พท ผศ พญ พัฒน์ศรี ศรีสุวรรณ · excretion ! glomerular...
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การใชยาในผสงอาย/
พ.ท. ผศ. พญ. พฒนศร ศรสวรรณ/
กองตรวจโรคผปวยนอก และเวชศาสตรครอบครว /
รพ.พระมงกฎเกลา/
30 พฤษภาคม 2562 /
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¨ To recognize priniciples of medication use in
older adults /
¨ To realize common medication-related
problems in primary care/
¨ To develop 3 simple steps of medication use in
older adults with multicomorbidity & frailty /
Objectives /
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1. Principle /
2. Primary care/
3. Multimorbidity & Frailty /
4. Take home messages /
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¨ Reduce body reserve: !¤ pharmacokinetics & Pharmacodynamic changes!¤ Functional decline!
¨ Atypical presentation: adverse drug events!
¨ Multiple pathology: multimorbidity !
¨ Polypharmacy !
¨ Social adversity: financial, support !
Pretorius RW,et al. Am Fam Physician 2013.
Medication use in older adults /
Farrell B,et al. Am Fam Physician 2019. !
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Pharmacokinetics changes /Physiological changes! Clinical impact ! Example !
Absorption !
!
Gastric pH: increase ! Active transport drug:
decrease!
Ketoconazole, itraconazole,
ferrous, Vit B12 !
Distribution!
!
Fat distribution: increase ! Fat-soluble half-life drug:
increase!
Diazepam, alprazolam,
chlordiazepoxide, lidocain !
Water distribution: decrease !
!
Water-soluble
concentration: increase!
Ethanol, digoxin, gentamicin,
lithium !
Metabolism ! Phase I (oxidative
metabolism): decrease !
CYP 3A4: half-life
increase!
Diazepam, alprazolam,
theophylline, propranolol !
Phase II (conjugate
metabolism): not change !
Not impact to half-life ! Lorazepam, oxazepam,
trizolam !
Excretion ! Glomerular fiitration rate:
decrease!
Renal excretion drug: long
half-life !
Digoxin, gentamicin, lithium,
cimetidine, metformin !
Stratton MA, et al. Primary Care Geriatrics 2007. !
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Medication use in older adults /
¨ Polypharmacy: 50% !
¨ Potentially inappropriate: 20% !
¨ Adverse drug events: 15% !
¨ Preventable: 50% !Farrell B,et al. Am Fam Physician 2019. ! Pretorius RW,et al. Am Fam Physician 2013.
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Decision making to prescribe /
1. Decision to prescribe!§ Evidence, risk/benefit !
2. Dose to prescribe!§ Absorbtion, distribution, metabolism, excretion !
3. Monitoring pharmacotherapy!§ Response, ADE: prescribing cascade!
4. Deprescribing !§ Course, life expectancy/function/prefer !
Farrell B,et al. Am Fam Physician 2019. !
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Decision to prescribe/
• Indication: UTI/
• Clinical: function/
• Urine/
• U/C /
Dose to prescribe/
• Drug /
• Ciprofloxacin, amoxicillin/clavulanate /
• Dose /
• Ciprofloxacin: reduction CrCl < 30 mL/min/
Monitoring /
• Response /
• Adverse drug events /
• Tendinopathy, tendon rupture/
Deprescribing /
• Duration/
• Rapid response: 7 days /
• Delayed response: 10-14 days /
• Replace catheter/ intermittence cath/
UTI: in-dwelling catheter /
Gene JL, et al. Sing Family Physician 2015. !
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Measure: appropriate prescribing /
Renom-Guiteras A,et al. !
Eur J Clin Pharmacol 2015 !
O’Mahony D, et al. !
Age Ageing 2013.
Tools !
Explicit criteria !
RDU Thai !Beers
criteria !STOPP/ START !
EU (7)-PIM!
Implicit criteria !
Indication effectiveness
dose interaction !
American Geriatric Society Beers Criteria. !
J Am Geriatr Soc 2019. !
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¨ DM: chlorpropamide, glibenclamide!
¨ CVS: nifedipine!
¨ Psychi: BZP (long-acting), TCA!
¨ Pain: pethidine !
¨ Antichoinergic: CPM,
orphenadine!
¨ Narrow level: dignoxin,
theophylline!
¨ Flunarizine, cinnarizine!
