Alpha 2 agonists pharmacology

Question 1

Alpha 2 agonists functions

Answer 1

-used for sedation, analgesia, muscle relaxation, anxiolysis

Question 2

Alpha 2 agonist structure

Answer 2

-contain benzene rings
-some have thiazine ring (xylazine)
-others contain imidazoline ring (dexmedetomidine)

Question 3

Lipophilicity of alpha 2 agonists

Answer 3

-high; cross membranes easily
*BBB, placental barrier, gut wall, mucous membranes

Question 4

Metabolism and excretion of alpha 2 agonists

Answer 4

hepatic metabolism

renal excretion

Question 5

Adrenergic receptors

Answer 5

Post ganglionic neurons of the sympathetic system

-NorEpi released from nerve terminal which stimulates the post synaptic alpha 1 and alpha 2 receptors AND acts on pre-synaptic alpha 2 receptors to inhibit its own release

Question 6

alpha 2 receptors location

Answer 6

-found in both pre-synaptic, post-synaptic, and extra-synaptic
-both peripheral and central (spinal/supraspinal)
-4 different subtypes (A,B,C,D)

Question 7

alpha 1 receptors

Answer 7

-mostly post-synaptic

-3 different subtypes (A,B,C)

Question 8

alpha 2 agonists

Answer 8

-both central and peripheral and their actions depend on
>interaction with alpha 2 and alpha 1 receptors
>interaction with imidazoline receptors (Dexmedetomidine)

Question 9

Alpha 2 agonists sedative effects

Answer 9

-Inhibit release of NE (and Ach, serotonin, dopamine)
-decrease sympathetic outflow
-produce generalized CNS depression, sedation, analgesia

Question 10

alpha 1 effects

Answer 10

-Vasoconstriction at vascular smooth muscle
-increase in inotropy at myocardium

Question 11

alpha 2 receptor post synaptic effects

Answer 11

-vasoconstriction at vascular smooth muscle
-vasoconstriction or vasodilation at endothelium

Question 12

alpha 2 pre synaptic effects

Answer 12

alleviation of vasoconstriction of vascular smooth muscle

Question 13

beta 1 and beta 2 post synaptic effects

Answer 13

Vasodilation at vascular smooth muscle

-Have increased inotropy and chronotropy at myocardium

Question 14

Alpha 2 agonists main targets

Answer 14

-not pure alpha 2 agonists; newer alpha 2 agonists have more specific action on the alpha 2 and less action on the alpha 1 receptors

Question 15

Action at alpha 1 receptors

Answer 15

-CNS stimulation (arousal, excitement, restlessness)
-can increase pain
-smooth muscle contraction
-vasoconstriction
-increased peripheral resistance
-increased blood pressure
-mydriasis
-relax GIT smooth muscle
-contraction of uterus and bladder sphincter
-bronchoconstriction
-decrease insulin secretion

Question 16

Action at alpha 2 receptors

Answer 16

-anxiolysis and sedation
-anesthetic sparing effect
-CNS depression
-anticonvulsant activity
-neuroprotectant (decrease in total intracranial blood volume)
-analgesia
-muscle relaxation
-increase uterine tone

Question 17

Alpha 2 agonists cardiovascular effect

Answer 17

-Peripheral vasoconstriction and increased BP
-Reflex increase in vagal tone (baroreceptor reflex)= bradycardia
-Arterial BP returns to near normal or slightly below
-Heart is unable to increase SV due to high afterload= decrease in CO

Question 18

How does alpha 2 agonists result in peripheral vasoconstriction and increased blood pressure

Answer 18

-activation of peripheral post synaptic alpha 2 receptors
-possibly some alpha 1 receptor activation

Question 19

How does alpha 2 agonists result in reflex increase in vagal tone/bradycarida?

Answer 19

-central pre-synaptic alpha 2 receptor and imidazoline receptor activation causing a central sympatholysis and relative increase in parasympathetic tone

-peripheral pre-synaptic alpha 2 receptor activation resulting in reduced NE release at sympathetic nerve terminals in heart

Question 20

How does alpha 2 agonists result in arterial BP returning to either normal or slightly below normal?

