CE Course Handout. Hurts So Good! Management of Dental Pain: An Update on Anesthetics, Analgesics, and Patient Care Considerations

Transcription

1 CE Course Handout Hurts So Good! Management of Dental Pain: An Update on Anesthetics, Analgesics, and Patient Care Considerations Friday, June 20, :30pm-5:30pm

2 Questions and Answers 100th Anniversary of Dental Hygiene Welcome! Hurts So Good! Management of Dental Pain: An Update on Anesthetics, Analgesics, and Patient Care Considerations Contact Information thomasviola.com facebook.com/tomviolarph facebook.com/dentalpharmacology facebook.com/dentallocalanesthesia 2014 Thomas A. Viola, R.Ph., C.C.P. All Rights Reserved Thomas A. Viola, R.Ph., C.C.P. All Rights Reserved Program Learning Objectives Upon successful completion of this program, participants should be able to: Explain the basic concepts of neurophysiology and nerve conduction and the mechanism of action of local anesthetic agents. Differentiate between the two major classes of local anesthetic agents with respect to their distribution, metabolism and routes of excretion. Program Learning Objectives Discuss the rationale for the use of vasoconstrictors in local anesthetic solutions and their potential effects in common organ system disease states. Specify the various local anesthetic agent combinations most commonly used in dentistry, and the rationale for their use in specific clinical situations. Discuss general adverse effects, contraindications and patient care considerations with the use of local anesthetics Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 4 Program Learning Objectives Describe the pharmacology and mechanism of action of non-opioid and opioid analgesics, including appropriate dosing, systemic and therapeutic effects, as well as potential for abuse. Understand the intended role of opioid and nonopioid analgesics in dental settings, especially situations which preclude their use. Part I The Concept of Pain Use case scenarios to develop a pain management plan based upon a patient s needs and underlying medical conditions Thomas A. Viola, R.Ph. All Rights Reserved 5

3 The Concept of Pain Pain is an unpleasant sensory and emotional experience in which the body is made urgently aware of actual or potential tissue damage. Proper management of pain requires an understanding of its complexity and an appreciation for the factors that determine its expression The Concept of Pain Nociception is the sensory detection, transduction, and neural transmission of noxious events. Pain Threshold The lowest intensity of painful stimulation at which the patient becomes aware of the pain Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 8 The Concept of Pain Two components of pain Perception The physical component of pain Involves the transmission of the pain impulse from the injured tissue to the brain Uniform from patient to patient Reaction The psychological component of pain Involves the patient s emotional response to pain Varies from patient to patient The Concept of Pain Factors that lower pain threshold Contribute to a greater reaction to pain Fear Depression Anxiety Fatigue Factors that raise pain threshold Contribute to a lesser reaction to pain Sleep Sympathy Placebo effect 2014 Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 10 The Concept of Pain Pain is a powerful motivator AND de-motivator for patients to seek help from their dental professional. Pain keeps some patients from seeking help Fear of painful procedure Memory of significant/lengthy post-operative pain Negative feedback reinforcement Treatment on inflamed, hypersensitive tissues Patient mentally fatigued after endurance of pain The Anatomy of Pain Chemical agents that occur naturally in the environment of pain receptors after acute tissue damage are algogenic substances. These include adenosine, adenosine triphosphate, serotonin, histamine, bradykinin, cytokines, and prostaglandins. The release of these substances leads to nociceptor activation, producing the pain impulse Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 12

4 The Anatomy of Pain For a person to feel pain, the pain impulse must be transmitted to the spinal cord and then to the cerebral cortex. The pain impulse is transmitted to the spinal cord by peripheral nerves. Part II Treatment and Management of Therapeutic Dental Pain At the dorsal horn of the spinal cord, peripheral nerves transmit the pain signal to CNS neurons 2014 Thomas A. Viola, R.Ph. All Rights Reserved 13 Local Anesthetics Neuroanatomy and Neurophysiology 2014 Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 16 Neuroanatomy and Neurophysiology The neuron is the structural and functional unit of the nervous system. Neuroanatomy and Neurophysiology There are two basic types of neurons. Responsible for transmission of impulses between the CNS and the rest of the body. Afferent (sensory) neurons Transmit impulses FROM the periphery TO the CNS Efferent (motor) neurons Transmit impulses FROM the CNS TO the periphery 2014 Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 18

5 Significance of Myelination Some neurons are myelinated while others are not. Significance of Myelination Schwann cells, which produce myelin, insulate and protect nerve membranes from their surrounding environments (white matter). Myelin serves as electrical insulation and influences the spread and speed of impulse propagation (the toothpick principle ) Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 20 Significance of Myelination Schwann cells and myelin sheaths are significant obstacles to the diffusion of local anesthetic agents. Local anesthetic agents cannot diffuse through Schwann cells. Local anesthetic agents are only effective at unmyelinated constrictions between Schwann Cells (nodes of Ranvier). Significance of Myelination Myelinated nerves conduct impulses more quickly and more effectively than unmyleinated nerves. Myelin insulation allows for stronger local currents, in excess of firing threshold of adjacent segments Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 22 Significance of Myelination Myelination allows impulses to attain sufficient energy to bypass nodes (saltatory conduction). Significance of Myelination Local anesthetic injections must be of sufficient volume to block enough adjacent nodes to counteract this skipping effect. Impulses traveling through Type A fibers are conducted so rapidly, they can skip over (bypass) blocked segments and travel directly to subsequent nodes. It is estimated that a minimum of 8-10mm of the nerve membrane must be flooded by anesthetic solution in order to achieve anesthesia This is especially true in larger, more heavily myelinated nerves such as the IAN 2014 Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 24

