Barbiturates

Introduction

The drugs within this group are short acting and have been classically used agents for anaesthesia. They produce a state of hypnosis and higher doses are required to produce an anaesthetised state but they are poor analgesics.

Mechanism of Action

Barbituates act by depressing the central nervous system (CNS) by acting at the Gamma Aminobutyric Acid A receptors (GABAa). They mimic and enhance GABA, which is the principle inhibitory neurotransmitter in the CNS. Once bound to the GABAa receptor they reduce the rate of GABA dissocation and thereby increase chloride conductance is maintained resulting in hyperpolarisation of the membrane and reduced neuronal excitability. However, as the concentration of barbituate increases, it starts to have a direct effect on the chloride conductance and it is this that is thought to bring about the anaesthetic effects, while the GABA related increases causes a sedative effect. They act to depress the motor centres allowing their use as an anticonvulsant agent, as well as depressing the sensory centres and inducing an anesthetised state.

Pharmacological Considerations

Barbituates are usually powders of the salt that require reconsititution using sterile water or saline. Onset of action and doses depends upon the amount of unbound and unionised form of the barbituate in the circulation. This is due to the ability of the drug to cross the blood-brain barrier. Barbituates are cumulative making them unsuitable to maintain anaesthesia.

Side Effects and Contraindications

• Patients with an acidaemia and hypoproteinaemia often require lower doses to produce an anaesthetised state due to the increase in unbound and unionised forms.
• Causes respiratory depression, particularly in the cat.
• Dose and rate depended cardiovascular depression.
• Hypotension due to peripheral vasodilation and reduction in cardiac output from myocardial depression and tachyarrhythmias.

Drugs in this Group

Thiopental

Thiopental (also Thiopentone) causes a rapid loss of conciousness with time of onset being influenced by premedication agents. It is considered a ultra short acting barbituate, with effects seen within 15-30s following injection, and has a rapid recovery period, commonly 10-15 minutes. The duration and depth of anaesthetic, however, depends upon the amount of drug injected, speed of injection, and rate of distribution in non-fatty and fatty tissues. Recovery is dependent on redistribution of thiopental from plasma to adipose tissue so animals with minimal fat will take longer to recover.

Thiopental is available as a yellowish powder, which once reconsituted and stored correctly, can be used for up to 3-4 days. It comes as 2.5%, 5% and 10% solutions.

As thiopental causes a reduction in intracranial pressure (ICP), it can be used in patients with head traumas, brain tumours or other reasons for a raised ICP.

The commercial preparation is a sodium salt which requires dilution in water or saline. The resulting solution has a strong alkaline pH which is extremely irritant and if injected extravascularly it causes tissue necrosis and skin sloughing. It is best to inject via an intravenous catheter but if it is injected subcutaneously, then bathe immediately with saline and lidocaine solution which will cause a local vasodilation and help dissipate the subcutaneous thiopental.

Thiopental is highly protein-bound and so the dose should be reduced, or thiopental avoided in animals with hypoproteinaemia.

Care should also be taken in sighthounds as they take longer to recover this may be because they have minimal fat or because they metabolise it differently.

Pentobarbital

Pentobarbital is an oxybarbiturate which is no longer available at anaesthetic doses, but used as an euthansia agent. It causes a rapid onset of anaesthesia (40-120s) but has a longer duration of action compared with thiopental (1-2 hours). Recovery is dependent on hepatic metabolism. Its main indication of use is for the treatment of intractable seizures, long term sedation in ICU and euthansia.