Vasopressin and its analogues in shock states: a review | Annals of Intensive Care

Vasopressin (arginine–vasopressin, AVP, also called “antidiuretic hormone” ADH) is a natural hormone with potent vasoconstrictive effects. Its vasoconstrictive property was discovered in the nineteenth century by Oliver et al. after analysis of post-pituitary gland extracts [1]. While its vasoconstrictor effects are due to activation of V1a receptors, vasopressin also activates V2 and V1b as well as oxytocin receptors, thereby promoting anti-diuresis and exerting procoagulant activity. During the last three decades, its vasoconstrictor properties have prompted growing interest for its use in the management of vasodilatory shock.

In this review, we aim at describing the (patho)-physiological rationale for the use of AVP in distributive shock. Thereafter, we will report main results from animal and human studies, and describe benefits and risks associated with administration of vasopressin or its analogues. Finally, we will focus on vasopressin and its agonists use in the setting of septic shock and vasoplegic shock after cardiac surgery.

Physiology of vasopressin and its receptors

Vasopressin is a nine-amino-acid peptide, synthesized in the hypothalamus as a “pre-pro-hormone”. This precursor circulates along axons of magnocellular neurons, through the pituitary stalk, to the post-pituitary gland. Vasopressin is stored in the post-pituitary gland, mostly in the intracellular compartment. After stimulation, only 10–20% of the amount of vasopressin can be immediately released into blood circulation.

Physiologically, plasma osmolality as well as blood volume and pressure are the main regulators of vasopressin secretion. Clearly, the former is the most important one: increased plasma osmolality sensed by hypothalamic osmoreceptors, leads to a pronounced increase in the plasma vasopressin level. A 2% decrease in whole body water leads to a doubling in vasopressin level [2].

The latter, via hypovolemia and hypotension, induces stimulation of atrial volume receptors and carotid baroreceptors, which results in vasopressin secretion. Secretion of vasopressin is more sensitive to small osmolarity variations as compared to hypotension-related vasopressin release that requires large pressure and volume variations [3].

Vasopressin has a short plasma half-life of 5–15 min, its clearance mainly depending on renal and liver vasopressinases [4].

In the periphery, vasopressin binds to 3 receptor subtypes, all belonging to the family of membrane-bound G protein-coupled receptors [5]:

• V1a receptors are located on vascular smooth muscle cells, their activation causes vascular smooth cell contraction.

• V2 receptors are located on basolateral surface of renal tubular cells, mainly on collecting ducts. Vasopressin binding induces aquaporin 2 recruitment, which allows an increase in permeability of epithelial membrane to water, leading to water re-absorption.

• V1b receptors are located in the anterior pituitary and in the pancreas. Vasopressin induces corticotropic axis stimulation (increase in cortisol) and insulin secretion.

Of note, other functions have been described. Vasopressin has procoagulant property: activation of V1a receptors leads to platelet aggregation, and extra-renal V2 receptors activation induces the release of coagulation factors [6, 7]. In addition, oxytocin and vasopressin can cross-activate their respective receptors [8, 9]. Figure 1 summarizes the physiologic effects of vasopressin.

Fig. 1

Physiological effects of vasopressin. AVP Arginine VasoPressin, AQP2 Aquaporin 2. Vasopressin is synthesized in the hypothalamus and circulates along axons of magnocellular neurons to the post-pituitary gland. After stimulation, vasopressin is released into blood circulation, to 3 receptor subtypes. Binding on V1a receptors induces vascular smooth cell contraction in the periphery and on renal efferent arteriole and platelet aggregation. Vasopressin binding on renal V2 receptors causes aquaporin 2 recruitment, leading to water re-absorption and on extra-renal V2 receptors induces the release of coagulation factors. Binding on V1b receptors induces corticotropic axis stimulation and insulin secretion. During septic shock, vasopressin plasma level is low. Administration of vasopressin or its analogues induces a strong vasoconstriction, leading to an increase in blood pressure, and higher glomerular filtration rate

The ratio of V1/V2 effects reflects vascular selectivity. This ratio is close to 1 for vasopressin, in other words natural AVP has no receptor selectivity. Synthetic analogues, which have been tested in pre-clinical shock models and/or patients with vasodilatory shock of various causes, have higher vascular specificity. For example, terlipressin (Phe(2)-Orn(8)-vasotocin) has a V1/V2 ratio around 2.2 [10].

Physiopathological mechanisms involved in septic shock

Septic shock is characterized by micro- and macrocirculatory disturbances with a decrease in peripheral vascular resistance, maldistribution of cardiac output to organs, and impairment of oxygen extraction. Several mechanisms contribute to sepsis-related vasodilatation, and vasodilatation occurs despite high endogenous catecholamines levels and activation of the renin–angiotensin–aldosterone system [11, 12].

The impact of vasopressin on the vasomotor tone is marginal in healthy subjects. During shock, blood vasopressin concentration is initially high. However, for similar levels of hypotension Landry et al. showed in 19 patients with septic shock that vasopressin plasma level was inappropriately low, as compared to 12 patients with cardiogenic shock [13]. Data regarding the natural course of vasopressin level was reported in a prospective cohort of 182 patients [14]: the more serious the infection (sepsis versus severe sepsis versus septic shock), the lower the vasopressin level was. In septic shock, after an initial and transient increase, plasma levels of vasopressin decreased until day 4 [15], which coincided with a decreased post-pituitary storage [16].

In addition to the deficiency of circulating vasopressin, Landry et al. also highlighted the hypersensitivity of patients with septic shock to exogenous vasopressin administration: while arterial hypotension was corrected [13, 17] in patients with septic shock, similar infusion rates had no effect on blood pressure in healthy subjects. All these observations together with the fact that exogenous vasopressin offers an alternative mechanism of action independent of adrenergic receptor activation prompted the interest for this hormone in the management of patients with septic shock [12].

Haemodynamic effects of V1a agonist administration in septic shock

V1a agonists and cardiovascular system

In the experimental model, vasopressin administration resulted in various effects depending on the shock model and on vasopressin dose. When vasopressin was administered in hypodynamic endotoxin shock model, a decrease in cardiac output and myocardial ischaemia was observed [18,19,20]. In a hyperdynamic model of shock, the impact of vasopressin was different according to its infusion rate. High dose of vasopressin (greater than 0.15 UI/min) resulted in a decrease in cardiac output, oxygen consumption and in regional organ blood flow [21, 22]. When lower doses of vasopressin were tested (less than 0.1 U/min), mean arterial pressure was increased, without detrimental effect on cardiac output [23]. In another animal model (porcine faecal peritonitis) with infusion of low dose of vasopressin, heart rate and cardiac output were decreased without increase in troponin level nor change in myocardial relaxation, suggesting that vasopressin was safe regarding the theoretical risk of coronary vasoconstriction [24].

Exploratory clinical studies highlighted that vasopressin or terlipressin administration in septic shock patients allowed an increase in blood pressure and a decrease in norepinephrine requirement. The effect of vasopressin on cardiac output is more controversial. On one hand, non-randomized clinical studies reported a decrease in cardiac output [25, 26], on the other hand, a randomized study with small sample size did not confirm this finding. Finally, cardiac output, with similar target of blood pressure, was similar [27] or higher [28] in patients receiving vasopressin in addition to norepinephrine. Of note, vasopressin administration was safe regarding coronary circulation: its administration was not associated with differences between troponin serum levels, electrocardiogram patterns in a secondary analysis of a randomized controlled trial comparing norepinephrine and vasopressin in septic shock patients [29].

V1a agonists and splanchnic circulation

Because of its strong vasoconstrictor effect, concerns have been raised about vasopressin use and its impact on splanchnic circulation with a fear of splanchnic ischaemia [30] and liver dysfunction [31]. These arguments were turned down with experimental studies. It was demonstrated that with adequate fluid resuscitation, mesenteric flow and ileal microcirculation were preserved in a rat model of resuscitated endotoxin shock model with low doses of terlipressin [23]. These findings were in accordance with results of prospective randomized experimental study in a model of hyperdynamic porcine endotoxemia, where terlipressin administration was not associated with detrimental effect on hepatosplanchnic perfusion, oxygen exchange and metabolism [32]. Conversely, in an endotoxic pig model with high doses of vasopressin administration (0.28 UI/min), a decrease in splanchnic blood flow with an increased lactate release was observed [19]. Interestingly regarding safety concerns, clinical trials [28, 33] did not report side effects on splanchnic circulation with vasopressin administration.

V1a agonists and renal circulation

Distribution of V1a receptors in renal circulation is heterogeneous. The vasoconstrictor effect of vasopressin at low dose acts predominantly on renal efferent arterioles and has negligible effect on the afferent arterioles. This mechanism is related to a local phenomenon of nitrogen monoxide release [34, 35].

The efferent vasoconstriction induces a theoretical increase in glomerular renal perfusion pressure that results in higher glomerular filtration. Indeed, the first clinical studies confirmed this finding with increased diuresis and creatinine clearance in patients treated with vasopressin [25, 27].

V1a agonists and skin circulation

Vasopressin induces vasoconstriction of cutaneous vessels, with a dose–effect relationship. In a retrospective study, Dünser et al. reported ischaemic lesions of skin in almost one-third of patients (19/63) exposed to vasopressin [36]. Risk factors associated with the occurrence of ischaemic cutaneous lesions were overweight, high dose of norepinephrine, transfusion of platelets and fresh frozen plasma, history of peripheral arterial occlusive disease and the occurrence of septic shock. Only these last two items remained associated with the occurrence of cutaneous complications after multivariate analysis.

Current knowledge of vasopressin and analogues use in the management of septic shock

Vasopressin

Administration of vasopressin with or without norepinephrine during septic shock has been studied in large-scale studies, which assessed whether vasopressin administration could result in an improvement in survival and renal function.

Russel et al. in the VASST study (VAsopressin in Septic Shock Trial) [37], compared the effect of vasopressin administration (n = 396) versus norepinephrine administration (n = 382) in patients with septic shock, in a randomized, double-blinded placebo-controlled study. The primary endpoint was mortality at day 28. An a priori stratification with respect to severity was integrated into the study design: severity was defined according to the norepinephrine infusion rates required to maintain arterial pressure, i.e. < vs ≥ 15 µg/min. The vasopressin infusion rate was 0.01–0.03 U/min. No differences were observed between groups in survival at day 28 and 90. Furthermore, there was no difference in organ failure occurrence between groups. Of note, safety profile was reassuring with no significant difference between groups in side effects occurrence. In contrast to the authors’ initial hypothesis that the more severe patients would benefit from the vasopressin treatment, outcome did not differ in the stratum of patients with norepinephrine doses ≥ 15 µg/min; in patients with norepinephrine infusion rates < 15 µg/min, vasopressin administration was associated with significantly improved survival at day 28 (26. 5% vs 35.7%, p = 0.05) and 90 (35.8% vs 46.1%, p = 0.04). It remains an open question, whether this effect was due to vasopressin per se and/or the fact that in the less severe patients, a higher proportion could be completely weaned from norepinephrine support [38]. A post hoc analysis of VASST study according to the Sepsis-3 definition confirmed this finding [39]: while in patients, who fulfilled the sepsis-3 criteria of septic shock, i.e. arterial hypotension requiring introduction of catecholamine to maintain mean blood pressure > 65 mmHg despite adequate fluid resuscitation and hyperlactatemia > 2 mmol/L, there was no difference in mortality, survival was increased in patients with hypotension requiring vasopressors alone without hyperlactatemia.

A further post hoc analysis of the VASST trial suggested an association between the use of vasopressin and hydrocortisone: vasopressin reduced mortality in patients, who—at the discretion of the attending physician—were treated with hydrocortisone. Conversely, in patients who did not received hydrocortisone, vasopressin administration was associated with higher mortality [40].

Another post hoc analysis of the VASST trial tried to assess the impact of vasopressin on kidney (dys)function: Gordon et al. analysed the 464 patients with acute kidney injury of VASST study cohort [41], categorizing them according to RIFLE classification [42]. Patients at “Risk” stage and treated with vasopressin had significantly less worsening of renal function (progression to “injury/failure” stage) than patients treated with norepinephrine.

The potential impact of hydrocortisone treatment together with a putative beneficial effect of vasopressin on AKI prompted the design of the VANISH study [43], which compared the effects of either vasopressin or norepinephrine as the vasopressor of first choice together with hydrocortisone or vehicle using a two-by-two factorial design. No interaction was identified between vasopressin and hydrocortisone [43]. Furthermore, neither mortality nor AKI were significantly influenced; nevertheless, the authors concluded that “the confidence interval included a potential clinically important benefit for vasopressin”, which should be tested further in larger trials.

Clearly, both the VANISH and VASST trials were “negative” in the sense that no superiority of vasopressin could be demonstrated. Nevertheless, these studies showed that vasopressin is not inferior to norepinephrine either, and, that its administration was not associated with higher rates of adverse effects, especially ischaemic events. Moreover, these studies demonstrated that vasopressin allows at least a reduction of norepinephrine infusion rates and fastened weaning from norepinephrine. In the context of “decatecholaminization”, vasopressin use limits norepinephrine infusion rates and potentially its related side effects [44]. Interestingly, in a retrospective study, patients with septic shock who received fixed-dose of vasopressin in association with norepinephrine had an improve prognosis when vasopressin infusion resulted in an increase in mean arterial pressure [45].

Vasopressin analogues: terlipressin and selepressin

Synthetic analogues of vasopressin with higher vascular selectivity (V1/V2 ratio > 1) were also studied in the setting of septic shock.

In a blinded, randomized study recruiting 32 patients with septic shock, terlipressin administration in combination with norepinephrine was superior to norepinephrine alone (complication and survival at day 7), but results have to be tempered due to the small sample size [46].

