Dr. Sanil Rege starts this video by discussing the Alpha 1 and Alpha 2 adrenergic receptors and their mechanism of action. He then discusses the mechanism of action of Prazosin and Clonidine in the context of the Alpha 1 and Alpha 2 receptors. Prazosin is an Alpha 1 adrenergic receptor antagonist and Clonidine is an Alpha 2 adrenergic receptor agonist. Finally, he shares his practical clinical experience with regards to both agents covering indications, optimum doses and side effects.

Discussion points:

Prazosin

• Unique therapeutic effects on nightmares and sleep disturbance associated with PTSD

• Orthostatic hypotension as a main side effect

• Minimum abuse potential

Clonidine

• Sleep deprivation is known to affect the clearance of metabolic waste products in the wakefulness pathways governed by locus coeruleus (NA neuron projections)

• Thus, manipulation of noradrenergic tone may enhance glymphatic clearance providing a neuroprotective effect for the brain.

• Clonidine is an α2 agonist (high affinity for all 3 α2 -receptor subtypes, α2A, α2B and α2C) which is known to increase NREM sleep. While low doses (e. g., 25 μg) have little effect on REM sleep, 150 mcg clonidine reduces REM sleep by about 50 %.

• Indications include primary insomnia in the paediatric population, insomnia in the context of ADHD, ASD, PTSD and Borderline personality disorder. [Nguyen et al., 2014], [Broese et al., 2012]

• Guanfacine is also an α2 agonist (specific α2A). Higher doses of about 2 mg can reduce REM sleep by 26 % which is less marked than clonidine.

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References

1. Nguyen, Mathew, et al. “A review of the use of clonidine as a sleep aid in the child and adolescent population.” Clinical pediatrics 53.3 (2014): 211-216.
2. Broese, M., et al. “α-Adrenergic receptor function, arousal and sleep: mechanisms and therapeutic implications.” Pharmacopsychiatry 45.06 (2012): 209-216.