LOCAL ANAESTHETICS Flashcards
Local anaesthetics prevent or relieve pain by _______________
They bind to a specific receptor site within the pore of the _____ channels in nerves and ___________ through this pore
interrupting nerve conduction
Na
block ion movement
Cocaine was discovered by _______ in ______ century
Indian natives chewed _______ extract of C.________ for its stimulatory and euphoric effects
Cocaine 1st Isolated by ______ in ____
He tasted it and noted that it caused a _________________
______________ studied cocaine physiological actions
serendipity
19th century; alkali
C.erythroxylum
Niemann in 1860
numbing of the tongue
Sigmund Freud
Cocaine is an ______ of ______ acid and the complex alcohol ______________________________
ester; benzoic
2-carbomethoxy,3- hydroxyl-tropane
Procaine was synthesized in ______
Hydrophilic moiety could be ______ or _______
Hydrophobic moiety must be _______
1905
tertiary or secondary amine
Aromatic
Cocaine
Ester (hydrolysed by __________ )or ______ linked (liver amidases)
Hydrophobicity increases both the ______ and the _________
Association of the drug at _______ sites enhances the __________ of the drug
plasma esterases; amide
potency; duration of action
hydrophobic; partitioning
SAR
Hydrophobicity also enhances _____ hence decreased ______
Molecular sizes influences ___________ from receptor site
Important In ________ tissues in which local anaesthetic bind during AP and dissociate During the period of ________________________.
_______ binding of local anaesthetic during action potential allows the _______ and ________ dependence of their action
toxicity ;Therapeutic index
rate of dissociation ; rapidly firing
membrane repolarization.
Rapid ; frequency
voltage
MOA
Local Anesthetic prevent the _________ and the _________ of the nerve impulse
Local Anesthetic block conduction by decreasing the (small or large?) (transient or prolonged?) increase In the permeability of excitable membranes to ______ that normally produceds ______________ of the membrane, Due to direct interaction with _______ gated _____ channels.
As the Local Anesthetic action progressively develops in a nerve, the threshold for ___________ gradually ______eases
generation ; conduction
large transient ; Na
light depolarization
voltage ; Na
electrical excitability ; increases
Frequency and voltage dependence of local anaesthetic
The degree of block depends on _________________________ and on its __________________
Resting nerve is much (more or less?) sensitive than repetitively stimulated
Higher frequency of stimulation the (more or less?) positive membrane potential cause a greater degree of anaesthetic block
nerve has been stimulated
resting membrane potentials
less ; more
Frequency and voltage dependence of local anaesthetic
local anaesthetic molecule in its ______ form gains access to its ______ site within the _____ only when the Na channel is in _______ state
They bind (Loosely or Tightly?) to and stabilizes the _________ state of the Na channel
local anaesthetic is slightly soluble as ____________________
Marketed as __________________ (HCl) thus increases their _______
It is the _______ species that interact with Na channels
charged ; binding
pore ; open state
tightly ; inactivated
unprotonated amines
water soluble salts (HCl); stability
cationic
Local Anesthetic Structures: Esters vs. Amides
Main issue:__________
Esters
Ester hydrolysis by _________
Amides
N-_______and ______ in the _____
If This patient has pre-existing ____ disease- we would worry about _______________
metabolic pathway
Hydrolysis; plasma cholinesterase
dealkylation; hydroxylation; liver
liver; accumulation of the drug
Entiomers
Substances of ______ shape
– Molecules existing in _______forms
Left and right handed
When dissolved in solution , they ______ polarized light
– _______ isomers
opposite
mirror image
rotate
– Optical
Important concept in local anesthetic toxicity
–______ handed molecules such as _______ are more toxic
Right
bupivacaine
Types of local anesthetic
_________
______ block
_________ block
IV
______ (CSF)
_________
Infilteration
Field
Nerve
Spinal
Epidural
Both ionized and non-ionized forms of Local Anesthetics are needed for function
T/F
T
In infected tissue, the local anesthetic is completely (ionized or non-ionized?) and won’t work- hence the need for _______ or _______
ionized
sedation
General anesthesia
Systemic Toxicity
CNS toxicity: due to ______ serum local
anesthetic blood levels
–___________________________________ is the most common etiologic factor in severe systemic reactions
•Toxicity can be gradual
– Same variables:
•Site, vascularity, total dose, use of a vasoconstrictor…
peak
Accidental intravascular injection
Systemic Toxicity
Symptoms: _________ symptoms to ______ or ______
Excitatory symptoms: Selective ————- of __________ neurons
Depression of CNS
______ channel block ______
Mild neurological
coma or death
depression of inhibitory
Na; centrally
Lipid soluble agents are (more or less?) potent and more toxic
More
Treatment of Toxicity
Get _______
Airway
–_______,_________, intubation or airway equipment
Drugs to stop seizure
____________,_________
•Other drugs/interventions
______________ management
assistance
Oxygen, ventilation
– Benzodiazepines, Barbiturates
Post seizure
Site of Injection: Likelihood of Toxicity
Most = ______> ________>_______
Least=________ < ___________
IV, Tracheal, Intercoastal
Subcutaneous , Sciatic/Femoral
LA
Duration =______ Binding = ____ Solubility
– Protein binding.
