Demeclocycline
Encyclopedia
Demeclocycline is a tetracycline antibiotic.
It is derived from a strain of Streptomyces aureofaciens
.
l infection
s.
Its use as an antibiotic is particularly in Lyme disease
, acne
and bronchitis
.
Resistance is gradually becoming more common, and demeclocycline is now rarely used for infections.
in many countries) in the treatment of hyponatremia
(low blood sodium
concentration) due to the syndrome of inappropriate antidiuretic hormone
(SIADH) when fluid restriction alone has been ineffective.
The use in SIADH actually relies on a side effect; demeclocycline induces nephrogenic diabetes insipidus
(dehydration due to the inability to concentrate urine). The use of demeclocycline in SIADH was first reported in 1975, and, in 1978, a larger study found it to be more effective and better tolerated than lithium carbonate
, the only available treatment at the time. Demeclocycline has since been the drug of choice for treating SIADH, although it may be superseded as vasopressin receptor antagonist
s, such as tolvaptan
, become available.
, demeclocycline is contraindicated in children and pregnant or nursing women. All members of this class interfere with bone
development and may discolour teeth
.
. Skin reactions with sunlight have been reported. Demeclocycline is unique in that it is the only tetracycline known to cause nephrogenic diabetes insipidus.
Tetracyclines bind to cations such as calcium
, iron
(when given orally), and magnesium
, rendering them insoluble and inabsorbable for the GI tract. Demeclocycline should not be taken with food (particularly milk and other dairy products) or antacid
s.
- and 50S
-RNA
, which impairs protein synthesis by bacteria. It is bacteriostatic (it impairs bacterial growth but does not kill bacteria directly).
It is not completely understood why demeclocycline impairs the action of antidiuretic hormone, but it is thought that it blocks the binding of the hormone to its receptor
.
It is derived from a strain of Streptomyces aureofaciens
Streptomyces aureofaciens
Streptomyces aureofaciens is a species of Streptomyces.It is the source of many tetracycline antibiotics....
.
In infections
It is officially indicated for the treatment of various types of bacteriaBacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
l infection
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
s.
Its use as an antibiotic is particularly in Lyme disease
Lyme disease
Lyme disease, or Lyme borreliosis, is an emerging infectious disease caused by at least three species of bacteria belonging to the genus Borrelia. Borrelia burgdorferi sensu stricto is the main cause of Lyme disease in the United States, whereas Borrelia afzelii and Borrelia garinii cause most...
, acne
Acne vulgaris
Acne vulgaris is a common human skin disease, characterized by areas of skin with seborrhea , comedones , papules , pustules , Nodules and possibly scarring...
and bronchitis
Bronchitis
Acute bronchitis is an inflammation of the large bronchi in the lungs that is usually caused by viruses or bacteria and may last several days or weeks. Characteristic symptoms include cough, sputum production, and shortness of breath and wheezing related to the obstruction of the inflamed airways...
.
Resistance is gradually becoming more common, and demeclocycline is now rarely used for infections.
In SIADH
It is widely used (though off-labelOff-label use
Off-label use is the practice of prescribing pharmaceuticals for an unapproved indication or in an unapproved age group, unapproved dose or unapproved form of administration...
in many countries) in the treatment of 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...
(low blood 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...
concentration) due to the syndrome of inappropriate antidiuretic hormone
Syndrome of inappropriate antidiuretic hormone
The syndrome of inappropriate antidiuretic hormone hypersecretion is characterized by excessive release of antidiuretic hormone from the posterior pituitary gland or another source. The result is hyponatremia and sometimes fluid overload...
(SIADH) when fluid restriction alone has been ineffective.
The use in SIADH actually relies on a side effect; demeclocycline induces nephrogenic 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...
(dehydration due to the inability to concentrate urine). The use of demeclocycline in SIADH was first reported in 1975, and, in 1978, a larger study found it to be more effective and better tolerated than lithium carbonate
Lithium carbonate
Lithium carbonate is a chemical compound of lithium, carbon, and oxygen with the formula Li2CO3. This colorless salt is widely used in the processing of metal oxides and has received attention for its use in psychiatry. It is found in nature as the rare mineral zabuyelite.-Properties:Like almost...
