M & M CH 16 Local Anesthetics Flashcards

1
Q

Na channels exist in at least three resting states

A

Resting (nonconducting)
Open (conducting)
Inactivated (nonconducting)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are the subunits of Voltage-gated sodium channels

A

One large alpha subunit
One or two Beta subunits

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Sensitivity of nerve fibers to inhibition by LAs is influenced by

A

Axonal diameter
Myelination
And other factors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

LA potency correlates with

A

Octanol solubility
Ability for LA to penetrate lipid membranes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

(T/F) Adding large alkyl groups to LAs decrease potency

A

FALSE it increases potency

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

(T/F) LA potency can be measured with MAC (minimum alveolar conc.)

A

FALSE no clinical measurement of LAs potency that is comparable to MAC exists

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Factors that affect onset of action of LA

A

lipid solubility
relative conc of the nonionized (free-base) form (B) and the ionized water-soluble form (BH+)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

The pKa is the pH at which there is an ____
fraction of ionized and nonionized drug

A

equal

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is the significance of the pKa in LA?

A

pKa represents the pH at which there is an equal fraction of ionized and nonionized drug

*plays a crucial role in determining the onset of action.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Mepivacaine and Lidocaine have (faster/slower) onset than more potent more lipid-soluble agents like ropivacaine or bupivacaine

A

Faster

*lipid soluble agents have a longer DOA but slower onset of action bec they slowly diffuse from lipid rich environment to aq. bloodstream

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

How do less potent and less lipid-soluble LAs compare in terms of onset?

A

Less potent and less lipid-soluble LAs have a faster onset compared to more potent, more lipid-soluble LAs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What determines the elimination and toxicity of local anesthetics in the blood?

A

pharmacokinetic profiles of LAs in blood are important in determining their elimination and toxicity.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Rank order of LA conc in blood and absorption r/t vascularity of site of injection

A

intravenous (or intraarterial) > tracheal > intercostal > paracervical > epidural >
brachial plexus > sciatic > subcutaneous

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Which injection site has the highest systemic absorption?

A

Intravenous (or intraarterial) injections

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Ester LAs are metabolized by

A

pseudocholinesterase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Amide LAs are metabolized by

A

(N-dealkylation and hydroxylation) by microsomal P-450 enzymes in the
liver.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

(T/F) In awake pt’s, rising LA conc in CNS produce signs of LA tox

A

True

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

(T/F) Major cardiovascular toxicity usually requires about three times the
local anesthetic concentration in blood as that required to produce
seizures

A

True

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Intravascular injection of this LA can cause cardiovascular toxicity. Including left
ventricular depression, av heart block, v-tach and v-fib

A

Bupivacaine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Hypersensitivity RXN’s (w/IgG & IgE) to LA are uncommon but can occur with

A

Ester compounds (i.e. procaine, benzocaine)
*PABA derivative compounds

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

resting membrane potential

A

-60 to -70 mV

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

transport of three sodium (Na) ions out of the
cell for every two potassium (K) ions it moves into the cell

A

sodium–potassium pump
(Na+-K+-ATPase)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

creates a conc gradient that favors movement of K ions from intracellular to extracellular and movement of Na ions in opposite direction

A

sodium–potassium pump
(Na+-K+-ATPase)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

(T/F) cell membrane is much more “leaky” to Na
ions than to K ions, so a relative excess of negatively charged ions (anions)
accumulates intracellularly.