6 Significance of Myelination Large, heavily myelinated nerves transmit impulses more rapidly than small, less myelinated nerves. Type A nerve fibers transmit impulses which are easily localized as to origin but at different speeds Type A beta fibers transmit sensations of touch, and vibration at 30 to 70 meters/second Type A delta fibers transmit sensations of sharp pain at 12 to 30 meters/second Significance of Myelination Differences in conduction velocities between specific Type A fibers underscore the Gate Control Theory. A neurological "gate" either blocks pain signals or permits them to travel to the brain. When occurring at the same time, vibration sensations arrive at the gate first, releasing inhibitory interneurons and closing the gate to sensations that arrive at the gate later (pain) Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 26 Significance of Myelination Nonmyelinated nerves conduct impulses more slowly than myleinated nerves. Type C nerve fibers transmit impulses which are difficult to localize as to origin Significance of Neuroanatomy Type C fibers transmit sensations of diffuse, dull ache and pain at 0.5 to 2 meters/second Type C fibers are more common in dental pulps than Type A 2014 Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 28 Significance of Neuroanatomy The perilemma and the perineurium are significant barriers to the diffusion of local anesthetic agents. Slow the diffusion of local anesthetic agents. Significance of Neuroanatomy The perilemma and the perineurium are significant barriers to the diffusion of local anesthetic agents. Slow the diffusion of local anesthetic agents. The larger the nerve, the greater the significance of these barriers in achieving profound anesthesia However, the lower number of fascicles in a nerve, the greater the incidence of local anesthesia induced paresthesia (ie. lingual nerve) The larger the nerve, the greater the significance of these barriers in achieving profound anesthesia However, the lower number of fascicles in a nerve, the greater the incidence of local anesthesia induced paresthesia (ie. lingual nerve) 2014 Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 30

7 Significance of Neuroanatomy Nerve fibers bundles are arranged into mantle and core segments. Significance of Neuroanatomy Mantle and core bundling impacts the order in which anesthesia develops. Mantle bundles innervate structures in close proximity IAN mantle bundles innervate the molar region Core bundles innervate structures at some distance away IAN core bundles innervate the chin and lips Molar regions anesthetize earlier and more easily Anterior regions anesthetize later and with more difficulty LA must penetrate through mantle to core LA arrives at the core in diluted form with fewer active molecules remaining 2014 Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 32 Significance of Neuroanatomy Presence of signs and symptoms of anesthesia is not a guarantee of profound anesthesia. Lack of profound anesthesia may be due to incomplete penetration of the LA agent to the deepest core bundles Effect of the Phospholipid Membrane 2014 Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 34 Effect of the Phospholipid Membrane The axolemma is a bi-layered phospholipid membrane. Hydrophilic heads of the phospholipids face outward toward the extracellular fluid. Lipophilic tails of the phospholipids face inward to create a fat core at the center of the membrane. Effect of the Phospholipid Membrane The axolemma regulates the movement of substances into and out of the neuron. Charged ions (which are water-soluble) can only pass through the membrane via channels. Sodium ions pass via sodium channels. Non-charged molecules (which are fat-soluble), can pass through the membrane with ease. Free-base local anesthetic agents pass easily 2014 Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 36

8 Effect of the Phospholipid Membrane The axolemma regulates the movement of substances into and out of the neuron. Charged ions (which are water-soluble) can only pass through the membrane via channels. Sodium ions pass via sodium channels. Effect of the Action Potential Non-charged molecules (which are fat-soluble), can pass through the membrane with ease. Free-base local anesthetic agents pass easily 2014 Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 38 Effect of the Action Potential Electrostatic attraction and ion pumps build negative electric potential along the axolemma up to a resting potential. Negatively charged protein molecules inside the axoplasm cannot cross the membrane. The sodium-potassium pump uses energy to move three sodium ions out of the neuron for every two potassium ions it moves in. Effect of the Action Potential Sodium channels are gated by positively-charged calcium ions which bind to unique receptor sites in the channel. By binding to these receptor sites, calcium ions block the inward flow of sodium ions and maintain the ionic separation and resting potential of the neuron Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 40 Effect of the Action Potential An action potential causes the neuron to fire and send an impulse. The neuron fires an action potential when enough sodium ions rush through the sodium channels into the axoplasm (depolarization). Effect of the Action Potential When the neuron is stimulated, calcium ions are released from their receptor sites and sodium rushes in. As sodium rushes into the channels, the membrane slowly depolarizes. The action potential is an explosion of electrical activity that is created by this depolarization which causes the firing threshold to be reached Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 42

