10. dr. abraham s. - gerontopharmacology

8/12/2019 10. Dr. Abraham S. - Gerontopharmacology

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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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Mrs O.75 year old


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Comorbidity:

COPD

82 DMII2x MIHeart failure

ObesityGegeneralisedosteoartrosisosteoporosis

Endometrial cancerDysplastic colonic polyp:arterial bleed2x ischaemic strokeCataract surgery03 breast cancer:lumpectomy + RT


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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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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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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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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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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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none


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!


T1/2 renallycleared drugs Digoxin, lithium,aminoglycosides


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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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none


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!


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?

10. dr. abraham s. - gerontopharmacology

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