Powerpoint presentation

• Review common drugs used in dentistry and used by our patients • Review mechanism of action • Review side effects of these drugs Drugs that we use/prescribe Drugs our patients take • Local anesthetics • Anti-hypertensives • Pain control • Anti-coagulants • Anti-resorptive • Herbal supplements Local Anesthetics
Local Anesthetics
Molecular structure • Molecular structure o Lipophilic group (aromatic ring) o intermediate chain (ester or o Cocaine (1860) o Lidocaine (Xylocaine) o Procaine (Novocain-1905) o Mepivicaine (Carbocaine) o ionizable group (usual y a tertiary o Tetracaine (Topical o Bupivicaine (Marcaine) o Articaine (Septocaine) o Ester: Pseudocholinesterase o Benzocaine (Topical) o Amide: Liver metabolism by Local Anesthetics
Local Anesthetics
Mechanism of Action Blockage of voltage gated Na channels Lipid solubility Protein binding (%)
o The drug must penetrate the neuron to act on intracellular end of the Na o Affect small fiber nerves first 1. C fibers (pain) 0.5% Bupivacaine 2. A delta (Pain, temp) 3. A beta (Touch, Pressure) Strongest, do not 4. A alpha (motor, Proprioception) JADA, Vol 131, May 2000 Local Anesthetics
Local Anesthetics
Maximum total Carpules mg/carpule o Initial: restlessness, confusion, peri-oral numbness, vertigo, tinnitis, slurred speech, auditory/visual hallucination and tonic-clonic seizures 2% Lidocaine 1:000,000 epi o Late: CNS depression respiratory col apse and death 3% Mepivacaine plain 4% Articaine 1:100,000 epi o Initial: Hypertension, tachycardia 0.5% Bupivacaine 1:200,000 o Late: Decreased contractility and cardiac output, hypotension Adapted from Stanley Malamed, Handbook of Local Anesthesia, Fifth Edition o Later: Sinus Bradycardia, ventricular dysrhythmias, circulatory arrest Local Anesthetics
Local Anesthetics
• Increases duration of action • Hemostasis (max effect takes 7 minutes) • Decreases uterine blood flow and activity • Hydro-dissection of surgical plane o Needs to be a intravascular injection • Aspirate and inject slowly!! • Avoid IAN blocks in patients with unstable/significant coronary artery disease to avoid intravascular entry No significant contraindication for the careful use of lidocaine o No more than 0.04mg = 40 ug epinepherine (2 carpules) with epinephrine in pregnant patients Compendium of Continuing Education in Dentistry, September 2012 Local Anesthetics
Local Anesthetics
• Mostly adverse reaction to epinephrine Rapid heart rate • Rare allergy to agent itself o Ester are metabolites resemble para-aminobenzoic acid which can elicit allergic reaction United States FDA Pharmaceutical Pregnancy Categories • Allergy to components of anesthetic Adequate and well-controlled human studies have failed to demonstrate a risk to the fetus in the first trimester of pregnancy (and there is no evidence of risk in later trimesters). o Methylparaben: multi use vials Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women OR Animal studies have shown an adverse effect, but adequate and well-controlled studies in pregnant women have o Bisulfites: preservative for vasoconstrictor failed to demonstrate a risk to the fetus in any trimester. Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in o Sulfa: articaine has small amount humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks. There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies • Consider referral to allergist in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks. Studies in animals or humans have demonstrated fetal abnormalities and/or there is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience, and the risks involved in use of the drug in pregnant women clearly outweigh potential benefits. Local Anesthetics
Pain Medications
