Pharmcaology ppt

PHARMACOLOGY OF LOCAL
ANESTHESIA
PRESENTED BY
DR/ NERMINE RAMADAN MAHMOUD
Lecturer Oral & Maxillofacial surgery in OMFS
department Faculty of Dentistry O6U
B.D FACULTY OF DENTISTRY, O6U , 2006
MSC ORAL & MAXILLOFACIAL SURGERY, FACULTY OF
DENTISTRY, CAIRO UNIVERSITY , 2012
PHD ORAL & MAXILLOFACIAL SURGERY, FACULTY OF
DENTISTRY, CAIRO UNIVERSITY, 2015

• Anaesthesia is the loss of consciousness and all form of
sensation.
• Local Anaesthesia is the local loss of pain, temperature,
touch, pressure and all other sensation.
• In dentistry, Only loss of pain sensation is desirable.
Local Analgesia.
Local anaesthesia / analgesia

• Local anesthetics produce a transient and
reversible loss of sensation (analgesia) in a
circumscribed region of the body without loss of
consciousness.
• Normally,
the process is
completely
reversible.

CONTENTS OF THE LOCALANESTHETIC
CARPULE (CARTRIDGE )
1- the anesthetic drug
2- vasoconstrictor
3- preservative
4- vehicle
5- distilled water
Pharmacology of local anesthesia

1- The anesthetic drug

Anesthesia
with V.C
Plain Anesthesia
without V.C
1- Local anesthetic agent
(L.A)
2- Vaso - Constrictor
(V.C)
3- Preservative for V.C agent
(anti-oxidant)
4- Vehicle (0.9 % NaCl )
to make solution isotonic
1- Local anesthetic agent
(L.A)
2- Vehicle (0.9 % NaCl )
to make solution isotonic
Constituents of the anesthetic carpule

Local anesthetic agents

Local anesthetic agents
Ester Amide

Local anesthetics generally have a lipid-
soluble hydrophobic aromatic group and a
charged, hydrophilic amide group.

The bond between these two groups
determines the class of the drug, and may
be amide or ester.

The clinically significant
differences between esters and
amides ??

Ester Amide
Linkage Easily broken Difficult
Stability in
the solution
Less More
Storing time Less More
Heat stable Less More
Autoclavable Not Yes
Allergy Produce PABA w
produce
allergic
reaction
Very rarely

Requirements of an ideal local anesthetic drug
1) should not be irritating to the tissue to which it is applied
2) should not cause any permanent alteration of nerve structure
3) its systemic toxicity should be low
4) must be effective regardless it is injected into the tissue or applied
topically to mucous membrane
5) time of onset of anesthesia should be as short as possible
6) duration of action must be long enough to permit completion of the
procedure
7) should have potency sufficient to give complete anesthesia without
the use of harmful concentrated solutions
8) should be relatively free from producing allergic reactions

Pharmacokinetics of local anesthetics
Uptake
Potency
Duration
Biotransformation
Excretion

1- Uptake
 Most L.A agents producing vasodilatation
 Vasodilatation results in:
- Increase rate of absorption
- Decrease duration of action
- Increase blood level & risk for
toxicity

1- Uptake
 Procaine is the most potent vasodilator
 Cocaine is the only L.A agents that produces
vasoconstriction

2- Potency
 The majority of local anesthetics are tertiary amines
 Few local anesthetic are secondary amines as procaine
 NH3  NR3
 Local anesthetic agent is prepared in the carpule in the
form of hydrochloride salt of tertiary amine (NR3-HCL)

The importance of the pKa of a local
anaesthetic drug.
All local anaesthetic agents are weak bases,
meaning that they exist in two forms:
- unionised (B) and
- ionised (BH+).

anaesthetic drug.
The pKa of a weak base defines the pH at which both
forms exist in equal amounts.
As the pH of the tissues differs from the pKa of the
specific drug, more of the drug exists either in its
charged or uncharged form.

anaesthetic drug.
Pka
drug
PH
tissue

The pKa of a local anaesthetic determines the
amount which exists in an ionised form at any
given pH.
At physiological pH (7.4)
all local anaesthetics are more ionised than
unionised (as all the pKa values are greater
than 7.4).