A

FALSE

There are more “Leaky” K ions than Na ions

*combined effects of Na+-K+-ATPase and K
ion leak account for the negative resting membrane potential

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Can generate action potentials
neurons or myocytes
26
These channels can produce and transmit membrane depolarization following chemical, mechanical and/or electrical stimuli.
voltage-gated Na channels in peripheral nerve axons
27
(T/F) Activation of voltage-gated Na channels causes a very brief (roughly 1 ms) change in the conformation of the channels, allowing an influx of Na ions and generating an action potential
True
28
The increase in Na permeability causes temporary depolarization of the membrane potential to
+35 mV
29
T/F When there is no more K+ influx, in voltage-gated Na ion channels the membrane returns to its resting potential
FALSE Occurs with Na ion influx, not K+
30
when can a signal be transmitted as a wave of depolarization along nerve membrane (impulse)
when stimulus is sufficient to depolarize membrane
31
Baseline conc gradients are maintained by ,
the sodium–potassium pump
32
(small/large) amount of Na ions pass into the cell during an action potential
small
33
When LA bind to ___ subunit, they prevent channel activation and Na influx through the individual channels
alpha
34
(T/F) LA binding to Na channels alters the resting membrane potential.
FALSE LA binding to Na channels DOES NOT alter the resting membrane potential
35
As more LAs bind to Na Channels, the threshold for excitation & impulse conduction in nerves (increases/decreases), the rate of rise and the magnitude of the action potential (increases/decreases), and impulse conduction velocity slows.
Increases Decreases
36
Why can action potentials no longer be generated when a sufficient fraction of Na channels have bound to LA?
LA prevents the normal influx of Na ions thru Na channels during depolarization, leading to the inability to generate action potentials.
37
What state of Na channels do LA have a greater affinity for: open, inactivated, or resting?
open or inactivated state
38
Explain the relationship between LA conc and the loss of action potentials
As LA conc increase, more Na channels become blocked, resulting in the loss of action potentials and the termination of impulse transmission.
39
How does the opening of channels during depolarization impact LA action?
As channels open during depolarization, they expose binding sites for local anesthetics. This increased availability enhances likelihood of LA binding to the channels and blocking sodium influx.
40
What is the term for the phenomenon where the fraction of Na channels binding a LA increases with frequent depolarization?
“use-dependent block” refers to the ↑binding of LAs to Na channels when nerve fibers experience frequent depolarizations.
41
Why is LA binding greater when nerve fibers experience frequent depolarizations compared to less frequent ones?
Frequent depolarizations increase the proportion of Na channels in open or inactivated states. These states are more susceptible to LA binding. ↑depolarization rates enhance LA efficacy.
42
What channels and receptors can LA bind and inhibit?
Ca++ K+ transient receptor potential vanilloid-1 (TRPV1) +many other channels and receptors.
43
tricyclic antidepressants (amitriptyline), meperidine, volatile anesthetics, Ca channel blockers, α2-receptor agonists, and nerve toxins may also inhibit
Na channels
44
Factors that influence the sensitivity of nerve fibers to inhibition by local anesthetics
axonal diameter myelination and other factors
45
Which type of nerve fibers are less sensitive to LA: Aα or Aδ fibers?
Larger, faster-conducting Aα fibers are less sensitive to local anesthetics than smaller, slower-conducting Aδ fibers.
46
(T/F) Larger unmyelinated fibers are less sensitive than smaller unmyelinated fibers.
TRUE smaller diameter = ↑sensitivity and ↓conduction velocity
47
(T/F) Small unmyelinated C fibers are sensitive to LA
FALSE small unmyelinated C fibers are relatively resistant to inhibition by LA compared to larger myelinated fibers.
48
What happens at steady state if sensory anesthesia is present?
all modalities are inhibited
49
Typical sequence of LA inhibition in a human peripheral nerve
autonomic before sensory before motor.
50
two main components of LAs
lipophilic group (usually an aromatic benzene ring) and a hydrophilic group (usually a tertiary amine) separated by an intermediate chain.