9 Effect of the Action Potential If the neuron does not depolarize enough to reach the firing threshold, an action potential is not generated. Effect of the Action Potential Positively-charged local anesthetic agents bind to these calcium ion receptor sites and effectively block the sodium channels. All or nothing phenomenon Weak stimuli that do not produce enough excitation do not give rise to depolarization and impulse propagation They decrease the depolarization of the neuron so firing threshold is never reached (impulse extinction) Affinity for these calcium ion receptors determines the duration of action for a specific LA agent 2014 Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 44 Mechanism of Action of Local Anesthetics Calcium ions displaced, receptor bound Sodium channel blocked Depolarization decreased Firing threshold never reached Action potential never generated Neuron blockade (anesthesia) Significance of Biochemistry 2014 Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 46 Significance of Biochemistry Significance of Biochemistry All local anesthetics have lipophilic (fat-soluble) and hydrophilic (water-soluble) segments, at opposite ends of the molecule. Local anesthetics are classified by the chemical linkage between these two opposite ends. Lipophilic Hydrophilic Lipophilic Hydrophilic The two opposite ends are joined by either an ester or amide chemical linkage. Anesthetics without a hydrophilic segment are not injected, but are used topically (benzocaine). Ester Linkage ( esters ) Amide Linkage ( amides ) 2014 Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 48

10 Significance of Biochemistry Ester anesthetics possess ester linkages while amide anesthetics possess amide linkages. Ester anesthetics ( one-eye ) Procaine Cocaine Propoxycaine Tetracaine Benzocaine Amide anesthetics ( two-eyes ) Articaine Bupivacaine Lidocaine Mepivacaine Prilocaine Significance of Biochemistry Local anesthetics are weak bases which combine with acids to form water soluble salts which are used clinically in aqueous solution. ACID + BASE Hydrochloric Acid (HCl) SALT + WATER + Lidocaine Lidocaine + Water (for topical use) HCl (for injection) 2014 Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 50 Significance of Biochemistry The relative proportion of the ionized form to the non-ionized form varies with the ph of the local anesthetic in aqueous solution. Low ph (in aqueous solution) Ester Local Anesthetic Agents Non-ionized free base Ionized cation 2014 Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 52 Ester Local Anesthetics Ester local anesthetics Types Short-acting Procaine (Novocain) Long-acting Tetracaine (Pontocaine) Uses No longer used widely in dentistry (allergies) Used topically OTC products (benzocaine) Amide Local Anesthetic Agents 2014 Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 54

11 Articaine (Septocaine) Clinical Advantages An amide that is mostly metabolized (90 to 95%) like an ester via hydrolysis in plasma before it reaches the liver Presence of sulfur atom in the ring structure increases lipophilic properties Articaine (Septocaine) Specific patient care considerations Associated with higher than average tendency to induce paresthesia Data suggests that 4% anesthetic solutions are more highly associated with paresthesia Not clinically useful (or available) without vasoconstrictor Do not use in patients with sulfite allergy 2014 Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 56 Sulfur vs. Sulfa vs. Sulfate vs. Sulfite Sulfite Sulfur atom is not the allergenic agent. Hypersensitivity is related to similarity to sulfur dioxide. Bupivacaine (Marcaine) Clinical Advantages Very useful in extended procedures (greater than 60 to 90 minutes) Provides extended postoperative pain control (up to 12 hours of relief) Sulfa (sulfonamide) Sulfur atom is not the allergenic agent. When metabolized by the liver, the resulting sulfonamide molecule is capable of attaching to proteins, forming larger molecules that could serve as allergens Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 58 Bupivacaine (Marcaine) Specific patient care considerations Due to very slow onset of bupivacaine, consider using other rapid onset agents first to allow treatment to begin Long duration of action increases risk of selfinflicted soft tissue injury Lidocaine (Xylocaine) Clinical Advantages The standard against which all other local anesthetic agents are compared Long, impressive record of reliability and safety (no reports of allergy, cross-allergenicity) 2014 Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 60

12 Lidocaine (Xylocaine) Specific patient care considerations Twice as toxic as prilocaine with greater overdose-inducing potential than articaine Available in numerous OTC first aid/sunburn relief products Lidocaine (Xylocaine) Specific patient care considerations Useful in piggy-backing to achieve profound anesthesia after initial failure Used in medicine in the treatment of cardiac arrhythmia and epileptic seizures Available as prescription transdermal patches (Lidoderm) 2014 Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 62 Mepivacaine (Carbocaine) Clinical Advantages An amide which is as potent as lidocaine but is a relatively weak vasodilator Effective for short duration procedures without a vasoconstrictor Useful in piggy-backing to achieve profound anesthesia after initial failure Mepivacaine (Carbocaine) Specific patient care considerations Use for patients for whom vasoconstrictors are contraindicated (such as sulfite allergy) Use for patients for whom the use of vasoconstrictors is against medical advice Less efficiently metabolized than other LA agents so there is a greater risk of toxicity in overdose 2014 Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 64 Prilocaine (Citanest) Clinical Advantages An amide which is metabolized in the liver but also in the lungs and kidneys as alternate sites (useful in patients with liver dysfunction) As potent as lidocaine but a relatively weak vasodilator Effective for short duration procedures without a vasoconstrictor Prilocaine (Citanest) Specific patient care considerations Use for patients for whom vasoconstrictors are contraindicated (such as sulfite allergy) Use for patients for whom the use of vasoconstrictors is against medical advice 2014 Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 66