• increased protein binding = ______eased duration
– Lipid solubility
• increased lipid solubility= ______eased duration
Protein; Lipid
Increased
Increased
Adjuncts also _______ Duration
Eg Vaso_______
Prolong
constrictors
Adjuncts of LA
Vasoconstrictors
– _________/________/ ________
•________ duration
•( Minimize or Maximize?) effect of LA vaso ________
•_____eased toxicity
•_____ease intensity of block
•_____eased bleeding
Epinephrine/Phenylephrine/ Levonordefrin
Prolong; Minimize
dilatation
Decr; incr; Decr
Most drugs must enter the circulation to attain therapeutic blood levels before they can exert their clinical action
local anesthetics, on the other hand, _______________________________________
cease to provide any clinical effect once they leave the site of administration and enter into the blood stream
Uptake of Local Anesthetics
all local anesthetics possess some degree of vasoactivity; most producing some level of vaso____
ester local anesthetics are potent vaso_______ drugs
dilation; dilating
Uptake of Local Anesthetics
Procaine (_______) possesses tremendous vaso________ abilities which are employed to halt _________
(________________)
Novocaine
dilating; arteriospasm
accidental IA injection
Uptake of Local Anesthetics
_______is the only local anesthetic that consistently produces vasoconstriction
Cocaine
Cocaine
initial vaso_________ intense vaso____________
dilation
constriction
vasodilation leads to ______eased rate of
absorption of the local anesthetic into the blood, thus decreasing the _________ and ________ of _________ while increasing the ______________________ and potential for ______ (_____ reaction)
increased; duration
depth of pain control
anesthetic blood concentration
overdose (toxic reaction)
Distribution of Local Anesthetics
once in the blood, local anesthetics are distributed to ____ tissues
brain, head, liver, lungs, kidneys and spleen have high levels of local anesthetics due to their _____________
skeletal muscle has the highest level because it has the ______________
all; high level of perfusion
largest mass of tissue in the body
_____________ has the highest level of distributed local anesthetic
skeletal muscle
The blood level of local anesthetics is influenced by:
1) Rate at which the drug is _______ into the cardiovascular system
2) Rate of ________ from the vascular compartment to the tissues
3)________ of the drug through metabolic or excretory pathways
absorbed
distribution
Elimination
Only some local anesthetics cross the blood brain barrier
T/F
F
All local anesthetics cross the blood brain barrier
All local anesthetics cross the placenta and enter the blood stream of the developing fetus
T/F
T
PABA Metabolism (_________ Acid)
Ester Local Anesthetics: plasma ________
•hydrolyzed in the plasma by the enzyme ____________
•the rate of hydrolysis is related to the degree of _________
ParaAminoBenzoic
pseudocholinesterase,
pseudocholinesterase
toxicity
Tetracaine is hydrolyzed the (slowest or fastest?) which makes it ____ times (more or less?) toxic than _____ which is hydrolyzed the (slowest or fastest?)
