GENERAL ANESTHETICS Flashcards

1
Q

what are GE

A

a mixture of drugs administered through the course of surgery

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2
Q

specific goals of GE

A

. inhibit neurotransmission = make patient unconcious
. induce analgesia
. induce amnesia (forget events during GE)
. muscle relaxation
. anxiolytic (can increase HR/BP)

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3
Q

what is analgesia

A

pain relief

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4
Q

what is amnesia

A

memory loss

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5
Q

what is anxiolytic

A

reduce anxiety

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6
Q

different classes of GE

A

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

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7
Q

classes of INHALATION anesthetics

A
N20 (nitric oxide) - dental surgery 
halogenated hydrocarbons
inert gases : Xenon (no chemical reaction)
/ether
/cholorform
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8
Q

what chemical characteristics do the classes of inhalation anesthetics share

A

nothing

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9
Q

Lipid theory

A
  1. VOLUME EXPANSION
    ethanol - causes slight expansion of pm = may alter properties of NT R/ion channels
  2. INCREASED MEMBRANE FLUIDITY
    some GE can alter the fluidity of membranes = may alter properties of NT R/ion channels
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10
Q

Direct effects on ligand-gated ion channels

A

increase of inhibitory GABA R

inhibit excitatory glutamate (NMDA R)

activation of two-pore K+ channels in CNS (suppress AP)

inhibit N ACh R

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11
Q

what are 2 proposed mechanisms of actions for GE

A

lipid theory

direct effects on ligand-gated ion channels

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12
Q

primary targets of GE

A
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

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13
Q

why is halothane (halogenated hydrocarbon) not used

A

oxidized to trifluoroacetate = trigger strong IS reaction
first-time form = sensitized IS - no response
second time = reaction (bronchioles swell up)

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14
Q

where is P450 found and what is its function

A

enzyme in the liver - bind to 02 and carry out drug metabolism
= inactivation of drug
= increase secretion of drug from body

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15
Q

allosteric agonists

A

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.

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16
Q

allosteric inhibitor

A

bind to another site on enzyme- alter confirmation interferes with substrate binding and inhibits the reaction

17
Q

describe GABAa R

A
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

18
Q

what do photoactivation studies show

A

specific binding sites for
ISOFLURANE (hydrogenated drugs)

PROPOFOL (IV GE)

19
Q

stages of anesthesia

A
  1. Analgesia - patient conscious but drowsy
  2. Excitement - patient unconscious but responds to painful stimuli: coughing, gagging, reflex movements, irregular breathing
  3. Surgical anesthesia - muscle relaxation, slow respiration, elimination of reflex responses
  4. Medullary paralysis - respiratory/vasomotor failure
    = death (AVOID STAGE!)
20
Q

why are gaseous GE difficult to work with

A

gases = hard to maintain proper dose

21
Q

blood: gas partition coefficient:

A

distribution between air in lungs and bloodstream

influences RATE of ONSET / recovery

LOWER = faster onset / recovery

22
Q

oil: gas partition coefficient:

A

distribution between lipids and dissolved gases in tissues

influences drug POTENCY / recovery rate

HIGHER = greater potency / slower recovery

23
Q

MAC

A

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)

24
Q

describe the relationship between MAC and oil: gas partition coefficient:

A

inversely proportional

25
Q

what does N20 do to MAC

A

lowers MAC for most halogenated HCs (added to gaseous GE)

26
Q

what is it hard to measure MAC / alternatives

A

unconscious state
immobility measure - induced by action on SC
major NT - glycine not GABA
*measure multiple biological responses

27
Q

what type of GE do you want and why

A

HIGH oil: gas partition coefficient
SMALL MAC
= more POTENT

28
Q

rates of EQ vary among inhalation anesthetics

A

want high rate: surgical time = expensive/high risk

29
Q

what 3 factors influence drug induction and recovery

A

respiration rate
cardiac output
tissue fat content

30
Q

what happens when you have reduced respiration efficiency/cardiac output

A

slower induction / recovery rate

longer time for drug to get into bloodstream and equilibrate / to escape through respiration for gaseous GE

31
Q

what happens when you have high fat composition

A

slow perfusion
large partition coefficient
slow equilibration
(drug goes to adipose tissue)

32
Q

what happens when you have low fat composition

A

fat perfusion
small partition coefficient
fast equilibration

33
Q

classes of IV anesthetics

A
  1. BENZODIAZEPINES
    enhance activity of GABAa R in CNS (reduce anxiety and memory)
  2. OPIATE analgesics - very potent analgesic activity
  3. THIOPENTAL - similar to 1.
  4. ETOMIDATE - similar to thiopental / more rapid metabolism + high TI
  5. KETAMINE - dissociative anesthetic (+) isomer more effective + fewer side effects
  6. PROPOFOL - similar to 1. + blocks VG NA+ channels in CNS/somatic muscle tissue (muscle relaxant)
34
Q

what is a barbiturate

A

sedative / sleep-inducing drug

35
Q

possible adverse effects of GE

A

.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

36
Q

PROPOFOL INFUSION SYNDROME

A

bradycardia - heart failure
metabolic acidosis (lactic acid lowers pH)
rhabdomyolysis (muscle degradation)
hyperlipidemia (high conc of fats/lipids in blood)
fatty liver