Alpha2 Adrenergic agonists Flashcards
What was Clonidine first developed as in the 1970s?
A nasal decongestant
Clonidine later revealed potent sympatholytic properties.
What additional properties were observed in clonidine
- decongestant effects
- Potent sympatholytic properties, but its use was somewhat limited due to sedation.
what is medetomidine ?
alpha-2 agonist.
What is dexmedetomidine, and what is its clinical use?
The active enantiomer of medetomidine, developed as a perioperative sedative and analgesic.
it is alpha-2 adrenergic agonists
What is the mechanism of action of alpha-2 adrenergic agonists?
They activate alpha-2 receptors.
What are the three subtypes of Alpha2 Adrenergic Agonists? and what are their functions?
- Alpha2a: Sedation, hypnosis, analgesia, sympatholysis
- Alpha2b: Mediates vasoconstriction, antishivering action, analgesia
- Alpha2c: Learning and startle response
Where does analgesia occur with alpha-2 adrenergic agonists?
At the spinal cord level (dorsal horn).
What clinical effect is linked to inactivation of the locus ceruleus?
Sedation
What hemodynamic effects are primarily caused by Alpha2 Adrenergic Agonists?
- Hypotension
- Bradycardia
they are mediated at the vasomotor center of the brainstem and the nucleus tractus solitarius.
What medications can help reverse hypotension caused by alpha-2 adrenergic agonists?
Ephedrine, phenylephrine, and dobutamine; norepinephrine and dopamine have less effect.
What happens when alpha-2b receptors are stimulated peripherally?
Causes transient hypertension after a rapid IV bolus.
What are the chemical categories of alpha-2 adrenergic agonists?
- Phenylethylates (methyldopa, guanabenz)
- Imidazolines (clonidine, dexmedetomidine)
- Oxalozepines
What is the potency of Clonidine at alpha2 compared to alpha1?
Clonidine is 200 times more potent at alpha2 than alpha1.
How lipid soluble is Clonidine?
Clonidine is moderately lipid soluble.
What is the absorption rate of Clonidine after oral administration?
Clonidine has complete absorption after oral administration.
What is the onset of action for Clonidine via intravenous administration?
60-90 minutes.
What is the onset of action for Clonidine via epidural administration?
15-20 minutes.
What is the elimination half-life of Clonidine?
The elimination half-life of Clonidine is 12-24 hours.
How does the alpha2 activity of Dexmedetomidine compare to Clonidine?
Dexmedetomidine has 8 times greater alpha2 activity than Clonidine.
What is the distribution half-life of Dexmedetomidine?
6 minutes.
What is the elimination half-life of Dexmedetomidine?
2 hours.
To what proteins is Dexmedetomidine highly bound?
Dexmedetomidine is highly bound to albumin and alpha1 glycoprotein.
How does Dexmedetomidine undergo metabolism?
Dexmedetomidine undergoes extensive liver metabolism and is a weak cytochrome p450 inhibitor.
How are the metabolites of Dexmedetomidine excreted?
Methyl and glucuronide conjugates are excreted via
kidneys
What are the clinical effects of Alpha2 Adrenergic Agonists?
Analgesia, sedation, hypotension/bradycardia, anti-shivering properties, and mild ventilatory depression.
- Analgesia is more prominent after spinal or epidural administration than intravenous.
- Sedation—mimics normal sleep; deeply sedated, but can rouse themselves to all most full consciousness
What are the uses of Alpha2 Adrenergic Agonists?
- Pre-op medication for sedation, anxiolysis, and amnesia.
- anesthetic sparing
- sedation
- prevention of drug withdrawal syndrome
- hemodynamic stablility
- enhancement of local anesthetic block
- postop analgesia
- analgesia for labor
- chronic pain
- cancer pain
- prevention of drug withdrawal
- prevention/treatment of shivering
They may decrease the dose of anesthetics/analgesics required intra-op.
What are some side effects of Alpha2 Adrenergic Agonists?
- May decrease dose of anesthetics/analgesics required intra-op
- Can cause xerostomia and decreased GI transit
- Blunts sympathetic response to intubation/induction
- May cause prolonged anesthesia and delayed emergence
- Use is limited by hypotension and bradycardia
Use is limited by hypotension and bradycardia.
In which special populations may Alpha2 Adrenergic Agonists show increased benefit?
- Drug addicts and alcoholics (increased sympathetic tone)
- Chronic cancer/non-cancer pain (require large doses of opioids)
- Hypertension
- Procedures where hypotension advantageous
- Ophthalmic surgery (lowers IOP)
- Adjuvant to ketamine (prevents post-op delirium)
What effect do Alpha2 Adrenergic Agonists have on sympathetic response?
They blunt the sympathetic response to intubation and induction.
What is a potential consequence of using Alpha2 Adrenergic Agonists?
They may cause prolonged anesthesia and delayed emergence.
What is the anesthetic sparing effect of Clonidine and Dexmedetomidine?
Clonidine can decrease the amount of anesthetics required by 20-40%, while Dexmedetomidine may decrease it by up to 90%.
What sedation effects do Alpha2 Adrenergic Agonists provide?
- They provide calm and relaxed sedation, allowing the patient to breathe but remain easily arousable.
What is the role of Alpha2 Adrenergic Agonists in preventing drug withdrawal syndrome?
They help in the prevention of drug withdrawal syndrome.
How do Alpha2 Adrenergic Agonists contribute to hemodynamic stability?
They blunt the release of catecholamines.
What are the local anesthetic block alpha 2 adrenergic agonists enhance?
- Intrathecal
- epidural
- caudal
- peripheral
How do Alpha2 Adrenergic Agonists enhance local anesthetic block intrathecally?
- They cause less vasoconstriction than epinephrine,
decreased cardiac output which decreases clearance of local anesthetics, and increase the quality and duration of the block. - However, they may cause hypotension.
- No more than 1 mcg/kg when co-administered with a local
What is the recommended dosage of Alpha2 Adrenergic Agonists when co-administered with a local anesthetic intrathecally?
No more than 1 mcg/kg.
What are the effects of Alpha2 Adrenergic Agonists in epidural administration?
- They provide a dosage of 1-4 mcg/kg, increasing the quality of the block, prolonging analgesia, and preventing shivering.
- They cause less hypotension compared to other methods.
What is the dosage of Alpha2 Adrenergic Agonists for caudal block?
0.75-3 mcg/kg
Increased duration of anesthesia/analgesia.
What is the use of Alpha2 Adrenergic Agonists in peripheral block?
- Adjuvant for brachial plexus block; increases duration of analgesia/anesthesia up to 24 hours.
- Also employed in Bier, retrobulbar, and intra-articular blocks
Alpha 2 adrenergic agonist use in ____ analgesia
postop
epidural infusion typically
What is the dosage of Alpha2 Adrenergic Agonists for analgesia during labor?
- 30-150 mcg epidural
- Decreases shivering but may cause hypotension, bradycardia, and can cross the placenta, potentially depressing fetal heart rate; thus, the dose should be limited to 1 mcg/kg.
What is the use of Alpha2 Adrenergic Agonists for chronic pain?
- Neuropathic pain—combination of epidural lidocaine/clonidine;
- sharp or shooting pain—transdermal patch.
What are the uses of Alpha2 Adrenergic Agonists in other pain?
- Cancer pain
–Epidural continuous infusion
–second line opioid sparing agent. - prevention of drug withdrawal,
- prevention/treatment of shivering.
How are Alpha2 Adrenergic Agonists used in cancer pain management?
- Epidural continuous infusion
- second line opioid sparing agent.