51
How are LAs classified based on the nature of the intermediate chain?
classified as either esters or amides based on the nature of the intermediate chain.
52
What charge do LAs carry at physiological pH?
LAs are weak bases and usually carry a positive charge at the tertiary amine group under physiological conditions.
53
(T/F) Articaine has a benzene ring
FALSE Articaine has a thiophene ring
54
The physicochemical properties of LAs depend on
substitutions in the aromatic ring the type of linkage in the intermediate chain the alkyl groups attached to the amine nitrogen
55
factors that correlate with clinical LA potency
octanol solubility ability to permeate lipid membranes.
56
factors that affect the minimum concentration of LA needed to block nerve impulse conduction
Fiber size, type, and myelination pH (an acidic environment antagonizes clinical nerve block) Frequency of nerve stimulation Electrolyte concentrations (hypokalemia and hypercalcemia antagonize blockade)
57
which is more potent due to larger alkyl group: bupivacaine or mepivacaine
bupivacaine
58
Does the onset of action directly correlate with the pKa of local anesthetics?
No, onset of action doesn't directly correlate with the pKa of LA For example, 2-chloroprocaine has the greatest pKa but has most rapid onset
59
How does the presence of epinephrine affect LA solutions?
Commercially formulated LA solutions w/epi are more acidic (pH 4–5) due to epi’s instability in alkaline environments. Acidity may result in a lower fraction of free base and a slower onset compared to plain solutions w/out epi
60
An example of a LA that does not exist in a charged form.
benzocaine
61
infected tissues effect on LAs
pH in infected tissue is more acidic, so LAs will be more in IONIZED form have a slower onset of action
62
What substance is commonly used for alkalinization n LA?
Sodium bicarbonate (8.4% solution) is often added to local anesthetic solutions to achieve alkalinization.
63
recommended ratio of sodium bicarbonate to LA
1 mL of 8.4% sodium bicarbonate is added per 10 mL of LA
64
Besides improving onset and quality, what additional benefit does alkalinization of LAs offer during subcutaneous infiltration?
alkalinization also decreases pain during subcutaneous infiltration procedures
65
proteins that primarily bind local anesthetics in the blood
mostly by α1-acid glycoprotein to a lesser extent, by albumin.
66
Which local anesthetics display some selectivity for sensory nerves?
Bupivacaine and ropivacaine exhibit some selectivity, especially during the onset and offset of block, for sensory nerves. However, the conc req. for anesthesia often result in some motor blockade.
67
How does absorption after topical application vary based on the site?
Most mucous membranes (such as tracheal or oropharyngeal mucosa) provide a min. barrier to LA penetration, resulting in a rapid onset of action. intact skin req. topical application of an increased conc. of lipid-soluble LA to ensure permeation and analgesia.
68
This is formulated to overcome the obstacles presented by intact skin.
EMLA cream *A mixture of lidocaine and prilocaine bases in an emulsion
69
Systemic absorption of injected LAs depends on blood flow, which is determined by
Site of injection Presence of additives Local anesthetic agent
70
Distribution depends on organ uptake, which is determined by
Tissue perfusion Tissue/blood partition coefficient Tissue mass
71
The addition of epinephrine causes vasoconstriction at the injection site, resulting in
Reduced peak local anesthetic concentration in blood Facilitated neuronal uptake Enhanced quality of analgesia Prolonged duration of analgesia Reduced toxic side effects
72
(T/F) Vasoconstrictors have more pronounced effects on shorter-acting agents than on longer-acting ones.
TRUE *adding epinephrine to lidocaine (short-acting) extends anesthesia duration significantly, but its effect on bupivacaine (long-acting) peripheral nerve blocks is limited
73
How can dexamethasone or other steroids affect local anesthetic blocks?
Coadministration of dexamethasone or other steroids with LAs can prolong blocks by up to 50%.
74
(More/Less) lipid-soluble LAs that are highly tissue bound are more slowly absorbed than less lipid-soluble agents
More
75
factors that influence the distribution of LAs in the body
tissue perfusion tissue/blood partition coefficient and tissue mass.
