Transcript local anesthetic agents

Pharmacology DENTALELLE TUTORING
Chapter 9
WHY IS EPI USED IN LOCAL
ANESTHETICS?
PROLONG DURATION
MEANING..THE LOCAL ANESTHETIC LASTS LONGER TO
ENSURE PROPER FREEZING OF THE TOOTH AND TISSUES
WAS COCAINE USED AS AN
ANESTHETIC?
YES..
..BUT NOT ANYMORE! IT WAS QUICKLY RECOGNIZED FOR
ITS ADDICTING PROPERTIES.
WHAT ARE SOME EXAMPLES OF
LOCAL ANESTHETICS USED TODAY?
• The amide lidocaine (Xylocaine) was released
in 1952
• mepivacaine (Carbocaine) was released in
1960
• More recently, bupivacaine (Marcaine) has
been made available for dental use
TRUE OR FALSE…
NO LOCAL ANESTHETIC IN USE TODAY MEETS ALL THE
NECESSARY REQUIREMENTS
TRUE
BUT…MANY ACCEPTABLE AGENTS ARE AVAILABLE
 potent local anaesthesia
 reversible local anaesthesia
 should be followed by complete recovery without
evidence of structural or functional nerve damage
 absence of adverse systemic effects &
allergic reactions
 rapid onset & good duration
 should have moderate lipid solubility which allows an
anesthetic agent to diffuse across lipid membranes
of all peripheral nerves (motor, sensory, autonomic)
 adequate tissue penetration
 low cost
 long shelf life (stability in solution)
 ease of metabolism & excretion
WHAT ARE THE TWO GROUPS OF
LOCAL ANESTHETICS?
AMIDES AND ESTERS
CROSS-HYPERSENSITIVITY BETWEEN AMIDES AND ESTERS
IS UNLIKELY
• A resting nerve fiber has a large number of
positive ions on the outside and a large
number of negative ions on the inside
• The nerve action potential results in the
opening of sodium channels and an inward flux
of sodium (Na+)
• This results in a change in potential
• The outward flow of potassium (K+) ions repolarizes the
membrane and closes the sodium channels
HOW DO LOCAL ANESTHETICS WORK?
IN RELATION TO NERVE IMPULSES?
DECREASING PERMEABILITY TO
SODIUM IONS…
AFTER COMBINING WITH THE RECEPTOR, LOCAL
ANESTHETICS BLOCK CONDUCTION OF NERVE IMPULSES BY
DECREASING THE PERMEABILITY OF THE NERVE CELL
MEMBRANE TO SODIUM IONS
Local anesthetics slows or blocks
depolarization by reducing Na+
permeability into the nerve
cytoplasm, thus inhibiting the flow of
K+ out of the cell.
↓
interferes with the function of the
neurons
↓
prevents the propagation of action
potential (the reproduction of nerve
transmission)
↓
prevents the onset of nerve
conduction & blocks nerve impulse
formation
The mechanism of local anesthetics
involves action on Axons and
Sodium channels
Local anesthetics bind to sodium channels found in the
axons of nerves. They stop the propagation of the
electrical impulse along the axon.
ARE LOCAL ANESTHETIC AGENTS
WEAK OR STRONG BASES?
WEAK BASES
WHEN THE ACIDITY OF THE TISSUE ↑, (AS IN INSTANCES OF
INFECTION), THE EFFECT OF A LOCAL ANESTHETIC ↓
THEREFORE, THE LOCAL ANESTHETIC IS A WEAK BASES.
Absorption & L.A.
local
anaesthetic
(L.A.)
L.A.
tooth
• ↓ pH
• ↑ ionization
• ↑ [H+]
infection
L.A.
L.A.
EG: Lidocaine’s
pKa =7.9(Weak
base drug)
*Weak bases are
better absorbed when
the pH is greater than
the pKa
In the presence of infection, there may be a reduced clinical
effect of L.A. due to the ↓’d pH level. The infection site is
more acidic and more ionized and less likely to absorb the
L.A drug (weak base).
