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  • POTENTIALLY INAPPROPRIATE MEDICATIONS FOR THE GERIATRIC

    POPULATIONIN THE PRACTICE OF DENTISTRY

    Arwa Farag, BDS, DMSc, DipABOM, DipABOP, FRCSEdApril 6th, 2017

  • DISCLOSURES

    GRANT/RESEARCH SUPPORT: NOVARTIS, GLAXOSMITHKLINE, BIOGEN

    IDEC, PROCTER & GAMBEL, & PRIVO

  • I WILL BE DISCUSSING OFF-LABEL USES OF THE FOLLOWING FDA APPROVED

    MEDICATIONS:

    DOXEPIN, GABAPENTIN, PREGABALIN, DULOXETINE& MILNACIPRAN

  • CONSUMPTION OF MEDICATIONS IN GERIATRIC POPULATION

    Geriatrics adult population aged 65 & above

    Represent 13% of the US population but consume

    40% of prescription drugs 35% of all OTC drugs

    Task force on Aging Research: Meds & Errors. https://www.ascp.com/sites/default/files/file_Task_Force_2009_FINAL-3.pdf Accessed June 15,2015

  • http://www.cdc.gov/nchs/data/databriefs/db42.htm

    Percentage of Prescription Medications Consumption in the US, by Age (CDC; 2007-2008)

  • INCREASED RISK FOR ADE & DRUG INTERACTIONS

    Co-existence of health-related comorbidities

    Polypharmacy

    Pharmacokinetic activities diminished GI absorption, drug distribution, hepatic metabolism & renal clearance

    Pharmacodynamic functions compromised drug-receptor interaction, signal transduction, protein transcription &

    cellular response

    Akhtar S, Ramani R. Anesthesiol Clin 2015;33(3):457-69Wehling M. J Am Geriatr Soc 2011;59(2):376-7

  • AS DENTISTS, WHY SHOULD WE CARE?

    ARE THERE GUIDELINES?

  • The Centers for Medicare/Medicaid Services (CMS) uses the National Committee for Quality

    Assurance (NCQA) & Pharmacy Quality Alliance (PQA)

    Evaluate the quality of care provided to their beneficiaries

    Monitor the use of high-risk medications in the elderly

    Both are based on the AGS Beers Criteria

    http://www.ncqa.org/hedis-quality-measurement/hedis-measures/hedis-2016/hedis-2016-ndc-license/hedis-2016-final-ndc-lists

    http://pqaalliance.org/images/uploads/files/2017_HRM.pdf

  • DESIGNATIONS OF QUALITY OF EVIDENCE

    Quality of Evidence CriteriaHigh Evidence 2 higher-quality RCT or consistent observational studies

    with no methodological flaws

    Moderate Evidence 1 higher-quality RCT2 higher-quality RCT with some inconsistency 2 consistent observational studies with no flaws

    Low Evidence Major inconsistenciesSignificant methodological flaws

    American Geriatrics Society Beers Criteria Update Expert P. J Am Geriatr Soc 2015;63(11):2227-46

  • DESIGNATIONS OF STRENGTH OF RECOMMENDATION

    Strength of Recommendation

    Rational

    Strong Harms, risks & adverse events clearly outweigh benefits

    Weak Inadequate evidence to determine net harms, adverse events & risks

    American Geriatrics Society Beers Criteria Update Expert P. J Am Geriatr Soc 2015;63(11):2227-46

  • TRICYCLIC ANTIDEPRESSANTS

  • TRICYCLIC ANTIDEPRESSANTSIndication Depression, anxiety disorders, PTSD, & panic attacks Chronic neuropathic pain

    Amitriptyline, nortriptyline, doxepin & imipramine

    In the H & N region Post-herpetic neuropathy Persistent dento-alveolar pain (PDAP) Burning mouth syndrome

    Attal N, et al. Eur J Neurol 2010;17(9):1113-e88Finnerup NB,et al. Pain 2005;118(3):289-305List T, et al. J Orofac Pain 2003;17(4):301-10

