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Flashcards in Anesthetics Deck (120)
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1

Properties of general anesthetics

-amnesia/unconsciousness
-analgesia
-blunting of reflexas
-muscle relaxation

2

What do you use to induce amnesia

N2O, benzodiazepines

3

What do you use to induce analgesia

opoids

4

What do you use to blunt reflexes

GA's, opoids

5

What do you use to relax muscle tone?

NMB's

6

What are the two types of anesthetics?

Inhaled & Intravenous

7

Desflurane

-inhaled

8

Sevoflurane

-inhaled
-(toxicity) can make CO with CO2 absorber-- but not really anymore

9

Isoflurane

-inhaled

10

Enflurane

-inhaled
-not used clinically in US
-(toxicity) Fluoride ion in this drug can cause renal failure

11

Halothane

-inhaled
-not used clinically in US
-used in children scared of IV- overdose to get to brain quickly (6x MAC)
-(toxicity) Can cause hepatitis in adults

12

Thiopental

-IV
-Can't be used for capital punishment

13

Etomidate

-IV
-Causes severe nausea and vomit
-Used in hemodynamically unstable patients (CHF, trauma patients)
-Doesn't affect bp

14

Propofol

-IV
-Michael Jackson
-Decr bp
-Potent respiratory depressant
*Can be used as a sole anesthetic agent-- but you need very high doses
-Can cause death
*NO muscle relaxation (exception)

15

Ketamine

-IV
-induces anesthesia
-dissociative
-at low doses potent analgesic and dysphoria
-dissociative anesthesia -- takes away emotion component of pain (I'm in pain but I don't know what that means)
-Hallucinations
-Potent sympathomimetic (CV stimulant)
-Preserves airway reflexes
-INCREASES cerebral blood flow

16

Methohexital

-IV

17

4 stages of inhalation anesthesia

1- Analgesia; airway reflexes intact, patient conscious.
-used to be used in labor and delivery
2- Excitement and disinhibition. We have reflex in glottis that causes vocal cords to close and cut off our airways (laryngospasm) --> can't breathe. We avoid this stage.
3- Surgical anesthesia. Patient can still breathe and maintain some level of bp. Where we want to be.
4- Medullary center depression.

18

What part of the brain is most susceptible to anesthesia?

Cerebral cortex

19

3 goals of the anesthesiologist

1- Maintain homeostasis: O2 and ventilation, CO and bp, protect unconscious patient from injury
2-Provide optimal conditions for the surgeon; a still and bloodless field
3-perioperative care; optimize patient pre-,intra-, and post- operatively

20

Most common OR injury

Corneal abrasions

21

We measure inhalation anesthesia in terms of _____

partial pressure NOT concentration

22

Describe the the state (S,L,G) of the inhalation anesthetics and how we administer it.

volatile liquids with low boiling point- so administer them in a vaporizer as a gas along with a carrier gas (O2 in the air or NO2)

23

The ____ soluble a anesthetic in blood, the _____ more molecules are needed to achieve a given partial pressure

more, more

24

_____ (more/less) soluble agents produce _____(slower/faster) induction AND ______(slower/faster) recovery

Less, faster, faster

25

What is the blood:gas partition coefficient?
What does a low B/G mean? do we want B/G to be low or high?

-ratio of blood conc to gas conc
-Low B/G = low solubility = faster acting
-want B/G to be low

26

How much is enough?
problem and solution?

-Partial pressure in the brain needed to block movement in response to incision
problem = we can put a probe in the brain and measure that
solution= measure partial pressure in expired gas.

27

What does 1 MAC (Min Alveolar Conc) signify?

1 MAC of anesthesia = amt alveolar conc at which 50% of healthy patients do not move purposefully in response to a skin incision.

