Drugs, Disease, and Dentistry Elizabeth A. VandeWaa, Ph.D. University of South Alabama Drugs and Dentistry Sedatives Local Anesthetics Pain Medications Bisphosphonates Drugs of Abuse Sedatives: Just Relax… SEDATIVES/ANXIOLYTICS Sometimes used as preanesthetic medications When used with nitrous oxide, typically less NO is needed (especially in children!!) Watch for oversedation and respiratory depresssion To Ease the “Stress”… SEDATIVES/ANXIOLYTICS Benzodiazepines (Alprazolam, Oxazepam, Midazolam, Diazepam) plus antihistamines (Benedryl) and/or Barbiturates (Secobarbital) Alprazolam one of the top 20 drugs prescribed in the US Loss of consciousness, respiratory depression, death. Antidote to BZD overdose is Flumazenil (Romazicon) Pros and Cons of Sedative Use Benzodiazepines Reversing agent; they work!; addictive; amnesia; patient needs care in getting to/from appointment Barbiturates No reversing agent; respiratory depression; patient care; sedating Antihistamines Long duration of sedation in the elderly; dizziness Potentially Problematic Drug Combinations SEDATIVES plus….. Chloral Hydrate plus Warfarin Prolongs bleeding time Chloral Hydrate plus Lasix Increases Barbiturates plus Valproic acid Prolonged HR, BP, diaphoresis sedation Barbiturates plus Warfarin Prolongs bleeding time Potentially Problematic Drug Combinations Benzodiazepines plus…. Rifampin Decreased sedation Carbamazepine Decreased sedation Calcium Channel Blockers Increased sedation Tagamet Increased sedation Erythromycin Increased sedation Protease Inhibitors Increased sedation Local Anesthetics— Comfortably Numb Articaine Fairly safe and superior to conventional anesthetics in controlling procedural pain when delivered via block injection or by infiltration Adverse effects of articaine (few) include mandibular nerve injury, hypoesthesia, pain, and tinnitus Local Anesthetic Use Safety Issues with these drugs Never underestimate the importance of the medical history. Always obtain complete information at the preoperative appointment and update it at the beginning of each appointment Before the local anesthetic is administered, address any fears or nervousness the patient may have. Local Anesthetics Safety issues with these drugs Make sure the patient is in a supine position for the injections. Watch patients throughout the administration of anesthetics. Do not leave them alone following the injection. Problematic Patients and LA Cardiac Patient When vasoconstrictors are used Patient on Tricyclic antidepressants Recreational drug user—stimulants Allergic patient Considerations with LA Recreational use of cocaine by patients can increase the risk of elevated blood pressure and cardiac arrhythmias with injectable anesthetics Paresthesia has been reported occasionally after local anesthesia with many of the amide linkages Considerations with LA Levonordefrin should not be used with tricyclic antidepressants, and reduced dosages of epinephrine are recommended. May want to avoid this vasoconstrictor altogether in patients with cardiovascular disease (or discuss with their cardiologist) LA Allergic Reactions Allergic reactions to amide linkage anesthetics are relatively rare and mostly attributed to the preservatives or antioxidants found in the anesthetic. Ester linkage anesthetics (such as Novocain) had a higher rate of reported allergy due to the para-aminobenzoic acid (PABA) preservative LA and Allergic Reactions Most reported allergic reactions are caused by the preservatives methylparaben and metabisulfite. Metabisulfite is added as an antioxidant when vasoconstrictors are used in anesthetics. For patients reporting a documented allergy to sulfites, avoid anesthetics containing vasoconstrictors. For these patients, plain anesthetics such as mepivacaine 3% or prilocaine 4% are available without the preservative. LA Allergic Reactions For documented allergy to both ester and amide groups, diphenhydramine can be used for procedures of short duration. One study found diphenhydramine efficacy similar to that of prilocaine. Larger studies needed to confirm this….but promising! Potentially Problematic Drug Combinations