Anesthetics
Authors: Lenz George R. , Schoepke Hollis G. , SPAULDING Theodore C. 
Published: July 2004

Anesthesia, which constitutes a state in which noxious events such as surgical procedures are imperceptible, may or may not be accompanied by loss of consciousness. A complete or general anesthetic given by the inhalation or intravenous routes produces hypnosis (profound sleep), analgesia, muscle relaxation, and protection against the increase in blood pressure and heart rate resulting from surgical stress (maintains homeostasis). An anesthetic which blocks the neural transmission of painful stimuli through afferent nerves and does not affect the level of consciousness can be classified as a local anesthetic. Induction of general anesthesia produces a progressive deepening of the anesthetic state and represents a descending desensitization of the central nervous system (CNS). A progression of clinical signs useful for estimating the depth of anesthesia. Four stages can be defined: first, a state of altered consciousness and analgesia begin; second, loss of consciousness, accompanied by irregular respiration and motor movement from depression of higher motor inhibitory centers with release of lower motor mechanisms, occurs; third, surgical anesthesia is reached, in which spinal cord and spinal reflexes are abolished, providing relaxation of skeletal musculature, and loss of corneal, conjunctival, pharyngeal, and laryngeal reflexes occurs progressively; fourth, onset of respiratory paralysis resulting from significant depression of the medullary respiratory center occurs, and subsequent cardiovascular collapse ensues. Monitoring via an electroencephalogram (EEG) and hemodynamic and blood gas monitoring help assess the depth of anesthesia. The potency of inhaled agents is expressed as the minimum alveolar concentration (MAC) that is required to prevent spontaneous movement in response to a surgical or equivalent stimulus in 50% of patients. The onset of action is fast (within 60 s) for the intravenous anesthetic agents and somewhat slower for inhalation and local anesthetics. Although the modern practice of anesthesia is exceedingly sophisticated, identification of the basic molecular mechanism underlying it is still lacking. Inhalational anesthetics are very diverse chemically and extrapolation from the effect of a particular agent to the physiological state of anesthesia is problematic. Anesthesia theories may be divided into two categories: lipid theories and protein theories. Lipid theory postulates that inhalational anesthetics exert their primary effects by dissolving in the lipid portions of nerves, altering the conductivity. In protein theories, the direct interaction of inhalation anesthetics and proteins has been proposed as the cause of anesthesia. All inhalation anesthetics agents introduced after 1950, except ethyl vinyl ether, contain fluorine. Agents such as ether, chloroform, trichloroethylene (Trilene), cyclopropane, and fluoroxene (Fluoromar), which were once used, have been displaced by the newer fluorinated anesthetics. The intravenous (iv) anesthetic agents are of two types: those which are used to induce, but not maintain, anesthesia, and those useful for induction and also maintenance. The need is for an anesthetic agent having an extremely fast rate of onset and limited side effects. Fast onset minimizes the stress and agitation. Among the various classes of compounds that have been used are barbiturates, opioids, steroids, benzodiazepines, and hindered phenols. Balanced anesthesia, a potent opioid combined with an inhalation agent, is often used. The inhalational agents probably exert their biological activity through physical effects, while function through a biological receptor‐mediated pathway. At the end of a surgery, the primary concern is to eliminate respiratory depressant effects. This reversal can also diminish analgesic effects. There are two types of reversal agents: pure antagonists and mixed agonist–antagonists. The antagonists naloxone and naltrexone are the most commonly used. Local anesthetics act by inhibiting the channel opening allowing influx of sodium ions. The degree of blockage depends not only on the amount of drug, but also on the rate of nerve stimulation. In the clinically useful agents the polar group is an ester or an amide, although activity may be maintained when the polar function is an ether, thioether, ketone, or thioester. The ideal agent should have a short onset of nesthesia and be useful for multiple indications.