Dexmedetomidine, sold under the trade name Precedex among others, is a

drug A drug is any chemical substance that causes a change in an organism's physiology or psychology when consumed. Drugs are typically distinguished from food and substances that provide nutritional support. Consumption of drugs can be via inhal ...

used in humans for sedation. Veterinarians use dexmedetomidine for similar purposes in treating cats, dogs, and horses. It is also used in humans to treat acute agitation associated with

schizophrenia Schizophrenia is a mental disorder characterized by continuous or relapsing episodes of psychosis. Major symptoms include hallucinations (typically hearing voices), delusions, and disorganized thinking. Other symptoms include social wi ...

or bipolar I or II disorder. Similar to

clonidine Clonidine, sold under the brand name Catapres among others, is an α2-adrenergic agonist medication used to treat high blood pressure, ADHD, drug withdrawal ( alcohol, opioids, or nicotine), menopausal flushing, diarrhea, spasticity, an ...

, it is a

sympatholytic A sympatholytic (or sympathoplegic) drug is a medication that opposes the downstream effects of postganglionic nerve firing in effector organs innervated by the sympathetic nervous system (SNS). They are indicated for various functions; for exampl ...

drug that acts as an

agonist An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...

of α₂-adrenergic receptors in certain parts of the brain. It was developed by Orion Pharma.

Medical uses

Intensive care unit sedation

Studies suggest dexmedetomidine for sedation in mechanically ventilated adults may reduce time to

extubation Tracheal intubation, usually simply referred to as intubation, is the placement of a flexible plastic tube into the trachea (windpipe) to maintain an open airway or to serve as a conduit through which to administer certain drugs. It is frequently ...

and ICU stay. Compared with other sedatives, some studies suggest dexmedetomidine may be associated with less

delirium Delirium (also known as acute confusional state) is an organically caused decline from a previous baseline of mental function that develops over a short period of time, typically hours to days. Delirium is a syndrome encompassing disturbances ...

. However, this finding is not consistent across multiple studies. At the very least, when aggregating many study results together, use of dexmedetomidine appears to be associated with less neurocognitive dysfunction compared to other sedatives. Whether this observation has a beneficial psychological impact is unclear. From an economic perspective, dexmedetomidine is associated with lower ICU costs, largely due to a shorter time to extubation.

Procedural sedation

Dexmedetomidine can also be used for procedural sedation such as during colonoscopy. It can be used as an adjunct with other sedatives like

benzodiazepine Benzodiazepines (BZD, BDZ, BZs), sometimes called "benzos", are a class of depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed to treat conditions such as anxiety disorders, ...

opioid Opioids are substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, replacement therapy for opioi ...

s, and propofol to enhance sedation and help maintain hemodynamic stability by decreasing the requirement of other sedatives. Dexmedetomidine is also used for procedural sedation in children. It can be used for sedation required for awake fibreoptic nasal intubation in patients with a difficult airway.

Adjunct in general anesthesia

It has also been used as an adjunct infusion during general anesthesia. In this application, it has been shown to decrease post-operative delirium, pain, nausea and opioid use.

Other

Dexmedetomidine may be useful for the treatment of the negative cardiovascular effects of acute

amphetamines Substituted amphetamines are a class of compounds based upon the amphetamine structure; it includes all derivative compounds which are formed by replacing, or substituting, one or more hydrogen atoms in the amphetamine core structure with su ...

and

cocaine Cocaine (from , from , ultimately from Quechua: ''kúka'') is a central nervous system (CNS) stimulant mainly used recreationally for its euphoric effects. It is primarily obtained from the leaves of two Coca species native to South Am ...

intoxication Intoxication — or poisoning, especially by an alcoholic or narcotic substance — may refer to: * Substance intoxication: ** Alcohol intoxication ** LSD intoxication ** Toxidrome ** Tobacco intoxication ** Cannabis intoxication ** Cocaine in ...

and

overdose A drug overdose (overdose or OD) is the ingestion or application of a drug or other substance in quantities much greater than are recommended.

. Dexmedetomidine has also been used as an adjunct to neuroaxial anesthesia for lower limb procedures. In 2022 it was approved by the FDA for the treatment of agitation in schizophrenia and bipolar disorder.

Side effects

There are no known contraindication to the use of dexmedetomidine. It has a biphasic effect on blood pressure with lower readings at lower drug concentrations and higher readings at higher concentrations. Common side effects include: hypotension, hypertension, with slight decreases in heart rate, arrhythmias, and hypoxia. Toxic doses may cause first-degree or second-degree

atrioventricular block Atrioventricular block (AV block) is a type of heart block that occurs when the electrical signal traveling from the atria, or the upper chambers of the heart, to ventricles, or the lower chambers of the heart, is impaired. Normally, the sinoatr ...

. These adverse events usually occur briefly after administering a loading dose of the drug. Thus, adverse effects may be reduced be omitting a loading dose.

Interactions

Dexmedetomidine may enhance the effects of other sedatives and anesthetics when co-administered. Similarly, drugs that lower blood pressure and heart rate, such as

beta blocker Beta blockers, also spelled β-blockers, are a class of medications that are predominantly used to manage abnormal heart rhythms, and to protect the heart from a second heart attack after a first heart attack ( secondary prevention). They are ...

s, may also have enhanced effects when co-administered with dexmedetomidine.