13 Prilocaine (Citanest) Specific patient care considerations Metabolized directly to orthotoluidine May produce methemoglobinemia Only at doses >600mg Relative contraindicated in patients with: Congenital or idiopathic methemglobinemia Anemia and sickle cell anemia Prilocaine (Citanest) Specific patient care considerations Associated with higher than average tendency to induce paresthesia Data suggests that 4% anesthetic solutions are more highly associated with paresthesia 2014 Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 68 Choosing A Local Anesthetic Agent Local Anesthetic Patient Management The most important factors in choosing a local anesthetic are the patient s physical condition and the length of the procedure. Certain conditions may rule out the use of certain agents or require dosage modification. The duration of action of the anesthetic must match the estimated length of the procedure as closely as possible Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 70 Medical History and Physical Evaluation Question #1 Is Today a Bad Day? Obtain and update a complete medical history and perform a physical evaluation of the patient, including determination of vital signs, at each appointment. The four vital signs Blood pressure Pulse Height Weight 2014 Thomas A. Viola, R.Ph. All Rights Reserved Thomas A Viola, R Ph All Rights Reserved 72

14 Medical History and Physical Evaluation Physical evaluation of the patient should be based on the American Society of Anesthesiologists (ASA) classification. ASA classification organizes patients into categories of health We can associate appropriate patient management considerations with each category Medical History and Physical Evaluation ASA Classification Class 1 Healthy patient with no current medical problems Patient management considerations» Can receive routine dental treatment and local anesthesia usually without issue» No treatment modifications necessary 2014 Thomas A Viola, R Ph All Rights Reserved Thomas A Viola, R Ph All Rights Reserved 74 Medical History and Physical Evaluation ASA Classification Class 2 Patient with mild to moderate systemic illness Patient management considerations» Consider stress reduction techniques» Consider limiting duration of treatment per appointment Medical History and Physical Evaluation ASA Classification Class 3 Patient with severe systemic disease that is incapacitating but not life-threatening Patient management considerations» Stress reduction techniques necessary» Medical consultations necessary 2014 Thomas A Viola, R Ph All Rights Reserved Thomas A Viola, R Ph All Rights Reserved 76 Medical History and Physical Evaluation ASA Classification Class 4 Patient with severe systemic disease that is limits activity and threatens life Patient management considerations» Elective care contraindicated» Emergency care in acute care setting Medical History and Physical Evaluation ASA Classification Class 5 Patient not expected to survive the next 24 hours Patient management considerations» Usually hospitalized Class 6 Clinically dead but life support maintained for organ donation Patient management considerations» None 2014 Thomas A Viola, R Ph All Rights Reserved Thomas A Viola, R Ph All Rights Reserved 78

15 Medical History and Physical Evaluation Question #2 Is Any Day a Good Day? ( for this patient) Determine if medical history and physical evaluation findings represent contraindications to dental treatment. Identify potential allergies, drug interactions or systemic illness for which the use of local anesthetic agents would be pose significant risk to the patient or would be contraindicated 2014 Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 80 Significant Drug Interactions with Local Anesthetics Local Anesthetic Interacting Drug Nature of Interaction Drug Interactions All local anesthetics Other local anesthetics (including topical) Toxicity of local anesthetics is additive when administered in combination All local anesthetics Opioid analgesics; CNS Depressants Additive sedation may occur; increased risk of local anesthetic overdose Lidocaine Tagamet (cimetidine) Competes for metabolism via liver enzymes, results in prolonged action of lidocaine and toxicity 2014 Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 82 Significant Drug Interactions with Vasoconstrictors Vasoconstrictor Interacting Drug Nature of Interaction Tricyclic Antidepressants (TCA s) Significant Drug Interactions with Vasoconstrictors Vasoconstrictor Interacting Drug Nature of Interaction Monoamine oxidase inhibitors (MAOI s) Epinephrine Amitriptyline (Elavil) Nortriptyline (Pamelor) Imipramine (Tofranil) Enhances cardiovascular action of epinephrine; may result in hypertensive crisis Severity: Inhibit reuptake of epinephrine; interaction is theoretical and may be seen only at high doses Epinephrine Phenelzine (Nardil) Tranylcypromine (Parnate) Selegiline (Emsam Patch) Interfere with enzymatic inactivation of epinephrine; may result in hypertensive crisis Severity: Epinephrine is primarily metabolized by COMT; interaction may be minimal Clomipramine (Anafranil) SSRI s not involved 2014 Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 84

