peripheral vascular system, atherosclerosis, pregnancy
Phenylalkylamines
Benzodiazepines	Elderly, angina pectoris, cardiac tachycardia of supraventricular nature, atherosclerosis
ACE inhibitors
With sulfhydryl group	Chronic heart failure, left ventricular dysfunction, relief of hypertensive crises, type 1 diabetes, the presence of protein in the urine, non-diabetic nephropathy
With carboxyl group	Chronic heart failure, type 2 diabetes mellitus, metabolic disorders, prevention of re-stroke, stable ischemia
AT-2 receptor blockers (sartans)	Type 2 diabetes mellitus, albumin protein in urine, renal hypertension, enlargement of the left ventricle, ineffectiveness of other drugs for high pressure

Today, sartans are the drugs of choice. Medicines have appeared in pharmacological practice relatively recently, but effectively reduce pressure. They are taken once a day and are valid 24-48 hours.

The list of drugs for hypertension

Hypertension Group	Act	List of drugs
Diuretic drugs (diuretics)	Activate the production and excretion of urine. As a result, the edema is removed from the walls of the vessels, their lumen increases - the pressure decreases.
Thiazide	Do not allow chlorine and sodium ions back into the renal tubules. Substances are removed and drag liquid.	Hydrochlorothiazide, Hypothiazide, Cyclomethiazide
Loop diuretics	Relax the smooth muscles of blood vessels, increase renal blood flow.	Torasemide Furosemide Bumetonide, Priretanide
Aldosterone receptor antagonists	Block the action of aldosterone, belong to potassium-sparing diuretics.	Eplerenone, Veroshpiron
Beta blockers	They inhibit the secretion of renin, which constricts the vessels of the hormone. Suitable for mono and combination therapy, treatment of persistent hypertension. Drugs of choice - after a heart attack, with chronic heart failure, angina pectoris, persistent atrial fibrillation.	Non-selective: Nebivolol Acridylol Carvedilol Atram Carvidil Rekardium Celiprolol. Selective: Bisoprolol Atenolol Coronal Hypertin Metoprolol Lokren.
ACE inhibitors	They block the enzyme that turns angiotensin into renin, prevent the thickening of the heart muscle, and treat its hypertrophy. Reduce blood flow to the heart.	With sulfhydryl group: Captopril Lotensin Zokardis. With a carboxyl group: Enalapril Lisinopril Prestarium Hortil Quadropril Thrandolapril.
Angiotensin-2 receptor blockers	Sartans reduce blood pressure gradually, do not provoke the effect of withdrawal. Effective in renal hypertension - relax the vascular walls. Provide a lasting effect for a month or two from the start of treatment.	Candesartan (has a maximum duration of effect - up to 48 hours); Losartan Valsartan Eprosartan Mikardis.
Calcium channel inhibitors	Increase physical stamina. They have proven themselves in the treatment of elderly patients with cerebral atherosclerosis, with arrhythmias and angina pectoris.	Amlodipine Calzigard Verapamil Cardil.

Hypertension drugs of central action:

• Clonidine. It has long been not used in standard therapy. But still has its adherents among the elderly who do not want to change treatment or are used to the active ingredients of the tablets.
• Moxonidine. Effective in metabolic syndrome and mild hypertension. It acts very softly. Analogs - Physiotens, Tenzotran, Moxonitex.
• Andipal. Easy remedy. More suitable for the treatment of vegetative-vascular dystonia. For the treatment of hypertension is not used.

A doctor should prescribe treatment and choose drugs. However, some information about medicines for hypertension will help the patient ask competent questions at the reception.

Injection contraception (IR) is used by over 18 million women worldwide. The composition of IR includes prolonged-acting progestogens, devoid of estrogenic and androgenic activity:

Depot-Medroxyprogesterone Acetate ("Chain-Provera") ..

-   norethisterone enanthate ("EET-EY"). IR contraceptive mechanism:

-   suppression of ovulation (inhibitory effect on the hypothalamic-pituitary system),

Changes in the physicochemical properties of the mucus of the cervical canal (its viscosity and fibrousness increase), preventing sperm penetration,

Violation of the level of enzymes that are "responsible" for the fertilization process,

Transformations in the endometrium that prevent implantation.

Contraceptive effectiveness IR -  0.5-1.5 pregnancies per 100 women / years.

IR usage mode:

"Depo-Provera-] 50" -  the first dose of the drug (150 mg / 1 ampoule) is administered in the first 5 days of the menstrual cycle: subsequent injections are made every 12 weeks (3 months + 5 days);

Yaeg-eya -   injections of the drug are made 1 time in 8 weeks (200 mg / 1 ampoule).

Shake the vial before administering IR. The drug is injected deep into the gluteal muscle. The injection area is not massaged. Fertility recovery occurs within 4-24 months after the last injection.

Indications:

-   the impossibility of regular daily intake of other

hormonal drugs if you want to increase the interval between births.

Late reproductive age (over 35 years old),

Contraindications to the appointment of estrogen (a number of extragenital diseases or the presence of estrogen-dependent complications in the anamnesis),

Lactation (6 weeks after birth)

Use as a “postabortion” contraception.

Contraindications:

Pregnancy

Pathological uterine bleeding of unclear genesis,

Planning a pregnancy in the near future (especially in patients aged 30 to 40 years),

Malignant diseases of the reproductive organs-n "." And systems (with the exception of endometrial cancer). And mammary glands,

NET-EN is not acceptable during lactation. Side effects:

-   menstrual irregularities (especially in the first months of contraception),

Galactorrhea,

Dizziness, headache,

Fatigue,

Irritability,

Depression,

Weight gain.