Local anesthetic toxicity is additive in combination. Combination therapy is acceptable, but total dose should not exceed maximum recommended doses. Watch this especially in pediatrics! A child may be 1/3 to1/4 the size of an adult, but the mouth is not. Thus, the drug need is about the same….but metabolic and excretory rates are usually reduced in children. Potentially Problematic Drug Combinations Amide local anesthetics (Lidocaine, Articaine, Mepivacaine, etc.) plus inhibitors of drug metabolism: Cimetidine, Propranolol The combination may prolong the effect of the local or may enhance toxicity of local Local Anesthetic Toxicity: CNS excitation, seizures, respiratory depression, cardiac arrest Potentially Problematic Drug Combinations Local anesthetic-induced methemoglobinemia Seen with very high doses of Prilocaine or Benzocaine, when patient is also taking Dapsone, or is either very old or very young, a COPD’er, anemic, or has G-6-PD deficiency. Will present with cyanosis, dyspnea, and increased heart rate. Methylene blue is the treatment. Local Anesthetics Safety issues with these drugs In an emergency, ensure that someone remains with the patient at all times, monitoring breathing and heart rate until the emergency is past or emergency medical personnel arrive. Be prepared to assist with CPR Know where emergency equipment is located Hair Color and Local Anesthesia? A pharmacogenomic phenomenon Redheads are more resistant to local (and general) anesthetics due to a mutation in the MC1R gene They may require a clinically significant higher dose of local anesthetics to numb pain Average is 20-25% more! Pregnancy and Locals Data indicate that lidocaine and prilocaine may be safest for use among pregnant and lactating women Pregnancy Category B No harm to animals, but adequate and well-controlled human studies have not been conducted….OR studies conducted have not shown adverse effects Pregnancy Category C No adequate trials in humans Problematic Drugs and Dentistry Drugs that cause gingival hyperplasia: Phenytoin (Dilantin) Cyclosporin A (Gengraf) Diltiazem (Cardizem) Verapamil (Isopten, Calan) Nifedipine (Procardia) Aggressive oral hygiene (especially flossing) seems to be helpful for this patient Gingival Hyperplasia Pain in Dentistry Pain Medications in Dentistry Two Types of Pain Two Types of Pain Medication Two Types of Patient! “Rate Your Pain” Two Types of Pain Acute Pain Related to procedure Short duration Inflammation-related, trauma related WILL “get better” Responds well to intervention, NSAIDs, ice, diversion Two Types of Pain Chronic Pain Hopefully NOT procedure-related, unless patient needs extensive work May be infection-related Pain will be described as dull, persistent, interfering with sleep—non-distractable Two Types of Pain Medication Opiates All CS, require prescription Compounded or single substances Short or long-acting REMS for some… Non-Opiates Some prescription, some not New formulations that may be helpful Multi-modal therapies Two Types of Patient… Type 1 Compliant Opiate-naïve Fairly high pain tolerance, “good soldier”, good patient…but also may be an “underreporter” Type 2 “Experienced”, possibly opiate tolerant Possible low tolerance to pain, but don’t rule out pharmacogenomics Controlled Substances Schedule I: No approved medical use. Schedule II: Written prescription, signed by prescriber. Oral orders ONLY in emergencies with a written Rx to follow within 72 h. No refills. Schedules III and IV: Oral or written prescriptions. May be refilled up to 5 times, but refills must be made within 6 months of original order. Pain Medications That May Pose Problems Opioids relieve dull, constant pain Can cause euphoria, sedation, reduction of anxiety Can cause tolerance and physical dependence…abuse liability And YOU may not be the only prescriber The Doctor Shopper Prescription Opiate Facts US consumes 80 % of the world’s opioids and 99% of the world’s hydrocodone Accidental overdoses of Rx opiates kill more people in 17 states than do car accidents Males are 1.5 times more likely to become addicted AL is in the top 25% of states with 8.5-12.6 