General Anesthetics Flashcards
General anesthesia
altered physiologic state with: - hypnosis - analgesia - amnesia - immobility - inhibition of autonomic and sensory reflexes \+/- muscle relaxation
Inhaled anesthetics chem structures
Nitrous oxide = inorganic gas
All others: volatile halogenated hydrocarbons/ethers
Hydrocarbon anesthetics
chloroform
cyclopropane
ethylene
halothana
Ether anesthetics
Diethyl ether enflurane methoxyflurane isoflurane fluoroxene sevoflurane desflurane
Uptake and distribution of gen anesthetics
Anesthesia induced when critical concentration reached in the brain
Expressed as partial pressure: Pbr/Fbr
Depth of anesthesia determined by Pbr
Concentration gradient - anesthetics
1) delivered
2) inspired (P1)
3) alveolar (PA)
4) arterial (Pa)
5) brain (Pbr)
FA/FI
rate of uptake of an inhaled anesthetic
ratio of alveolar anesthetic concentration/inspired anesthetic concentration
determined by:
- solubility in blood
- partial pressure difference between alveoli and pulmonary venous blood
- alveolar ventilation
Solubility of gen anesthetics
Expressed as partition coefficients (blood/gas)
Modern agents are less soluble in blood than in gas
Higher the blood/gas solubility, the longer it takes “blood pool” to fill –> the longer it takes until equilibrium reached between alveoli and blood, and eventually brain
Want low solubility to reach brain faster
Relative solubility of gen anesthetics
Desflurane>nitrous oxide> sevoflurane > isoflurane > halothane
MAC (gen anesthetics)
Minimal Alveolar Concentration
concentration of an inhaled anesthetic in alveoli at 1 atm that prevents movement in response to a painful stimulus in 50% of patients
~1.2 MAC prevents movement in 95% of patients
Factors decreasing an agent’s MAC
increased age low temperature pregnancy opioids other anesthetics/CNS drugs
MACs of several agents
Nitrous oxide: 105% Desflurane: 6 Sevoflurane: 1.71 Isoflurane: 1.15 Halothana: 0.75
MAC with 70% nitrous oxide
desflurane: 2.83
Sevoflurane: 0.66
Isoflurane: 0.5
Halothane: 0.29
Meyer-Overton rule
MAC inversely correlates with lipid solubility
= the more lipid-soluble the agent, the more potent it is
Gen anesthetics MOA
Facilitation of inhibition
- increase GABAa receptor-mediated transmission
- increased background (leak) K_ conductance
Inhibition of excitation
- reduce glutamate/ACh receptor-mediated transmission
Metabolism of general anesthetics
Metabolites may be hepato/nephrotoxic
Degree of metabolism may influence rate of decrease in alveolar partial pressure at conclusion of anesthetic
General rule: rate of metabolism of inhaled anesthetics tend to follow solubility in blood
Methoxyflurane metabolism
40-50% metabolized
chief metabolite: fluoride
Nephrotoxicity/hepatotoxicity
Halothane metabolism
15-20% metabolized
chief metabolite: trifluoracetic acid
Hepatotoxicity/nephrotoxicity
Sevoflurane metabolism
3% metabolized
Chief metabolite: fluoride (short lived)
increased degradation by soda lime to a vinyl ether ("Compound A")
Low potential for toxicity
Nephrotoxicity in ratsIsoflurane metabolism
0.2% metabolized
chief metabolite: trifluoracetic acid
low potential for toxicity
Desflurane metabolism
0.02% metabolized
resistant to metabolism
high molecular stability; no significant toxicity
Nitrous oxide
0.0004% metabolized
chief metabolite: nitrogen
? toxicity of free radicles
GA effect on CNS
reduced cerebral metabolic rate
- greatest with isoflurane: ?cerebral protection
- enflurane: epileptic activity in EEG
Cerebral vasodilatation
- increased cerebral blood flow
- nitrous oxide: only modest effect (low potency)
GA effect on CV system
reduced arterial BP due to
- reduced CO (halothane) and/or
- reduced total PVR (e.g. isoflurane)
Ventricular arrhythmias (halothane) - sensitization of myocardium to circulating catecholamines
N2O: mild sympathetic stimulation
- laughing gas
- rarely used due to nausea/vomiting
GA effect on respiratory system
Respiratory depression
- increased rate and reduced depth of breathing (tidal volume)
- net effect: reduced alveolar ventilation/ increased PaCO2
- -> reduction in respiratory response to increased PaCO2
Decreased airway resistance
- advantage for patients with asthma (inhibition of bronchiole smooth muscle)
GA effect on kidneys
reduced renal blood flow
- low GFR, urine output
GA effect on skeletal muscle
muscle relaxation
potentiation of effects of nondepolarizing muscle relaxants (greatest with isoflurane)
GA effect on uterus
Uterine relaxation (halothane and all other volatile agents) Could lead to prolonged uterine atony/severe blood loss in parturients Delivery: spinal anesthetic, not general
Balanced anesthesia
combination of agents to maximize advantages, minimize adverse effects
Combination of iv + potent inhaled drugs
many anesthesiologists prefer to decrease total dose of a potent inhaled drug that a patient receives with any one of a number of iv drugs
Thiopental uses/MOA
iv anesthetic
barbiturate
Rapid induction of hypnosis (no analgesia)
facilitation of inhibitory NT via GABAa
Thiopental pharmacokinetics
rapid induction in one “arm-brain circulation time” patient normally wakes up ~5 min after a single bolus injection
when tissues are saturated, elimination and not redistribution determines time of emergenc
t1/2 ~ 11 h
Thiopental adverse effects
hypotension - exaggerated with hypovolemia - dose reductions necessary in elderly Respiratory depression Histamine release Arterial occlusion possible
Propofol uses/MOA
iv anesthetic
2,6-diisopropylphenol
sedation, induction, and maintenance of anesthecia (TIVA - total IV anesthesia)
smooth induction, pleasant dreams, rapid, clear-headed wakening
antiemetic
no analgesia
facilitates inhibitory transmission via GABAa
Propofol PK
rapid induction similar to thiopental, even more rapid awakening (3min after iv bolus)
rapid metabolism in liver, t1/2 ~1 hour
no significant redistribution - useful for infusion
Propofol adverse effects
pronounced hypotension
- greater than with thopental
- marked dose reductions necessary in elderly
Respiratory depression & apnea
injection pain
potential for sepsis - dispensed in egg lecithin/soy bean oil
use formulation soon after opening
Ketamine uses/MOA
iv anesthetic
PCP derivative
state of “dissociative anesthesia” - patient appears conscious but unable to respond to/process sensory input
little cardiorespiratory depression and maintain airway reflexes
bronchodilating properties
unpleasant dreams common
Induction of anesthesia in trauma/shock
battlefield surgery
analgesia in burn patients
im induction in children
Antagonist at NMDA receptors (a type of glutamate receptor)
Ketamine PK
rapid induction after iv bolus (slower than thiopental, propofol)
hepatic metabolism
t1/2 ~3 hour
Etomidate
iv anesthetic imidazole derivative minimal effects on hemodynamics - useful for induction of unstable patients No analgesia Kinetics/MOA similar to propofol produces adrenal suppression
