Anxiety And Adhd Medication

- April 13, 2017

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Guanfacine (brand name Estulic, Tenex and the extended release Intuniv; not to be confused with guaifenesin, an expectorant) is a sympatholytic drug used in the treatment of attention deficit hyperactivity disorder (ADHD), anxiety, and hypertension. It is a selective ?2A receptor agonist. These receptors are concentrated heavily in the prefrontal cortex and the locus coeruleus, with the potential to improve attention resulting from interaction with receptors in the former. Guanfacine lowers both systolic and diastolic blood pressure by activating the central nervous system ?2A norepinephrine autoreceptors, which results in reduced peripheral sympathetic outflow and thus a reduction in peripheral sympathetic tone.

Guanfacine is currently approved and marketed in the United States and Europe as Intuniv for the treatment of ADHD in children and adolescents aged 6-18 years.


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Medical uses

Hypertension

It has been shown to reduce hypertension not just in the short-term, but also in long-term studies to be able to achieve normalization in the blood pressure of 54% of patients treated over a year and 66% over two years. The average reduction in mean arterial pressure of all patients was 16% at the end of the first year and 17% at the end of the second year.

Attention deficit hyperactivity disorder

Guanfacine is used alone or with stimulants to treat children and teenagers with attention deficit hyperactivity disorder. Its effectiveness in this condition is likely due to its ability to strengthen prefrontal cortical regulation of attention and behavior.

Anxiety

Another psychiatric use of guanfacine is for treatment of anxiety, such as generalized anxiety disorder and posttraumatic stress disorder (PTSD) symptoms. Guanfacine and other ?2A agonists have anxiolytic-like action, reducing the emotional responses of the amygdala, and strengthening prefrontal cortical regulation of emotion, action and thought. These actions arise from both inhibition of stress-induced catecholamine release, and from prominent, post-synaptic actions in prefrontal cortex. Due to its prolonged half-life, it also has been seen to improve sleep interrupted by nightmares in PTSD patients. All of these actions likely contribute to the relief of the hyperarousal, re-experiencing of memory, and impulsivity associated with PTSD. Guanfacine appears to be especially helpful in treating children who have been traumatized or abused.

Tourette syndrome and Tics

According to recent studies (Srour et al., 2008) there is controversy as to guanfacine's usefulness in treating tics. There has been success when tic symptoms are co-morbid with ADHD, and as such, guanfacine and other ?2A-adrenergic agonists (clonidine) are commonly the first choice for treatment.

Treatment of withdrawal syndrome

Guanfacine is also being 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.


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Adverse effects

Side effects of guanfacine are dose-dependent. Adverse effects by incidence:

Very common (>10% incidence) adverse effects:

Common (1-10% incidence) adverse effects:

Adverse effects with unknown frequency:

Interactions

  • CYP3A4 or CYP3A5 enzyme inhibitors -- Use caution. Elevates plasma concentration of guanfacine.
  • CYP3A4 enzyme inducers -- May decrease medication response.
  • Valproic acid -- Use caution. Elevates plasma concentration of valproic acid.
  • Antihypertensive drugs -- Use caution. Potential for additive pharmacodynamic effects (hypotension, syncope, etc.).
  • CNS depressant drugs -- Use caution. Potential for additive pharmacodynamic effects (sedation, somnolence, etc.).

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Pharmacokinetics and metabolism

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. In animal models, guanfacine's enhancing effects on the working-memory functions of the pre-frontal cortex 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 alpha-2a-adrenoceptors that guanfacine stimulates through binding.


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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 contributing to valvulopathy, theoretically.


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History

In 2010, guanfacine was approved by the FDA for the treatment of attention deficit hyperactivity disorder for people 6-17 years old.

Source of the article : Wikipedia



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