Guanfacine
ADHD medicines
ADHD medicines
A central alpha-2A agonist: a non-stimulant for ADHD (extended-release) and an older antihypertensive. Causes sleepiness and low blood pressure.
Quick facts
- Group
- ADHD medicines
- Target
- Alpha-2A adrenergic receptor (agonist)
- Used for
- ADHD · Hypertension
- Key effects
- Sleepiness · Low blood pressure · Dry mouth
- Monitor
- Sleepiness · Signs of rebound when stopping
- ATC
- C02AC02
No doses: the clinician sets them by the current guideline.
Mechanism of action
No guanfacine-bound structure exists. The figure shows dexmedetomidine, another alpha-2 agonist, in the agonist pocket of the human alpha-2A receptor (with its G protein), where guanfacine also binds.
Guanfacine stimulates alpha-2A adrenergic receptors. In the brainstem this lowers sympathetic outflow to the heart and vessels, so blood pressure and heart rate fall. In the prefrontal cortex, alpha-2A stimulation is thought to strengthen the networks for attention and impulse control, which is the basis of its use in ADHD. It is more selective for alpha-2A than clonidine.
- Guanfacine activates alpha-2A receptors
- Brainstem: less sympathetic outflow, lower blood pressure and heart rate
- Prefrontal cortex: better attention and impulse control
- Stopping suddenly can cause rebound hypertension
Indications
- ADHD (extended-release), alone or added to a stimulant Attention-deficit/hyperactivity disorder (ADHD) →
- Hypertension (immediate-release) Arterial hypertension →
Adverse effects
Common
- Sleepiness, fatigue and lethargy
- Low blood pressure, dizziness and slow heart rate
- Dry mouth, abdominal pain, nausea
- Irritability and insomnia
Contraindications
- Hypersensitivity to guanfacine
Key interactions
- Strong or moderate CYP3A4 inhibitors (ketoconazole, clarithromycin)
- Higher guanfacine exposure: more sedation and hypotension
- Strong or moderate CYP3A4 inducers (rifampicin, carbamazepine)
- Lower levels and loss of effect
- Alcohol, sedatives and other CNS depressants
- Additive sedation
- Other drugs that lower heart rate or blood pressure
- Additive bradycardia and hypotension
What is monitored
- Heart rate and blood pressure before starting, after each change and periodically
- Sleepiness
- Signs of rebound when stopping
Administration and safety
- Extended-release tablets are swallowed whole, not crushed, chewed or broken
- Extended-release tablets are not given with a high-fat meal
- Stopping is done by gradual tapering, never abruptly
Pregnancy and breastfeeding
Decades of use have not shown a clear risk of birth defects, but experience in pregnancy is limited.
Nursing care
- Measures heart rate and blood pressure before starting and after each change
- Teaches the family not to stop it suddenly and to avoid dehydration and overheating
- Warns about sleepiness before driving, cycling or other risky activities
- Asks about fainting and dizziness when standing up
Pharmacokinetics
- Absorption
- Taken by mouth; the extended-release tablet is not interchangeable with the immediate-release one
- Metabolism
- Liver, mainly by CYP3A4
- Half-life
- About 17 hours (immediate-release), shorter in young people
Test yourself
Think of the answer, then tap the question to see it.
Which receptor does guanfacine stimulate, and how does it lower blood pressure?
The alpha-2A adrenergic receptor; it reduces sympathetic outflow from the brainstem.
What happens if guanfacine is stopped abruptly?
Rebound hypertension, which can be severe.
Which two common side effects most often limit guanfacine in ADHD?
Sleepiness and low blood pressure (with slow heart rate).
Connections
← Back to the class: ADHD medicines
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: DailyMed - GUANFACINE tablet, extended release (DailyMed (U.S. National Library of Medicine), 2026); DailyMed - GUANFACINE tablet (DailyMed (U.S. National Library of Medicine), 2026); Guanfacine: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026).
Spotted a mistake?We are always improving for the community. Tell us what is wrong and our team will review it.Report a mistake
Representative model, for educational purposes only.