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Flashcards in Anesthesia Part I Deck (198)
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1
Q

Difference btwn pharmakodynamics and pharmakokinetics:

A

Dynamics - how works

Kinetics - what body does to the drug

2
Q

In LA, we are inhibiting Afferent or Efferent nn.

A

Afferent

efferent goes out

3
Q

T/F
Onset, Duration, Potency, no allergic rxns, Stably, Sterile, readily undergoes biotransformation - are all desireable properties of LA’s and no LA meets ALL criteria

A

True

4
Q

LA’s prevent both the ____ and the _____- of a nerve impulse

A

generation

conduction

5
Q

What is the primary action of LA’s in producing a conduction roadblock?

A

Decrease permeability of ion channels to sodium

*blocks sodium channels

6
Q

Where do LA’s work?

A

Na channels

7
Q

LA’s prevent Sodium channels from assuming what state?

A

Open (active)

8
Q

The primary effects of LA’s occur during what phase?

A

depolarization

9
Q

LA’s decrease the rate of ______ and prolong the rate of ________

A

depolarization

repolarization

10
Q

T/F

Mostly LA works on C fibers, but we could go after myelinated fibers as well

A

True

11
Q

What phospholipid bilayer membrane acts as a barrier to LA’s

The outer layer of a neuron underlying its sheath:

A

Neurolemma

Axolemma

12
Q

T/F

The myelin sheath insulates the axon both electrically and pharmacologically

A

True

13
Q

T/F

The Nodes of Ranvier are the only site where molecules of LA have access to the nerve membrane - lots of Na channels

A

True

14
Q

How many Nodes of Ranvier must be blocked to ensure effective anesthesia?

How many mm?

A

2-3 nodes

8-10 mm

15
Q

What fiber carries information related to sharp pain?

What fiber carries information related to dull, aching pain?

A

A- delta

C fibers

*easier for LA to affect unmyelinated C fibers

16
Q

What normally regulates the movement of Na ions across the nerve membrane?

A

Ca ions

*increase permeability of Na

17
Q

LA molecules act by ______ antagonism with Calcium on the nerve membrane

A

Competitive

18
Q

T/F

LA produce a depolarizing nerve blockade

A

False

*nondepolarizing

19
Q

Mechanism of LA, displace _______

Bind ______

A

Ca++ ions

receptor site

20
Q

LA molecules have a ______ aromatic ring

An intermediate linkage of either _____ or ______

And a terminal _______

A

lipophilic

Amide/Ester

amine

21
Q

Only ____ containing LA’s are available in the US and can be identified by a Nitrogen in the Intermediate Linkage

A

Amide

22
Q

All LA’s are weak _____

A

bases

23
Q

What chemical property of LA’s correlates with Potency?

A

Lipid Solubility of the Aromatic Ring

24
Q

Bupivacaine is more/less potent than Lidocaine

It is prepared at ___% concentration

*Lidocaine prepared at ____% concentration

A

more

  1. 5%
    * 2%
25
Q

In an LA molecule, what part is soluble in lipid?

Water?

A

aromatic

amino

26
Q

What part of LA molecule is the “on-off switch” allowing LA to exist as either lipid or water soluble conformations?

A

Terminal amine

*tertiary/quaternary forms

27
Q

Intermediate chain is either an Amide broken down in the _____

or and Ester broken down in the ______

A

Liver

Blood

28
Q

What allows LA to be effective in tissues (chemical structure)?

A

Spacing between aromatic ring and secondary/tertiary amine

29
Q

LA’s are prepared as weak ______

Are combined with an acid to form a ______ (this makes stable/injectable solution)

A

bases

salt

30
Q

All LA’s are prepared as what?

Injected as what?

A

Weak bases

Acidic (HCl stored)

31
Q

The salt form of LA exists as a ____ structure and will not penetrate the neuron

When exposed to physiologic pH (7.4), a proportion of molecules will convert to _______ structure that is lipid soluble

This determines what?

A

quaternary

tertiary

time of onset

32
Q

What predicts the proportion of LA molecules in quaternary/tertiary structure when exposed to 7.4 physiologic pH?

A

pKa (ionization constant)

33
Q

What speeds the onset of action and increases the clinical effectiveness of LA’s?

A

Increasing pH

34
Q

pH varies a lot in extracellular fluids but remains constant where?

