Canonical Question
Antihypertensive
Master answer
Potential Clinical Uses of α2 adrenoreceptor agonist
| α2 Agonist Uses | Clonidine |
|---|---|
| Essential and secondary Hypertension Hypertensive Crisis | • Marked hypertensive response (α1) – Seen in infusion acutely, not common with PO • Hypertensive crisis on withdrawal (2° upregulation of NA with chronic use) following – long infusion – cessation of chronic use PO • Prolonged refractory ↓MAP 2° to prolonged elimination t½ 9-18hrs |
| Migraine | • Hypotension • Sedation • Prolonged offset |
| Chronic Pain | • Ceiling effect (partial agonist) • Dose limited by side-effects (dry-mouth, hypotension, sedation) |
| Opiate Withdrawal | • Dose limited by side-effects (dry-mouth, hypotension, sedation) |
| Spinal anaesthesia / ↓ post-op shivering | • Ceiling effect (partial agonist) • Long time to peak effect • Long elimination t½ 9-18hrs |
| ICU Sedation or Anaesthetic Augmentation (50% MAC sparing) Procedural Sedation | • Long time to peak effect (~90min IV, 3hrs PO). • Prolonged refractory ↓MAP limits use in peri-operative setting • Dexmedetomadine preferred due to shorter t½ |
| Palliation | • Treatment of symptoms of distress (intractable pain, agitation or delirium) at the end of life. • Limited by hypotension and sedation |
| Antiemesis | • Limited use due to side effects of sedation and dry mouth |
Alpha 2 Adrenoceptor Details (include some details if you have time)
- Gi-PCR (↓Adenylyl cyclase activity → ↓ cAMP → ↓ PKA activation → Effects)
- Three main types 2A, 2B and 2C vary by location.
Important Locations:
- Postsynaptic α2 receptors in CNS
- Locus coerrulus (hypnosis)
- Spinal cord (analgesia)
- Lateral Reticular Nucleus (↓SNS tone, ↑ PSNS tone)
- Presynaptic α2 receptors in Sympathetic terminals of blood vessels
- ↓Noradrenalin release (vasodilation)
Clonidine
Class: Imidazole Derivative
Administration: PO 1-2 mcg/kg oral for premed, IV (150mcg in 2mL) 1-2mcg/kg bolus, Relatively long-time to peak effect (~90min IV, 3hrs PO)
Mechanism:
- Relative selectivity α1:α2 = 1:400 (vs dexmedetomadine (1:1600))
- Stimulation of presynaptic alpha 2 receptors
- ↓’s NAd release from sympathetic nerve terminals via negative feedback mechanism.
- Hypnosis
- Hyperpolarisation of Lateral reticular nucleus → ↓ central SNS tone and ↑ central PSNS tone
- Anti-emesis
- CTZ desensitisation, ↓ Intragastric pressure, anti-sialogogue
- Analgesia (dorsal horn of the spinal cord)
- Augment endogenous opiate release
- ↓Aδ- C fibre afferent activity
- Modulates descending noradrenergic pathways (↓’d Norad and Neuropeptide Y release)
- Long term dosing → ↓ responsiveness of peripheral vessels to vasoactive substances
For Further Reading:
Click to Open CICMWrecks Table: Alpha-2 agonist agents
CICMWrecks 2021
Exam appearances
| Exam | Exact wording | Relationship | Success |
|---|---|---|---|
| 2007B Q17 | List the potential clinical uses of an alpha 2 adrenoceptor agonist. Outline the limitations of clonidine for each use. G | historical_member | — |