In 2018, Liu et al. reported results of a randomized multicentric double-blind study, aimed at comparing terlipressin and norepinephrine as first-line vasopressor agent in septic shock [47]. In this study, 526 patients were analysed: 260 received up to 4 mg terlipressin per day, and 266 received norepinephrine. There was no difference in mortality at day 28 between groups (primary endpoint). Likewise, improvement and variation of SOFA score until day 7 were comparable. Terlipressin administration was associated with an increase in adverse effects (30% vs 12%, p < 0. 01). The most common was digital ischaemia (12.6% in terlipressin group versus 0.35% in norepinephrine group, p < 0.001). 76% of adverse effects occured during the first 24 h.

A more recent synthetic V1a agonist, selepressin, was reported, in a sheep model of faecal peritonitis, to be superior to norepinephrine and vasopressin. If, in established septic shock, selepressin maintained mean arterial pressure to a similar extent as did vasopressin and norepinephrine, selepressin administration resulted in reduced lung edema [48]. These results were in accordance with previous study, highlighting the reduced vascular leakage with selepressin administration [49].

Recently, the SEPSISACT study [50] compared with a randomized placebo-controlled trial the addition of selepressin to norepinephrine. This study was divided in two parts: the first was aimed at assessing the best-performing regimen of selepressin (between three dosing regimens of selepressin), and, in the second part, the authors compared this selepressin regimen to placebo. Among the 817 patients who completed the trial, no difference between the two groups on the primary composite endpoint was observed (ventilator and/or vasopressor free days within 30 days). Likewise, no difference in secondary endpoints was observed (mortality, need for renal replacement therapy and length of stay in the intensive care unit). Selepressin administration was not associated with higher rate of side effects.

A meta-analysis of 20 study including patients with septic shock suggested a potential improvement of survival with the use of vasopressin (9 studies) and its analogues (11 studies), when compared with adrenergic vasopressors (mostly norepinephrine). This meta-analysis underlined the additional risk of digital ischaemia [51]. In a recent meta-analysis of individual patients data from randomized studies (1453 septic shock patients) [52], no difference in mortality was found between vasopressin and norepinephrine. Furthermore, vasopressin use was not associated with more undesirable effect, but safety profiles were different: vasopressin led to more digital ischaemia, but fewer arrhythmias. This decrease in the incidence of arrhythmias was also reported in a meta-analysis dedicated to this specific question [53]. In this analysis were included randomized controlled trials aimed at comparing the association of vasopressin with norepinephrine to catecholamines alone for patients with distributive shock.

Current knowledge of vasopressin and analogues use in the management of vasoplegic shock after cardiac surgery

Furthermore, vasopressin was evaluated in the setting of vasoplegic shock after cardiac surgery. In 2003, among 48 patients with vasoplegic shock following cardiac surgery, a combination of vasopressin and norepinephrine versus norepinephrine alone showed an improvement of haemodynamic parameters, and fewer new-onset tachyarrhythmias when vasopressin was associated [28].

In VANCS trial [54], a randomized controlled monocentric study, patients in post-operative of cardiac surgery with refractory hypotension after fluid resuscitation, without cardiac output impairment (> 2. 2 L/min/m²), received vasopressin (0.01 at 0.06 U/min) or norepinephrine (10 at 60 µg/min). The primary composite endpoint (death or major complication in the 30 post-operative days) occurred more frequently in norepinephrine group than in the vasopressin group. Interestingly, patients treated with vasopressin presented less new-onset tachyarrhythmias. There were no harm effects (digital, myocardial, mesenteric ischaemia nor hyponatremia) in the vasopressin group.

Vasopressin: Pediatric Medication | Memorial Sloan Kettering Cancer Center

This information from Lexicomp^® explains what you need to know about this medication, including what it’s used for, how to take it, its side effects, and when to call your healthcare provider.

Brand Names: US

Vasostrict

What is this drug used for?

• It is used to treat low blood pressure.
• If your child has been given this drug for some other reason, talk with the doctor about the benefits and risks. Talk with the doctor if you have questions or concerns about giving this drug to your child.

What do I need to tell the doctor BEFORE my child takes this drug?

• If your child is allergic to this drug; any part of this drug; or any other drugs, foods, or substances. Tell the doctor about the allergy and what signs your child had.

This drug may interact with other drugs or health problems.

Tell the doctor and pharmacist about all of your child’s drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe to give this drug with all of your child’s other drugs and health problems. Do not start, stop, or change the dose of any drug your child takes without checking with the doctor.

What are some things I need to know or do while my child takes this drug?

• Tell all of your child’s health care providers that your child is taking this drug. This includes your child’s doctors, nurses, pharmacists, and dentists.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• Some people have had a health problem called diabetes insipidus after this drug was stopped. Signs included passing more urine; dilute urine; and signs of high sodium levels like thirst, feeling irritable, feeling very tired or weak, twitching, seizures, or passing out. Tell the doctor right away if your child has any of these signs after stopping this drug.

If your child is pregnant or breast-feeding a baby:

• Talk with the doctor if your child is pregnant, becomes pregnant, or is breast-feeding a baby. You will need to talk about the benefits and risks to your child and the baby.

What are some side effects that I need to call my child’s doctor about right away?

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your child’s doctor or get medical help right away if your child has any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of low sodium levels like headache, trouble focusing, memory problems, feeling confused, weakness, seizures, or change in balance.
• Any unexplained bruising or bleeding.
• Very bad belly pain.
• Chest pain or pressure.
• Fast, slow, or abnormal heartbeat.
• Shortness of breath, a big weight gain, or swelling in the arms or legs.
• Not able to pass urine or change in how much urine is passed.
• Change in skin color to black or purple.
• Skin sores.

What are some other side effects of this drug?

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your child’s doctor or get medical help if your child has any side effects that bother your child or do not go away.

These are not all of the side effects that may occur. If you have questions about side effects, call your child’s doctor. Call your child’s doctor for medical advice about side effects.

You may report side effects to your national health agency.

How is this drug best given?

Give this drug as ordered by your child’s doctor. Read all information given to you. Follow all instructions closely.

• It is given as an infusion into a vein over a period of time.
• It may be given into a vein by a doctor or other health care provider.

What do I do if my child misses a dose?

• This drug will be given on an as needed basis in a health care setting.

How do I store and/or throw out this drug?

• If you need to store this drug at home, talk with your child’s doctor, nurse, or pharmacist about how to store it.

General drug facts

• If your child’s symptoms or health problems do not get better or if they become worse, call your child’s doctor.
• Do not share your child’s drug with others and do not give anyone else’s drug to your child.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.
• Some drugs may have another patient information leaflet. If you have any questions about this drug, please talk with your child’s doctor, nurse, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

Consumer Information Use and Disclaimer

This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine. The use of this information is governed by the Lexicomp End User License Agreement, available at https://www.wolterskluwer.com/en/solutions/lexicomp/about/eula.

Last Reviewed Date

2020-04-07

Copyright

© 2021 UpToDate, Inc. and its affiliates and/or licensors. All rights reserved.

List of antidiuretic hormones uses and safety recommendations

ADH treats medical conditions such as diabetes insipidus, bleeding disorders, and bedwetting

Antidiuretic hormones list | What are antidiuretic hormones? | How they work | Uses | Types | Who can take antidiuretic hormones? | Safety | Side effects | Costs

Antidiuretic hormone (ADH) is used to regulate the body’s fluid balance. This hormone works with your kidneys to manage the amount of water released from your body and, in general, decreases the production of urine. ADH is often administered to treat certain medical conditions, including diabetes insipidus, bleeding disorders, and bedwetting problems. 

Continue reading to learn more about antidiuretic hormone, its uses, and its side effects.

Other antidiuretic hormones

• DDAVP (desmopressin)
• Noctivia (desmopressin)
• Pitressin (vasopressin)
• Vasostrict (vasopressin)

What are antidiuretic hormones?

ADH, otherwise known as vasopressin or arginine vasopressin (AVP), is a peptide hormone produced in the brain. Specifically, it is produced in the hypothalamus gland and stored in the pituitary gland. These glands are important parts of the body’s endocrine system, which produces and secretes hormones. ADH regulates how the kidneys concentrate urine or retain water. In turn, by regulating water retention in the body, ADH helps manage blood pressure and fluid volume. 

This hormone promotes the reabsorption of water in the kidneys and decreases the excretion of water in the urine. In other words, ADH helps conserve the fluid volume in the body and decreases water dilution of the urine caused by certain health conditions. This results in more water volume in the bloodstream, more concentrated urine, and less water loss. Higher levels of antidiuretic hormone can cause blood vessels to constrict, which increases blood pressure, and is especially useful for treating hypovolemic shock. 

In the case of diabetes insipidus, low ADH levels can result in excessive urination and thirst. Large amounts of water are then lost through urination and can lead to a depletion of body fluid (dehydration). Desmopressin, which is a synthetic and more potent version of vasopressin, is a first-line therapy for diabetes insipidus. 

How does antidiuretic hormone work?

The release of ADH from the pituitary gland is usually triggered by a decrease in blood volume or a decrease in blood pressure, which is often caused by dehydration or blood loss. The release of ADH is also sensitive to changes in osmolality, or the concentration of salt (sodium) and other electrolytes in the blood. Osmotic sensors and baroreceptors detect changes in the osmolality of the blood to regulate ADH release. 

An increase in salt concentrations in the blood can trigger the release of ADH, keeping more fluid volume in the bloodstream and combatting the effects of dehydration. Water is reabsorbed back into the blood circulation when ADH binds to receptors on the collecting ducts in the kidney. ADH stimulates the positioning of aquaporin 2 water channels into the membrane of the kidney tubules, which reabsorb water back into the blood. This action causes urine to become more concentrated.

What are antidiuretic hormones used for?

ADH medications may be prescribed to treat different conditions including:

Types of antidiuretic hormones

Vasopressin

Vasopressin is a hormone responsible for maintaining fluid balance through the reabsorption of water in the kidneys. Vasopressin is typically administered in a hospital setting as a subcutaneous (subQ) or intramuscular (IM) injection. It can also be administered as a continuous intravenous (IV) infusion. Vasostrict (vasopressin) may be used to treat diabetes insipidus or to treat low blood pressure in patients experiencing shock. 

Desmopressin

Desmopressin is a synthetic form of the antidiuretic hormone vasopressin. It is given to treat diabetes insipidus, primary nocturnal enuresis, spontaneous bleeding or hemorrhage, hemophilia A, von Willebrand’s disease, and nocturia. Desmopressin is available as an oral tablet, sublingual tablet, nasal spray, and injectable solution under different brand names. Stimate is supplied in a spray and used to stop bleeding that can occur from hemophilia A or von Willebrand’s disease. Nocdurna is provided as a tablet dissolved under the tongue and used for nocturia. DDAVP is supplied as an oral tablet, nasal spray, and injectable solution, and it can be used to manage thirst and too much urination caused by different conditions.  

Who can take antidiuretic hormones?

Adults

Antidiuretic hormone is given to adults to treat several conditions. Diabetes insipidus is treated with DDAVP nasal spray, oral tablets, or sublingual tablets. Therapy is continued until symptoms such as dehydration and increased urine production are resolved. 

In adults with mild hemophilia A or von Willebrand’s disease, Stimate, or desmopressin nasal spray, is used for short-term minor bleeding or before minor invasive procedures that could result in bleeding. 

Nocturia that remains uncontrolled despite other treatments can be managed with sublingual Nocdurna or oral DDAVP in adults.

Children

Children can safely take different forms of desmopressin. However, children tend to have more changes in fluid volume and may develop low sodium more quickly than adults. Fluid restrictions and monitoring of blood sodium levels are necessary when treating children with DDAVP. 

DDAVP can be administered as a nasal spray or oral tablet to treat bedwetting in children. Fluids should be restricted for an hour before the dose and eight hours following the dose. 

Seniors

Seniors can take desmopressin for appropriate conditions. For example, geriatric patients may be able to take desmopressin sublingual tablets for nocturia, or they may be prescribed intranasal desmopressin to treat diabetes insipidus. However, there may be an increased risk of hyponatremia, or low blood sodium levels, so blood sodium levels may need to be monitored throughout treatment. Fluid intake in seniors may also need to be decreased to avoid the possibility of water intoxication and hyponatremia. 

Are antidiuretic hormones safe?

Severe allergic reactions have occurred with desmopressin. Desmopressin administration may result in fluid retention. It should be used with caution in patients with heart failure. Some product formulations are contraindicated in patients with heart failure, uncontrolled hypertension, increased intracranial pressure, or urinary retention.  

Black Box Warnings

Desmopressin carries a Black Box Warning stating it can cause hyponatremia (low sodium levels). Patients with an increased risk of severe hyponatremia should not take desmopressin. Serum sodium concentrations should be measured before starting desmopressin and monitored during the treatment course.

Antidiuretic hormone recalls

The following list details medications that have been recalled.

Antidiuretic hormone restrictions

Antidiuretic hormones should not be taken in combination with certain medications. Certain medications may enhance the effect of antidiuretic hormones and increase the risk of water intoxication with hyponatremia. These medications include:

• Intranasal corticosteroids
• Oral corticosteroids
• Inhaled corticosteroids
• Loop diuretics
• Thiazide diuretics
• Selective serotonin reuptake inhibitors
• Tricyclic antidepressants
• Nonsteroidal anti-inflammatory drugs (NSAIDs)
• Opioid analgesics

Specific medications that may interact with antidiuretic hormone medications include:

This may not be a complete list of possible drug interactions. Consult a healthcare provider for other possible drug interactions that can occur while taking antidiuretic hormones. 

