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.
The 2006 European Federation of Neurological Societies guideline recommends that thrombolysis is only used in people who deteriorate despite adequate treatment, and other causes of deterioration have been eliminated. It is unclear which drug and which mode of administration is the most effective. Bleeding into the brain and in other sites of the body is a major concern in the use of thrombolysis. American guidelines make no recommendation with regards to thrombolysis, stating that more research is needed.In those where a venous infarct or hemorrhage causes significant compression of surrounding brain structures, decompressive craniectomy is sometimes required. Raised intracranial pressure, if severe or threatening vision, may require therapeutic lumbar puncture (removal of excessive cerebrospinal fluid), or neurosurgical treatment (optic nerve sheath fenestration or shunting). Venous stenting is emerging as a minimally invasive, safer alternative to shunting. In certain situations, anticonvulsants may be used to try to prevent seizures. These situations include focal neurological problems (e.g. inability to move a limb) and focal changes of the brain tissue on CT or MRI scan. Evidence to support or refute the use of antiepileptic drugs as a preventive measure, however, is lacking. Prognosis
In 2004 the first adequately large scale study on the natural history and long-term prognosis of this condition was reported; this showed that at 16 months follow-up 57.1% of people had full recovery, 29.5%/2.9%/2.2% had respectively minor/moderate/severe symptoms or impairments, and 8.3% had died.