Dexmedetomidine Research Paper
PHARMACOLOGY
Dexmedetomidine is the S-enantiomer of medetomidine(28), used widely in the veterinary practice. Chemically Dexmedetomidine is (S)-4-[1-(2,3-dimethylphenyl)ethyl]-3H-imidazole.
ALPHA – 2 ADRENORECEPTOR The primary sympathetic neurotransmitter nor-adrenaline and adrenaline exert their central and peripheral actions through specialised receptors called adrenergic receptors. Adrenergic receptors are present in nearly all the peripheral tissues and in the central nervous system neurons. Three types of adrenergic receptors are present – alpha 1, alpha 2 and alpha 3(29). They belong to the cell surface G-protein coupled type of receptors. Alpha 2 receptors are subdivided into three subtypes alpha 2A, alpha 2B and alpha 2C(30). …show more content…
Alpha 2 agonists produce diverse response like analgesia, anxiolysis, sedation and sympatholysis. Recently the Food and Drug Administration approved the usage of two novel alpha 2 agonists – clonidine and dexmedetomidine for the usage in Intensive Care Unit sedation. Its use has now been investigated as an adjuvant to prolong the effects of epidural, spinal and peripheral nerve blocks.
MECHANISM OF ACTION :
1. Inhibits the adenylate cyclase enzyme(31) responsible for the production of 3,6 – cyclic adenosine monophosphate resulting in decreased availability of cyclic AMP. Cyclic AMP mediates phosphorylation of many of the intra-cellular target proteins. This results in hyper-polarisations of the neuronal cell membrane which results in decreased firing rate of excitable cells.
2. N-type voltage gated calcium channels are inhibited resulting in decreased entry of calcium ions which results in decreased catecholamine secretion.
3. Activates the alpha 2 adrenoreceptor in the pre-synaptic region resulting in decreased release of sympathetic …show more content…
The ratio of alpha 2 : alpha 1 activity for dexmedetomidine is 1620 : 1 and 220 : 1 for clonidine. Hence dexmedetomidine is a more selective alpha 2 adrenergic agonist than clonidine.
PHARMACO-KINETICS
ABSORPTION : Dexmedetomidine is inactive orally and the conventional route of administration is the intra-venous route. Dexmedetomidine has good bio-availability with nasal, intra-muscular, buccal, sublingual, neuraxial, intra-gastric and intra-articular routes.
DISTRIBUTION : Elimination half life - 2-3 hours Volume of distribution - 118 litres
PROTEIN BINDING : Dexmedetomidine is 95% protein bound to albumin. Protein bound fraction decreases with hepatic impairment. Dexmedetomidine does not displace phenytoin, propranolol, warfarin, digoxin and theophylline from plasma proteins.
METABOLISM : Biotransformation occurs in the liver to inactive metabolites. Metabolism occurs by N-methyl glucuronidation in the liver and the glucuronide metabolites are excreted in the urine. Hence the dosage of dexmedetomidine must be decreased in patients with hepatic
Dexmedetomidine is the S-enantiomer of medetomidine(28), used widely in the veterinary practice. Chemically Dexmedetomidine is (S)-4-[1-(2,3-dimethylphenyl)ethyl]-3H-imidazole.
ALPHA – 2 ADRENORECEPTOR The primary sympathetic neurotransmitter nor-adrenaline and adrenaline exert their central and peripheral actions through specialised receptors called adrenergic receptors. Adrenergic receptors are present in nearly all the peripheral tissues and in the central nervous system neurons. Three types of adrenergic receptors are present – alpha 1, alpha 2 and alpha 3(29). They belong to the cell surface G-protein coupled type of receptors. Alpha 2 receptors are subdivided into three subtypes alpha 2A, alpha 2B and alpha 2C(30). …show more content…
Alpha 2 agonists produce diverse response like analgesia, anxiolysis, sedation and sympatholysis. Recently the Food and Drug Administration approved the usage of two novel alpha 2 agonists – clonidine and dexmedetomidine for the usage in Intensive Care Unit sedation. Its use has now been investigated as an adjuvant to prolong the effects of epidural, spinal and peripheral nerve blocks.
MECHANISM OF ACTION :
1. Inhibits the adenylate cyclase enzyme(31) responsible for the production of 3,6 – cyclic adenosine monophosphate resulting in decreased availability of cyclic AMP. Cyclic AMP mediates phosphorylation of many of the intra-cellular target proteins. This results in hyper-polarisations of the neuronal cell membrane which results in decreased firing rate of excitable cells.
2. N-type voltage gated calcium channels are inhibited resulting in decreased entry of calcium ions which results in decreased catecholamine secretion.
3. Activates the alpha 2 adrenoreceptor in the pre-synaptic region resulting in decreased release of sympathetic …show more content…
The ratio of alpha 2 : alpha 1 activity for dexmedetomidine is 1620 : 1 and 220 : 1 for clonidine. Hence dexmedetomidine is a more selective alpha 2 adrenergic agonist than clonidine.
PHARMACO-KINETICS
ABSORPTION : Dexmedetomidine is inactive orally and the conventional route of administration is the intra-venous route. Dexmedetomidine has good bio-availability with nasal, intra-muscular, buccal, sublingual, neuraxial, intra-gastric and intra-articular routes.
DISTRIBUTION : Elimination half life - 2-3 hours Volume of distribution - 118 litres
PROTEIN BINDING : Dexmedetomidine is 95% protein bound to albumin. Protein bound fraction decreases with hepatic impairment. Dexmedetomidine does not displace phenytoin, propranolol, warfarin, digoxin and theophylline from plasma proteins.
METABOLISM : Biotransformation occurs in the liver to inactive metabolites. Metabolism occurs by N-methyl glucuronidation in the liver and the glucuronide metabolites are excreted in the urine. Hence the dosage of dexmedetomidine must be decreased in patients with hepatic