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Flashcards in General anesthetics Deck (108):
1

what are the desirable components of general anesthesia?

reversible immobility in response to noxious stimulus

2

Examples of inhalational, volatile agents?

isoflurane, sevoflutran, desflurane, halothane, enflurane, diethyl ether, chloroform, cyclopropane,

3

Examples of inhalational, gas agents?

nitric oxide

4

Examples of Intravenous agents?

barbiturates, benzodiazepines, etomidate, ketamine, propofol,

5

Midazolam, diazepam

benzos that reduce anxiety

6

Pentobarbital

barbiturates, sedation

7

Diphenhydramine

Antihistamines, prevent of allergic reactions

8

Ondansetron

antiemetic, prevents aspiration of stomach contents, reduces postsurgical nausea and vomiting

9

Fentanyl

opioid, provides analgesia

10

Scopolamine

anticholinergic, amniesia, prevents bradycardia and fluid secretion

11

Muscle relaxant

Facilitation of intubation

12

Examples of preanesthetics

Midazolam, diazepamPentobarbital, diphenhydramine, ondansetronFentanyl, Scopolamine, muscle relaxants

13

Ideal Physicochemical anesthetic

water soluble, stable on shelf, lipophilic, small injection volume

14

Ideal Pharmacokinetic anesthetic

rapid onset, short duration, nontoxic metabolites

15

Ideal Pharmacodynamic anesthetic

wide margin of safety, no interpatient variability in effects, nonallergenic, nontoxic to tissues

16

Parenteral anesthetics

barbiturates - thippental opioids - fentanyl benzos - midazolam others - etomidate, propofol

17

Mechanisms of Action

Enhanced GABA effect on GABAa receptors Block nicotinic receptor subtypes (analgesia) Activate Tandem pore-domain K channels (hyperpolarize Vm) Inhibit NMDA (glutamate) receptors Inhibit synaptic proteins (decrease NT release) (amnesia) enhance glycine effect on glycine R's (immobility) alpha2A adrenergic receptor agonist - dexmedetomidineVoltage gated ion channels - Ca and Na - impaired function

18

Enhanced GABA effect on GABAa receptors

inhaled anesthetics BarbituratesBenzos Etomidate Propofol

19

block nicotinic receptor subtypes (analgesia)

moderate to high conc's of inhaled anesthetics

20

Activate tandem pore-domain K channels (hyperpolarize Vm)

inhaled anesthetics, NO, ketamine, xenon

21

Inhibit NMDA (glutamate) receptors

NO, ketamine, xenon, high dose barbiturates

22

how do you measure amount of inhaled anesthetics?

partial pressure or "tension" in inspired air

23

Speed of induction of anesthesia depends on?

inspired gas partial pressure (GA concentration) Ventilation GA solubility (less soluble GAs equilibrate more quickly with blood and into tissues such as the brain)

24

Name some major nuclei involved in arousal and respiration

Lateral hypothalamus - orexin Locus ceruleus - NorEpi Basal forebrain - Ach Tuberomammillary nucleus - Histamine Pedunculopontine tegmental area - Ach Laterodorsal tegmental area - Ach PAG - dopamine Preoptic area - Galanin, GABADR- serotonin

25

solubility effects arterial anesthetic levels

most = desflurane, NO, sevoflurane, isoflurane, halothane

26

Modern agents are

Ethers

27

Measures of Anesthetic potency

MAC: Minimum alveolar concentration equilibrium concnetration required to prevent the response to a painful stumulus in 50% of patients OR conc at 1 atm that produces immobility in 50% of pts or animals exposed to a noxious stimulus like an EC50 useful for comparison of drugs b/c are consistent and reproducible

28

MAC awake

MAC at which response to commands are lost

29

MAC bar

blunt autonomic response

30

MAC intubation

response to intubation

31

1.3 MAC

conc. more than 99% will not respond to stimuli

32

when several GAs are mixed, the MAC values

are additive

33

MAC is increased by

Hyperthermia, elevated CNS catecholamine NT release, chronic alcohol use, acute cocaine use, hypernatremia

34

MAC is decreased by

Hypothermia, pregnancy, shock, increasing age, acute alcohol ingestion, CNS-depressant drugs, decreased CNS NT release

35

Inhaled anesthetics from less to most potent

NO, Desflurane, Sevoflurane, Ether, Enflurane, Isoflurane, Halothane

36

all agents result in predictable and dose dependent

Hypnosis, amnesia, analgesia, inhibition of autonomic reflexes, muscle relaxation (except N2O)

37

Induction speed is affected by

Solubility Ventilation rate cardiac output

38

Vessel Rich group Uptake and distribution

CNS and visceral organs high blood flow (75%) and low capacity

39

Muscle Group Uptake and distribution

skin and muscle moderate flow and high capacity

40

Fat group uptake and distribution

low flow and high capacity

41

Vessel poor group uptake and distribution

bone, cartilage, ligamentslow flow and low capacity

42

What terminates anesthetic activity

commonly by redistribution of drug from brain to the blood and out through the lungs

