Clonidine, sold under the brand name Catapres among others, is an
α2-adrenergic agonist medication used to treat
high blood pressure,
ADHD,
drug withdrawal
Drug withdrawal, drug withdrawal syndrome, or substance withdrawal syndrome, is the group of symptoms that occur upon the abrupt discontinuation or decrease in the intake of pharmaceutical or recreational drugs.
In order for the symptoms of wit ...
(
alcohol,
opioids, or
nicotine
Nicotine is a natural product, naturally produced alkaloid in the nightshade family of plants (most predominantly in tobacco and ''Duboisia hopwoodii'') and is widely used recreational drug use, recreationally as a stimulant and anxiolytic. As ...
),
menopausal flushing,
diarrhea
Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin w ...
,
spasticity
Spasticity () is a feature of altered skeletal muscle performance with a combination of paralysis, increased tendon reflex activity, and hypertonia. It is also colloquially referred to as an unusual "tightness", stiffness, or "pull" of muscles ...
, and certain pain conditions.
It is used by mouth, by injection, or as a skin patch.
[ Onset of action is typically within an hour with the effects on blood pressure lasting for up to eight hours.][
Common side effect include dry mouth, dizziness, headaches, hypotension, and sleepiness.][ Severe side effects may include hallucinations, heart arrhythmias, and confusion.] If rapidly stopped, withdrawal effects may occur.[ Use during ]pregnancy
Pregnancy is the time during which one or more offspring develops (gestation, gestates) inside a woman, woman's uterus (womb). A multiple birth, multiple pregnancy involves more than one offspring, such as with twins.
Pregnancy usually occur ...
or breastfeeding
Breastfeeding, or nursing, is the process by which human breast milk is fed to a child. Breast milk may be from the breast, or may be expressed by hand or pumped and fed to the infant. The World Health Organization (WHO) recommends that br ...
is not recommended.[ Clonidine lowers blood pressure by stimulating α2 receptors in the brain, which results in relaxation of many arteries.][
Clonidine was patented in 1961 and came into medical use in 1966.] It is available as a generic medication.[ In 2020, it was the 75th most commonly prescribed medication in the United States, with more than 9million prescriptions.
]
Medical uses
Clonidine is used to treat high blood pressure, attention deficit hyperactivity disorder
Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by excessive amounts of inattention, hyperactivity, and impulsivity that are pervasive, impairing in multiple contexts, and otherwise age-inap ...
(ADHD), drug withdrawal
Drug withdrawal, drug withdrawal syndrome, or substance withdrawal syndrome, is the group of symptoms that occur upon the abrupt discontinuation or decrease in the intake of pharmaceutical or recreational drugs.
In order for the symptoms of wit ...
( alcohol, opioids, or smoking), menopausal flushing, diarrhea
Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin w ...
, and certain pain conditions. It also sees some use off-label for episodic insomnia
Insomnia, also known as sleeplessness, is a sleep disorder in which people have trouble sleeping. They may have difficulty falling asleep, or staying asleep as long as desired. Insomnia is typically followed by daytime sleepiness, low energy, ...
, restless-legs syndrome, and anxiety
Anxiety is an emotion which is characterized by an unpleasant state of inner turmoil and includes feelings of dread over anticipated events. Anxiety is different than fear in that the former is defined as the anticipation of a future threat wh ...
, among other uses.[
]
Resistant hypertension
Clonidine may be effective for lowering blood pressure in people with resistant hypertension.
Clonidine works by slowing the pulse rate and exerts a reduction of serum concentrations of renin
Renin (etymology and pronunciation), also known as an angiotensinogenase, is an aspartic protease protein and enzyme secreted by the kidneys that participates in the body's renin–angiotensin–aldosterone system (RAAS)—also known as the r ...
, aldosterone, and catecholamines.
Attention deficit hyperactivity disorder
Clonidine may improve symptoms of attention deficit hyperactivity disorder in some people but causes many adverse effects and the beneficial effect is modest. In Australia, clonidine is an accepted but not approved use for ADHD by the TGA. Clonidine, along with methylphenidate
Methylphenidate, sold under the brand names Ritalin and Concerta among others, is the most widely prescribed central nervous system (CNS) stimulant medication used to treat attention deficit hyperactivity disorder (ADHD) and, to a lesser exten ...
