pharm of general and local anesthetics and muscle relaxants Flashcards
1
Q
primary goals of anesthesia
A
- induction of unconscious sedation
- induction of intraoperative amnesia
- analgesia
- immobility
2
Q
combination of drugs used is determined by
A
the specific requirements of each surgical procedure
3
Q
area that unconsciousness/sedation targets
A
cortex thalamus reticular activation system
4
Q
area that amnesia targets
A
- hippocampus
- amygdala
- pre-frontal cortex
5
Q
area targeted to induce immobility
A
spinal cord neuromuscular junction
6
Q
analgesics act on the
A
spinal cord
7
Q
analgesics act on the
A
spinal cord
8
Q
anesthetics reduce the activity of neural circuits to produce _______ or _______
A
sedation or unconsciousness
9
Q
mechanism of anesthetics
A
- promote opening of GABAA receptor CL- channels and hyper polarize post-synaptic neurons - some other mechanisms not understood that well
10
Q
mechanism of anesthetics
A
- stimulate GABAergic synapses - inhibit glutaminergic synapses all to reduce neural output of circuits / AP promote opening of GABAA receptor CL- channels and hyper polarize post-synaptic neurons - some other mechanisms not understood that well
11
Q
type of inhaled gas
A
nitrous oxide
12
Q
volatile liquids
A
halothane, enflurane, isoflurane, sevoflurane, desflurane all ethers except halothane all halogenated
13
Q
mechanism of benzodiazepine
A
increase CL- influx, hyper polarizing postsynaptic neurons and reduced neuronal firing
14
Q
clearance of inhaled anesthetics is by
A
exhalation
15
Q
no renal clearance or liver metabolism of inhaled anesthetics except for
A
halothane, whose metabolites are hepatotoxic
16
Q
clearance from the body of IGAs is accomplished through _____ as the equilibria shift ____ after administration is stopped
A
exhalation left
17
Q
clearance from the body of IGAs is accomplished through _____ as the equilibria shift ____ after administration is stopped
A
exhalation left
18
Q
is halothane used?
A
no because it has hepatotoxic effects
19
Q
the pharmacokinetic profile of IGA are strongly influenced by
A
- the rate of ventilation during administration - the solubility of the drug in plasma
20
Q
the most clinically relevant value associated with IGAs
A
the minimum alveolar concentration MAC
21
Q
MAC
A
minimum alveolar concentration - the concentration of the drug that must be achieved in the alveoli in order to anesthetize 50% of patients
22
Q
higher rate of ventilation _____ the onset time
A
decreases
23
Q
FI
A
concentration of the drug in the inhaled gas
24
Q
FA
A
concentration of the drug in the alveoli
25
higher rate of ventilation _____ the onset time
decreases (more quickly drug equilibrates in lungs)
26
FA
concentration of the drug in the alveoli
27
FA/FI = 1
the drug has reached equilibrium in the alveoli
28
FA/FI = 1
the drug has reached equilibrium in the alveoli
29
why does one gas have a different onset time as another?
depends on the solubility in plasma
30
why does one gas have a different onset time as another?
depends on the solubility in plasma
31
the _____ water soluble drugs have the fastest onset time
least
32
responsible for onset and recovery times of drugs
water solubility
33
highly soluble drugs take longer to _____ the blood and take longer to \_\_\_\_\_\_
- saturate
- enter the brain
34
Low B/G means
less water soluble and faster onset and recovery
35
high B/G means
more water soluble and slower onset and slower recovery
36
the drug can enter the brain when it is
fully saturated with dissolved drug
37
drugs with a faster recovery time
are less soluble in water/ have a low B/G coefficient
38
blood gas partition coefficient
expresses solubility as a ratio of the amount of drug that dissolves in blood vs the amount that remains a gas
39
MAC produces of lack of movement in response to a surgical stimulus in
%50 of patients
40
the lower the MAC, the ____ the potency
higher
41
the IGAs must cross the epithelial cell layers in the \_\_\_\_, _____ and the ______ in order to reach the neurons of the brain
alveoli, the capillaries, and the blood-brain barrier
42
the more hydrophobic
the more potent (requires a lower concentration to produce the same effect)
43
This correlation shows that as \* hydrophobicity increases from left to right, \* potency increases from top to bottom
The Meyer-Overton correlation.
44
MAC of 6% means that
6% of total alveolar gas volume must be the drug in order to anesthetize 50% of people
45
MAC is not clinically useful because
it anesthetizes 50% of patients but we need 100% of patients
46
the concentration of the drug that can anesthetize 99% of patients
1.3MAC
(30% higher than MAC for each drug)
47
does nitrous oxide produce full unconsciousness in a patient?
no because the MAC is 104 so 1.3 MAC is so high
48
phases of drugs
induction, maintainence, recovery
49
inhaled anesthetics that can be used during the induction or mainenance phases
nitrous oxide and fluranes
50
all of the fluranes, except \_\_\_\_\_\_\_\_, produce bronchodilation
nitrous oxide
advantageous for patients with obstructive lung disease
51
suppopsed mechanism of fluranes
fluranes appear to to interfere with parasympathetic stimulation of bronchoconstriction by reducing the influx of Ca2+ into bronchiole smooth muscle cells either directly by blocking Ca2+ channels or indirectly by inhibiting the activity of protein kinase C.