76
Which organs play a crucial role in the initial rapid removal of local anesthetics from the blood?
Highly perfused organs -->brain, lung, liver, kidney, and heart
77
What happens after the initial rapid removal of local anesthetics from the blood?
a slower redistribution of local anesthetics to a wider range of tissues
78
Why are patients with right-to-left cardiac shunts more susceptible to toxic side effects of lidocaine?
because the lung extracts significant amounts of LA during the “first pass,” leading to ↑exposure and potential toxicity.
79
How does increasing lipid solubility affect the distribution of LA?
Greater lipid solubility is associated with ↑plasma protein binding and enhanced tissue uptake of LA from an aqueous compartment.
80
Which tissue provides the largest reservoir for local anesthetic distribution in the bloodstream?
Muscle *because of its large mass
81
Ester local anesthetics are predominantly metabolized by
pseudocholinesterase (aka butyrylcholinesterase)
82
Ester hydrolysis is rapid, and the water-soluble metabolites are excreted in
the urine
83
Are patients with genetically deficient pseudocholinesterase at increased risk for toxic side effects from ester local anesthetics?
Theoretically, yes. But, clinical evidence for this increased risk is lacking, likely bec alternative metabolic pathways are available in the liver.
84
How does cocaine differ in terms of metabolism compared to other ester anesthetics?
Cocaine is primarily metabolized via ester hydrolysis in the liver
85
What enzymes are involved in the metabolism of amide LAs?
by microsomal P-450 enzymes in the liver
86
How do decreases in hepatic function or liver blood flow affect amide metabolism? (e.g., due to cirrhosis, congestive heart failure, β-blockers, or H2-receptor blockers)
can reduce the rate of amide metabolism may lead to ↑blood conc. and an ↑risk of systemic toxicity
87
only local anesthetic that is metabolized to o-toluidine
Prilocaine *produces o-toluidine as a metabolite
88
The production of o-toluidine by prilocaine can result in
methemoglobinemia *in a dose-dependent manner.
89
(T/F) Classical teaching suggested that a defined dose of prilocaine (around 20 mg/kg) must be exceeded to produce significant methemoglobinemia
FALSE dose is around 10mg/kg
90
Recent studies have demonstrated that younger, healthier patients can develop medically important methemoglobinemia even after ___ doses of prilocaine (compared to older, sicker patients).
lower
91
What other LA ingredient (besides o-toluidine) can also cause dangerous levels of methemoglobinemia?
Benzocaine *common ingredient in topical local anesthetic sprays
92
Treatment of medically important methemoglobinemia includes
intravenous methylene blue (1–2 mg/kg of a 1% solution over 5 min) **Methylene blue reduces methemoglobin (Fe3+) to hemoglobin (Fe2+)
93
Why can increased circulating concentrations of LAs lead to systemic toxicity?
because voltage-gated Na channels, which regulate action potentials in neurons and impulse generation in heart, are affected
94
(T/F) Mixtures of local anesthetics have additive toxic effects
TRUE *injecting a solution combining 50% of a toxic dose of lidocaine and 50% of a toxic dose of bupivacaine is likely to produce toxic effects
95
Why are tables of “maximum safe doses” considered nearly nonsensical?
The maximum safe dose of LAs depends on various factors: including the patient, the specific nerve block, the rate of injection, and other individual considerations. Therefore, fixed tables of maximal safe doses are not practical
96
Local anesthetic systemic toxicity (LAST) refers to the adverse effects of
LAs affecting the CNS ** The CNS is particularly vulnerable to these toxic effects
97
Premonitory signs and symptoms of increasing LA conc. in awake patients?
Circumoral numbness Tongue paresthesia Dizziness Tinnitus Blurred vision A feeling of impending doom
98
Signs that indicate increasing LA conc. in awake patients
Restlessness Agitation Nervousness Garrulousness
99
What typically precedes tonic–clonic seizures in cases of LA toxicity?
Muscle twitching *often occurs before tonic–clonic seizures
100
How does the conc. of LAs relate to the risk of seizures?
Potent and highly lipid-soluble LAs can produce seizures at lower blood conc. compared to less potent agents
101
Benzodiazepines, propofol, and hyperventilation can (raise/lower) the seizure threshold