Answer 20

-decreased vasoconstriction from reduced NE release
-decreased HR

Question 21

Alpha 2 agonist ECG abnormalities

Answer 21

-occur because of the increase in parasympathetic tone
>bradycardia
>second degree AV block

Question 22

alpha 2 agonists respiratory effects

Answer 22

-RR may be reduced; and compensate for this by increasing tidal volume
-blood gases remain virtually unchanged
-take care in patients with CNS depression (sedated with other drugs like opioids as respiratory depression can be profound)

Question 23

Alpha 2 agonists effect on musculoskeletal relaxation

Answer 23

-mainfests as ataxia or recumbency
-central actions as imidazoline, glycine, and GABA A receptors
-possible local anesthetic actions

Question 24

Alpha 2 agonists effect on endocrine

Answer 24

-reduced ADH secretion and responsiveness lead to diuresis
-reduced insulin results in hyperglycemia and glycosuria/osmotic diuresis
-decreased urine specific gravity due to increase in urine volume

Question 25

Alpha 2 agonists effect on uterine

Answer 25

may effect uterine tone and intra-uterine pressure
*can result in early abortion, or early delivery

Question 26

Alpha 2 agonists effect on GI

Answer 26

-reduced motility, secretions, and blood flow
-prolonged transit time
-nausea and vomiting (alpha 2 receptor activation in the chemoreceptor trigger zone)

Question 27

Alpha 2 agonists effect on thermoregulation

Answer 27

-central depression of thermoregulation
-reduction in heat production may be offset by reduction in heat loss from peripheral vasoconstriction
-monitor for hypothermia

Question 28

Alpha 2 agonists effect on liver

Answer 28

-reduces blood flow

Question 29

Alpha 2 agonists effect on kidneys

Answer 29

-reduces blood flow
-may improve glomerular filtration rate (GFR)

Question 30

Alpha 2 agonists effect on ocular effects

Answer 30

-mydriasis
-reduced aqueous humour production
-decreased in intraocular pressure

Question 31

Interaction of alpha 2 adrenergic and opioid receptors

Answer 31

-Related; combination of the two= synergistic analgesia

-When combined, can relieve withdrawal symptoms of opioids HOWEVER opioid antagonists do not alter alpha 2 actions

Question 32

Nociceptive signals and alpha 2 agonists

Answer 32

-work at various points in pain pathway
>inhibit NT release from primary afferent fibers to second order neurons
>affect pre and post synaptic modulation of nociceptive in the dorsal horn
>influence descending modulatory systems from the brain stem
>alter ascending modulation of nociception in diencephalon and limbic areas

Question 33

Alpha 2 agonists analgesia

Answer 33

-used for moderate to severe pain; visceral and somatic pain

-can be used for opioid tolerance and chronic pain

Question 34

Alpha 2 agonists in large animals

Answer 34

-More efficacious than opioids and NSAIDs in horses
-less unwanted side effects

Question 35

Timing and analgesia threshold with alpha 2 agonists

Answer 35

Low doses: sedative and analgesic effects are dose dependent

Increasing dose: produces a ceiling on degree of analgesia produced

Further dosing: lengthens duration of sedation and severity of side effects

Question 36

Alpha 2 agonists during inflammation

Answer 36

-Analagesic and antihyperalgesic effects are most pronounced
>effects depend on stage of inflammatory effects
-greatest effects are often in middle on inflammatory process
>up regulation of alpha 2 or imidazoline receptors

Question 37

Atipamezole

Answer 37

-most selective alpha 2 antagonist available
-competitive antagonist
-reversal of both sedation and analgesia
-only labelled for IM administration

Question 38

Side effects of atipamezole

Answer 38

-muscle tremours
-tachycardia
-over-alertness
-transient hypotension
- panting
-defecation
-vomiting

Question 39

Tohimbine

Answer 39

-general CNS stimulant with some antagonist action at alpha 2 receptors ‘
>can result in tachycardia

-used for reversal of xylazine in horses, dogs, cats. Not used in cattle

Question 40

Tolazoline

Answer 40

-True alpha 2 receptor antagonist
>can cause excitement when administered IV

-most suitable volume use in cattle