16 Significant Drug Interactions with Vasoconstrictors Vasoconstrictor Interacting Drug Nature of Interaction Non- selective beta-blockers Epinephrine Propranolol (Inderal) Timolol (Blocadren) Blockade of beta receptors enhances alpha receptor activity, rapid increase in blood pressure followed by reflex bradycardia Contraindications Sotalol (Betapace) Nadolol (Corgard) Severity: Avoid use of epinephrine if possible; monitor for increased systolic, diastolic pressure 2014 Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 86 Contraindications Absolute Contraindications Patient has a documented allergy to a local anesthetic agent Possible cross-sensitivity to all other agents in same chemical class. Use agents in different chemical class. Patient has a documented allergy to bisulfites Avoid anesthetics that contain vasoconstrictors. Use anesthetics without vasoconstrictors. Contraindications Relative Contraindications Patient has methemoglobinemia Avoid use of prilocaine. Use other amide local anesthetic agents. Patient has significant liver dysfunction Use amide local anesthetics cautiously. Articaine (Septocaine), which is co-metabolized in the plasma, may be alternative. Patient has significant renal dysfunction Use amide local anesthetics cautiously Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 88 Contraindications Relative Contraindications (continued) Patient has hyperthyroidism Avoid high concentrations of vasoconstrictors. Use local anesthetic preparations with 1:200,000 or 1:100,000 epinephrine or use mepivacaine 3% or prilocaine 4% (no vasoconstrictor). Patient has significant cardiovascular disease Avoid high concentrations of vasoconstrictors. Use local anesthetic preparations with 1:200,000 or 1:100,000 epinephrine or use mepivacaine 3% or prilocaine 4% (no vasoconstrictor). Question #3 The Epinephrine Question (What Would Malamed Do?) 2014 Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 90

17 Considerations with Epinephrine Upon injection, local anesthetic agents produce vasodilation which varies by agent, patient and site of injection. Increased blood flow TO and AWAY from injection site. Results from relaxation of vascular smooth muscle. Significant vasodilation: articaine Minimal vasodilation: mepivacaine Significant vasoconstriction:??? Considerations with Epinephrine The side effects of epinephrine absorption must be weighed against the side effects of absorbed local anesthetic. Epinephrine may cause adverse effects in patients with pre-existing cardiovascular disease. However, rapid absorption and repeated doses of local anesthetic (with a vasoconstrictor) may result in adverse effects as well Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 92 Considerations with Epinephrine The benefit of using epinephrine to achieve profound anesthesia may outweigh the risk in patients with controlled cardiovascular disease. Pain-induced stress leads to the release of endogenous epinephrine. This may exacerbate cardiovascular disease. Considerations with Epinephrine If the patient is cleared for treatment, then epinephrine should be used in the lowest possible effective concentration. Use of epinephrine is contraindicated in situations of severe uncontrolled cardiovascular disease. However, these situations in themselves are contraindications to elective dental treatment! 2014 Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 94 Considerations with Epinephrine The dose of epinephrine in a dental cartridge is far less than doses used clinically in treating anaphylaxis. However, epinephrine should be avoided in: Patients with uncontrolled hypertension Considerations with Epinephrine In normal healthy patients, the maximum recommended dose of epinephrine is 0.2 mg per appointment, or 11 cartridges of 1:100,000 dilution. Patients with uncontrolled hyperthyroidism Patients with severe uncontrolled cardiac disease 2014 Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 96

18 Considerations with Epinephrine In patients with clinically significant cardiovascular impairment, the maximum recommended dose of epinephrine is 0.04 mg per appointment, or 2 cartridges of 1:100,000 dilution. 1:50,000 dilution = 1 cartridge 1:100,000 dilution = 2 cartridges 1:200,000 dilution = 4 cartridges Questions and Answers Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 98 Part III Treatment and Management of Post-therapeutic Dental Pain Non-Narcotic Analgesics (COX Inhibitors) 2014 Thomas A. Viola, R.Ph. All Rights Reserved 100 COX Inhibition Phospholipids (phospholipase) Arachidonic Acid Aspirin Aspirin Formulations Regular ASA (81mg vs. 325mg) (COX-1) Physiologic Prostaglandins GI protection Renal protection Smooth muscle relaxes Regulate blood clotting (COX-2) Pathologic Prostaglandins Inflammation Pain sensitization Leukocytosis Enteric coated ASA (dissolves in intestines) Often formulated with caffeine 2014 Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 102

19 Aspirin Aspirin Formulations Combination products With a buffer Decreases GI side effects (Bufferin) With an opioid Decreases amount of opioid (Percodan) Equianalgesia 650mg of aspirin = 650 mg acetaminophen= 200 mg of ibuprofen = 275 mg of naproxen Aspirin Mechanism of action Inhibits the enzymes COX-1 and COX-2 Decreases pain, fever and inflammation Decreases uterine contraction and inflammation Decreases clotting inducers Low doses result in reduced platelet aggregation 2014 Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 104 Aspirin Therapeutic Uses Antiplatelet Used in low doses to prevent MI or stroke Antipyretic Lowers body temp if above normal Analgesic Used to treat mild to moderate pain Antiinflammatory Decreases pain, redness and swelling Aspirin Adverse reactions Gastrointestinal ulceration Decreased production of protective prostaglandins Decreased protective mucous Increased gastric acid secretion Nausea and vomiting GI bleeding 2014 Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 106 Aspirin Adverse reactions (continued) Altered bleeding time Irreversibly reduces platelet aggregation Platelet adhesiveness is reduced for the life of the platelet Replacement of platelets needed for normal clotting May result in excessive or prolonged bleeding after procedures Aspirin Patient care considerations Reye's syndrome Possible hepatotoxicity/encephalopathy Topical application to oral mucosa May result in severe ulceration Zero-order kinetics Increases risk of overdose and toxicity 2014 Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 108

