Pharmacology -

DENTALELLE TUTORING

Pharmacology -

Chapter 9

WHY IS EPI USED IN LOCAL ANESTHETICS?

MEANING. .THE LOCAL ANESTHETIC LASTS LONGER TO ENSURE PROPER FREEZING OF THE TOOTH AND TISSUES

PROLONG DURATION

WAS COCAINE USED AS AN ANESTHETIC?

. .BUT NOT ANYMORE! IT WAS QUICKLY RECOGNIZED FOR ITS ADDICTING PROPERTIES.

YES..

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

HISTORY

NO LOCAL ANESTHETIC IN USE TODAY MEETS ALL THE NECESSARY REQUIREMENTS

TRUE OR FALSE…

BUT…MANY ACCEPTABLE AGENTS ARE AVAILABLE

TRUE

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

IDEAL LOCAL ANESTHETIC PROPERTIES OF THE IDEAL

LOCAL ANESTHETIC

WHAT ARE THE TWO GROUPS OF LOCAL ANESTHETICS?

CROSS -HYPERSENSITIVITY BETWEEN AMIDES AND ESTERS IS UNLIKELY

AMIDES AND ESTERS

ACTION OF NERVE FIBERS• 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

MECHANISM OF ACTION

IN RELATION TO NERVE IMPULSES?

HOW DO LOCAL ANESTHETICS WORK?

AFTER COMBINING WITH THE RECEPTOR, LOCAL ANESTHETICS BLOCK CONDUCTION OF NERVE IMPULSES BY DECREASING THE PERMEABILITY OF THE NERVE CELL

MEMBRANE TO SODIUM IONS

DECREASING PERMEABILITY 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

MECHANISM OF ACTION

ACTION OF NERVE

FIBERS

SUMMARIZED

The mechanism of local anesthetics involves action

on Axons and Sodium channels

MECHANISM OF ACTION

ACTION OF NERVE

FIBERS

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?

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.

WEAK BASES

Absorption & L.A.

infection

tooth • ↓ pH• ↑ ionization

• ↑ [H+]

localanaesthetic

(L.A.)L.A.

L.A.

L.A.

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).

*Weak bases are better absorbed when the pH is greater than

the pKa

EG: Lidocaine’s pKa =7.9(Weak

base drug)

IF INFECTION IS PRESENT, HOW DOES THE LOCAL ANESTHETIC

REACT?

IN THE PRESENCE OF AN ACIDIC ENVIRONMENT, SUCH AS INFECTION OR INFLAMMATION, THE AMOUNT OF

FREE BASE IS REDUCED

IT IS HARDER TO FREEZE –LIKELY INFECTION MUST BE CLEARED BEFORE FREEZING IS

DONE.

WHAT DOES ADME STAND FOR?

ABSORPTIONDISTRIBUTIONMETABOLISMEXCRETION

VERY IMPORTANT!

WHAT IS ABORPTION?

ABSORPTION DEPENDS ON ITS ROUTEWHEN INJECTED INTO TISSUES THE RATE DEPENDS ON

THE VASCULARITY OF THE TISSUES

ROUTE

ABSORPTION

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.

PHARMACOKINETICS

WHAT CAN BE ADDED TO REDUCE THE RATE OF ABSORPTION?

A VASOCONSTRICTOR

ABSORPTION

• Addition of vasoconstrictor to local anesthetic: Reduces the blood supply to the

areaso 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 areaLimits systemic absorptionReduces systemic toxicity

PHARMACOKINETICS

WHY IS REDUCING THE RATE OF ABSORPTION SO IMPORTANT?

REDUCES SYSTEMIC TOXICITY

WHAT IS DISTRUBUTION?

LOCAL ANESTHETICS CROSS THE PLACENTA AND BLOOD-BRAIN BARRIER

LOCAL ANESTHETIC DISTRUBUTED THROUGHOUT

METABOLISMLA 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

PHARMACOKINETICS

WHAT IS EXCRETION?

