anesthetics I-II Flashcards
Physicochemical properties of inhaled general anesthetics that determine anesthetic potency.
Volatile anesthetics are uncharged, nonpolar molecules with seemingly unrelated structures. More potent general anesthetics are more soluble in oil. Ie. nitrous oxide is very insoluble, whereas methoxyflurane is very oil soluble
define potency of anesthetics
potency=1/MAC (MAC = Minimum Alveolar Concentration of a GA that produces insensibility to pain in 50% of subjects)
Current thinking regarding the mechanism of action of inhaled anesthetics in producing anesthesia.
There is a lipid theory and a protein theory
Lipid theory of inhaled anesthetics
Suggests that volatile general anesthetics exert their effects by partitioning into the lipid component of the nerve cell membrane
protein theory of inhaled anesthetics
Proposes that anesthetics act via interactions with hydrophobic pockets in membrane proteins. The fundamental idea is that partitioning of volatile anesthetic into the cell membrane perturbs the normal function of integral membrane proteins, possibly causing depressed membrane excitability.
Anesthetic size cut-off and how this relates the mechanism
For a series of structurally-related compounds that differ only in size, only compounds below a certain size cut-off have anesthetic effects. This can be explained by assuming that anesthetic molecules must fit into pockets of specific size within membrane proteins, such as ion channels. This supports the protein theory
Action of volatile anesthetics on the nervous system
General anesthetics depress neuronal excitability in the CNS. The best described effect is a potentiation of GABAA receptor activity which prologs inhibitory postsynaptic potentials. Also, potentiation of brainstem glycine receptors, inhibition of nicotinic receptors and potentiation of TASK-1 K channels
role of conduction block in anesthesia
Impaired conduction of action potentials ONLY occurs at concentrations above clinical range, so conduction block does not underlie anesthesia. Conduction in peripheral nervous system is normal in anesthetized patients
Brain regions involved in general anesthesia
Hypothalamic nuclei involved in sleep, reticular formation of brainstem (pain sensation, alertness and sleep), hippocampus (memory)
anesthetic concentrations
Because the pockets are not specific binding sites, volatile anesthetics exert clinically-relevant effects only at concentrations much higher (∼1-100 mM) than those needed for drugs with specific binding sitesBecause the pockets are not specific binding sites, volatile anesthetics exert clinically-relevant effects only at concentrations much higher (∼1-100 mM) than those needed for drugs with specific binding sitesBecause the pockets are not specific binding sites, volatile anesthetics exert clinically-relevant effects only at concentrations much higher (∼1-100 mM) than those needed for drugs with specific binding sitesBecause the pockets are not specific binding sites, volatile anesthetics exert clinically-relevant effects only at concentrations much higher (∼1-100 mM) than those needed for drugs with specific binding sites
Ideal characteristics of a general anesthetic.
rapid and smooth onset of action, a rapid recovery from anesthesia upon termination of drug administration, and the drug would have a wide margin for safe use as well.
Signs and stages in the development of general anesthesia.
- Stage I – analgesia • Stage II – excitement, delirium
- Stage III – surgical anesthesia (this stage is not reached by N2O) Plane 1-regular, metronomic respirations. Plane 2- onset of muscular relaxation, fixed pupils. Plane 3- good muscular relaxation, depressed excursion of intercostal muscles during respiration. Plane 4- diaphragmatic breathing only, dilated pupils • Stage IV – medullary paralysis-Respiratory failure, vasomotor collapse and resulting circulatory failure lead to death within minutes.• Stage I – analgesia • Stage II – excitement, delirium
- Stage III – surgical anesthesia (this stage is not reached by N2O) Plane 1-regular, metronomic respirations. Plane 2- onset of muscular relaxation, fixed pupils. Plane 3- good muscular relaxation, depressed excursion of intercostal muscles during respiration. Plane 4- diaphragmatic breathing only, dilated pupils • Stage IV – medullary paralysis-Respiratory failure, vasomotor collapse and resulting circulatory failure lead to death within minutes.• Stage I – analgesia • Stage II – excitement, delirium
- Stage III – surgical anesthesia (this stage is not reached by N2O) Plane 1-regular, metronomic respirations. Plane 2- onset of muscular relaxation, fixed pupils. Plane 3- good muscular relaxation, depressed excursion of intercostal muscles during respiration. Plane 4- diaphragmatic breathing only, dilated pupils • Stage IV – medullary paralysis-Respiratory failure, vasomotor collapse and resulting circulatory failure lead to death within minutes.• Stage I – analgesia • Stage II – excitement, delirium
- Stage III – surgical anesthesia (this stage is not reached by N2O) Plane 1-regular, metronomic respirations. Plane 2- onset of muscular relaxation, fixed pupils. Plane 3- good muscular relaxation, depressed excursion of intercostal muscles during respiration. Plane 4- diaphragmatic breathing only, dilated pupils • Stage IV – medullary paralysis-Respiratory failure, vasomotor collapse and resulting circulatory failure lead to death within minutes.
Descending depression
progressive loss of function from higher (e.g., cognition and consciousness) to lower (e.g., respiratory control) levels within the central nervous system. Seen with general anesthesia
Sequence of events following general anesthesia progression
• alteration of consciousness and often analgesia • loss of temperature regulation • unconsciousness • effects on eye motion, pupil size and light reflex • loss of muscle tone • respiratory failure • cardiovascular failure • coma and death
time course of surgical anesthesia
• Induction: time between initiation of administration of anesthetic and attainment of surgical anesthesia, that is, until Stage III is reached • Maintenance: time during which surgical anesthesia is in effect (surgery carried out during this period) • Recovery: time following termination of administration of anesthetic until complete recovery of patient from anesthesia
depth of anesthesia depends on…
concentration of anesthetic in brain
The rate at which an effective concentration of anesthetic is reached in the brain depends upon…
(1) concentration of the anesthetic in inspired air, (2) alveolar ventilation rate, (3) pulmonary blood flow (cardiac output) (4) blood:gas partition coefficient, and (5) potency (oil:gas partition coefficient).
What is the maintenance stage of inhaled anesthesia
A steady state condition in which the anesthetic gas partial pressure in lung = anesthetic gas partial pressure in blood = anesthetic gas partial pressure in body tissues. In other words, no net uptake or loss of anesthetic occurs during this time. At steady state, the concentration of anesthetic in the brain is determined solely by the inspired anesthetic concentration.
Four phases of reaching steady state anesthesia
(I) lung factors, (II) uptake of anesthetic by blood from alveoli, (III) uptake from blood to body tissues, and (IV) tissue distribution.
Discuss phase 1 of steady state anesthesia
lung factors: The rate of increase in anesthesia partial pressure is proportional to rate of ventilation, so over ventilation increases rate of induction of anesthsia. Also, respiratory depression can prolong recovery time
How is depth of anesthesia affected by ventilation rate
it is not affected at all
Discuss phase 2 of reaching steady state anesthesia
uptake by blood from alveoli: rate of uptake is inversely related to anesthetic’s solubility in blood and pulmonary blood flow/cardiac output