Methemoglobinemia Hemoglobin deficiency occuring when hemoglobin is oxidized to methemoglobin and cannot bind or carry oxygen • Excessive doses of Articaine (> 500 mg/6 carpules) or Prilocaine (> 600 mg) • Acetaminophen • Accumulation of oxidized metabolite, ortho-toluidine • Decreased pulse oximetry reading, cyanosis, dark blood • Reversal with 1-2 mg/kg methylene blue IV over 5 minutes Mechanism of action • Binds opioid receptors (3 groups) found in CNS, PNS and GI • Semi-synthetics supraspinal analgesia respiratory depression physical dependence spinal analgesia spinal analgesia respiratory depression respiratory depression • Undersirable • Hepatic metabolism into active metabolites o Drug interactions o Individual specific response: good and bad metabolizers o Adjunctive with sedation o Mental clouding o Both naturally occurring (opium poppy) or synthesized from morphine o Derived from codeine o Combination with acetaminophen, ASA or NSAIDs o w/Acetaminophen (Vicodin, Norco), w/Ibuprofen (Vicoprofen) o Active metabolite: morphine  M3G, M6G o Active metabolite  hydromorphone o Analgesic effect depends on individual's liver metabolism o Good/poor metabolizers have similar response o Paroxetine, Fluoxetine, diphenhydramine, bupropion block metabolism o Derived from thebaine (poppy derivative) o Not commonly used in dentistry o w/Acetaminophen (Percocet), w/Aspirin (Percodan) o Mimics endogenous endorphins o Immediate or extended release (Oxycontin) o Works much better IV than PO (extensive first pass metabolism, 40-50% o Many metabolites o Active metabolites: M3G, M6G o Good/poor metabolizers Synthetic hybrid o Weak opioid agonist + inhibitor of seratonin and o Metabolite normeperidine cause undesirable effects norepinepherine reuptake system • Dysphoria, tremors, seizures o Metabolite O-desmethyltramadol is potent opioid receptor • MAOI  Life threatening serotonin syndrome • Hypertensive crisis, hyperpyrexia, cardiovascular collapse o Side effects: HA, N/V, seizure, somnolence o Low respiratory effects and abuse potential o Rapid onset, short duration of action o 100 times more potent than morphine (high lipophilicity) o Transdermal patch, lollipops, IV Pain Medication
Comparison of potency Strength
Equivalent Dose
• Acetaminophen • Local tissue damage  Release of inflammatory mediators • Prostaglandins E1, E2, F1α, F2 α Increase vascular permeability • Prostaglandins • Leukotrienes Increase hyperalgesia in sensory afferent nerves Inhibit platelet adhesion Increase vascular permeability Inhibit platelet adhesion Decrease vascular tone Reduce platelet adhesion Prostaglandin Pathway
• Maintains homeostasis of different organ systems. • Creates mucosal lining that is protective • Control blood flow, renin release and salt/water o Heart o Brain o Vasculature • Platelet function • analgesia, antipyretic, anti-inflammatory Non-selective (COX 1, COX 2) Partial-selective (COX 2 > COX 1)
Ibuprofen (Motrin, Advil)
Etodolac (Lodine) Naproxen (Aleve) Meloxicam (Mobic) Nabumetone (Relafen) Salicylates (irreversible COX1) COX-2 inhibitors
Celecoxib (Celebrex) FDA alert Rofecoxib (Vioxx) withdrawn from market Medium Dose
High or Max Dose
o Chronic renal failure Ibuprofen (Motrin) • Decrease blood flow and Naproxen (Aleve) 1250mg/day (divided) glomerular filtration* Etodolac (Lodine) o Bleeding (prolonged o Severe allergic reaction Meloxicam (Mobic) Nabumetone (Relafen) 1000mg qd 2000mg/day (qd or divided bid) o Edema o Dizziness Celecoxib (Celebrex) Rofecoxib (Vioxx) 50mg qd for max of 5 days (acute pain) o Increased liver enzymes Pain Medication
• Analgesic, antipyretic, mild anti-inflammatory • Mechanism of action unknown o Reduces prostaglandins by inhibition of COX?? • Acetaminophen o Metabolite NAPQI (N-acetylimidoquinone) is toxic to liver o < 4,000 mg per day for adults o Use narcotic formulations with less tylenol (325 vs 500 mg) Pain Management Strategies
• 2 medications with different mechanisms of action are better than a lot of 1 medication o NSAIDs around the clock for pain and inflammation • Cephalosporins o Narcotics to supplement, alternate or as needed • Begin pain medication before or right after treatment to • Metronidazole counteract initial hyperalgesia • Take medication ahead of pain, not after experiencing it • Fluoroquinolones Antibiotics
• Cellulitis or abscess • Pericoronitis • Osteomyelitis o Fascial planes/Soft tissue • Prophylactic o Deeper fascial planes • Preventative? o Potentially fatal Cellulitis