kg prescription painkillers/10,000 people sold/year Drug overdose death rate about 13/100,000 Highest in rural counties, females, middle-aged Prescription Opiate Facts Hydrocodone/APAP is the #1 prescribed drug in the US!!!! 1 in 20 people in US take opiates for nonmedical use Enough Rx painkillers were prescribed in 2010 to medicate EVERY adult in the US around –the-clock for one month State-by-State Opioid Related Deaths Prescribing Opiates Dentists prescribe 12% of all opiates in the US Accounting for 1 billion doses per year Opiates should be prescribed on a fixed schedule, not as prn medications Vicodin (Hydrocodone) and Percocet (Oxycodone) are the most commonly prescribed Hydrocodone is the most prescribed drug in the US There is a movement to ban Vicodin and Percocet from commerce Keeping Current With Drugs to Manage Pain Opiates are and will be mainstays of chronic pain management Problems associated with use fall into 2 categories Prescriber education, liability, prescriptive authority User abuse, diversion With Respect to Costs… Prescription drug abuse accounts for 1 million ED visits/year Equal to the number due to illegal drugs 60% of hospital costs related to opioid overdoses are paid for with public funds What to do? What To Do? Judicious Approach to Prescribing Institute clear policies and stick to those policies. If patients report that their medications have been stolen, require that they report that to the police and bring a police report to visit for verification. Statewide databases that allow for tracking of patient prescriptions, including prescriptions for all schedule II drugs. REMS programs Fire the patient! Opioid Sources in the Last 6 Months Source Bought from a dealer Someone gave them Bought from a patient who sells their medication Patients, % 84.2 83.0 74.7 Legitimate prescription for pain Stolen Prescription from physician but no legitimate reason 57.7 44.1 30.6 Prescription from multiple physicians 23.6 Internet 8.9 Prescription from physician who prescribes 3.4 illegally Forged prescription Other source 2.8 3.8 Risk Evaluation and Mitigation Strategies REMS is being proffered as a way to decrease the risks associated with longterm opiate use/abuse—long-acting drugs included first Morphone, morphine SR, hydromorphone ER, methadone, oxycodone CR, oxymorphone ER, transdermal fentanyl and transdermal buprenorphine, morphine/naltrexone ER Drug companies pay to educate prescribers. IR drugs now being included Will REMS Work? FDA is asking that the training be mandatory for anyone with a DEA# Advantages? OBVIOUS! Helpful to the patient, prescriber Disadvantages? OBVIOUS! Though most prescribers are on board with the idea….time, inconvenience The fear is that other drugs will be “switched to” Making Opiates Safer--Latest Legislation A bill introduced July 19, 2012 in the U.S. House would require most painkillers to have safeguards to prevent abuse If pain medications did not adopt the safety features outlined in the bill, they would be removed from the Food and Drug Administration’s (FDA) approved list of generic drugs Opioids for Pain Opioids used to treat chronic pain include morphine sulfate (morphine, MSIR, MSContin, Roxanol, Kadian, Avinza) IR/ER, oxycodone (Oxycontin, OxyIR) IR/ER, oxymorphone (Opana) IR/ER, fentanyl (Duragesic) (IR/ER), methadone, tramadol (Ultram, Ultracet) IR/ER, hydromorphone (Dilaudid) IR, hydrocodone/acetaminophen (Vicodin, Lorset, Lortab, Norco) IR, and percocet (oxycodone/acetaminophen) IR. Tramadol (Ultram, Ryzolt) Weak agonist at mu receptors, considered non-narcotic; also blocks NE and serotonin reuptake Good PO for moderate to moderately severe ACUTE pain Not a CS, but….avoid prescribing to patients with a history of drug abuse—diversion a problem Many drug interactions—watch for serotonin syndrome, seizures!! Try limit use to about 5 days Requires metabolism, and 5-15% of the population are slow metabolizers Do NOT use ER tablets in patients with hepatic impairment! Tapentadol (Nucynta) A non-racemic molecule that is a moderate mu-opiate agonist and only effects the uptake of norepinephrine into nerve endings