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Drugs > Phenothiazines > Flashcards

Phenothiazines Flashcards

1
Q

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

A

Sedation

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2
Q

How are phenothiazines classified?

A

Major tranquilizers

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3
Q

What is the most common phenothiazine in vet med?

A

acepromazine

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4
Q

Describe the molecular structure of a phenothiazine

A

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

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5
Q

What is the MOA of a phenothiazine?

A

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

Serotonin antagonism at the 5HT1 and 2 receptors

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6
Q

Where is acepromazine metabolized?

A

the liver

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7
Q

How are acepromazine metabolites excreted?

A

conjugated and unconjugated metabolites are excreted in urine

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8
Q

What are the metabolites of acepromazine in horses?

A

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

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9
Q

How do phenothiazines affect MDR1 dogs?

A

alters production of ATP-binding transporters resulting in increased toxicity

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10
Q

What is the general pharmacokinetic profile of a phenothiazine?

A

large volume of distribution and highly protein bound

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11
Q

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

A

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

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12
Q

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

A

10-15 min IV and ~30 min IM

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13
Q

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

A

3.1 hours

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14
Q

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

A

7.1 hours

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15
Q

What are the CNS effects of phenothiazines?

A
  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
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16
Q

What are the CV effects of phenothiazines?

A
  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
17
Q

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

A

decreases

18
Q

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

A

20-30%

19
Q

Is MAP reduction dose dependent in a dog receiving acepromazine?

A

Yes

20
Q

What are common respiratory effects of a phenothiazine?

A
  • 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
21
Q

What are the musculoskeletal effects of phenothiazines?

A
  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
22
Q

What are the GI effects of phenothiazines?

A
  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
23
Q

What are the urinary effects of phenothiazines?

A
  1. decreased systemic vascular resistance –> increased renal perfusion (MAP 60-160mmHg)
  2. reductions in urethral pressure in male cats under GA
24
Q

Common side effect of a phenothiazine?

A

Platelet Aggregation.

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

25
Q

Do phenothiazines affect thermoregulation?

A

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

26
Q

Does acepromazine lower the seizure threshold in dogs?

A

No, no evidence to support that anecdote

27
Q

Can phenothiazines have antihistamine action?

A

Yes. Demonstrated H1 receptor blockade with acepromazine

28
Q

What happens to the spleen after administration of acepromazine?

A

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%

29
Q

Anything we need to know about phenothiazines and brachycephalics?

A

No

30
Q

What about equine recoveries and acepromazine?

A

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

31
Q

WHAT ABOUT THE PENISES?!

A

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

32
Q

Does acepromazine produce analgesia/

A

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

33
Q

Do phenothiazines reduce MAC?

A

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

34
Q

are phenothiazines classified as anxiolytics?

A

No.

35
Q

Anything weird with mice/guinea pigs?

A

Yes. Phototoxicity seen with chlorpromazine administration

36
Q

When would you not give a phenothiazine?

A

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

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