20 Aspirin Drug interactions Increased effectiveness of other drugs Mechanism Displacement of plasma-protein bound drugs Common Drugs Affected Coumadin (warfarin) Result Increased risk of hemorrhage Aspirin Drug interactions Decreased effectiveness of other drugs Mechanism Decrease renal prostaglandins Increase sodium/fluid retention Common Drugs Affected Antihypertensives??? Result Exacerbated cardiovascular disease 2014 Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 110 Aspirin Contraindications of aspirin Peptic ulcer Pregnancy Gout Hemophilia History of hypersensitivity Cross-sensitivity with NSAIA s NSAIA s Types ibuprofen (Motrin, Advil) naproxen sodium (Anaprox, Aleve) naproxen (Naprosyn) indomethacin (Indocin) etodolac (Lodine) nabumetone (Relafen) meloxicam (Mobic) 2014 Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 112 NSAIA s Types Other COX-1 inhibitors offer no apparent advantage over ibuprofen or naproxen in the treatment of dental pain diclofenac diflunisal flurbiprofen ketoprofen meclofenamate NSAIA s Mechanism of action Inhibit the enzymes COX-1 and COX-2 Decrease pain, fever and inflammation Decrease uterine contraction and inflammation Decrease clotting inducers More effective if given before painful stimuli is experienced 2014 Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 114

21 NSAIA s Pharmacologic effects Antipyretic Lower body temp if above normal Analgesic Treatment of mild to moderate pain Very effective in the treatment of dental pain Antiinflammatory Treatment of inflammatory joint disease Treatment of dysmenorrhea Treatment of acute attacks of gout NSAIA s Adverse reactions Gastrointestinal ulceration Decrease production of protective prostaglandins Decrease protective mucous Increase gastric acid secretion Nausea and vomiting GI bleeding 2014 Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 116 NSAIA s Adverse reactions (continued) Altered bleeding time Reversibly reduce platelet aggregation Platelet adhesiveness reduced only until drug is excreted No replacement of platelets needed for normal clotting May result in excessive or prolonged bleeding after procedures Lesser effect than aspirin NSAIA s Adverse reactions (continued) CNS effects Sedation, confusion, dizziness, vertigo Advise patients to use caution when driving Renal effects Increase incidence of UTI and cystitis Increase risk of renal failure 2014 Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 118 NSAIA s Adverse reactions (continued) Cardiovascular effects Exacerbate cardiovascular disease Decrease renal prostaglandins Increase sodium and fluid retention Interfere with cardioprotective effects of once-daily aspirin Oral effects Ulcerative stomatitis Xerostomia NSAIA s Patient care considerations Hypersensitivity reactions Cross-sensitivity with ASA and other NSAIA s Anaphylactoid reactions Dermatological reactions Stevens Johnson Syndrome (SJS) Toxic epidermal necrolysis (TEN) 2014 Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 120

22 NSAIA s Patient care considerations (continued) Teratogenic effects Decrease uterine prostaglandins Premature closures in fetal circulation Prolonged gestation Iatrogenic disease Available OTC Not listed as medications on medical history Maximum daily dose of ibuprofen: 3200mg Maximum daily dose of naproxen: 1500mg NSAIA s Drug interactions Increased effectiveness of other drugs Mechanism Displacement of plasma-protein bound drugs Common Drugs Affected Coumadin (warfarin) Result Increased risk of hemorrhage 2014 Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 122 NSAIA s Drug interactions (continued) Increased effectiveness of other drugs Mechanism Decreased renal excretion Common Drugs Affected Lithium Result Increased muscle rigidity NSAIA s Drug interactions (continued) Decreased effectiveness of other drugs Mechanism Decrease renal prostaglandins Increase sodium/fluid retention Common Drugs Affected Antihypertensives??? Result Exacerbated cardiovascular disease 2014 Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 124 Contraindications Asthma NSAIA s NSAIA s Contraindications Renal function impairment Cardiovascular disease with fluid retention Pregnancy Peptic ulcer/ulcerative colitis History of hypersensitivity Cross-sensitivity with aspirin 2014 Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 126

