Guanfacine (trade names Estulic, Tenex, and, in extended release form, Intuniv) is a sympatholytic drug used to treat hypertension and attention deficit hyperactivity disorder (ADHD). It is a selective ?2A receptor agonist.
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Medical uses
Guanfacine is used alone or with stimulants to treat children and teenagers with attention deficit hyperactivity disorder. It is also used to treat high blood pressure.
Adverse effects
Side effects of guanfacine are dose-dependent.
Very common (>10% incidence) adverse effects include sleepiness, tiredness, headache, and stomach ache.
Common (1-10% incidence) adverse effects include decreased appetite, depressed mood, anxiety, irritability, mood changes, insomnia, nightmares, dizziness, lack of energy, slowed heart beat, low blood pressure, feeling faint when standing quickly, vomiting, nausea, diarrhea, constipation, dry mouth, urinary incontinence, and rashes.
Typical side effects such as fatigue, irritability and stomach upset can take a week or two to subside. Increases in dosage can have the same adjustment period.
Interactions
Guanfacine availability is significantly affected by the CYP3A4 and CYP3A5 enzymes, and drugs that inhibit or induce those enzymes change the amount of guanfacine in circulation and thus its efficacy and adverse effects, and likewise guanfacine affects those drugs. Because of its affects on the heart, it needs to be used with caution with other drugs that may affect heart; likewise other drugs that may cause sedation.
Pharmacology
Guanfacine is a highly selective agonist of the ?2A adrenergic receptor, with negligible affinity for any other receptor. However, it may also be a potent 5-HT2B receptor agonist, potentially (theoretically) contributing to valvulopathy.
Mechanism of action
Guanfacine works by activating ?2A adrenoceptors in the central nervous system. This results in reduced peripheral sympathetic outflow and thus a reduction in peripheral sympathetic tone, which lowers both systolic and diastolic blood pressure. In ADHD, guanfacine works by strengthening regulation of attention and behavior by the prefrontal cortex. These enhancing effects on prefrontal cortical functions are thought to be due to inhibition of cAMP-mediated signaling, which is effected by the Gi proteins that are generally coupled to the post-synaptic ?2A adrenoceptors that guanfacine stimulates through binding.
Pharmacokinetics
Guanfacine has an oral bioavailability of 80%. There is no clear evidence of any first-pass metabolism. Elimination half-life is 17 hours with the major elimination route being renal. The principal metabolite is the 3-hydroxy-derivative, with evidence of moderate biotransformation, and the key intermediate being an epoxide. It is also shown that elimination in patients with impaired renal function does not differ significantly from those with normal renal function. As such, metabolism by liver is the assumption for those with impaired renal function, as supported by increased frequency of known side effects of orthostatic hypotension and sedation.
History
In 2010, guanfacine was approved by the FDA for the treatment of attention deficit hyperactivity disorder for people 6-17 years old.
Guanfacine is approved and marketed in the United States and Europe
Research
Guanfacine has been studied in anxiety disorders and post traumatic stress syndrome in children and adults; it has shown little to no efficacy yet caused adverse effects like dry mouth and light-headedness.
Results of studies using guanfacine to treat Tourette's have been mixed.
Guanfacine has been investigated for treatment of withdrawal for opioids, ethanol, and nicotine. Guanfacine has been shown to help reduce stress-induced craving of nicotine in smokers trying to quit, which may involve strengthening of prefrontal cortical self-control.
Source of the article : Wikipedia
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