IF INFECTION IS PRESENT, HOW DOES
THE LOCAL ANESTHETIC REACT?
IT IS HARDER TO FREEZE –LIKELY
INFECTION MUST BE CLEARED BEFORE
FREEZING IS DONE.
IN THE PRESENCE OF AN ACIDIC ENVIRONMENT, SUCH AS
INFECTION OR INFLAMMATION, THE AMOUNT OF FREE BASE
IS REDUCED
WHAT DOES ADME STAND FOR?
VERY IMPORTANT!
ABSORPTION
DISTRIBUTION
METABOLISM
EXCRETION
WHAT IS ABORPTION?
ROUTE
ABSORPTION DEPENDS ON ITS ROUTE
WHEN INJECTED INTO TISSUES THE RATE DEPENDS ON THE
VASCULARITY OF THE TISSUES
Reducing the rate of systemic absorption of
a local anesthetic is important when it is
used in dentistry because the chance of
systemic toxicity is reduced.
– A vasoconstrictor is often added to the
local anesthetic to reduce the rate of
absorption.
WHAT CAN BE ADDED TO REDUCE
THE RATE OF ABSORPTION?
A VASOCONSTRICTOR
• Addition of vasoconstrictor to local anesthetic:
Reduces the blood supply to the area
so as to ↓ rate of diffusion of anaesthetic
into the blood vessels
this also prolongs the duration &
effectiveness of the desired action
decreases bleeding in the area
Limits systemic absorption
Reduces systemic toxicity
WHY IS REDUCING THE RATE OF
ABSORPTION SO IMPORTANT?
REDUCES SYSTEMIC TOXICITY
WHAT IS DISTRUBUTION?
LOCAL ANESTHETIC DISTRUBUTED
THROUGHOUT
LOCAL ANESTHETICS CROSS THE PLACENTA AND BLOOD BRAIN BARRIER
LA agents are metabolized differently, depending
on whether they are amides or esters.
• AMIDES: are metabolized primarily by the liver
• In severe liver disease or with alcoholism, amides may
accumulate and produce systemic toxicity
• ESTERS: are hydrolyzed by plasma
pseudocholinesterases and liver esterases
WHAT IS EXCRETION?
EXCRETED BY KIDNEYS
METABOLITES AND SOME UNCHANGED DRUG OF BOTH
ESTERS AND AMIDES ARE EXCRETED BY THE KIDNEYS
WHAT NERVE DOES LOCAL
ANESTHETIC BLOCK?
PERIPHERAL NERVE CONDUCTION
THE MAIN CLINICAL EFFECT OF LOCAL ANESTHETIC IS
REVERSIBLE BLOCKAGE OF PERIPHERAL NERVE
CONDUCTION
COMMON ORDER OF NERVE
FUNCTION LOSS
1. Autonomic *is the most sensitive to inhibition
by local anesthetic agents
2.
3.
4.
5.
6.
7.
8.
9.
Cold
Warmth
Pain
Touch
Pressure
Vibration
Proprioception
Motor
The order of loss
of nerve function
The order of nerve
impulse return:
opposite (reverse)
WHY ARE LOCAL ANESTHETICS
SUCCESSFUL IN TREATING ARRHYTMIAS?
WHAT DO PLASMA LEVELS HAVE TO
DO WITH LOCAL ANESTHETIC?
ADVERSE REACTIONS AND TOXICITY
• Although toxicity to local anesthetics is
rare in the doses normally used in
dentistry, patients can still suffer from a
classic toxic reaction.
LOCAL ANESTHETIC TOXICITY
causes stimulation of the CNS
including:
restlessness,
tremors
seizures
followed by CNS depression and
coma.
HOW MANY CARPS ARE MAX FOR
LIDOCAINE?