, the only available treatment at the time. Demeclocycline has since been the drug of choice for treating SIADH, although it may be superseded as vasopressin receptor antagonist
Vasopressin receptor antagonist
A vasopressin receptor antagonist is an agent which interferes with action at the vasopressin receptors. They can be used in the treatment of hyponatremia, especially in patients with congestive heart failure or liver cirrhosis.-Tetracyclines:...
s, such as tolvaptan
Tolvaptan
Tolvaptan , also known as OPC-41061, is a selective, competitive vasopressin receptor 2 antagonist used to treat hyponatremia associated with congestive heart failure, cirrhosis, and the syndrome of inappropriate antidiuretic hormone . Tolvaptan was approved by the U.S...
, become available.
Contraindications
As other tetracyclinesTetracycline antibiotics
Tetracyclines are a group of broad-spectrum antibiotics whose general usefulness has been reduced with the onset of bacterial resistance. Despite this, they remain the treatment of choice for some specific indications....
, demeclocycline is contraindicated in children and pregnant or nursing women. All members of this class interfere with bone
Bone
Bones are rigid organs that constitute part of the endoskeleton of vertebrates. They support, and protect the various organs of the body, produce red and white blood cells and store minerals. Bone tissue is a type of dense connective tissue...
development and may discolour teeth
Tooth
Teeth are small, calcified, whitish structures found in the jaws of many vertebrates that are used to break down food. Some animals, particularly carnivores, also use teeth for hunting or for defensive purposes. The roots of teeth are embedded in the Mandible bone or the Maxillary bone and are...
.
Side effects and interactions
These are similar to those of other tetracyclinesTetracycline antibiotics
Tetracyclines are a group of broad-spectrum antibiotics whose general usefulness has been reduced with the onset of bacterial resistance. Despite this, they remain the treatment of choice for some specific indications....
. Skin reactions with sunlight have been reported. Demeclocycline is unique in that it is the only tetracycline known to cause nephrogenic diabetes insipidus.
Tetracyclines bind to cations such as calcium
Calcium
Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...
, iron
Iron
Iron is a chemical element with the symbol Fe and atomic number 26. It is a metal in the first transition series. It is the most common element forming the planet Earth as a whole, forming much of Earth's outer and inner core. It is the fourth most common element in the Earth's crust...
(when given orally), and magnesium
Magnesium
Magnesium is a chemical element with the symbol Mg, atomic number 12, and common oxidation number +2. It is an alkaline earth metal and the eighth most abundant element in the Earth's crust and ninth in the known universe as a whole...
, rendering them insoluble and inabsorbable for the GI tract. Demeclocycline should not be taken with food (particularly milk and other dairy products) or antacid
Antacid
An antacid is a substance which neutralizes stomach acidity.-Mechanism of action:Antacids perform a neutralization reaction, increasing the pH to reduce acidity in the stomach. When gastric hydrochloric acid reaches the nerves in the gastrointestinal mucosa, they signal pain to the central nervous...
s.
Mechanism of action
As with related tetracycline antibiotics, demeclocycline acts by binding to the 30S30S
30S is the smaller subunit of the 70S ribosome of prokaryotes. It is a complex of ribosomal RNA and ribonucleoproteins that functions in mRNA translation...
- and 50S
50S
50S is the larger subunit of the 70S ribosome of prokaryotes. It is the site of inhibition for antibiotics such as macrolides, chloramphenicol, clindamycin, and the pleuromutilins. It includes the subunits 5S and 23S.-Structure:...
-RNA
RNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....
, which impairs protein synthesis by bacteria. It is bacteriostatic (it impairs bacterial growth but does not kill bacteria directly).
It is not completely understood why demeclocycline impairs the action of antidiuretic hormone, but it is thought that it blocks the binding of the hormone to its receptor
Receptor (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...
.