Clonidine, sold under the brand name Catapres among others, is an
α2A-adrenergic receptor agonist medication used to treat
high blood pressure
Hypertension, also known as high blood pressure, is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms itself. It is, however, a major ri ...
,
attention deficit hyperactivity disorder
Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by symptoms of inattention, hyperactivity, impulsivity, and emotional dysregulation that are excessive and pervasive, impairing in multiple con ...
(ADHD),
drug withdrawal
A drug is any chemical substance other than a nutrient or an essential dietary ingredient, which, when administered to a living organism, produces a biological effect. Consumption of drugs can be via insufflation (medicine), inhalation, drug i ...
(e.g.,
alcohol
Alcohol may refer to:
Common uses
* Alcohol (chemistry), a class of compounds
* Ethanol, one of several alcohols, commonly known as alcohol in everyday life
** Alcohol (drug), intoxicant found in alcoholic beverages
** Alcoholic beverage, an alco ...
,
opioids
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, ...
, 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 (American English), also spelled diarrhoea or diarrhœa (British English), is the condition of having at least three loose, liquid, or watery bowel movements in a day. It often lasts for a few days and can result in dehydration d ...
,
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.
The drug is often prescribed off-label for
tics
A tic is a sudden and repetitive motor movement or vocalization that is not rhythmic and involves discrete muscle groups. Tics are typically brief and may resemble a normal behavioral characteristic or gesture.
Tics can be invisible to the obs ...
. It is used
orally
The word oral may refer to:
Relating to the mouth
* Relating to the mouth, the first portion of the alimentary canal that primarily receives food and liquid
**Oral administration of medicines
** Oral examination (also known as an oral exam or oral ...
(by mouth), by
injection
Injection or injected may refer to:
Science and technology
* Injective function, a mathematical function mapping distinct arguments to distinct values
* Injection (medicine), insertion of liquid into the body with a syringe
* Injection, in broadca ...
, or as a
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 ointm ...
skin patch.
Onset of action is typically within an hour with the effects on blood pressure lasting for up to eight hours.
Common side effects include
dry mouth
Xerostomia, also known as dry mouth, is a subjective complaint of dryness in the mouth, which may be associated with a change in the composition of saliva, reduced salivary flow, or have no identifiable cause.
This symptom is very common and is o ...
,
dizziness
Dizziness is an imprecise term that can refer to a sense of disorientation in space, vertigo, or lightheadedness. It can also refer to Balance disorder, disequilibrium or a non-specific feeling, such as giddiness or foolishness.
Dizziness is a ...
,
headaches
A headache, also known as cephalalgia, is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches.
Head ...
,
hypotension
Hypotension, also known as low blood pressure, is a cardiovascular condition characterized by abnormally reduced blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood and is ...
, and
sleepiness
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 ...
.
Severe side effects may include
hallucinations
A hallucination is a perception in the absence of an external stimulus that has the compelling sense of reality. They are distinguishable from several related phenomena, such as dreaming ( REM sleep), which does not involve wakefulness; pse ...
,
heart arrhythmias, and
confusion
In psychology, confusion is the quality or emotional state of being bewildered or unclear. The term "acute mental confusion" .
If rapidly stopped, withdrawal effects may occur, such as
a dangerous rise in blood pressure.
Use during
pregnancy
Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins.
Conception (biology), Conception usually occurs ...
or
breastfeeding
Breastfeeding, also known as nursing, is the process where breast milk is fed to a child. Infants may suck the milk directly from the breast, or milk may be extracted with a Breast pump, pump and then fed to the infant. The World Health Orga ...
is not recommended.
Clonidine lowers blood pressure by stimulating
α2-adrenergic 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
A generic drug is a pharmaceutical drug that contains the same chemical substance as a drug that was originally protected by chemical patents. Generic drugs are allowed for sale after the patents on the original drugs expire. Because the active ch ...
.
[ In 2022, it was the 71st most commonly prescribed medication in the United States, with more than 9million prescriptions.