  • http://pharmacologycorner.com/differences-between-tricyclic-antidepressants-and-selective-serotonin-norepinephrine-reuptake-inhibitors-mechanism-of-action/

  • WHY NOT SUITABLE FOR GERIATRICS? Hyposalivation Constipation Urine retention

    (-) Muscarinic receptors

    Sedation Hypotension

    (-) H1 histamine & 1-adrenergic receptors

    Muscle weakness Cognitive impairment Cardiotoxicity

    (-) Na+ & Ca++ channels

    Hepatotoxicity Drug interactionCYP450

    Gillman PK. Br J Pharmacol 2007;151(6):737-48Christensen P, Thomsen HY, Pedersen OL, et al. Psychopharmacology (Berl) 1985;87(2):212-5

  • TRICYCLIC ANTIDEPRESSANTS

    Beers Criteria

    STOPP List

    AvoidEvidence HighRecomdStrong

    Coupland C, et al.. BMJ 2011;343:d4551Nelson JC, Devanand DP. J Am Geriatr Soc 2011;59(4):577-85

    Scharf M, et al. J Clin Psychiatry 2008;69(10):1557-64

  • ALTERNATIVESMedication Indication Precautions

    Doxepin BMS & PHN Max 6 mg/day

    Gabapentin TN, PHN, PDAP & BMS Moderate* & severe renal impairment (RI) 700 mg/day

    Pregabalin TN, PHN, PDAP & BMS Moderate* RI 75 mg/daySevere RI 25-50 mg/day

    Duloxetine BMS & PDAP Moderate* RI 60 mg/daySevere* RI avoid all SNRIs

    Milnacipran BMS & PDAP Moderate* RI 100 mg/daySevere* RI avoid all SNRIs

    Topical capsaicin PHN & BMS Intraoral concentration 0.01%-0.025% combined with 2%-5% lidocaine

    * Moderate renal impairment = eGFR of 30-59 mL/min Severe renal impairment = eGFR of 15-29 mL/min

  • BENZODIAZEPINES

  • BENZODIAZEPINES

    Indications Sedative, hypnotic, anticonvulsant & anxiolytic

    Anxiety disorders, PAs, muscle spasms, seizures & insomnias

    In the H & N region BMS, PDAP & some TMDs

    Clonazepam & sometimes diazepam

    Heckmann SM, Kirchner E, Grushka M, Wichmann MG, Hummel T. Laryngoscope 2012;122(4):813-6Gremeau-Richard C, Woda A, Navez ML, et al. Pain 2004;108(1-2):51-7

    Martin WJ, & Forouzanfar T. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2011;111(5):627-33

  • http://intranet.tdmu.edu.ua/data/kafedra/internal/pharmakologia/classes_stud/en/pharm/prov_pharm/ptn/Pharmacology/3%20year/09%20General%20CNS%20depressants.htm

  • BENZODIAZEPINES

    Beers Criteria

    STOPP List

    AvoidEvidenceModerate

    Recomd Strong

    llain H, Bentue-Ferrer D, Polard E, Akwa Y, Patat A. Drugs Aging 2005;22(9):749-65Finkle WD, Der JS, Greenland S, et al. J Am Geriatr Soc 2011;59(10):1883-90

    Paterniti S, Dufouil C, Alperovitch. J Clin Psychopharmacol 2002;22(3):285-93

  • WHY NOT SUITABLE FOR GERIATRICS?

