Pharm: Anesthesia Flashcards
What factors determine the systemic distribution of a local anesthetic drug injected at one site?
the dosage administered
vascularity of the site of admin
strength of binding of local anesthetic to tissue
presence of vasoconstricting substances - lower systemic absorption by decreased blood flow
How does pH affect local anesthetics?
cationic (charged) form of local anesthetics responsible for blocking Na channels from cytoplasmic side
pH in areas of inflammation more acidic - more anesthetic is protonated - lowers cellular concentration
What is a separation of fxn caused by the structure of local anesthetics?
charged amine group provides for electrostatic block of ion conduction through voltage-gated Na channel
hydrophobic aromatic group facilitates partitioning of local anesthetic into plasma membrane of target neurons
What is the metabolism and elimination of local anesthetics?
metabolic processing by plasma (for esters) or liver (for amides) enzymes to water soluble products excreted in urine
ester linked rapidly broken down in plasma by esterases
amide-linked modified and hydrolyzed in liver after traveling through circulation
What accounts for the difference in use-dependence seen with lipophilic vs. less lipophilic drugs?
approach from cytoplasm - binding site only accessible in open or inactive state
approach from within membrane (lipophilic) - binding site accessible in all states, less use dependent (and less common)
How do local anesthetics affect pain fibers without affecting others, including motor?
use dependence - pain fibers fire more rapidly with longer duration APs
smaller pain fibers less myelinated than motor fibers - more channels per given area
What are the types of toxicity of local anesthetics?
CNS toxicity: sleepiness, light headedness, visual/auditory disturbances, restlessness, higher doses –> convulsions, CNS depression, death
neurotoxicity
CV toxicity: pacemaker malfxn, loss of contraction strength and dilation of arterioles, severe symptoms rare unless large dose
smooth muscle: inhibit contractility of bowel and intestinal, may increase tone
respiratory depression
hematologic toxicity
alleric rxns
radiculopathy
cauda equina syndrome
What are the stages of the depth of anesthesia?
Stage I: decreased perception, calm
Stage II: excitement, delirium, irregular respiration, amnesia begins
Stage III: surgical anesthesia, regular or no breathing, complete absence of perception
Stage IV: medullary compression/coma
What is the meaning of the blood:gas partition coefficient?
high coefficient = high solubility = low effective gas concentration = lower anesthetic effect
What are the pharmacokinetics of anesthetic gas uptake?
gas inspired (Fi) --> builds in alveolus (FA) --> concentrates in arterial circulation (Fa) --> goes to brain all values directly proportional FA/Fi < 1 as brain concentration increases, reverse true upon emergence Fa/FA <1 upon induction and maintenance
What are the five major factors affecting how quickly gas builds up in the alveoli (Fi–>FA)?
concentration of anesthetic in inspired air
pulmonary ventilation
solubility (rate of induction inversely proportional)
pulmonary blood flow - dilution effect means high blood flow slows buildup of anesthetic
AV concentration gradient - continued gradient allows more uptake, gases distribute into various tissues according to individual partition coefficients for each tissue
What does a V/Q mismatch cause?
increased A-a gradient and slows rise of Fa
How are inhaled anesthetics eliminated?
once FA/Fi >1, gas will diffuse back into alveolar compartment down concentration gradient and into air
diffusion is major route
same factors that increase induction increase elimination
What is the role of biotransformation in the pharmacokinetics of inhaled anesthetics?
minimal effect on elimination except halothane which has extensive metabolism
What is the minimum alveolar concentration (MAC)?
measure of potency of inhalation agent
MAC of gas at which 50% of pts will not move in response to noxious stimuli
Lower MAC = more potent
Why is respiratory depression not considered an adverse event w potent inhalation anesthetics?
apnea is goal because intention is to assume control of patient’s respiration w mechanical ventilation
different than IV where spontaneous respiration should be maintained
How is malignant hyperthermia involved in inhalation anesthetics?
potential with any except NO
has hypercarbia, tachy, and HTN followed by hypotension
treatment = cessation of anesthetic, cooling, IV hydration, IV dantrolene (Ca channel antagonist)
risk = mutation in ryanodine receptor
What are factors that decrease MAC?
elderly, opioids/benzos, acute alcohol intox, NO
What are factors that increase MAC?
youth, acute cocaine use, chronic alcohol abuse, TCA’s/MAOI’s
What is the Meyer-Overton principle of mechanism of action of inhalation anesthetics?
degree of lipid solubility of volatile anesthetics directly correlates with potency (MAC) - support for theory that hydrophobic gas molecules partition into cell membrane and alter permeability to alter/abate APs
= nonspecific interxn, mostly disproven
What is the more recent theory of mechanism of action of volatile anesthetics?
direct interxn of gas molcules w neuronal membrane proteins to alter: ion channel activity, intracellular signaling, NT release, NT binding/reuptake
supported by steep dose-response curve
What are the components for general anesthesia for a major surgical procedure?
sedative/amnestic, analgesic, induction agent, muscle relaxant, maintenance anesthetic, maybe relaxant reversal