METABOLITES AND SOME UNCHANGED DRUG OF BOTH ESTERS AND AMIDES ARE EXCRETED BY THE KIDNEYS

EXCRETED BY KIDNEYS

WHAT NERVE DOES LOCAL ANESTHETIC BLOCK?

THE MAIN CLINICAL EFFECT OF LOCAL ANESTHETIC IS REVERSIBLE BLOCKAGE OF PERIPHERAL NERVE

CONDUCTION

PERIPHERAL NERVE CONDUCTION

COMMON ORDER OF NERVE FUNCTION LOSS

1. Autonomic *is the most sensitive to inhibition by local anesthetic agents

2. Cold3. Warmth4. Pain5. Touch6. Pressure7. Vibration8. Proprioception9. Motor

PHARMACOLOGIC EFFECTS

PERIPHERAL NERVE

CONDUCTION (BLOCKER)

The order of nerve impulse return:

opposite (reverse)

The order of loss of nerve function

WHY ARE LOCAL ANESTHETICS SUCCESSFUL IN TREATING ARRHYTMIAS?

WHAT DO PLASMA LEVELS HAVE TO DO WITH LOCAL ANESTHETIC?

ADVERSE REACTIONS AND TOXICITY

ADVERSE REACTIONS

• Although toxicity to local anesthetics is rare in the doses normally used in dentistry, patients can still suffer from a classic toxic reaction.

ADVERSE REACTIONS

LOCAL ANESTHETIC TOXICITY causes stimulation of the CNS

including:restlessness, tremorsseizures 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

MALIGNANT HYPERTHERMIA

• 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.

ADVERSE REACTIONS

. .WHAT IS BEST?

IF A WOMAN IS PREGNANT AND ANESTHETIC MUST BE GIVEN…

LIDOCAINE

AMIDES OR ESTERS?

WHAT TYPE HAS A GREAT POTENTIAL FOR ALLERGY?

ESTERS

ALLERGYIF A PATIENT REPORTS A

HISTORY OF ALLERGIES TO ALL LOCAL ANESTHETIC

AGENTS

Can use antihistaminediphenhydramine

(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

ADVERSE REACTIONS

WHICH INGREDIANT REDUCES BLEEDING?

VASOCONSTRICTORS

IF A PATIENT HAS ASTHMA, HOW MUST YOU BE CAREFUL?

THE ANTIOXIDANT FOR THE VASOCONSTRICTOR MAY PRODUCE A HYPERSENSITIVITY REACTION THAT

EXHIBITS ITSELF AS AN ACUTE ASTHMATIC ATTACK

ANTIOXIDANT IN LOCAL

WHERE IS TOPICAL PLACED?

THE MUCOUS MEMBRANE OF THE SKIN

I. Amides (Only class of anaesthetics used parenterally)

i. Lidocaine (Xylocaine)ii. Mepivacaine (Carbocaine)iii. prilocaine (Citanest; Citanest Forte)iv. bupivacaine (bu·piv·a·caine)

I. Esters (No esters are currently available in a dental cartridge)

i. procaineii. propoxycaineiii. Tetracaine

LOCAL ANESTHETIC AGENTS

**Esters are not used in dentistry as local

anesthetics, but used topically.

eg. Benzocaine.

SOME COMMONLOCAL ANESTHETIC AGENTS

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)• Prilocaine epi (Citanest

Forte)

• similar to lidocaine• rapidly metabolized

SEE NOTE

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

LOCAL ANESTHETIC

AGENTS

AMIDES

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

LOCAL ANESTHETIC

AGENTS

AMIDES

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

LOCAL ANESTHETIC

AGENTS

AMIDES

WHAT IS BOTH AN ESTER AND AN AMIDE?

ARTICAINE

OVERVIEW

The vasoconstrictors are members of the autonomic

nervous system drugs called the

ADRENERGIC AGONISTSor sympathomimetics.

VASOCONSTRICTORS

OVERVIEW

• 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

VASOCONSTRICTORS

OVERVIEW

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.