]
Medical uses
Clonidine is used to treat high blood pressure
Hypertension, also known as high blood pressure, is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms itself. It is, however, a major ri ...
, attention deficit hyperactivity disorder
Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by symptoms of inattention, hyperactivity, impulsivity, and emotional dysregulation that are excessive and pervasive, impairing in multiple con ...
(ADHD); drug withdrawal
A drug is any chemical substance other than a nutrient or an essential dietary ingredient, which, when administered to a living organism, produces a biological effect. Consumption of drugs can be via insufflation (medicine), inhalation, drug i ...
, including from (alcohol
Alcohol may refer to:
Common uses
* Alcohol (chemistry), a class of compounds
* Ethanol, one of several alcohols, commonly known as alcohol in everyday life
** Alcohol (drug), intoxicant found in alcoholic beverages
** Alcoholic beverage, an alco ...
, opioids
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, ...
, and/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 (American English), also spelled diarrhoea or diarrhœa (British English), is the condition of having at least three loose, liquid, or watery bowel movements in a day. It often lasts for a few days and can result in dehydration d ...
, and certain pain conditions. In addition, it also sees some use off-label for episodic insomnia
Insomnia, also known as sleeplessness, is a sleep disorder where people have difficulty sleeping. They may have difficulty falling asleep, or staying asleep for as long as desired. Insomnia is typically followed by daytime sleepiness, low ene ...
, and tics
A tic is a sudden and repetitive motor movement or vocalization that is not rhythmic and involves discrete muscle groups. Tics are typically brief and may resemble a normal behavioral characteristic or gesture.
Tics can be invisible to the obs ...
(e.g. from Tourette Syndrome
Tourette syndrome (TS), or simply 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) tic. Common tics are blinkin ...
, restless legs syndrome
Restless legs syndrome (RLS), also known as Willis–Ekbom disease (WED), is a neurological disorder, usually chronic, that causes an overwhelming urge to move one's legs. There is often an unpleasant feeling in the legs that improves temporaril ...
, and anxiety
Anxiety is an emotion characterised by an unpleasant state of inner wikt:turmoil, turmoil and includes feelings of dread over Anticipation, anticipated events. Anxiety is different from fear in that fear is defined as the emotional response ...
, among others).[
]
Resistant hypertension
Clonidine may be effective for lowering blood pressure in people with resistant hypertension
Hypertension, also known as high blood pressure, is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms itself. It is, however, a major risk ...
.
Clonidine works by slowing the pulse rate
In medicine, the pulse refers to the rhythmic pulsations (expansion and contraction) of an artery in response to the cardiac cycle (heartbeat). The pulse may be felt (palpated) in any place that allows an artery to be compressed near the surface ...
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 reni ...
, aldosterone
Aldosterone is the main mineralocorticoid steroid hormone produced by the zona glomerulosa of the adrenal cortex in the adrenal gland. It is essential for sodium conservation in the kidney, salivary glands, sweat glands, and colon. It plays ...
, and catecholamines
A catecholamine (; abbreviated CA), most typically a 3,4-dihydroxyphenethylamine, is a monoamine neurotransmitter, an organic compound that has a catechol (benzene with two hydroxyl side groups next to each other) and a side-chain amine.
...
.
Uses
Borderline personality disorder
Clonidine has been studied off-label in borderline personality disorder (BPD) to address specific acute symptoms such as hyperarousal, inner tension, dissociation, self-injurious urges, and sleep disturbances.
A pilot study administering oral clonidine (75–150 μg) to 14 female BPD patients demonstrated rapid decreases in aversive inner tension, dissociative symptoms, urges to self-harm, and suicidal ideation—typically peaking within 30–60 minutes of dosing.
In a double-blind, placebo-controlled crossover trial involving 18 patients (with and without comorbid PTSD), clonidine significantly reduced hyperarousal symptoms measured by the Clinician-Administered PTSD Scale (P = 0.003), irrespective of PTSD diagnosis. It also notably improved subjective sleep latency (P = 0.005) and restorative sleep quality (P = 0.014).