Individuals with kidney impairment are usually recommended to avoid taking an antidiuretic hormone depending on the severity of the problem. Those with a known hypersensitivity to any ingredients in antidiuretic hormone medications should also avoid treatment with antidiuretic hormones. Signs and symptoms of an allergic reaction may include trouble breathing, rash, and swelling of the face or throat. Antidiuretic hormone medications are not recommended in those with hyponatremia or a history of hyponatremia because treatment with antidiuretic hormone can increase the risk of low blood sodium levels. 

Can you take antidiuretic hormone medications while pregnant or breastfeeding?

Antidiuretic hormone medications are generally considered safe while pregnant, and they are often the treatment of choice for diabetes insipidus in pregnant patients. These medications can also be given for bleeding conditions during pregnancy. However, they should only be used if the benefits outweigh the potential risks. 

Antidiuretic hormone may pass into breast milk in small amounts. However, it is unlikely that vasopressin or desmopressin will cause adverse effects in a breastfed infant. Consult a healthcare provider for medical advice before taking an antidiuretic hormone medication while pregnant or breastfeeding.

Are antidiuretic medications controlled substances?

No, antidiuretic medications are not controlled substances. 

Common antidiuretic hormones side effects

The most common side effects of antidiuretic hormones include:

• Nausea
• Vomiting
• Diarrhea
• Stomach pain
• Indigestion
• Weakness
• Headache
• Dizziness
• Flushing
• Loss of appetite

More severe but rare side effects of antidiuretic hormones include:

• Low sodium levels
• Mental and mood changes
• Allergic reactions

This list of side effects is not comprehensive. Speaking with a healthcare professional is the best way to get a complete list of side effects and determine whether taking antidiuretic hormone treatment is suitable for you.

Tell your healthcare provider if you have any of the following before taking an antidiuretic hormone medication:

• Any drug allergies
• Kidney disease
• History of low sodium levels
• Heart failure
• Hypertension
• Syndrome of inappropriate antidiuretic hormone secretion (SIADH)
• Type IIB von Willebrand disease
• Adrenal gland problems
• Diarrhea
• Eating disorders
• Consumption of more water than normal
• Nasal issues, including recent nasal surgery

How much do antidiuretic hormones cost?

Antidiuretic hormone medications are available in brand name and generic formulas.   Medicare plans and other insurance plans will usually cover antidiuretic hormone medications depending on the formulation and condition being treated. Costs will vary depending on your insurance plan. Without insurance, the price can vary widely depending on the medication and quantity of medication prescribed. However, using a prescription discount card from SingleCare may help reduce the cost of antidiuretic hormone medications. 

Antidiuretic Hormone

Antidiuretic Hormone

Roughly 60% of the mass of the body is water, and despite wide variation in the amount of water taken in each day, body water content remains incredibly stable. Such precise control of body water and solute concentrations is a function of several hormones acting on both the kidneys and vascular system, but there is no doubt that antidiuretic hormone is a key player in this process.

Antidiuretic hormone, also known commonly as arginine vasopressin, is a nine amino acid peptide secreted from the posterior pituitary. Within hypothalamic neurons, the hormone is packaged in secretory vesicles with a carrier protein called neurophysin, and both are released upon hormone secretion.

Physiologic Effects of Antidiuretic Hormone

Effects on the Kidney

The single most important effect of antidiuretic hormone is to conserve body water by reducing the loss of water in urine. A diuretic is an agent that increases the rate of urine formation. Injection of small amounts of antidiuretic hormone into a person or animal results in antidiuresis or decreased formation of urine, and the hormone was named for this effect.

Antidiuretic hormone binds to receptors on cells in the collecting ducts of the kidney and promotes reabsorption of water back into the circulation. In the absense of antidiuretic hormone, the collecting ducts are virtually impermiable to water, and it flows out as urine.

Antidiuretic hormone stimulates water reabsorbtion by stimulating insertion of “water channels” or aquaporins into the membranes of kidney tubules. These channels transport solute-free water through tubular cells and back into blood, leading to a decrease in plasma osmolarity and an increase osmolarity of urine.

Effects on the Vascular System

In many species, high concentrations of antidiuretic hormone cause widespread constriction of arterioles, which leads to increased arterial pressure. It was for this effect that the name vasopressin was coined. In healthy humans, antidiuretic hormone has minimal pressor effects.

Control of Antidiuretic Hormone Secretion

The most important variable regulating antidiuretic hormone secretion is plasma osmolarity, or the concentration of solutes in blood. Osmolarity is sensed in the hypothalamus by neurons known as an osmoreceptors, and those neurons, in turn, stimulate secretion from the neurons that produce antidiuretic hormone.

When plasma osmolarity is below a certain threshold, the osmoreceptors are not activated and secretio of antidiuretic hormone is suppressed. When osmolarity increases above the threshold, the ever-alert osmoreceptors recognize this as their cue to stimulate the neurons that secrete antidiuretic hormone. As seen the the figure below, antidiuretic hormone concentrations rise steeply and linearly with increasing plasma osmolarity.

Osmotic control of antidiuretic hormone secretion makes perfect sense. Imagine walking across a desert: the sun is beating down and you begin to lose a considerable amount of body water through sweating. Loss of water results in concentration of blood solutes – plasma osmolarity increases. Should you increase urine production in such a situation? Clearly not. Rather, antidiuretic hormone is secreted, allowing almost all the water that would be lost in urine to be reabsorbed and conserved.

There is an interesting parallel between antidiuretic hormone secretion and thirst. Both phenomena appear to be stimulated by hypothalamic osmoreceptors, although probably not the same ones. The osmotic threshold for antidiuretic hormone secretion is considerably lower than for thirst, as if the hypothalamus is saying “Let’s not bother him by invoking thirst unless the situation is bad enough that antidiuretic hormone cannot handle it alone.”

Secretion of antidiuretic hormone is also stimulated by decreases in blood pressure and volume, conditions sensed by stretch receptors in the heart and large arteries. Changes in blood pressure and volume are not nearly as sensitive a stimulator as increased osmolarity, but are nonetheless potent in severe conditions. For example, Loss of 15 or 20% of blood volume by hemorrhage results in massive secretion of antidiuretic hormone.

Another potent stimulus of antidiuretic hormone is nausea and vomiting, both of which are controlled by regions in the brain with links to the hypothalamus.

Disease States

The most common disease of man and animals related to antidiuretic hormone is diabetes insipidus. This condition can arise from either of two situations:

• Hypothalamic (“central”) diabetes insipidus results from a deficiency in secretion of antidiuretic hormone from the posterior pituitary. Causes of this disease include head trauma, and infections or tumors involving the hypothalamus.
• Nephrogenic diabetes insipidus occurs when the kidney is unable to respond to antidiuretic hormone. Most commonly, this results from some type of renal disease, but mutations in the ADH receptor gene or in the gene encoding aquaporin-2 have also been demonstrated in affected humans.

The major sign of either type of diabetes insipidus is excessive urine production. Some human patients produce as much as 16 liters of urine per day! If adequate water is available for consumption, the disease is rarely life-threatening, but withholding water can be very dangerous. Hypothalamic diabetes insipidus can be treated with exogenous antidiuretic hormone.

Updated 2018. Send comments to [email protected]

A Bosnian translation of this page by Amina Dugalic is available at Bosnian Translation

A Finnish translation of this page by Elsa Jansson is available at Finnish translation

A Ukrainian translation of this page by Olena Chervona is available at Ukrainian Translation

Vasopressin | biochemistry | Britannica

Vasopressin, also called antidiuretic hormone, hormone that plays a key role in maintaining osmolality (the concentration of dissolved particles, such as salts and glucose, in the serum) and therefore in maintaining the volume of water in the extracellular fluid (the fluid space that surrounds cells). This is necessary to protect cells from sudden increases or decreases in water content, which are capable of interfering with proper cell function. Normal serum osmolality ranges from about 285 to 300 milliosmoles per kilogram (mOsm/kg) in healthy people. Vasopressin and a hormone called oxytocin evolved from a single primordial neurohypophyseal hormone called vasotocin, which is present in lower vertebrates.

Special nerve cells called osmoreceptors in the hypothalamus are very sensitive to changes in serum osmolality. The osmoreceptors are closely associated with the same nerve cells that produce and secrete vasopressin. Serum osmolality that increases or decreases by as little as 1 percent can cause respective decreases or increases in vasopressin release. The immediate effect of an increase in serum osmolality—for example, if a person becomes dehydrated (e.g., loses water by excessive perspiration)—is a stimulation the osmoreceptors. This stimulation leads to the separation of vasopressin from molecules of neurophysin, to which vasopressin is loosely attached within the secretory cells. Vasopressin is then released from the posterior pituitary gland, leading to the subsequent retention of water by the kidneys. Conversely, the immediate effect of a decrease in serum osmolality—for example, if a person becomes overhydrated (e.g., drinks too much water)—is the inhibition of the osmoreceptors. This inhibition leads to a decrease in vasopressin secretion and a subsequent increase in water excretion. The osmoreceptors are also closely linked to the thirst centre, which is stimulated by high serum osmolality and is inhibited by low serum osmolality in the same way as is vasopressin secretion.

Read More on This Topic

human nervous system: Vasopressin and cardiovascular regulation

Vasopressin is a peptide hormone that is synthesized in magnocellular neurons of the supraoptic and paraventricular nuclei…

In the kidneys, vasopressin acts on the cells of the collecting ducts. These cells contain receptors for vasopressin that are linked to vesicles that contain special water channels (aquaporins). When the cells are stimulated by vasopressin, the aquaporins fuse with the region of the cell membrane that is exposed to urine, allowing water to enter the cells. The water is then returned to the circulation. This causes the volume of urine to decrease and the urinary content of sodium, chloride, and other substances to increase. When this occurs, the urine is said to be concentrated.

Vasopressin is also released in response to a decrease in blood volume. Special pressure sensors called baroreceptors can detect arterial blood pressure; they are located in the carotid sinus, which is intimately associated with each carotid artery high in the neck, and in a group of specialized cells in the left atrium of the heart. When blood volume increases, the tissues of the carotid sinus and left atrium are stretched, and the nerves in the baroreceptors are stimulated. These nerves carry impulses to the vasopressin-producing nerve cells that inhibit the secretion of vasopressin, resulting in increased water excretion. Conversely, if blood volume decreases, the stretch of the carotid sinus and left atrium decreases, vasopressin release increases, and water excretion decreases, thereby helping to restore blood volume to normal. Other stimuli of vasopressin release include pain, stress, and several drugs, including opiate drugs.

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Ready or not, two drugs for autism edge closer to clinic | Spectrum

Power puff: Inhaling vasopressin may improve social skills in autistic children.

Ralf Geithe / iStock

Two drugs that alter the activity of the hormone vasopressin seem to improve social communication in people with autism. The findings come from two independent clinical trials published today in Science Translational Medicine^1,2.

The results are encouraging, but some experts urge caution, saying the methods used to assess the drugs were not designed for that purpose.

Vasopressin is related to oxytocin, a hormone thought to govern social bonding. But vasopressin’s link to autism is far from simple: There’s evidence implicating both too little and too much of the hormone in people with the condition.

The two drugs also target vasopressin in opposite ways. One of them, balovaptan, blocks a receptor for vasopressin in the brain and dampens the hormone’s activity. The other is a nasal spray containing vasopressin. Despite their opposing modes of action, both drugs appear to boost social function in autistic people; neither has serious side effects.

The findings are noteworthy because no drugs are available to treat autism’s core traits, says Eric Hollander, professor of psychiatry and behavioral sciences at Albert Einstein College of Medicine in New York and a principal investigator on the balovaptan trial.

“These two studies provide important information that the vasopressin or vasopressin and oxytocin systems are important in social communication,” he says. “Different agents affecting these systems may ultimately be helpful in terms of new treatments for autism.”

Still, both studies rely on a questionnaire that is not designed to measure a drug’s effectiveness, says Lawrence Scahill, director of clinical trials at the Marcus Autism Center in Atlanta.

“Both of these studies suggest that the mechanism is worth further study,” Scahill says. “But I think we want to be careful not to overinterpret the findings.”

Dose effect:

In the balovaptan trial, led by the Swiss drug company Roche, researchers at 26 sites across the United States randomly assigned 223 men with autism to take the drug once a day for 12 weeks. The pills contained either 1.5, 4 or 10 milligrams of balovaptan or a placebo.

The men who took balovaptan fared no better than controls on a caregiver questionnaire called the Social Responsiveness Scale, the study’s primary outcome measure. But those taking the two highest doses improved in their social and communication abilities, based on the Vineland Adaptive Behavior Scales, a secondary measure. The men showed no difference on scales measuring repetitive behaviors, anxiety or mood, among other traits.

The Roche researchers were unavailable for comment, but Hollander says these results are promising.

“It’s tough to show good response rates in multisite trials, where you have high placebo responses and site-specific effects,” Hollander says. “But they do get a nice dose-related effect on this social communication domain.”

The results of the trial prompted the U.S. Food and Drug Administration to grant the drug ‘breakthrough’ status in January 2018. The researchers are testing the drug in two new clinical trials: One involves autistic children in the U.S., and the other includes adults in Europe, Canada and the U.S.

Sniff test:

In the trial of the vasopressin spray, parents of autistic children aged 6 to 12 years gave their children a nasal spray twice a day for four weeks. Of the 30 children in the trial, 17 got the vasopressin spray, and the rest sniffed a placebo.

Children in the vasopressin group significantly improved in their social skills, based on the Social Responsiveness Scale, the primary outcome measure. Clinician ratings of these abilities, parent ratings of anxiety, and the children’s performance on two of four tests of social cognition also all pointed to an improvement. None of the children who got vasopressin became more aggressive, as some rodents do³.

