พท ผศ พญ พัฒน์ศรี ศรีสุวรรณ · excretion ! glomerular...

การใชยาในผสงอาย/

พ.ท. ผศ. พญ. พฒนศร ศรสวรรณ/

กองตรวจโรคผปวยนอก และเวชศาสตรครอบครว /

รพ.พระมงกฎเกลา/

30 พฤษภาคม 2562 /

¨ 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 /

1.   Principle /

2.   Primary care/

3.   Multimorbidity & Frailty /

4.   Take home messages /

¨ 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. !

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. !

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.

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. !

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. !

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. !

¨ 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. !

¨ Long-acting BZP !

¤ Diazepam !

¤ Chlorazepate!

¤ Chlordiazepoxide !

¨ < 5%!

¨ Polypharmacy:

medication

reconciliation !

¨ > 50%!

ผปวยนอก/ ผปวยใน/

ตวชวด/

ชยรตน ฉายากล และคณะ. คมอการดำเนนงานโครงการรพ.สงเสรมการใชยาอยางสมเหตผล 2558. !



1.  Avoid !

2.  Interaction: diseases & syndromes!

3.  Caution !

4.  Drug-drug interactions!

5.  Kidney function !

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. !

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 !


Strong anticholinergics /

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 !


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!


Cardiovascular/

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 !


Endocrine /

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 !


Gastrointestinal /

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 !


Pain medications /

Beers Criteria 2015: Removed /




Beers Criteria 2015:/

Added /

1.   Principle /




Chau SH, et al. Int Clin Pharm 2016. !

Drug-related problems (DRP): older adults/

DRP: overtreatment & undertreatment/

Chau SH, et al. Int Clin Pharm 2016. !

PROTON PUMP INHIBITORS!

Thailand Dyspepsia Guidelines: 2018 /

Pittayanon R, et al. !

J Neurogastroenterol Motil 2019. !

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 /

Netherlands Guidelines /

Flinterman LE, !

et al.!

Front Public

Health 2018.. !

Risk associate: long-term PPI use/

Nehra AK, et al. Mayo Clin Proc 2018./

Farrell B, et al. Can Fam Physician 2017. !

ASPIRIN!

Lifetime events: healthy elderly /

McNeil JJ, et al. N Engl J Med 2018..!

Major hemorrhage/Incidence CVD/


Aspirin/

Williams B, et al. European Heart Journal 2018. !

Williams B, et al. European Heart Journal 2018. !

ASA: time to benefit & age /

Dixon D, et al. ACSAP 2018. !

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 /

LIPID!

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. !

2019 ACC/AHA guideline /

Lin K, et al. Am Fam Physician 2019..!

แนวทางเวชปฏบตการใชยารกษาภาวะไขมนผดปกต !

เพอปองกนโรคหวใจและหลอดเลอด พ.ศ. 2559 !

Primary prevention/

Primary prevention: DM/

แนวทางเวชปฏบตการใชยารกษาภาวะไขมนผดปกต เพอปองกนโรคหวใจและหลอดเลอด พ.ศ. ๒๕๕๙ !

Statin

แนวทางเวชปฏบตการใชยารกษาภาวะไขมนผดปกต เพอปองกนโรคหวใจและหลอดเลอด พ.ศ. ๒๕๕๙ !

USPSTF: statin for primary prevention CVD/

Ngo-Mtzger Q, et al. Am Fam Physician 2017..!

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.!

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. !

Patient-related factors: lipid treatment/

Bertolotti M, et al. Gerontol Int 2019..!

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%!

Drug: side effect &

comorbid condition in

primary care/

Merel SE, et al. J Am Geriatr Soc 2017. !

drug-drug interactions in primary care /

Merel SE, et al. J Am Geriatr Soc 2017. ! Carpenter M, et al. Am Fam Physician 2019. !

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 /

Carpenter M, et al. Am Fam Physician 2019. !

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/

1.   Principle /




Decision making: multiple chronic conditions /

Ouellet GM, et al. Ther Adv Drug Saf 2018. !

Current & future !

Evidence !

4. Deprescribing !

Decision making: multimorbidity /

Boyd C, et al. J Am Geriatr Soc 2019. !

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 /

Zanker J, et al. J Am Geriatr Soc 2019. !

Time to benefit/

• Age < 70 year: 19 months /

• Age > 70 year: 8 months /

Thompson W, et al. J Am Geriatr Soc 2019.!

Deprescribing/

Farrell B, et al. Am Fam Physician 2019.!

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./

Steinman MA, et al. J Am Geriatr Soc 2019./

1.   Principle /




¨ 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 /

พท ผศ พญ พัฒน์ศรี ศรีสุวรรณ · excretion ! glomerular...

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