A systematic review of psychopharmacology in BPD identified clonidine as a promising adjunctive therapy targeting noradrenergic dysregulation, especially in comorbid PTSD cases. However, it emphasized the limitations of small sample sizes and called for larger placebo-controlled trials.
Clinicians often employ clonidine when BPD patients present with acute emotional dysregulation, intrusive dissociation, or insomnia. Clinical anecdotal reports and patient experiences have also highlighted its practical utility.
''Note: Clonidine is not FDA-approved for the treatment of borderline personality disorder. Its use in this context should be considered investigational and symptom-targeted.''
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
Australia, officially the Commonwealth of Australia, is a country comprising mainland Australia, the mainland of the Australia (continent), Australian continent, the island of Tasmania and list of islands of Australia, numerous smaller isl ...
, 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 a central nervous system (CNS) stimulant used in the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. It may be taken Oral adm ...
, 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
Stimulants (also known as central nervous system stimulants, or psychostimulants, or colloquially as uppers) are a class of drugs that increase alertness. They are used for various purposes, such as enhancing attention, motivation, cognition, ...
medications. Some studies show clonidine to be more sedating
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, ...
than guanfacine
Guanfacine, sold under the brand name Tenex ( immediate-release) and Intuniv ( extended-release) among others, is an oral alpha-2a agonist medication used to treat attention deficit hyperactivity disorder (ADHD) and high blood pressure.
Co ...
, which may be better at bedtime along with an arousing stimulant
Stimulants (also known as central nervous system stimulants, or psychostimulants, or colloquially as uppers) are a class of drugs that increase alertness. They are used for various purposes, such as enhancing attention, motivation, cognition, ...
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 where people have difficulty sleeping. They may have difficulty falling asleep, or staying asleep for as long as desired. Insomnia is typically followed by daytime sleepiness, low ene ...
. Unlike stimulant medications, clonidine is regarded as having no abuse potential, and may even be used to reduce abuse of drugs including nicotine and cocaine.
In the US, only the extended-release form of clonidine is approved for ADHD treatment.
Drug withdrawal
Clonidine may be used to ease drug withdrawal symptoms associated with abruptly stopping the long-term use of opioids
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, ...
, alcohol
Alcohol may refer to:
Common uses
* Alcohol (chemistry), a class of compounds
* Ethanol, one of several alcohols, commonly known as alcohol in everyday life
** Alcohol (drug), intoxicant found in alcoholic beverages
** Alcoholic beverage, an alco ...
, benzodiazepines
Benzodiazepines (BZD, BDZ, BZs), colloquially known as "benzos", are a class of central nervous system (CNS) depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed to treat co ...
, 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 arising from the sudden cessation or reduction of opioids where previous usage has been heavy and prolonged. Signs and symptoms of withdrawal can include drug craving, anxiety, restless legs syndrome, naus ...
symptoms by reducing the sympathetic nervous system
The sympathetic nervous system (SNS or SANS, sympathetic autonomic nervous system, to differentiate it from the somatic nervous system) is one of the three divisions of the autonomic nervous system, the others being the parasympathetic nervous sy ...
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
Hypertension, also known as high blood pressure, is a Chronic condition, long-term Disease, medical condition in which the blood pressure in the artery, arteries is persistently elevated. High blood pressure usually does not cause symptoms i ...
, hyperhidrosis
Hyperhidrosis is a medical condition in which a person exhibits excessive perspiration, sweating, more than is required for the Thermoregulation, regulation of body temperature. Although it is primarily a physical burden, hyperhidrosis can deterio ...
(excessive sweating), hot and cold flashes, and akathisia
Akathisia (IPA: /æ.kə.ˈθɪ.si.ə/) is a movement disorder characterized by a subjective feeling of inner restlessness accompanied by mental distress and/or an inability to sit still. Usually, the legs are most prominently affected. Those 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 drug withdrawal syndrome of infants, caused by the cessation of the administration of drugs which may or may not be licit. Tolerance, ...
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
A neonatal intensive care unit (NICU), also known as an intensive care nursery (ICN), is an intensive care unit (ICU) specializing in the care of ill or premature newborn infants. The NICU is divided into several areas, including a critical c ...