43

What GAs can lead to liver toxicity

halothane and methoxyflurane

44

properties of NO

MAC > 100%: incomplete anesthetic good analgesia No metabolism rapid onset and recovery used along with other anesthetic fast induction and recovery

45

properties of Halothane

first halogenated inhalational anesthetic not pungent (used for induction w/ children, few side effects in childern) Medium rate of onset and recovery although inexpensive, its use has declined sensitizes the heart to epi-induced arrhythmias rare halothane induced hepatitis

46

properties of Desflurane

most rapid onset of action and recovery of halogenated GAs (low PC) widely used for outpatient surgery irritating to the airway in awake patients and causes coughing, salivation, and bronchospasm (poor induction agent) used for maintenance of anesthesia

47

properties of Sevoflurane

very low blood: gas partition coefficient w/ relatively rapid onset of action and recovery widely used for outpatient surgery not irritating to the airway useful induction agent, particularly in childern

48

properties of Isoflurane

medium rate of onset and recovery used for induction and maintenance of anesthesia isoflurane "was" the most commonly used inhalational GA in the US. Largely replaced by Desflurane damages mitochondria

49

properties of Methoxyflurane

widely considered obsolete slow onset and recovery extensive hepatic/renal metabolism, w/ release of F- ion causing renal dysfunction

50

Malignant Hyperthermia

esp. when halogenated GA used with succinlycholineRx: dantrolene (immediately)

51

Halothane toxicity

halothane undergoes >40% hepatic metabolism rare cases of postoperative hepatitis occur Halothane can sensitize the heart to Epi (arrhythmias)

52

Methoxyflurane toxicity

Fluoride release during metabolism (>70%) may cause renal insufficiency after prolonged exposure

53

NO toxicity

megaloblastic anemia may occur after prolonged exposure due to decreases in methionine synthase activity (vit B12 def)

54

N&V toxicity

GA effect the chemoreceptor trigger zone and brainstem vomiting center RX: ondansetron (5HT antagonist) to prevent, avoidance of N2O, ketorolac vs. opioid for analgesia, droperidol, metaclopromide and dexamethasone asso with intravenous anesthetics N2O greatest culprit

55

Drug disposition affect on toxicity

Absorption, distribution, metabolism and elimination Distribution - results in termination of effects of most anesthetics, alteration in physiology (hemodynamics, disease states) Metabolism & elimination - plays a small role in termination of effects

56

Metabolism as % of administered dose

Halothane - 20% Sevoflurane - 2-5% Isoflurane - 0.2% Desflurane - 0.02%

57

Intravenous anaesthetic properties

rapid onset (sec), rapid awakening (mins), danger of overdose due to irrevocability of iv injection redistribution determines duration of action

58

Biotransformation and elimination of most anesthetics is

slow long elimination half lives, but short effects duration of effects is dose-dependent - anesthetic doses result in brief effects, redosing used to prolong effects

59

Thiopental

"Truth serum", most frequently used barbiturate, ultra short acting drug, BUT has a long elimination half life duration of action is dose-related anesthetic induction dose lasts 5 minutes

60

Properties of Thiopental

rapid unconsciousnessgood amnesia, poor analgesia, poor muscle relaxation pleasant induction for the patient

61

Thiopental Mechanism of action

Binds to GABAa receptor - increases chloride ion flux into cell and stimulates inhibitory neuronal systems

62

Thiopental CNS effects

reduces cerebral metabolism and oxygen utilization reduces cerebral blood flow, oxygen consumption, blood volume, intracranial pressure, not cerebral perfusion pressure protects brain against hypoxic/ischemic injury

63

Thiopental Cardiovascular Direct effects

peripheral vasculature: BP, vascualr resistance and cardiac output may decrease it transiently, venodilation may result due to increased venous capacitance and in hypotension in pts in shock,

64

Thiopental Cardiovascular Indirect effects

Heart rate increased via barostatic reflex

65

Additional Thiopental organ effects

pts with high sympathetic tone will experience large drop in blood pressure
ex. hypovolemia and heart failure
due to redistribution of cardiac output

66

Thiopental Respiratory effects

depresses respiration in dose dep fashion - depresses response to hypoxemia and hypercapnia
muscle relaxants required due to retention of tracheal/laryngeal reflexes - hiccups
Thiopental depresses mucociliary clearance

67

midalozam and lorazepam

benzos
Best amnestic agents
excellent anxiolytics, anti-convulsants, muscle relaxants
bind to distinct sites on GABAa receptor

68

Midazolam in vial: pH = 3.5

allows the imidazole ring to remain open
maintains water solubility

69

Midazolam in plasma: pKa = 6.2

on injection, the ring closes and the basic drug becomes 94% unionized
increases lipid solubility, which decreases time to onset on action

70

Midalozam CNS effects

dose related effects on cerebral metabolism and blood flow
raises seizure threshold - good anticonvulsant
EEG: beta activity
antegrade, not retrograde amnesia