¨ Anticoagulant: warfarin !
หลกเลยง/ ระมดระวง/
Rational drug use (RDU) in older adults /
ชยรตน ฉายากล และคณะ. คมอการดำเนนงานโครงการรพ.สงเสรมการใชยาอยางสมเหตผล 2558. !
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¨ Long-acting BZP !
¤ Diazepam !
¤ Chlorazepate!
¤ Chlordiazepoxide !
¨ < 5%!
¨ Polypharmacy:
medication
reconciliation !
¨ > 50%!
ผปวยนอก/ ผปวยใน/
ตวชวด/
ชยรตน ฉายากล และคณะ. คมอการดำเนนงานโครงการรพ.สงเสรมการใชยาอยางสมเหตผล 2558. !
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American Geriatric Society Beers Criteria. !
J Am Geriatr Soc 2019. !
1. Avoid !
2. Interaction: diseases & syndromes!
3. Caution !
4. Drug-drug interactions!
5. Kidney function !
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Beers criteria 2019 /
q Anticholinergic !q Central nervous
system !q Cardiovascular!q Endocrine !q Gastrointestinal !q Pain medications!
American Geriatric Society Beers Criteria. J Am Geriatr Soc 2019. !
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Group / Type / Example /
Histamine ! Antihistamines !
(First generation)!
Brompheniramine, chlorpheniramine,
cyproheptadine, dimenhydrinate,
diphenhydramine (oral), hydroxyzine,
hyoscyamine!
Psychiatric ! Antidepressants ! Amitriptyline, nortriptyline !
Antipsychotics ! Chlorpromazine, clozapine, olanzapine!
Motor ! Skeletal muscle relaxants! Orphenadrine !
Antiparkinsonian ! Benztropine, trihexyphenidyl !
GU! Antimuscarinics (urinary incontinence)! Oxybutynin, tolterodine !
American Geriatric Society Beers Criteria. J Am Geriatr Soc 2019. !
Strong anticholinergics /
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Central nervous system/
q Antidepressants (TCA): sedate, orthostatic hypotension !
q Antipsychotics (dementia): stroke, cognitive decline, mortality !
q Benzodiazepines: cognitive impairment, delirium, falls fractures, motor vehicle crashes !
American Geriatric Society Beers Criteria. J Am Geriatr Soc 2019. !
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q Antihypertensive agents!q Alpha-1 blocker (doxazosin): OH!
q Nifedipine, immediate release !q Digoxin !q Avoid: fist-line AF, HF !q Avoid dose > 0.125mg/day !q Adjust dose CKD stage IV-V!
American Geriatric Society Beers Criteria. J Am Geriatr Soc 2019. !
Cardiovascular/
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q Sulfonylureas, long acting !q Chlorpropamide, glimepiride, glibenclamide!
q Insulin, sliding scale: without basal or long-acting insulin !
q Hormone!q Estrogens: carcinogenic, lack cardio/cognitive
protective !q Androgens: cardiac problems !
American Geriatric Society Beers Criteria. J Am Geriatr Soc 2019. !
Endocrine /
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q Metoclopramide!q Extrapyramidal effects!
q Duration < 12 weeks!
q Proton-pump inhibitors!q Clostridium difficile, bone loss, fracture!
q Avoid use > 8 weeks unless high-risk !
American Geriatric Society Beers Criteria. J Am Geriatr Soc 2019. !
Gastrointestinal /
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q NSAIDs!q GI: 1% in 3-6 months, 2-4% in 1 year!
q Increase BP, kidney injury !
q Indomethacin: most adverse effects!
q Muscle relaxants!q Poorly tolerated !
American Geriatric Society Beers Criteria. J Am Geriatr Soc 2019. !
Pain medications /
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Beers Criteria 2015: Removed /
American Geriatric Society Beers Criteria. J Am Geriatr Soc 2019. !
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American Geriatric Society Beers Criteria. !
J Am Geriatr Soc 2019. !
Beers Criteria 2015:/
Added /
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1. Principle /
2. Primary care/
3. Multimorbidity & Frailty /
4. Take home messages /
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Chau SH, et al. Int Clin Pharm 2016. !
Drug-related problems (DRP): older adults/
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DRP: overtreatment & undertreatment/
Chau SH, et al. Int Clin Pharm 2016. !