, has been studied for treatment of ADHD. While not as effective as methylphenidate in treating ADHD, clonidine does offer some benefit; it can also be useful in combination with stimulant medications. Some studies show clonidine to be more sedating than guanfacine
Guanfacine, sold under the brand name Tenex among others, is an oral medication used to treat attention deficit hyperactivity disorder (ADHD) and high blood pressure. Guanfacine is FDA-approved for monotherapy treatment of ADHD as well as being ...
, which may be better at bedtime along with an arousing stimulant in the morning. Clonidine has been used to reduce sleep disturbances in ADHD, including to help offset stimulant-associated insomnia
Insomnia, also known as sleeplessness, is a sleep disorder in which people have trouble sleeping. They may have difficulty falling asleep, or staying asleep as long as desired. Insomnia is typically followed by daytime sleepiness, low energy, ...
.
Drug withdrawal
Clonidine may be used to ease drug withdrawal symptoms associated with abruptly stopping the long-term use of opioids, alcohol, benzodiazepines and nicotine
Nicotine is a natural product, naturally produced alkaloid in the nightshade family of plants (most predominantly in tobacco and ''Duboisia hopwoodii'') and is widely used recreational drug use, recreationally as a stimulant and anxiolytic. As ...
. It can alleviate opioid withdrawal
Opioid withdrawal is a set of symptoms (a syndrome) arising from the sudden withdrawal or reduction of opioids where previous usage has been heavy and prolonged. Signs and symptoms of withdrawal can include drug craving, anxiety, restless legs, ...
symptoms by reducing the sympathetic nervous system response such as tachycardia
Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal ( ...
and hypertension, hyperhidrosis
Hyperhidrosis is a condition characterized by abnormally increased sweating, in excess of that required for regulation of body temperature. Although primarily a benign physical burden, hyperhidrosis can deteriorate quality of life from a psycholog ...
(excessive sweating), hot and cold flashes, and akathisia
Akathisia is a movement disorder characterized by a subjective feeling of inner restlessness accompanied by mental distress and an inability to sit still. Usually, the legs are most prominently affected. Those affected may fidget, rock back a ...
. It may also be helpful in aiding smokers to quit. The sedation effect can also be useful. Clonidine may also reduce severity of neonatal abstinence syndrome
Neonatal withdrawal or neonatal abstinence syndrome (NAS) or neonatal opioid withdrawal syndrome (NOWS) is a withdrawal syndrome of infants after birth caused by ''in utero'' exposure to drugs of dependence, most commonly opioids. Common signs and ...
in infants born to mothers that are using certain drugs, particularly opioids. In infants with neonatal withdrawal syndrome, clonidine may improve the neonatal intensive care unit Network Neurobehavioral Score.
Clonidine has also been suggested as a treatment for rare instances of dexmedetomidine
Dexmedetomidine, sold under the trade name Precedex among others, is a drug 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 ...
withdrawal.
Spasticity
Clonidine has some role in the treatment of spasticity, acting principally by inhibiting excessive sensory transmission below the level of injury. Its use, however, is mainly as a second or third line agent, due to side effects such as hypotension
Hypotension is low blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure is indicated by two numbers, the systolic blood pressure (the top number) and the dia ...
, bradycardia, and drowsiness
Somnolence (alternatively sleepiness or drowsiness) is a state of strong desire for sleep, or sleeping for unusually long periods (compare hypersomnia). It has distinct meanings and causes. It can refer to the usual state preceding falling asleep ...
.
Other uses
Clonidine also has several off-label use
Off-label use is the use of pharmaceutical drugs for an unapproved indication or in an unapproved age group, dosage, or route of administration. Both prescription drugs and over-the-counter drugs (OTCs) can be used in off-label ways, although ...
s, and has been prescribed to treat psychiatric disorder
A mental disorder, also referred to as a mental illness or psychiatric disorder, is a behavioral or mental pattern that causes significant distress or impairment of personal functioning. Such features may be persistent, relapsing and remitt ...
s including stress
Stress may refer to:
Science and medicine
* Stress (biology), an organism's response to a stressor such as an environmental condition
* Stress (linguistics), relative emphasis or prominence given to a syllable in a word, or to a word in a phrase ...