Network Neurobehavioral Score.
Clonidine has also been suggested as a treatment for rare instances of dexmedetomidine
Dexmedetomidine, sold under the brand name Precedex among others, is a medication used for sedation. Veterinarians use dexmedetomidine for similar purposes in treating cats, dogs, and horses. It is also used in humans to treat acute agitation as ...
withdrawal.
Spasticity
Clonidine has some role in the treatment of spasticity caused by spinal cord injury, acting principally by inhibiting excessive sensory transmission Its use, however, is mainly as a second or third line agent, due to side effects such as hypotension
Hypotension, also known as low blood pressure, is a cardiovascular condition characterized by abnormally reduced blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood and is ...
, bradycardia
Bradycardia, also called bradyarrhythmia, is a resting heart rate under 60 beats per minute (BPM). While bradycardia can result from various pathological processes, it is commonly a physiological response to cardiovascular conditioning or due ...
, 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 ...
. Clonidine can be administered intrathecal
Intrathecal administration is a route of administration for drugs via an injection into the spinal canal, or into the subarachnoid space (sin. ''intrathecal space'') so that it reaches the cerebrospinal fluid (CSF). It is useful in several applic ...
ly, which confers various benefits, including a reduction or prevention of the blood pressure lowering effects and increased effectiveness against spasticity. The effectiveness of intrathecal clonidine is comparable to that of intrathecal baclofen for spasticity.[
]
Clonidine suppression test
The reduction in circulating norepinephrine by clonidine was used in the past as an investigatory test for phaeochromocytoma
Pheochromocytoma is a rare tumor of the adrenal medulla composed of chromaffin cells and is part of the paraganglioma (PGL) family of tumors, being defined as an intra-adrenal PGL. These neuroendocrine tumors can be sympathetic, where they relea ...
, which is a catecholamine-synthesizing tumor, usually found in the adrenal medulla
The adrenal medulla () is the inner part of the adrenal gland. It is located at the center of the gland, being surrounded by the adrenal cortex. It is the innermost part of the adrenal gland, consisting of chromaffin cells that secrete catecho ...
. 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.
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 mo ...
s, and has been prescribed to treat psychiatric disorder
A mental disorder, also referred to as a mental illness, a mental health condition, or a psychiatric disability, is a behavioral or mental pattern that causes significant distress or impairment of personal functioning. A mental disorder is ...
s including stress, hyperarousal
The fight-or-flight or the fight-flight-freeze-or-fawn (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 describ ...
caused by post-traumatic stress disorder
Post-traumatic stress disorder (PTSD) is a mental disorder that develops from experiencing a Psychological trauma, traumatic event, such as sexual assault, domestic violence, child abuse, warfare and its associated traumas, natural disaster ...
, borderline personality disorder
Borderline personality disorder (BPD) is a personality disorder characterized by a pervasive, long-term pattern of significant interpersonal relationship instability, an acute fear of Abandonment (emotional), abandonment, and intense emotiona ...
, and other anxiety disorder
Anxiety disorders are a group of mental disorders characterized by significant and uncontrollable feelings of anxiety and fear such that a person's social, occupational, and personal functions are significantly impaired. Anxiety may cause phys ...
s. Clonidine is also a mild 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 ...
, and can be used as premedication
Premedication is using medication before some other therapy (usually surgery or chemotherapy) to prepare for that forthcoming therapy. Typical examples include premedicating with a sedative or analgesic before surgery; using prophylactic (preven ...
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 a neurological disorder, usually chronic, that causes an overwhelming urge to move one's legs. There is often an unpleasant feeling in the legs that improves temporaril ...
. 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, en ...
. It has also been successfully used topically in a clinical trial as a treatment for diabetic neuropathy
Diabetic neuropathy includes various types of nerve damage associated with diabetes mellitus. The most common form, diabetic peripheral neuropathy, affects 30% of all diabetic patients. Studies suggests that cutaneous nerve branches, such as the s ...
