Alpha-2 agonist antihypertensives.
An imidazole.
Reduces hypertension, tachycardia and norepinephrine release in response to stress induced by anesthesia and surgical procedures.
Bioavailability 75-95%
Protein binding 20-40%
Hepatic metabolsim to inactive metabolites, and 40-50% urine excererion.
Half-life 12-33 hours
Routes are oral or transdermal and epidural.
Used to treat several medical conditions: hypertension, drug, neuropathic pain, detoxification of nicotine, alcohol and opioids, sleep hyperhidrosis, anaesthesia, to counter the side effects of stimulant medications such as methylphenidate or amphetamine, insomnia, relief of menopausal symptoms, used in conjunction with stimulants to treat attention-deficit hyperactivity disorder (ADHD), and may reduce tics, epidurally for pain during myocardial infarction, postoperative and intractable pain, to treat the hyperarousal symptoms of post-traumatic stress syndrome.
A centrally acting alpha-2-adrenergic agonist that blunts central sympathetic outflow and has analgesic, anxiolytic, and anti-inflammatory effects.
Clonidine is also a mild sedative.
Has been prescribed to treat psychiatric disorders including stress, sleep disturbances, borderline personality disorder, and anxiety disorders.
Treats high blood pressure by stimulating presynaptic α2 receptors in the vasomotor center of the brain, which decreases cardiac output and peripheral vascular resistance.
Decreases presynaptic calcium levels, and inhibits the release of norepinephrine and decreases in sympathetic tone.
Antihypertensive effect of clonidine may be due to agonism on the imidazoline receptor which mediates the sympatho-inhibitory actions of imidazolines to lower blood pressure.
Prolongs the effects of analgesia when used with a local anesthetic.
Adverse effects include, lightheadedness, dry mouth, dizziness, hypotension and constipation.
Clonidine also has peripheral alpha agonist activity which can on occasion lead to hypertension.
For oral therapy a total dosage of 0.2–0.4 mg daily is taken in divided doses.
May cause rebound hypertension or hypotension on withdrawal, so the drug should generally be tapered off when discontinuing therapy.
Treatment of clonidine withdrawal hypertension may involve re-introduction of clonidine for mild cases, or alpha and beta blockers for more significant hypertension.
Clonidine selectively stimulates receptors in the brain that monitor catecholamine levels in the blood. and provides a negative feedback loop that begins with descending sympathetic nerves from the brain that control the production of catecholamines in the adrenal medulla.
Causes the brain to reduce its signals to the adrenal medulla, which in turn lowers catecholamine production and blood levels with lowered heart rate and blood pressure.
Suddenly withdrawal of clonidine may cause the sympathetic nervous system to producing high levels of epinephrine and norepinephrine, causing rebound hypertension.