“Multiple independent assessments show that the drug was more effective than placebo,” says co-lead investigator Karen Parker, associate professor of psychiatry and behavioral sciences at Stanford University in California.

Paradoxically, the children with the highest blood levels of vasopressin before treatment tended to show the biggest effects, and only these children improved in their repetitive behaviors. Parker is unsure why that is, but perhaps the dose was too low to benefit those with less vasopressin, she says.

Clinical caveats:

Some experts, including the researchers themselves, caution that the results are preliminary, however, and need to be repeated in larger groups of children.

“The results of a small study can be deceptive,” says Scahill. “And when you have this many outcome measures in a small study, some things are possible to turn up as statistically significant by chance. ”

Others have questions about how two drugs with opposite modes of action lead to similar effects.

“They’re really divergent approaches to targeting the vasopressin system,” says Elizabeth Hammock, assistant professor of psychology and neuroscience at Florida State University in Tallahassee. “And we don’t know for sure how either is working.”

However, the experts note, it’s difficult to compare trials with such different designs and sets of participants.

“Autism is a very heterogeneous disorder,” says Antonio Hardan, professor of psychiatry and behavioral sciences at Stanford University, who co-led the nasal spray trial. “It may be possible, with autism, to see abnormalities that relate to either too much vasopressin or too little.”

Hardan and Parker are testing the spray in a new trial of 100 children with autism.

Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)

Syndrome of inappropriate antidiuretic hormone secretion occurs when excessive levels of antidiuretic hormones (hormones that help the kidneys, and body, conserve the correct amount of water) are produced. The syndrome causes the body to retain water and certain levels of electrolytes in the blood to fall (such as sodium). SIADH is rare in children.

SIADH tends to occur in people with heart failure or people with a diseased hypothalamus (the part of the brain that works directly with the pituitary gland to produce hormones). In other cases, a certain cancer (elsewhere in the body) may produce the antidiuretic hormone, especially certain lung cancers. Other causes may include the following:

• Meningitis (inflammation of the meninges, the membranes that cover the brain and spinal cord)

• Encephalitis (inflammation of the brain)

• Brain tumors

• Psychosis

• Lung diseases

• Head trauma

• Guillain-Barré syndrome (a reversible condition that affects the nerves in the body. GBS can result in muscle weakness, pain, and even temporary paralysis of the facial, chest, and leg muscles. Paralysis of the chest muscles can lead to breathing problems. )

• Certain medications

• Damage to the hypothalamus or pituitary gland during surgery

• Thyroid or parathyroid hormone deficiencies

• HIV

• Hereditary causes

Each person may experience symptoms differently. Symptoms, in more severe cases of SIADH, may include:

• Nausea or vomiting

• Cramps or tremors

• Depressed mood,memory impairment

• Irritability

• Personality changes, such as combativeness, confusion, and hallucinations

• Seizures

• Stupor or coma

The symptoms of SIADH may resemble other problems or medical conditions. Always consult your child’s doctor for a diagnosis.

In addition to a complete medical history and physical examination, to confirm diagnosis of SIADH, blood and urine tests will need to be performed to measure sodium, potassium, and osmolality (concentration of solution in the blood and urine).

Specific treatment for SIADH will be determined by your doctor based on:

• Your age, overall health, and medical history

• Extent of the disease

• Your tolerance for specific medications, procedures, or therapies

• Expectations for the course of the disease

• Your opinion or preference

The most commonly prescribed treatment for SIADH is fluid and water restriction. If the condition is chronic, fluid restriction may need to be permanent. Treatment may also include:

• Certain medications that inhibit the action of ADH (also called vasopressin)

• Surgical removal of a tumor that is producing ADH

• Other medicines to help regulate body fluid volume

Vasopressin: Mechanism of Action and Clinical Physiology | Natochin

The range of problems in the physiology, biochemistry, and clinical practice of arginine-vasopressin (antidiuretic hormone – ADH) is diverse, the available data cannot be fully presented either in a large review or in a fairly voluminous monograph. Retention of the term ADH along with vasopressin is justified, since in a number of vertebrate species the function of ADH is performed by other nanopeptides of the pituitary gland, including lysine-vasopress-

¹ This work was supported by the Russian Foundation for Basic Research (grants 99-04-49198 and 00-15-97803) and the Program of the Presidium of the Russian Academy of Sciences.syn, arginine-vasotocin, hydrin 2 [17, 54, 65]. Original articles, reviews [4, 6, 63], monographs and collections [54, 86] are devoted to vasopressin. Clinical syndromes associated with inadequate secretion of ADH (Schwartz-Barter syndrome), deficiency of secretion of ADH (not diabetes mellitus), and insensitivity of tubule cells to this hormone (nephrogenic diabetes insipidus) have been identified [3, 5]. The absence of a kidney response to ADH may be due to a defect in many elements of the cascade, on which the increase in water permeability in response to hormone intake depends.The forms of diabetes caused by mutations in the Y ₂ receptor gene [21, 83] and the aquaporin 2 gene have been described [80]. In this article, attention will be paid to the issues of the mechanism of action and clinical physiology of vasopressin, in the solution of which our team took part, and the results of the studies gave a new vision of a number of these problems.

In 1895 G. Oliver and E. Schafer discovered the ability of an extract of the posterior lobe of the pituitary gland to increase blood pressure, and in 1913 R. von den Velden discovered its antidiuretic effect in diabetes insipidus.For a long time it was believed that the pressor agent and the antidiuretic principle are different substances until their chemical identity was established. In the 1920s, when the concept of hormone was formulated, this active principle was called vasopressin. Its synthesis was carried out by V. Du Vigneaud, a biochemist at George Washington University in St. Louis, who was awarded the Nobel Prize for the synthesis of oxytocin and vasopressin. Arginine-vasopressin is a nanopeptide: Cis-Tyr-Phen-Glu-Asp-Cis-Pro-Apr-Gly; in the 1960s, its analogue, 1-deamino-8O-arginine-vasopressin (dDAVP, desmopressin), was synthesized in Czechoslovakia, which has received wide clinical use as an agonist of Vj receptors [54].

Vasopressin functions

ADH is produced in the nuclei of the hypothalamus, its function, starting with tailless amphibians, is in osmotic regulation, in the retention of water in the body [17, 65]. In tailless amphibians (frogs, toads), ADH increases the water permeability of epithelial cells of the skin, urinary bladder, renal tubules, enhances the transport of sodium ions, which ensures osmoregulation [17, 66]. Water enters the internal environment through the integument in fresh water, is absorbed into the blood in the final tubules and in the bladder.Vasopressin and, accordingly, agonists of V, – and Y ₂ -receptors have different effects, they affect vascular tone [24, 29], antidiuretic effect [46, 54], affect the function of platelets [16], promote the release Coagulation factor VIII [54], have an inotropic effect in the muscle of the ventricle of the heart [31], affect behavior [35, 73, 81], modulate vocal function [36], and when injected into certain parts of the brain, induce hyperglycemia [ 87], affect body temperature [75], intraocular pressure [34] and the composition of inner ear fluids [47].

The human body as an integral system interacts with the environment and adapts to its changing conditions, including water, salt and temperature regimes. Vasopressin determines the maintenance of a stable osmotic pressure in the blood and thus outside the cell fluid [6, 17]. A study of the physicochemical parameters of blood serum in healthy people under normal and extreme conditions, as well as in patients with a number of pathological conditions, showed that the most strictly controlled systems of regulation control the osmolality of the extracellular fluid, the concentration of free Ca ²⁺ , pH , the variability of the concentration of ions K ⁺ and a number of other substances [60].When examining almost 200 cosmonauts and astronauts after the flight, no differences were found in the mean values ​​of blood serum osmolality as compared to the initial, pre-flight values, but the variability of this indicator after landing increased by 44% (60]. The volume of cells depends on the exact fluid: blood wasps increase – the cell volume decreases, hypoosmia sets in – and it increases. This is due to the fact that through the permeable plasma membrane from the cell during hyperosmia, water flows along the osmotic gradient into the extracellular fluid.When the reabsorption of water in the human kidney increases with the syndrome of inadequate secretion of ADH, the osmolality of the blood decreases, hypoosmia sets in, and the extracellular fluid becomes more hypotonic than the intracellular contents. Water through water channels (aqua-porins) along the osmotic gradient begins to enter the cells, this leads to their swelling. A change in cell volume causes shifts in metabolism in a cell, a change in its functional state, and its response to regulatory extracellular influences, including the action of hormones and mediators.

If we bring together many of the listed effects of vasopressin into the main physiological purpose of this hormone, it can be suggested that it consists in creating conditions for stabilizing the volume of cells in the body by maintaining euosmia and bringing blood volume into line with the capacity of the vascular bed. … This largely determines the effective operation of the physiological systems of the body, the productivity of which is determined by the high stability of the physicochemical parameters of the fluids of the internal environment, which depend on the systems of ossicular regulation and volume regulation.Only under conditions of constancy of the composition of the pericellular environment can cells accurately respond to signals arriving at them (nerve stimuli, hormones, locally formed physiologically active substances).

When a person gets into a desert environment, works in a hot workshop, there is a shortage of water in the body, and thirst appears. The desire to drink water arises to compensate for the loss of fluid, at the same time the water storage systems in the body are activated. The signal about blood osmolality, perceived by osmoreceptors [4, 55], is transmitted to the neurons of the nuclei of the hypothalamic region of the brain.In hyperosmia, these neurons are activated, arigine-vasopressin is secreted from the endings of axons in the posterior lobe of the pituitary gland into the human blood, its concentration in human blood increases from 1 to 5 pg / ml. The secretion of vasopressin increases with hypovolemia and stress [4].

Effects of vasopressin in the kidney “

With the blood flow, ADH reaches the kidneys and in the cells of the collecting ducts increases the permeability of the plasma membranes for water. As a result, the absorption of water into the blood from the lumen of the renal tubules increases to restore water balance.The membranes of the cells of the renal tubules (collecting ducts) facing the extracellular fluid contain vasopressin receptors [37]. After interaction of vasopressin with V ₂ receptors of basolateral membranes, the concentration of cAMP in the cell increases, this secondary mediator activates protein kinase A, and aquaporin 2 water channels are incorporated into the luminal membrane [46, 63, 69]. The result is an increase in the permeability of tubule cells for water, an increase in its absorption into the blood, and a return to the normal blood osmolality.This scheme is described in manuals [4, 6, 54], according to which osmotic homeostasis depends on the efficiency of the osmoregulatory reflex and the concentration in the blood of one hormone, vasopressin. The concentration of ADH in blood plasma is determined by the ratio of its secretion by the pituitary and the rate of blood clearance, i.e., by enzymatic cleavage of the hormone and its removal by the liver or kidney. It is believed that the water permeability of the osmoregulatory epithelium depends only on shifts in the concentration of ADH in blood plasma [4, 63], but one of our experiments has shaken this generally accepted scheme [64], see.below.

Vasopressin receptors are found in the plasma membranes of various kidney cells. ADH increases the water permeability of the cells of the connecting part of the nephron and collecting ducts [19], changes the ratio of the volume of filtered fluid in the glomeruli of different populations of nephrons during the transition from water diuresis to antidiuresis [6]; in the membranes of cells of the thick ascending part of the Henle loop, stimulation of Y ₂ -receptors leads to the formation of cAMP and an increase in the reabsorption of Na, Ca, Mg ions [37], in the cells of the collecting ducts of the cortex, ADH stimulates the transport of chlorine ions [27], and in the cells of the collecting ducts on the renal medulla, where there is a transporter urea [18], ADH enhances its reabsorption. In postnatal ontogeny, vasopressin restores nephron heterogeneity in rats with hereditary diabetes insipidus (Brattleborough line) [85]. Vasopressin affects glomerular filtration due to changes in vascular tone and the effect on mesangial cells [6]. Their reduction leads to a decrease in the surface of the capillaries, through the wall of which the liquid is ultrafiltered into the cavity of the glomerular capsule, and the glomerular ultrafiltration coefficient decreases. This effect is due to the formation of cAMP and does not depend on the secretion of renin.All of the above effects of vasopressin are aimed at ensuring maximum reabsorption of osmotically free water and osmotic concentration of urine. This requires an increase in the osmolality of the medulla, an increase in the permeability of plasma membranes for water.

Effects of stimulation of various types of vasopressin receptors

Several types of vasopressin receptors, V „V _la , V ₂ , have been described [15, 44, 46, 61], and genes associated with them and their mutations have been identified [48, 53, 70, 79]. Stimulation of V. receptors provides modulation of the effect of vasopressin [1, 33], vasoconstriction [61], glycogenolysis, release of ACTH, and contraction of intestinal muscles. Remestip, a specific receptor agonist of this type, is used in acute hemorrhagic gastritis, postoperative intestinal obstruction, and bleeding caused by esophageal varices. Stimulation of V receptors affects vascular tone [54], intraocular pressure [34], blockade of central V receptors reduces the hypotensive state [23].In turn, antagonists of Y _1a / Y ₂ receptors [88], selective antagonists of V, and Y ₂ receptors have found application in experimental studies [43, 76, 77] and clinical practice [20 ] in the treatment of hypoosmia, hyponatremia [72], and hypertensive conditions [84].

Stimulation of Y ₂ receptors causes an increase in the water permeability of osmoregulatory epithelial cells, including the collecting ducts in the kidney [46, 54], and the release of blood coagulation factor VIII. This determines the effectiveness of an agonist of these desmopressin receptors in diabetes insipidus, nocturnal enuresis, Willebrandt disease, complex forms of hemostasis disorders (uremic bleeding, cirrhosis) and treatment of side effects of drugs and hemostasis disorders (aspirin, ticlopedin) [68, 78]. Stimulation of Y ₂ receptors, along with an increase in water reabsorption in the collecting ducts of the renal medulla, promotes an increase in urea reabsorption; in the cells of the thick ascending part of the Henle loop, the reabsorption of Na, Mg, K, and Ca ions increases.

