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 HISTORY 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

No local anesthetic in use today meets all THE NECESSARY requirements TRUE OR FALSE… No local anesthetic in use today meets all THE NECESSARY requirements

But…many acceptable agents are available TRUE But…many acceptable agents are available

IDEAL LOCAL ANESTHETIC PROPERTIES OF THE IDEAL LOCAL ANESTHETIC 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 FOR TEST KNOW THE PROPERTIES (BOX 9-1; PAGE 113)

WHAT ARE THE TWO GROUPS OF LOCAL ANESTHETICS?

Cross-hypersensitivity between amides and esters is unlikely

MECHANISM OF ACTION 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

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

interferes with the function of the neurons MECHANISM OF ACTION 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 ACTION OF NERVE FIBERS SUMMARIZED A SUMMARY

MECHANISM OF ACTION The mechanism of local anesthetics involves action on Axons and Sodium channels ACTION OF NERVE FIBERS Propagation can refer to: Reproduction, and other forms of multiplication or increase 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?

Therefore, the local anesthetic is a 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.

EG: Lidocaine’s pKa =7.9(Weak base drug) Absorption & L.A. local anaesthetic (L.A.) L.A. tooth L.A. EG: Lidocaine’s pKa =7.9(Weak base drug) ↓ pH ↑ ionization ↑ [H+] L.A. *Weak bases are better absorbed when the pH is greater than the pKa REPEAT FROM CHAPTER 2 p 17 infection 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?

Absorption depends on its route When injected into tissues the rate depends on the vascularity of the tissues

PHARMACOKINETICS 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.

WHAT CAN BE ADDED TO REDUCE THE RATE OF ABSORPTION?

A VASOCONSTRICTOR

Addition of vasoconstrictor to local anesthetic: PHARMACOKINETICS ABSORPTION 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

AMIDES: are metabolized primarily by the liver PHARMACOKINETICS METABOLISM 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 PHARMACOLOGIC EFFECTS COMMON ORDER OF NERVE FUNCTION LOSS Autonomic *is the most sensitive to inhibition by local anesthetic agents Cold Warmth Pain Touch Pressure Vibration Proprioception Motor PERIPHERAL NERVE CONDUCTION (BLOCKER) The order of loss of nerve function Proprioception (pro-pree-o-ception): an unconscious perception of stimuli from within the body detected from nerve stilmuli 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

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.

LOCAL ANESTHETIC TOXICITY causes stimulation of the CNS including: ADVERSE REACTIONS 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

MALIGNANT HYPERTHERMIA ADVERSE REACTIONS 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.

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

diphenhydramine (Benadryl) ADVERSE REACTIONS ALLERGY 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

LOCAL ANESTHETIC AGENTS Amides (Only class of anaesthetics used parenterally) Lidocaine (Xylocaine) Mepivacaine (Carbocaine) prilocaine (Citanest; Citanest Forte) bupivacaine (bu·piv·a·caine) Esters (No esters are currently available in a dental cartridge) procaine propoxycaine Tetracaine Esters, such as benzocaine, are commonly used topically **Esters are not used in dentistry as local anesthetics, but used topically. eg. Benzocaine.

LOCAL ANESTHETIC AGENTS SOME COMMON LOCAL ANESTHETIC AGENTS 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) Prilocaine epi (Citanest Forte) similar to lidocaine rapidly metabolized FOR TESTING PURPOSES, WILL ONLY SEE THE GENERIC NAME MORE THAN THE BRAND NAMES – IF YOU SEE A BRAND NAME IT WILL BE BESIDE THE GENERIC NAME

WHAT IS THE MOST COMMON LA USED IN DENTISTRY?

LIDOCAINE 2% - (1:100 000 EPI)

LOCAL ANESTHETIC AGENTS (Carbocaine, Isocaine) AMIDES 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 TRUE STATEMENTS ABOUT MEPIVACAINE – KNOW FOR EXAM

Severeal cases of METHEMOGLOBINEMIA LOCAL ANESTHETIC AGENTS 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 AMIDES

WHICH ONE HAS THE LONGEST DURATION OF ACTION?

MARCAINE

LOCAL ANESTHETIC AGENTS 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 AMIDES

WHAT IS BOTH AN ESTER AND AN AMIDE?