. Clonidine can also be used for migraine
Migraine (, ) is a complex neurological disorder characterized by episodes of moderate-to-severe headache, most often unilateral and generally associated with nausea, and light and sound sensitivity. Other characterizing symptoms may includ ...
headaches and hot flash
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 may typically last from t ...
es associated with menopause
Menopause, also known as the climacteric, is the time when Menstruation, menstrual periods permanently stop, marking the end of the Human reproduction, reproductive stage for the female human. It typically occurs between the ages of 45 and 5 ...
. Clonidine has also been used to treat refractory diarrhea
Diarrhea (American English), also spelled diarrhoea or diarrhœa (British English), is the condition of having at least three loose, liquid, or watery bowel movements in a day. It often lasts for a few days and can result in dehydration d ...
associated with irritable bowel syndrome
Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterized by a group of symptoms that commonly include abdominal pain, 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—including flatus (gas), liquid stool elements and mucus, or solid feces. FI is a sign or a symptom ...
, diabetes, diarrhea associated with opioid withdrawal, intestinal failure, neuroendocrine tumor
Neuroendocrine tumors (NETs) are neoplasms that arise from cells of the endocrine (hormonal) and nervous systems. They most commonly occur in the intestine, where they are often called carcinoid tumors, but they are also found in the pancreas, lu ...
s, and cholera
Cholera () is an infection of the small intestine by some Strain (biology), strains of the Bacteria, bacterium ''Vibrio cholerae''. Symptoms may range from none, to mild, to severe. The classic symptom is large amounts of watery diarrhea last ...
. Clonidine can be used in the treatment of Tourette syndrome
Tourette syndrome (TS), or simply 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) tic. Common tics are blinkin ...
(specifically for tics
A tic is a sudden and repetitive motor movement or vocalization that is not rhythmic and involves discrete muscle groups. Tics are typically brief and may resemble a normal behavioral characteristic or gesture.
Tics can be invisible to the obs ...
). Clonidine has also had some success in clinical trials for helping to remove or ameliorate the symptoms of hallucinogen persisting perception disorder
Hallucinogen persisting perception disorder (HPPD) is a non-psychotic disorder in which a person experiences apparent lasting or persistent visual hallucinations or perceptual distortions after using drugs, including but not limited to psychedeli ...
(HPPD).
Injection of α2-adrenergic 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.
Pregnancy and breastfeeding
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; a nursing infant's serum clonidine concentration is approximately 2/3 of the mother's. 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 they are standing up ( orthostasis) or sitting down. Primary orthostatic hypotension is also often referred to as ne ...
* 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 aslee ...
(dose-dependent)
* Dry mouth
Xerostomia, also known as dry mouth, is a subjective complaint of dryness in the mouth, which may be associated with a change in the composition of saliva, reduced salivary flow, or have no identifiable cause.
This symptom is very common and is o ...
* Headache (dose-dependent)
* Fatigue
* Skin reactions (if given transdermally)
* Hypotension
Hypotension, also known as low blood pressure, is a cardiovascular condition characterized by abnormally reduced blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood and is ...
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
Erectile dysfunction (ED), also referred to as impotence, is a form of sexual dysfunction in males characterized by the persistent or recurring inability to achieve or maintain a Human penis, penile erection with sufficient rigidity and durat ...
Uncommon (0.1–1% frequency):
* Delusional perception
* Hallucination
* Nightmare
* Paresthesia
Paresthesia is a sensation of the skin that may feel like numbness (''hypoesthesia''), tingling, pricking, chilling, or burning. It can be temporary or Chronic condition, chronic and has many possible underlying causes. Paresthesia is usually p ...
* Sinus bradycardia
Sinus bradycardia is a sinus rhythm with a reduced rate of electrical discharge from the sinoatrial node, resulting in a bradycardia, a heart rate that is lower than the normal range (60–100 beats per minute for adult humans).
Signs and sympt ...
* Raynaud's phenomenon
Raynaud syndrome, also known as Raynaud's phenomenon, is a medical condition in which the spasm of small arteries causes episodes of reduced blood flow to end arterioles. Typically the fingers, and, less commonly, the toes, are involved. Rare ...
