Mechanism of Action
Mechanism of Action
- Selective agonist at presynaptic alpha-2 adrenoceptors:
- Less selective than dexmedetomidine with ratio of alpha-1:alpha-2 1:200
- Acts particularly on the locus coeruleus in the floor of the fourth ventricle, producing depression of thalamic transmission to the cerebral cortex
- Primarily responsible for sedation, anxiolysis and analgesia
- Reduce sympathetic outflow resulting in hypotension and bradycardia
- Some activity at alpha-1 receptors:
- Produces vasoconstriction at higher doses
- Produces centrally mediated hypotension
- Selective agonist at presynaptic alpha-2 adrenoceptors:
- Less selective than dexmedetomidine with ratio of alpha-1:alpha-2 1:200
- Acts particularly on the locus coeruleus in the floor of the fourth ventricle, producing depression of thalamic transmission to the cerebral cortex
- Primarily responsible for sedation, anxiolysis and analgesia
- Reduce sympathetic outflow resulting in hypotension and bradycardia
- Some activity at alpha-1 receptors:
- Produces vasoconstriction at higher doses
- Produces centrally mediated hypotension
Systemic Effects
Systemic Effects
CNS
- Sedation and anxiolysis:
- Effects comparable to normal sleep
- May be more co-operative and communicative than patients sedated with other drugs
- Decreases cerebral blood flow, but does not lower intracranial pressure
- Decreases intraocular pressure
AS
- Decreases gastric and small bowel motility
- Acts as an antisialogogue
RS
- Very minimal respiratory depression
- At therapeutic doses no change in respiratory rate or PaCO2
CVS
- Usually exerts biphasic effect on blood pressure:
- Causes hypotension at lower doses due to predominate effects on imidazoline and alpha-2 receptors
- Higher doses stimulate peripheral alpha-1 receptors, thereby causing vasoconstriction, which may increase blood pressure
- May cause a decrease in heart rate (average response 20% decrease)
- No effect on cardiac contractility, and the cardiac output is well maintained
RenS
- Acts as a diuretic due to inhibition of ADH
Side Effects & Toxicity
Side Effects & Toxicity
- Excessive sedation, confusion, hallucinations
- Hypotension (initial transient hypertension on injection)
- Bradycardia, heart block
- Dry mouth
- Constipation
- Excessive sedation, confusion, hallucinations
- Hypotension (initial transient hypertension on injection)
- Bradycardia, heart block
- Dry mouth
- Constipation