, sleep disorders
A sleep disorder, or somnipathy, is a medical disorder of an individual's sleep patterns. Some sleep disorders are severe enough to interfere with normal physical, mental, social and emotional functioning. Polysomnography and actigraphy are tests ...
, hyperarousal
The fight-or-flight or the fight-flight-or-freeze response (also called hyperarousal or the acute stress response) is a physiological reaction that occurs in response to a perceived harmful event, attack, or threat to survival. It was first des ...
caused by post-traumatic stress disorder
Post-traumatic stress disorder (PTSD) is a mental and behavioral disorder that can develop because of exposure to a traumatic event, such as sexual assault, warfare, traffic collisions, child abuse, domestic violence, or other threats o ...
, borderline personality disorder, and other anxiety disorders. Clonidine is also a mild sedative, and can be used as premedication before surgery or procedures. It has also been studied as a way to calm acute manic episodes. Its epidural use for pain during heart attack, and postoperative and intractable pain has also been studied extensively. Clonidine can be used in restless legs syndrome
Restless legs syndrome (RLS), also known as Willis-Ekbom disease (WED), is generally a long-term disorder that causes a strong urge to move one's legs. There is often an unpleasant feeling in the legs that improves somewhat by moving them. This ...
. It can also be used to treat facial flushing and redness associated with rosacea
Rosacea is a long-term skin condition that typically affects the face. It results in redness, pimples, swelling, and small and superficial dilated blood vessels. Often, the nose, cheeks, forehead, and chin are most involved. A red, enlarg ...
. It has also been successfully used topically in a clinical trial as a treatment for diabetic neuropathy. Clonidine can also be used for migraine headaches and hot flash
Hot flashes (also known as hot flushes) are a form of flushing, often caused by the changing hormone levels that are characteristic of menopause. They are typically experienced as a feeling of intense heat with sweating and rapid heartbeat, and ...
es associated with menopause
Menopause, also known as the climacteric, is the time in women's lives when menstrual periods stop permanently, and they are no longer able to bear children. Menopause usually occurs between the age of 47 and 54. Medical professionals often ...
. Clonidine has also been used to treat refractory diarrhea
Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin w ...
associated with irritable bowel syndrome
Irritable bowel syndrome (IBS) is a "disorder of gut-brain interaction" characterized by a group of symptoms that commonly include abdominal pain and or abdominal bloating and changes in the consistency of bowel movements. These symptoms may ...
, fecal incontinence
Fecal incontinence (FI), or in some forms encopresis, is a lack of control over defecation, leading to involuntary loss of bowel contents, both liquid stool elements and mucus, or solid feces. When this loss includes flatus (gas), it is referre ...
, diabetes, diarrhea associated with opioid withdrawal, intestinal failure, neuroendocrine tumors, and cholera. Clonidine can be used in the treatment of Tourette syndrome
Tourette syndrome or Tourette's syndrome (abbreviated as TS or Tourette's) is a common neurodevelopmental disorder that begins in childhood or adolescence. It is characterized by multiple movement (motor) tics and at least one vocal (phonic) ...
(specifically for tics
A tic is a sudden, repetitive, nonrhythmic motor movement or vocalization involving discrete muscle groups.American Psychiatric Association (2000)DSM-IV-TR: Tourette's Disorder.''Diagnostic and Statistical Manual of Mental Disorders'', 4th ed., ...
). Clonidine has also had some success in clinical trials for helping to remove or ameliorate the symptoms of hallucinogen persisting perception disorder (HPPD).
Injection of α2 receptor agonists into the knee joint space, including clonidine, may reduce the severity of knee pain after arthroscopic
Arthroscopy (also called arthroscopic or keyhole surgery) is a minimally invasive surgical procedure on a joint in which an examination and sometimes treatment of damage is performed using an arthroscope, an endoscope that is inserted into the j ...
knee surgery.
