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ANESTHESIA > 10 – Alpha2-Agonists > Flashcards

10 – Alpha2-Agonists Flashcards

1
Q

Alpha2 agonists provide

A
  • Sedation
  • Analgesia
  • Muscle relaxation
  • Anxiolysis
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2
Q

Alpha2 agonists examples

A
  • Dexmedetomidine
  • Xylazine
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3
Q

Alpha2 agonists pharmacology

A
  • High lipophilicity (BBB, placenta, gut wall, mucous membranes)
  • Hepatic metabolism
  • Renal excretion
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4
Q

Post-ganglionic neurons of SYMPATHETIC system are

A
  • Adrenergic
    o NE released from nerve terminal
    o Stimulates post-synaptic alpha1 and alphs2 receptors
    o Acts at pre-synaptic alpha2 receptors to INHIBIT its own release (negative feedback on itself)
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5
Q

Alpha 1 receptors

A
  • Generally, post-synaptic
  • 3 different subtypes
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5
Q

Alpha2 agonists act both centrally and peripherally and their actions depend on

A
  • Interaction with alpha2 (and alpha1) receptors
  • Interaction with Imidazoline (I1 and I2) receptors (Dexmedetomidine)
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5
Q

Alpha 2 receptors

A
  • Widely distributed in body
  • Pre-, post-, and extra-synaptic
  • Peripheral and central
  • 4 different subtypes
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6
Q

Alpha2 agonists: sedative effects

A
  • Inhibit NE release
  • Decrease sympathetic outflow
  • Inhibit release of other NTs (ACh, serotonin, dopamine)
  • Produces GENERALIZED CNS depression, sedation and analgesia (ex. other side effects)
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7
Q

Alpha1 receptor: CV effects

A
  • Vascular smooth muscle: vasoconstriction
  • Myocardium: positive inotropy
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8
Q

Alpha 2 receptor, post/extra synaptic: CV effects

A
  • Vascular smooth muscle: vasoconstriction
  • Endothelium: vasoconstriction or vasodilation
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9
Q

Alpha 2 receptor, pre-synaptic: CV effects

A
  • Vascular smooth muscle: alleviation of vasoconstriction
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10
Q

Beta 1 receptor: CV effects

A
  • Vascular smooth muscle: vasodilation
  • Myocardium: positive inotropy and chronotropy
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11
Q

Beta 2 receptor: CV effects

A
  • Vascular smooth muscle: vasodilation
  • Myocardium: positive inotropy and chronotropy
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12
Q

Alpha2-agonists are NOT pure alpha2-agonists

A
  • Newer alpha2 agonists have more SPECIFIC action on alpha2 and less action on alpha 1
  • Ex. dexmedetomidine (much more specific)
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13
Q

Action at alpha 1 receptors

A
  • CNS stimulation: arousal, excitement, restlessness
  • Can exacerbate pain
  • Smooth muscle constriction
  • Vasoconstriction
  • Increased peripheral resistance
  • Increased BP
  • Mydriasis
  • Relaxes GIT smooth muscle
  • Contraction
  • Contraction of uterus and bladder sphincter
  • Bronchoconstriction
  • Decrease insulin secretion
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14
Q

Action at alpha 2 receptors

A
  • Anxiolysis and sedation
  • Anesthetic sparing effect
  • CNS depression
  • Anticonvulsant activity
  • Neuroprotectant: decrease total intracranial blood volume
  • Analgesia
  • Muscle relaxation
  • Increase uterine tone
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15
Q

Alpha2 agonists: CV effects

A
  • Peripheral vasoconstriction and increased BP (hypertension)
  • Reflex increase in vagal tone (baroreceptor reflex)->BRADYCARDIA
  • Arterial BP returns to near normal
  • Heart is unable to increase SV dueto high afterload=decreased CO
    *do NOT want to use in an animal that already has a low CO OR kidney or liver failure
    *use in YOUNG, HEALTHY patients
16
Q

Alpha2 agonists: bradycardia

A
  • Central pre-synaptic alpha2 receptor and Imidazoline receptor activation=central sympatholytic and relative increase in PS tone
  • Peripheral pre-synaptic alpha2 receptor activation=reduced NE release at the sympathetic nerve terminals in the heart
    *arterial BP returns to normal: due to decreased vasoconstriction and HR
17
Q

Alpha2 agonists: ECG abnormalities

A
  • Due to increased PS tone!
  • Bradycardia
  • Second degree AV block
    o Normal P w/QRST, then a P with no QRST, then P with no QRST
18
Q

Would you treat a second degree AV block from alpha2 agonists?