8.5 CARPS
WHY WOULD A HEMATOMA BE
PRODUCED?
POOR INJECTION TECHNIQUE OR
EXCESSIVE VOLUME
WOULD COULD RESULT IN RIDIGITY
OF MUSCLES?
MALIGNANT HYPOTHERMIA
• An autosomal dominant trait characterized by often
fatal hyperthermia with rigidity of muscles occurring
in affected people exposed to certain anaesthetic
agents
– particularly halothane & succinylcholine (G.A.’s)
• NOT related to amides!
– In the past, the belief was that the amide local
anesthetics might precipitate malignant hyperthermia, but
they are currently no longer implicated. Patients with a
family history of malignant hyperthermia can be given
amide local anesthetic agents.
IF A WOMAN IS PREGNANT AND
ANESTHETIC MUST BE GIVEN…
..WHAT IS BEST?
LIDOCAINE
WHAT TYPE HAS A GREAT POTENTIAL
FOR ALLERGY?
AMIDES OR ESTERS?
ESTERS
IF A PATIENT REPORTS A
HISTORY OF ALLERGIES TO ALL
LOCAL ANESTHETIC AGENTS
Can use antihistamine
diphenhydramine (Benadryl)
as a local anesthetic
• Antihistamines, because of their similarity in structure to
local anesthetics, have some local anesthetic action
– diphenhydramine (Benadryl) in a concentration of 1%
plus 1:100,000 epinephrine is recommended to be
given by injection to produce a block
– No prepared product is available; this combination
must be prepared from its constituents
WHICH INGREDIANT REDUCES
BLEEDING?
VASOCONSTRICTORS
IF A PATIENT HAS ASTHMA, HOW
MUST YOU BE CAREFUL?
ANTIOXIDANT IN LOCAL
THE ANTIOXIDANT FOR THE VASOCONSTRICTOR MAY
PRODUCE A HYPERSENSITIVITY REACTION THAT EXHIBITS
ITSELF AS AN ACUTE ASTHMATIC ATTACK
WHERE IS TOPICAL PLACED?
THE MUCOUS MEMBRANE OF THE
SKIN
I.
Amides (Only class of anaesthetics used
parenterally)
i.
ii.
iii.
iv.
I.
Lidocaine (Xylocaine)
Mepivacaine (Carbocaine)
prilocaine (Citanest; Citanest Forte)
bupivacaine (bu·piv·a·caine)
Esters (No esters are currently available in a
dental cartridge)
i.
ii.
iii.
procaine
propoxycaine
Tetracaine
**Esters are not used
in dentistry as local
anesthetics, but used
topically.
eg. Benzocaine.
SEE
NOTE
LA AGENT
NOTES
• procaine
• no longer used
• lidocaine (Xylocaine)
• most common used
• least painful
• can only use 100,000epi
• mepivacaine (Carbocaine;
Isocaine)
• shortest duration
• when no epi is needed.
• bupivicaine (Marcaine)
• Painful
• longest duration 6-8 hours
• articaine (Septocaine)
• the most potent
• prilocaine plain (Citanest)
• similar to lidocaine
• Prilocaine epi (Citanest Forte) • rapidly metabolized
WHAT IS THE MOST COMMON LA
USED IN DENTISTRY?
LIDOCAINE 2% - (1:100 000 EPI)
mepivacaine
(Carbocaine, Isocaine)
• similar effectiveness as lidocaine
• BUT is NOT effective topically.
• produces LESS vasodilation than lidocaine therefore
can be used as a 3% solution WITHOUT a
vasoconstrictor.
– BUT systemic toxicity more likely
• Is combined with levonordefrin (not epinephrine) as
the vasoconstrictor
– usual dosage in dentistry: 2% solution with 1:20,000
levonordefrin
• It can be used for SHORT procedures when a
vasoconstrictor is contraindicated.