No metabolic activation is required for analgesia and there are no active metabolites This is an advantage over Tramadol It does not appear to cause the confusional states sometimes associated with tramadol May be able to reduce morphine dose Useful for ACUTE pain C-II controlled substance NSAIDs for Pain Most widely used group of drugs for pain Side effects include GI bleeds/distress and renal and hepatotoxicity No reduction of inflammation with acetaminophen Watch use in children, in alcohol use, high BP, liver disease, renal disease NSAIDs in Dental Practice Lornoxicam (Xefo, Xafon, Lorcam, Acabel) Patients receiving this drug in a single dose of 8 mg during dental procedures or immediately after reported a “high level” of pain relief. Relief was comparable to a 200-400 mg dose of Ibuprofen. Diclofenac Potassium (Cambio, Cataflam) 50 mg tablets, IR preps gave patients good pain relief, but are not recommended for use beyond 48 h due to hepatotoxicity. Newer Formulations of NSAIDs Ibuprofen Sprix nasal spray; Caldalor IV IV formulation (800 mg) reduces opiate need by about 25% post-op No real worries about renal function since use is short-term Acetaminophen IV for acute pain, or combined with an opiate Ofirmev; fast, penetrates CNS, anti-pyretic 1000 mg in those weighing >50 kg every 6 h For Chronic Pain… Determine if infection is a possibility, then treat! Consider other sources, such as intracranial, vascular/myofascial, neurogenic, TMJ, ear, eye, nasal, paranasal sinus, lymph node, and salivary gland pathology, as well conditions such as untreated coronary vasospasm and refractory angina. For Chronic Pain… Atypical facial pain or atypical odontalgia of unknown etiology (termed persistent facial pain of unknown etiology [PFPUE]) can be managed by multimodal drug therapy A combination of opiates, NSAIDs, antiseizure agents, sedatives, antidepressants may all be used Cognitive/behavior therapy may also be introduced Treatment of Pain—Multimodal Therapies Opioids can help with ascending pain pathways in chronic pain management. Plus an antagonist to deal with opioid ADRs NSAIDs can be used to decrease prostaglandin formation centrally, and also to affect substance P and serotonin pathways. Membrane stabilizing drugs such as seizure meds alter ion flux in nerve membranes, blunting depolarization, affecting both pain transmission and perception. Anticonvulsants Used for Pain Gabapentin (Neurontin), Pregabalin (Lyrica), Tiagabine (Gabatril), Topiramate (Topamax). Good for neuropathic pain, pain due to nerve injury, sensory neuropathy. May cause drowsiness, dizziness, report any vision changes!! Anticonvulsants Used for Pain Carbamazepine (Tegretol) Valproic acid (Depakote) Phenytoin (Dilantin) Clonazepam (Klonopin) Lamotrigine (Lamictal) Levetiracetam (Keppra) Oxcarbazepine (Trileptal) Zonisamide (Zonegran) Antidepressants for Pain Work best for neuritic or neuropathic pain, less helpful for musculoskeletal pain Agitated or anxious patients do best with antidepressants that are more sedating Most common SE are drowsiness, constipation, dry mouth, blurred vision. Watch for Serotonin Syndrome. Antidepressants for Pain BENEFITS Not as much GI upset as NSAIDs May help with sleep May reduce depression associated with chronic pain May relieve anxiety associated with pain May increase effects of other pain meds Are non-addictive Safety is documented Antidepressants Commonly Prescribed for Pain TCAs: Amitriptyline (Elavil), Desipramine (Norpramin), Imipramine (Tofranil), and Nortriptyline (Aventyl, Pamelor) Desipramine has lowest SE profile SSRIs: Duloxetine (Cymbalta), Venlafaxine (Effexor), Mirtazepine (Remeron) Best profile for pain. Other SSRIs not as effective for chronic pain New Uses of Old Drugs for Pain Muscle Relaxants Cyclobenzaprine (Flexeril)—this is really a TCA, so it has all the TCA side effects Carisoprodol (Soma)—now banned by European Medicines Agency (our equivalent of the DEA) due to abuse issues—watch for abuse potential! Methocarbamol (Robaxin) and Metaxolone (Skelaxin)—older; sedation is main effect/SE Orphenadrine (Norflex)—this is actually Benedryl, so