Similar concern is appropriate when it is used with sedating medications.Guanfacine is known to lower the users tolerance for alcohol, heightening its effect, and alcohol use may prolong the effects of the medication. Pharmacology
Guanfacine is a highly selective agonist of the α2A adrenergic receptor, with low affinity for other receptors. However it may also be a potent 5-HT2B receptor agonist, which can be associated with valvulopathy, although not all 5-HT2B agonists have this effect. Mechanism of action
Guanfacine works by activating α2A adrenoceptors within the central nervous system. This leads to 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 believed to be due to drug stimulation of post-synaptic α2A adrenoceptors on dendritic spines. cAMP-mediated opening of HCN and KCNQ channels is inhibited, which enhances prefrontal cortical synaptic connectivity and neuronal firing. The use of guanfacine for treating prefrontal disorders was developed by the Arnsten Lab at Yale University. 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 is an epoxide. Elimination is not impacted with impaired 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 1986, guanfacine was approved by the FDA for the treatment of hypertension under the brand name Tenex (Drugs@FDA). In 2010, guanfacine was approved by the FDA for the treatment of attention deficit hyperactivity disorder for people 6–17 years old. It was approved for ADHD by the European Medicines Agency under the name Intuniv in 2015. It was added to the Australian Pharmaceutical Benefits Scheme for the treatment of ADHD in 2018. Brand names
Brand names include Tenex, Afken, Estulic, and Intuniv (an extended release formulation). Research
Guanfacine has been studied as a treatment for post-traumatic stress disorder (PTSD). Evidence of efficacy in adults is limited, but one study found positive results in children with comorbid ADHD. It may be also useful in adult PTSD patients who do not respond to SSRIs.Results of studies using guanfacine to treat Tourettes 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 cortex meditated self-control. References
External links
"Guanfacine". Drug Information Portal. U.S. National Library of Medicine.