Phenothiazines

Introduction

Phenothiazines have tranquilising, sedative and anxiolytic properties, but do NOT provide analgesia. As well as these effects on the CNS, phenothiazines also affect the cardiovascular system and the gastrointestinal tract.

Drugs in this Group

Phenothiazines include:

• Acepromazine
• Proprionylpromazine
• Chlorpromazine
• Promazine
• Methotrimeprazine
• Promethazine

Acepromazine

Acepromazine (ACP) is commonly used in veterinary practice as a sedative and as a premedicant. It is available in liquid, gel and tablet form and so may be administered orally (with 20-55% bioavailability), i/m, i/v or s/c. The intramuscular route is preferred as fewer side effects are apparent. Administration in this way leads to a 20 minute onset of drug action. The time to onset is only 5 minutes if acepromazine is given intravenously, but the drug must be given slowly to avoid causing vasodilation and hypotension. The duration of effects is 4-6 hours.

Lower doses of acepromazine affect animal behaviour, whereas higher doses give sedation. However, the level of sedation is not increased by increasing the drug dose further; this merely increases the duration of sedation. Acepromazine's sedative effect is greatest in young, anxious animals.

Acepromazine potentiates the actions of several other drugs. These include local anaesthetic agents, general anaesthetics and opioids (forming the principal of neurolept analgesia). Administration of the drug may also lower the threshold for seizures but, interestingly, acepromazine may be used as an anticonvulsant. ACP is also anti-emetic.

Use of acepromazine is contra-indicated in breeding stallions, as it may cause penis protrusion and priapism. In Boxers spontaneous fainting and syncope can occur due to sinoatrial block caused by excessive vagal tone, so acepromazine should be given in low doses or avoided in this breed. Giant breeds of dog require lower doses of the drug.

Methotrimeprazine

Methotrimeprazine has potent analsgesis as well as tranquilising, sedatice and anxiolytic actions. It is a component of small animal immobilon, along with etorphine.

Side Effects and Contraindications

In addition to the CNS, phenothiazines also act on:

• The cardiovascular system, where they bind to alpha-1 adrenoreceptors leading to vasodilation, hypotension and hypothermia.
• The gastrointestinal tract, where they have an antispasmodic effect.
• Other receptors. Blockade of muscarinic receptors, histamine receptors and 5-HT occurs.
• Hypovolaemia - due to the vasodilator effects of ACP it's use is contraindicated in animals with, or suspected of having hypovolaemia

Acepromazine can cause penis protrusion and priapism in stallions, and may lower the seizure threshold.