* Pruritus
An itch (also known as pruritus) is a sensation that causes a strong desire or reflex to scratch. Itches have resisted many attempts to be classified as any one type of sensory experience. Itches have many similarities to pain, and while both ...
* Urticaria
Hives, also known as urticaria, is a kind of skin rash with red or flesh-colored, 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 typically ...
Rare (<0.1% frequency):
* Gynaecomastia
Gynecomastia (also spelled gynaecomastia) is the non-cancerous enlargement of one or both breasts in men due to the growth of breast tissue as a result of a hormone imbalance between estrogens and androgens. Updated by Brent Wisse (10 Novemb ...
* 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 scarring ...
* Hyperglycemia
Hyperglycemia is a condition where unusually high amount of glucose is present in blood. It is defined as blood glucose level exceeding 6.9 mmol/L (125 mg/dL) after fasting for 8 hours or 10 mmol/L (180 mg/dL) 2 hours after eating.
Blood gluc ...
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 180 mmHg systolic or 120 mmHg diastolic) is referred to as a hypertensive crisis (sometimes termed malignant or accelerated hypertension), due to the high risk of complications. People ...
, 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
Alpha (uppercase , lowercase ) is the first letter of the Greek alphabet. In the system of Greek numerals, it has a value of one. Alpha is derived from the Phoenician letter ''aleph'' , whose name comes from the West Semitic word for ' ...
and beta
Beta (, ; uppercase , lowercase , or cursive ; or ) is the second letter of the Greek alphabet. In the system of Greek numerals, it has a value of 2. In Ancient Greek, beta represented the voiced bilabial plosive . In Modern Greek, it represe ...
blockers for more urgent situations. Beta blockers should never be used alone to treat clonidine withdrawal as alpha vasoconstriction would still continue.
Pharmacology
Mechanism of action
Clonidine crosses the blood–brain barrier
The blood–brain barrier (BBB) is a highly selective semipermeable membrane, semipermeable border of endothelium, endothelial cells that regulates the transfer of solutes and chemicals between the circulatory system and the central nervous system ...
.
High blood pressure
Clonidine treats high blood pressure by stimulating α2 receptors in the brainstem, which decreases peripheral vascular resistance
Vascular resistance is the resistance that must be overcome for blood to flow through the circulatory system. The resistance offered by the systemic circulation is known as the systemic vascular resistance or may sometimes be called by another ter ...
, lowering blood pressure. It has specificity towards the presynaptic
In the nervous system, a synapse is a structure that allows a neuron (or nerve cell) to pass an electrical or chemical signal to another neuron or a target effector cell. Synapses can be classified as either chemical or electrical, depending o ...
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 carbo ...
in the brainstem
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 conti ...
. This binding has a sympatholytic
A sympatholytic (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 example, t ...
effect, suppresses release of norepinephrine
Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic compound, organic chemical in the catecholamine family that functions in the brain and human body, body as a hormone, neurotransmitter and neuromodulator. The ...
, 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. It is secreted alongside other neurotransmitters such as GABA and glu ...
which if released would increase vascular resistance
Vascular resistance is the resistance that must be overcome for blood to flow through the circulatory system. The resistance offered by the systemic circulation is known as the systemic vascular resistance or may sometimes be called by another ter ...
.[
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
The sympathetic nervous system (SNS or SANS, sympathetic autonomic nervous system, to differentiate it from the somatic nervous system) is one of the three divisions of the autonomic nervous system, the others being the parasympathetic nervous sy ...
; this effect acts upstream of the central α2 agonist effect of clonidine.
Clonidine may also cause bradycardia
Bradycardia, also called bradyarrhythmia, is a resting heart rate under 60 beats per minute (BPM). While bradycardia can result from various pathological processes, it is commonly a physiological response to cardiovascular conditioning or due ...