Slowest
16; more
Chloroprocaine
Fastest
Slower Hydrolyzation = ____eased Toxicity
Increased
Metabolism of Local Anesthetics
2) Amide Local Anesthetics:
primary site of metabolism of amide local anesthetics is the _____
Prilocaine is metabolized in the ____________
liver
liver and lung
virtually the entire metabolic process occurs in the ________ for Lidocaine, Mepivicaine, Articaine, Bupivacaine and Etidocaine
liver
______ function and hepatic ______ greatly affect the rate of metabolism (biotransformation) of amide local anesthetics
liver
perfusion
significant ______________ (ASA IV/ASA V patients) represents a relative contraindication to the use of amide local anesthetics
liver dysfunction
Articaine has a (shorter or longer?) half-life than other amides because a portion of its metabolism occurs in the ________________
Shorter
blood by plasma cholinesterase
metabolism byproducts of _____ local anesthetics can possess clinical activity if allowed to ______ in the blood
amide
accumulate
All local anesthetics have the ability to cause sedation
T/F
T
large doses of Prilocaine can produce a side effect called __________
___________ , a primary metabolite of Prilocaine, induces the formation of methemoglobin
Methemoglobinemia
orthotoluidine
large amounts of Lidocaine produce a ________ effect which is due primarily to two metabolites _________ and _______________
sedation
glycine xylidide and monoethylglycinexylidide
If the local anesthetic has two “i”s in its name; it’s an (ester or amide?)
Amide
Excretion of Local Anesthetics
_________ are the major excretory organs for both local
anesthetics
esters appear in very (small or large?) concentrations in the urine; this is because they are almost completely __________
kidneys; small; hydrolyzed in plasma
Excretion of Local Anesthetics
Procaine (Novocaine) appears in the urine as 90% _____ and 2% _________
10% of Cocaine is found _______ in the urine
PABA; unchanged
unchanged
Excretion of Local Anesthetics
patients undergoing ——— are likely to be unable to excrete the _______ portion of the esters or amides thus increasing toxicity
dialysis
unchanged
Systemic Actions of Local Anesthetics
the pharmacological action of local anesthetics on the CNS is ________
At high levels, local anesthetics will produce ______-______ ————-
depression
tonic- clonic convulsions
Systemic Actions of Local Anesthetics
Procaine, Lidocaine, Mepivacaine, Prilocaine and Cocaine generally produce anti-________ properties; this occurs at a blood level considerably (below or above?) that at which the same drugs cause seizures
convulsant
Below
Procaine, Lidocaine and Mepivacaine have been used therapeutically to terminate or decrease the duration of ___________________________________ seizures; anti-convulsant levels
(.___to ___ micrograms/ml)
both grand mal and petit mal
5 to 4
The depressant action of local anesthetics raise the ________ by decreasing the ______ of cortical neurons in epileptic patients
seizure threshold
excitability
Preconvulsive Signs and Symptoms
_______ of the tongue and circumoral regions
anesthetic has been transported to these areas by the _________ rather than the _________ of the anesthetic
if ______ or ______ occurs in the first 5 to 10 minutes after local anesthetic delivery, it should serve as a warning that convulsive activity could be possible
numbness
cardiovascular system ; local delivery
excitation or sedation
U.S. Air Force an U.S. Navy pilots are grounded for ______ following administration of ______ due to its mild effects of ______ and/or drowsiness
24 hours
Lidocaine
sedation
Convulsive Phase
duration of seizures is related to _______ of anesthetic and inversely related to ___________ evels
at a normal pCO2, a Lidocaine blood level between 7.5 and 10 micrograms/ml usually result in a convulsive episode
when CO2 levels are increased, the blood level of local anesthetic necessary for seizures _____eases while the duration of the seizure _____eases
seizures usually last _____________________
cerebral blood flow and cerebral metabolism _____ease during a seizure
_____eased blood flow to the brain leads to an increase in the __________________________________________ to the brain causing a (shorter or longer?) seizure
blood level ; arterial pCO2 levels
decreases ;increases
less than or equal to one minute
increase; increased
volume of local anesthetic being delivered
longer
Convulsive Phase
-____eased cerebral metabolism leads to (acidosis or alkalosis?) which (shortens or prolongs ?) the seizure activity even in the presence of declining local anesthetic levels in the blood
-seizures gradually subside , leading to generalized CNS _______ , respiratory _________ , respiratory ________, death
incr; acidosis; prolongs
depression; depression
arrest
local anesthetics have a direct action of the myocardium and peripheral vasculature
T/F
T
(CVS or CNS?) is more resistant to the effects local anesthetics than the (CVS or CNS?)
