Chapter 13 Medicinal Chemistry and pharmacology : Drug Affecting the Nervous System vol.4

Chapter 13 今日のメモ☆
神経系第四回目はAnesthetics[麻酔]に関する項です。

Kinds of Anesthetics
＊Ideal general anesthetics
 induce anesthesia[感覚消失] rapidly and smoothly and permit rapid recovery of the patient once administration of the agent ceases.

- Volatile[揮発性] or inhalation anesthetics (gas or vapor[蒸気])
    * Nitrous oxide(N₂O)
    * nonflammable[不燃性] halogenated hydrocarbon & ether ; e.g., halothane, methoxyflurane

 - Nonvolatile or intravenous(i.v.), intramuscular(i.m.) anesthetics (aqueous solution)
    * water-soluble(short acting) ; barbiturates, cyclohexylamine, benzo-diazepines, butyrophenone, opioid
    * aqueous propylene glycol solution(compatible) ; imidazole, etomidate
    * emulsion(not mixed with others) ; dialkylphenol, propofol

Pharmacology
 - General anesthetics
    depress the CNS ; reversible loss of consciousness & loss of sensation

 - Inhalational anesthetics
    absorbed and excreted through the lungs.  these drugs are supplemented with below,
    * Analgesics[鎮痛薬] : concentration of anesthetics↓
    * Skeletal muscle relaxants : muscle relaxation during surgery
    * Antimuscarinic agents : buccal & bronchiolar secretions↓

Therapeutic indications
 - Inhalational anesthetics : general surgical anesthesia
 - Nonvolatile anesthetics : induce dowsiness and procide relaxation before the inhalational anesthetics
※ use of previous popular volatile anesthetics was discontinued due to their toxicity, flammable[引火性] and explosive[爆発性] properties.
    e.g., chloroform, cyclopropane, diethylether

Adverse effects
 - depress respiration, circulation and the CNS
 - hepatic & kidney function↓
 - cardiac dysrhythmia[不整脈] (e.g., halothane)


Today's question
- Anesthetics(麻酔剤)の問題
Q: The brief duration of action of an ultra-short-acting barbiturate is the result of a
(A) slow rate of metabolism in the liver.
(B) low lipid solubility, resulting in a minimal
(C) high degree of binding to plasma proteins.
(D) rapid rate of redistribution from the brain owing to its high liposolubility.
(E) slow rate of excretion by the kidneys.





A: (D)
Ultra-short-acting barbiturates are characterized by having branched or unsaturated 5,5-side chains and by having a sulfur atom in place of oxygen in the 2 position of the barbituric acid molecule.  These modifications of barbituric acid result in an extremely liposoluble molecule that is very soluble in lipid tissues.  After administration, an ultra-short-acting barbiturate readily crosses the blood-brain barrier but then is quickly redistributed into extracerebral tissue, resulting in a rapid loss of activity.  While these agents do remain in the body for a long time and seem to have slow rates of metablism and excretion, their long retention time is due more to their slow rate of leaching out of lipid tissue.