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PROTON PUMP INHIBITORS!
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Thailand Dyspepsia Guidelines: 2018 /
Pittayanon R, et al. !
J Neurogastroenterol Motil 2019. !
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Thailand Dyspepsia Guidelines: 2018 /
Pittayanon R, et al. J Neurogastroenterol Motil 2019. !
Co-prescribing PPI: NSAID/ASA-induce dyspepsia in /
high-risk patients /
High-risk patients /• History: complicated peptic ulcer (bleed/perforate)/
• > 2/4 /
1. Age > 65 years /
2. History uncomplicated peptic ulcer/
3. NSAIDs /
4. ASA, steroids, anticoagulants /
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Netherlands Guidelines /
Flinterman LE, !
et al.!
Front Public
Health 2018.. !
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Risk associate: long-term PPI use/
Nehra AK, et al. Mayo Clin Proc 2018./
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Farrell B, et al. Can Fam Physician 2017. !
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ASPIRIN!
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Lifetime events: healthy elderly /
McNeil JJ, et al. N Engl J Med 2018..!
Major hemorrhage/Incidence CVD/
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American Geriatric Society Beers Criteria. J Am Geriatr Soc 2019. !
Aspirin/
Williams B, et al. European Heart Journal 2018. !
Williams B, et al. European Heart Journal 2018. !
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ASA: time to benefit & age /
Dixon D, et al. ACSAP 2018. !
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Antiplatelet: DM/
Age >50 yrs> 1/5 factors /
• Smoking /
• FH of CVD /
• HT/
• Dyslipidemia /
• Albuminuria /
แนวทางเวชปฏบตสำหรบโรคเบาหวาน 2560 /
Aspirin/
76-162 mg/
day /
Age > 70
years /
Balance risk/
befenit /
ADA 2019 /
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LIPID!
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Statin: over/under utilized /
Chou R, et al. JAMA 2016. !
Under-utilized: 40-60% in acute MI!
Over-utilized: 30% Cancer use in 30 days of dying !
Afialalo J, et al. J Am Coll Cardiol 2008. ! Stavrou EP, et al. BMJ Open 2012. !
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2019 ACC/AHA guideline /
Lin K, et al. Am Fam Physician 2019..!
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แนวทางเวชปฏบตการใชยารกษาภาวะไขมนผดปกต !
เพอปองกนโรคหวใจและหลอดเลอด พ.ศ. 2559 !
Primary prevention/
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Primary prevention: DM/
แนวทางเวชปฏบตการใชยารกษาภาวะไขมนผดปกต เพอปองกนโรคหวใจและหลอดเลอด พ.ศ. ๒๕๕๙ !
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Statin
แนวทางเวชปฏบตการใชยารกษาภาวะไขมนผดปกต เพอปองกนโรคหวใจและหลอดเลอด พ.ศ. ๒๕๕๙ !
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USPSTF: statin for primary prevention CVD/
Ngo-Mtzger Q, et al. Am Fam Physician 2017..!
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TC & Mortality /
Cumulative survival !
1.0 !!!
0.8 !!
!
0.6 !!
!
0.4 !!
!
0.2 !!
!
!
!
0 1 2 3 4 5 6 !
Too low TC /
Increase mortality /
in the elderly /
Age > 75 yrs (av. 81 yrs)!
N = 700 !
Not use drug !
Tuikkara P, et al. !
Scandinavian Journal !
of Primary Health !
Care 2010.!
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Screening: malnutrition in elderly /
Topics / Scores /
S ! sadness! GDS 10-15 = 1, > 16 = 2 !
C ! cholesterol ! 180 mg/dL = 1, 160 mg/dL = 2 !
A! albumin ! < 4 g/L = 1, < 3.5 g/L = 2 !
L ! loss of weight ! - Loss 0.91 Kg in 1 mo = 1 !
- Loss 2.27 Kg in 6 mo = 2 !
E ! eating ! Feeding problems!
S ! shopping ! Insufficient money, buy/ prepare food !
Morley JE. J Am Geriatr Soc 1989. ! Thomas DR, et al. Am J Clin Nutr 2002. !
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Patient-related factors: lipid treatment/
Bertolotti M, et al. Gerontol Int 2019..!
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Adverse drug
events: /
Older community-
dwellng patients /
Cahir C, et al. Ann Fam Med 2019. !