A
  • Depends on how often it occurs and their BP
  • If BP good=normal
  • Low heart rate = give anti-cholinergics
19
Q

Alpha2 agonists: respiratory effects

A
  • RR may be reduced (compensate by increasing TV
  • Blood gases remain unchanged
  • *when combine with other sedation drugs (opioids)=can see respiratory depression
20
Q

Alpha2 agonists musculoskeletal relaxation (side effect)

A
  • Manifests as ataxia or recumbency
  • Central actions as: Imidazoline, glycine, and GABAa receptors
  • Possible local anesthetic actions
21
Q

Alpha 2 agonists: endocrine (diuresis) (side effect)

A
  • Reduced ADH secretion and responsiveness leads to diuresis
  • Reduced insulin: hyperglycemia and glycosuria/osmotic diuresis
  • Decreased urine specific gravity due to INCREASE in urine volume
  • *most evident when doing a standing procedure in a horse
22
Q

Alpha2 agonists: uterine (side effects)

A
  • May effect uterine tone and intra-uterine pressure
  • *1st and 3rd trimester pregnancy
    o Could result in abortion or early labor and delivery
23
Q

Alpha2 agonists: GI (side effects)

A
  • Reduced motility, secretions and blood flow
  • Prolonged transit time
  • Nausea and vomiting
24
Q

Alpha2 agonists: thermoregulation (side effects)

A
  • Central suppression of thermoregulation
  • Reduction in heat production may be offset by REDUCTION in heat loss from peripheral constriction
  • Monitor for hyperthermia
25
Q

Alpha2 agonists: liver (side effects)

A
  • Reduces blood flow
26
Q

Alpha2 agonists: kidneys (side effects)

A
  • Reduces blood flow
  • Imay improve glomerular filtration rate?
27
Q

Alpha2 agonists: ocular effects (side effects)

A
  • Mydriasis
  • Reduced aqueous humour production
  • Decrease in intraocular pressure
28
Q

Alpha2 adrenergic and opioid receptors are intimately related

A
  • Combination of alpha2 and opioid=profound synergistic analgesia
29
Q

Widespread location of alpha2 receptors: may suppress nociceptive signals at VARIOUS points in PAIN PATHWAYS

A
  • Inhibit NT release from primary afferent fibers to second order neurons
  • Affect pre- and post-synaptic modulation occuring in dorsal horn
  • Influence DESCENDING modulatory systems from the brain stem
  • Alter ASCENDING modulation of nociception in the diencephalon and limbic areas
30
Q

Alpha2 agonists: potent analgesia for moderate to severe pain

A
  • Depends on route of administration
  • Effective for visceral AND somatic pain
  • *can be used as a rescue analgesic for opioid tolerance and chronic pain (Ketamine)
31
Q

Alpha2 particularly useful for large animals

A
  • More efficacious than opioids and NSAIDs in horses
  • Less unwanted side effects
32
Q

Low doses of alpha2 agonists:

A
  • Sedative and analgesic effects are DOSE-DEPENDENT
  • *increasing doses produces a ceiling on degree of analgesia produced
    o Further increasing only lengthens duration and severity of side effects
33
Q

Alpha2-agonists: analgesic and antihyperalgesic effects most profound during inflammation

A
  • Effects depend on stage of inflammatory process
  • Greatest effects often in middle of inflammatory process
  • Up regulation of alpha2 or imidazoline recptors
34
Q

Alpha2 antagonist examples

A
  • Antipamezole
  • Yohimbine
  • Tolazoline
35
Q

Atipamezole

A
  • Most selective alpha2 antagonist available
  • Competitive antagonists
  • *reversal of SEDATION and ANALGESIA
  • Only labelled for IM administration
  • *start low and titrate to effect
36
Q

Atipamezole is often accompanied by (side effects)

A
  • Muscle tremors
  • Tachycardia
  • Over-alertness
  • Transient hypotension
  • Panting
  • Defecation
  • Vomiting
  • *opposite of the alpha2 agonists side effects
37
Q

Yohimbine

A
  • General CNS stimulant with antagonist action at alpha2 receptors
  • Tachycardia is possible
  • Used for xylazine (horse, dogs, cats)
  • Not in cattle: volume is TOO large
38
Q

Tolazoline

A
  • True alpha2 antagonist
  • More suitable volume in cattle
  • Can cause excitement when administered IV
  • *give half dose IV and half IM to decrease excitement

ANESTHESIA (27 decks)

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