CVS
CNS
Cardiovascular Effects of Local Anesthetics
increased local anesthetic blood levels result in _______ eased myocardial depolarization, with ,________ in resting membrane potential and ____________ of the stages of repolarization
decr
no change
no prolongation
local anesthetics ____ease myocardial excitation, ____ease conduction rate and _____ease the force of contraction
decr; decr; decr
Heart
Lidocaine is used therapeutically for _____________ contractions (PVCs) and ventricular ________
Local anesthetics cause ____tension from the direct _______ action on vascular smooth muscle
pre-ventricular
tachycardia
hypo
relaxant
Lung Toxicity
local anesthetics have a direct ______ action on bronchial smooth muscle
generally, respiratory function is _______ by local anesthetics until ______ levels are achieved
relaxant
unaffected
near overdose
Local Tissue Toxicity
skeletal muscle will heal within _______ of being injected with local anesthetic
longer acting local anesthetics ( _________ ) produce (more or less?) damage to skeletal muscle than do shorter acting agents
two weeks
Bupivacaine
More
Malignant Hyperthermia:
pharmacogenic disorder in which a _________ alters the person’s _______________. Tachycardia, tachypnea (rapid breathing), unstable blood pressure, cyanosis, fever muscle rigidity and death; 68% mortality rate.
genetic variant
response to certain drugs
Malignant Hyperthermia Association of the U.S. determined that there are no documented cases in Dental or Medical literature supporting the concept of _______ local anesthetics triggering malignant hyperthermia
amide
Local and regional anesthesia involves the reversible ______ of a ________ to prevent ______________ without rendering ________
numbing
specific region of the body
any sensation of pain
the patient unconscious
Local anesthesia involves reversibly blocking __________ and _______ near the site of administration (limited area)
Regional anesthesia involves reversibly blocking nerve areas and pain conduction of a __________
Both forms makes use of special drugs called _____________________
nerve endings and pain conduction
large part of the body
LOCAL ANESTHETICS
TYPES
Local Anesthesia
–______
–__________
Regional Anesthesia
– _________
– _________
– _________
– _________ block
– _________ block
Topical; Infiltration
– Epidural
– Spinal
– Caudal
– Sympathetic block – Limb block
CHEMISTRY
Local anesthetic agents are composed of –_________________ portion
–____________
–_________________ portion
Lipophilic aromatic
Intermediate chain
Hydrophilic amine
CHEMISTRY
The intermediate chain has either an _______ linkage or an _______ linkage
ESTER
AMIDE
CLASSIFICATION of LA
ESTERS
LIST 5
AMIDE
LIST 6
Cocaine
Benzocaine
Chloroprocaine
Procaine
Tetracaine
Lidocaine .
Bupivacaine.
Ropivacaine.
Etidocaine.
Mepivacaine.
Prilocaine.
Cocaine
– Used ________
– Has a (slow or rapid?) onset of action; ___
– Duration of up to ———
– Causes VASO________ unlike others
– Lower concentrations are used for the ______
– Higher ones are used on the _______ and ________ mucosa.
topically
Rapid; 1 minute
2 hours; CONSTRICTION
eye; nasal and pharyngeal
Cocaine
– It can be occasionally combined with _______ cocaine
– This can be ______ because the _______ potentiates the ______ toxicity
– It can also _______ the CNS leading to ———— and __________ (e.g., restlessness, excitement)
– Overdosage leads to ———- followed by CNS __________
Epinephrine
hazardous; catecholamine; cardiovascular
stimulate; euphoria and cortical stimulation
convulsions; depression.
Benzocaine
– Benzocaine is a _____ derivative
– Used ______ on the ———- and ———
– Has a (low or high?) rate of absorption
– (Low or High?) incidence of systemic toxicity.
