Remestip

Remestip contains the component terlipressin, which is an artificial analogue of the substance vasopressin (acts as a natural hormone of the posterior pituitary lobe).

The therapeutic effect of terlipressin is based on a combination of the specific effect of the elements formed during its enzymatic cleavage. Among the notable properties of the substance emit antihemorrhagic and potent vasoconstrictor. Of the visible actions, the reduction of blood flow within the parenchyma of the internal organs is most noticeable, due to which there is a weakening of blood circulation inside the liver and pressure in the portal vein area.

Indications Remestipa

It is used for such violations:

• bleeding from the gastrointestinal tract - due to esophageal veins enlarged due to varicose veins, as well as ulcerative lesions;
• bleeding that occurs in the area of the urogenital tract - from the uterus, triggered by functional disorders, abortion, childbirth, and other causes;
• bleeding caused by surgical procedures (for example, organs in the pelvic area or peritoneum).

Locally can be used for gynecological procedures associated with the uterine cervix.

Release form

The release of the component is in the form of injectable medicinal fluid - in ampoules with a capacity of 2 or 10 ml. In a pack - 5 such ampoules.

Pharmacodynamics

Testing pharmacodynamics of drugs showed that terlipressin, like other similar peptides, provokes the development of spasm of venules with arterioles mainly inside the parenchyma of the internal organs, and in addition, a reduction in the smooth muscles of the esophageal wall and an increase in tone along with intestinal motility in general.

In addition to the effects exerted on vascular smooth muscle, the substance has a stimulating effect on the uterine smooth muscle, also in cases where the woman is not pregnant.

Testing the effect of the drug, conducted with the participation of people and animals, showed that it demonstrates the highest activity inside the skin and internal organs.

There are no clinical symptoms of antidiuretic effects of terlipressin.

Pharmacokinetics

By itself, terlipressin does not show activity on relatively smooth muscles, but it acts as a chemical depot of the components possessing medicinal activity, which are formed during enzymatic cleavage. This effect develops at a lower rate than the effect of lysine-vasopressin, but it has a longer duration.

Lysine-vasopressin is often biologically transformed inside the kidneys with the liver and other tissues.

The pharmacokinetics of the introduced element are most fully described by the 2-component model. The half-life term is 40 minutes, the metabolic clearance indicator is 9 ml / kg per minute, and the distribution volume is 0.5 l / kg. The expected plasma indicator of lysine-vasopressin is noted after about half an hour after the use of terlipressin. Cmax values are observed after 1-2 hours.

Dosing and administration

First performed in / in injections of 2 mg of the substance with a 4-hour interval. It is necessary to continue such therapy until 24 hours have elapsed from the time the bleeding was stopped (but this period should be a maximum of 48 hours). After using the initial portion, it can be reduced to 1 mg with a 4-hour interval for persons weighing <50 kg or with the development of side signs.

Bleeding associated with esophageal veins affected by varicose veins should be treated by applying a portion of 1000 mcg (adult) at 4-6-hour intervals within 3-5 days. In order to prevent recurrence of bleeding, therapy is continued for another 1-2 days from the moment it stops. The retestyp is applied bolus, in / in a way or through short infusion. The drug is administered undiluted or after dissolution using 0.9% NaCl.

For other types of bleeding in the gastrointestinal tract, the same dosage is used with the same time interval. The drug can be used to provide emergency care without reference to surgical procedures - if there is a suspicion of the presence of bleeding in the upper part of the gastrointestinal tract.

Hemorrhages that occur in the region of the internal organs of the child are stopped by administering a portion of 8–20 µg / kg with a 4–8-hour interval. The drug is used for the entire period of the presence of bleeding; to prevent the occurrence of relapses, the same measures are used as in adults. If a patient has sclerotic varicose veins inside the esophagus, a single bolus application in a dose of 20 µg / kg is required.

Bleeding associated with the urogenital tract: due to the presence of a difference in the activity of the action of endopeptidase within the blood plasma and tissues, the limits of the size of the dosage portions are quite large - 0.2-1 mg; they should be used with a 4-6 hour break.

