ETOMIDATE

Etomidate is a short-acting intravenous anesthetic agent that is often used for induction of anesthesia and procedural sedation. It is particularly important in specific clinical situations due to its unique properties and advantages:

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1. Hemodynamic stability: Etomidate has minimal negative effects on the cardiovascular system, making it an ideal choice for patients with compromised cardiovascular function or hemodynamic instability. It causes less hypotension compared to other induction agents like propofol, making it safer for patients with heart disease, shock, or hypovolemia.

2. Rapid onset and short duration: Etomidate has a rapid onset of action (usually within 30-60 seconds) and a short duration, allowing for quick induction of anesthesia and rapid recovery. This makes it suitable for short procedures or as an induction agent before the administration of longer-acting anesthetics.

3. Minimal respiratory depression: Etomidate has less impact on respiratory function compared to other anesthetic agents. It usually does not cause significant respiratory depression, which can be an advantage in patients with compromised respiratory function or when spontaneous ventilation is desired.

4. Cerebral protection: Etomidate has been shown to reduce intracranial pressure and cerebral metabolic rate. This property can be beneficial in neurosurgical procedures or in patients with traumatic brain injury, where maintaining cerebral perfusion and reducing intracranial pressure is essential.

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Here are the main steps in etomidate's mechanism of action:

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1. Binding to GABA-A receptors: Etomidate acts by binding to a specific allosteric site on the GABA-A receptor complex, which is a ligand-gated ion channel composed of several protein subunits. This binding site is distinct from the site where the endogenous ligand GABA binds.

2. Modulation of GABA-A receptors: When etomidate binds to the GABA-A receptor, it enhances the receptor's affinity for GABA, making it more responsive to the neurotransmitter. This leads to an increased frequency of the opening of the chloride ion channels associated with the GABA-A receptor complex.

3. Increase in chloride ion conductance: The enhanced responsiveness of the GABA-A receptors to GABA results in an increased influx of chloride ions into the neuron. This causes hyperpolarization of the neuronal membrane, making it more difficult for the neuron to generate action potentials and transmit signals.

4. Inhibition of neuronal activity: The overall effect of etomidate's action on the GABA-A receptors is the suppression of neuronal excitability within the central nervous system. This leads to the rapid onset of unconsciousness and general anesthesia.

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                                                                                                      Key points about Etomidate

• Etomidate is a carboxylated imidazole.

• The imidazole nucleus renders etomidate, like midazolam, water soluble at an acidic pH and lipid soluble at physiologic pH.

• Etomidate is a relatively selective as a modulator of GABAA receptors.

• 99% unionized at physiologic pH.

• Etomidate is rapidly metabolized by hydrolysis of the ethyl ester side chain to its carboxylic acid ester.

• Hepatic microsomal enzymes and plasma esterases are responsible for this hydrolysis.

• Involuntary myoclonic movements are common during the induction.

• Hiccups upon injection are common.

• Nausea and vomiting is increased in patients receiving etomidate.

• Etomidate is a potent direct cerebral vasoconstrictor that decreases cerebral blood flow and CMRO2.

• Caution in administration of etomidate to patients with a history of seizures (may stimulate seizure foci).

• Etomidate causes adrenocortical suppression by producing a dose-dependent inhibition of cortisol and aldosterone synthesis.

• Etomidate inhibits the enzymes by 11-beta-hydroxylase and 17-alpha-hydroxylase.

• Of the commonly used intravenous anesthetics, etomidate produces the least cardiovascular disturbance.

• Minimal change in HR, SV, or CO.

• It may also precipitate a porphyria crisis.

• Pain on injection is common due to propylene glycol solution.

• Etomidate is 75% bound to albumin.

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