VASOCONSTRICTORS

IF A CLIENT HAS UNCONTROLLED BLOOD PRESSURE – CAN LA BE GIVEN IN A

CONTROLLED DOSE?

NO – IT IS BEST TO DELAY TREATMENT

OVERVIEW

A CARDIAC PATIENT can be given

2.0 CARTRIDGES of

1:100,000 epinephrine without

exceeding the cardiac dose.

VASOCONSTRICTORS

WHAT IS THE MAXIMAL SAFE DOSE FOR A HEALTHY CLIENT?

THE MAXIMAL SAFE DOSE OF EPINEPHRINE FOR THE HEALTHY PATIENT IS 0 .2 MG AND FOR THE CARDIAC

PATIENT IS 0 .04 MG

0.2 MG OF EPI

SOME COMMON TOPICAL ANESTHETICS

TOPICAL AGENT NOTES• Cocaine • highly effective

• Not in use now• Benzocaine • The only use for

the Ester• The most common

used before LA• Lidocaine • commonly used

before procedures

• 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.

TOPICAL ANESTHETICS

AMIDES

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.

INSTRUCTIONS FOR PATIENTS RECEIVING LOCAL ANESTHETICS

CHAPTER 10

CAN NITROUS OXIDE BE USED ALONE AS AN ANESTHETIC?

NO!

WHAT ARE THE STAGES/PLANES OF ANESTHESIA?

STAGE I – ANALGESIASTAGE I I – DELIRIUM OR EXCITEMENTSTAGE I I I – SURGICAL ANAESTHESIA

STAGE IV – RESPIRATORY OR MEDULLARY PARALYSIS

STAGES…

STAGES AND PLANES OF ANESTHESIA

STAGE I – ANALGESIA

↓ sensation of painpatient conscious and responsivenitrous oxide in dental office is an

exampleend of this stage marked by loss of

consciousness

MECHANISM OF ACTION

STAGES AND PLANES OF ANESTHESIA

STAGE I – ANALGESIA

MECHANISM OF ACTION

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.

STAGES AND PLANES OF ANESTHESIA

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.

MECHANISM OF ACTION

STAGES AND PLANES OF ANESTHESIA

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.

MECHANISM OF ACTION

STAGES AND PLANES OF ANESTHESIA

STAGE III – SURGICAL ANAESTHESIADivided 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

MECHANISM OF ACTION

STAGES AND PLANES OF ANESTHESIA

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.

MECHANISM OF ACTION

STAGES AND PLANES OF ANESTHESIA

MECHANISM OF ACTION

Stage I – Induction PeriodNitrous oxide, as used in the dental office, maintains the patient in STAGE I

Analgesia AnalgesiaAmnesiaEuphoriaconsciousness

Stage II – Induction Period Excitement ExcitementDeliriumcombativeness

Stage IIIWhere most major surgery is performedDivided into four planes

Surgical Anesthesia

UnconsciousnessRegular respirationDecrease in eye movementloss of respiratory control

Stage IV Medullary Depression

Respiratory arrestCardiac depression and arrestNo eye movement

FOR GENERAL ANESTHETICS – WHAT ARE TWO TYPES?

INHALATION AND INTRAVENOUS (IV)

THE LESS SOLUBLE THE ANESTHETIC IS IN BODY TISSUES, THE MORE RAPID THE ONSET AND RECOVERY.

REMEMBER..

CLASSIFICATION OF ANESTHETIC AGENTS

Nitrous oxide (NO2) =

Rapid onset and low solubility in blood

These physical factors allows the anesthesiologist to adjust quickly the

desired level of anesthesia.

GENERAL ANESTHETICS

PHYSICAL FACTORS

WHAT IS MAC?