Raise *Propofol (0.5–2 mg/kg) quickly and reliably terminates seizure activity (as do comparable doses of benzodiazepines or barbiturates)
102
Both respiratory and metabolic acidosis (raise/lower) the seizure threshold.
Lower
103
intravenous ____ to terminate local anesthetic-induced seizures
lipid
104
What is most important in managing LA toxicity?
Maintaining a clear airway with adequate ventilation and oxygenation
105
______ infusions are used to inhibit ventricular arrhythmias
Lidocaine
106
Actions of infused LAs?
can inhibit ventricular arrhythmias decrease cerebral blood flow attenuate the rise in intracranial pressure during intubation for pt's with decreased intracranial compliance
107
(T/F) Infusions of lidocaine and procaine have been used to supplement general anesthetic techniques, as they are capable of reducing the MAC of volatile anesthetics by up to 60%.
FALSE 40%
108
What additional benefits do lidocaine infusions offer?
inhibit inflammation and reduce postoperative pain decrease postoperative opioid requirements, leading to shorter hospital stays after surgery
109
symptoms that indicate an overdose of cocaine
restlessness emesis (vomiting) tremors convulsions arrhythmias respiratory failure and cardiac arrest.
110
What complications were associated with unintentional injection of chloroprocaine into the subarachnoid space during epidural anesthesia?
total spinal anesthesia marked hypotension and prolonged neurological deficits
111
The neural toxicity associated with chloroprocaine may be due to a combination of its low pH and the presence of a preservative
sodium bisulfite *Chloroprocaine is available in a preservative (bisulfite)-free formulation that has been used safely and possibly proves that the compound itself has minimal direct neurotoxicity
112
Administration of this LA in continuous spinal anesthesia has been associated with cauda equina syndrome
5% lidocaine *possibly due to pooling of drug around cauda equina
113
(T/F) Lidocaine depresses the ventilatory response to low PaO2 (hypoxic drive)
True
114
apnea after administration of a “high” spinal or epidural anesthetic is nearly always the result of
hypotension and brain ischemia rather than phrenic block.
115
What effect does intravenous lidocaine have on reflex bronchoconstriction associated with intubation?
Intravenous lidocaine (1.5 mg/kg) may block the reflex bronchoconstriction sometimes associated with intubation.
116
tachycardia and hypertension can occur with LA concentrations that produce CNS excitation or from
injection or absorption of epinephrine (often combined with local anesthetics)
117
How do local anesthetics affect myocardial contractility and conduction velocity?
depress myocardial contractility and conduction velocity at higher blood concentrations
118
What causes the depression of myocardial automaticity (spontaneous phase IV depolarization)?
direct actions on the cardiac muscle membrane, through inhibition of cardiac Na channels In intact organisms, it can also occur due to inhibition of the autonomic nervous system.
119
At low concentrations, all local anesthetics inhibit ________ leading to vasoconstriction
nitric oxide
120
At higher concentrations, LAs (except cocaine) produce
smooth muscle relaxation and arterial vasodilation, including arteriolar vasodilation
121
T/F Major cardiovascular toxicity usually requires about twice times the LA conc in blood as that required to produce seizures
FALSE requires THREE times the LA conc
122
How is the HTN associated with laryngoscopy and intubation often attenuated?
can be mitigated by intravenous administration of lidocaine (at a dose of 1.5 mg/kg) 1–3 minutes prior to instrumentation.
123
usual presenting signs of cardiac local anesthetic systemic toxicity (LAST) during general anesthesia
Cardiac arrhythmias or circulatory collapse
124
Overdoses of lidocaine can lead to marked
left ventricular contractile dysfunction
125
What severe cardiovascular complications can result from unintended intravascular injection of bupivacaine during regional anesthesia?
severe cardiovascular LAST (local anesthetic systemic toxicity) including: left ventricular depression, atrioventricular heart block, and life-threatening arrhythmias such as ventricular tachycardia and fibrillation.
126
What are some predisposing risk factors for bupivacaine-induced toxicity?
pregnancy, hypoxemia, and respiratory acidosis. Young children may also be at increased risk