In the case of bleeding from the uterus, having a juvenile character, dosages of 5–20 mg / kg are used.

When used locally in the case of gynecological procedures associated with the uterine neck, 400 μg of the substance is required to be dissolved in 0.9% NaCl to obtain a volume of 10 ml. It is necessary to enter means paracervical or intracervical. In this case, the therapeutic effect begins after 5-10 minutes. If necessary, the portion can be re-entered or increased.

[2]

Use Remestipa during pregnancy

Use of medication during pregnancy is impossible. It was revealed that it leads to uterine contraction and an increase in the level of intrauterine pressure during the early stage of pregnancy, and in addition it is able to weaken the intrauterine circulation. In tests on rabbits, abnormalities in the development of the fetus and spontaneous miscarriages were noted.

There is no information as to whether the medicine is excreted from the mother’s milk. In animals, the excretion of drugs with milk was not investigated. The risk of adverse effects on infants cannot be ruled out. The question of whether to stop breastfeeding or cancel treatment should be addressed, taking into account all the risk factors and benefits of each of the decisions.

Contraindications

Among the contraindications:

• strong sensitivity associated with the active component or any of the auxiliary elements of the drug;
• development of septic shock in persons with poor cardiac output.

Side effects Remestipa

Among the side effects are:

• cardiac abnormalities: arrhythmia or bradycardia is often observed, as well as ischemia manifestations in ECG. Sometimes there is tachycardia, heart failure, atrial fibrillation, extrasystoles of the ventricles, myocardial infarction, pains affecting the sternum, tachycardia of the type of pirouette and overhydration with pulmonary edema;
• problems associated with the vessels: mainly peripheral ischemia, peripheral vasoconstriction, pallor of the epidermis, and a decrease or increase in blood pressure are noted. Occasional intestinal ischemia, hot flashes, and peripheral cyanosis are observed;
• disorders of respiratory function: sometimes there is respiratory failure, bronchial spasm, difficulty breathing or stopping it, as well as pain during the respiratory process. Occasionally dyspnea occurs;
• lesions associated with the gastrointestinal tract: often there is a temporary diarrhea and transient pain in the abdominal area, having a spastic nature. Transient vomiting or nausea is sometimes observed;
• NS abnormalities: headaches often develop. Sometimes epileptic seizures are observed. A single apoplexy occurs;
• problems with metabolic processes: sometimes, in the absence of control over the indicators of fluid, hyponatremia appears;
• lesions of the subcutaneous layers and the epidermis: sometimes there is lymphangitis or local skin necrosis;
• disorders of the genitals: women often have pains of a spastic nature, affecting the lower region of the abdominal zone. Sometimes uterine ischemia develops or uterine tone increases;
• problems in the injection area: often necrosis develops in such areas.

There are some data on the development of signs of intolerance.

[1]

Overdose

It is forbidden to use portions above 2 mg for a 4-hour period, because in such cases there are severe adverse symptoms associated with the operation of the CAS.

To control the increasing values of blood pressure (which can occur with the introduction of Remestip), it is required to use sympatholytics or clonidine.

Atropine is used to eliminate bradycardia.

Interactions with other drugs

Terlipressin enhances the effect of indiscriminate β-blockers in reducing the severity of portal hypertension.

Combination with medications that provoke bradycardia (among them sufentanil and propofol) may cause the development of a severe form of this disease and a decrease in the severity of cardiac output.

[3], [4]

Storage conditions

The retestyp must be kept in a closed place from small children at temperature elevations in the range of 2-8 ° C. Substance freezing is prohibited.

During the 1st month, the drug may be contained at temperatures of not more than 25 ° C.

Shelf life

The remestip is allowed to apply for a 24-month term from the time the drug was manufactured.

Analogs

Analogues of the substance are the medicines Adipresin, Uropres, Minirin with Glipresin, and in addition D-void, H-desmopressin and Desmopressin.