T H E T E R M M I N I M A L A LV E O L A R C O N C E N T R AT I O N ( M A C ) I S U S E D T O C O M PA R E P O T E N C Y O F G E N E R A L A N E S T H E T I C I N H A L AT I O N A G E N T S

M A C I S T H E D E F I N E D A S T H E M I N I M U M A LV E O L A R C O N C E N T R AT I O N O F A N E S T H E T I C AT 1 AT M O S P H E R E R E Q U I R E D T O

P R E V E N T 5 0 % O F PAT I E N T S F R O M R E S P O N D I N G T O A S U P R A M A X I M A L S U R G I C A L S T I M U LU S

MINIMAL ALVEOLAR CONCENTRATION

CLASSIFICATION OF ANESTHETIC AGENTS

Of the following general anesthetic agents NITROUS OXIDE has the largest MAC

valueMAC of:

nitrous oxide > 100; halothane 0.75,

enflurane of 1.68. isoflurane is 1.15

GENERAL ANESTHETICS

PHYSICAL FACTORS

Lower MAC values indicate a more potent

anesthetic

WHAT IS NITROUS OXIDE?

ANTIANXIETY AGENT + ANALGESIC AGENT

COLORLESS AND ODOURLESS GAS

WHAT IS BALANCED ANESTHESIA?

Rapidly acting IV agent + N2O-O2 (nitrous oxide & oxygen) combination + volatile anaesthetic =

balanced anaesthesia

COMBINATION OF…

WHY IS NITROUS OXIDE NOT GOOD TO USE AS A GENERAL ANESTHETIC ALONE?

B E CA U S E O F I T S L O W P O T E N CY ( M A C > 1 0 0 ) , I T I S U N S AT I S FA CT O RY A S A G E N E R A L A N E S T H E T I C W H E N U S E D A L O N E

I F, H O W E V E R , A N E S T H E SI A I S F I R S T I N D U CE D W I T H A R A PI D LY A CT I N G I V A G E N T A N D N 2 O / O 2 I S A D M I N I S T E R E D I N

CO M B I N AT I O N W I T H A VO L AT I L E A N E S T H E T I C , E XC E L L E N T B A L A N CE D A N E S T H E SI A I S PR O D U CE D

MAC > 100

NITROUS OXIDE

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.

GENERAL ANESTHETICS

NITROUS OXIDE

The average percentage of nitrous oxide required for patient comfort is 35%.

• DELIVERY: 100% O2 (2-3 minutes) → N2O added in

5-10% increments → until patient response indicates level of sedation reached→ after termination of N2O, 100% O2 (at least 5 minutes)

GENERAL ANESTHETICS

WHY SHOULD THE CLIENT BE PLACED ON 100% OXYGEN

AFTERWARDS?

TO AVOID DIFFUSION HYPOXIA

NITROUS OXIDE

• Advantages of the N2O/O2 technique

rapid onset – less than 5 minuteseasy administration – inhalation (no

needles)close control – via flow meters rapid recovery – no need for

designated driveracceptability for children –

apprehensive childrenrelaxed dental team

GENERAL ANESTHETICS

NITROUS OXIDE• 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

GENERAL ANESTHETICS

PHARMACOLOGIC EFFECTS

WHAT COLOR IS THE NITROUS TANK?

* *REMEMBER THIS!

BLUE

NITROUS OXIDE• Complications have been the result of

misuse or faulty installation of equipment

GENERAL ANESTHETICS

ADVERSE REACTIONS

• 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?

USE OF NITROUS OXIDE IS CONTRAINDICATED IN PATIENTS WITH ANY TYPE OF

UPPER RESPIRATORY OR PULMONARY OBSTRUCTION

IF THEY HAVE TROUBLE BREATHING…

NITROUS OXIDE

• 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

GENERAL ANESTHETICS

CONTRAINDICATIONS AND DENTAL ISSUESPREGNANCY CONSIDERATIONS

OTHER GENERAL ANESTHETICS

CHARACTERISTICS OF PROPOFOLa. Rapid onset of actionb. Potent vasodilatorc. Undergoes phase II metabolism in the liverd. Intravenous anesthetice. An agent that is unrelated to any other general anesthetic

GENERAL ANESTHETICS

propofol(Diprivan)

INTRAVENOUS

WHAT ARE THE PROPERTIES OF GOOD GENERAL ANESTHETIC?

NO TOXIC EFFECTS…