127
How does bupivacaine compare to lidocaine in terms of changes in conduction and arrhythmia risk?
bupivacaine is associated with more pronounced changes in conduction and a greater risk of arrhythmias than comparable doses of lidocaine.
128
What is the difference between the R(+) and S(–) optical isomers of bupivacaine?
The R(+) optical isomer of bupivacaine blocks more avidly and dissociates more slowly from cardiac sodium channels than the S(–) optical isomer (levobupivacaine or ropivacaine).
129
Is bupivacaine-induced cardiac toxicity be challenging to manage?
Yes. Its difficult and resistant to standard resuscitation drugs
130
alternative treatment for bupivacaine-intoxicated patients who do not respond to standard therapy
bolus administration of nutritional lipid emulsions at 1.5 mL/kg *Lipid emulsions are advocated as a first-line treatment for cardiovascular LAST
131
How does ropivacaine compare to bupivacaine in terms of motor block and therapeutic index?
Ropivacaine produces less motor block when injected at the same volume and conc as bupivacaine. appears to have a greater therapeutic index than racemic bupivacaine, likely reflecting its formulation as a pure S(–) enantiomer.
132
How are cocaine’s cardiovascular reactions different from other local anesthetics?
unlike those of any other local anesthetic Inhibits the normal reuptake of norepinephrine by adrenergic nerve terminals, thereby potentiating the effects of adrenergic stimulation.
133
cardiovascular responses are associated with cocaine
hypertension and ventricular ectopy
134
initial treatment for systemic cocaine toxicity
benzos to reduce central stimulation
135
use of cocaine when applied topically
produces vasoconstriction when applied topically useful agent to reduce pain and bleeding related to nasal intubation in awake patients
136
cocaine-induced arrhythmias treatment
with α-adrenergic antagonists and amiodarone
137
Commercial multidose preparations of amides often contain methylparaben, which has a chemical structure vaguely similar to that of
PABA *speculation on whether this preservative may be responsible for most of the apparent allergic responses to amide agents due to its similarity to PABA
138
Local anesthetics are mildly _____ when directly injected into skeletal muscle, either intentionally (e.g., trigger-point injection treatment of myofascial pain) or unintentionally.
myotoxic
139
What is the usual regeneration time after injection-induced myotoxicity?
Regeneration usually occurs within 4 weeks after the injection
140
Compounding the local anesthetic with steroid or epinephrine (worsens/improves) myonecrosis.
worsens
141
When infused into joints for prolonged periods, local anesthetics can produce severe
chondromalacia
142
How does lidocaine affect normal blood coagulation?
mildly depresses normal blood coagulation, leading to reduced thrombosis and decreased platelet aggregation.
143
What effect do α2-adrenergic agonists (e.g., clonidine) have on LA analgesia?
α2-adrenergic agonists potentiate LA analgesia produced after epidural or peripheral nerve block injections
144
What is the role of pseudocholinesterase in the metabolism of succinylcholine and ester LAs?
Both depend on pseudocholinesterase for metabolism. However, no evidence that the potential competition between ester local anesthetics and succinylcholine for the enzyme has any clinical significance
145
How might epidural chloroprocaine interfere with neuraxial morphine’s analgesic actions?
may interfere with the analgesic actions of neuraxial morphine, particularly after cesarean delivery
146
How do opioids affect analgesia produced by epidural and spinal local anesthetics?
Opioids potentiate the analgesia produced by epidural and spinal local anesthetics
147
Which drugs decrease hepatic blood flow and affect amide local anesthetic clearance?
H2-receptor blockers and β-blockers decrease amide local anesthetic clearance by reducing hepatic blood flow
148
What can prolong the metabolism of ester local anesthetics?
Pseudocholinesterase inhibitors (e.g., organophosphate poisons) can prolong the metabolism of ester local anesthetics
149
How does dibucaine relate to genetically abnormal pseudocholinesterases?
Dibucaine (an amide local anesthetic) inhibits pseudocholinesterase. The extent of inhibition by dibucaine defines one form of genetically abnormal pseudocholinesterases.