As the drug must enter the cell in order to have
its effect it must pass through the lipid cell
membrane
Unionised drug will do this more readily than
ionised drug.

However the proportions vary between the drugs:
lignocaine has a pKa of 7.9 and is approximately
25% unionised at pH 7.4 .
Bupivacaine has a pKa of 8.1 and hence less of the
drug is unionised at pH 7.4 (about 15%).
why lignocaine has a faster onset of action than
bupivacaine.

Therefore the drug which is more unionised at
physiological pH will reach its target site more
quickly than the drug which is less so.
This explains why lignocaine has a faster onset of
action than bupivacaine.

(NR3 – HCL )
The free base (NR3) of the hydrochloride salt of tertiary amine
is liberated from its salt (HCL ) by interaction with
alkaline medium , alkaline PH , (body fluids ,
NaHCO3)
(NR3-HCL) + NaHCO3  NR3 + NaCL +H2CO3
?

In presence of
tissue infection or
inflammation
(acidic PH)

In presence of tissue infection or inflammation
(acidic PH)
The free base (NR3) of the hydrochloride salt of tertiary
amine (NR3 – HCL ) fall to liberated from its salt (HCL) &
failure of anesthesia occurs
(NR3-HCL) + ACIDIC PH -- (NR3-HCL)

Local anesthetics with lower pK have a more
rapid onset of action (more uncharged form
more rapid diffusion to cytoplasmic side of Na+
channel)
pK % free base
at pH 7.7
Onset of anesthesia
(min)
lidocaine 7.9 25 2-4
bupivacaine 8.1 18 5-8
procaine 9.1 2 14-18
Duration
(minutes)
180-600
90-200
60-90

3- Duration
Factors affecting duration & depth of anesthetic action :
1- factors related to individual :
Individual response variation

3- Duration
2- factors related to anesthetic agent :
1- lipid solubility
2-concentration & type of drug
3- +/- V.C
4- duration of exposure

3- Duration
3- factors related to injection technique :
1- infiltration / nerve block
2- volume of solution
3- accuracy of technique
4- anesthetic variations

3- Duration
4- factors related to site of injection :
1- alkalinity : affect ionization of drug & rate of liberation of
free base
2- vascularity of tissue

4- Biotransformation ( metabolism )
Ester Amide
Metabolized in Plasma Liver
By Plasma pseudo-
cholinesterase
enzyme
Microsomal
enzyme
And in Liver
By Esterase enzyme
Toxicity occurs
in patients with
Plasma pseudo
cholinesterase
enzyme deficiency
Impaired liver
function
Liver dysfunction

Biotransformation of L.A drugs
Ester group undergo biotransformation in :
- Liver by the esterase enzyme
- Plasma by cholinesterase enzyme
Amide group undergo biotransformation in:
- Liver

5- Excretion
Both groups of local anesthetics & their metabolites are
excreted by kidneys
Patients with renal dysfunction may be unable to eliminate
local anesthetic & their metabolites from the blood with
increase risk of toxicity

Systemic actions of Local anesthetics
• Drugs temporary interrupt nerve conduction
when absorbed into it and have little or no
irritating effect when injected
• They are all synthetic compounds except
the cocaine
CVS & CNS are susceptible to L.A action

Local anaesthetic agents:
• Are drugs that block nerve
conduction when applied locally to
nerve tissues in appropriate
concentrations, acts on any part of
the nervous system, peripheral or
central and any type of nerve fibres,
sensory or motor.

- CNS
- CVS
- RESPIRATORY SYSTEM
- DRUG INTERACTION
- MALIGNANT HYPERTHERMIA (MH)

Effects of local anesthetics on CNS
• As is the case with CNS depressants generally (e.g.,
alcohol) local anesthetics (at toxic doses) produce a
biphasic pattern of excitation followed by depression
• The excitatory phase likely reflects the preferential
blockade of inhibitory neurons and effects can range from
mild hyperactivity to convulsions)
• The subsequent depressive phase can progress to
cardiovascular collapse and even death if unmanaged.