• Early infectious process spreading to surrounding fascial planes and soft • Rubor (erythema), Dolor (pain), Tumor (swelling), Calor (heat), loss of • No drainable abscess • Treatment o Antibiotics o Remove offending agent o Consider surgical exploration to Micro-organisms in dental infections
• Advanced infection • Organized fluid collection Gram-positive cocci Streptococcus spp. Peptostreptoccus spp. Gram-negative cocci (Viellonella spp.) Gram-positive rods 14 o Requires I+D, possible  Eubacterium spp. Lactobacillus spp. Actinomyces spp.  o Hospital admission/IV Clostridia spp. Gram-negative rods  Bacteroides spp. Fusobacterium spp. Excerpted from Contemporary Oral and Maxillofacial Surgery, Third Edition, 1998 Antibiotics
Micro-organisms in dental infections
Mechanism of action Organism Percentage AEROBIC Gram-positive cocci  Streptococcus spp. Streptococcus (Group D) spp Streptococcus Group spp. Staphylococcus spp. Eikenella spp. Gram-negative cocci (Neisseria spp.) Gram-positive rods (Corynebacterium spp.) Gram-negative rods (Haemophilus spp.) Miscellaneous and undifferentiated Excerpted from Contemporary Oral and Maxillofacial Surgery, Third Edition, 1998 Antibiotics
Mechanism of action Penicillin family • Bactericidal • Inhibits cell wall synthesis by interfering with transpeptidaton o Kills bacteria or cross-linkage, thus exposing the osmotically less stable membrane  cell lysis o Pencillins, fluoroquinolones, metronidazole • Bactericidal • Bacteriostatic • Allergy is common (10%) o Limit growth of bacteria by interefering with bacterial cellular metabolism o Works together with body's immune system to remove o 500mg tabs (#30) = $26 o 500mg q6h x 7 days o In higher doses, can be bacteriocidal o Can combine with Flagyl broaden spectrum of coverage. Cost o Clindamycin, macrolides effective combination. Antibiotics
Penicillin resistance • More gram-negative coverage Beta-Lactam Ring • Can be dosed TID or BID • Cleaved by beta-lactamases • Recommended as first line for prophlyaxis produced by resistant bacteria Beta-lactamase inhibitors • Clavunic acid • Sublactam • Tazobactam Antibiotics
Cephalorosporins • Amoxicillin + clavunic acid • β-lactam antibiotic o B-lactamase inhibitor • 4 generations (gram positive  gram negative) • 1st generation good for oral organisms • Good for more severe odontogenic infections o Cephalexin (Keflex) • First line for sinusitis • Bactericidal, less susceptible to β-lactamases • 10% cross-reactivity in PCN allergic pts o Ampicillin + sublactam (Unsasyn) o Pipercillin + tazobactam (Zosyn) Antibiotics
Clindamycin (Cleocin) Clindamycin (Cleocin) • Inhibits protein synthesis by binding to the 50s ribosomal subunit of bacteria. o 150-450 mg PO q6-8h • Bacteriostatic; bactericidal in higher doses o Higher doses for active infection • Good against oral organisms (Strep, Staph, Bacteroides) and o Elixir is rancid (switch to Azithromycin) majority of anaerobes o 150 mg (30 ea) : $24.99 • Achieves high levels in bone, excellent penetration in abscesses o 300 mg (30 ea) : $79.99 • First line option in penicillin allergic patients Antibiotics
Metronidazole (Flagyl) Metronidazole (Flagyl) • Disrupts bacterial nucleic acid synthesis • Dosage Forms • Bactericidal against anaerobic species • Do not drink alcohol! – Disulfiram-like reaction: flushing, tachycardia, palpitations, o 500-750 mg q 6-12 h • Treatment of chose for C. difficile associated diarrhea o 250mg ( #90) $16 • Resistance non-existent o 500mg ( #30) $13 • Prescribe in combination with aerobic covering abx Antibiotics
Fluoroquinolones • Azithromycin (Zithromax), Erythromycin • ciprofloxacin (Cipro), levofloxacin (Levaquin), moxifloxacin • Drug of choice for URI, pneumonias • Binds to 50S subunit of bacterial ribosomes, inhibiting bacterial • Inhibit DNA gyrase and topoisomerase involved in DNA protein synthesis • Bacteriostatic • Bacteridicdal • Good for gram-negative bacteria o Greater gram positive coverage with levofloxacin and o Greater anaerobic coverage with moxifloxacin • Not recommended for children (joint toxicity in animals) Antibiotics