23 Types Celecoxib Selective COX-2 Inhibitors Mechanism of action Inhibit COX-2 to a greater extent than COX-1 Decrease pathologic prostaglandin production Decreases pain sensitizers Decreases fever/inflammation inducers Maintain physiologic prostaglandin production Fewer GI side effects Celecoxib Pharmacologic effects Analgesic Treatment of mild to moderate pain Less effective than traditional NSAIA s in the treatment of dental pain Antiinflammatory Treatment of inflammatory joint disease Treatment of dysmenorrhea Treatment of acute attacks of gout 2014 Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 128 Celecoxib Adverse reactions (continued) Altered bleeding time Reversibly reduce platelet aggregation Platelet adhesiveness reduced only until drug is excreted No replacement of platelets needed for normal clotting May result in excessive or prolonged bleeding after procedures Lesser effect than aspirin Celecoxib Adverse reactions (continued) CNS effects Sedation, confusion, dizziness, vertigo Renal effects Increase incidence of UTI and cystitis Increase risk of renal failure Oral effects Ulcerative stomatitis Xerostomia Taste alteration 2014 Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 130 Celecoxib Adverse reactions (continued) Cardiovascular effects Thrombotic events Myocardial infarction, stroke (fatal!) Exacerbate cardiovascular disease Decrease renal prostaglandins Increase sodium and fluid retention Interfere with cardioprotective effects of once-daily aspirin Celecoxib Patient care considerations Hepatic effects Elevated liver enzymes Anaphylactoid reactions Contraindicated in patients with sulfa allergy Teratogenic effects Decrease uterine prostaglandins Premature closures in fetal circulation Prolonged gestation 2014 Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 132

24 Celecoxib Drug interactions Increased effectiveness of other drugs Mechanism Displacement of plasma-protein bound drugs Common Drugs Affected Coumadin (warfarin) Result Increased risk of hemorrhage Celecoxib Drug interactions (continued) Increased effectiveness of other drugs Mechanism Decreased renal excretion Common Drugs Affected Lithium Result Increased muscle rigidity 2014 Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 134 Celecoxib Drug interactions (continued) Decreased effectiveness of other drugs Mechanism Decrease renal prostaglandins Increase sodium/fluid retention Common Drugs Affected Antihypertensives Result Exacerbated cardiovascular disease Celecoxib Drug interactions (continued) Increased effectiveness of celecoxib Mechanism Decrease hepatic metabolism of celecoxib Common Drugs Affected Diflucan (fluconazole) Result Exacerbated liver toxicity 2014 Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 136 Types Tylenol, Panadol Acetaminophen (APAP) Mechanism of action Unknown (hypothesized) Decreases PG synthesis in CNS Elevates overall pain threshold Decreases PG synthesis in hypothalamus Reduces fever Acetaminophen (APAP) Pharmacologic effects Antipyretic Lowers body temp if above normal Analgesic Used to treat mild to moderate pain Very effective in the treatment of dental pain Considered the most safe analgesic 2014 Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 138

25 Acetaminophen (APAP) Adverse reactions Hepatotoxicity Approximately 4% of every dose is converted to a liver-toxic metabolite Inactivated by gluthathione in liver Possible liver failure in acute overdose or chronic high-dose ingestion Maximum daily dose of APAP: 4000mg to be 3200mg) (soon Acetaminophen (APAP) Adverse reactions Hepatotoxicity (continued) Exacerbated by liver-enzyme inducing drugs Alcohol, cigarette smoking, anticonvulsants Delayed reaction Peak hepatotoxicity occurs 3 to 4 days after acute intoxication IF patient survives, recovery may take up to three months 2014 Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 140 Acetaminophen (APAP) Contraindications Hepatitis or other known decreased liver function Chronic alcohol ingestion Anti-Gout Agents Other liver microsomal enzyme inducing drugs Impaired renal function 2014 Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 142 Anti-Gout Agents Gout Increase in uric acid Deposition of urate crystals. in joints Treatment Colcrys (colchicine) Interferes with inflammatory response Uloric (febuxostat), Zyloprim (allopurinol) Decreases uric acid production Opioid Analgesics (Substance P Inhibitors) Indomethacin NSAIA - decreases inflammatory response 2014 Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 144

26 Opioid Analgesics Substance P facilitates the transfer of pain impulse from peripheral neurons to CNS signaling neurons. Opioid Analgesics Spinal interneurons respond to stimulation from CNS neurons by releasing endogenous opiates, which block transmission of pain impulses. In the dorsal horn of the spinal cord, peripheral pain neurons meet CNS signaling neurons. Endogenous opiates (also known as enkephalins) bind to opiate receptors on the peripheral pain neuron to inhibit the release of substance P Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 146 Opioid Analgesics By binding with any free opiate receptors, opioid analgesics further inhibit the release of substance P and thus further block transmission of pain impulses to the brain. Opioid analgesics supplement and mimic the pain-blocking effect of the endogenous opiates. Opioid Analgesics Opioid Analgesics used in Dentistry Codeine Combination with APAP (Tylenol w/codeine) Hydrocodone Combination with APAP (Vicodin, Lortab) Combination with ibuprofen (Vicoprofen) Oxycodone Combination with APAP (Percocet, Endocet) Combination with ASA (Percodan) Combination with ibuprofen (Combunox) Propoxyphene Combination with APAP (Darvocet) 2014 Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 148 Opioid Analgesics Pharmacokinetics Absorption Absorbed through skin, mucous membranes Transdermal patches very effective Metabolism Liver High first-pass effect Pharmacologic effects Analgesia Opioid Analgesics Cough suppression Used to treat severe non-productive coughs Treatment of diarrhea and traveler s sickness 2014 Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 150

