Alpha-2 agonists

Question 1

A2 adrenergic drugs - List of agonists

Answer 1

Xylazine - Detomidine - Dexmedetomidine - Romifidine - Clinidine

Question 2

A2 adrenergic drugs - List of antagonists (reversals)

Answer 2

Yohimbe - Atipamezole (most A2 selective) - Tolazoline (least a2 selective)

Question 3

Xylazine - species used, sensitivities

Answer 3

Best for horses, deer, elk - Sensitivity: Cattle > camelids > small ruminants > cat/dog/horse > Swine > Rodents (not used in dog/cats much)

Question 4

Detomidine

Answer 4

Horses (sublingual gel option) & Cattle

Question 5

Dexmedetomidine / Medetomidine

Answer 5

Dogs, cats, exotics

Question 6

Romifidine

Answer 6

Horses (maybe less ataxia than with xylazine)

Question 7

Clonidine

Answer 7

Humans for blood pressure

Question 8

A2 agonists mechanism of action

Answer 8

G-protein coupled receptor activation - Reduce cAMP activity - Increase K+ efflux - Hyperpolarization - Decreased NE release

Question 9

A2 receptor location

Answer 9

Throughout body: Pre & Postsynaptic (neurons & tissues) - Extrasynaptically in vasculature, platelets

Question 10

A2 agonist effect on A1 receptors

Answer 10

Varying degrees of effects - Paradoxical excitement - A2:A1 selectivity is known for most drugs

Question 11

A2 agonist & imidazoline ring

Answer 11

Most contain imidazoline ring (I2 receptors)

Question 12

Different I receptors

Answer 12

I1 = blood pressure, I2= pain modulation, I3=insulin (no I2 activity with xylazine)

Question 13

a2:a1 Selectivities : In order most selective to least

Answer 13

Dexmedetomidine > Romifidine > Detomidine > Xylazine

Question 14

A2 agonist effects overview

Answer 14

Sedative - some muscle relaxation - mild analgesia - Biphasic CV effects - Mild respiratory depression (especially sheep) - Emetic in cats

Question 15

A2 agonist sedation receptor location

Answer 15

a2 receptors in brain

Question 16

A2 agonist analgesia receptor location

Answer 16

a2 receptors in brain & spinal cord

Question 17

A2 agonist muscle relaxation receptor location

Answer 17

Spinal cord interneurons

Question 18

A2 agonist emesis receptor location

Answer 18

especially in cats - stimulation of a2 receptors in emetic center & CRTZ

Question 19

A2 agonist CV effects on initial peripheral phase

Answer 19

Initial peripheral phase : peripheral vasoconstriction - reflex increase in parasympathetic tone (vagal) - Bradycardia - AV block may be seen

Question 20

A2 agonist Anticholinergics

Answer 20

Atropine / Glycopyrrolate -Not generally used - Measure blood pressure - Can lead to hypertension & dysrhythmias - increase workload & oxygen demand of heart

Question 21

A2 agonist CV effects on subsequent/central phase

Answer 21

Cardiac output can decrease 30-50% - Decreased sympathetic flow (NE) heart rate stays low - peripheral vasodilation (central effects on vasomotor center) low catecholamine levels - Hypotension & Bradycardia -

Question 22

A2 agonist respiratory effects

Answer 22

Centrally mediated decrease in resp rate (but mild)- Sheep and goats anomaly

Question 23

Sheep and goat respiratory effect of a2 agonist

Answer 23

Increased respiratory rate, airway pressures & elastase - activation of pulmonary macrophages - Increases in CO2, hypoxemia, pulmonary edema - Unboarn, near term lambs (drugs cross placenta!)

Question 24

A2 agonist typical administration

Answer 24

IV or IM (avoid intra-arterial!)

Question 25

What happens if you inject an A2 agonist intra-arterially?

Answer 25

Seizures may occur (especially intracarotid injection in horse)

Question 26

Alternative A2 administration

Answer 26

SQ (but immediate vasoconstriction, low distribution) - CRI/Epidurally - Some transmucosal (detomidine gel for horse)

Question 27

A2 agonist distribution

Answer 27

Wide - Cross BBB/CNS and Placenta

Question 28

A2 agonist metabolism & excretion

Answer 28

Metab in liver, excreted in urine

Question 29

Effects of A2 agonist @ GI

Answer 29

Reduce GI motility - Reduced acid secretion

Question 30

Effects of A2 agonist @ Renal

Answer 30

Decreased ADH --> diuresis

Question 31

Effects of A2 agonist @ Uterus

Answer 31

Stimulate contractions --> abortion in ruminants

Question 32

Hyperglycemic effects of A2 agonist

Answer 32

Minor. Decreased insulin release --> increased blood sugar

Question 33

Hypothermic Effects of A2 agonist

Answer 33

Sparks shivering response in response to body temp - Increased by a'terations in vascular

Question 34

A2 agonist cautions

Answer 34

Avoid if cardiovascular/liver/kidney dz or pregnancy present - Less effective in excitable patients - Seizures with intra-arterial injections - Caution with Epi or atropine - Caution with sheep (pulmonary changes) & deer (delayed HS)

Question 35

Amitraz

Answer 35

a2 agonist - Sign of toxicity=sedation - Reverse with amitraz (Mitaban)

Question 36

A2 antagonist adverse effects

Answer 36

CNS excitement - Hypotension/Bradycardia - Salivation - Diarrhea