Moxiflocaxin (Avelox) • Second-line, broad spectrum abx for odontogenic infections • Serious, growing problem o Concern for emerging antibiotic resistance • Excellent for intra-oral organisms o Overuse and misuse of antibiotics • Dosage forms o Poor patient compliance with antibiotic regiment o Evolutionary potential of bacteria • Superbugs resistant to multiple antibiotics o 400mg po or IV once daily x 5-10 days o MRSA: staph aureus resistant to penicillin, methicillin, tetracycline, erythromycin o Expensive ( no generic) o VRE: enterococcus resistant to vancomycin, linezolid o 400mg tab (#30) $490 Antibiotics
Adverse reactions o Drug inactivation or modification (penicillins) • Mild cases are common (1 in 3 people) o Alteration of target site (penicillins) • Loose stools, more frequent BMs o Alteration of metabolic pathoway • Caused by alteration/imbalance of colonic micro-organsims o Reduced drug accumulation (fluoroquinolones) • Changes in carbohydrate metabolism and decreased fatty acid absorption cause an osmotic diarrhea • Can occur with ANY antibiotic o More commonly: penicillins, clindamycin, fluoroquinolones, • Probiotics may be protective Antibiotics
Adverse reactions Prophylaxis for cardiac patients C. Difficile colitis American Heart Association • Revised in 2007 to cover only the highest risk patients Serious problem, significant cause of mobidity/mortality among – No convincing evidence that antimicrobial prophyaxis provides significant elderly hospitalized patients benefit in preventing infective endocarditis • Clostridium difficile is natural colonizer in 20% of patients • Procedures involving manipulation of gingival tissue, periapical region of teeth, or perforation of oral mucosa • Symptoms: watery diarrhea 10-15 times daily, abdominal o Does not include routine cleaning pain/cramping, fever, leukocytosis, foul odor • Highest risk cardiac conditions only o Prosthetic heart valves o Prior history of infective endocarditis o Stop offending agent o Unrepaired cyanotic congenital heart disease o Completely repaired congenital heart defects with prothetic material o Flagyl 500 mg PO TID o Repaired congenital defects with residual defects o Cardiac valvulopathy in a transplanted patient Antibiotics
Prophylaxis for orthopedic patients American Academy of Orthopedic Surgeons, 2013 • Amoxicillin is good first line drug for odontogenic infections • Antibiotic prophylaxis administered prior to dental procedures • Augmentin is good for secondary space or sinus involvement for 2 years after prosthetic joint implantation, unless patient is • Penicillin/Flagyl is a cost effective option immunocompromised • Clindamycin is first line for PCN allergic patients – Use higher dose for active infections • Azithromycin is suitable third alternative or when elixir is needed in PCN allergic patients • Moxifloxacin is an expensive, last resort option • Be conservative in prescribing antibiotics to avoid development of resistance and adverse reactions • Start with smaller guns so you have a backup option Drugs our patients take • 29-31% of American adults (58-65 • Anti-hypertensives million) have hypertension • Diabetic medications • Options for therapy • Anti-coagulants • Anti-resorptive o Angiotensin-converting enzyme (ACE) inhibitors • Herbal supplements o Angiotensin II receptor blockers o Calcium channel blockers o Beta blockers o Combination therapy Choice of therapy in primary hypertension: Recommendations, 2013 UpToDate Which drug to choose? Which drug to choose? • Goal is < 140/90 mm Hg • First line drugs • All agents are roughly equally effective in lowering BP o Thiazide diuretics (African Americans) o Good response in 30-50% of patients with mild hypertension o calcium channel blockers Wide interpatient variability ACE inhibitors (diabetics, younger age) o ARBs (diabetics, younger age) o Patients respond differently to different medications • Start with one drug, assess patient response, side effects o Side effect profile o Start 2 drugs initially if BP is 20/10 mm Hg above goal • Race/Age considerations • Increase dose (side effect profile increases) one step o Younger people respond better to ACE inhibitors or ARBs • If ineffective, try drug 2 (50% chance of responding) o African Americans respond better to diurectics and poorly to • If ineffective, try drug 3 (60-80% chance of responding) ACE inhibitors or beta blockers Choice of therapy in primary hypertension: Recommendations, 2013 UpToDate Choice of therapy in primary hypertension: Recommendations, 2013 UpToDate ACE inhibitors
