Etomidate,CAS 33125-97-2 functional indications, general anesthesia induction (short-term anesthesia must be combined with analgesics).

Introduction of Drugs
Etomidate, a hypnotic intravenous anesthetic, is a derivative of Imidazoles with high safety and is one of the commonly used drugs for anesthesia induction. Etomidate has been used clinically for 30 years. Etomidate, a non-barbiturate intravenous sedative, is an hydroxylated salt of imidazole. Its structural formula is shown in the figure below, with the molecular formula C14H16N2O2 and molecular weight 244.29. Etomidate is insoluble in water and unstable in neutral solutions.

Clinical Application
There are two main dosage forms in clinical application :① water agent: injection prepared by etomidate dissolved in 35% propylene glycol; ② Fat emulsion: injection prepared by etomidate dissolved in 20% medium-long chain triglyceride. In addition to the main solvent, the main difference between the two dosage forms is the difference in osmotic concentration. The osmotic concentration of water agent was 4640mOsm/L, which was much higher than the physiological osmotic concentration. The osmotic concentration of the emulsion was 390mOsm/L, close to the range of physiological osmotic concentration. Therefore, compared with water, fat emulsion can significantly reduce injection pain and vascular damage and other side effects. Etomidate does not precipitate when mixed with common anesthesia drugs such as muscle relaxants, vasoactive agents or lidocaine. Etomidate injection should be stored at 2℃~25℃ and should not be frozen.

Characteristics of drug efficacy
1. Etomidate has a slight effect on cardiovascular function. The heart rate, mean arterial pressure, mean pulmonary artery pressure, pulmonary capillary wedge pressure, central venous pressure, stroke volume, cardiac index, pulmonary vascular resistance and peripheral vascular resistance were almost unchanged between patients with heart disease and patients with normal clinical dose.

The hemodynamic stability of etomidate is related to the fact that it does not affect the baroreceptor function, the peripheral vascular systolic function and the myocardial contractility.

2. Etomidate has central sedative, hypnotic and amnestic effects in the central nervous system, but has no analgesic and muscle relaxant effects. The pharmacological action of etomide is mainly related to the GABAA receptor, and the hypnotic effect is more related to the β2 and β3 subunits of GABAA receptor than to the α1 subunit, and GABAA receptor antagonists can antagonize the effect. The plasma drug concentration required for the maintenance of etomidate anesthesia is about 300-500, and the plasma drug concentration is about 150-300 during sedation. When the plasma drug concentration drops to about 150-250, the recovery can be achieved.

A single intravenous injection of 0.2 to 0.3 etomidate, without affecting the mean arterial pressure, reduced cerebral blood flow by 34%, but decreased cerebral oxygen metabolic rate (CMRO2) by 45%. Therefore, the ratio of cerebral oxygen supply and demand increased significantly. In addition, etomidate can significantly reduce intracranial pressure with the increase of dose, so etomidate is beneficial to maintain cerebral perfusion pressure. Because etomidate can reduce brain oxygen metabolism rate and intracranial pressure, it has certain brain protective effect.

3. Respiratory system etomidate has little effect on respiratory system, including spontaneous respiration, ventilation and airway reactivity. Therefore, the application of etomidate has obvious advantages for maintaining spontaneous respiration, and no histamine release has been observed even when etomidate is applied to patients with airway hyperresponsiveness.

4. The therapeutic index of other etomidate (LD50/ED50) was 26.4, and the safe dose range was wide.

Guidance: The pharmacological characteristics of etomidate are an important basis and basis for clinical application: etomidate has sedative, hypnotic and amnotic effects, but has no analgesic and muscle relaxant effects. It is an important sedative in the combination of general anesthesia drugs. Etomidate has a rapid effect, rapid metabolism and clearance in vivo. CSHT study indicated that there was no significant accumulation in vivo after continuous infusion. Etomidate has little effect on respiration, and can reduce intracranial pressure while reducing cerebral metabolic rate, without affecting cerebral perfusion pressure. Etomidate emulsion can significantly reduce injection pain and vascular injury and other adverse reactions, all of which provide a good background for clinical application.

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