52
most potent coronary vasodilator of the fluranes
isoflurane
this is advantagous in patients with coronary artery disease or ischemic heart disease
53
two important disadvantages of IGA
- more likely to produce post operative nausea and vomiting (PONV) than IV anesthetics
- malignant hyperthermia
54
PONV in IV anesthetics
less than half the patients reported PONV side effects compared to inhaled anesthetics
55
malignant hyperthermia
patients with rare polymorphisms of the ryanodine receptor
56
inheritance mode of malignant hyperthermia
autosomal dominant
57
mechanism of malignant hyperthermia
In patients with ryanodine receptor mutations, IGAs stimulate the opening of the Ca2+ channel causing persistent muscle contraction.
This leads to rigidity resulting from the muscle contraction, to acidosis resulting from the anaerobic breakdown of glycogen, and to hyperthermia, or high fever, resulting from the heat generated by these processes.
58
ryanodine receptor is located in
skeletal muscle cells -
acts as a channel to release Ca2+ from the SR causing persistent muscle contraction
59
symptoms of malignant hyperthermia
increased heart rate and respiratory rate
60
treatment for malignant hypertermia
dantrolene
which is an inhibitor of the ryanodine receptor Ca 2+
61
dantrolene
which is an inhibitor of the ryanodine receptor Ca 2+, prevents Ca2+ from being released
62
inhaled anesthetics toxicities
there may be some chronic toxicities that result
- mutagenicity
- teratogenicity
- carcinogenicity
63
IV anesthetics enhance _____ \_\_\_\_\_\_ signals or inhibit ________ \_\_\_\_\_\_ signaling or both
- inhibitory GABA
- excitatory glutamate
64
ketamine acts primarly as an ______ at ______ synapses
- inhibitor
- at stimulatory glutamate synapses
- it is a non competitive NMDA (glutamate) receptor antagonist
65
GABA-A positive modulators
- propofol
- thiopental
- etomidate
66
benzodiazeprine anxiolytics
midazolam
(similar to gaba pos modulators)
67
IV anesthetics: hydrophobicity ______ with potency and _____ both onsent time and duration of action
- correlates
- shortens
68
the more hydrophobic the drug is
the faster the onset time
also the faster it will redistribute out of the brain and shorter will be its duration of action
69
After administration is stopped, the anesthetic...
diffuses out of the brain and redistributes to other tissues particularly those that are highly perfused, such as skeletal muscle, or that are lipid-rich, such as adipose tissue.
70
unlike IGAs, IV antibiotics are metabolized
in the liver and/or kidneys
71
where to IV anesthetics travel?
to lipophilic tissues such as the brain and spinal cord
over time - lipid rich and highly perfused, lipid poor and highly perfused, lipid rich and poorly perfused.
72
73
high volume of distribution
most drug is in the tissue not the plasma
74
propofol
GABA positive modulator and powerful anti emetic
75
propofol and PONV
anti emetic so it can help prevent nausea if used in conjuction with IGAs used in induction or maintenance stages
76
propofol toxicity
hypersensitivity reactions - egg protein lecithin (highly hydrophobic, a soybean oil/lecithin emulsifyingagent)
77
thiopental
more complex than a GABA-A positive modulator (like benzodiazepines)
78
Thiopental is a GABAA positive modulator at ____ concentrations, and an _____ at higher concentrations (that produce unconsciousness)
- low (just helps increase CL-)
- agonist (releases the CL- itself)
79
anesthetic effects of ketamine
- amnesia
- analgesia
- unconsciousness/sedatoin
80
unconsciousness/sedation
etomidate
ketamine
propofol
thiopental
81
produces dissociative effects, disorientation, hallucinations, bad dreams
ketamine
(similar to ilicit drug PCP)
82
ketamins dissociative effects can produce
psychosis like symptoms during recovery
83
ketamine is contraindicated in
patients with schizophrenia
84
thiopental and propofol (increase/decrease) systemic BP, respiratory rate, and cerebral blood flow
decrease
85
ketamine (increase/decrease) systemic BP and blood flood
increases
86
all of the IV anesthetics (GABA effectors) decrease
respiratory rate
87
surgical amnesia is primarly achieved with
benzodiazepine anxiolytic drugs
like midazolam
88
surgical analgesia is primarly the role of
opiods
89
psychosis like symptoms
amnesia, derealization, depersonalizatoin, identity alteration, identity confusion
90
benzodiazepine
(GABA A receptor positive modulators, not agonsits) so they increase GABA potency
91
flumazenil
benzodiazepine reversal agent
can be used to treat BZ overdose
92
93
Inhibition of ascending pain pathways, stimulation of descending modulatory pain pathways
opiods
94
at slide 42