Mechanism of antidiuretic action of vasopressin

At the turn of the 50-60s, it became obvious that in response to the action of a peptide hormone on a cell, a substance is formed in it, which causes a change in chemical processes in the cell and ultimately changes its functions. The elucidation of the mechanism of action of ADH largely depended on the results of studies, crowned with the award of several Nobel Prizes in Physiology or Medicine – among them the discovery of E. W. Sutherlen about the role of cAMP in the mechanism of action of hormones [82], the creation of R.Yalow’s radioimmune method for the determination of peptide hormones, including vasopressin, which replaced the biological testing of its activity, was studied by S. Bergstrom, B. Samuelson, and J. Wein, who discovered prostaglandins, which turned out to be physiological competitors of the antidiuretic effect of vasopressin [2, 10, 19].

Peptide hormones are unable to penetrate through the cell membrane, and the physiological response of the cell depends on the intracellular signaling system.Vasopressin does not penetrate into the cell; vasopressin receptors are built into the plasma membrane of the cell, facing from its outer side to the extracellular fluid. The composition of this fluid is constantly renewed; it is formed from the blood and is soon removed from the tissue by blood or lymphatic vessels in order to maintain the required concentration of ADH. ADH diffuses into the extracellular fluid from the blood, interacts with the receptor built into the plasma membrane of the cell, the conformation of the receptor molecule changes, and further events occur from the inner side of the plasma membrane of the cell. The effect of ADH was reproduced by adding cAMP to the cell or by inhibiting the activity of cAMP phosphodiesterase, which increased its lifetime in the cell due to slowing down the cleavage of cAMP [63]. The hormone sensitive complex consists of three components: the vasopressin receptor, the conjugation unit (G-protein), and adenylate cyclase. The end result of the interaction of the hormone with the receptor is the activation of the enzyme adenylate cyclase, which promotes the conversion of ATP into cAMP; the latter inside the cell stimulates a specific functional response of the cell to ADH.-receptor, cAMP is formed and aquaporin 2 is incorporated into the luminal membrane [12, 50, 52, 58], which increases its permeability to water [56, 58] and begins its absorption along the osmotic gradient into the blood. As a result, the concentration of dissolved substances in the blood is normalized, and the osmolality of the blood is restored. Under pathological conditions, the nephrotoxic effect of cisplatin decreases the content of aquaporins [49].

To avoid mistakes and “foreign” cAMP from another cell or from the blood could not activate the processes in this cell, the plasma membrane is impermeable to ATP and cAMP, the latter acts inside its own cell and is inactivated in it by cAMP phosphodiesterase.It is possible to lengthen the lifetime of cAMP in the cell by reducing the activity of cAMP phosphodiesterase; theophylline and, to a lesser extent, caffeine are inhibitors of this enzyme.

In addition to cAMP, there are secondary messengers of a different chemical nature, which are involved in intracellular signaling upon activation of V. receptors by vasopressin. Inositol triphosphate, diacylglyserin, and Ca ions are involved as a secondary mediator [39]. In granular cells of the epithelium of the urinary bladder and in the cells of the renal tubules, they reduce the effect of ADH associated with the stimulation of the transport of ions and water [46].

The idea of ​​the role of hyaluronidase in the mechanism of action of vasopressin and an increase in water permeability was expressed by AG Ginetsinsky [32], a heated debate continued for many years, and until now the question of the place of this mechanism in the unified scheme of ADH action remains controversial. At the same time, until recent years, there is a search for the role of this enzyme in the action of ADH [30, 41, 42, 45].

Modulation of vasopressin effect

Stimulation of Vj receptors of membranes of renal tubules or urinary bladder cells by vasopressin under its action from the extracellular fluid led to the accumulation of cAMP in the cell and incorporation into the luminal membrane of aquaporin 2 [52, 69].Simultaneous action of vasopressin and V receptor antagonists on the basal plasma membrane enhances the effect of vasopressin associated with an increase in water permeability and reabsorption of ions in the initial parts of the distal tubule [33]. These data suggest that V ₂ – and V. -receptors are built into the basal plasma membrane; the former in this case are triggers (they stimulate the process), and the latter are modulators of the physiological effect; they change the strength of the reaction without giving the opportunity for an overreaction. Vasopressin receptors are also present on the apical plasma membrane, ie, they are directed towards the lumen of the tubule and towards the bladder cavity [R]. When an agonist acts on these receptors, the response of cells to simultaneous stimulation of V ₂ peuenTors of the basolateral cell membranes changes.

Autacoids and restoration of cell water resistance after the action of ADH

Above, we discussed the unexpected result of an experiment on the bladder, which showed that balanced regulation of osmotic blood pressure is based not only on the secretion and inactivation of ADH, but also on the local production of physiologically active substances [9, 64].In these experiments, it was first established that the water permeability of epithelial cells of osmoregulatory organs depends on endogenous production at very low concentrations of autacoids, and the molecular mechanisms of the function of this system were revealed [52, 64]. In experiments on an isolated frog bladder, which is involved in osmoregulation in amphibians along with kidneys [17], and its epithelial cells react to ADH in the same way as epithelial cells of the collecting duct of mammalian kidneys, the molecular mechanisms of the reaction to ADH were found to be similar. in humans and tailless amphibians [63].The water permeability of the frog urinary bladder mucosa, as well as of the mammalian kidney collecting duct cells, can be increased by this hormone 50 times or more [64]. In experiments in vitro, the bladder with hypotonic saline injected inside it was placed in Ringer’s solution, saline was present on the side of the serous membrane of the urinary bladder, and a hypotonic solution was inside the bladder on the side of the mucous membrane, which made it possible for water to move along osmotic gradient with increasing water permeability of epithelial cells.10 M arginine-vasotocin was added to the solution near the serous membrane, the water permeability increased tenfold. After a while, this saline solution containing ADH was changed to fresh Ringer’s solution without the hormone. Increased water permeability slowly It was suggested that for a slow decrease in permeability even in in vitro experiments depends on the binding of a part of ADH to the receptor, and it is necessary to more vigorously wash the remaining ADH by frequent changes of physiological solution. This procedure was performed; at first, the water permeability began to decrease, and then increased to values ​​comparable to the effect of ADH [64]. To explain this paradoxical situation, it was suggested that the restoration of water impermeability is also a regulated process, and the cells secrete a locally acting physiologically active substance that restores the water impermeability of the epithelium. It was shown that, in the absence of ADH and removal of autacoids, the molecular mechanism of increase in permeability is the same – a correlation was found between the increase in permeability and accumulation of cAMP in the cell [64], the formation of aggregates of intramembrane particles was found in the luminal membrane of the cell [52], which serve accumulations of aquaporins embedded in the membrane.

Biochemical identification of substances that reduce water permeability showed that frog bladder cells secrete eicosanoids, in particular, prostaglandin E ₂ [64]. They were detected in the fluid taken after incubation of the bladders in saline, and after the addition of prostaglandins E ₂ , EF _{2 a} K solution at the serous membrane, the increased permeability of the urinary bladder for water decreased to normal low values. [13].

Usually, much attention is paid to the mechanism of increasing water permeability upon the addition of ADH [3, 5, 6], but the question of regulating the transition from the state of high tubule permeability for water during its reabsorption to the water permeability of the tubular wall, when the release is ensured, has been little developed. water from the body. It is believed that it is enough to stop secretion and remove ADH from the blood, and by itself it will be restored to the permeability of the tubular wall. There is evidence of endocytosis of aquaporins [26], but it is important to find out which system regulates this process.This is also of great clinical importance, since in a number of pathological conditions an increase in water reabsorption leads to hypoosmia, hyponatremia, the treatment of which is not an easy task in the absence of clinically available watercolors, antagonists. ADH.

The kidney was formed in evolution as a polyfunctional organ subordinate to multiple control of extrarenal factors of regulation – nervous and endocrine and the system of autoregulation, in particular, renal blood flow, glomerular filtration.A large number of physiologically active substances are synthesized and act in the kidney, which control a number of its functions and change the response of tubular cells to hormones and mediators. In the kidney, metabolic products of arachidonic acid are formed and act locally [2, 10, 51]; there is also a distribution of the receptors of these physiologically active substances specific to the cell membranes of different parts of the nephron. For prostaglandin E ₂ , several types of receptors have been identified, their localization in the kidney has been established [62] and the features of secondary mediators upon activation of different types of receptors have been established.This predetermines the possibility of both activation (or suppression) of certain functions of cells of a given type, and modulation of the effect of vasopressin and other hormones acting on the same cells.

In the absence of vasopressin in the blood, the kidneys excrete hypotonic urine. Our data showed that the maintenance of low permeability, the transition to the state of water impermeability, and the maintenance of this state turned out to be regulated processes dependent on substances acting on the cell from outside, forcing it to obey the stimuli coming to the cell membrane.Their peculiarity is that these stimuli emanate from a given or neighboring cell, make it obey them and rebuild its work. It turned out that the increase in osmotic permeability without ADH is due to the fact that prostaglandins synthesized by it are removed from the cell membranes [9, 74], and restoration of water resistance upon removal of ADH requires the presence of prostaglandins. In our experiments with the use of cyclooxygenase inhibitors (valtoren, indomethacin) and blockade of phospholipase A, using kinacrine, it was shown that a decrease in the secretion of prostaglandins halts the restoration of water impermeability.

Syndrome of inappropriate secretion of vasopressin

This condition, which depends on a sharp increase in blood concentration of ADH, is accompanied by hypoosmia and is observed in a number of forms of pathology – diseases of the central nervous system (cerebral thrombosis, acute psychosis, trauma, acute intermittent porphyria, acute idiopathic polyneuritis syndrome, sub dural hematoma, encephalitis, subarachnoid bleeding, meningitis), diseases of the chest cavity organs (pneumonia, asthma, tuberculosis), tumors and metastases of tumors of a number of organs (pancreas, stomach, small cell lung carcinoma, etc.) (see table). Undoubtedly, correction of hypoosmia and hyponatremia is required [22, 25, 40].

Changes in the concentration of vasopressin in blood plasma in physiological and pathological conditions (modified according to [7])

Increase in vasopressin concentration

Arterial hypotension

Pregnancy

Pain syndrome

Bronchogenic carcinoma

Gestosis

Hyperosmia

Hypovolemia

Dehydration

Congestive heart failure

Drug therapy (apo morphine, vincristine, nicotine, cyclophosphamide) Meningitis

Insufficiency of glucocorticoids

Nephrogenic diabetes insipidus

Pneumonia

Brain tumor (primary, metastases)

Tumors of the APUD-system

Acute intermittent porphyria

Syndrome of excess secretion of ADH

Julien-Barré Syndrome Stress

Nausea

Pulmonary tuberculosis Tuberculous meningitis Encephalitis

Decrease in vasopressin concentration

Hypervolemia

G hypoosmia

Nephrotic syndrome

Consumption of excess water Psychogenic polydipsia

Central diabetes insipidus

The reason for the decrease in blood osmolality is the increased reabsorption of water in the kidney as a result of the high concentration of vasopressin in the blood.It is clinically important to differentiate this syndrome from conditions accompanied by hypoosmia, such as psychogenic polydipsia, water intoxication, and hypocorticism. Differential diagnostic method consists in measuring the osmolality of blood serum: if it is higher than 295 mOsm / kg H ₂ O, then polyuria of the pituitary genesis, the patient’s thirst is due to hyperosmia. If the osmolality of blood plasma is below 280 mOsm / kg H ₂ O, one can think of primary polydipsia, water intoxication, syndrome of inadequate secretion of vasopressin.In this syndrome, the osmolality of urine will exceed the osmolality of the blood, osmotically concentrated urine will be excreted due to the action of vasopressin on the kidney, while primary polydipsia is characterized by polyuria with low osmolality of urine due to the intake of large amounts of water and the resulting decrease in secretion vasopressin.

Nocturnal enuresis, chronic renal failure (CRF)

Naturally, the question arose about the clinical significance of the results of the study of the interaction of vasopressin and autacoids, the elucidation of possible dysfunctions of this system in humans, and the methods of treating such conditions, if they are found.The studies were carried out in pediatric and nephrological clinics and two forms of pathology were characterized – in one case (nocturnal enuresis), the development of the disease is associated with a deficiency of ADH or a decrease in its effect, in the other (CRF), the state of the kidney is so altered that osmotic concentration, and then the osmotic dilution of urine under the action of ADH turns out to be impracticable.

One of the most common forms of pathology in children is nocturnal enuresis, which affects 15 to 28% of children in some countries.According to one of the hypotheses, its mechanism is explained by the fact that during nocturnal enuresis and some other forms of pathology, an inverted rhythm of vasopressin secretion is observed (in healthy people, the secretion of ADH increases at the same time) [14, 28, 71] – it does not increase at night, as normal, but decreased, as a result of which a large diuresis is observed, and due to a defect in the perception of an increased flow of fluid into the bladder during deep sleep, excesses in the form of nocturnal enuresis are observed. Along with this variant of pathogenesis, there is another.It was shown that these children have decreased reabsorption of ions in the thick ascending part of Henle’s loop, which causes an increase in nighttime urination [68]. A decrease in the absorption of ions in the cells of these kidney tubules could be due to insufficient secretion of vasopressin into the blood or its ineffective action, if some factors prevent the cell’s response to the hormone, such a role could be played by excessive secretion of autacoids in these patients [67]. It was found that in 85% of patients with nocturnal enuresis, desmopressin has a normalization of water and ion transport in the kidney and a beneficial clinical effect; a good result in some children was observed when they were treated with cyclooxygenase blockers and, due to this, a decrease in the secretion of autacoids [68].

