Mechanism of Action
Mechanism of Action
- Selective agonist at presynaptic alpha-2 adrenoceptors:
- More selective than clonidine with ratio of alpha-1:alpha-2 1:1,620
- More pronounced effect on central alpha-2 receptors
- 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, with more potent sedative effect than clonidine
- Reduces sympathetic outflow resulting in hypotension and bradycardia
- Some limited activity at alpha-1 receptors
- Some limited activity at imidazole receptors (though less than clonidine)
- Selective agonist at presynaptic alpha-2 adrenoceptors:
- More selective than clonidine with ratio of alpha-1:alpha-2 1:1,620
- More pronounced effect on central alpha-2 receptors
- 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, with more potent sedative effect than clonidine
- Reduces sympathetic outflow resulting in hypotension and bradycardia
- Some limited activity at alpha-1 receptors
- Some limited activity at imidazole receptors (though less than clonidine)
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
- May cause vasoconstriction, hypertension and reflex bradycardia if given as a bolus (boluses not recommended)
- At therapeutic doses central effect on sympathetic outflow causes:
- Bradycardia (average response 20% decrease)
- Vasodilation and hypotension (effects more predictable than clonidine)
- 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