Light-activated derivatives of clonidine (adrenoswitches) have been developed for research purposes and shown to control pupillary reflex with light in blind mice by topical application.
Clonidine suppression test
The reduction in circulating norepinephrine by clonidine was used in the past as an investigatory test for phaeochromocytoma
Pheochromocytoma (PHEO or PCC) is a rare tumor of the adrenal medulla composed of chromaffin cells, also known as pheochromocytes. When a tumor composed of the same cells as a pheochromocytoma develops outside the adrenal gland, it is referred t ...
, which is a catecholamine-synthesizing tumor, usually found in the adrenal medulla. In a clonidine suppression test, plasma catecholamine levels are measured before and 3 hours after a 0.3 mg oral test dose has been given to the patient. A positive test occurs if there is no decrease in plasma levels.
Pregnancy and breastfeeding
Clonidine is classed by the FDA as pregnancy category C. It is classified by the TGA of Australia as pregnancy category B3, which means that it has shown some detrimental effects on fetal development in animal studies, although the relevance of this to human beings is unknown.[ Clonidine appears in high concentration in breast milk and nursing infants have approximately 2/3 of serum clonidine concentrations as the mother. Caution is warranted in women who are pregnant, planning to become pregnant, or are breastfeeding.
]
Adverse effects
The principal adverse effects of clonidine are sedation, dry mouth, and hypotension (low blood pressure).[
By frequency]
Very common (>10% frequency):
* Dizziness
* Orthostatic hypotension
Orthostatic hypotension, also known as postural hypotension, is a medical condition wherein a person's blood pressure drops when standing up or sitting down. Primary orthostatic hypertension is also often referred to as neurogenic orthostatic hyp ...
* Somnolence
Somnolence (alternatively sleepiness or drowsiness) is a state of strong desire for sleep, or sleeping for unusually long periods (compare hypersomnia). It has distinct meanings and causes. It can refer to the usual state preceding falling asleep ...
(dose-dependent)
* Dry mouth
Xerostomia, also known as dry mouth, is dryness in the mouth, which may be associated with a change in the composition of saliva, or reduced salivary flow, or have no identifiable cause.
This symptom is very common and is often seen as a side eff ...
* Headache (dose-dependent)
* Fatigue
* Skin reactions (if given transdermally)
* Hypotension
Hypotension is low blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure is indicated by two numbers, the systolic blood pressure (the top number) and the dia ...
Common (1-10% frequency):
* Anxiety
* Constipation
* Sedation (dose-dependent)
* Nausea/vomiting
* Malaise
* Abnormal LFTs
* Rash
* Weight gain/loss
* Pain below the ear (from salivary gland)
* Erectile dysfunction
Uncommon (0.1-1% frequency):
* Delusional perception
* Hallucination
* Nightmare
* Paresthesia
* Sinus bradycardia
Sinus bradycardia is a sinus node dysfunction giving a heart rate that is lower than the normal 60–100 beats per minute (bpm) in humans. Bradycardia is generally defined to be a heart rate of under 60 bpm.
Signs and symptoms
The decreased hea ...
* Raynaud's phenomenon
Raynaud syndrome, also known as Raynaud's phenomenon, eponymously named after the physician Auguste Gabriel Maurice Raynaud, who first described it in his doctoral thesis in 1862, is a medical condition in which the spasm of small arteries cau ...
* Pruritus
Itch (also known as pruritus) is a sensation that causes the desire or reflex to scratch. Itch has resisted many attempts to be classified as any one type of sensory experience. Itch has many similarities to pain, and while both are unpleasant ...
* Urticaria
Hives, also known as urticaria, is a kind of skin rash with red, raised, itchy bumps. Hives may burn or sting. The patches of rash may appear on different body parts, with variable duration from minutes to days, and does not leave any long-last ...
Rare (<0.1% frequency):
* Gynaecomastia
Gynecomastia (also spelled gynaecomastia) is the abnormal non-cancerous enlargement of one or both breasts in males due to the growth of breast tissue as a result of a hormone imbalance between estrogens and androgens. Updated by Brent Wisse (1 ...
* Impaired ability to cry
* 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 ...
