Pharmacology: Pharmacodynamics: HYDEX is a relatively selective alpha2-adrenoceptor agonist with sedative properties. Alpha2 selectivity is observed in animals following slow intravenous infusion of low and medium doses (10-300 mcg/kg). Both alpha1 and alpha2 activity is observed following slow intravenous infusion of high doses (≥1000 mcg/kg) or with rapid intravenous administration.
It has a sympatholytic effect through decrease of the release of noradrenaline (norepinephrine) in sympathetic nerve endings. The sedative effects are mediated through decreased firing of locus coeruleus, the predominant noradrenergic nucleus, situated in the brainstem. Dexmedetomidine has analgesic and anaesthetic/analgesic-sparing effects. The cardiovascular effects depend on the dose; with lower infusion rates the central effects dominate leading to decrease in heart rate and blood pressure. With higher doses, peripheral vasoconstricting effects prevail leading to an increase in systemic vascular resistance and blood pressure, while the bradycardic effect is further emphasised. Dexmedetomidine is relatively free from respiratory depressive effects when given as monotherapy to healthy subjects.
Pharmacokinetics: Dexmedetomidine exhibits a rapid distribution phase with a distribution half-life (T½) of approximately 6 minutes; a terminal elimination half-life (T½) of approximately 2 hours; and steady-state volume of distribution (Vss) of approximately 118 L. Clearance is estimated to be approximately 39 L/hr. The mean body weight associated with this clearance estimate was 72 kg. Dexmedetomidine exhibits linear kinetics in the dosage range of 0.2 to 0.7 mcg/kg/hr when administered by IV infusion for up to 24 hours. Target concentrations are usually in the range of 0.3 to 0.6 ng/mL. Protein binding to both albumin and α1 acid glycoprotein is 94%. Dexmedetomidine undergoes almost complete biotransformation with very little unchanged in urine and feces. Biotransformation involves both direct glucuronidation as well as cytochrome P450 mediated metabolism. There are no active metabolites. Similar kinetic data was noted in pediatric patients. Onset of action with loading infusion is 10 to 20 minutes, and the duration of action after the infusion is stopped is 10 to 30 minutes.