A

interior nerve

35
Q

Changes in extracellular pH profoundly alter what?

A

Ability of LA to block nerve impulses

36
Q

Without a vasoconstrictor (epi) what is the pH of LA’s?

With epi?

What does this explain?

A
  1. 5
  2. 3

burning sensation of LA’s

37
Q

LA’s exist simultaneously as the base and the what?

A

Cation

RNH+ RN + H+

38
Q

In order to get through the membrane, what form does the LA take?

In order to bind the receptor sites to block Na channels what form does the LA take?

A

Base molecule (RN) *lipophilic

Cation (RNH+) *hydrophilic

39
Q

What form, Cation or Base, is the predominant in LA drug solutions?

A

RNH+ Cation

40
Q

What is the sequence of Form when injecting and LA - as injected?

In response to 7.4 tissue pH?

Once exposed to axoplasm?

A

Cationic

Base (to pass through membrane)

Cation

41
Q

Only ____ molecules can penetrate the nerve membrane

Only ____ molecules can bind receptor sites in channels

A

base

cation

42
Q

Low pH shifts LA to what form?

If this exists in tissues what happens?

A

Cationic

decreases effectiveness b/c won’t be able to penetrate membrane

43
Q

The inclusion of more Cations in an injectable solution produces greater stability, increased solubility of powdered drug in water, and ease of sterilization

A

True

44
Q

pH = pKa

A

50% Cation, 50% base

45
Q

The higher the pKa, the more _____ form

This means what for the LA

A

Cationic

Longer onset

46
Q

pKa ranges for LA’s are usually what (very narrow)?

A

7.7 to 8.1

47
Q

What drug is very potent but very slow diffusing?

  • slowest diffusing, but used in prolonged operations
  • highest pKa of any LA
A

Bupivacaine

48
Q

The higher the pKa, the more _____ the ____ the onset, the more _____ it will be once inside the membrane

The lower the pKa, the more ____ , the ____ onset, the less _____ will be once inside the membrane

A

cations, greater time of onset, more effective

base, faster the onset, less effective

49
Q

What additive to LA’s that prolongs shelf life can trigger rxn if allergic to sulfites?

A

Sodium bisulfite

50
Q

What has a slower onset, LA’s with or without vasoconstrictors?

A

Without

*more base faster the onset - so acidic solutions take a longer time to buffer and cross membranes

51
Q

LA’s are effective on axons and free nerve endings and are can’t penetrate skin

A

True

*except for EMLA, but slowly

52
Q

Where can topicals diffuse to reach free nerve endings?

A

Mucous membranes

Injured skin

53
Q

Why are topical nerve blocks ineffective in mucous membranes?

A

Low buffering capacity

54
Q

Increasing the pH of a topical does what?

A

Increases potency

less H+, less cation, more base

55
Q

T/F

Topicals are usually more concentrated than the injection version

A

True

56
Q

Outside of nerve sheath:

Outside of nerve bundles:

Outside of nerves:

A

Epineurium

Perineurium

Endoneurium

57
Q

In a nerve sheath, what is the greatest barrier to the penetration of LA?

A

Perineurium

58
Q

What are the 1st bundles in a fascisulus reached by LA?

What are the last?

A

Mantle bundles

Core bundles

59
Q

T/F
Mantle bundles innervate something close by

Core bundles innervate something far away

A

True

60
Q

T/F

In no clinical situation are all fibers in a peripheral nerve blocked

A

True

61
Q

Relate pKa and onset of action:

A

Lower pKa, greater onset of action

*more diffusable through membrane

62
Q

What relates to potency?

What relates to duration of action?

A

Lipid solubility

Degree of protein binding (bupivacaine)

63
Q

Duration of action and potency are opposites

A

True

Cationic is related to duration of action

Lipid solubility is related to potency

64
Q

What affects both potency and duration of LA’s?

A

Vasoactivity

vasodilators decrease

vasoconstrictors increase

65
Q

T/F

All LA’s are vasodilators, this is why we add vasoconstrictors (like epi)

A

True

66
Q

T/F

Mantle bundles lose LA more readily than core bundles and recovery is a slower process than induction

A

True

67
Q

Increasing tolerance to a drug that is administered repeatedly

A

Tachyphylaxis

68
Q

Tachyphylaxis is more likely to develop in what case?