28

(T/F) MAC is the same in every patient

F, MAC different in each patient

29

What factors decrease MAC?

pregnancy, age (except early age- neonate has lower MAC than an infant), infirmity

30

(T/F) Anesthesia is always titrated to effect

T

31

Factors that influence alveolar partial pressure during induction (how fast the patient goes under)

-solubility: lower sol = faster rise
-Conc: higher conc = faster rise
-Alveolar ventilation: normal is optimal
-CO: lower CO = faster rise *counterintuitive. The less blood that passes through the brain, the longer the vapor can stay there.
-venous blood conc: higher conc = faster rise

32

Factors that influence alveolar conc during emergency (how fast the patient comes out)

-Same as during induction BUT
-Inspired conc cannot be less than zero. We cannot suck the vapor out
-Long anesthetic time = higher venous conc; slower drop in alveolar conc (slows the emergence)

33

Physiologic effects of general anesthetics
-cellular metabolism

Cellular metab decreases
-O2 consumption decr
-Myocardial oxygen consuption decr
-O2 demand decr
-O2 supply decr to meatch decr demand

34

Physiologic effects of general anesthetics
-Sympathetic tone

Symp tone decreases
-Arteries dilate
-Veins dilate
-Myocardial contractility decr
-HR variable; some cause decr while some case reflex mediated incr

35

Physiologic effects of general anesthetics
-Direct CV effects

-Decr contractility -- clinical significance is variable
-Sinus node rate changes
-Some directly dilate arteries

36

Physiologic effects of general anesthetics
-Respiratory effects

-Bronchodilation
-Decr TV (tidal vol)-more, Incr RR (respiratory rate)-less = net result of ventrilation is decr
-Decr response to hypercarbia
-NO response to hypoxemia
-CO2 apnea threshold increases

37

Physiologic effects of general anesthetics
-Effects on the brain

-All functions decrease
-Cerebral blood flow incr with halogenated agents (mismatch bw cerebral metabolic rate for O2 is decr)--concern with icreased ICP, so don't use in intracrainial neurosurgery.

38

Physiologic effects of general anesthetics
-Muscle
-Kidney
-Liver

-Muscle done decr
-GFR decr
-Hepatic blood flow decr with CO

39

Toxicity of inhalation anesthetics:
-Renal

-Fluoride ions with enflurane cause renal failure

40

Toxicity of inhalation anesthetics:
-Hepatic

-Metabolites of Halothane can cause hepatitis
-Don't really see hepatic problems in children, more in adults

41

Toxicity of inhalation anesthetics:
-Respiratory

-Sevoflurane can make CO with CO2 absorber
but don't really see this anymore

42

Toxicity of inhalation anesthetics:
-Malignant hyperthermia

-Every anesthesiologist worries about this
-Inherited genetically
-Strictly a disease of anesthesia-- disorder of muscle metabolism. We get hyper-metabolic state where the muscles go into contraction and rapid myolysis and extreme increase in CO2 production.
-Caused by succinylcholine and potent inhalation anesthetics (so not NO but everything else)

43

IV anesthetics pharmacokinetics

-like other drugs, effect is proportional to conc
-rapid onset from rapid rise in conc with bolus
-short duration from rapid redistribution
-prolonged effect from large dose/long duration filling Vd

44

IV anesthetics pharmacodynamics

-same as inhaled agents: decr O2 consumption, decr CO and MAP, decr minute ventilation
BUT they decr cerebral blood flow

45

IV anesthetics pharmacodynamics are the same for that of inhalation agents except IVs decr cerebral blood flow. Which IV drug is the exception and does not decr cerebral blood flow?

Ketamine -- it incr cerebral blood flow

46

Benzodiazepines
-What is the partial antagonist?

-sedatives only (not anesthetics -- though can use them to induce anesthesia but NOT to maintain it)
-cause amnesia and unconsciousness
-does NOT cause analgesia
-Whats good about this class is the effects are partially antagonized by flumazenil

47

Opoids
-What drug reverses the effects of opoids?

