Desmopressin
Encyclopedia
Desmopressin is a synthetic
replacement for vasopressin
, the hormone
that reduces urine
production. It may be taken nasally, intravenously, or as a tablet. Doctors prescribe Desmopressin most frequently for treatment of diabetes insipidus
bedwetting or nocturia.
, a peptide containing nine amino acids.
Compared to vasopressin, desmopressin's first amino acid has been deaminated
, and the arginine
at the eighth position is in the dextro rather than the levo form (see stereochemistry
).
Desmopressin binds to V2 receptor
s in renal
collecting ducts, increasing water reabsorption. It also stimulates release of von Willebrand factor
from endothelial cells due to stimulation of the V1a receptor.
Desmopressin is degraded more slowly than recombinant
vasopressin, and requires less frequent administration. In addition, it has little effect on blood pressure
, while vasopressin may cause arterial hypertension.
. Drug therapy tends to have its place only when the mouthpiece system is impractical or not effective. Examples of these situations are overnight camp and sleepovers.
US drug regulators banned treating sleep apnea with desmopressin nasal sprays after two patients died and 59 other patients suffered seizures. The patients were using desmopressin when they developed Hyponatremia
, an imbalance of the body's sodium levels.
FDA regulators said that desmopressin tablets could still be considered safe for Sleep Apnea
treatment, as long as the patient was otherwise healthy. Patients must stop taking desmopressin if they become sick and have severe vomiting and diarrhea, fever, the flu, or severe cold. They should also be very cautious during hot weather or following strenuous exercise that may make them thirsty.
A healthy body needs to maintain a balance of water and salt (sodium
). If sodium levels become too low (hyponatremia
) – either as a result of increased water take-up or reduced salt levels – a person may have seizures and, in extreme cases, may die.
(with subsequent increase in factor VIII
survival secondary to vWF complexing) in patients with coagulation
disorders such as von Willebrand disease
, mild hemophilia A (factor VIII deficiency), and thrombocytopenia
. It can be used with uremic induced platelet dysfunction. It is not effective in the treatment of hemophilia B (factor IX deficiency), severe hemophilia A, or von Willebrand 2B.
(DI), to replace endogenous ADH that is missing in the central nervous system type of this disorder (decreased production of ADH from hypothalamus). It is also used in the diagnostic workup for diabetes insipidus, in order to distinguish central from nephrogenic DI.
Chemical synthesis
In chemistry, chemical synthesis is purposeful execution of chemical reactions to get a product, or several products. This happens by physical and chemical manipulations usually involving one or more reactions...
replacement for vasopressin
Vasopressin
Arginine vasopressin , also known as vasopressin, argipressin or antidiuretic hormone , is a neurohypophysial hormone found in most mammals, including humans. Vasopressin is a peptide hormone that controls the reabsorption of molecules in the tubules of the kidneys by affecting the tissue's...
, the hormone
Hormone
A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...
that reduces urine
Urine
Urine is a typically sterile liquid by-product of the body that is secreted by the kidneys through a process called urination and excreted through the urethra. Cellular metabolism generates numerous by-products, many rich in nitrogen, that require elimination from the bloodstream...
production. It may be taken nasally, intravenously, or as a tablet. Doctors prescribe Desmopressin most frequently for treatment of diabetes insipidus
Diabetes insipidus
Diabetes insipidus is a condition characterized by excessive thirst and excretion of large amounts of severely diluted urine, with reduction of fluid intake having no effect on the concentration of the urine. There are several different types of DI, each with a different cause...
bedwetting or nocturia.
Chemistry
Desmopressin (1-desamino-8-D-arginine vasopressin) is a modified form of the normal human hormone arginine vasopressinVasopressin
Arginine vasopressin , also known as vasopressin, argipressin or antidiuretic hormone , is a neurohypophysial hormone found in most mammals, including humans. Vasopressin is a peptide hormone that controls the reabsorption of molecules in the tubules of the kidneys by affecting the tissue's...
