IV Anesthetics Flashcards
How does anesthesia work?
No idea. Macroscopic: transmission disrupted throughout CNS, decerebration does not alter requirements. Microscopic: Axonal disruption needs higher concentration than synaptic disruption, blockage of excitatory and enhancement of inhibitory transmission, intracellular calcium alters pre and other ions alter post synaptic. Molecular: potency of an anesthetic is proportional to its lipid solubility (Meyer-Overton rule), suggests lipophilic site of action though both lipid and protein involved.
GABA receptor
Inhibitory, has 2 alpha, 2 beta and 1 gamma binding site with specific sites to bind benzodiazepines, barbiturates
Central Drug Distribution in the body
Liver, brain, heart and kidneys - the plasma & vessel-rich group of tissues. Elimination of IV medication occurs through the central compartment (area of action for sedatives & narcotics)
Peripheral Drug Distribution in the body
Muscle, bone, skin & fat - the vessel-poor group
Distribution of Cardiac Output in the body
vessel rich group is only 10% body mass - gets 75%, vessel poor group is 20% body mass - gets only 0.5%, muscle 50% body mass - gets 19%, fat 30% body mass - gets 6%
How drug binding affects distribution
Protein binding decreases available drug. Albumin binds acidic drugs (barbiturates), A1AG binds basic drugs (locals)
Factors affecting distribution
Protein binding, protein availability, lipid solubility, ionization
How protein availability affects distribution
Decrease albumin = decreased acidic drug binding, usually with liver, kidney or heart failure or cancer. Increased A1AG increased binding basic drugs - from trauma, infection, MI or chronic pain
Initial volume of distribution
describes distribution of a drug throughout the body after dosing and prior to reaching steady state equilibrium
Benzodiazepine Use
Sedation, anxiolysis, anticonvulsant effects, spinal-cord mediated muscle relaxation, anterograde amnesia, high doses - unconsciousness & respiratory depression. (NOT ANALGESIC)
Benzodiazepine Therapeutic Indexes
Above 100, when used with narcotic decreases to <10
Benzodiazepine site on GABA A receptor
Facilitates action of GABA at alpha subunit, enhances opening of chloride channels, hyperpolarization of postsynaptic membrane, postsynaptic neurons resistance to excitation
Flumazenil
Specific & exclusive BZD competitive antagonist with high affinity for BZD receptor, reverses all BZD effects in dose dependent manner without abrupt reversal (wake up a little, not acutely anxious
Flumazenil onset of action
30 seconds to 2 minutes
Flumazenil redistribution
7-15 minutes, may need re-dosing
Flumazenil dosing
0.2 mg IV over 15 seconds, wait 45 seconds, redoce 0.2 mg increments over 15 seconds.. do not exceed 3.0 mg/hour. If no response after 1 mg consider other options
Other BZD reversals
Nonspecific, unpredictable & inconsistent– physostigmine causes Ach buildup, aminophylline may antagonize sedative effects of adenosine in CNS
Alpha 2 adrenoreceptors
Membrane spanning G proteins, cause inhibition of adenylate cyclase, modulation of ion channels, alpha 2B & alpha 2C receptors in the brain & spinal cord - stimulation leads to sympatholysis, sedation & antinociception
Albumin binds what kind of drugs?
Acidic (Barbiturates)
A1AG binds what kind of drugs?
Basic (Locals)
Low albumin results from?
CHF, liver disease, kidney disease, cancer
High A1AG results from?
MI, trauma, infection, chronic pain