– duration of action of about 30 minutes
prilocaine
(Citanest, Citanest Forte)
Severeal cases of
METHEMOGLOBINEMIA
(cyanosis of the lips & mucous membranes & occasionally respiratory &
circulatory distress)
have been reported with use of prilocaine
– should not be administered to patients in which
problems with oxygenation may be critical
WHICH ONE HAS THE LONGEST
DURATION OF ACTION?
MARCAINE
buprivacaine
(Marcaine)
• Has the longest duration of action.
– major advantage  greatly prolonged duration of
action.
– indicated in lengthy dental procedures when
pulpal anesthesia of greater than 1.5 hours is
needed or when postoperative pain is expected.
• Related to lidocaine & mepivacaine
• More potent but less toxic than the other
amides
• Available in dental cartridges as a 0.5%
solution with 1:200,000 epinephrine
WHAT IS BOTH AN ESTER AND AN
AMIDE?
ARTICAINE
The vasoconstrictors are members
of the autonomic nervous system
drugs called the
ADRENERGIC AGONISTS
or sympathomimetics.
• NO vasoconstrictor means:
– the anesthetic drug is more quickly
removed from the injection site and
distributed into systemic circulation
than if the solution contained a
vasoconstrictor
– more likely to be toxic than those
given without a vasoconstrictor
Plain anesthetics without vasoconstrictor
will exhibit a SHORTER duration of action
and result in a MORE RAPID buildup of a
systemic blood level.
– Any advantage gained by eliminating the
vasoconstrictor must be weighed against the
potential for adverse effects from the epinephrine.
IF A CLIENT HAS UNCONTROLLED BLOOD
PRESSURE – CAN LA BE GIVEN IN A
CONTROLLED DOSE?
NO – IT IS BEST TO DELAY
TREATMENT
A CARDIAC PATIENT
can be given
2.0 CARTRIDGES
of
1:100,000 epinephrine
without
exceeding the
cardiac dose.
WHAT IS THE MAXIMAL SAFE DOSE
FOR A HEALTHY CLIENT?
0.2 MG OF EPI
THE MAXIMAL SAFE DOSE OF EPINEPHRINE FOR THE
HEALTHY PATIENT IS 0.2 MG AND FOR THE CARDIAC
PATIENT IS 0.04 MG
TOPICAL AGENT
• Cocaine
• Benzocaine
•
•
•
•
NOTES
highly effective
Not in use now
The only use for the
Ester
The most common
used before LA
commonly used
before procedures
• Lidocaine
•
• Tetracaine)
• –solution/ointment
WHAT IS ORAQIX?
SOMETHING THE RDH CAN USE TO
FREEZE THE GUMS
lidocaine & prilocaine
(Injection-Free Anesthesia)
(Oraqix)
• May be combined for injection-free local
anesthesia.
– The combination of Oraqix applied into the
periodontal pocket offers pain relief during scaling
and root planing procedures
– Duration of action: approx. 20min.
– The onset of action: approx. 30sec after
application.
WHAT IS THE MOST COMMONLY USED
TOPICAL?
BENZOCAINE
• Patients should be advised to tell you if they are
feeling anxious, nervous, or if they are having heart
palpitations.
• Most of these symptoms can be avoided by lowering
the dose or switching to another LA
• Some LA may cause drowsiness
• Patients should use caution if an opioid analgesic or
antianxiety drug is also Rx
• Avoid driving or doing anything that require thought
or concentration
• Have the patient avoid eating or drinking very hot or
cold food or drink. The local anesthetic may make it
difficult to detect temperature changes.
CHAPTER 10
CAN NITROUS OXIDE BE USED ALONE
AS AN ANESTHETIC?
NO!
WHAT ARE THE STAGES/PLANES OF
ANESTHESIA?