, a peptide containing nine amino acids.
Compared to vasopressin, desmopressin's first amino acid has been deaminated
Deamination
Deamination is the removal of an amine group from a molecule. Enzymes which catalyse this reaction are called deaminases.In the human body, deamination takes place primarily in the liver, however glutamate is also deaminated in the kidneys. Deamination is the process by which amino acids are...
, and the arginine
Arginine
Arginine is an α-amino acid. The L-form is one of the 20 most common natural amino acids. At the level of molecular genetics, in the structure of the messenger ribonucleic acid mRNA, CGU, CGC, CGA, CGG, AGA, and AGG, are the triplets of nucleotide bases or codons that codify for arginine during...
at the eighth position is in the dextro rather than the levo form (see stereochemistry
Stereochemistry
Stereochemistry, a subdiscipline of chemistry, involves the study of the relative spatial arrangement of atoms within molecules. An important branch of stereochemistry is the study of chiral molecules....
).
Mode of action
Desmopressin works by limiting the amount of water that is eliminated in the urine.Desmopressin binds to V2 receptor
Arginine vasopressin receptor 2
Arginine vasopressin receptor 2 is a protein that acts as receptor for arginine vasopressin. AVPR2 belongs to the subfamily of G-protein-coupled receptors...
s in renal
Kidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
collecting ducts, increasing water reabsorption. It also stimulates release of von Willebrand factor
Von Willebrand factor
von Willebrand factor is a blood glycoprotein involved in hemostasis. It is deficient or defective in von Willebrand disease and is involved in a large number of other diseases, including thrombotic thrombocytopenic purpura, Heyde's syndrome, and possibly hemolytic-uremic syndrome...
from endothelial cells due to stimulation of the V1a receptor.
Desmopressin is degraded more slowly than recombinant
Recombinant DNA
Recombinant DNA molecules are DNA sequences that result from the use of laboratory methods to bring together genetic material from multiple sources, creating sequences that would not otherwise be found in biological organisms...
vasopressin, and requires less frequent administration. In addition, it has little effect on blood pressure
Blood pressure
Blood pressure is the pressure exerted by circulating blood upon the walls of blood vessels, and is one of the principal vital signs. When used without further specification, "blood pressure" usually refers to the arterial pressure of the systemic circulation. During each heartbeat, BP varies...
, while vasopressin may cause arterial hypertension.
Sleep Apnea
Doctors prescribe desmopressin frequently for treatment. It is usually in the form of Desmopressin acetate, DDAVP. Patients taking DDAVP are 4.5 times more likely to sleep without disruption than with placebo. That said, the first-line treatment is usually mouthpieceMouthguard
A mouthguard is a protective device for the mouth that covers the teeth and gums to prevent and reduce injury to the teeth, arches, lips and gums...
. Drug therapy tends to have its place only when the mouthpiece system is impractical or not effective. Examples of these situations are overnight camp and sleepovers.
US drug regulators banned treating sleep apnea with desmopressin nasal sprays after two patients died and 59 other patients suffered seizures. The patients were using desmopressin when they developed Hyponatremia
Hyponatremia
Hyponatremia is an electrolyte disturbance in which the sodium concentration in the serum is lower than normal. In the vast majority of cases, hyponatremia occurs as a result of excess body water diluting the serum sodium and is not due to sodium deficiency. Sodium is the dominant extracellular...
, an imbalance of the body's sodium levels.
FDA regulators said that desmopressin tablets could still be considered safe for Sleep Apnea
Sleep apnea
Sleep apnea is a sleep disorder characterized by abnormal pauses in breathing or instances of abnormally low breathing, during sleep. Each pause in breathing, called an apnea, can last from a few seconds to minutes, and may occur 5 to 30 times or more an hour. Similarly, each abnormally low...
treatment, as long as the patient was otherwise healthy. Patients must stop taking desmopressin if they become sick and have severe vomiting and diarrhea, fever, the flu, or severe cold. They should also be very cautious during hot weather or following strenuous exercise that may make them thirsty.
