Flashcards in Inhaled Anesthetics- General Deck (87)
Dependent upon affinity for water or affinity for fat (fat/water partition coefficient). States anesthetics are soluble in fat
Cell membranes mostly lipid therefore majority of anesthetic effects come from effects on cell membranes
Concept of MAC
Analogous to plasma EC50 - 50% of nonparalyzed do not move with surgical stimulus. Universal measurement for inhaled anesthetic potency
Protein Centered Theory
Signaling proteins (ion channels/receptors) are the molecular site of action
Effects of Inhaled anesthetics on ligand gated ion channels
Potentiate GABA & Glycine, Inhibit Acetylcholine & glutamate
Effects of inhaled anesthetics on voltage gated ion channels
Nervous system - reduction in amplitude through sodium channels, CV system - reduction in amplitude and duration through calcium & potassium channels
Intracellular signaling mechanisms that inhaled anesthetics work on
G-protein coupled receptors, protein phosphorylation, gene expression
Cellular mechanisms of inhaled anesthetics
Hyperpolarize neurons - decrease neuronal excitability (determined by resting membrane potential, threshold potential & input resistance. Alter transmitter release presynaptic & neurotransmitter responses postsynaptic
How do volatile anesthetics enhance inhibitory synaptic transmission postsynaptically?
Potentiating ligand-gated ion channels activated by GABA & glycine, extrasynaptically by enhancing GABA receptors & leak currents, & presynaptically by enhancing basal GABA release
How do volatile anesthetics suppress excitatory synaptic transmission?
Presynaptically by reducing glutamate release (volatile agents) and postsynaptically by inhibiting excitatory ionotropic receptors activated by glutamate (gaseous agents)
Desired effects of inhalation agents
Immobility, unconsciousness, no learning/memory, sedation, neuroprotection, CV & respiratory protectants
How immobility is mediated
Probably by spinal cord NMDA receptors, requires 2.5-4X MAC needed for amnesia & unconsciousness
How unconsciousness is mediated
Hyperpolarization of thalamic sites, *dimmer, not on/off*, depends on interrupting synchronicity between multiple neural networks
How learning & memory is mediated
Possibly hippocampal & amygdala dependent (usually 0.3-0.4 MAC is enough)
How sedation is mediated in potent agents vs gases?
Potent agents probably stimulate GABA, gases (N2O & Xenon) possibly antagonize NMDA
How neuroprotection is mediated
All potent agents prevent apoptosis, decrease CMRO2 (by increasing inhibitory and decreasing excitatory transmission).
What is a neurological risk of inhaled anesthetics
Neurotoxicity- irreversible cell damage by N2O & less by potent agents
CV Effects of gases - general
Dose dependent myocardial depression, hypotension, SVR, direct negative chronotropic effects, sensitized to arrhythmogenicity, direct coronary artery vasodilation in vitron, coronary vasoconstriction in vivo
Pulmonary Effects of gases - general
Significant respiratory depression via central depression
Why are volatile anesthetics fluorinated?
Reduce or eliminate toxicity via metabolism, reduce/eliminate flammability, allow increased speed of induction and recovery from anesthesia
Basic hydrocarbon structures useful as fluorinated anesthetics include what?
ethane, methyl ethyl ether & propyl methyl ether
Most to least pungent anesthetic
Desflurane, isoflurane, halothane, sevoflurane
Potent inhaled anesthetics pulmonary effects- specifics
Decrease tidal volume in dose dependent manner (get less than adequate increase in RR & increased resting end tidal CO2). Decrease FRC, bronchodilation, increase activity of laryngeal irritant receptors and decrease activity of pulmonary irritant receptors, can adversely effect hypoxic pulmonary vasoconstriction. Effects on PVR are relatively small
Why does FRC decrease
Loss of intercostals, altered respiratory pattern, cephalad movement of diaphragm, altered thoracic blood volume
How are potent inhaled anesthetics bronchodilators
Decreases intracellular calcium concentration & reduces calcium sensitivity- Relaxes airway smooth muscle by directly depressing smooth muscle contractility- it directly effects bronchial epithelium and airway smooth muscle cells through phosphorylated myosin light chain, and indirectly inhibits reflex neural pathways.
What does an increase in pulmonary vascular resistance cause
Corresponding increase in pulmonary arterial pressure which promotes interstitial fluid transudation
When is pulmonary vascular resistance lowest
At lung volume equivalent to FRC
How do inhaled anesthetics effects hypoxic pulmonary vasoconstriction
Through vasodilation of pulmonary vascular bed and dose dependent myocardial depression, blood flow will get to the area that was restricted (such as in the case of a tumor)
Inhaled anesthetics protein binding site, effect & target
Amphiphilic site, effect: conformational flexibility/ligand binding, target: ion channels/receptors and signaling proteins