Benzodiazepines

Chapter 185 Benzodiazepines



Ralph C. Harvey, DVM, MS, DACVA



KEY POINTS



• Benzodiazepines are associated with less adverse respiratory and cardiovascular effects than most alternative tranquilizers or sedatives.

• Benzodiazepines are a first line of defense for seizure control.

• Short-term appetite stimulation in critically ill cats is often successful with small doses of benzodiazepines.

• Accidental ingestion of benzodiazepines is treated with supportive care, emetics or activated charcoal, or both, and flumazenil may be administered in severe cases with marked central nervous system depression.


INTRODUCTION


Benzodiazepines have a wide range of applications in critically ill patients. As a group these drugs offer effects that include sedation, anxiolysis, and anticonvulsant activity, with minor cardiovascular and respiratory effects. They can be used as part of an anesthetic induction protocol for balanced anesthesia, with analgesic drugs to enhance patient comfort and sedation, as well as treatment of status epilepticus. The most commonly used benzodiazepine in veterinary medicine is diazepam, although midazolam appears to be growing in popularity. Benzodiazepines are considered controlled substances in the United States (C-IV) and, as such, require appropriate storage and documentation.1



ACTION


The primary mechanism of action of benzodiazepines is believed to be via the inhibitory neurotransmitter γ-aminobutyric acid (GABA). Benzodiazepines bind to stereo-specific receptors that facilitate the inhibitory actions of GABA.1,2 The mechanism of action may also involve antagonism of serotonin and diminished release or turnover of acetylcholine in the Central nervous system (CNS).1 Benzodiazepines act at the limbic, thalamic, and hypothalamic level of the CNS with anxiolytic, sedative, hypnotic, skeletal muscle relaxant, and anticonvulsant properties. In humans, benzodiazepines are also recognized to have anterograde amnestic effects, providing amnesia for events that occur subsequent to the administration of the drug.2 Benzodiazepines are generally considered to provide no analgesia.


Benzodiazepines are metabolized in the liver to active metabolites that, after conjugation, are excreted in the urine.2



DIAZEPAM VERSUS MIDAZOLAM


Diazepam and midazolam have similar pharmacologic actions in dogs and cats. The major difference between these drugs is that diazepam is not water soluble and is formulated in a 40% propylene glycol and 10% alcohol vehicle.1 Propylene glycol is an irritant to blood vessels and will cause phlebitis and thrombosis after repeated or continuous administration in a peripheral vein. For this reason diazepam should be given only as a constant rate infusion (CRI) or multiple repeated intermittent doses via a central vein. Prolonged administration of diazepam can also cause propylene glycol toxicity, which can have life-threatening effects including metabolic acidosis, hyperosmolality, neurologic sequelae, and organ dysfunction.3 Propylene glycol toxicity is of particular concern in cats, so diazepam infusions are not recommended in this species.4 Diazepam will also adsorb to plastic, so doses should not be stored in plastic syringes for any length of time, and infusion lines may require precoating with the drug before administration. Both diazepam and midazolam should be protected from light.


In contrast to diazepam, midazolam is water soluble and is well absorbed after intramuscular injection but is poorly bioavailable when given per rectum to dogs, so this route of administration is not recommended.1 Diazepam rectal gel is available for human use and may offer a viable alternative for at-home treatment of seizures using rectal diazepam. Midazolam can be given as a CRI through a peripheral vein.



BENZODIAZEPINES AND CATS


The sedative effects of benzodiazepines are highly variable in dogs and cats. They may demonstrate aberrant behavior after benzodiazepine administration including excitation, irritability, and depression. Patients that are already somewhat obtunded are likely to be effectively sedated, particularly if the benzodiazepine is combined with an opioid. Healthier dogs and cats may demonstrate dysphoria; this is more likely when the drugs are used as sole agents.


A rare complication of oral diazepam in cats is fulminant hepatic failure. This has been reported as an idiosyncratic reaction resulting in acute hepatic necrosis.5 This has not been reported in association with other routes of administration.

Related posts:

  1. Deteriorating Mental Status
  2. Hyperthermia and Fever
  3. Ventilator-Associated Lung Injury
  4. Allergic Airway Disease in Dogs and Cats and Feline Bronchopulmonary Disease

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Sep 10, 2016 | Posted by in SMALL ANIMAL | Comments Off on Benzodiazepines

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