* Nasal dryness
* Colonic pseudo-obstruction
* Alopecia
Hair loss, also known as alopecia or baldness, refers to a loss of hair from part of the head or body. Typically at least the head is involved. The severity of hair loss can vary from a small area to the entire body. Inflammation or scar ...
* Hyperglycemia
Withdrawal
Because clonidine suppresses sympathetic outflow, resulting in lower blood pressure, sudden discontinuation can result in acute hypertension due to a rebound in sympathetic outflow. In extreme cases, this can result in a hypertensive crisis
Severely elevated blood pressure (equal to or greater than a systolic 180 or diastolic of 120—sometimes termed malignant or accelerated hypertension) is referred to as a hypertensive crisis, as blood pressure at this level confers a high risk ...
, which is a medical emergency.
Clonidine therapy should generally be gradually tapered when discontinuing therapy to avoid rebound effects
The rebound effect, or rebound phenomenon, is the emergence or re-emergence of symptoms that were either absent or controlled while taking a medication, but appear when that same medication is discontinued, or reduced in dosage. In the case of re ...
from occurring. Treatment of clonidine withdrawal hypertension depends on the severity of the condition. Reintroduction of clonidine for mild cases, alpha and beta blockers for more urgent situations. Beta blockers never should be used alone to treat clonidine withdrawal as alpha vasoconstriction would still continue.
Pharmacology
Mechanism of action
Clonidine crosses the blood–brain barrier.
High blood pressure
Clonidine treats high blood pressure by stimulating α2 receptors in the brainstem, which decreases peripheral vascular resistance, lowering blood pressure. It has specificity towards the presynaptic
In the nervous system, a synapse is a structure that permits a neuron (or nerve cell) to pass an electrical or chemical signal to another neuron or to the target effector cell.
Synapses are essential to the transmission of nervous impulses from ...
α2 receptors in the vasomotor center
The vasomotor center (VMC) is a portion of the medulla oblongata. Together with the cardiovascular center and respiratory center, it regulates blood pressure. It also has a more minor role in other homeostatic processes. Upon increase in carbon ...
in the brainstem. This binding has a sympatholytic effect, suppresses release of norepinephrine
Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad' ...
, ATP, renin, and neuropeptide Y
Neuropeptide Y (NPY) is a 36 amino-acid neuropeptide that is involved in various physiological and homeostatic processes in both the central and peripheral nervous systems. NPY has been identified as the most abundant peptide present in the ma ...
which if released would increase vascular resistance
Vascular resistance is the resistance that must be overcome to push blood through the circulatory system and create flow. The resistance offered by the systemic circulation is known as the systemic vascular resistance (SVR) or may sometimes be cal ...
.[
Clonidine also acts as an agonist at imidazoline-1 (I1) receptors in the brain, and it is hypothesized that this effect may contribute to reducing blood pressure by reducing signaling in the sympathetic nervous system; this effect acts upstream of the central α2 agonist effect of clonidine.]
Clonidine may also cause bradycardia, theoretically by increasing signaling through the vagus nerve. When given intravenously, clonidine can temporarily increase blood pressure by stimulating α1 receptors in smooth muscles in blood vessels. This hypertensive effect is not usual when clonidine is given by mouth or by the transdermal
Transdermal is a route of administration wherein active ingredients are delivered across the skin for systemic distribution. Examples include transdermal patches used for medicine delivery.
The drug is administered in the form of a patch or ointme ...
route.
Plasma concentration of clonidine exceeding 2.0 ng/mL does not provide further blood pressure reduction.
Attention deficit hyperactivity disorder
In the setting of attention deficit hyperactivity disorder
Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by excessive amounts of inattention, hyperactivity, and impulsivity that are pervasive, impairing in multiple contexts, and otherwise age-inap ...
(ADHD), clonidine's molecular mechanism of action occurs due to its agonism at the alpha-2A adrenergic receptor
The alpha-2A adrenergic receptor (α2A adrenoceptor), also known as ADRA2A, is an α2 adrenergic receptor, and also denotes the human gene encoding it.
Receptor
α2 adrenergic receptors include 3 highly homologous subtypes: α2A, α2B, and α2 ...