-Analgesics NOT anesthetics
-reduce req amt of anesthetic agents
-All effects are 100% reversible with naloxone

48

Local anesthetics

-substances that cause temporary blockade of neural transmission when applied to nerve axons
-block voltage gated Na channels --therefore interrupt nerve impulses in axons

49

Physical properties of local anesthetics

-weak bases, poorly water soluble
-synthetic -- derived from cociane
-Have hydrophilic (aromatic ring) and lipophilic end (tertiary amine) joined by an aster or amide linkage
-Made available clinically as salts to incr solubility and stability

50

Local anesthetics
-which is causes a shorter duration of action, ester linkage or amide linkage, why?

-Ester links bc they are more prone to hydrolysis than amide links, esters usually have a shorter duration

51

Charged or uncharged form of local anesthetic causes the rxn? Why is this a problem?

Charged. Problem bc uncharged form is the form that can get to the site of action not the charged form.

52

Mech of action of local anesthetics

Disruption of membrane depolarization by:
-blocking Na conduction into cell
-Influx of K is unchanged
-Cellular integrity and function unchanged

53

What form of the LA blocks the Na ad produces temporary dysfunction?

cationic form

54

What does blockade of Na channel in LA mech of action req and what is it dependent on?

-dep on conc
-req distribution of several contiguous channels to overcome the natural reserve of conduction in mammalian nerves

55

Is the interaction of LA with the Na channel reversible? When does action end?

-It is reversible
-Ends when the conc of LA falls below a critical min level

56

What is differential sensitivity

-Small unmyelinated fibers (B and C fibers) are more sensitive to LA
-Large myelinated (A fibers) require larger amounts of LA to be blocked

57

What is the frequency dependent block?

-Enhanced action of LA on a nerve which is stim or actively firing compared to nerve not firing nor active

58

Why are nerves with higher firing freq and more pos membrane pot more sensitive to LA block

-bc the charged local anesthetic molecules are more likely to have access to the binding sites in the open Na+ channel.

59

According to freq dependent block for LAs
Are fibers with a high firing rate and longer duration of AP more or less sensitive to lower concs of local anesthetics? What kind of fibers?

--More sensitive
-Sensory fibers, especially pain fibers

60

Why do we need a lower conc of anesthetics to knock out pain than we do to knock out motor function?

Sensory fibers have longer AP duration and higher firings rate-- so more sensitive to lower concs of LAs

61

What fiber type is the most sensitive to LA? Type A, B or C?

Type-C

62

What does the ester vs amide linkage in LAs determine and influence?

-determines route of metabolism
-Indirectly influences specific toxicities
-Determines potency and duration

63

What do physicochemical properties of LAs affect?

-onset of action
-potency
-duration of action

64

What is pKa?
-What is the range for most LAs? What is the exception

pH as which 50% of the molecules are in the charged (ionized) quaternary form and 50% are in uncharged (unionized) form.
-Range 7.5 - 9 (weak bases) --therefore charged/ionized cationic form will be large percentage at physiological pH
*Exception - Benzocaine has pHa of 3.5 (exists solely as nonionized base)

65

Are LA solutions (vials) off the shelf acidic or basic relative to their pKa, why?

-acidic -- to incr stability and shelf life

66

What form of the LA (ionized or unionized) is necessary for nerve penetration? Ad which form delays onset of action?

-Nonionized form for nerve penetration
-ionized form to delay action

67

Where is the receptor site for LAs?

inner vestibule of the Na channel (this is deep inside the neuron)

68

We need unionized form to penetrate nerve, but we want ionized for at the site of action, how does this happen?

-After penetration of cytoplasm (by nonionic form), equilibration leads to formation and binding of the charged cation at the Na channel

69

(T/F) Potency is indirectly proportional to lipid solubility

F- it is directly proportional
-The cell wall is a lipid structure. Potency is really more about ability to penetrate nerve rather than at site of action

70

(T/F) Duration of action is directly proportional to protein binding.
-What does protein binding also relate to?

