Phenothiazines

Question 1

What is the most common use of phenothiazines in vet med?

Answer 1

Sedation

Question 2

How are phenothiazines classified?

Answer 2

Major tranquilizers

Question 3

What is the most common phenothiazine in vet med?

Answer 3

acepromazine

Question 4

Describe the molecular structure of a phenothiazine

Answer 4

Three-ring structure where two benzene rings are linked by sulfur and nitrogen atoms

Question 5

What is the MOA of a phenothiazine?

Answer 5

blockade of dopamine receptors in the basal ganglia and limbic portions of the forebrain.

Serotonin antagonism at the 5HT1 and 2 receptors

Question 6

Where is acepromazine metabolized?

Answer 6

the liver

Question 7

How are acepromazine metabolites excreted?

Answer 7

conjugated and unconjugated metabolites are excreted in urine

Question 8

What are the metabolites of acepromazine in horses?

Answer 8

2-(1-hydroxyethyl)promazine and 2-(1-hydroxyethyl)promazine sulfoxide

Question 9

How do phenothiazines affect MDR1 dogs?

Answer 9

alters production of ATP-binding transporters resulting in increased toxicity

Question 10

What is the general pharmacokinetic profile of a phenothiazine?

Answer 10

large volume of distribution and highly protein bound

Question 11

What is the oral pharmacokinetic profile of acepromazine in a dog?

Answer 11

sedation after an oral dosage of 1.3-1.5mg/kg will last approximately 4 hours. Bioavailability is approximately 20%

Question 12

What is the time to clinical effect in a dog of acepromazine IV and IM?

Answer 12

10-15 min IV and ~30 min IM

Question 13

What is the elimination half-life of a phenothiazine in a horse?

Answer 13

3.1 hours

Question 14

What is the elimination half-life of a phenothiazine in a dog?

Answer 14

7.1 hours

Question 15

What are the CNS effects of phenothiazines?

Answer 15

1. sedation
2. decreased motor activity
3. limited effect on coordination at clinical dosages (dogs)
4. can cause extrapyramidal signs (rigidity, tremors, akinesia) at high doses

Question 16

What are the CV effects of phenothiazines?

Answer 16

1. blockade of alpha1 adrenergic receptors in vasculature (peripheral vasodilation and hypotension)
2. mild increase in heart rate (reflex tachycardia) can be seen
3. vasodilation persists longer than sedation d/t > affinity of acepromazine for the alpha1 receptor vs the D1/2 receptors

Question 17

Does acepromazine increase or decrease the incidence of catecholamine-induced arrhythmias?

Answer 17

decreases

Question 18

You gave 0.1 mg/kg acepromazine to a dog. How much does SV, CO and MAP decrease?

Answer 18

20-30%

Question 19

Is MAP reduction dose dependent in a dog receiving acepromazine?

Answer 19

Yes

Question 20

What are common respiratory effects of a phenothiazine?

Answer 20

• clinically, mild to no respiratory effects
• RR may decrease, but minute volume remains normal
• laryngeal fxn does not seem to be effects
• acepromazine attenuates the shunt d/t V/Q mismatch in horses

Question 21

What are the musculoskeletal effects of phenothiazines?

Answer 21

1. muscle relaxation d/t central effect as there is no activity at the NMJ
2. good muscle relaxation
3. acepromazine decreases the incidence of malignant hyperthermia in pigs

Question 22

What are the GI effects of phenothiazines?

Answer 22

1. antiemesis d/t D1/2 blockade in the chemoreceptor trigger zone
2. may be most effective for opioid-induced nausea and vomiting
3. decreased GES tone and prolonges gastric emptying time
4. potentially can promote GER

Question 23

What are the urinary effects of phenothiazines?

Answer 23

1. decreased systemic vascular resistance –> increased renal perfusion (MAP 60-160mmHg)
2. reductions in urethral pressure in male cats under GA

Question 24

Common side effect of a phenothiazine?

Answer 24

Platelet Aggregation.

Platelet aggregation decreased in dogs that received acepromazine assessed using impedance method

Question 25

Do phenothiazines affect thermoregulation?

Answer 25

Yes. Decreased catecholamine binding in the thalamus alters central control of thermoregulation. Altered basomotor tone in peripheral vessels decreases the ability to retain heat

Question 26

Does acepromazine lower the seizure threshold in dogs?

Answer 26

No, no evidence to support that anecdote

Question 27

Can phenothiazines have antihistamine action?

Answer 27

Yes. Demonstrated H1 receptor blockade with acepromazine

Question 28

What happens to the spleen after administration of acepromazine?

Answer 28

HCT reduction d/t splenic sequestration. Spleen becomes enlarged and can persist 2-3 hours post sedation in cats. PCV can drop by as much as 20-30%

Question 29

Anything we need to know about phenothiazines and brachycephalics?

Answer 29

No

Question 30

What about equine recoveries and acepromazine?

Answer 30

Acepromazine administration was associated with decreased morbidity and mortality in the peri-anesthetic period

Question 31

WHAT ABOUT THE PENISES?!

Answer 31

Penile prolapse can occur in horses, classified concurrently as paraphimosis and priapism. Typically resolves within 30 minutes.

Question 32

Does acepromazine produce analgesia/

Answer 32

No, it is not associated with analgesia d/t a direct receptor mechanism. It can, however, alter perception of pain d/t central effects

Question 33

Do phenothiazines reduce MAC?

Answer 33

Yes! has been demonstrated in dogs, ponies, and goats at dosages between 0.02-0.2mg/kg. MAC reduction is 30-40% with iso and halothane

Question 34

are phenothiazines classified as anxiolytics?

Answer 34

No.

Question 35

Anything weird with mice/guinea pigs?

Answer 35

Yes. Phototoxicity seen with chlorpromazine administration

Question 36

When would you not give a phenothiazine?

Answer 36

if the patient is bleeding, dehydrated, and/or hypovolemic (no shocky patients either)