sedation and inhibition of motor function will be seen Older Drugs being Used in Multimodal Strateiges Tizanidine (Zanaflex)—an agent for spasticity that shows some evidence for the treatment of chronic pain, musculoskeletal pain, and neuropathic pain Alpha-agonist similar to clonidine; since it causes significant sedation, should be reserved for night time use Lioresal (Baclofen)—antispasmodic that is being used (off-label) for musculoskeletal pain. Sedation is side effect of note. Benefits of Multimodal Therapy Using multi-modal analgesia (“balanced analgesia”)… Benefit the patient in that it can bring sedation, pain relief while reducing dependence/tolerance, and reduce tissue destruction Benefit the prescriber in that it may mitigate some of the adverse effects of opioids, may reduce tolerance/dependence Bisphosphonates: Implications in Dental Practice Bone Disorders Osteoporosis Mainly seen in females, but males can be afflicted, too More than 10 million women have osteoporosis Another 34 million have reduced bone mass Osteoporosis is the cause of 1.5 million fractures/year Of the 300,000 people who get hip fractures/year, 50,000 die Osteoporosis accounts for more than 432,000 hospital admits/year, 2.5 million office visits, and 180,000 nursing home admits Price tag: $17 billion/year Bone Resorption Bone Disorders After osteoporosis, Paget’s disease of the bone is the most common bone disorder in the US. 3% of people over age 40; 10% of those over age 80 Currently, about 8.2 million sufferers Bisphosphonates Oral bisphosphonates include: IV bisphosphonates include: Alendronate (Fosamax) Risedronate (Actonel) Ibandronate (Boniva) Tiludronate (Skelid) Etidronate (Didronel) Clodronate (Bonefos) Zoledronate (Zometa, Pamidronate (Aredia) Etidonrate (Didronel) Reclast) Bisphosphonate Use Oral BPs are among the top 25 prescribed drugs in the US Have a high therapeutic index Oral BPs decrease fractures in the hips and vertebrae by 50% IV BPs increase compliance and decrease fractures by 70% Indications for Bisphosphonate Use Postmenopausal osteoporosis Osteoporosis in men Glucocorticoid-induced osteoporosis Paget’s disease Hypercalcemia of malignancy Mechanism of Action of BPs BPs are incorporated into bone and inhibit resorption by decreasing number and activity of the osteoclasts. Since these drugs are derivatives of pyrophosphate, they “look” like a normal bone constituent. When they are resorbed by osteoclasts, they inhibit their activity They decrease numbers of osteoclasts by reducing osteoclast recruitment and by stimulating osteoblasts So…if BPs Get Concentrated in the Jaw… They slow down the activity of osteoclasts This leads to areas of bone that do not get resorbed, and instead die and become avascular and necrotic If the mucosa happens to be damaged by an invasive procedure at the same time, the exposed bone cannot heal Osteonecrosis of the Jaw BP Use and the Oral Health Professional 3 million take these meds orally In 2003, iv bisphosphonates were linked to osteonecrosis of the jaw In 2004, some of the drugs on the market issued warning statements in their prescribing information This occurred when patients also had cancers, significant osteoporosis or some other disease process In 2005 a report came out that 7 of 63 oral bisphosphonate users developed osteonecrosis of the jaw Legal cases began (for Fosamax) in August 2009 Bisphosphonates—Bad to the Bone? Consider potential risks In 0.1-7% of patients—GI upset, pain, esophageal pain or ulceration In <1% of patients—chest pain, angioedema, and osteonecrosis of the jaw New warnings for atypical femur fractures IV infusion may induce renal failure, atrial fibrillation (<0.1%) ONJ in the Left Jaw Drug Facts About BPs and ONJ Doses for patients receiving chemotherapy are up to 12-50 times higher than those for osteoporosis Half-life of these drugs is long—from several days for Ibandronate (Boniva) to up to 12 years for Alendronate (Fosamax) Elimination appears to be biphasic, with up to 40% of the dose leaving after 90 days Patients Most at Risk for ONJ Take BPs by the IV route Are immunosuppressed Secondary to GC use