Thiazide diuretic Chlorthalidone • Inhibits sodium reabsorption in renal ascending loop of Henle • Reduce extracellular fluid volume, cardiac output  decrease BP • Preferred first-line drug (esp in African-Americans) • Adverse effects o Electrolye abnormalities (hypokalemia, alkalosis) o photosensitivity Choice of therapy in primary hypertension: Recommendations, 2013 UpToDate Choice of therapy in primary hypertension: Recommendations, 2013 UpToDate angiotensin II receptor blockers (ARB) Lisinopril (Prinivil), enalapril (vasotec), ramipril (Altace), quinapril Valsartan (Diovan), lorsartan (cozaar) • Acts on renin-angiotensin-aldosterone system • First line therapy for patients with • Good for those intolerant to ACE inhibitors o Diabetics (kidney protective) Indications and efficacy similar to ACE inhibitors o asymptomatic LV dysfunction o Particularly pts with severe hypertension with LVH on ECG • Adverse effects o Chronic kidney disease • Adverse effects o Cough o Hypotension o Metabolic abnormalities (hyperkalemia) Choice of therapy in primary hypertension: Recommendations, 2013 UpToDate Choice of therapy in primary hypertension: Recommendations, 2013 UpToDate calcium channel blockers Amlodipine (Norvasc) Metoprolol (Lopressor), atenolol (ternormin), carvedilol (coreg) • Inhibit release of calcium • Block beta receptors in sympathetic nervous system o Vascular smooth muscle: reduce contraction, vasodilation o Decrease heart rate o Decrease renin secretion • Dihydropyridine class • Not recommended as first line therapy, especially ages > 60 o Cardiac muscle: reduce force of contraction and conduction o Inferior protection against stroke risk o Small increase in mortality • Adverse effects • Good after MI and stable pts with HF or asymptomatic LVD o Peripheral edema • Adverse effects o Heart failure o Beta blocker withdrawal o Bronchoconstriction o Depression, fatigue, sexual dysfunction Choice of therapy in primary hypertension: Recommendations, 2013 UpToDate Choice of therapy in primary hypertension: Recommendations, 2013 UpToDate Diabetes Overview • Hyperglycemia associated with microvascular and macrovascular • Increased risk for infections, poor healers o Lack of endogenous insulin (absolute in type 1; relative in type 2) o Resistance to insulin a target sites (muscle, fat and liver) • Risk factors o Obesity (90% type 2 diabetics are obese) o Race (Native Americans, Hispanics, African Americans, Asians) o Family history • Presentation o Asymptomatic o Polyuria, polyphagia, polydipsia o Blurred vision, extremity parestheisa, yeast infections Initial management of blood glucose in adults with type 2 diabetes, 2013 UpToDate Diabetes Overview Treatment Algorithm o HbA1c > 6.5% o Fasting plasma glucose level of ≥ 126 mg/dl o 2 hr plasma glucose level of ≥ 200 mg/dl o Random plasma glucose of ≥ 200 mg/dl in a patient with o Lifestyle modifications • Diet (caloric restriction, low carbohydrate) • Weight loss (5-10% loss associated with improvements in Initial management of blood glucose in adults with type 2 diabetes, 2013 UpToDate Initial management of blood glucose in adults with type 2 diabetes, 2013 UpToDate Diabetic drugs
Diabetic drugs
