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

medication Medication (also called medicament, medicine, pharmaceutical drug, medicinal product, medicinal drug or simply drug) is a drug used to medical diagnosis, diagnose, cure, treat, or preventive medicine, prevent disease. Drug therapy (pharmaco ...

used for

sedation Sedation is the reduction of irritability or agitation by administration of sedative drugs, generally to facilitate a medical procedure or diagnostic procedure. Examples of drugs which can be used for sedation include isoflurane, diethyl ether, ...

Veterinarian A veterinarian (vet) or veterinary surgeon is a medical professional who practices veterinary medicine. They manage a wide range of health conditions and injuries in non-human animals. Along with this, veterinarians also play a role in animal r ...

s 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 variously by hallucinations (typically, Auditory hallucination#Schizophrenia, hearing voices), delusions, thought disorder, disorganized thinking and behavior, and Reduced affect display, f ...

bipolar disorder Bipolar disorder (BD), previously known as manic depression, is a mental disorder characterized by periods of Depression (mood), depression and periods of abnormally elevated Mood (psychology), mood that each last from days to weeks, and in ...

. It is administered as an

intravenous Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutr ...

solution Solution may refer to: * Solution (chemistry), a mixture where one substance is dissolved in another * Solution (equation), in mathematics ** Numerical solution, in numerical analysis, approximate solutions within specified error bounds * Solu ...

or as a buccal or

sublingual Sublingual (List of abbreviations used in medical prescriptions, abbreviated SL), from the Latin for "under the tongue", refers to the pharmacological route of administration by which substances diffuse into the blood through Tissue (biology), t ...

film. Similar to

clonidine Clonidine, sold under the brand name Catapres among others, is an α2A-adrenergic receptor agonist medication used to treat high blood pressure, attention deficit hyperactivity disorder (ADHD), drug withdrawal (e.g., alcohol, opioids, or nic ...

, dexmedetomidine is a sympatholytic drug that acts as an

agonist An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an R ...

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 and ICU stay. Compared with other

sedative A sedative or tranquilliser is a substance that induces sedation by reducing irritability or Psychomotor agitation, excitement. They are central nervous system (CNS) Depressant, depressants and interact with brain activity, causing its decelera ...

s, some studies suggest dexmedetomidine may be associated with less

delirium Delirium (formerly acute confusional state, an ambiguous term that is now discouraged) is a specific state of acute confusion attributable to the direct physiological consequence of a medical condition, effects of a psychoactive substance, or ...

. 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), colloquially known as "benzos", are a class of central nervous system (CNS) depressant, depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed t ...

opioid Opioids are a class of Drug, drugs that derive from, or mimic, natural substances found in the Papaver somniferum, opium poppy plant. Opioids work on opioid receptors in the brain and other organs to produce a variety of morphine-like effects, ...

s, and

propofol Propofol is the active component of an intravenous anesthetic formulation used for induction and maintenance of general anesthesia. It is chemically termed 2,6-diisopropylphenol. The formulation was approved under the brand name Diprivan. Nu ...

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, or simply amphetamines, are a chemical class, class of compounds based upon the amphetamine structure; it includes all derivative (chemistry), derivative compounds which are formed by replacing, or substitution reacti ...

and

cocaine Cocaine is a tropane alkaloid and central nervous system stimulant, derived primarily from the leaves of two South American coca plants, ''Erythroxylum coca'' and ''Erythroxylum novogranatense, E. novogranatense'', which are cultivated a ...

intoxication 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. Retrieved on September 20, 2014.

. Dexmedetomidine has also been used as an adjunct to neuroaxial anesthesia for lower limb procedures. It has been successfully used to treat opioid withdrawal symptoms. 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 by 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 ( arrhythmia), and to protect the heart from a second heart attack after a first heart attack ( secondary prevention ...

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

Pharmacology

Pharmacodynamics

Dexmedetomidine is a highly selective α₂-adrenergic receptor

. It possesses an α₂:α₁ selectivity ratio of 1620:1, making it 8times more selective for the α₂-adrenergic receptor than the related drug

. Unlike

s and other

s such as

, dexmedetomidine is able to achieve its effects without causing

respiratory depression Hypoventilation (also known as respiratory depression) occurs when ventilation is inadequate (''hypo'' meaning "below") to perform needed respiratory gas exchange. By definition it causes an increased concentration of carbon dioxide (hypercapni ...

. Dexmedetomidine induces sedation by decreasing activity of noradrenergic

neuron A neuron (American English), neurone (British English), or nerve cell, is an membrane potential#Cell excitability, excitable cell (biology), cell that fires electric signals called action potentials across a neural network (biology), neural net ...

s 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 in the reticular ...