A

If nerve function allowed to return prior to second injection

69
Q

3 factors that affect the rate of removal of an LA:

A

Degree of protein binding

vascularity of injection site

presence or absence of vasoconstrictor

70
Q

The first-in-class anesthetic reversal agent is called ______ .

It significantly shortens recovery time and is a _____

Injection site used:

A

Oraverse

Vasodilator

same

71
Q

When do LA’s stop providing clinical effects?

A

When enter bloodstream

*can have other effects

72
Q

The only LA that is a vasoconstrictor?

A

Cocaine

73
Q

3 significant vasodilatory effects of LA:

A

Increase rate of absorption into blood

Decrease duration/quality of pain control

Increase blood conc. and potential for overdose (toxicity)

74
Q

Once in the bloodstream, highly perfused organs receive more LA but the greatest percentage goes where?

A

Skeletal muscle

75
Q

LA readily crosses BBB and placenta

A

True

76
Q

Elimination of LA’s follow what order kinetics

A

1st order kinetics

half lives (time necessary to remove 50%)

77
Q

Esters are hydrolyzed in the blood by ______

byproduct is _____ excreted in the urine

Inherited disorder (1 in 2800) unable to hydrolyze esters in blood and contraindication for LA esters:

A

plasma cholinesterase

PABA

Atypical pseudocholinesterase

78
Q

Amides are metabolized where?

What is a relative contraindication to use of these LA’s?

A

Liver

ASA IV to V liver dysfunction

79
Q

What LA undergoes primary metabolism in the liver with some in the lung, and can induce the formation of methemoglobin?

A

Prilocaine

80
Q

What is the primary metabolite of Prilocaine (that leads to methemoglobin formation)

A

orthotoluidine

81
Q

What metabolites of Lidocaine are responsible for producing sedation?

A

monoethylglycinexylidide

glycine xylidide

82
Q

Systemic actions of LA’s are related to the blood/plasma levels of the LA’s

A

True

83
Q

LA readily crosses the BBB and has what pharmacological action?

A

CNS depression

84
Q

Overdose/Toxicity of LA’s usually looks like what?

However, some LA’s have ____ properties at lower/non toxic levels

A

Tonic-Clonic convulsions *inhibit inhibition

anticonvulsant

85
Q

CVS effect of LA’s

What LA is used as an anti-arrhythmic?

A

myocardial depression

Lidocaine

86
Q

All LA’s are vasodilators and create what in terms of BP?

A

hypotension

87
Q

LA’s have negative CVS effects at what blood levels?

Slight increase BP due to symp activity at what levels?

Mild hypotension at what levels?

A

Significantly elevated

non-overdose levels

approaching od levels

88
Q

When does LA produce profound hypotension?

A

Overdose levels

89
Q

What LA may produce fatal ventricular fibrillation at overdose?

A

Bupivacaine

90
Q

What is more sensitive to irritating properties of LA than other tissues?

Most often associated with what?

A

Skeletal

Bupivacaine

91
Q

At non-overdose levels LA’s are a respiratory relaxant, and at overdose levels they can produce what?

A

resp arrest

92
Q

Neuromuscular blockage is _____ when LA used w/ other relaxants

DDI’s are ____ with other CNS depressants

A

Additive

Additive

93
Q

Amides were once thought to contribute to what?

*there is no literature to support and is a genetic variant

A

Malignant hyperthermia

94
Q

We only use Amide LA’s in dentistry in the US, but where do we use esters?

A

topicals

95
Q

Short duration of action for LA’s:

Intermediate

Long

A

20-40 minutes

70 minutes

8 hours

96
Q

T/F

A nerve block will provide longer duration of pulpal/soft tissue anesthesia compared to supraperiosteal infiltration

A

True

97
Q

T/F

A larger than recommended dose increases duration

A

False

98
Q

2 drugs with long duration:

2 drugs with short duration:

A

bupivacaine 0.5%, prilocaine 4% w/ epi

mepivacaine 4%, prilocaine 4%

99
Q

T/F

1:50k or 1:100k will be better for hemostasis

A

True

100
Q

A true, documented, reproducible allergy is what for an LA?

When to use alternative or lowest dose w/ least conc?