In some patients with nocturnal enuresis, a different genesis was revealed – nocturnal polyuria is caused by a decrease in the reabsorption of Na and Mg ions with accompanying anions, ie, saluresis rather than water diuresis is observed [63]. A highly reliable correlation was revealed between an increase in the excretion of Na and Mg ions, which made it possible to suppose the localization of a decrease in the reabsorption of these ions in the cells of the thick ascending part of the Henle loop, where ADH acts and can be opposed by prostaglandin E ₂ .It is known that the reabsorption of Na ions is stimulated in the cells of this tubule by vasopressin [37, 38]; therefore, it has been shown to compensate for its deficiency. It turned out that an increase in saluresis is accompanied by an increase in urinary excretion of prostaglandin E ₂ [57]. It could be assumed that the use of desmopressin or voltaren (a prostaglandin synthetase inhibitor) would increase the reabsorption of Na, Mg and water ions and would have a therapeutic effect in nocturnal enuresis: desmopressin> was effective in 85% of patients, voltaren – in 35% [63].Obviously, the pathogenesis of the disease is polymorphic and the choice of the type of drug therapy should depend on the nature of the disturbances in the regulatory system in a given patient [63, 78]. We suggested the existence of diseases, the pathogenesis of which is based on excessive local secretion of autacoids, which determines the clinical picture of the disease; they were called autocoidosis [8].

On the other hand, diseases were found in which ADH is ineffective, and increased secretion of autacoids plays a compensatory role and helps to maintain the functional efficiency of the kidney for a longer time.An example is the end stages of chronic renal failure: the secretion of prostaglandin E ₂ in the kidney reduces the reabsorption of ions in the thick ascending part of the Henle loop [67] and promotes an increase in urine output, the release of end metabolic products, and allows patients to preserve their lives longer without being connected to an artificial kidney. In patients with chronic renal failure, in whom the decrease in glomerular filtration rate is 30 ml / min or less, isostenuria is present and vasopressin is ineffective in regulating renal function. Our data allow us to correctly explain the fact that patients with chronic renal failure are not shown to use nonsteroidal anti-inflammatory drugs, which is known to clinicians.It is clear that their consumption would lead to a decrease in the secretion of prostaglandins, and therefore to a decrease in urine output and thereby to an increase in uremia.

Autakoids are important in the regulation of blood pressure (endothelium, prostaglandin F _{2 a} , thromboxane A ₂ , prostaglandin 1 ₂ , endothelium hyperpolarizing factor, etc.) along with efferent nerves II, angiotensin kate with holamines, vasopressin. The revelation of the multiplicity of endocrine factors that are involved in the regulation of kidney function, regulation of vascular tone, raises the problem of the interdependence of the effect of vasopressin and autacoids.

Conclusion

These data are essential for general endocrinology. Usually, 2 levels of physiological regulation in the human body are considered – nervous and endocrine regulation. In the first case, the signal is transmitted through efferent nerve fibers to the cells of certain organs and tissues, in the second, the hormone enters the bloodstream and is simultaneously carried throughout the body. The facts presented in the review on the example of the regulation of water metabolism with the participation of vasopressin show the significance of another level of the regulatory system associated with the local release of physiologically active substances by cells of the effector organ into the intercellular fluid, acting on the same (autocrine) or adjacent (paracrine) cell and opposing vaso pressin.This ensures a balance in the regulation system, restoring the waterproofness of the epithelium. Autacoids affect membrane receptors and stimulate the formation of specific secondary messengers. If previously the regulation of water metabolism was considered only as a function of the action of one hormone – ADH, now it becomes obvious that a pair of substances functions: vasopressin – autacoid, in particular, prostaglandin E ₂ . Thus, in the endocrine regulation of water metabolism, a pair of physiologically active substances also plays a role – vasopressin and au tacoid, and not 2 hormones, as in many other cases – insulin / glucagon, aldosterone / atrial natriuretic factor, parathyroid hormone / calcitonin.This is an example of another type of regulation in combination with the nervous and endocrine systems. It is noteworthy that, like the regulation of water metabolism, an equally important role in energy metabolism is played by leptin discovered in the mid-1990s, which is formed in white fat cells and signals the state of fat stores. When these cells are filled with fat, leptins are secreted and the appetite center is inhibited. The appearance in evolution of regulation with the formation of physiologically active substances that determine the body’s attitude to water and food, not in one endocrine organ, but in a large number of cells of effector organs, probably increased the reliability of the system.Autacoids, along with vasopressin, are important in the regulation of water-salt metabolism not only in healthy organisms, but also in human pathology, and the elimination of these defects has a therapeutic effect in pharmacological blockade of hyperproduction of autacoids.

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Desmopressin hormone analogs: are they really effective?

Nocturnal urinary incontinence in a child is a common problem.Perhaps precisely because it is often encountered and has become habitual, mothers are in no hurry to recognize incontinence as a disease and expect that over time everything will pass.

However, it has long been proven that bedwetting (enuresis) is a disease that must be treated. And, like any disease, they have causes of a different nature and nature.

Natural hormone vasopressin

One of the most common reasons is the lack of the vasopressin hormone in the child’s body.This substance, produced by the pituitary gland, can reduce the amount of urine the body produces at night. Due to this function, vasopressin has received the definition of an antidiuretic hormone. By decreasing the volume of urine produced, vasopressin increases its concentration.

When the child’s body lacks this hormone, an excessive volume of fluid is released at night, which the child is not able to retain.

Treatment in such a situation is to make up for the deficiency with the help of synthetic analogs of the natural hormone.Synthetic hormones enter the body in the form of drugs.

Synthetic hormone desmopressin

Desmopressin is an artificially created structural analogue of the antidiuretic hormone vasopressin, which is produced in the body at night and has an antidiuretic function. Today desmopressin is available as injections, nasal medications, and tablets. In the treatment of enuresis in a child, quickly dissolving, sublingual tablets are mainly used, which he can easily dissolve (sublingual tablets include, for example, minirin).

Desmopressin treatment is usually started with a primary dose of 0.1 mg once at bedtime. If no improvement is observed within a week, the dose of the drug is gradually increased, a single dose at bedtime remains.

Desmopressin begins to perform antidiuretic function within 15 minutes after administration and continues for 8-12 hours. As a rule, the course of treatment is from 6 weeks to 3 months, sometimes it stretches to six months. The amount and conditions for taking the medication can also vary, each case is individual, and the decision must be made by a specialist.

The high effectiveness of the treatment of enuresis with desmopressin has been proven – in the first week, the number of episodes of uncontrolled urination in bed decreases by up to 85%. Desmopressin treatment is effective against childhood nocturnal polyuria. even long-term therapy using this analog does not give any significant side effects and does not affect blood coagulation.

The key to successful desmopressin treatment is following the instructions of a specialist.So, the child needs to go to the toilet before taking the pill, and then not drink liquid until morning.

Desmopressin analogs

Among the analogs of desmopressin, the following substances are currently distinguished:

• Terlipressin;
• Vasomirin;
• Adiuretin;
• Apo-Desmopressin
• Lysinvasopressin.

These analogues, however, are much less popular than desmopressin.This is explained by the fact that desmopressin is indeed much more effective than the mentioned substances, since of all synthetically reproduced hormones, it is the closest to natural.

Its functioning corresponds to that of vasopressin, which is produced by the body. Moreover, desmopressin surpasses the natural substance in some respects! So, this synthetic hormone has less effect on the smooth muscles of the vascular system and internal organs, so there are no spastic side effects.

Unlike vasopressin, its structural artificial analogue, desmopressin, does not increase blood pressure, and its effect is generally longer and more gentle. Thus, the artificial change in the vasopressin molecule when creating a synthetic analogue of desmopressin was aimed at improving the natural hormone, adjusting its work, minimizing side effects.

Vasopressin: action, methods of application and dosage of the drug

Everyone knows how important water is for the human body.Most sources cite 70% as the average body water content for the average person in adulthood. Only surrounded by water can human cells perform their functions and provide homeostasis (constancy of the internal environment of the body). In the course of metabolic processes, the water balance is constantly disturbed, therefore there are mechanisms that contribute to maintaining the constancy of the environment.

• synthesis
• functions
• excess
• deficiency
• analysis
• experiment with ADH

One of these mechanisms is hormonal. Antidiuretic hormone (ADH) , or vasopressin, regulates the retention and excretion of water from the body. It starts the process of reabsorption in the microstructures of the kidneys, during which secondary urine is formed. Its amount is dosed and should not exceed 1.5-2 liters per day. Even when the body is dehydrated, the action of vasopressin in combination with other hormones prevents the internal environment from drying out.

Indications for use

The drug Vasopressin is prescribed in the following cases:

• treatment of pituitary insipidus insipidus;
• Stopping certain types of bleeding that can occur with pathologies of the esophagus, intestinal diverticulosis, as well as varicose veins.

This agent is an antidiuretic hormone of the hypothalamus, which helps to increase the reabsorption of fluids by the kidneys, as well as to increase the concentration of urine with a simultaneous decrease in its volume.

In the human body, the synthesis of this hormone is carried out in the large cell neurons of the hypothalamus. Being synthesized in the body of a neuron, with the help of axons, it is redirected to synapses, after which the synaptic vesicles begin to accumulate. Then, at the time of the action of a nerve impulse on a neuron, this hormone is excreted into the blood.

The drug Vasopressin,

The drug of the same name is a synthetic variant of the hormone Vasopressin, which, as a rule, is produced in the form of special solutions that are intended for injection or internasal administration.

Interacting with V and Vi receptors located on the walls of vascular smooth muscles, this drug regulates vasoconstriction.

Vasopressin has a beneficial effect on the state of the nervous system by reducing aggression and improving the memory process.

Tests for detection: norm, deviations

A blood test for ADH is prescribed with strong thirst and increased urine output or decreased urine output, edema, headache and muscle weakness. The rate of content in the blood depends on the osmolarity of the plasma. Therefore, this indicator is first determined, and then the level of vasopressin.

The result is calculated individually according to the tables. For example, with an osmolarity of 280-285 mOsm / kg, ADH should be up to 2.3 pmol / L. An unreliable diagnostic result is possible with alcohol intake, physical or emotional stress, smoking on the eve of the examination.

Contraindications

In order not to cause irreparable harm to your health, it is important to know in what cases it is necessary to avoid the use of Vasopressin.

The main contraindications to the use of this medicinal product are:

• the occurrence of severe allergic reactions to the active substance;
• ischemic heart disease;
• Diseases affecting peripheral vascular function;
• Violation of the processes of coronary circulation.

In addition to the listed contraindications, it should be borne in mind that the internal nasal method of using Vasopressin is unacceptable in the presence of diseases such as sinusitis or rhinitis.

Functionality of the hypothalamus hormone

Lack of vasopressin in the body leads to the emergence of a specific and rather complex disease – diabetes insipidus. Its symptoms are:

• Increased daily urine volume – 8 liters or more;
• Intense thirst;
• Desiccation of mucous membranes – mouth, nose, eyes, trachea, bronchi, stomach;
• Increased weakness of the body;
• Increased emotional response and external stimuli.

The causes of diabetes insipidus can be both vasopressin deficiency and infection of the body. Tumor neoplasms of the hypothalamus and pituitary gland are not excluded. Kidney disease, manifested in impaired synthesis and regulation of vasopressin, can be the cause of diabetes insipidus.

Histogenic diabetes insipidus also occurs in women during pregnancy as a result of the breakdown of the amino acid arginine in the structure of the hormone vasopressin.

If vasopressin is in excess in the body, then there is a syndrome of inadequate secretion of Schwartz-Barter. This means that fluid begins to accumulate in the body, provoking the onset of water intoxication.

Side effects

In some cases, taking the hormonal drug Vasopressin may be accompanied by side effects:

• headaches and dizziness;
• nausea and vomiting;
• painful sensations and inflammations of the skin directly in those places where the drug was injected;
• spasms occurring in the abdominal region;
• Allergic manifestations in the form of rashes on the skin, sometimes accompanied by itching.

In addition, if the drug is used at an overestimated dosage, ventricular arrhythmia, coronary heart disease, bowel pathology, skin necrosis, myocardial infarction and even cardiac arrest may occur. However, such side effects occur in extremely rare cases.

Directions for use

In order to obtain the best therapeutic result and avoid even the slightest side effects, Vasopressin must be used in strict accordance with the instructions in the instructions.

There are two ways to use this synthetic hormonal preparation – internasal and injectable. The second method – injection – in turn, can be carried out both intravenously and intramuscularly.

Cortisozol is called the stress hormone. For what functions it is responsible in the female and male body, you can find out here.

The main function of prolactin is to provide breastfeeding. Information on how and when to get tested for prolactin can be found in this material.

Treatment

To get rid of excess antidiuretic hormone it is necessary to use antagonists, they are called vaptans. During the day during the detection of the disease, it is necessary to observe the level of fluid consumed. Do not drink less than 500-1000 ml of water.

The hormone vasopressin does not have many different functions, but if the activity of its secretion is disrupted, diseases can appear. In order to prevent the development of diseases, it is recommended to visit a specialist and examine the body at least 1-2 times a year.

Dosage

Depending on the symptoms of the disease, the drug Vasopressin is used in different dosages.

For the treatment of diabetes insipidus, the internal route of administration of the drug is mainly used.

In this case, the doctor prescribes the dosage and course of treatment individually in each case.

In order to stop any type of bleeding, a solution is prepared consisting of 100 IU of Vasopressin and 250 ml of a 5% glucose solution.

Using a special dispenser, inject into the central or peripheral vein. Until the bleeding stops completely, 0.3 IU of solution is injected every thirty minutes, increasing the dosage by 0.3 IU. After the bleeding has stopped, the dosage is reduced. The maximum allowable dosage in this case is 0.9 IU of Vasopressin.