– Contraindicated in patients with known sensitivity to ____-linked anaesthetics or _____-containing compounds.
PABA
topically; skin and mucous surface
Low ; low
ester; PABA
Chloroprocaine
– Formed from the combination of ______ and ————
– Has a (lesser or greater?) potency and (more or less?) toxicity than ordinary procaine
– (Slowly or Rapidly?) hydrolysed cholinesterase ((short or. Long?) T1/2)
– Commonly used in __________.
CHLORINE and PROCAINE
Greater ; less
Rapidly; short
obstetrics
Procaine
– (Slowly or Rapidly?) ______ by _______
– Not effective _______
– Employed for _______, ____ block, and ______ anaesthesia.
– Relatively (slow or rapid?) onset
– Has a (short or long?) duration of action; _______
– Can be combined with ________.
– Available in _________ with __________ as the vasoconstrictor.
Rapidly hydrolysed by plasma cholinesterase
topically
infiltration, nerve block, and spinal anaesthesia.
slow; short ; 1 hr
epinephrine ; dental cartridges
phenylephrine
Tetracaine
– It is an _________ of _________
– Usually given _________
– Can also be used for _________ anaesthesia.
– Can be combined with _________
– It has approximately a ____-minute onset
– About _________ duration of action.
ester ; PABA
topically; spinal
Epinephrine; 5-minute
2 to 3 hours
Tetracaine is considerably (more or less?) potent and (more or less?) toxic than procaine and cocaine.
More
More
Lidocaine
- Used in _______, ________ blocks, _____ and _______ anesthesia
–
– Has anti-_________ properties
– Has a (slower or faster?) onset and duration of action than procaine.
infiltration, regional nerve blocks, spinal and topical anesthesia
anti-arrhythmic properties
faster
Most commonly used Local anesthetic is ???
Lidocaine
Bupivacaine
– Has particularly (short or long?) duration of action; ______
– Often used for _________________________
– Also used for _______ anaesthesia in obstetrics
– Can be combined with ________
long ; 24 hrs
post- operative analgesia.
epidural anaesthesia
Epinephrine
Most potent local anaesthetic agent is ????
Bupivacaine
Ropivacaine
– Recently developed (short or long?) -acting _____-linked local anesthetic.
– Its primary advantage over bupivacaine is its lesser degree of __________.
long ; amide
cardiotoxicity.
Ropivacaine
Its duration of action is similar to that of _________, but it is slightly (more or less?) potent and requires (lesser or higher?) concentrations to achieve the same degree of block.
bupivacaine
Less
Higher
Etidocaine
– Chemically similar to ________
– Has a (more or less?) prolonged action than lidocaine
– Used for ________ blocks, including ________ anesthesia.
– Its use in ________ is limited
– Can be combined with ________.
lidocaine; more
regional ;epidural
obstetrics ;epinephrine.
Mepivacaine
– (Shorter or Longer?) acting than lidocaine
– Has a more (gradual or rapid?) onset of action (—————).
– _________ application is not effective.
Longer
rapid ;3–5 minutes
Topical
Mepivacaine
– It has been widely used in _________, but its use has declined recently because of the ____________________________ effects it produces.
– It can be used with _______ or _______ (_____ use only).
obstetrics
early transient neurobehavioral
epinephrine or levonordefrin
dental
Prilocaine
– Onset of action is slightly (shorter or longer?) than that of lidocaine
– Duration of action is ________.
– Prilocaine is 40% (more or less?) toxic acutely than lidocaine
– Suitable for _______ anesthetia
– Metabolized by the ____ to ________,
– Metabolite can cause _____________.
longer ; comparable.
less ; regional anesthetia
liver ; orthotoluidine
METHAEMOGLOBINEMIA.
ADVERSE EFFECT :Specific
– Procaine
——————— ————-
– Prilocaine
________________
Eczematoid dermatitis
Methaemoglobinaemia
General adverse effect
Cardiovascular
Vaso____ (except _______)
_____tension
_______arrhythmia
dilation
Cocaine
Hypo
Brady