A

absolute contraindication

relative contraindication

101
Q

T/F

You should have a minimum of 2 different drugs of varying duration of action in your practice

A

True

102
Q

Short duration pulpal LA:

Intermediate pulpal LA:

Long pulpal LA:

A

30 min

60 min

90 min

103
Q

The first synthetic LA was an Ester called…

It has the greatest _____ of LA’s

It had a slow onset with means a high…

A

Novocain (procaine HCl)

vasodilation

pKa

104
Q

What Ester combo LA was removed from the US market in 1996, was very toxic, and limited utility?

A

procaine HCl (novacaine) + propoxycaine

105
Q

Norepinepherine isn’t recommended why?

A

Necrosis

106
Q

What is the Gold Standard LA - the drug against which all others are compared?

A

Lidocaine HCl

107
Q

lidocaine is better than procaine (novacaine) in onset, potency, duration

worse in toxicity

A

True

108
Q

T/F

Allergy to amide LA is common

A

False

*non-existent

109
Q

What are the 2 pharmacologically active/potentially toxic metabolites to lidocaine HCl

A

monoethylglyceine

xylidide

110
Q

Lidocaine onset of action

Effective dental concentration:

Safe for lactation?

pregnancy category:

A

Rapid, 2-3 minutes

2%

safe - doesn’t enter milk

B

111
Q

What are the 3 formulations of lidocaine (w/ colors)

A

lidocaine 2% w/ epi 1:50k (green)

lidocaine 2% w/ epi 1:100k (red)

lidocaine 2% plain (light blue) *vasodilatory, few applications

112
Q

The duration and depth of anesthesia differs how between Red and Green?

lidocaine 2% 1:100k vs. lidocaine 2% 1:50k

A

Doesn’t

113
Q

Why is Red lidocaine 2% 1:100k preferred for dental procedures?

A

Safer

*for hyper responders, elderly, ASA, cardiac risk

114
Q

What are the 1st signs/symptoms of LA overdose?

A

drowsiness, loss of consciousness, resp arrest

115
Q

B/c Licodane is a depressant, what other use does it have for the CNS?

A

Anticonvulsant

116
Q

What LA has similar actions to Lidocaine and lacks the duration of Bupivacaine?

A

mepivacaine HCl

117
Q

What is the color/concentration of mepivacaine HCl

*similar to Lidocaine pharmacologically

A

mepivacaine HCl 3% w/o vasoconstrictor TAN

mepivacaine HCl 2% w/ levonordefrin 1:20k BROWN

118
Q

What is the weakest vasodilator of all injectable LA?

A

mepivacaine

119
Q

T/F

mepivacaine w/ levonordefrin 1:20k provides same hemostasis as epi

A

False

120
Q

Like Lidocaine, Mepivacaine has near non-existant allergy and also possesses anticonvulsant properties

Also, follows more classic OD presentation of CNS stimulation followed by crash

A

True `

121
Q

Relative potencies of LA’s:

A

procaine

lidocaine, mepivacaine, prilocaine

articaine

bupivacaine

122
Q

Mepivacaine Toxicity:

Metabolism:

Onset:

Safe during lactation?

A

similar to Articaine and Lidocaine

Liver: hydroxylation & N-demethylation

1-2 minutes (rapid)

unknown, use w/ caution

123
Q

What drug is similar to Mepivacaine pharmacologically?

A

prilocaine HCl

124
Q

prilocaine was thought to have decreased toxicity to lidocaine, but what was discovered?

A

reduces oxygen carrying capacity

***methemoglobinemia

125
Q

Why is Prilocaine’s end product CO2

A

Secondary Amine

126
Q

What metabolite of Prilicaine induces formation of methemoglobin?

A

Orthotoluidine

127
Q

T/F

Because Prilocaine reduces blood Oxygen carrying capacity, this limits the dose that can be safely given

A

True

128
Q

T/F

despite its complications, Prilocaine is metabolized much more rapidly/completely than Lidocaine

A

True

129
Q

What LA has biotransformation take place in the Lungs and Kidney as well as the Liver?

A

Prilocaine

130
Q

What LA has faster Renal Clearance than all other Amides?

A

Prilocaine

131
Q

What LA is considered to be less toxic systemically than comparable potent amides?

A

Prilocaine

*removed from circulation fast

132
Q

The 2 formulations of Prilocaine:

A

4% Plain Black

4% w/ epi 1:200k Yellow

133
Q

Why does Prilocaine 4% plain work well?