27 Opioid Analgesics Mechanism of action Bind to opiate receptors Inhibit substance P Active at other specific receptors in the brain Unique pharmacologic and adverse effects Opioid Analgesics Mechanism of action (continued) Active at other specific receptors in the brain Unique pharmacologic and adverse effects Mu receptors Analgesia Sedation Euphoria Respiratory depression Reduced GI motility Physical dependence 2014 Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 152 Opioid Analgesics Mechanism of action (continued) Active at other specific receptors in the brain Unique pharmacologic and adverse effects Delta receptors Respiratory depression Physical dependence Kappa receptors Sedation Reduced GI motility Miosis Dysphoria 2014 Thomas A. Viola, R.Ph. All Rights Reserved 153 Adverse reactions CNS effects CNS depression CNS stimulation Opioid Analgesics Cardiovascular effects Peripheral vasodilation Orthostatic hypotension Respiratory effects Respiratory depression leads to death from overdose 2014 Thomas A. Viola, R.Ph. All Rights Reserved 154 Opioid Analgesics Adverse reactions Ocular effects Miosis (constricted pupils) GI effects Constipation Reduced GI motility Nausea and emesis Direct stimulation of the chemoreceptor trigger zone Opioid Analgesics Patient care considerations Hepatic first-pass effect Hypersensitivity reactions Dermatological reactions (pruritis, flushing) Addiction and dependence Tolerance develops to most effects Withdrawal symptoms upon abrupt cessation 2014 Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 156

28 Opioid Analgesics Patient care considerations Analgesics used in dentistry combine opioid analgesics and non-opioid analgesics May result in unintentional overdose of non-opioid ingredients when self-administered Opioid Analgesics Drug interactions Increase risk of additive adverse effects Increase risk of CNS depression Increase risk of respiratory depression Alcohol, anti-anxiety medications Increase risk of constipation Anticholinergics 2014 Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 158 Opioid Analgesics Contraindications Chronic respiratory disease (COPD) Head injuries Treatment of Opioid Analgesic Addiction Hepatic, renal function impairment Prostatic hypertrophy, constipation 2014 Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 160 Treatment of Opioid Analgesic Addiction Narcan (naloxone) Pure opioid antagonist Used in the treatment of opioid overdose Found in dental office emergency kit Treatment of Opioid Analgesic Addiction Subutex (buprenorphine) Taken as part of a treatment plan in the management of current opioid addiction Partial opioid agonist and antagonist Naltrexone Opioid antagonist Taken voluntarily to maintain opioid-free state after rehabilitation from opioid addiction Blocks effects if opioids are taken (but not adverse effects) 2014 Thomas A. Viola, R.Ph. All Rights Reserved 161 Suboxone (buprenorphine plus naloxone) Taken as part of a treatment plan in the management of current opioid addiction Naloxone blocks effects if recipient attempts to illicitly liquify and inject this drug 2014 Thomas A. Viola, R.Ph. All Rights Reserved 162

29 Preventing Opioid Analgesic Diversion Preventing Opioid Analgesic Diversion Since dental offices are potential sources of opioid analgesics, the dental team must take precautions to prevent diversion. Preventing opioid analgesic diversion in the dental office requires that the dental team Recognize drug-seeking behavior Prescribe opioid analgesics appropriately Thomas A. Viola, R.Ph. All Rights Reserved 163 Utilize strategies to prevent order alteration 2014 Thomas A. Viola, R.Ph. All Rights Reserved 164 Preventing Opioid Analgesic Diversion Preventing Opioid Analgesic Diversion Recognizing drug-seeking behavior Emergency calls or visits near the end of office hours, especially before weekends/holidays Requesting specific drugs by name Repeated loss of prescriptions Prescription Drug Monitoring Program!!! Reluctance to provide prior medical records or information for other treating physician(s). Don t bill my insurance, I ll pay cash 2014 Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 166 Preventing Opioid Analgesic Diversion Safeguarding prescription pads Store prescription pads in secure locations away from patient areas Entrust access to blank prescription pads to as few employees as possible Order small quantities of prescription pads at one time to facilitate tracking Do not pre-sign blank prescriptions and do not use prescriptions with pre-printed DEA numbers Preventing Opioid Analgesic Diversion Preventing prescription alteration Complete all required information on the prescription blank, including patient s full name, address and date of birth Date all prescriptions and use words and numbers to indicate quantity to be dispensed Enter the exact number of refills authorized or the word zero if none are authorized (do not leave blank) 2014 Thomas A. Viola, R.Ph. All Rights Reserved Thomas A. Viola, R.Ph. All Rights Reserved 168

30 100th Anniversary of Dental Hygiene Hold for 2015 logo slide Questions and Answers Contact Information thomasviola.com facebook.com/tomviolarph facebook.com/dentalpharmacology facebook.com/dentallocalanesthesia 2014 Thomas A. Viola, R.Ph., C.C.P. All Rights Reserved