T--the greater the protein binding, the longer it takes to wash out the drug.
-relates to toxicity --high protein binding reduces amt of free drug

71

LA metabolism of esters

hydrolysis in the blood by pseudo or butyrylcholinesterase (prod in liver), or red cell esterases

72

LA metabolism of amides
-What does it req?

-metabolized by cyt p450s (liver enzyme)-- so requires intact liver

73

What about the metabolism of LAs would give a prolongation of action

-atypical pseudocholinesterase or liver disease

74

What is the absorption of LA determined by?
-How can we alter the blood flow?

-dosage (how much you give them)
-site of injection
-drug-tissue binding
-local tissue blood flow
-physicochemical properties of the drug
-alter blood flow by adding vasoconstrictor (like epi) to the LA

75

LA-Rank the following in terms of absorption rate from highest (most susceptible) to lowest
-Epidural block
-Brachial plexus block
-Intercostal block
-Sciatic and Femoral nerve block
-Caudal block

1- Intercostal block (usually blocking more than one intercostal nerve so better chance to absorb it)
2- Caudal block
3- Epidural block
4- Brachial plexus block
5-Sciatic and Femoral nerve block

76

(T/F) The rank of rate of absorption in each part of body (ex- intercostal) will be different depending on which drug you use.

F - The relationship is always the same no matter the LA drug. Some drugs might have more or less responses but the ration is the same always.

77

LA toxicity:
What are the CNS initial symptoms (lower dose)?

-Lightheadedness
-Peri-oral numbness
-Dizziness
-Visual and Auditory disturbances (Tinnitus)
-Disorientation
-Drowsiness

78

For LA toxicity, which signs to we see first, CNS or cardiac?

CNS

79

LA toxicity:
What are the CNS signs with higher-doses?
When do they occur?

-Muscle twitching
-Convulsions
-Unconsciousness
-Coma
-Respiratory depression and arrest
-CV depression and collapse
-> Often occur after initial CNS excitation followed by a rapid CNS depression

80

LA toxicity:
What are the direct cardiac effects?
Which drug is especially cardiotoxic?

-Myocardial depression, cardiac dysrhythmias and cardio-toxicity in pregnancy
-Negative inotropic effects on cardiac muscle that lead to hypotension.
-> Bupivicaine is especially cardiotoxic

81

LA toxicity:
-What are the peripheral effects of low and high doses?

Low doses -- vasconstriction

High doses -- vasodilation (hypotension)

82

LA toxicity:
-What are the hematological sigs
-What drugs cause this?

-Methemoglobinemia
-Common with prilocaine and benzocaine

83

What does local tissue manifestations in LAs cause?

-Muscle necrosis

84

What are people allergic to in LAs? What is this due to?

-Ester LA
-Due to para-amino benzoic acid (PABA)

85

What are the treatment options of LA toxicity?

-Stop injection
-Airway, O2
-Treat seizures with benzodiazepines
-Cardiac: CPR, ACLS

86

What is a new treatment option of LA toxicity? What does it do?

-Intralipid
-It blunts the cardiotoxicity of bufiviciane

87

How do we treat methemoglobinemia (LA toxicity)?

It's spontaneously reversed or use Methylene Blue

88

Allergic rxns in LAs usually due to? Are the common or rare?

-Rare
-Due to preservatives (mathylparaben)

89

How do we treat muscle tissue necrosis (LA toxicity)?

-spontaneously reversed in ~2 weeks

90

What happens in complication of the central neuraxial block.
-What does central mean here?
-What happens when levels exceed T10 and Y$
-What are the contraindication of the neuraxial blockade?

Central = spinal or epidural anesthesia
-Above T10 --Knocking out 2 of 3 resevoirs --Causes profound hypotension (bc decr venous return)
-Above T4 -- Knocking out all 3 major venous resevoirs --bradycardia makes things worse (can cause cardiac arrest)
-Contraindications: aortic stenosis, shock and coagulopathy

91

Cocaine

-First LA
-Naturally occurring ester
-High local neural toxicity
-High abuse pot
-Still popular topical anesthetic bc of vasoconstrictive properties

92

Novocaine

-Ester LA (modification of cocaine)
-First injectable LA synthesized
-Metabolized by pseudocholinesterase
-Excreted by the kidneys
-Very short acting-- so unlikely to get toxicity

93

Tetracaine
-Which body part is this commonly used on?

