29.3 Alpha 2 Adrenergic Agonists, Alpha 1 antagonists: Clonidine, Guanfacine, Prazosin, Yohimbine Flashcards
Clonidine mechanism?
Mechanism: Alpha-2 Adrenergic Receptor Agonist and reduces plasma norepinephrine, generally serving to reset the body’s sympathetic tone at a lower level and decrease arousal.
Clonidine Kinetics/dynamics?
Kinetics/Dynamics: Well-absorbed from GI tract, reach peak plasma levels 1-3 hours after oral administration, half life is 6-20 hours.
Clonidine Therapeutic Indications?
Main Therapeutic Indications:
- Withdrawal from opioids, Alcohol, Benzos, Nicotine
- Tourette’s Disorder and other Tic Disorders
- ADHD and aggression in children (although Guanfacine more common)
- PTSD
Other: Anxiety disorders, OCD, mania (may be synergistic with Lithium or Tegretol). A clonidine patch can reduce the hyper salivation and dysphagia caused by clozapine.
Clonidine Adverse Effects?
Common Adverse Effects: sedation and hypotension (from actions in the CNS that reduce sympathetic tone and cause vasodilation). Cardiac effects in children. Dry mouth/eyes, dizziness, nausea, constipation.
Uncommon: CNS effects such as insomnia, anxiety, depression, vivid dreams, and even hallucinations. Fluid retention is also possible. Some people experience sexual dysfunction.
Clonidine precautions?
Should not be taken by adults with BP below 90/60 or cardiac arrhythmia, especially bradycardia.
Avoid in pregnancy and nursing. Avoid in Elderly.
What happens in Clonidine overdose?
May present with coma and constricted pupils, similar to opioid overdose. Other symptoms include hypotension, bradycardia, and reduced respiratory rate.
Clonidine withdrawal?
Anxiety, restlessness, perspiration, tremor, abdominal pain, palpitations, headache, and a dramatic increase in blood pressure.
These symptoms may appear about 20 hours after the last dose of clonidine.
Clonidine drug interactions?
Because it causes sedation, especially early in therapy, interacts with other drugs that CNS depressants.
Dose reduction may be required in agents that interfere with AV node and sinus node, such as beta blockers or CCB’s.
Should not be given with Tricyclics.
Clonidine dosage, formulations and clinical guidelines?
Available in 0.1, 0.2 and 0.3 mg tablets. Also comes in weekly transdermal formulations at 0.1, 0.2 and 0.3 mg per day.
Usual starting dose is 0.1 mg BID, and can be raised by 0.1 mg per to to an appropriate level up to 1.2 mg per day.
Must always be tapered because withdrawal can occur about 20 hours after last dose.
Transition from oral to transdermal formulations should be accomplished gradually by overlapping for 3-4 days.
Although Guanfacine are similar in many properties, name some differences?
- Less sedation and hypotension
- More selective and less potent
- Longer half life, less withdrawal side effects
Guanfacine dosage, formulation and clinical guidelines?
Available in 1 and 2 mg tablets. Also comes in ER release preparation (Intuniv).
Usual starting doses is 1 mg before sleep, can be increased to 2 mg before sleep after 3-4 weeks.
Mechanism of Prazosin?
Alpha 1 adrenergic antagonist which decreases TPR.
General hypotensive and nightmare suppression mechanism is unknown.
Name the general function of the various Alpha and Beta adrenergic receptors?
Alpha 1: Vasoconstriction, increase TPR, mucosal decongestion, pupil dilation, pilomotor contraction, hyperglycemia.
Alpha 2: reduces presynaptic neurotransmitter (epi/norepi) release, reduces sympathetic outflow.
Beta 1: Increase heart rate, force of contraction, velocity of conduction
Beta 2: pulmonary and cardio vasodilation, bronchiodilation, uterine relaxation, hyperglycemia, lactic acidemia.
Beta 3: Adipose thermogenesis, lipolysis.
DA Receptor: splanchnic area vasodilation.
Kinetics/dynamics of Prazosin?
Plasma peak concentrations at around 3 hours
Plasma half life 2-3 hours
Precautions and adverse reactions of Prazosin?
Most common: Dizziness, headache, drowsiness, lack of energy, weakness, palpitations, nausea.
Should not be used in pregnancy or nursing.
Caution when used in conjunction with other hypotensive, especially PDE-5 inhibitors.