Pharmacology

Pharmacodynamics

Dexmedetomidine is a highly selective α₂-adrenergic agonist. It possesses an α₂:α₁ selectivity ratio of 1620:1, making it eight times more selective for the α₂-receptor than clonidine. Unlike opioids and other sedatives such as propofol, dexmedetomidine is able to achieve its effects without causing respiratory depression. Dexmedetomidine induces sedation by decreasing activity of noradrenergic neurons in the

locus ceruleus The locus coeruleus () (LC), also spelled locus caeruleus or locus ceruleus, is a nucleus in the pons of the brainstem involved with physiological responses to stress and panic. It is a part of the reticular activating system. The locus coer ...

in the

brain stem The brainstem (or brain stem) is the posterior stalk-like part of the brain that connects the cerebrum with the spinal cord. In the human brain the brainstem is composed of the midbrain, the pons, and the medulla oblongata. The midbrain is cont ...

, thereby increasing the downstream activity of inhibitory gamma-aminobutyric acid (GABA) neurons in the

ventrolateral preoptic nucleus The ventrolateral preoptic nucleus (VLPO), also known as the intermediate nucleus of the preoptic area (IPA), is a small cluster of neurons situated in the anterior hypothalamus, sitting just above and to the side of the optic chiasm in the brain ...

. In contrast, other sedatives like propofol and benzodiazepines directly increase activity of gamma-aminobutyric acid neurons. Through action on this endogenous sleep-promoting pathway the sedation produced by dexmedetomidine more closely mirrors natural

sleep Sleep is a sedentary state of mind and body. It is characterized by altered consciousness, relatively inhibited Perception, sensory activity, reduced muscle activity and reduced interactions with surroundings. It is distinguished from wakefuln ...

(specifically stage 2

non-rapid eye movement sleep Non-rapid eye movement sleep (NREM), also known as quiescent sleep, is, collectively, sleep stages 1–3, previously known as stages 1–4. Rapid eye movement sleep (REM) is not included. There are distinct electroencephalographic and other ch ...

), as demonstrated by EEG studies. As such, dexmedetomidine provides less amnesia than benzodiazepines. Dexmedetomidine also has analgesic effects at the spinal cord level and other supraspinal sites.

Pharmacokinetics

Intravenous dexmedetomidine exhibits linear pharmacokinetics with a rapid

distribution half-life Biological half-life (also known as elimination half-life, pharmacologic half-life) is the time taken for concentration of a biological substance (such as a medication) to decrease from its maximum concentration ( Cmax) to half of Cmax in the bl ...

of approximately 6 minutes in healthy volunteers, and a longer and more variable distribution half-life in ICU patients. The terminal

elimination half-life Biological half-life (also known as elimination half-life, pharmacologic half-life) is the time taken for concentration of a biological substance (such as a medication) to decrease from its maximum concentration ( Cmax) to half of Cmax in the bl ...

of intravenous dexmedetomidine ranged 2.1 to 3.1 hours in healthy adults and 2.2 to 3.7 hours in ICU patients.

Plasma protein binding Plasma protein binding refers to the degree to which medications attach to proteins within the blood. A drug's efficiency may be affected by the degree to which it binds. The less bound a drug is, the more efficiently it can traverse or diffuse th ...

of dexmedetomidine is about 94% (mostly albumin). Dexmedetomidine is metabolized by the liver, largely by

glucuronidation Glucuronidation is often involved in drug metabolism of substances such as drugs, pollutants, bilirubin, androgens, estrogens, mineralocorticoids, glucocorticoids, fatty acid derivatives, retinoids, and bile acids. These linkages involve glycosi ...

(34%) as well as by oxidation via

CYP2A6 Cytochrome P450 2A6 (abbreviated CYP2A6) is a member of the cytochrome P450 mixed-function oxidase system, which is involved in the metabolism of xenobiotics in the body. CYP2A6 is the primary enzyme responsible for the oxidation of nicotine and ...

and other

Cytochrome P450 Cytochromes P450 (CYPs) are a superfamily of enzymes containing heme as a cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various compo ...

enzymes. As such, it should be used with caution in people with liver disease. The majority of metabolized dexmedetomidine is excreted in the urine (~95%). It can be absorbed sublingually.

History

Dexmedetomidine was approved in 1999 by the US Food and Drug Administration (FDA) as a short-term sedative and analgesic (<24 hours) for critically ill or injured people on mechanical ventilation in the

intensive care unit 220px, Intensive care unit An intensive care unit (ICU), also known as an intensive therapy unit or intensive treatment unit (ITU) or critical care unit (CCU), is a special department of a hospital or health care facility that provides intensi ...

(ICU). The rationale for its short-term use was due to concerns over withdrawal side effects such as rebound high blood pressure. These effects have not been consistently observed in research studies, however.

Veterinary use

Dexmedetomidine, under the trade name Dexdomitor (

Orion Corporation Orion Corporation ( fi, Orion Oyj), founded in 1917 and headquartered at Espoo, Finland, is a globally operating Finnish company which develops, manufactures and markets human and veterinary pharmaceuticals and active pharmaceutical ingredients ...

), was approved in the European Union in for use in cats and dogs in 2002, for sedation and induction of general anesthesia. The FDA approved dexmedetomidine for use in dogs in 2006 and cats in 2007. In 2015, the European Medicines Agency and the FDA approved an oromucosal gel form of dexmedetomidine marketed as Sileo (

Zoetis Zoetis Inc. (/zō-EH-tis/) is an American drug company, the world's largest producer of medicine and vaccinations for pets and livestock. The company was a subsidiary of Pfizer, the world's largest drug maker, but with Pfizer's spinoff of its 83 ...

) for use in dogs for relief of noise aversion.

References

External links

* * {{Portal bar , Medicine 27-Hydroxylase inhibitors Alpha-2 adrenergic receptor agonists Anxiolytics Enantiopure drugs Imidazoles