In order to reduce the risk of complications and side effects, it is recommended to simultaneously inject Nitroglycerin intravenously with Vasopressin.Its optimal dosage is 10 mcg per minute, increasing by the same amount every 15 minutes.

If any side effects occur, the procedure must be stopped immediately.

Structure and relationship to oxytocin

Vasopressin is a peptide consisting of nine amino acids (nonapeptide). (NB: the value of 164 amino acids in the above table is obtained before the hormone is activated by cleavage). The amino acid sequence of arginine vasopressin: Cis – Tyr – Phen – GLN – ASN – Cis – O – Arg – Gly, while the cysteine ​​residues form disulfide bonds.Lysine vasopressin has lysine instead of arginine.

The structure of oxytocin is very similar to that of vasopressin: it is also a disulfide-bridged nonapeptide and its amino acid sequence differs only in two positions. The two genes are located on the same chromosome, separated by a relatively small distance of less than 15,000 in most species. Magnocellular neurons that produce vasopressin adjacent to magnocellular neurons produce oxytocin, and they are similar in many ways.The similarity of the two peptides can cause some cross-reactions: oxytocin has a mild antidiuretic effect, and high AVP levels can cause uterine contractions

Below is a table showing the superrodynes of the neuropeptides vasopressin and oxytocin:

14

-Tyr-Phe-Gln-Asn-Cys-Pro-Arg-Gly-Nh3

Octopus Vasotocin is the evolutionary ancestor of all vertebrate neurohypophyseal hormones.

Overdose

In case of an overdose of the drug Vasopressin, side effects may develop in the form of:

• intoxication;
• hyperexcitability;
• headaches and confusion;
• muscle spasms;
• coma;
• hyponatremia;
• lowering blood pressure;
• soreness in the abdomen;
• vomiting.

To get rid of these phenomena, symptomatic therapy should be carried out immediately.

If vasopressin is elevated

Excessive production of ADH is rare, this condition is called Parkhon’s syndrome. The syndrome of excessive secretion of vasopressin is characterized by hyponatremia, decreased density of blood plasma, and the release of concentrated urine.

That is, due to increased hormone production, water intoxication and massive loss of electrolytes develop (fluid accumulates in the body, and trace elements are removed from it).

Patients with this pathology complain about:

• Decreased urine output and a small amount of urine excreted.
• Rapid weight gain.
• Convulsions.
• Increasing weakness.
• Nausea.
• Headache.
• Loss of appetite.

In severe cases, the patient falls into a coma and dies, which is a consequence of the suppression of vital body functions and cerebral edema.

The reasons for the development of Parkhon’s syndrome can be:

• Some neoplasms (for example, small cell lung tumors).
• Diseases of the brain.
• Cystic fibrosis
• Bronchopulmonary pathologies.

One of the provoking factors in the development of this condition may be the intake of certain drugs (if they are intolerant) NSAIDs, barbiturates, opiates, psychotropics, and so on.

Therapy of Parkhon’s syndrome is reduced to the appointment of vasopressin antagonists (vaptans), as well as to limiting the volume of fluid consumed to half a liter-liter per day.

Analogues

Vasopressin has several analogs, which are characterized by a similar effect and indications for use.

Remestip (Terlipressin)

Desmopressin and Terlipressin are the most popular and effective Vasopressin analogues. Other substitutes include Adiuretin, Vazomirin, Minirin, Nativa, Presynex, Remistip, and Emosynt.

Desmopressin is available in three dosage forms – tablets, spray and drops. It is intended for the treatment of central diabetes insipidus, nocturnal polyuria in adults and primary enuresis in children over five years of age.

Terlipressin, belonging to the category of synthetic polypeptides, is used to eliminate bleeding of various types – uterine, gastrointestinal, and also associated with surgical interventions.

The normal level of calcitonin in women fluctuates depending on age. But the deviation from the “golden mean” speaks of serious failures in the body.

The stability of the menstrual cycle and other functions of the body depends on the content of estradidol in the body of women.What indicator of this hormone is the norm, read here.

Progesterone during pregnancy is responsible for the correct functioning of the whole organism of the expectant mother. And pregnancy itself is possible only due to the optimal level of this hormone.

Main functions of ADH

Vasopressin is necessary to maintain the required amount of fluid in the body. Its main purpose is to delay the removal of water. This is due to the stimulation of its reabsorption from the primary urine in the kidney tubules. Under the influence of ADH, the following changes occur:

• urination decreases;
• the amount of salt in the urine increases;
• increased blood volume in the vascular bed;
• plasma osmolarity (concentration) decreases.

The sodium level determines the osmolarity in the liquid portion of the blood. If it is less than 275 mosm / kg, then vasopressin is not required, its secretion by the pituitary gland stops, and the kidneys filter a lot of urine of low concentration.When the value rises to 300 mOsm / kg, thirst arises, ADH passes into the bloodstream, reaches the kidneys and inhibits the excretion of water.

Publications in mass media

(Pituitrinum)

Synonyms.

Composition and form of release. 1 ml ampoules containing 5 U of pituitrin. The main active ingredients of the drug are oxytocin and vasopressin.

Indications. To stimulate and enhance the contractile activity of the uterus, hypotonic bleeding in the early postpartum period, to normalize the involution of the uterus in the postpartum and post-abortion periods.It is also used for bedwetting and diabetes insipidus.

Pharmacological action. Myometrium contains receptors specific for the hormone oxytocin, and their stimulation leads to a contraction of the smooth muscles of the uterus by increasing the intracellular concentration of calcium ions. Moreover, with an increase in the duration of pregnancy, the number of oxytocin receptors in the uterus gradually increases, reaching a maximum by the end of pregnancy, and the reaction of the uterine muscles will increase.Under the influence of oxytocin, the amplitude and duration of uterine contractions increases, leading to relaxation and smoothing of the cervical canal neck. Vasopressin causes narrowing of capillaries and an increase in blood pressure, is involved in regulating the constancy of osmotic blood pressure, causing an increase in water reabsorption in the convoluted tubules of the kidneys and a decrease in chloride reabsorption.

When administered parenterally, the effect of the drug develops within a few minutes and lasts for 2-3 hours.

Pharmacokinetics. Pituitrin is destroyed in the gastrointestinal tract, therefore it is administered parenterally. T 1/2 of the drug is several minutes.

Side effects. Large doses of the drug can cause cerebral vasospasm, hemodynamic disturbances, collapse.

Contraindications. Severe atherosclerosis, myocarditis, hypertension, thrombophlebitis, sepsis, nephropathy of pregnant women, scars on the uterus, threat of uterine rupture, abnormal fetal position.

Adverse reactions when interacting with other drugs. When combined with drugs that increase blood pressure, hypertension may develop.

Information for the patient. The drug is administered parenterally under close medical supervision.

Flumed-Farm S.R.L – Desmop 10mcg / doza 7ml

COMPOSITION

1 dose contains:

Active oe substance : desmopressin – 10 μg;

B auxiliary substances: sodium chloride, citric acid monohydrate, sodium hydrogen phosphate anhydrous, benzalkonium chloride solution, purified water.

PREPARATION DESCRIPTION

Transparent, colorless liquid.

PHARMACOTHERAPY GROUP and ATC code

Hormones of the posterior lobe of the pituitary gland. Vasopressin and analogues, H01BA02.

PHARMACOLOGICAL PROPERTIES

Pharmacodynamics

Desmopressin is a structural analogue of the natural hormone vasopressin (antidiuretic hormone).Desmopressin is synthesized by changing the structure of the vasopressin molecule by deamination of 1-cysteine ​​and replacing 8-L-arginine with D-arginine. The drug increases the affinity of the epithelium of the distal convoluted tubules and increases their water reabsorption. Prescribing the drug for diabetes insipidus leads to a decrease in urine volume, a simultaneous increase in its osmotic pressure and a decrease in blood osmolarity. This leads to a decrease in the frequency of urination and nocturia. The antidiuretic effect after nasal administration of 20 mcg lasts for 10 hours.

Pharmacokinetics

Bioavailability after intranasal administration of the drug is 10%. A significant concentration of desmopressin in the blood was determined 50 min after administration. The half-life after introduction into the nose is 2-3 hours. The drug is excreted through the kidneys.

THERAPEUTIC INDICATIONS

– Treatment of diabetes insipidus of central genesis;

– Differential diagnosis of diabetes insipidus;

– Treatment of post-traumatic polyuria and polydipsia, conditions after hypophysectomy, surgery or trauma in the pituitary gland;

– Treatment of nocturia in adults;

– Primary nocturnal enuresis in children under 5 years of age;

– Testing the ability of the kidneys to concentrate urine.

METHOD OF APPLICATION AND DOSES

The drug is administered intranasally.

One DESMOP dose contains 10 μg of desmopressin.

Before using the drug, it is imperative to sanitize the nasal cavity. The applicator is placed inside the nasal cavity and pressed once. To re-dose, the drug is injected into the other nostril. After application, the applicator is covered with a protective cap.

Diabetes insipidus, post-traumatic polyuria and polydipsia, condition after hypophysectomy, surgery or trauma in the pituitary gland

The dose is selected individually, but the recommended starting dose is:

Adults: 10-20 mcg 1-2 times a day;

Children over 1 year old: 10 mcg 1-2 times a day.

In case of fluid retention / hyponatremia, discontinuation of therapy and dose adjustment are required.

Nocturia

The dose is selected individually by the doctor. The dose can range from 10 μg to 40 μg of desmopressin.

If the desired therapeutic effect is not achieved after 4 weeks of administration, treatment should be discontinued.

Nocturnal enuresis

The dose is selected individually by the doctor. The dose can range from 10 μg to 40 μg of desmopressin.

In long-term treatment, there should be a break of at least a week every three months to assess whether there has been a spontaneous cure.

Testing kidney function

Adults: 40 mcg.

Children over 1 year old: 20 mcg.

Children under the age of 1 year up to 10 mcg.

After administration of DESMOP – urine collected within the first hour is not used for analysis. After 8 hours, 2 portions of urine are collected to determine its osmolarity. Fluid intake should also be investigated.

SIDE EFFECTS

Adverse reactions are listed in accordance with MedDRA by device, system organs and frequency:

very frequent (> 1/10),

frequent (> 1/100 and

infrequent (> 1/1000 and

rare (> 1/10000, <1/1000),

very rare (<1/10000),

with unknown frequency (cannot be estimated from the available data).

Endocrine disorders

Very rare: hyponatremia.

Heart disorders

Unknown: hypertension, refractory hypertension.

Vascular diseases

Unknown: May cause strokes in patients with coronary artery disease.

Mental disorders

Rare: emotional disorders in children.

Disorders of the nervous system

Rare: headache, cerebral edema, impaired consciousness, convulsions caused by hyponatremia.

Respiratory, chest and mediastinal phenomena

Often: epistaxis, nasal congestion, rhinitis.

Phenomena of the gastrointestinal tract

Often: nausea, vomiting, abdominal pain.

Disorders of the skin and subcutaneous tissue

Very rare: allergic reactions, hypersensitivity reactions (itching, rash, fever, bronchospasm, anaphylaxis).

With a decrease in doses, side effects disappear, except for allergic reactions.

CONTRAINDICATIONS

– Hypersensitivity to desmopressin and other components of the drug;

– Congenital or psychogenic polydipsia;

– Heart failure and other conditions requiring the use of diuretics;

– Moderate or severe renal failure (creatinine clearance less than 50 ml / min).

OVERDOSE

Symptoms: fluid retention, headache, nausea, vomiting, moderate hypertension, tachycardia, hot flashes, in severe cases, hyponatremia and convulsions.

Treatment: Treatment of hyponatremia individually. In case of asymptomatic hyponatremia, stop using the drug and limit fluid intake. In hyponatremia, isotonic solution or hypertonic sodium chloride solution is recommended. In cases where fluid retention is severe (convulsions, loss of consciousness), it is recommended to combine furosemide.

PRECAUTIONS AND APPLICATION FEATURES

During the kidney function test, fluid intake will be limited to 0.5 liters per day, especially up to 1 hour before and 8 hours after drug administration.

DESMOP will be used with caution in young and adult patients with fluid-electrolyte imbalance, patients with an increased risk of intracranial hypertension and thrombosis.

The drug is not recommended for patients with changes in the nasal mucosa (scars, edema, etc.) because they can lead to uneven and uncertain absorption of the drug.

The drug should be used with caution in patients with cystic fibrosis. Treatment without restriction of fluid intake can lead to water retention in the body and / or hyponatremia (headache, nausea, vomiting, weight gain, in severe cases – convulsions, cerebral edema, coma).

Fluid intake should be monitored in children and the elderly to prevent overhydration.

Patients with fluid and electrolyte imbalances (systemic infections, fever, syndrome of inappropriate antidiuretic hormone secretion) and patients with intracranial hypertension should be especially careful when consuming fluids.

In the treatment of diabetes insipidus, it is necessary to use the minimum effective dose, periodic determination of urine volume and osmolarity, and in some cases, plasma osmolarity.

Desmopressin treatment should be discontinued for intercurrent acute illnesses characterized by fluid and electrolyte imbalance (systemic infections, fever, and gastroenteritis).

Use in children will be supervised by adults to prevent overdose.

This product contains benzalkonium chloride. This is an irritant. May cause skin reactions.

Use during pregnancy and lactation

The drug should be used with caution during pregnancy, that is, it is necessary to carefully analyze the ratio of the expected benefit to the mother / potential risk to the fetus.

The results of the analysis of the milk of nursing mothers who received high doses of desmopressin (300 μg of intranasal aerosol solution) show that significantly less desmopressin is transmitted to newborns than doses that affect diuresis.