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 co ...

, thereby increasing the downstream activity of inhibitory

γ-aminobutyric acid GABA (gamma-aminobutyric acid, γ-aminobutyric acid) is the chief inhibitory neurotransmitter in the developmentally mature mammalian central nervous system. Its principal role is reducing neuronal excitability throughout the nervous system. GA ...

(GABA) neurons in the ventrolateral preoptic nucleus. In contrast, other sedatives like propofol and

s directly increase activity of GABAergic neurons. Through action on this endogenous sleep-promoting pathway the sedation produced by dexmedetomidine more closely mirrors natural

sleep Sleep is a state of reduced mental and physical activity in which consciousness is altered and certain Sensory nervous system, sensory activity is inhibited. During sleep, there is a marked decrease in muscle activity and interactions with th ...

(specifically stage 2 non-rapid eye movement sleep (NREM)), as demonstrated by

EEG Electroencephalography (EEG) is a method to record an electrogram of the spontaneous electrical activity of the brain. The bio signals detected by EEG have been shown to represent the postsynaptic potentials of pyramidal neurons in the neoc ...

studies. As such, dexmedetomidine provides less

amnesia Amnesia is a deficit in memory caused by brain damage or brain diseases,Gazzaniga, M., Ivry, R., & Mangun, G. (2009) Cognitive Neuroscience: The biology of the mind. New York: W.W. Norton & Company. but it can also be temporarily caused by t ...

than benzodiazepines. Dexmedetomidine also has

analgesic An analgesic drug, also called simply an analgesic, antalgic, pain reliever, or painkiller, is any member of the group of drugs used for pain management. Analgesics are conceptually distinct from anesthetics, which temporarily reduce, and in s ...

effects at the

spinal cord The spinal cord is a long, thin, tubular structure made up of nervous tissue that extends from the medulla oblongata in the lower brainstem to the lumbar region of the vertebral column (backbone) of vertebrate animals. The center of the spinal c ...

level and other supraspinal sites.

Pharmacokinetics

Intravenous dexmedetomidine exhibits linear pharmacokinetics with a rapid distribution half-life of approximately 6minutes in healthy volunteers, and a longer and more variable distribution half-life in ICU patients. The terminal

elimination half-life Biological half-life (elimination half-life, pharmacological 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 blood plasma. ...

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

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

of dexmedetomidine is about 94% (mostly

albumin Albumin is a family of globular proteins, the most common of which are the serum albumins. All of the proteins of the albumin family are water- soluble, moderately soluble in concentrated salt solutions, and experience heat denaturation. Alb ...

). Dexmedetomidine is

metabolized Metabolism (, from ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cellular processes; the co ...

by the

liver The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...

, 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 gly ...

(34%) as well as by

oxidation Redox ( , , reduction–oxidation or oxidation–reduction) is a type of chemical reaction in which the oxidation states of the reactants change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is ...

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 an ...

and other

cytochrome P450 Cytochromes P450 (P450s or CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that mostly, but not exclusively, function as monooxygenases. However, they are not omnipresent; for examp ...

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

s. As such, it should be used with caution in people with

liver disease Liver disease, or hepatic disease, is any of many diseases of the liver. If long-lasting it is termed chronic liver disease. Although the diseases differ in detail, liver diseases often have features in common. Liver diseases File:Ground gla ...

or hepatic impairment. The majority of metabolized dexmedetomidine is excreted in the

urine Urine is a liquid by-product of metabolism in humans and many other animals. In placental mammals, urine flows from the Kidney (vertebrates), kidneys through the ureters to the urinary bladder and exits the urethra through the penile meatus (mal ...

(~95%). It can also be absorbed

sublingually Sublingual (abbreviated SL), from the Latin for "under the tongue", refers to the pharmacological route of administration by which substances diffuse into the blood through tissues under the tongue. Many drugs are absorbed through sublingual a ...

History

Dexmedetomidine was developed by Orion Pharma and is marketed under the names dexdor and Precedex; in 1999 the US Food and Drug Administration (FDA) approved it as a short-term sedative and analgesic (<24 hours) for critically ill or injured people on mechanical ventilation in the

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 intensive care medicine. An inten ...

. 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 brand name Dexdomitor ( Orion Corporation), was approved in the European Union 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 by pharmaceutical company Zoetis for use in dogs for relief of noise aversion.

References

{{Portal bar , Medicine 27-Hydroxylase inhibitors Alpha-2 adrenergic receptor agonists Analgesics Antihypotensive agents Anxiolytics Drugs developed by Pfizer Enantiopure drugs Imidazoles Phenethylamines Sedatives Veterinary drugs