GENERAL ANESTHETICS Flashcards
what are GE
a mixture of drugs administered through the course of surgery
specific goals of GE
. inhibit neurotransmission = make patient unconcious
. induce analgesia
. induce amnesia (forget events during GE)
. muscle relaxation
. anxiolytic (can increase HR/BP)
what is analgesia
pain relief
what is amnesia
memory loss
what is anxiolytic
reduce anxiety
different classes of GE
INHALATION: gaseous state = drugs are inhaled
used to maintain long duration anesthesia
IV: drugs are water-soluble - injected
used to rapidly initiate anesthesia//supplement inhalation anesthetics
classes of INHALATION anesthetics
N20 (nitric oxide) - dental surgery halogenated hydrocarbons inert gases : Xenon (no chemical reaction) /ether /cholorform
what chemical characteristics do the classes of inhalation anesthetics share
nothing
Lipid theory
- VOLUME EXPANSION
ethanol - causes slight expansion of pm = may alter properties of NT R/ion channels - INCREASED MEMBRANE FLUIDITY
some GE can alter the fluidity of membranes = may alter properties of NT R/ion channels
Direct effects on ligand-gated ion channels
increase of inhibitory GABA R
inhibit excitatory glutamate (NMDA R)
activation of two-pore K+ channels in CNS (suppress AP)
inhibit N ACh R
what are 2 proposed mechanisms of actions for GE
lipid theory
direct effects on ligand-gated ion channels
primary targets of GE
GABAa receptor: (multisubunit receptor) halogenated hydrocarbons - gaesous . propofol IV . etomidate Allosteric Agonists . thiopental
Glutamate NMDA receptor:
ketamine - IV
N20
Xenon
most GE bind to at least 2 targets
inhibition synaptic transmission = common feature
why is halothane (halogenated hydrocarbon) not used
oxidized to trifluoroacetate = trigger strong IS reaction
first-time form = sensitized IS - no response
second time = reaction (bronchioles swell up)
where is P450 found and what is its function
enzyme in the liver - bind to 02 and carry out drug metabolism
= inactivation of drug
= increase secretion of drug from body
allosteric agonists
change enhance binding of the agonist
(eg. GABA on GABAa R - binds, channel opens - Cl- enter cell = re/hyperpolarisation - prevent A.P
= GABA can bind at lower conc.
allosteric inhibitor
bind to another site on enzyme- alter confirmation interferes with substrate binding and inhibits the reaction
describe GABAa R
cylindrical 5 protein subunit 2 alpha 2 beta 1 gamma (similar to N ACh R)
GABA binds to the alpha subunit (interface) - similar to ACh
what do photoactivation studies show
specific binding sites for
ISOFLURANE (hydrogenated drugs)
PROPOFOL (IV GE)
stages of anesthesia
- Analgesia - patient conscious but drowsy
- Excitement - patient unconscious but responds to painful stimuli: coughing, gagging, reflex movements, irregular breathing
- Surgical anesthesia - muscle relaxation, slow respiration, elimination of reflex responses
- Medullary paralysis - respiratory/vasomotor failure
= death (AVOID STAGE!)
why are gaseous GE difficult to work with
gases = hard to maintain proper dose
blood: gas partition coefficient:
distribution between air in lungs and bloodstream
influences RATE of ONSET / recovery
LOWER = faster onset / recovery
oil: gas partition coefficient:
distribution between lipids and dissolved gases in tissues
influences drug POTENCY / recovery rate
HIGHER = greater potency / slower recovery
MAC
minimal alveolar concentration
= concentration of anesthetic in the blood that eliminates sensitivity to pain + induces an unconscious state in 50% of patients (ED50 of other drugs)
describe the relationship between MAC and oil: gas partition coefficient:
inversely proportional
what does N20 do to MAC
lowers MAC for most halogenated HCs (added to gaseous GE)
what is it hard to measure MAC / alternatives
unconscious state
immobility measure - induced by action on SC
major NT - glycine not GABA
*measure multiple biological responses
what type of GE do you want and why
HIGH oil: gas partition coefficient
SMALL MAC
= more POTENT
rates of EQ vary among inhalation anesthetics
want high rate: surgical time = expensive/high risk
what 3 factors influence drug induction and recovery
respiration rate
cardiac output
tissue fat content
what happens when you have reduced respiration efficiency/cardiac output
slower induction / recovery rate
longer time for drug to get into bloodstream and equilibrate / to escape through respiration for gaseous GE
what happens when you have high fat composition
slow perfusion
large partition coefficient
slow equilibration
(drug goes to adipose tissue)
what happens when you have low fat composition
fat perfusion
small partition coefficient
fast equilibration
classes of IV anesthetics
- BENZODIAZEPINES
enhance activity of GABAa R in CNS (reduce anxiety and memory) - OPIATE analgesics - very potent analgesic activity
- THIOPENTAL - similar to 1.
- ETOMIDATE - similar to thiopental / more rapid metabolism + high TI
- KETAMINE - dissociative anesthetic (+) isomer more effective + fewer side effects
- PROPOFOL - similar to 1. + blocks VG NA+ channels in CNS/somatic muscle tissue (muscle relaxant)
what is a barbiturate
sedative / sleep-inducing drug
possible adverse effects of GE
.temporary cardiac/respiratory depression
. ventricular fibrillation (stage 2 prolonged)
. halogenated HCs = respiratory irritation + malignant hyperthermia (rise in body temp)
.N20 = asphyxiation(loss of 02), bone marrow depression (suppression of vitamin B12 synthesis)
.THIOPENTAL - LOW TI (cardiorespiratory depression)
. ETOMIDATE: period of involuntary movements prolonged
. KETAMINE hallucinations/stroke (increase intracranial pressure)
. PROPOFOL - PRIS
PROPOFOL INFUSION SYNDROME
bradycardia - heart failure
metabolic acidosis (lactic acid lowers pH)
rhabdomyolysis (muscle degradation)
hyperlipidemia (high conc of fats/lipids in blood)
fatty liver