Influence on the ability to drive a car and equipment

The drug does not affect the ability to drive a car or operate machinery.

INTERACTION WITH OTHER DRUGS, OTHER FORMS OF INTERACTION

When administered together with oxytocin, an increase in antidiuretic effect and a decrease in uterine perfusion pressure will be taken into account.Clofibrate, indomethacin and carbamazepine increase the antidiuretic effect of desmopressin, while glibenclamide and lithium salts decrease.

Chlorpromazine, tricyclic antidepressants, selective serotonin reuptake inhibitors, NSAIDs can stimulate the secretion of antidiuretic hormone, which can potentiate the action of the drug and increase the risk of fluid retention.

RELEASE FORM, PACKAGING

Nasal spray, solution, 10 mcg / dose.3.5 ml / 25 doses or 7 ml / 50 doses in glass vials. The cardboard box contains 1 bottle with a dispenser, a nasal applicator, a protective cap and instructions for use.

STORAGE CONDITIONS

Store at temperatures below 25 ° C.

Store in original packaging to protect from light and moisture.

Keep out of the reach of children!

SHELF LIFE

3 years.

Do not use after the expiry date printed on the package.

RELEASE CONDITIONS

Prescribed by a doctor.

which drugs and drugs to take

Groups of drugs

For the treatment to be successful, they affect the entire chain of cause-and-effect relationships that provoke heart pain. There is no single drug that solves this problem. Everyone needs an individual combination of several means, which the doctor selects taking into account the results of all tests.The modern pharmaceutical market is releasing new drugs that combine several properties as much as possible so that a person does not have to drink pills in handfuls, but they are often not enough. According to the standards of treatment, remedies for pain in the heart are selected from the following groups:

List of drugs

If the heart hurts, a person must know the names of the drugs in order to alleviate the condition before visiting a doctor or the arrival of an ambulance. The best option is to have these medicines in your home first aid kit:

• Validol belongs to reflex medicines.Its main substance is menthol solution. The medicine does not work directly on pain in the heart, but it calms the nervous system and dilates blood vessels. It goes well with Nitroglycerin. Due to the reception of the latter, the patient often has side effects. “Validol” stops them and relieves anxiety, which torments a person with pain in the heart;
• “Nitroglycerin” – nitrate, which is a group of peripheral vasodilators. Created on the basis of the substance of the same name. Apply a medicine to relieve an attack of angina pectoris.Acts by dilating blood vessels and improving blood circulation. Take “Nitroglycerin” sublingually (under the tongue). Thanks to this, the effect is felt in the next two to three minutes. If the action is weak, then repeated use is allowed after 5-10 minutes. The maximum dosage at a time should not exceed three tablets. If there is no result, you will need to call an ambulance, since there is a chance of developing a heart attack;

• “Aspirin” is created on the basis of acetylsalicylic acid.Reduces pain, removes fever, reduces inflammation, improves blood flow and prevents platelets from sticking to the artery wall. Due to the effect, the drug is actively used as a prophylactic agent for many heart diseases. “Aspirin” will not be able to stop angina pectoris, but with prolonged use, the chance of developing an attack will decrease;

• “Amlodipine” is a group of calcium channel blockers. Its main active ingredient is amlodipineabesylate. By preventing the ingress of calcium ions into cardiomyocytes, the drug dilates blood vessels and stabilizes the heart rhythm.Relief comes after just one dose of the medicine;
• “Anaprilin” is a beta-blocker based on propranolol hydrochloride. An improvement in the condition occurs after one dose of the drug. Stable stabilization of pressure and heart rate – in the second or third week of treatment;
• “Gemfibrozil” refers to fibrates and is popular due to its low toxic composition. The drug is based on the active substance of the same name. Thanks to this medicine, fatty acids are removed from the body, triglyceride production is reduced and cholesterol is removed.Prescribed with poor diet efficiency and poor blood biochemistry indicators;
• “Rosuvastatin” belongs to statins, serves to lower the level of bad cholesterol. Its main active ingredient is rosuvastatin. The drug is popular in people with hypercholesterolemia and atherosclerosis;
• “Ascorutin” is a vitamin complex based on ascorbic acid and rutin. In the treatment of diseases of the cardiovascular system, the drug is used to strengthen blood vessels and relieve inflammation from them.A long course of admission allows you to achieve the normalization of metabolism and improve the protective properties of the body;
• “Asparkam” is used to normalize the electrolyte balance and restore the usual heart rhythm. The main active ingredients of the drug are magnesium and potassium.

Effects of ecstasy on the body

The main effects are stimulating, euphorizing and empathogenic. In many ways, the effect of ecstasy depends on the dose, the level of addiction to the drug, the emotional state and physical condition of the person.The action of the pill appears after 20-60 minutes after ingestion and lasts from 2 to 5-6 hours. The peak of euphoria is reached after 1.5-2 hours, then the plateau phase begins, which lasts about 3 hours and ends with the return of all psychophysiological parameters to normal.
Users can take multiple pills at once or take an extra dose during a plateau to prolong the ecstasy “onset”. The clinical manifestations of drug intoxication can vary greatly, as the amount of MDMA varies widely in products from different manufacturers.The effects caused by taking ecstasy are classified into psychological and physiological.

Psychological Effects

The euphorizing and empathogenic properties of ecstasy are the basis of the drug’s popularity. Users experience an uplifting mood, a desire to communicate, and a decrease in fear and anxiety. Sometimes there are paradoxical reactions of increasing aggression and anger. The most common effects of the drug on the psyche are manifested through:

• weakening of psychological problems that prevent interaction with other people (reduction of shyness, complexes, anxiety)
• simplification of verbal communication, deterioration of the fluency of pronunciation and speech structure
• increased need for love and acceptance , a feeling of closeness with others
• a feeling of inner well-being, happiness and harmony
• memory impairment, concentration of attention, the ability to solve intellectual problems

Physiological effects

Ecstasy tablets excite the nervous system, including the part that innervates the internal organs …Under the influence of the drug, the content of certain hormones – prolactin, oxytocin, cortisol and vasopressin – increases. Main physiological effects:

• Increased blood pressure, increased heart rate
• Increased energy production in the brain
• Capillary constriction, difficulty in sweating, increased body temperature
• Pupil dilation and deterioration of their response to light
• Chewing sculptural muscles
• Blurring and duality of visually perceived objects;
• nausea, decreased appetite
• impaired coordination of movements, muscle pain and convulsions;
• Difficulty urinating

First aid measures

If the condition deteriorates sharply, it is necessary to urgently call an ambulance or ask nearby people about it.Before her arrival, the following drugs are taken:

• “Aspirin”;

• “Nitroglycerin”;
• Validol.

Aspirin is drunk first of all, because it thinns the blood and promotes the rapid absorption of other drugs. “Nitroglycerin” will dilate blood vessels and reduce the feeling of discomfort, and “Validol” will remove anxiety. After the ambulance arrives, tell the doctors which heart pain pills have been used since the onset of the attack.

What should be done if the patient has no heartbeat?

Cardiac arrest can be suspected if a person suddenly lost consciousness and does not respond to external stimuli (hit on the cheeks, loudly clap your hands, spray your face with water).So, if someone has lost consciousness with you, you need to immediately check the pulse on the main vessels. To do this, the middle of the neck (Adam’s apple in men) is groped with the pads of the fingers and is shifted sideways until it stops in the sternocleidomastoid muscle. It is along its course that the carotid arteries are located (photo 1).

It is also necessary to check whether the person is breathing or not. How to do this is shown in photo 2.

Putting your ear to the victim’s nose, and looking at his chest, you can hear breathing, notice the raising and lowering of the chest.

If there is no heartbeat or spontaneous breathing, you must immediately call an ambulance and immediately begin cardiopulmonary resuscitation. Actions consist in an indirect heart massage, which is performed by compressions on the chest, and artificial ventilation of the lungs by mouth-to-mouth or mouth-to-nose breathing. If there is only one resuscitator, preference is given to compressions. It is important not to stop providing assistance until the arrival of the team or the restoration of cardiac activity, because in 6-10 minutes irreversible hypoxic changes occur in the brain, which leads to the death of its cells and severe neurological disorders in the future (if the measures are successful).

In many countries, defibrillator stands are installed in public places to provide immediate assistance to a dying person. This significantly increases the chances of effectively and timely resuscitating a person.

Course of treatment

During the active phase of pain in the region of the heart, the patient must take off the squeezing clothes and relax. Such actions will ease the condition, allow you to understand the nature of the pain and figure out what to do next:

• stitching and aching sensations in the heart, which are accompanied by a rapid pulse, an attack of suffocation, fever and headache, are stopped by Validol.They put it under the tongue. Relief occurs in 10-15 minutes. If this drug is not available, use alcoholic tinctures on lemon balm, hawthorn, peppermint and other herbs with a sedative effect. Usually pains of this nature are manifested due to stress, vascular dystonia and overwork. They are unstable and often change location and intensity;
• Sharp, dull and compressive pain in the chest indicates angina pectoris. If discomfort manifests itself when walking, overwork and stress, then the problem is related to cardiac ischemia.First, take Validol or an alcoholic herbal tincture. When there is no effect, put “Nitroglycerin” under the tongue. The procedure can be repeated after 10 minutes. It was not possible to achieve the result – you will need to call an ambulance;
• Painful sensations of an acute and sharp nature, aggravated by movement and having precise localization, indicate the development of back diseases. They alleviate the condition with the help of non-steroidal anti-inflammatory drugs (Nurofen, Ibuprofen), produced in tablet form and in the form of topical agents (ointment, gel, cream).For the best effect, it is recommended to apply them simultaneously.

Popular drug for hypertension recognized as dangerous to the heart

The drug nifedipine, intended for the treatment of hypertension and angina pectoris, increases the risk of sudden cardiac arrest, found out cardiologists from the Academic Medical Center in Amsterdam. They presented the results at the annual congress

of the European Heart Rhythm Association in Lisbon.

Nifedipine inhibits the flow of calcium ions through the membrane of cardiomyocytes and vascular smooth muscles, which leads to a decrease in the accumulation of calcium inside cells.This causes the coronary arteries and blood vessels to dilate, thus reducing the stress on the heart and increasing the oxygen supply to the myocardium.

Under the influence of the drug, blood pressure decreases, chest pain associated with myocardial hypoxia disappears or decreases.

In Russia, the drug is dispensed by prescription.

Sudden cardiac arrest causes about half of all deaths from heart disease in Europe. First, arrhythmia develops, then, if this condition is not treated in time, the heart stops.

Researchers wanted to investigate whether drugs for the treatment of angina pectoris containing nifedipine, amlodipine, and dihydropyridines are associated with an increased risk of sudden cardiac arrest. After analyzing the data of more than 10 thousand patients, they found that

the use of nifedipine in high doses, more than 60 mg per day, was associated with an increased risk of cardiac arrest.

The rest of the studied drugs for angina pectoris did not give such an effect.

Additionally, scientists tested the results on human heart cells.The data were confirmed – high doses of nifedipine contributed to the occurrence of fatal arrhythmias, blocking calcium channels and thereby reducing the action potential of cells.

“Nifedipine and amlodipine are commonly used by many cardiologists and other physicians, and the choice is often influenced by physician preference and personal experience,” notes Dr. Hanno Tan, lead author of the study. – Both drugs are generally considered equally effective and safe, and neither has previously been associated with sudden cardiac arrest.This study suggests that high doses of nifedipine may increase the risk of sudden cardiac arrest due to fatal cardiac arrhythmias, while amlodipine does not. The results are confirmed in other studies and they may have to be taken into account when considering the use of a particular drug. ”

The product has been in use for many years. However, the causes of cardiac arrest outside the hospital cannot always be reliably diagnosed, so this pattern was only discovered now, upon closer examination.

However, Tang urges not to make hasty conclusions.

His work is the first to establish a link between nifedipine and cardiac arrest, so the results have yet to be verified in other studies.

Earlier it became known about recalls

of the preparations “Erespal”, “Erispirus” and “Epistat” containing fenspiride, as they can affect heart health.

The withdrawal from circulation of the drug “Erespal”, which caused questions from the French authorities, became known on 14 February.“The Federal Service for Surveillance in Healthcare informs the subjects of medicines circulation a letter from the representative office of Servier Laboratories, France, about the revocation of registration certificates and the withdrawal from circulation of all series of Erespal medicines … due to the unfavorable benefit-risk ratio “When using these drugs”, – said in the document of Roszdravnadzor. At the same time, the territorial bodies of Roszdravnadzor need to ensure control over the withdrawal from circulation of all series of these drugs – we are talking about film-coated tablets and 2 mg / ml syrup.

Earlier, the French supervisory authorities decided to withdraw drugs containing fenspiride from circulation.

This became known from the message of the Russian representative office of pharmacological (Servier), the owner of the registration certificate for “Erespal” (called “Pnevmorel” in Europe).

Later, the Hungarian pharmaceutical company Gedeon Richter Ltd, against the background of the situation with Erespal, decided to withdraw from circulation and no longer supply the country with an analogue of this medicine – Epistat.“Taking into account these data and taking into account the fact that“ Erespal ”is prescribed for the treatment of respiratory diseases (rhinopharyngitis, laryngitis, tracheobronchitis, bronchitis (with or without chronic respiratory failure), bronchial asthma (as part of complex therapy), respiratory phenomena (cough, hoarseness, sore throat) with measles, whooping cough and flu, with infectious diseases of the respiratory tract, accompanied by cough, when standard antibiotic therapy is indicated), otitis media and sinusitis of various etiologies, for which there are alternative methods of therapy, it was decided the withdrawal from circulation of medicinal products Erespal®, 80 mg, film-coated tablets and Erespal®, 0.