or chemotherapy Have an invasive procedure plus the above Treatment of ONJ Depends on the severity of the process Stage I Disinfectant Stage II rinses Disinfectant rinses Systemic antimicrobials Pain meds Stage III As above, plus surgical debridement or resection Management of the Patient on Oral BPs Based on expert panel convened by ADA: Comprehensive oral exam prior to beginning BPs, if possible Thorough medical history Sterile technique Disinfectants and antibiotics as warranted Judicious use of invasive surgical techniques In Patients Taking Biphosphonates… Maintain good oral hygiene Do root canals rather than extractions Make sure not to injure soft tissue during routine cleanings Do nonsurgical management of any dental infection Concomitant estrogen and/or GC use MAY increase risk of a bad outcome Recommendations DRUG HOLIDAY!! If the BP has been taken continuously more than 3 years, a drug holiday of 3 months before and 3 months after elective dental alveolar surgery is recommended to prevent ONJ If the drug holiday is not authorized or not agreed to, explain risks of ONJ No drug holiday needed for root canals, root scaling, or restorative procedures In Orthodontia No invasive procedures No invasive laser therapy No extractions No implants, miniscrews Tooth movement in these patients may be slowed Relapse rates may be higher Not with BPs on Board Drugs of Abuse and Effects on the Mouth Methamphetamine Meth Mouth Meth Mouth Methamphetamine and Tooth Damage Methamphetamine causes tooth and mouth damage due to: Its vasoconstrictive effect on blood vessels Its effect to cause the user to crave sweets Its effect to cause the user to not make dental hygiene a priority! Inhalation Damage Meth Mouth ADA Position on Management of Meth User Emphasize good oral hygiene and risk of meth use Assess and treat damage from drug and xerostomia—topical fluorides, remineralization products, etc. Encourage use of artificial sweeteners Use pain meds, anesthesia, adjunctive meds with care Smokeless Tobacco Smokeless Tobacco Demographics 15% of high school senior boys are current users (higher in rural areas) 2/3 of high school boys have tried it; 15% of high school girls have Of those who have tried it, 90% say they first tried it in ELEMENTARY SCHOOL Smokeless tobacco is easier to become addicted to than cigarettes due to the higher nicotine content Tobacco Risks—Snuff Users Oral cancer is one of the “top ten” most common cancers in the world—the risk is increased 4-fold for the smokeless tobacco user. Halitosis, tooth discoloration, gum recession, and tooth decay are common outcomes associated with smokeless tobacco use. High amounts of sugar and nicotine in the products account for these. Cancer in Teeth from a Smokeless Tobacco User Early Lesion from Smokeless Tobacco Squamous Cell Carcinoma Ulceration from Smokeless Tobacco!! WHO Recommendations for Dental Exams in Tobacco Users Extraoral Exam: Inspect face, head, and neck for growths, asymmetry. Perioral and Intraoral Exam: Inspect lips, labial mucosa, sulcus, tongue, hard and soft palates for lesions, ulcerations, etc. Dental and Periodontal Exam: Look for color changes on the root and coronal surface of the teeth; look for gingival recession. Tobacco Risks--Smokers Smokers have 67% greater tooth loss than nonsmokers Smokers have more gingival inflammation and supragingival plaque Four times more likely to have an oral lesion than a non-smoker Smokers have a higher incidence of periodontitis—2.5-3 fold—but may not have bleeding gums due to the nicotine in tobacco Smoker’s Teeth—Coming Soon to a Cigarette Pack Near You? New “Marketing”--Thailand But the Biggest Deterrent of All… If We’ve Missed Anything…. Hole in Soft Palate Due to Cocaine Recap…. Consider the impact of patient medications—licit or illicit—on the mouth and teeth When prescribing CS, be aware of REMS programs for the protection of yourself and your patient; limit pill count! Watch drug combinations Watch susceptible populations—children, elderly, patients with hepatic or renal impairment; consider pharmacogenomics
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