10. dr. abraham s. - gerontopharmacology
TRANSCRIPT
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Geriatric Pharmacology
Oscar de VriesInternal and Geriatric Medicine VU University Medical Center
Amsterdam
Geriatric pharmacology
Indonesia 2012
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Geriatric Pharmacology
Mrs O.75 year old
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Geriatric Pharmacology
Comorbidity:
COPD
82 DMII2x MIHeart failure
ObesityGegeneralisedosteoartrosisosteoporosis
Endometrial cancerDysplastic colonic polyp:arterial bleed2x ischaemic strokeCataract surgery03 breast cancer:lumpectomy + RT
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Geriatric Pharmacology
Mw O.- medication in 2009
Mixtard 30/70 60-0-66 ESeretide 2 dd 2 puffssalbutamol 8 dd 2 puffsipratropium 8 dd 2 puffstiotropium 1 dd 18 g
Acetylcystein 3 dd 1 ampFluimucil 2 dd 500 mg tabpromethazin 2 dd 25 mgtriamtereen 1 dd 50 mgnitrostat z.n.
verapamil ret. 1 dd 180 mgmagnesiumoxide 4 dd 1000mg
paracetamol/coden 8 dd500-20 mgdiazepam 2 dd 10 mgcalciumcarbonaat 1 dd 1000mgcolecalciferol 1 dd 400 IE
temazepam 1 dd 20 mg a.n.omeprazol 3 dd 40 mgferrofumarate 3 dd 200 mgacetylic acid 1 dd 38 mgbisacodyl 3 dd 15 mgatorvastatin 1 dd 40 mgbumetanide 1 dd 3 mg
Functional decline and not feeling well since 6 months
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Geriatric Pharmacology
Multimorbidity = (too) many specialists involved
2008; diagnostics and/or therapy by:
Gasteroenterology: endoscopyOrthopaedics: hip pain e.c.i.
Anaesthesiology: hip pain e.c.i.
Pulmonology: asthma?Geriatrics: DM, polypharmacy, heart failureRehabilitation medicine: hip pain e.c.i.
Ophthalmology: cataract, retinopathyPlastic surgery: abdominal fat reduction?
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What to do??????
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Geriatric Pharmacology
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Geriatric Pharmacology
65 and older : >40% of extramural prescription drugs( 16% of the Dutchpopulation)65 and older :
40%: no medication 20%: 1 drug
40%:
2 drugs On average 3 different drugs
a day
Do we have a problem?
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Geriatric Pharmacology
Characteristics of medication use in the elderly
80% of all prescriptions for elderly is a repeatorder
10-15% of hospital admissions in the elderlycaused by medication use
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Top 5 drugs in the elderly (NL 2010)
acetylsalicylatemetoprolol
simvastatinomeprazolfurosemide
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4 generic drugs (%)
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Polypharmacy
More adverse events
Reduced adherenceMore inappropriate medicationMore morbidity, loss of function and mortality
More costs
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Exclusion criteria in 283 RCTs
7.839.2
Related to gender:MaleFemale
38.5 Age > 65
54.1Medication related
81.3Co-morbidities
85.5Inability to giveinformed consent
No (%) of trialsExclusion criteria
JAMA. 2007;297(11):1233-40.
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Influence of pharmaceutical companies
Study design: new drug compared to inferior drug or too
low doseSelection bias: study population does not represent arelevant population
Publication bias: negative resultats are not published ornot released for meta-analyses
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Evidence based medicine
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Conflict of interest and positive conclusionsof meta-analyses
Sponsoring by 1 company:55% favorable outcome92% favorable conclusion
Sponsoring by 2 or more companies:57% favorable outcome79% favorable conclusion
Non profit sponsoring:No difference between outcome and conclusion
Yank V. et al. BMJ 2007;335:1202-5
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What if doctors, like Nascar drivers, wore their sponsor logos?New Yorker Magazine (2011)
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Study population:age 71 jr (SD 5 yr)
GFR < 50ml: 1-2%
Diabetes Obes Metab. 2009;11:804-12.
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Pharmacodynamical changes inthe elderly
(what does the substance to the body? )
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Farmacodynamics II
Central nervous system:increased central parasympatic responsiveness.
For example: anticholinergicsCardiovascular:
decrease -adrenergic responsiveness and baroreceptorreflex.