STAGES…
STAGE I – ANALGESIA
STAGE II – DELIRIUM OR EXCITEMENT
STAGE III – SURGICAL ANAESTHESIA
STAGE IV – RESPIRATORY OR MEDULLARY PARALYSIS
STAGE I – ANALGESIA
↓ sensation of pain
patient conscious and responsive
nitrous oxide in dental office is an
example
end of this stage marked by loss of
consciousness
STAGE I – ANALGESIA
Nitrous oxide, as used in the dental office,
maintains the patient in STAGE I
 Is characterized by the development of analgesia or
reduced sensation to pain.
 The patient is conscious and can still respond to
commands.
 Reflexes are present, and respiration remains regular.
 Some amnesia may also be present.
STAGE II – DELIRIUM OR EXCITEMENT
Begins with unconsciousness.
Involuntary movement & excitement.
Respiration becomes irregular, and muscle
tone increases.
Sympathetic stimulation produces tachycardia,
mydriasis, and hypertension (↑ BP).
Emesis (vomiting) and incontinence
(defecation) can occur.
STAGE III – SURGICAL ANAESTHESIA
This is the stage in which most major surgery
is performed
The loss of respiratory control (i.e., diminished
carbon dioxide response, paralysis of
intercostal muscles) first occurs during stage
III
Paralysis of intercostal muscles begins in plane III
and is complete in plane IV of stage III anesthesia.
STAGE III – SURGICAL ANAESTHESIA
 Divided into four planes differentiated by eye
movements, depth of respiration, muscle relaxation:
• Plane I & II
– return of REGULAR respiration, muscle relaxation
and normal HR & pulse rate
• Plane III
– ↓ skeletal muscle tone, dilated pupils, ↓ BP
• Plane IV
– characterized by intercostal muscle paralysis
(diaphragmatic breathing remains) & absence of
all reflexes
STAGE IV – RESPIRATORY OR MEDULLARY
PARALYSIS
Characterized by complete cessation of
respiration and circulatory failure.
Pupils are maximally dilated, and blood
pressure falls rapidly.
If this stage is not reversed immediately, the
patient will die.
Respiration must be artificially maintained.
Stage I – Induction Period
Nitrous oxide, as used in the
dental office, maintains the
patient in STAGE I
Analgesia
Analgesia
Amnesia
Euphoria
consciousness
Stage II – Induction Period
Excitement
Excitement
Delirium
combativeness
Stage III
Surgical
Where most major surgery is Anesthesia
performed
Divided into four planes
Unconsciousness
Regular respiration
Decrease in eye movement
loss of respiratory control
Stage IV
Respiratory arrest
Cardiac depression and arrest
No eye movement
Medullary
Depression
FOR GENERAL ANESTHETICS – WHAT
ARE TWO TYPES?
INHALATION AND INTRAVENOUS (IV)
REMEMBER..
THE LESS SOLUBLE THE ANESTHETIC IS IN BODY TISSUES,
THE MORE RAPID THE ONSET AND RECOVERY.
Nitrous oxide (NO2)
=
Rapid onset and low solubility in blood
These physical factors allows the
anesthesiologist to adjust quickly the desired
level of anesthesia.
WHAT IS MAC?
MINIMAL ALVEOLAR
CONCENTRATION
THE TERM MINIMAL ALVEOLAR CONCENTRATION (MAC) IS
USED TO COMPARE POTENCY OF GENERAL ANESTHETIC
INHALATION AGENTS
MAC IS THE DEFINED AS THE MINIMUM ALVEOLAR
CONCENTRATION OF ANESTHETIC AT 1 ATMOSPHERE REQUIRED
TO PREVENT 50% OF PATIENTS FROM RESPONDING TO A
SUPRAMAXIMAL SURGICAL STIMULUS
Of the following general anesthetic agents
NITROUS OXIDE has the largest MAC value
MAC of:
nitrous oxide > 100;
halothane 0.75,
enflurane of 1.68.
isoflurane is 1.15
Lower MAC
values indicate
a more potent
anesthetic
WHAT IS NITROUS OXIDE?
