Doxapram An analeptic, in medicine, is a central nervous system stimulant. The term analeptic typically refers to respiratory analeptics (for example, doxapram). Analeptics are central nervous system stimulants that include a wide variety of medications used to treat depression, attention deficit hyperactivity disorder (ADHD), and respiratory depression. Analeptics can also be used as convulsants, with low doses causing patients to experience heightened awareness, restlessness and rapid breathing.
|
|
Analeptics can be used to increase the speed of recovery from propofol, remifentanil, and sevoflurane. In clinical settings, analeptics such as Doxapram have been used to help patients recover from anesthesia better, as well as removing some of the potential negative side effects of potent anesthetics.
|
|
After their introduction in the early 20th century, analeptics were used to study the new life-threatening problem of barbiturate overdose. Prior to the 1930s naturally occurring stimulants such as camphor and caffeine were utilized in the treatment of barbiturate overdose. Between 1930 and 1960 synthetic analeptics such as nikethamide, pentylenetetrazol, bemegride, amphetamine, and methylphenidate replaced the naturally occurring compounds in treating barbiturate overdose. Recently, analeptics have been turned to the treatment of ADHD due to more efficient ways to treat barbiturate overdoses.
|
|
Analeptics are a diverse group of medications which work through a variety of chemical pathways; however, there are four main mechanisms which analeptic medications work through in order to stimulate respiration. Analeptics can act as potassium channel blockers, ampakines, and serotonin receptor agonists, and adenosine antagonism. Two common potassium channel blockers are Doxapram and GAL-021. Both act on potassium channels in Carotid Bodies.
|
|
Doxapram Analeptics have been used throughout history for two main purposes. One purpose is to help patients recover from anesthesia more efficiently. Another purpose is the management of respiratory distress and apnea, particularly in infants.
|
|
The primary medical use of these drugs is as an anesthetic recovery tool or to treat emergency respiratory depression. Other drugs of this category are prethcamide, pentylenetetrazole, and nikethamide. Nikethamide is now withdrawn due to risk of convulsions. Analeptics have recently been used to better understand the treatment of a barbiturate overdose.
|
|
He was born on 1 March 1908. In 1934 he graduated from Second Moscow Medical Institute named after Pirogov. In 1938 he started his work at the National research institute for chemistry and pharmacy. In 1939 he got his PhD in pharmacology, his doctoral thesis dealt with pharmacology of respiratory analeptics and synthesis of originally soviet drug cytiton.
|
|
One of the first widely used analeptics was strychnine, which causes CNS excitation by antagonizing the inhibitory neurotransmitter glycine. Strychnine is subcategorized as a convulsant along with picrotoxin and bicuculline, though these convulsants inhibit GABA receptors instead of glycine. Strychnine was used until the early 20th century, when it was found to be a highly toxic convulsant. Strychnine is now available as a rodenticide as well as an adulterant in drugs such as heroin.
|
|
AMPA Ampakines are the second common form of analeptics which elicit a different mechanism for an analeptic response. They bind to AMPA receptors, or amino-3-hydroxy-5-methyl-D-aspartate receptors, within the pre-Bötzinger complex. The pre-Bötzinger complex is part of the ventral respiratory group and the induction of long term potentials in the postsynaptic membrane of these neurons leads to an increased respiratory rate. The endogenous AMPA receptor ligand is glutamate and ampakines mirror glutamate's interaction with the receptors.
|
|
Ligand binding causes AMPA receptors to open and allow for sodium ions to flow into the cell, leading to depolarization and signal transduction. At this time, CX717 is the most successful ampakine in human trials and has very few side effects. The third common mechanism which analeptics take advantage of is to act as serotonin receptor agonists. Buspirone and Mosapride successfully increased respiration in animals by binding to serotonin receptors which are G protein coupled receptors which, upon activation, induce a secondary messenger cascade and in this case that cascade leads to an analeptic response.
|
|
The detection of xylazine in biological fluids in humans involves various screening methods, such as urine screenings, thin layer chromatography (TLC), gas chromatography mass spectrometry (GC-MS), Remedi HS Bio-Rad Laboratories, and liquid chromatography mass spectrometry (LC-MS). Multiple drugs have been used as supportive therapeutic intervention such as lidocaine, naloxone, thiamine, lorazepam, vecuronium, etomidate, propofol, tolazoline, yohimbine, atropine, orciprenaline, metoclopramide, ranitidine, metoprolol, enoxaparin, flucloxacillin, insulin, and irrigation of both eyes with saline. Effects of xylazine are also reversed by the analeptics 4-aminopyridine, doxapram, and caffeine, which are physiological antagonists to central nervous system depressants. Combining yohimbine and 4-aminopyridine in an effort to antagonize xylazine is superior as compared to the administration of either of these drugs individually due to reduction of recovery time.
|
|