71

Midazolam CV effects

hypotensive effect similar to thiopental
hypotension exaggerated in hypovolemia
synergistic sedative effect exists with opioids

72

Midazolam Respiratory effects

hypnotic dose causes apnea
amnestic dose gives minimal depression

73

Opioid actions

analgesic action via mu receptors
-ones with some hypnotic action, not reliable for amnesia
used for premedication, induction and maintenance of anesthesia and postoperative pain control

74

Opioid side effects

nose and whole body - Pruritis
chest wall rigidity
Patients forget to breathe

75

Ketamine mechanism of action

arylcyclohexylamine - like PCP
Non competitive NMDA antagonist
-only IV agent that works mostly via inhibition of stimulatory neuronal systems
-acts on Cortex, limbic system, hippocampus, spinal cord

76

'Dissociative' anesthetic

individuals cognitive function is separated from his physical being

77

Ketamine CNS effects

Fast acting antidepressant
unpleasant dreams, hallucinations and delirium
incidence higher in adults, females, habitual dreamers, psychological problems
Benzos, barbs, N2O reduce incidence of these effects
increases intracranial pressure 1-60 mmHg
Nystagmus

78

Ketamine organ side effects

salivary and tracheobronchial secretions are markedly increased
reduced with atropine

79

Ketamine CV side effects

central sympathetic stimulation results in increased HR, BP, epi and nor epi levels
-offers advantage over thiobarbs when sympathetic stimulation is helpful
-direct myocardial depressant

80

Ketamine Ventilation side effects

small doses given slowly result in minimal ventilatory depression - profound analgesia reduces airway reflexes
rapid infusion, or combination with benzos potentiates depressant effects
sympathetic stimulation results in bronchdilation via direct smooth muscle effects

81

Etomidate is a _______ derivative

imidazole

82

Etomidate CNS side effects

lowers cerebral blood flow and thus intracranial pressure
lowers cerebral metabolic rate for oxygen

83

Etomidate respiration side effects

minimal ventilatory depressant
lower incidence of apnea - good for short procedures

84

Etomidate CV side effects

minimal changes in all parameters

85

Etomidate Musculoskeletal side effects

myoclonus

86

Propofol mechanism of action

diisopropyl phenol
some action at GABAa complex - binds to a distinct site
may enhance Cl- conductance at glycine receptors

87

Propofol CNS side effects

reduces cerebral blood flow and meatbolism
autoregulation is maintained in animal studies, along with response to changes in cardiac output

88

Propofol CV side effects

decreased mean BP, vascular resistance, HR and cardiac output
central venous pressure unchanged

89

What burns on injection?

Propofol
phenol component

90

Propofol pharma properties

extremely fast acting - conversation resumed in recovery, clearance exceeds hepatic blood flow
Euphoric - pts feel better the next day
"milk of amnesia": Fospropofol - prodrug faster onset

91

Dexmedetomidine site of action

brain (locus ceruleus), spinal cord and autonomic nerves
CNS effects - sedation/hyponsis, anxiolysis and analgesia
Autonomic nerves - decrease in sympathetic activity, BP and HR

92

selectivity of alpha2/1

Dexmedetomidine > medetomidine > clonidine > I-medetomidine

93

Prolonged recovery with

Midazolam
opiates

94

Respiratory depression

midazolam
propofol
opiates

95

Significant hypotension

midazolam
propofol
dexmedetomidine

96

Cumulative effects seen with

midazolam
opiates

97

Constipation

opiates

98

Lack of orientation and cooperation seen with

midazolam
propofol
opiates

99

Desflurane

must be delivered using a special vaporizer

100

NO, nitrous oxide

good analgesia
rapid onset/recovery
safe, nonirritating
incomplete anesthesia
no muscle relaxation
must be used with other anesthetics for surgical anesthesia

101

Halothane

reduces hepatic and renal blood flow
lowers BP
sensitizes myocardium to actions of catecholamine
hepatic toxicity
arrhythmias

102

Isoflurane

good muscle relaxant
rapid recovery
stability of cardiac output
does not raise intracranial pressure
no sensitization of heart to Epi

103

Sevoflurane

potential renal toxicity at low flows
bronchial smooth muscle relaxation good for patients with asthma
rapid onset/recovery
not irritating; useful in childern

104

Thiopental advantages and disadvantages

poor analgesia
causes significant nausea
little muscle relaxation
laryngospasm
rapid onset of action
potent anesthesia

105

Propofol

poor analgesia
not likely to cause nausea
rapid onset
lowers intracranial pressure

106

Dexmedetomidine

no respiratory depression
blunts undesirable CV reflexes

107

where are opioid receptors and peptides located ?

CNS, PNS, and GI tract

108

Opioid receptors are inhibitory, they

inhibit release of some NT (5HT, GABA, glutamate, Ach)
and enable the release of dopamine (contributes to dependence potential of opiates)