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Questions and Answers
What is the mechanism of action (MOA) of Precedex?
What is the mechanism of action (MOA) of Precedex?
Potent alpha2 agonist (CNS & PNS)
What type of sedative hypnotic is Precedex?
What type of sedative hypnotic is Precedex?
- Barbiturate
- GABA
- NONGABA (correct)
- Opioid
What causes the hypnotic effect of Precedex?
What causes the hypnotic effect of Precedex?
Presynaptic alpha 2 receptor stimulation in CNS inhibits locus coeruleus in the pons.
Precedex is ________ times more selective for alpha 2 and ___________ times more selective than clonidine for alpha 2.
Precedex is ________ times more selective for alpha 2 and ___________ times more selective than clonidine for alpha 2.
What pathways does Precedex activate to produce sedation?
What pathways does Precedex activate to produce sedation?
At what level does the analgesic effect of Precedex occur?
At what level does the analgesic effect of Precedex occur?
Which of the following are presynaptic alpha 2 receptor actions? (Select all that apply)
Which of the following are presynaptic alpha 2 receptor actions? (Select all that apply)
What are the postsynaptic alpha 2 receptor actions? (Select all that apply)
What are the postsynaptic alpha 2 receptor actions? (Select all that apply)
What are the clinical uses of Precedex? (Select all that apply)
What are the clinical uses of Precedex? (Select all that apply)
Precedex is highly __________ soluble & ____________% protein bound.
Precedex is highly __________ soluble & ____________% protein bound.
How is Precedex metabolized?
How is Precedex metabolized?
Where is Precedex excreted?
Where is Precedex excreted?
Does Precedex have an active metabolite?
Does Precedex have an active metabolite?
What is the elimination half-time of Precedex?
What is the elimination half-time of Precedex?
What is the loading and maintenance dosing for Precedex?
What is the loading and maintenance dosing for Precedex?
What is the onset time of Precedex after a loading dose?
What is the onset time of Precedex after a loading dose?
Precedex produces a ________ dependent DEC in CBF.
Precedex produces a ________ dependent DEC in CBF.
Does Precedex affect CMRO2 or ICP?
Does Precedex affect CMRO2 or ICP?
What type of sleep does Precedex sedation mimic?
What type of sleep does Precedex sedation mimic?
Does Precedex provide reliable amnesia?
Does Precedex provide reliable amnesia?
Does Precedex impair evoked potentials during neuromonitoring?
Does Precedex impair evoked potentials during neuromonitoring?
Precedex can be useful for '______ ______' testing during neuro procedures.
Precedex can be useful for '______ ______' testing during neuro procedures.
What are the most common cardiovascular side effects associated with Precedex? (Select all that apply)
What are the most common cardiovascular side effects associated with Precedex? (Select all that apply)
DEC HR & BP seen from DEC SNS result from ______________ alpha 2 stimulation.
DEC HR & BP seen from DEC SNS result from ______________ alpha 2 stimulation.
DEC SNS also results in DEC myocardial ________ & ___________.
DEC SNS also results in DEC myocardial ________ & ___________.
What effect can rapid IV bolus administration of Precedex have?
What effect can rapid IV bolus administration of Precedex have?
What respiratory effect of Precedex is advantageous for 'difficult airway' management?
What respiratory effect of Precedex is advantageous for 'difficult airway' management?
Precedex produces an antishivering effect by ___________ the thermoregulatory response.
Precedex produces an antishivering effect by ___________ the thermoregulatory response.
Precedex (INC/DEC) incidence of ED in pedi.
Precedex (INC/DEC) incidence of ED in pedi.
Analgesia is produced by ________ -# stimulation in the _________ ________ of the SC by DEC substance P & glutamate release.
Analgesia is produced by ________ -# stimulation in the _________ ________ of the SC by DEC substance P & glutamate release.
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Study Notes
Dexmedetomidine (Precedex) Overview
- Potent alpha2 agonist affecting both CNS and PNS.
- Classified as a non-GABA, non-barbiturate sedative-hypnotic.
Mechanism of Action
- Hypnotic effects arise from presynaptic alpha2 receptor stimulation in the CNS, inhibiting the locus coeruleus, linked to wakefulness and vigilance.
- Approximately 1600 times more selective for alpha2 receptors than other agents and eight times more selective than clonidine.
- Activates pathways that reduce sympathetic nervous system (SNS) activity, allowing for easy arousal from sedation.
- Analgesic effects manifest at the spinal cord level.
Receptor Actions
- Presynaptic alpha2 actions:
- Inhibits norepinephrine (NE) release.
- Produces sedation and decreases minimum alveolar concentration (MAC).
- Postsynaptic alpha2 actions:
- Decreases sympathetic nervous system (SNS) tone, blood pressure (BP), and heart rate (HR).
- Reduces opioid requirements for analgesia.
Clinical Uses
- Effective for sedation during awake fiberoptic intubations.
- Acts as an adjunct to general anesthesia, sparing anesthetic (up to 90% decrease in MAC).
- Provides analgesia and aids in withdrawal from alcohol, opioids, and cocaine.
- Useful for anxiolysis in preoperative pediatric cases, and prolonging motor/sensory blocks with local anesthetics.
Pharmacokinetics
- Highly lipid-soluble; 90% protein-bound.
- Metabolized in the liver through cytochrome P450 enzymes with both Phase I (methylation, hydroxylation) and Phase II (conjugation) processes.
- Excreted via kidneys and gastrointestinal tract, with no known active metabolites.
- Short elimination half-time of 2 to 3 hours.
Dosing Information
- Loading dose of 0.5-1 mcg/kg administered over 10-15 minutes; maintenance infusion of 0.3-0.7 mcg/kg/hr.
- Onset of action occurs within 10-20 minutes post-loading, with a duration of 10-30 minutes after stopping the infusion.
Effects on Cerebral Hemodynamics
- Dose-dependent reduction in cerebral blood flow (CBF) with no change in cerebral metabolic rate of oxygen consumption (CMRO2) or intracranial pressure (ICP), indicating an uncoupling between CBF and CMRO2.
- Sedation mimics natural sleep patterns.
Memory and Neuromonitoring
- Amnesia is not reliably produced; may not impair evoked potentials during neuromonitoring.
- Useful for "wake-up" testing during neuro procedures.
Cardiovascular and Respiratory Effects
- Common cardiovascular side effects include bradycardia and hypotension resulting from peripheral alpha2 stimulation and reduced SNS tone.
- Rapid IV bolus can initially increase BP due to vasoconstriction before the central response takes over.
- Maintains respiratory function with minimal reduction in ventilation and absence of respiratory depression, beneficial for managing difficult airways.
Antishivering and Pediatric Considerations
- Impairs the thermoregulatory response to produce an antishivering effect.
- Reduces the incidence of emergence delirium (ED) in pediatric patients.
Analgesia Mechanism
- Analgesic efficacy is linked to alpha2 stimulation in the dorsal horn of the spinal cord, decreasing the release of substance P and glutamate.
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