COLORLESS AND ODOURLESS GAS
ANTIANXIETY AGENT + ANALGESIC AGENT
WHAT IS BALANCED ANESTHESIA?
COMBINATION OF…
Rapidly acting IV agent + N2O-O2 (nitrous oxide &
oxygen) combination + volatile anaesthetic =
balanced anaesthesia
WHY IS NITROUS OXIDE NOT GOOD TO
USE AS A GENERAL ANESTHETIC ALONE?
MAC > 100
BECAUSE OF ITS LOW POTENCY (MAC > 100), IT IS
UNSATISFACTORY AS A GENERAL ANESTHETIC WHEN USED
ALONE
IF, HOWEVER, ANESTHESIA IS FIRST INDUCED WITH A RAPIDLY
ACTING IV AGENT AND N2O/O2 IS ADMINISTERED IN
COMBINATION WITH A VOLATILE ANESTHETIC, EXCELLENT
BALANCED ANESTHESIA IS PRODUCED
THEREFORE,
Nitrous oxide combined with a halogenated
inhalational anesthetic (N2O/O2)
DECREASES THE MAC
• N2O/O2 is given throughout most surgical procedures that
necessitate the use of general anesthesia because it reduces
the concentration of other agents needed to obtain the desired
depth of anesthesia.
The average percentage of nitrous
oxide required for patient comfort is
35%.
•
DELIVERY:
 100% O2 (2-3 minutes) → N2O added in 510% increments → until patient response
indicates level of sedation reached→ after
termination of N2O, 100% O2 (at least 5
minutes)
WHY SHOULD THE CLIENT BE PLACED
ON 100% OXYGEN AFTERWARDS?
TO AVOID DIFFUSION HYPOXIA
• Advantages of the N2O/O2 technique
 rapid onset – less than 5 minutes
 easy administration – inhalation (no needles)
 close control – via flow meters
 rapid recovery – no need for designated driver
 acceptability for children – apprehensive
children
 relaxed dental team
• The best indicator of the degree of sedation
is the patient’s response to questions
•
•
•
•
– The patient may exhibit slurred speech or a slow
response
The patient is relaxed and cooperative and reports a
feeling of euphoria
The patient is easily able to maintain an open-mouth
position in the desired plane
The patient’s eyes may be closed but can be opened
easily
The respiration, pulse, rate, and blood pressure are
within normal limits
WHAT COLOR IS THE NITROUS TANK?
BLUE
**REMEMBER THIS!
• Complications have been the result of misuse
or faulty installation of equipment
• NO2 tank → blue
• O2 tank → green
DON’T GET THESE
MIXED UP!!
• Cylinders are “pin coded” to prevent mixing
of cylinders and lines
• NO2 concentration should be automatically
limited and have a fail-safe system that
shuts off automatically if the O2 runs out
WHEN SHOULD NITROUS NOT BE
USED?
IF THEY HAVE TROUBLE BREATHING…
USE OF NITROUS OXIDE IS CONTRAINDICATED IN PATIENTS
WITH ANY TYPE OF
UPPER RESPIRATORY OR PULMONARY OBSTRUCTION
PREGNANCY CONSIDERATIONS
• Safety of use in pregnant patients or
administration by pregnant operators is in
question
– The incidence of spontaneous abortion or
miscarriages is higher in female operating
personnel chronically exposed to anesthetic agents
or in wives of male operators
INTRAVENOUS
propofol
(Diprivan)
CHARACTERISTICS OF PROPOFOL
a. Rapid onset of action
b. Potent vasodilator
c. Undergoes phase II metabolism in the liver
d. Intravenous anesthetic
e. An agent that is unrelated to any other general
anesthetic
WHAT ARE THE PROPERTIES OF GOOD
GENERAL ANESTHETIC?
NO TOXIC EFFECTS…