Alpha 2 Agonists and Antagonists

Question 1

What are alpha2 agonists commonly used for

Answer 1

sedation and pre-anesthetic medication

Question 2

Are alpha2 agonists reversible?

Answer 2

Yes

Question 3

What is an overview of the mechanism of action for alpha2 agonists?

Answer 3

They bind to alpha2 and alpha1 adrenergic receptors (adrenoceptors).

Question 4

What is the alpha2 to alpha1 ratio for dexmedetomidine?

Answer 4

1620:1

Question 5

What is the alpha2 to alpha1 ratio for medetomidine?

Answer 5

1620:1

Question 6

What is the alpha2 to alpha1 ratio for romifidine?

Answer 6

340:1

Question 7

What is the alpha2 to alpha1 ratio for detomidine?

Answer 7

260:1

Question 8

What is the alpha2 to alpha1 ratio for clonidine?

Answer 8

220:1

Question 9

What is the alpha2 to alpha1 ratio for xylazine?

Answer 9

160:1

Question 10

How many alpha2 subtypes have been identified?

Answer 10

Three: alpha2A, alpha2B, alpha2C

Question 11

Are there any other alpha2 subtypes that have been identified?

Answer 11

Yes, in some species: cattle, and rats, an alpha2D receptor has been identified that functions similarly to alpha2A

Question 12

What is the mechanism of action of an alpha2 agonist?

Answer 12

So it binds to the adrenoceptors which are G-protein coupled receptors with an inhibitory action.

Question 13

What happens when you activate an adrenoceptor?

Answer 13

inhibition of cAMP production, a decrease in cellular activity, cellular hyperpolarization

Question 14

How does cellular hyperpolarization occur when an adrenoceptor is activated?

Answer 14

inhibition of voltage-gated Ca2+ channels and stimulation of inwardly rectifying K+ channels

Question 15

What kind of effect do alpha2 agonists have within the CNS?

Answer 15

antisympathetic

Question 16

where are alpha2 adrenoceptors located?

Answer 16

in the CNS and PNS as well as other tissues and organs

Question 17

Are alpha2s pre or post-synaptic?

Answer 17

They can be both

Question 18

What kind of receptors are presynaptic alpha2s?

Answer 18

autoreceptors and heteroreceptors

Question 19

what kind of effects do autoreceptor alpha2s have?

Answer 19

adrenergic effects - norepinephrine

Question 20

What kind of effects to heteroreceptor alpha2s have?

Answer 20

non-adrenergic effects - serotonin, GABA, acetylcholine

Question 21

What kind of effects do alpha2s have on the nervous system?

Answer 21

sedation, hypothermia, muscle relaxation (can lead to ataxia/recumbency)

Question 22

How do alpha2s cause sedation?

Answer 22

they activate the alpha2 receptors in the locus coeruleus in the brain

Question 23

Where is analgesia “induced” in the CNS

Answer 23

the brainstem and dorsal horn of the spinal cord. Analgesia is co-localized with opioid receptors, potential for synergy

Question 24

What are the initial CV effects of an alpha2?

Answer 24

vasoconstriction, increased SVR, baroreceptor-mediated bradycardia, decreased CO

Question 25

What is the secondary CV effects of an alpha2?

Answer 25

decreased sympathetic tone via central effects, peripheral vasodilation, bradycardia

Question 26

What kind of arrhythmias can you see with alpha2s?

Answer 26

sinus bradycardia, profound sinus arrhythmia in some species, first and second-degree AV block

Question 27

What kinds of effects can you see on the respiratory system secondary to alpha2 administration?

Answer 27

decreased respiratory rate, central ventilatory drive is decreased in dogs, upper airway resistance increases in horses

Question 28

Does hypoxemia occur with alpha2 administration?

Answer 28

generally very minimally

Question 29

Of all the species, which one is more sensitive to the respiratory effects of alpha2s?

Answer 29

ruminants

Question 30

What happens to sheep when you give an alpha2?

Answer 30

hypoxemia! D/t pulmonary hypertension and interstitial edema

Question 31

What are the renal effects of an alpha2 administration?

Answer 31

renal blood flow decreases, decreases in ADH results in diuresis

Question 32

What are the endocrine effects of an alpha2 administration?

Answer 32

decreased stress response, decreased insulin release, can lead to hyperglycemia and osmotic diuresis

Question 33

What are the GI effects of alpha2 administration?

Answer 33

relaxed LES, vomiting, nausea, inhibition of gastric emptying, decreased intestinal motility

Question 34

What is clonidine used for in dogs?

Answer 34

An oral anxiolytic

Question 35

What pharmacological profile do you need to be aware of with clonidine?

Answer 35

highly lipid soluble, large volume of distribution, two compartment model, centrally-mediated hypotensive effects will predominate

Question 36

What kind of hypotensive effects are seen with clonidine?

Answer 36

Centrally-mediated hypotensive effects predominate

Question 37

What pharmacological profile do you need to be aware of with xylazine?

Answer 37

Highly lipid soluble, large volume of distribution EXTENSIVE liver metabolism, phase I transformation via CYP3A microsomes

Question 38

In what species is xylazine particularly used in?

Answer 38

Equines! Sedation, short-term analgesia, and a preanesthetic

Question 39

Does xylazine result in increased uterine tone?

Answer 39

Yes.

Question 40

What species is the most sensitive to xylazine? The least sensitive to xylazine?

Answer 40

Most = cattle Least = pigs

Question 41

Where is detomidine metabolised?

Answer 41

Liver

Question 42

Which has the longer duration of action: xylazine or detomidine?

Answer 42

Detomidine

Question 43

What is medetomidine a derivative of?

Answer 43

detomidine

Question 44

How and where is medetomidine metabolised?

Answer 44

liver metabolism via hydroxylation and conjugation in DOGS. the hydroxylated compound is excreted in urine in cats (as they are glucuronide deficient)

Question 45

Dexmedetomidine is the inactive enantiomer of medetomidine - T or F?

Answer 45

FALSE! Dexmedetomidine is the active enantiomer of medetomidine

Question 46

How and where is dexmedetomidine metabolised?

Answer 46

Liver metabolism via hydroxylation and glucuronidation (species differences in efficiency)

Question 47

What are the pharmacological profile highlights of romifidine?

Answer 47

similar duration of action to detomidine, marketed for horses in the US, may produce less ataxia compared to other alpha2s in equines

Question 48

Where is romifidine metabolised?

Answer 48

liver metabolism and renal excretion

Question 49

What is the alpha2 to alpha1 ratio of yohimbine?

Answer 49

40:1

Question 50

Does yohimbine have a large or small volume of distribution?

Answer 50

LARGE volume of distribution, but a relatively slow clearance

Question 51

What happens when yohimbine is used as an alpha2 reversal in cats/dogs?

Answer 51

sedation may be incompletely reversed, side effects: dysphoria, vocalization, GI effects are reversed

Question 52

What can be seen with yohimbine administration in equines?

Answer 52

respiratory distress, tachycardia, and death have been seen in equines after IV administration. IM administration is recommended

Question 53

Which reversal has the lowest affinity for alpha2 receptors?

Answer 53

Tolazoline

Question 54

What negative effect can be seen in camelids that receive tolazoline?

Answer 54

death