A

Weak vasodilator

*but NOT as weak as mepivacaine

134
Q

What LA is good for epi sensitive pts?

A

Prilocaine

*least conc epi will produce lengthy anesthesia

135
Q

Anything that produces ______ will be a relative contraindication to prilocaine

*this includes acetaminophen and phenacetin

A

methemoglobin (emia)

136
Q

Prilocaine HCl potency:

toxicity:

metabolism:

excretion:

vasodilation:
onset:

concentration:

lactation safe?

A

equal to lidocaine, mepivacaine

half as toxic as lidocaine

liver, lungs, kidneys - rapid/complete

kidneys - fast renal clearance

less than lidocaine, more than mepivacaine

2-4 minutes

4%

use w/ caution - thought to enter breast milk

137
Q

What LA is classified as an Amide but has a different ring structure?

This is a ______ ring - has a _____ atom on it that Increases solubility that has a ______ side chain

A

articaine

Thiophene - Sulfur, Ester

138
Q

What LA is biotransformed in plasma and liver?

*rapidly in plasma

A

articaine

*ester off thiphene ring + amide

139
Q

What has the fastest onset of the 5 injectable amide LA’s?

A

articaine

140
Q

Articaine has a high pKa, meaning fewer ____ molecules

Despite this, it’s Sulfur/Ester ring makes it more _____

A

base

lipophilic

141
Q

Articaine is available in what 2 formulations?

A

articaine 4% w/ epi 1:100k gold

articaine 4% w/ epi 1:200k silver

142
Q

Because articaine has rapid metabolism and clearance, it presents ____ risk for systemic toxicity

A

less

143
Q

What is the knock on articaine that probably isn’t true?

A

paresthesia risk

144
Q

T/F

Methemoglobiniemia may be a risk of articaine but no cases have been reported in dentistry

A

True

145
Q

articaine HCl potency:

metabolism:

Excretion:

Vasodilation:

half life:

A

1/3 more potent than Lidocaine, mepivacaine, prilocaine

amide - liver ester - plasma cholinesterase

kidneys

equal to lidocaine, greater than mepivacaine/prilocaine

146
Q

What LA has a lengthy duration and is usually only used in OS?

A

bupivacaine

147
Q

Because bupivacaine lasts for so long, this decreases use of what?

A

post-op opioids

148
Q

The slowest onset LA due to high pKa

A

bupivacaine

149
Q

bupivacaine isn’t recommende for what 2 demographics?

A

children

at risk for self injury (disabled)

150
Q

What LA has the most profound vasodilating properties?

A

bupivacaine

151
Q

Overdoses with ____ are uncommon, but more severe and not easily reduces b/c it is ______

A

bupivacaine

cardiotoxic

152
Q

Adverse events with bupivacaine are rare b/c we use a lower dose than in medicine

A

True

153
Q

bupivacaine formulation (and color)

A

bupivacaine 0.5% w/ epi 1:200k Blue

154
Q

bupivacaine: Potency:

Toxicity:

Metabolism:

Extretion:

Vasodilation:

Onset:

half life:

A

most potent

most toxic

liver (slow by amidases)

kidney

most potent vasodilator

slowest (6-10 minutes)

longese - 2.7 hrs

155
Q

Atrqumatic injections involve pre-injection numbing

A

True

156
Q

Topical LA’s don’t contain what?

A

vasoconstrictors

157
Q

T/F

blood levels by topical LA’s can be as high as those injected

A

True

158
Q

Many LA’s aren’t used topically why?

A

concentrations would be too high - risk for OD

159
Q

almost all LA’s aren’t used topically with what notable exception?

A

Lidocaine

160
Q

What ester is never injected, always Topical:

A

benzocaine

161
Q

benzocaine may produce allergy w/ prolonged use why?

A

PABA metabolite

162
Q

What topical is a ketone, equal in potency to cocaine, slow onset, unsuited for injection, and must be compounded at the pharmacy?

A

dyconine hydrochloride

163
Q

2 forms of topical lidocaine:

A

lidocaine base 5% (poorly soluble)

lidocaine hydrochloride 10% (soluble)

164
Q

What is the most potent dental topical LA with that also has a long duration or 45 minutes?

