Week 2 - Volatile Anesthetics Flashcards
What are the sites of desired anesthetic actions in the nervous system?
Cortex/Thalamus/Brainstem = Unconsciousness (Glutamate Blockade)
Spinothalamic Tract = Analgesia (NMDA, K channel, AMPA)
Spinal Cord Central Pattern Generators = Immobility (Glycine Receptors)
Amygdala/Hippocampus = Amnesia (GABA) (nACHr -may cause hyperalgesia)
What is the Meyer-Overton Correlation?
Lipid-Based Theory related to Inhaled Anesthesia
- Chemically indifferent substances that are soluble in fat are anesthetics
- Relative potency dependent on their affinity for water and fat (Fat/Water Partition coefficient)
- Potency is proportional to lipid solubility as measured by oil-gas partition coefficient
What is the Unitary Theory related to inhaled anesthesia?
Cell membranes were mostly lipid therefore the majority of anesthetic effects must come from the effects on the cell membranes
What is the concept of MAC?
It is analogous to plasma EC50
Universal measure for inhaled anesthetic potency (was developed to compare agents)
Product of an anesthetics oil gas partition coefficient and MAC is a Konstant
What is the protein centered theory related to inhaled anesthetics?
Signaling proteins (ion channels/receptors) are the molecular site of action
If we interrupt a protein channel we can get the desired effect
What are the molecular targets of inhaled anesthetics?
Ligand Gated Ion Channels (potentiation of GABA/Glycine)
Voltage Gated Ion Channels (Na, Ca, K)
Intracellular Signaling Mechanisms (G-protein coupled, protein phosphorylation, gene expression)
How do Iso, Sevo, and N2O affect GABAa receptors?
ISO = sig. potentiation
SEVO = sig. potentiation
N2O = no effect at clinically relevant concentrations
How do Iso, Sevo, and N2O affect Glycine receptors?
ISO = sig. potentiation
SEVO = sig. potentiation
N2O = no effect at clinically relevant concentrations
How do Iso, Sevo, and N2O affect nACH receptors?
ISO = some inhibition
SEVO = some inhibition
N2O = no effect at clinically relevant concentrations
How do Iso, Sevo, and N2O affect 5-HT3 receptors?
ISO = sig. inhibition
SEVO = sig. inhibition
N2O = sig. inhibition
How do Iso, Sevo, and N2O affect AMPA receptors?
ISO = sig potentiation
SEVO = sig inhibition
N2O = sig inhibition
How do Iso, Sevo, and N2O affect NMDA receptors?
ISO = sig. inhibition
SEVO = sig. inhibition
N2O = sig. inhibition
How do Iso, Sevo, and N2O affect Na channels?
ISO = sig. inhibition
SEVO = sig. inhibition
N2O = no effect at clinically relevant concentrations
How do Iso, Sevo, and N2O affect Ca channles?
ISO = sig. inhibition
SEVO = sig. inhibition
N2O = no effect at clinically relevant concentrations
How do inhalation agents affect neuronal excitability?
they hyperpolarize neurons
neuronal excitability is determined by resting membrane potential, threshold potential, and in put resistance
What are the presynaptic and postsynaptic effects of inhalation agents
Presynaptic = alter transmitter release
Postsynaptic = alter neurotransmitter responses
What are the desired effects of inhalation agents?
- Sedation
- Learning and Memory
- Unconsciousness
- Neuroprotection (prevent apoptosis, decrease CMRO)
- Dose dependent myocardial depression and HoTN; decreases Ca availability/sensitivity
- Significant respiratory depression via central depression
- Immobility (requires 2.5-4x MAC needed to produce amnesia/unconsciousness)
GABA-ergic effects of volatile anesthetics
- Decrease CMRO
- Loss of consciousness
- Postop N/V
- Resp Depression, Spinal analgesia, Immobility
- Myocardial Depression, Cardiac Dysrhythmias, Anesthetic Preconditioning
- Skeletal Muscle Relaxation, Malignant Hyperthermia
- Hepatic Toxicity
- Vasodilation
- Supraspinal analgesia
State whether volatile anesthetic activate or inhibit the following:
1) Inhibitory GABAa receptors
2) Inhibitory Glycine receptors
3) Excitatory NMDA-type glutamate receptors
4) Neuronal nACH receptors
5) K(2p) and K leak channels
6) Voltage gated Na channels
- Activate inhibitory GABAa receptors
- Activate inhibitory Glycine receptors
- Inhibit excitatory NMDA-type glutamate receptors
- Inhibit neuronal nACH receptors
- Activate K2p and K+ leak channels
- Inhibit multiple voltage gated Na+ channels
Why are volatile anesthetics fluorinated?
Reduce or eliminate toxicity (metabolism)
Reduce or eliminate anesthetic flammability
Allow increased speed of induction and recovery from anesthesia
Rank Halothane, Desflurane, Sevoflurane, and Isoflurane based on number of Fluorine molecules
- Halothane (3)
- Isoflurane (5)
- Desflurane (6)
- Sevoflurane (7)
What are the boiling points (*C) of Halothane, Isoflurane, Desflurane, and Sevoflurane?
HAL = 50.2 ISO = 48.5 DES = 23.5 (room temp, thus needs special vaporizer) SEVO = 58.5
What are the saturated vapor pressures (mmHg) of Halothane, Isoflurane, Desflurane, and Sevoflurane?
HAL = 243 ISO = 239.5 DES = 669.2 SEVO = 157
What are the MACs (Vd %) of Halothane, Isoflurane, Desflurane, and Sevoflurane?
HAL = 0.74% ISO = 1.15% DES = 6% SEVO = 2%
What are the Blood/Gas coefficients of Halothane, Isoflurane, Desflurane, and Sevoflurane?
HAL = 2.3 ISO = 1.4 DES = 0.42 SEVO = 0.69
What are the Brain/Blood coefficients of Halothane, Isoflurane, Desflurane, and Sevoflurane?
HAL = 2.9 ISO = 2.6 DES = 1.3 SEVO = 1.7
What are the Muscle/Blood coefficients of Halothane, Isoflurane, Desflurane, and Sevoflurane?
HAL = 3.5 ISO = 4 DES = 2 SEVO = 3.1
What are the Fat/Blood coefficients of Halothane, Isoflurane, Desflurane, and Sevoflurane?
HAL = 60 ISO = 45 DES = 27 SEVO = 48
Define ____/Blood coefficients
the amount of molecules attached for every one free molecule
the lower the coefficient the faster moving drug (more free molecules)
What are the pulmonary effects of inhaled anesthetics?
Dose dependent decrease in title volume
Less than adequate increase in RR
Increased resting ETCO2
Increase activity of laryngeal irritant receptors
Decrease activity of pulmonary irritant receptors
Decrease in FRC (Functional Residual Capacity)
Why is there a decrease in FRC with inhaled anesthetics? How do you overcome it?
Loss of intercostals
Altered respiratory pattern
Cephalad movement of diaphragm
Altered thoracic blood volume
Leads to a drop in O2 levels, overcome this effect by preoxygenating prior to admin (Obese/Pregnant have even lower FRC)
How do inhaled anesthetics cause bronchodilation?
- Directly depressing smooth muscle contractility
- Direct effects on bronchial epithelium/airway smooth muscle cells
- Indirect inhibition of reflex neural pathways
- Block voltage gated Ca channels
- Depletion of Ca stores in sarcoplasmic reticulum
- Possible potentiation of GABAergic mechanisms
(not noticeable under normal conditions, great for bronchospastic conditions, less evident with DES)