LOCAL ANAESTHETICS Flashcards by Iseoluwa Ojo

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

block ion movement

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

Cocaine is an ______ of ______ acid and the complex alcohol ______________________________

ester; benzoic

2-carbomethoxy,3- hydroxyl-tropane

How well did you know this?

Not at all

Perfectly

Procaine was synthesized in ______

Hydrophilic moiety could be ______ or _______

Hydrophobic moiety must be _______

1905

tertiary or secondary amine

Aromatic

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

Important concept in local anesthetic toxicity

–______ handed molecules such as _______ are more toxic

Right

bupivacaine

How well did you know this?

Not at all

Perfectly

Types of local anesthetic

_________
______ block
_________ block
IV
______ (CSF)
_________

Infilteration

Field

Nerve

Spinal

Epidural

How well did you know this?

Not at all

Perfectly

Both ionized and non-ionized forms of Local Anesthetics are needed for function

T/F

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

Lipid soluble agents are (more or less?) potent and more toxic

How well did you know this?

Not at all

Perfectly

Treatment of Toxicity

Get _______

Airway
–_______,_________, intubation or airway equipment

Drugs to stop seizure
____________,_________
•Other drugs/interventions

______________ management

assistance

Oxygen, ventilation

– Benzodiazepines, Barbiturates

Post seizure

How well did you know this?

Not at all

Perfectly

Site of Injection: Likelihood of Toxicity

Most = ______> ________>_______

Least=________ < ___________

IV, Tracheal, Intercoastal

Subcutaneous , Sciatic/Femoral

How well did you know this?

Not at all

Perfectly

Duration =______ Binding = ____ Solubility

– Protein binding.
• increased protein binding = ______eased duration

– Lipid solubility
• increased lipid solubility= ______eased duration

Protein; Lipid

Increased

How well did you know this?

Not at all

Perfectly

Adjuncts also _______ Duration

Eg Vaso_______

Prolong

constrictors

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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

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

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

(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