, theoretically by increasing signaling through the vagus nerve. When given intravenously, clonidine can temporarily increase blood pressure by stimulating α1 receptors in smooth muscle
Smooth muscle is one of the three major types of vertebrate muscle tissue, the others being skeletal and cardiac muscle. It can also be found in invertebrates and is controlled by the autonomic nervous system. It is non- striated, so-called bec ...
s in blood vessels. This hypertensive effect is not usual when clonidine is given orally 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 ointm ...
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 symptoms of inattention, hyperactivity, impulsivity, and emotional dysregulation that are excessive and pervasive, impairing in multiple con ...
(ADHD), clonidine's molecular mechanism of action occurs due to its agonism
Agonism (from Greek 'struggle') is a political and social theory that emphasizes the potentially positive aspects of certain forms of conflict. It accepts a permanent place for such conflict in the political sphere, but seeks to show how indivi ...
at the α2A adrenergic receptor, the subtype of the adrenergic receptor
The adrenergic receptors or adrenoceptors are a class of G protein-coupled receptors that are targets of many catecholamines like norepinephrine (noradrenaline) and epinephrine (adrenaline) produced by the body, but also many medications like b ...
that is most principally found in the brain. Within the brain, the α2A 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. It is the association cortex in the frontal lobe. The PFC contains the Brodmann areas BA8, BA9, BA10, BA11, BA12, ...
(PFC), among other areas. The α2A 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 compound, organic chemical in the catecholamine family that functions in the brain and human body, body as a hormone, neurotransmitter and neuromodulator. The ...
. Thus, clonidine's agonism on α2A 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
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 ...
(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 α2A 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 GHRH 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 ...
. 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 hyposomatotropism, 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 present low blood ...
in children.
Pharmacokinetics
After being ingested, clonidine is absorbed into the blood stream rapidly with an overall bioavailability
In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation.
By definition, when a medication is administered intravenously, its bioavailability is 100%. H ...
around 70–80%. Peak concentrations Peak or The Peak may refer to:
Basic meanings Geology
* Mountain peak
** Pyramidal peak, a mountaintop that has been sculpted by erosion to form a point Mathematics
* Peak hour or rush hour, in traffic congestion
* Peak (geometry), an (''n''-3)-di ...
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, spinal cord and retina. The CNS is so named because the brain integrates the received information and coordinates and influences the activity o ...
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 is compo ...
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 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 ...
into inactive metabolite
In biochemistry, a metabolite is an intermediate or end product of metabolism.
The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...
s, with roughly the other half being excreted unchanged by the kidneys
In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and right in the retro ...
. 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.
CYP2 ...
(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. These genes encode monooxygenases which catalyze many reactions involved in the synthesis of cholesterol, steroids and other ...
(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 is ...
, and CYP3A4
Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine, which in humans is encoded by ''CYP3A4'' gene. It organic redox reaction, oxidizes small foreign organic molecules ( ...
. 4-hydroxyclonidine, the main metabolite of clonidine, is also an α2A 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 is a mathematical and scientific description of exponential or gradual decay.
Half-life, half life or halflife may also refer to:
Film
* Half-Life (film), ''Half-Life'' (film), a 2008 independent film by Jennifer Phang
* ''Half Life: ...
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.
CYP2 ...
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 and 23.4 hours (]mean
A mean is a quantity representing the "center" of a collection of numbers and is intermediate to the extreme values of the set of numbers. There are several kinds of means (or "measures of central tendency") in mathematics, especially in statist ...
12.7). A similar N=5 study by Davies et al. (1977) found a narrower range of half-lives, between 6.7 and 13 hours (mean 8.6), while an N=8 study by Keraäen et al. that included younger patients found a somewhat shorter mean 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 is 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 is marketed as a combination drug
A combination drug is a combination of two or more pharmaceutical drugs as active ingredients combined into a single dosage form, typically as a ''fixed-dose combination'', with each constituent standardized to specifications of a fixed dose. Fix ...
with chlortalidone 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.[
]
References
External links
* Alpha-2 agonists i
ADHD
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Alpha-2 adrenergic receptor agonists
Anilines
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Attention deficit hyperactivity disorder management
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