• Short-acting sulfonylurea • First line choice for treatment of type 2 diabetes • Stimulates release of insulin from pancreatic beta cells • Decreases hepatic glucose production, increases peripheral • Reduces HbA1c 1-2% insulin sensitivity • Effectiveness decreases over time • Generally reduces HgA1c by 1.5% points • Adverse effects • Often leads to modest weight reduction or stabilization • Cardiovascular benefits • Adverse effects o GI related (diarrhea, N/V, flatulence) o Lactic acidosis (rare but serious) Initial management of blood glucose in adults with type 2 diabetes, 2013 UpToDate Initial management of blood glucose in adults with type 2 diabetes, 2013 UpToDate Diabetic drugs
Diabetic drugs
• Type 1 diabetic (absolute insulin deficiency) • Rapid acting (lispro, aspart, glulisine) • Type 2 diabetics o Given before meals o Traditionally reserved for those who have failed PO agents o Continuous infusion via insulin pump to provide basal levels o Data support using insulin earlier and more aggressively o Inducing normoglycemia improves endogenous insulin • Intermediate to long acting (NPH, lantus, ) secretion and insulin sensitivity resulting in better glycemic o Given once or twice daily to provide basal insulin levels Initial management of blood glucose in adults with type 2 diabetes, 2013 UpToDate Initial management of blood glucose in adults with type 2 diabetes, 2013 UpToDate Diabetic drugs
Diabetic drugs
Duration of action 45 to 75 minutes Two to four hours About 30 minutes Two to four hours Five to eight hours Insulin glargine 20 to >24 hours Three to nine hours 6 to 24 hours* Insulin degludec Initial management of blood glucose in adults with type 2 diabetes, 2013 UpToDate Initial management of blood glucose in adults with type 2 diabetes, 2013 UpToDate Blood clot formation at site of vessel injury • Clopidogrel (Plavix) 1. Platelet plug formation • Warfarin (Coumadin) 2. Coagulation cascade • Dabigatran etexilate 3. Antithrombotic control mechanisms, termination of clotting 4. Fibrinolysis (removal of clot) Overview of hemostasis, 2013 UpToDate ASA Plavix Coumadin Pradaxa Overview of hemostasis, 2013 UpToDate • Aspirin, Plavix • Irreversible COX 1 inhibition, preventing thromboxane A2 • Primary and secondary prevention of formation (binds platelet molecules together) • Strong evidence for benefits of ASA in decreasing risk of CVD events in a wide range of patients o Primary prevention of first CV event in moderate to high risk patients o Peripheral vascular disease o Secondary prevention of CVD after vascular event o Coronary artery stent thrombosis • No difference in efficacy between low vs high dose • Adverse effects – Bleeding (GI) Benefits and risks of aspirin in secondary and primary prevention of cardiovascular disease, 2013 UpToDate clopidogrel (Plavix) Management of patients on ASA/plavix • Irreversible inhibition of ADP receptor on platelets (activation • Do not hold ASA/plavix for patients undergoing routine • Undergoes liver metabolism to its active form o Use local hemostatic measures (gelfoam, collaplug, surgicel,…) o Poor metabolizers have decreased response o Hold firm manual pressure and do not discharge until hemostasis is o Life threatening thromboembolic event vs minor bleeding o Patients intolerant to ASA (GI ulcer) • For larger surgeries o In combination with ASA after coronary stent placement to o Talk to physician, assess risk level prevent thrombosis o May be able to hold 1 antiplatelet agent if on ASA + plavix • Adverse effects o May be able to hold both for 4 days o Compromise: some platelet action with less risk of thromboembolic event o Platelets lifespan is 7 days o Less GI side effects vs ASA Antithrombotic therapy for percutaneous coronary intervention and secondary prevention Antithrombotic therapy for percutaneous coronary intervention, 2013 UpToDate of stroke, 2013 UpToDate warfarin (coumadin) warfarin (coumadin) • Inhibits vitamin-K dependent clotting factors (II, VII, IX, X), • Can do routine extractions with INR < 3.0-3.5 o Most patients will be in this range • Peak effect in 36-72 hrs o Use local hemostatic measures • Larger surgical procedures in higher risk patients may require o Atrial Fibril ation o Prosthetic heart valve o Enoxaparin (Lovenox) o Deep vein thrombosis/pulmonary embolism o Anti-phospholipid syndrome • Shortcomings o Interacts with