A

tetracaine hydrochloride

165
Q

What combo topical LA contains 3 esters and has a duration of up to 45 minutes?

A

benzocaine, butamben, tetracaine

Cetacaine

166
Q

What topical has higher concentrations of base forms of drugs, a long onset on skin, and a fast onset on mucosa?

A

Eutectic mixtures

167
Q

2.5% lidocaine and 2.5% prilocaine Topical has what 2 formulations?

A

EMLA - medicine

Oraqix - dentistry

168
Q

Where is Oraqix used?

It is a ____ mixture

Duration:

A

Intrapocket

Eutectic

20 min

169
Q

Vasoconstrictors minimize the risk of LA toxicity, increase duration of action of LA, and provide hemostasis

A

True

170
Q

2 Vasoconstrictors in Dental Anesthetics:

A

epinephrine (naturally occurring)

levonordefrin (synthetic)

171
Q

catechol ring:

A

aromatic with a couple hydroxyls

*add a terminal amine = catecholamine

172
Q

The dilution ratio:

A

grams drug dissolved: milliliters of solvent

grams: mL

173
Q

Dilution ratio of epi used for anyphylaxis

A

1:1000

174
Q

1:100,000 epi used is 1 gram: 100,000 mL solvent

A

True

175
Q

epi concentration can be 1:1k, 1:50k, 1:100k, 1:200k

What is the concentration of levonordefrin?

A

1:20,000

176
Q

What is the only product that used levonordefrin?

A

mepivacaine 2% (brown)

1:20,000

177
Q

Match colors: Lidocaine 2% epi 1:100k:

lidocaine 2% epi 1:50k

lidocaine plain

mepivacaine 2% levonordefrin 1:20k

mepivacaine 3%

prilocaine 4% epi 1:200k

prilocaine 4%

bupivacaine 0.5% epi 1:200k

articaine 4% api 1:100k

articaine 4% epi 1:200k

A

red

green

blue

brown

tan

yellow

black

blue

gold

silver

178
Q

most effective and widely used vasoconstrictor that affects heart and vasculature

peaks in plasma:

subsides:

A

epinephrine

5 minutes

20-30 min

179
Q

What is an absolute contraindication to epi

A

Graves disease

180
Q

Epinephrine is especially prone to deterioration via…

A

oxidation

181
Q

Beta 1 = ______ effects

A

Cardiac

182
Q

Beta 2 = ______ effects

A

coronary arteries, airway, skeletal

183
Q

Epi always increases ____ BP

A

systolic

184
Q

Epi decreases Diastolic pressure in what dose?

Increase in what dose?

A

small (beta 2)

large (alpha)

185
Q

What type of epi effects predominate in hemostasis?

A

Alpha

186
Q

In epi decline what type of effects predominate?

A

Beta-2

*vasodilation, post op bleeding

187
Q

T/F

epi raises blood sugar levels

A

True

188
Q

Endogenous epi is terminated by COMT and MAO in the liver

Exogenous epi is terminated by ______

A

COMT

189
Q

A healthy pt can take how many mg of epi?

Cardiac dose?

A

0.2 mg (200 mcg)

.04 mg (40 mcg)

190
Q

Limit Epi dose with what Cardio pts? (2)

A

ASA III and ASA IV

191
Q

1:50k epi cartridge max for healthy pt (0.2 mg):

ASA III/IV pt (.04 mg):

A

5.5

1

*double these for 1:100k, double again for 1:200k

192
Q

1:50k dilution is most effective at hemostasis, but what is the dilution of choice for at risk individuals?

A

1:100k

193
Q

levonordefrin is a 75% _____ stimulator and a 25% ____ stimulator

A

direct alpha

beta

194
Q

levonordefrin is ___% as potent as epi

A

15%

195
Q

levonordefrin has more CNS/CVS effects compared to epi

A

False

*Less

196
Q

levonordefrin, Hemostasis:

Resp:

CNS:

Metabolic:

Termination:

A

less than epi

less than epi

less potent than epi

less than epi

COMT (no MAO)

197
Q

levonordefrin max dose health pts:

cardiac dose:

A

1 mg = (20 ml 1:20,000) = 11 cartridges

0.2 mg = 4 ml of 1:20,000 = 2 cartridges

198
Q

Do not inject vasoconstrictors intravascularly, use safe injection technique ____

A

aspiration

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