A healthy body needs to maintain a balance of water and salt (sodium
Sodium
Sodium is a chemical element with the symbol Na and atomic number 11. It is a soft, silvery-white, highly reactive metal and is a member of the alkali metals; its only stable isotope is 23Na. It is an abundant element that exists in numerous minerals, most commonly as sodium chloride...
). If sodium levels become too low (hyponatremia
Hyponatremia
Hyponatremia is an electrolyte disturbance in which the sodium concentration in the serum is lower than normal. In the vast majority of cases, hyponatremia occurs as a result of excess body water diluting the serum sodium and is not due to sodium deficiency. Sodium is the dominant extracellular...
) – either as a result of increased water take-up or reduced salt levels – a person may have seizures and, in extreme cases, may die.
Coagulation disorders
Desmopressin can be used to promote the release of von Willebrand factorVon Willebrand factor
von Willebrand factor is a blood glycoprotein involved in hemostasis. It is deficient or defective in von Willebrand disease and is involved in a large number of other diseases, including thrombotic thrombocytopenic purpura, Heyde's syndrome, and possibly hemolytic-uremic syndrome...
(with subsequent increase in factor VIII
Factor VIII
Factor VIII is an essential blood clotting factor also known as anti-hemophilic factor . In humans, Factor VIII is encoded by the F8 gene...
survival secondary to vWF complexing) in patients with coagulation
Coagulation
Coagulation is a complex process by which blood forms clots. It is an important part of hemostasis, the cessation of blood loss from a damaged vessel, wherein a damaged blood vessel wall is covered by a platelet and fibrin-containing clot to stop bleeding and begin repair of the damaged vessel...
disorders such as von Willebrand disease
Von Willebrand disease
von Willebrand disease is the most common hereditary coagulation abnormality described in humans, although it can also be acquired as a result of other medical conditions. It arises from a qualitative or quantitative deficiency of von Willebrand factor , a multimeric protein that is required for...
, mild hemophilia A (factor VIII deficiency), and thrombocytopenia
Thrombocytopenia
Thrombocytopenia is a relative decrease of platelets in blood.A normal human platelet count ranges from 150,000 to 450,000 platelets per microliter of blood. These limits are determined by the 2.5th lower and upper percentile, so values outside this range do not necessarily indicate disease...
. It can be used with uremic induced platelet dysfunction. It is not effective in the treatment of hemophilia B (factor IX deficiency), severe hemophilia A, or von Willebrand 2B.
Diabetes insipidus
Desmopressin is used in the treatment of central diabetes insipidusNeurogenic diabetes insipidus
Neurogenic diabetes insipidus, more commonly known as central diabetes insipidus, is due to a lack of vasopressin production in the brain...
(DI), to replace endogenous ADH that is missing in the central nervous system type of this disorder (decreased production of ADH from hypothalamus). It is also used in the diagnostic workup for diabetes insipidus, in order to distinguish central from nephrogenic DI.
Side effects
- headacheHeadacheA headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...
s - facial flushingFlushing (physiology)For a person to flush is to become markedly red in the face and often other areas of the skin, from various physiological conditions. Flushing is generally distinguished, despite a close physiological relation between them, from blushing, which is milder, generally restricted to the face, cheeks or...
- nauseaNauseaNausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
- hyponatremiaHyponatremiaHyponatremia is an electrolyte disturbance in which the sodium concentration in the serum is lower than normal. In the vast majority of cases, hyponatremia occurs as a result of excess body water diluting the serum sodium and is not due to sodium deficiency. Sodium is the dominant extracellular...
- seizures
Further reading
- Leissinger C, Becton D, Cornell C Jr, Cox Gill J. High-dose DDAVP intranasal spray (Stimate) for the prevention and treatment of bleeding in patients with mild haemophilia A, mild or moderate type 1 von Willebrand disease and symptomatic carriers of haemophilia A. Haemophilia 2001;7:258-66. PMID 11380629.