    Increased susceptibility to drug interaction Increased susceptibility to AEs:

    cognitive impairment, dizziness, delirium, fatigue, falls, & mind cloudiness

    WHY? CYP3A4 interactions long-acting agents:

    clonazepam T 21-70 hours diazepam T 19-60 hours

    Berlin A, Dahlstrom H. Eur J Clin Pharmacol 1975;9(2-3):155-9Cloyd JC, Lalonde RL, Beniak TE, Novack GD. Epilepsia 1998;39(5):520-6

    Kaplan SA, Jack ML, Alexander K, Weinfeld RE. J Pharm Sci 1973;62(11):1789-96 Riss J, Cloyd J, Gates J, Collins S. Acta Neurol Scand 2008;118(2):69-86

  • IMPACT OF MEDICATION CLASSES ON FALLS IN GERIATRICS

    Drug class Odds ratio 95% CIAntihypertensive agents 1.24 1.011.50Diuretics 1.07 1.011.14 blockers 1.01 0.861.17Sedatives and hypnotics 1.47 1.351.62

    Neuroleptics/antipsychotics 1.59 1.371.83

    Antidepressants 1.68 1.471.91Benzodiazepines 1.57 1.431.72Narcotics 0.96 0.781.18

    Woolcott J., Richardson K., Wiens M., Patel B., Marin J., Khan K., et al. . (2009. Arch Intern Med 169: 19521960

  • https://www.drugabuse.gov/related-topics/trends-statistics/overdose-death-rates

  • ALTERNATIVES

    Moderate renal impairment = creatinine clearance of 30-59 mL/min* Severe renal impairment = creatinine clearance of 15-29 mL/min

    Medication Indication Precautions

    Doxepin BMS & PHN Max 6 mg/day

    Gabapentin PHN, PDAP & BMS Moderate* & severe RI 700 mg/day

    Pregabalin PHN, PDAP & BMS Moderate* RI 75 mg/daySevere RI 25-50 mg/day

    Duloxetine BMS & PDAP Moderate* RI 60 mg/daySevere* RI avoid all SNRIs

    Milnacipran BMS & PDAP Moderate* RI 100 mg/daySevere* RI avoid all SNRIs

    Topical capsaicin

    PHN & BMS Intraoral concentration 0.01%-0.025% combined with 2%-5% lidocaine

  • SKELETAL MUSCLE RELAXANTS

  • SKELETAL MUSCLE RELAXANTS

    Indication in the H & N region Regional myofascial pain & myospasm

    Tension type headache & tardive dyskinesia

    Cyclobenzaprine, carisoprodol, metaxalone & methocarbamol

    Mechanism of action Incompletely elucidated CNS conductivity (brain stem & spinal cord)

    cyclobenzaprine inhibit alpha motor neurons activity + TCA

  • Katzung, Bertram G., Susan B. Masters, and Anthony J. Trevor. 2012. Basic & clinical pharmacology. New York: McGraw-Hill Medical

  • WHY NOT SUITABLE FOR GERIATRICS? Cognitive impairment Sedation Falls & fractures

    CNS depression

    Cardiotoxicity Hyposalivation Blurred vision

    Anticholinergic/TCA-like

    Average of 50 hours (cyclobenzaprine)Prolonged T1/2

    Hepatotoxicity Drug interactionCYP450 (1A2 & 3A4)

    SAMHSA. Choice: Current Reviews for Academic Libraries 2011;49(3):545-45Witenko C, Moorman-Li R, Motycka C, et al. P T. 2014;39(6):427-35

    Dillon C, Paulose-Ram R, Hirsch R, Gu QP. (NHANES III). Spine 2004;29(8):892-96

  • Annually, 15% (300,000) of muscle relaxants prescribed in the US are given to patients over the age of 65

  • MS relaxants are associated with a 50% increased risk of ADEs majority related to CNS depression

    & sedation [RR=2.04 (95% CI, 1.233.37)]

  • SKELETAL MUSCLE RELAXANTS

    Beers Criteria

    STOPP List

    AvoidEvidence Moderate

    Recomd Strong

    Rudolph JL, Salow MJ, Angelini MC, McGlinchey RE. Arch Intern Med 2008;168(5):508-13American Geriatrics Society Beers Criteria Update Expert P. J Am Geriatr Soc 2015;63(11):2227-46

  • - Uncovering & addressing the underlying problem

    Depression, anxiety, posture, parafunctional movements

    - Co

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