For example: -blocking agents, vasodilating agents, digoxin
Relevance:
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Drugs with a strong anticholinergic effect
Anti-aritmics : disopyramide Anti-emetics : cyclizine, dimenhydrinate, meclozine Antihistaminics : clemastine, meclozine, promethazine Anti-Parkinson drugs : biperideen, pergolide, orfenadrine, levo-
dopa Classic antipsychotics: chloorpromazine, haloperidol, cisordinol Atypical antipsychotics: clozapine, olanzapine Spasmolytics : atropine, oxybutynine, tolterodine
Tricyclische antidepressive drugs Anaesthetics: e.g. propofol
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Medication Anticholinergic activity(in atropine equivalent)captopril 0,02coden 0,11dipyridamol 0,11isosorbidedinitrate 0,15furosemide 0,22nifedipine 0,22ranitidine 0,22digoxin 0,25theofyllin 0,44prednisolon 0,55cimetidine 0,86
Anticholinergic activity of somemuch prescribed drugs
Tune L et al. Am J Psychiatry 1992; 149: 1393-1394 .
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Pharmacokinetical changes inthe elderly
(what does the body to the substance? )
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Geriatric Pharmacology
Pharmacokinetical changes in old age
factor difference clinical effect example
Resorption acidity intestinalresorption
none
First pass-effect liver blood flow biological
availability
Nitrates, opioids,
Ca-antagonists
Distribution fat body fat protein binding
Lip: Hydr: plasma conc. start dose
DiazepamEthanolDigoxin
Metabolism CYP-450 T1/2 fase 1 drugs Interactions!
Elimination renal blood flow glomeric filtration
T1/2 renallycleared drugs Digoxin, lithium,aminoglycosides
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Geriatric Pharmacology
Pharmacokinetical changes in old age
factor difference clinical effect example
Resorption acidity intestinalresorption
none
First pass-effect liver blood flow biological
availability
Nitrates, opioids,
Ca-antagonists
Distribution fat body fat protein binding
Lip: Hydr: plasma conc. start dose
DiazepamEthanolDigoxin
Metabolism CYP-450 T1/2 fase 1 drugs Interactions!
Elimination renal blood flow glomeric filtration
T1/2 renallycleared drugs Digoxin, lithium,aminoglycosides
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Geriatric Pharmacology
Cytochrome P450
CYPfamily
substrate Inhibitor Inductor
1A2 clozapine cimetidine carbamazepinetheofylline ciprofloxacin phenytoin
fluvoxamine rifampicinsmoking
2C9 tolbutamide amiodaron carbamazepinephenytone cimetidine phenytoinwarfarin fluconazol rifampicine
miconazol phenobarbitalfluvoxamine
2C19 diazepam co-trimoxazole carbamazepinecitalopram fluvoxamin phenytoin
clopidogrel fluoxetine rifampicinePPIs esomeprazol ethanol
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Cytochrome P450
CYPfamily
substrate Inhibitor Inductor
2D6 tricyclischeantidepressive
fluoxetineparoxetine
dexamethasonrifampicin
antipsychotics ritonavirmetoprolol kinidinepropranolol sertraline
3A4 calciumantagonists
calciumantagonists
rifampicincarbamazepine
carbamazepine amiodaron phenytoincisapride imidazoles glucocorticoidsfentanyl macrolidesterfenadine Protease inhibitorssimvastatin SSRIs
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Geriatric Pharmacology
Pharmacokinetical changes in old age
factor difference clinical effect example
Resorption acidity intestinalresorption
none
First pass-effect liver blood flow biological
availability
Nitrates, opioids,
Ca-antagonists
Distribution fat body fat
protein binding
Lip: Hydr: plasma conc.
start dose
DiazepamEthanol
DigoxinMetabolism CYP-450 T1/2 fase 1 drugs Interactions!
Elimination renal blood flow glomeric filtration
T1/2 renallycleared drugs
Digoxin, lithium,aminoglycosides
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Evaluate medication periodically!
IndicationEffectivenessDosage
Practical instructions
Drug-drug interactionDrug-disease interactionDuplication
Duration
Qualitative: Medication Apropriateness Index (MAI)
Fitzgerald LS, Hanlon JT, et al. Ann Pharmacother. 1997;31:543-8.
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Evaluate medication periodically!
What should be added?
IndicationEffectivenessDosage
Practical instructions
Drug-drug interaction
Drug-disease interactionDuplicationDuration
Qualitative: Medication Apropriateness Index (MAI)
Fitzgerald LS, Hanlon JT, et al. Ann Pharmacother. 1997;31:543-8.
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Periodical drug regimen evaluation (2)
Explicit:
Updated Beers criteriaJ Am Geriatr Soc. 2012;60:616-31.
STOPP (Screening Tool of Older Peoples potentiallyinappropriate Prescriptions) and START (ScreeningTool to Alert doctors to the Right Treatment) criteria
Barry JP et al. Age Ageing. 2007;36:632-638.
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Take home question
Is this drug really beneficial for my geriatric patient?