, the subtype of the adrenergic receptor that is most principally found in the brain. Within the brain, the alpha-2A adrenergic receptors are found within the prefrontal cortex
In mammalian brain anatomy, the prefrontal cortex (PFC) covers the front part of the frontal lobe of the cerebral cortex. The PFC contains the Brodmann areas BA8, BA9, BA10, BA11, BA12, BA13, BA14, BA24, BA25, BA32, BA44, BA45, BA46 ...
(PFC), among other areas. The alpha-2A adrenergic receptors are found on the presynaptic cleft of a given neuron, and, when activated by an agonist, the effect on downstream neurons is inhibitory. The inhibition is accomplished by preventing the secretion of the neurotransmitter norepinephrine
Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad' ...
. Thus, clonidine's agonism on alpha-2A adrenergic receptors in the PFC inhibits the action of downstream neurons by preventing the secretion of norepinephrine.
This mechanism is similar to the brain's physiological inhibition of PFC neurons by the locus ceruleus (LC), which secretes norepinephrine into the PFC. Although norepinephrine can also bind to target adrenergic receptors on the downstream neuron (otherwise inducing a stimulatory effect), norepinephrine also binds to alpha-2A adrenergic receptors (akin to clonidine's mechanism of action), inhibiting the release of norepinephrine by that neuron and inducing an inhibitory effect. Because the PFC is required for working memory and attention, it is thought that clonidine's inhibition of PFC neurons helps to eliminate irrelevant attention (and subsequent behaviors), improving the person's focus and correcting deficits in attention.
Growth hormone test
Clonidine stimulates release of HGH hormone from the hypothalamus, which in turn stimulates pituitary release of growth hormone
Growth hormone (GH) or somatotropin, also known as human growth hormone (hGH or HGH) in its human form, is a peptide hormone that stimulates growth, cell reproduction, and cell regeneration in humans and other animals. It is thus important in h ...
. This effect has been used as part of a "growth hormone test," which can assist with diagnosing growth hormone deficiency
Growth hormone deficiency (GHD), or human growth hormone deficiency, is a medical condition resulting from not enough growth hormone (GH). Generally the most noticeable symptom is that an individual attains a short height. Newborns may also prese ...
in children.
Pharmacokinetics
After being ingested, clonidine is absorbed into the blood stream rapidly with an overall bioavailability around 70 - 80%. Peak concentrations in human plasma occur within 60–90 minutes for the "Immediate Release" (IR) version of the drug, which is shorter than the "Extended Release" (ER/XR) version. Clonidine is fairly lipid soluble with the logarithm of its partition coefficient (log P) equal to 1.6; to compare, the optimal log P to allow a drug that is active in the human central nervous system
The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...
to penetrate the blood brain barrier
Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the c ...
is 2.0. Less than half of the absorbed portion of an orally administered dose will be metabolized by the liver
The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it ...
into inactive metabolites, with roughly the other half being excreted unchanged by the kidneys
The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; bloo ...
. About one-fifth of an oral dose will not be absorbed, and is thus excreted in the feces. Work with liver microsomes shows in the liver clonidine is primarily metabolized by CYP2D6
Cytochrome P450 2D6 (CYP2D6) is an enzyme that in humans is encoded by the ''CYP2D6'' gene. ''CYP2D6'' is primarily expressed in the liver. It is also highly expressed in areas of the central nervous system, including the substantia nigra.
CYP2D ...
(66%), CYP1A2
Cytochrome P450 1A2 (abbreviated CYP1A2), a member of the cytochrome P450 mixed-function oxidase system, is involved in the metabolism of xenobiotics in the human body. In humans, the CYP1A2 enzyme is encoded by the ''CYP1A2'' gene.
Function
...
(10-20%), and CYP3A
Cytochrome P450, family 3, subfamily A, also known as CYP3A, is a human gene locus. A homologous locus is found in mice.
The CYP3A locus includes all the known members of the 3A subfamily of the cytochrome P450 superfamily of genes. These genes ...
(0-20%) with negligible contributions from the less abundant enzymes CYP3A5
Cytochrome P450 3A5 is a protein that in humans is encoded by the ''CYP3A5'' gene.