Decreased libido. Method Limitations:

-   menstrual irregularities, especially in the first months of contraception (dysmenorrhea, acyclic uterine bleeding, oligomenorrhea, amenorrhea),

The need for regular injections.

Advantages of the method:

-

Simplicity and privacy of use,

Low metabolic rate (due to lack of estrogen component),

Therapeutic effect in endometriosis. premenstrual and menopausal syndromes, dysfunctional uterine bleeding, algomenorrhea. "hyper-polymenorrhea. hyperplastic processes in the endometrium. recurrent inflammatory diseases of the internal genital organs.

-   use additional contraception within two weeks after the first injection of the drug,

Injections of the drug should be carried out every 3 months (+5 days) in a medical institution,

If any complaints appear (profuse uterine bleeding, headaches, depression, weight gain, frequent urination deserve special attention) consult a doctor.

Stop administering the drug a few months before the planned pregnancy (it must be borne in mind that fertility is restored after 4-24 months after discontinuation of injection),

With prolonged amenorrhea, consult a doctor to exclude pregnancy.

Monitoring patients using IR:

-   inspection and identification of complaints every 3 months,

With prolonged intermenstrual bleeding, it is necessary to exclude pregnancy, inflammatory processes of the genitals, organic diseases: after the exclusion of these conditions, additionally appoint ethinyl estradiol (daily from 0.05-0.1 mg) from day 7 to day 21 of the cycle (but not more than 1-2 cycles) or estradiol ( 1

zraza tablet / day) for three days; in the absence of a positive effect or excessive bleeding - introduce 5 mg of estradiol cypionate: if necessary, repeat the drug after 24 hours; ongoing bleeding is an indication for hysteroscopy with treatment and diagnostic curettage of the endometrium.

4.4. Subcutaneous implants

Norplant C ^ ogr1apG) -  manufacturer "Le1ga5 Rnpt-seips15"  Finland. It is represented by flexible silastic capsules with a length of 3.4 cm and a diameter of 2.5 mm, each of which contains 35 mg of levonorgestrel. Norplant-2 - consists of 2 capsules 44 mm long and 2.4 mm in diameter, containing 35 mg of levonorgestrel.

Contraceptive mechanism  based on the release of levonorgestrel norplant with capsules at a constant rate (30 μg / day), which provides the following effects:

Suppression of ovulation,

Change in the nature of cervical mucus, difficulty in sperm penetration,

Endometrial atrophy, which prevents implantation,

Premature luteolysis.

The contraceptive effectiveness of the norplant -  0.5-Part 5 pregnancies per 100 women / years.

The method of application. Before replanting the capsule, a detailed gynecological examination is performed. Capsules are implanted fan-shaped into the subcutaneous fatty tissue of the inner surface of the forearm through a 1 mm skin incision using a special trocar. The procedure is performed under local anesthesia in compliance with aseptic rules. Capsules should be placed shallow (after wound healing they are easily palpated through the skin) for more --^

easy to extract. The contraceptive effectiveness of nor-plant is maintained for 5 years. norplant-2 - for 3 years.

Introduction time:

-   in the first 7 days of the menstrual cycle,

Immediately after an abortion,

6-8 weeks after the birth (provided that before that the patient did not live sexually or was protected using other methods of contraception).

Delete  implants are performed under local anesthesia: a) at the request of the patient at any time, b) according to indications, c) by the end of 5 years of use.

Indications for the use of subcutaneous implants:

-   late reproductive age

The patient’s desire to increase the interval between births,

The presence of estrogen-dependent adverse reactions in history

Extragenital diseases that prevent the use of combined estrogen-progestogen drugs,

Uterine fibroids of small sizes (up to 8 weeks),

Conditions in which progestogens have a therapeutic effect (fibrocystic mastopathy, hyperpolymenorrhea, algomenorrhea, ovulatory pain).

Contraindications:

-   pregnancy,

Uterine bleeding of unknown origin,

Malignant tumors of the reproductive system. Side effects and complications:

-   menstrual irregularities (40-45%), mainly in the first 6-12 months (metrorrhagia. menorrhagia, oligomenorrhea, amenorrhea).

The inflammatory process in the field of capsule administration.

Galactorrhea.

Nausea,

Headache (5-20%), dizziness.

Acne (5-20%), hirsutism,

Weight gain

Depression

The formation of functional ovarian cysts,

Ectopic pregnancy (0.28 per 100 women / years, which is lower than the frequency of its development among women who are not protected from pregnancy).

Method Limitations:

-   the relative high cost of the drug,

Frequent menstrual irregularities. Advantages of the method:

-   high contraceptive effect,

The possibility of use in extragenital diseases, excluding the use of combined estrogen-progestogen drugs,

Minor metabolic changes in carbohydrate and lipid metabolism, the absence of adverse effects on the cardiovascular system,

Convenience associated with a single use and continuous, prolonged action,

Eliminates the need for daily intake of the drug,

Reversibility

Therapeutic effect for hyperpolymenorrhea, algomeno-rea. ovulatory pain, fibrocystic mastopathy

Reducing the risk of developing endometrial cancer. Recommendations for patients using subcutaneous implants:

-   it should be borne in mind that the maximum contraceptive effect of the drug begins 24 hours after the administration of the capsule,

Do not wet the injection site until the skin incision is completely healed,

By the end of 5 years, the capsules should be removed.

If the following complaints and symptoms appear, consult your doctor:

a) soreness, swelling, hyperemia in the area of \u200b\u200bcapsule administration.

b) lack of menstruation or heavy uterine bleeding (to exclude pregnancy or organic pathology),

c) pains localized in the lower abdomen (to exclude an ectopic pregnancy or complicated functional ovarian cysts - rupture, torsion of the “legs” of the cyst),

g) capsule expulsion,

e) migraine-like headaches, visual impairment.