Veterinary Drug Handbook (VDH) is the reference veterinarians turn to when they want an independent source of information on the drugs that are used in veterinary medicine today.

THIAMYLAL SODIUM

Note: Thiamylal is not available commercially at the time of this update but is still listed in the
FDA's "Green Book". Most veterinary anestheisologists are recommending using thiopental asan alternative. The monograph remains in the VDH with the hope that the product may find its wayback to the market in the near future.
Chemistry - A thiobarbiturate, thiamylal sodium occurs as a pale yellow, hygroscopic powder withan unpleasant odor. It is soluble in water and a 5% solution in water has a pH of 10.5-11.5.

Storage, Stability, Compatibility

Thiamylal is stable in the dry form when stored in airtightvials. Thiamylal should be diluted with only sterile water for injection, sodium chloride injection, or D5W (Note: A veterinary manufacturer (Bio-Ceutic) recommends using only sterile water orsodium chloride for injection). After reconstitution, solutions are stable for 2 days when refrigerated(6 days according to some sources), but should generally be used within 24 hours. Do notadminister any solution that has a visible precipitate. Little specific compatibility information isavailable other than not mixing with atropine, succinylcholine or tubocararine. Because of theirchemical similarities, the compatibility listings in the thiopental monograph may be used as generalguidelines with regard to thiamylal.

Pharmacology - THIAMYLAL SODIUM

The thiobarbiturates, because of their high lipid solubility, rapidly enter the CNSand produce profound hypnosis and anesthesia. See the monograph: Barbiturates, Pharmacologyof, for more information.

Uses, Indications

Because of their rapid action and short duration, the thiobarbiturates are excellent induction agents for general anesthesia when used with other anesthetics or as the soleanesthetic agent for very short procedures.

Pharmacokinetics - THIAMYLAL SODIUM

Following IV injection of therapeutic doses, hypnosis and anesthesia occurwithin one minute. The drug rapidly enters the CNS and then redistributes to muscle and adiposetissue in the body. The short duration of action of these agents is due less to rapid metabolism thanto this redistribution out of the CNS and into muscle and fat stores. Greyhounds and other sighthounds may exhibit longer recovery times than other breeds, which may be due to these breed'slow body fat levels or differences in the metabolic handling of these agents.
Thiamylal is metabolized by the hepatic microsomal system. There was no information foundregarding specific pharmacokinetic parameters in humans, dogs or horses. A paper on the pharmacokinetics of thiamylal in cats (Wertz et al. 1988) found a rapid first distribution phase (t1/2 =1.91 minutes) followed by a second slower distributory phase (t1/2 = 26.5 minutes). The elimination half-life in cats was found to average 14.3 hours with a short period of anesthesia induced(dosage of 13.2 mg/kg IV) followed by a prolonged state of sedation. The authors concluded thatbased on the pharmacokinetic profile in cats, thiamylal should be used as an induction agent onlyfollowed by other anesthetic agents (e.g., halothane). Contraindications/Precautions - The following are considered to be absolute contraindicationsto the use of thiobarbiturates: abscence of suitable veins for IV administration, history of hypersensitivity reactions to the barbiturates, and status asthmaticus. Relative contraindications include:metabolic acidosis, severe cardiovascular disease or preexisting ventricular arrhythmias, shock, increased intracranial pressure, myasthenia gravis, asthma, and conditions where hypnotic effectsmay be prolonged (e.g., severe hepatic disease, myxedema, severe anemia, excessive premedication, etc). These relative contraindications do not preclude the use of thiamylal, but dosage adjustmentsmust be considered and the drug must be given slowly and cautiously.
Because greyhounds (and other sight hounds) metabolize thiobarbiturates much more slowly thanmethohexital, many clinicians recommend using methohexital instead. Siamese cats may developmore CNS depression than other feline breeds.
Thiobarbiturates readily crosses the placental barrier and should be used with caution duringpregnancy.
Extravasation and intra-arterial injections should be avoided because of the high alkalinity of thesolution. Severe CNS toxicity and tissue damage has resulted in horses receiving intra-carotidinjections of thiobarbiturates. Do not administer intrapleurally or intraperitoneally.

Adverse Effects, Warnings

The manufacturer (Bio-Ceutic) lists the following possible adversereactions: circulatory depression, thrombophlebitis, pain at injection site, respiratory depressionincluding apnea, laryngospasm, bronchospasm, salivation, emergence delirium, injury to nervesadjacent to injection site, skin rashes, urticaria, nausea, and emesis.
In dogs, thiamylal has an approximate arrhythmogenic incidence of 60-85%. Ventricular bigeminyis the most common arrhythmia seen, is usually transient (over within 2 minutes) and generallyresponds to additional oxygen. Incidence may be reduced to approximately 25% by using aphenothiazine tranquilizer pre-operatively. Although the incidence of arrhythmias is higher withthiamylal than thiopental, thiamylal is considered to be less cardiotoxic. Administration ofcatecholamines may augment the arrhythmogenic effects of the thiobarbiturates, while lidocainemay inhibit it. Systemic arterial pressure may be increased, but this is probably only clinical ysignificant in patients with preexisting small vessel disease.
Repeated administration of thiamylal is not advised as recovery times can be become significantlyprolonged. Should parasympathetic side effects (e.g., salivation, bradycardia) occur, they may bemanaged with the use of anticholinergic agents (atropine, glycopyrrolate).
Overdosage - Treatment of thiobarbiturate overdosage consists of supporting respirations (O2, mechanical ventilation) and giving cardiovascular support (do not use catecholamines, e.g., epinephrine, etc).

Drug Interactions

A fatal interaction has been reported in a dog receiving the proprietaryproduct, Diathal® (procaine penicillin G, dihydrostreptomycin sulfate, diphemanil methylsulfate, and chlorpheniramine maleate) and thiamylal. Avoid using thiamylal with this combination.
The ventricular fibrillatory effects of epinephrine and norepinephrine are potentiated whenused with thiobarbiturates and halothane.
CNS and respiratory depressant effects of CNS depressants (narcotics, phenothiazines, antihistamines, etc.) may be enhanced by thiobarbiturate administration.
Thiamylal with furosemide may cause or increase postural hypotension. Sulfisoxasole IV hasbeen shown to compete with thiopental at plasma protein binding sites. This may also occur withthiamylal and other sulfonamides.
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