• ADEs 39%!
• Most common drug:
Antithrombotic!
• Common problems!
1. Muscle pain/
weakness 75%!
2. Dizziness 61%!
3. Unstediness 52%!
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Drug: side effect &
comorbid condition in
primary care/
Merel SE, et al. J Am Geriatr Soc 2017. !
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drug-drug interactions in primary care /
Merel SE, et al. J Am Geriatr Soc 2017. ! Carpenter M, et al. Am Fam Physician 2019. !
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Drugs with chelation risk/
Carpenter M, et al. Am Fam Physician 2019. !
Before / After/
Tetracycline/ 2 hours / 4 hours /
Fluoroquinolone
thyroid /
2 hours / 6 hours /
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Carpenter M, et al. Am Fam Physician 2019. !
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Herb & drug interactions /
Asher GN, , et al. Am Fam Physician 2017./
Herb / Action / Drug / Consequence /
Ginkgo biloba / Inhibit platelet aggregation / Warfarin / Increase bleeding risk/
Asian ginseng / CYP3A4 inducer/ Amlodipine, Simvastatin / Decrease effectiveness /
Garlic / P-gp inducer / Colchicine, Digoxin /
Rosuvastatin /
Decrease effectiveness /
/
Curcumin / CYP1A2 inducer/
/
Antidepressants /
Antipsychotics /
Decrease effectiveness /
/
Green tea extract/ P-gp inhibitor/ Simvastatin / Increase concentration/
OATP1A1, OATP1A2
inhibitor/
Statins /
Fluoroquinolones /
Increase concentration/
/
Senna / Bowel movement/ Thiazide/ Decrease effectiveness /
Potassium loss /
/
Digitalis /
Antiarrhythmic (quinidine) /
intoxication/
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1. Principle /
2. Primary care/
3. Multimorbidity & Frailty /
4. Take home messages /
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Decision making: multiple chronic conditions /
Ouellet GM, et al. Ther Adv Drug Saf 2018. !
Current & future !
Evidence !
4. Deprescribing !
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Decision making: multimorbidity /
Boyd C, et al. J Am Geriatr Soc 2019. !
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Identify & communicate /
¨ Patient’s health priorities /
¤ AD, HT, DLP, insomnia,
fall with colles’ fracture/
¨ Patient’s health trajectory /
1. Fall with colles’ fracture/
2. AD, insomnia /
3. CVD: HT, DLP /
Zanker J, et al. J Am Geria tr Soc 2019.!
Wilkosz P, et al. Int Psychogeriatr 2010. !
Osteoporotic fracture/• Mortality 1 year:/
• Overall: 20%/
• Hip: 36%/
Alzheimer’s disease /
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Zanker J, et al. J Am Geriatr Soc 2019. !
Time to benefit/
• Age < 70 year: 19 months /
• Age > 70 year: 8 months /
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Thompson W, et al. J Am Geriatr Soc 2019.!
Deprescribing/
Farrell B, et al. Am Fam Physician 2019.!
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STOPPFrail /
¨ Screening Tool of Older Persons Prescriptions in Frail adults with limited life
expectancy /
¨ Without indication or poor compliance /
¨ 25 medications /
• Musculoskel: calcium, antiresorptive,
NSAIDs /
• Hormone: estrogen, corticosteroids /
• Infection: prophylactic antibiotics /
• Supplement: multivitamin, nutritional
supplement/
• CVD: lipid-lowering, alpha-blockers (HT),
oral diabetes, ACE-inh, ARB/
• Neuro: neuroleptics, memantin, muscarinic
antagonists /
• GI: PPIs, H2-blocker, antispasmodic/
• GU: 5-alpha-reductase inh, alpha-1-selective
blockers /
• Resp: theophylline, leukotriene antagonist/ Lavan AH, et al. Age Ageing 2017./
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Steinman MA, et al. J Am Geriatr Soc 2019./
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1. Principle /
2. Primary care/
3. Multimorbidity & Frailty /
4. Take home messages /
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¨ Decision to prescribe, Dose, monitor, deprescribing /
¨ Potentially Inappropriate Medication/
¤ Strong anticholinergics /
¤ PPIs, ASA, lipid/
¨ Adverse drug events /
¨ Multimorbidity & frailty /
¤ Function & life expectancy /
Take home messages /