Effects of local anesthetics on heart
• Local anesthetics can reduce
myocardial excitability
pacemaker activity
prolong the refractory period of myocardial tissue – this is the basis
of the antiarrhythmic effects of local anesthetics
• Local anesthetic-induced
myocardial depression
hypotension)
can also be a manifestation of toxicity and can lead to
cardiovascular collapse and even death!

Effects of local anesthetics on respiratory system
Unaffected by L.A until overdose levels .
Overdose  respiratory arrest
Due to generalized CNS depression

Effects of local anesthetics on malignant
hyperthermia (MH)
Disorder in which a genetic variant in an individual
alters his response to certain drug
Tachycardia / unstable blood pressure / cyanosis /
fever (up to 42 C) / muscle rigidity / death

Functional consequences of Na+ channel blockade by
local anesthetics
• nerves: decrease or abolition of conduction
• vascular smooth muscle: vasodilatation
• heart: decreased excitability (reduced pacemaker activity,
prolongation of effective refractory period)
• central nervous system: increased excitability, followed by
generalized depression

Clinical aspects
local anesthetic toxicity (cont’d)
• allergic reactions: restricted to esters – metabolized to
allergenic p-amino benzoic acid (PABA) (∴ amides usually
preferred for nerve block)
• cardiovascular: may be due to anesthetic (cardiodepression,
hypotension) or vasoconstrictor (hypertension, tachycardia) ∴
monitor pulse/blood pressure
• CNS: excitability (agitation, increased talkativeness – may
→ convulsions) followed by CNS depression (∴
care in use of CNS depressants to treat convulsions - may
worsen depressive phase – convulsions usually well tolerated
if brain oxygenation maintained between seizures)

2- The vasoconstrictor

Pharmacology of vasoconstrictors
V.C commonly used in conjunction with injected
L.A are chemically similar to the sympathetic
nervous system mediators i.e :
- epinephrine &
- norepinephrine

Advantage of V.C
1- delayed absorption of anesthetic drug
2- it decrease the amount of solution needed
3-controls the rate at which the anesthetic
drug enters the circulation (decrease risk of
toxicity)
4- haemostasis
5- it causes local anaemia

What happens if you don’t use a
vasoconstrictor?
*Plain local anesthetics are vasodilators by nature
1) Blood vessels in the area dilate
2) Increase absorption of the local anesthetic into the
cardiovascular system (redistribution)
3) Higher plasma levels  increased risk of toxicity
4) Decreased depth and duration of anesthesia  diffusion
from site
5) Increased bleeding due to increased blood perfusion to the
area

Contra-Indication of V.C
Relative Absolute
1- diabetes 1- toxic goiter
2- hypertension (hyperthyroidism)
3- cardiac
4- pregnancy

1- diabetes : as V.C counteract the action of insulin
i.e (increase blood glucose level )
2- hypertension : as V.C raises patient’s blood pressure
3- cardiac : as V.C stimulate the heart, produce tacchycardia
& increase H.R
This is doubtful because of small amount used about 0.04 mg
if 2ml of 1: 50 000 Is used & this is about 1/5 permissible
dose that can be given to cardiac patient without ill effect

4- pregnancy :
because V.C causes uterine contraction & may
cause abortion
5- hyperthyroidism (toxic goiter) :
because V.C esp. adrenaline may cause thyroid
crisis & sudden death
(Prilocaine with felypressine)

3- VEHICLE

3- VEHICLE
1- add to L.A carpule to make solution
‘isotonic’
2- 0.9 % sodium chloride
- Ringer solution (0.5% sodium chloride +
0.4 % potassium chloride)

4- PRESERVATIVE

4- PRESERVATIVE
1- Is added to L.A carpule to prevent the oxygenation
of the V.C
2- Na Metabisulphite is the most commonly used
preservative
3- Na Metabisulphite when oxygenated is transferred
to Na metabisulphate with a characteristic yellowish
discoloration of carpule