food, other medications o Difficult to manage, requires multiple blood draws Therapeutic use of warfarin, 2013 UpToDate Anti-resorptives dabigatran etexilate (Pradaxa) • Direct thrombin inhibitor • Bisphosphonate • Undergoes liver metabolism to convert to active form – Alendronate (Dosamax) • Maximum effect within 2-3 hrs after ingestion, half life 12-14 hrs – Ibandronate (Boniva) – Pamidronate (Aredia) o Deep vein thrombosis/pulmonary embolism – Risedronate (Actonel) o Atrial fibrillation – Zoledronic acid (Reclast, • Lower rates of both embolic events and major bleeding vs • Denosumab (Prolia) • Does not require laboratory monitoring, less susceptible to dietary/drug interactions • Drawbacks: BID dosing, higher cost, no reversal agent Anti-resorptive related osteonecrosis of the
Anti-resorptive related osteonecrosis of the
jaws (ARONJ)
jaws (ARONJ)
• Formerly BRONJ • Risk factors • Use: osteoporosis, metastatic bone disease, bony malignancy • Osteoblastic bone formation ↔ osteoclastic bone breakdown o Prolonged use of AR agents (> 2 yrs) • Osteoclastics are inhibited, thus breaking the normal cycle of o Denture wearing • Necrosis of the jaw can occur spontaneously but more commonly associated with tooth extractions • Frequency difficult to assess (no good clinical trials) o <1% with PO meds (osteoporotic patients) o 13% with IV meds (cancer patients) Managing the care of patients receiving antiresortive therapy for prevention and Managing the care of patients receiving antiresortive therapy for prevention and treatment of osteoporosis, ADA 2011 treatment of osteoporosis, ADA 2011 denosumab (Prolia) • Monoclonal antibody targeting RANKL, key component in pathway for osteoclast formation and activation • Not considered first line for postmenopausal women with uncomplicated osteoporosis • Can be initial therapy for pts at high risk for fracture, intolerant, unresponsive to other therapies, impaired renal function Herbal Supplements Management recommendations Based on expert clinical opinion; no good evidence exists • 60 million Americans used herbal supplements on a regular basis • Prior to anti-resorptive therapy, patients should seek dental • Less than 10% of herbal supplement users inform their consultation to optimize oral health physicians before surgery • During anti-resorptive therapy, prior to extraction/implant o View that herbals are "natural" and do not have side effects o <3 yrs on PO medications (unless on corticosteroids): • Herbal supplements have significiant medicinal activity and potential for adverse effects and drug interactions o > 3 yrs on PO medications: 3 month holiday before/after o IV medications: drug holiday efficacy unknown; can consider burying roots + endo • Good informed consent AAOMS Position Paper on BRONJ, 2009 Update Overview of herbal medicine and dietary supplements, UpToDate 2013 Herbal Supplements Bleeding • Ginkgo biloba o Antioxidant properties, vascular problems, memory loss, dementia, macular degeneration o Antiplatelet effects: interacts with NSAIDs o Lowers BP, lowers cholesterol, cardio-protective o Nausea, motion sickness, aids digestion o Increases physical/mental energy, enhances performace Overview of herbal medicine and dietary supplements, UpToDate 2013

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Harvard Journal of Law & Technology Volume 24, Number 2 Spring 2011 REVERSE SETTLEMENTS AS PATENT INVALIDITY SIGNALS Gregory Dolin, M.D.* TABLE OF CONTENTS I. INTRODUCTION .282 II. THE HATCH-WAXMAN ACT .286 A. The Structure and Purposes of the Act . 286 B. The Mechanics of the Hatch-Waxman Act. 290 III. REVERSE SETTLEMENTS .293

Microsoft word - abstract book 2nd bioscience and biotechnology

i 2nd International Conference on Bioscience and Biotechnology: pave the way to a better life, Udayana University, Bali, 23-24 September 2010 TABLE OF CONTENTS Table of Contents ii Preface from Chairman of Organizing Committee List of Abstract xiii Agricultural Technology and Food Science ii 2nd International Conference on Bioscience and Biotechnology: pave the way to a