Tissue distribution
''CYP3A5'' encodes a member of the cytochrome P450 superfamily of enzymes. Like most of the cytochrome P450, the CYP3A5 is expressed in the ...
, CYP1A1
Cytochrome P450, family 1, subfamily A, polypeptide 1 is a protein
that in humans is encoded by the ''CYP1A1'' gene.
The protein is a member of the cytochrome P450 superfamily of enzymes.
Function
Metabolism of xenobiotics and drugs
CYP1A1 ...
, and CYP3A4. 4-hydroxyclonidine, the main metabolite of clonidine, is also an alpha-2A agonist but is non lipophilic and is not believed to contribute to the effects of clonidine since it does not cross the blood–brain barrier.
Measurements of the half-life
Half-life (symbol ) is the time required for a quantity (of substance) to reduce to half of its initial value. The term is commonly used in nuclear physics to describe how quickly unstable atoms undergo radioactive decay or how long stable at ...
of clonidine vary widely, between 6 and 23 hours, with the half-life being greatly affected by and prolonged in the setting of poor kidney function. Variations in half-life may be partially attributable to CYP2D6
Cytochrome P450 2D6 (CYP2D6) is an enzyme that in humans is encoded by the ''CYP2D6'' gene. ''CYP2D6'' is primarily expressed in the liver. It is also highly expressed in areas of the central nervous system, including the substantia nigra.
CYP2D ...
genetics. Some research has suggested the half-life of clonidine is dose dependent and approximately doubles upon chronic dosing, while other work contradicts this.[ Following a 0.3 mg oral dose, a small study of five patients by Dollery et al (1976) found half-lives ranging between 6.3 - 23.4 hours (mean 12.7). A similar N=5 study by Davies et al. (1977) found a narrower range of half-lives, between 6.7 - 13 hours (average 8.6 hours),] while an N=8 study by Keraäen et al. that included younger patients found a somewhat shorter average half-life of 7.5 hours.
History
Clonidine was introduced in 1966. It was first used as a hypertension treatment under the trade name of Catapres.
Society and culture
Brand names
As of June 2017, clonidine was marketed under many brand names worldwide: Arkamin, Aruclonin, Atensina, Catapin, Catapres, Catapresan, Catapressan, Chianda, Chlofazoline, Chlophazolin, Clonid-Ophtal, Clonidin, Clonidina, Clonidinã, Clonidine, Clonidine hydrochloride, Clonidinhydrochlorid, Clonidini, Clonidinum, Clonigen, Clonistada, Clonnirit, Clophelinum, Dixarit, Duraclon, Edolglau, Haemiton, Hypodine, Hypolax, Iporel, Isoglaucon, Jenloga, Kapvay, Klofelino, Kochaniin, Lonid, Melzin, Menograine, Normopresan, Paracefan, Pinsanidine, Run Rui, and Winpress. It was marketed as a combination drug
A combination drug or a fixed-dose combination (FDC) is a medicine that includes two or more active ingredients combined in a single dosage form. Terms like "combination drug" or "combination drug product" can be common shorthand for a FDC prod ...
with chlortalidone
Chlortalidone, also known as chlorthalidone, is a thiazide-like diuretic drug used to treat high blood pressure, swelling including that due to heart failure, liver failure, and nephrotic syndrome, diabetes insipidus, and renal tubular aci ...
as Arkamin-H, Bemplas, Catapres-DIU, and Clorpres, and in combination with bendroflumethiazide
Bendroflumethiazide, formerly bendrofluazide, trade name Aprinox, is a thiazide diuretic used to treat hypertension.
Bendroflumethiazide is a thiazide diuretic which works by inhibiting sodium reabsorption at the beginning of the distal convolut ...
as Pertenso.[
]
See also
* Ajmalicine
Ajmalicine, also known as δ-yohimbine or raubasine, is an antihypertensive drug used in the treatment of high blood pressure. It has been marketed under numerous brand names including Card-Lamuran, Circolene, Cristanyl, Duxil, Duxor, Hydroxysarp ...
* Serpentine
References
External links
*
* Alpha-2 agonists i
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