Maximum doses of L.A agents

Dilution of L.A agents

Concentration of V.C in L.A
1/ 50.000  0.02 mg/ml
1/100.000  0.01 mg/ ml
1/200,000  0.005 mg/ml

2 % lidocaine of 1/100.000 epinephrine in patient
weighted 90 kg .. What is the max permissible dose ?
Lidocaine max.dose 300 mg / normal 4.4 mg/kg
90 kg X 4.4 = 396 mg  over absolute maximum
2% lidocaine means = 20 mg/ml
(2g/100 ml = 2000 mg / 100 ml
Carpule 1.8 ml of solution
So  20 X 1.8 = 36 of lidocaine / carpule

How much lidocaine in cartridge of 2% lidocaine with
1/100.000 epinephrine
2% lidocaine = 20 mg/ml
20mg/ml X 1.8 ml / cartridge = 36 mg lidocaine/ cartridge
Epinephrine 1/100.000 = 0.01 mg/ml
0.01 mg/ml X 1.8 ml/ cartridge = 0.018 mg epinephrine / cart
Maximum epinephrine dose 0.2 mg
1 carpule of 1:100,000 = 0.018 mg

So maximum permissible dose of 2% lidocaine with
1/100.000
Maximum epinephrine dose 0.2 mg
1 carpule of 1:100,000 = 0.018 mg
0.2 / 0.018 = 11 carpules

So maximum permissible dose of 2% lidocaine with
1/100.000 in cardiac patient
Maximum epinephrine dose 0.05mg
1 carpule of 1:100,000 = 0.018 mg
0.05 / 0.018 = 2.7 carpules

1.8 ml Cartridge of 2% Lidocaine 1:100,000 epi
Maximum Epinephrine: 11 Cartridges
Maximum Anesthetic: 300 mg
1.8 ml Cartridge of 2% Lidocaine 1:200,000 epi
Maximum Epinephrine: 22 Cartridges
Maximum Anesthetic: 300 mg

Max allowed dose (mg / kg) X (weight in kg / 10) X
(1/concentration of L.A) = ml lidocaine
7 mg / kg for lidocaine with epinephrine , using 1 %
lidocaine with epinephrine for 60 kg patient
7 X 6 X 1 = 42 ml lidocaine
With epinephrine 7 mg/ kg
Without epinephrine 3 mg/ kg

How much Epinephrine in CV
patients?
Maximum Epinephrine
0.04 mg
Two cartridges of 1:100,000 epinephrine

Keep in mind
1- The main agent in the carpule is the L.A agent
2- the other ingredients of the local anethetic carpule
are added :
a- to potentiate the action of the L.A agent
b- to prevent deterioration of the contents

TOPICALANESTHETICS

TOPICALANESTHETICS
The use of topically applied L.A is an important component
of atraumatic administration of intraoral L.A
The concentration of a local anesthetic applied topically is
typically greater than that of the same local anesthetic
administered by the injection
The higher the conc facilitates diffusion of the drug thru
mucous membrane
Lidocaine (xylocaine) is the most commonly used

Clinical aspects
Applications of local anesthesia:
 nerve block: injected locally to produce regional anesthesia
(e.g., dental and other minor surgical procedures)
 topical application: to skin for analgesia (e.g., benzocaine) or
mucous membranes (for diagnostic procedures)
 spinal anesthesia: injection into CSF to produce anesthesia for
major surgery (e.g., abdomen) or childbirth
 local injection: at end of surgery to produce long-lasting post-
surgical analgesia (reduces need for narcotics)
 i.v. infusion: for control of cardiac arrhythmias (e.g., lidocaine
for ventricular arrhythmias)

Pharmcaology ppt

Recommended

Recommended

More Related Content

What's hot

What's hot (20)

Viewers also liked

Viewers also liked (7)

Similar to Pharmcaology ppt

Similar to Pharmcaology ppt (20)

Recently uploaded

Recently uploaded (20)

Pharmcaology ppt