-Ester LA
-Slow onset due to high pKa
-Long duration
-Great topical anesthetic --> used on the eye

94

What does a high pKa indicate?

agent is mostly ionized

95

2-Chloroprocaine

-Ester LA
-Safest in terms of toxicity
-Duration 45-60 min (short)
-Rapid termination of effect (rapidly metabolized-- why it's safe)
-IV -- causes thrombophlebitis

96

Benzocaine

-First synthetic LA (ester)
-Effective only in high conc
-Mostly used in mucous membranes (very effective for topical, not really used for anything else.)
-Causes methemoglobinemia

97

Lidocaine

-First amide LA -- all others are compared to this one
-Metabolized in liver
-Excreted by kidneys
-Can give IV to treat arrhythmias

98

Dibucaine

-Amide LA
-High potency and toxicity
-Inh plasma cholinesterase -- used to determine if person has atypical cholinesterase
-Only use topical as cream

99

Mepivacaine

-Amide LA
-Similar to lidocaine, but less vasodilation
-Slightly greater potency and duration
-Use: epidural, spinal, peripheral nerve block, local infiltration
-Potential for accumulation --> unsuitable for prolonged epidural infusion

100

Bupivacaine

-Amide LA
-Greater potency and duration (can add epi for longer duration)
-Good for spinal anesthesia
-Slower onset
-Several concs used
-Sig freq dependent block
-Has cardiotoxicity (much more than any other anesthetic)

101

Ropivacaine

-Amide LA
-Almost pure S isomer (so not racemic mixture)
-Less potent and shorter duration than Bupivacaine
-Less cardiotoxic
-Better freq dep block
-Sev concs used

102

Prilocaine

-Amide LA (most rapidly metabolized amide LA)
-Produced methemoglobinemia

103

Epi

-Adjuvant to LA
-Decreases absorptions and prolongs duration (bc vasoconstrictor-- allows drug to stay in the area)
-Also used as a monitor

104

Bicarbonate

-Adjuvant to LA
-Incr pH of solution, accelerating onset
-May decr duration
-May precipitate in Ropivacaine and Bupivacaine (what does this mean?)

105

What are 2 adjuvants for LA?

Epi and bicarb

106

Partial pressure

Basic principle of anesthesiology; the tendency of an anesthetic dissolved in blood to come out of solution.

107

Anesthetic effect is the result of ______ NOT ______

pp NOT conc

108

Fentanyl

-IV
-Analgesia

109

Low B/G coeff

low solubility and faster acting

110

MAC

That alveolar concentration at which 50% of healthy patients do not move purposefully in response to a skin incision

111

Minimum alveolare conc

MAC

112

Nitrous oxide

anesthetic with the highest MAC

113

What is an IV effect diff from inhalation effect?
-And what drug is the exception?

Unlike inhaled agents, decrease cerebral blood flow (except Ketamine)

114

Flumazenil

Partial benzodiazepine antag

115

LA mech of action
-what is not affected?

Disruption of membrane depolarization by blocking Na+ conduction into the cell (K+ influx unchanged, cellular integrity not affected); concentration dependent

116

Unmyelinated nerve fibers

Small (B and C) fibers appear more sensitive to local anesthetics

117

Myelinated nerve fibers

Large A fibers require larger amounts of local anesthetic to be blocked

118

What does low CO do to induction of inhaled anesthetics?

accelerates it

119

What is duration of action proportional to?

Directly proportional to protein binding; also relates to toxicity - high protein binding reduces amount of free drug

120

Which LA are longer acting?

Bupivacaine and Ropivacaine