ARTICAINE

VASOCONSTRICTORS OVERVIEW The vasoconstrictors are members of the autonomic nervous system drugs called the ADRENERGIC AGONISTS or sympathomimetics.

NO vasoconstrictor means: 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.

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 VASOCONSTRICTORS OVERVIEW 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

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) TOPICAL ANESTHETICS 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. AMIDES

WHAT IS THE MOST COMMONLY USED TOPICAL?

BENZOCAINE

INSTRUCTIONS FOR PATIENTS RECEIVING LOCAL ANESTHETICS 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

STAGES AND PLANES OF ANESTHESIA MECHANISM OF ACTION STAGES AND PLANES OF ANESTHESIA 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

STAGES AND PLANES OF ANESTHESIA MECHANISM OF ACTION STAGES AND PLANES OF ANESTHESIA 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.

STAGES AND PLANES OF ANESTHESIA STAGE II – DELIRIUM OR EXCITEMENT MECHANISM OF ACTION 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.

STAGES AND PLANES OF ANESTHESIA STAGE III – SURGICAL ANAESTHESIA 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.

STAGES AND PLANES OF ANESTHESIA STAGE III – SURGICAL ANAESTHESIA MECHANISM OF ACTION STAGES AND PLANES OF 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 Muscles of respiration = intercostal muscle

STAGES AND PLANES OF ANESTHESIA 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.

STAGES AND PLANES OF ANESTHESIA MECHANISM OF ACTION STAGES AND PLANES OF ANESTHESIA Stage I – Induction Period Nitrous oxide, as used in the dental office, maintains the patient in STAGE I Analgesia Amnesia Euphoria consciousness Stage II – Induction Period Excitement Delirium combativeness Stage III Where most major surgery is performed Divided into four planes Surgical Anesthesia Unconsciousness Regular respiration Decrease in eye movement loss of respiratory control Stage IV Medullary Depression Respiratory arrest Cardiac depression and arrest No eye movement SUMMARY OF THE STAGES INDUCTION Refers to quick change in the patient’s state of consciousness from stage I to stage III

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.

CLASSIFICATION OF ANESTHETIC AGENTS GENERAL ANESTHETICS CLASSIFICATION OF ANESTHETIC AGENTS PHYSICAL FACTORS Nitrous oxide (NO2) = Rapid onset and low solubility in blood These physical factors allows the anesthesiologist to adjust quickly the desired level of anesthesia. Whereas, Halothane = intermediate onset and higher solubility in blood. Table 10-4 page 130 gives the physical properties of some of the anesthetics

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

CLASSIFICATION OF ANESTHETIC AGENTS GENERAL ANESTHETICS CLASSIFICATION OF ANESTHETIC AGENTS PHYSICAL FACTORS 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

GENERAL ANESTHETICS 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. Nitrous oxide does not increase the MAC of halogenated anesthetics. Nitrous oxide is commonly given with halogenated anesthetics without fear of toxic reactions. Nitrous oxide has no influence on the metabolism of halogenated anesthetics, many of which are sparingly metabolized.

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) The percentage of nitrous oxide required for patient comfort is variable and may range from 10% to 50%.

WHY SHOULD THE CLIENT BE PLACED ON 100% OXYGEN AFTERWARDS?

TO AVOID DIFFUSION HYPOXIA

NITROUS OXIDE Advantages of the N2O/O2 technique GENERAL ANESTHETICS NITROUS OXIDE 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

PHARMACOLOGIC EFFECTS GENERAL ANESTHETICS NITROUS OXIDE PHARMACOLOGIC EFFECTS 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!

DON’T GET THESE MIXED UP!! GENERAL ANESTHETICS NITROUS OXIDE ADVERSE REACTIONS Complications have been the result of misuse or faulty installation of equipment NO2 tank → blue O2 tank → green DON’T GET THESE MIXED UP!! Know the colour of the tanks/cylinders. 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

CONTRAINDICATIONS AND DENTAL ISSUES PREGNANCY CONSIDERATIONS GENERAL ANESTHETICS NITROUS OXIDE CONTRAINDICATIONS AND DENTAL ISSUES 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

OTHER GENERAL ANESTHETICS CHARACTERISTICS OF PROPOFOL 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…