Geriatric pharmacology

Geriatric Pharmacology

Indonesia 2012

Oscar de Vries
Internal and Geriatric Medicine
VU University Medical Center
Amsterdam

Geriatric Pharmacology

Mrs O.
75 year old

Comorbidity:
Geriatric Pharmacology

COPD
82 DMII
2x MI
Heart failure
Obesity
Gegeneralised
osteoartrosis

osteoporosis

Endometrial cancer

Dysplastic colonic polyp:
arterial bleed

2x ischaemic stroke

Cataract surgery

03 breast cancer:
lumpectomy + RT

Mw O.- medication in 2009

Geriatric Pharmacology

Mixtard 30/70 60-0-66 E

Seretide 2 dd 2 puffs
salbutamol 8 dd 2 puffs
ipratropium 8 dd 2 puffs
tiotropium 1 dd 18 g
Acetylcystein 3 dd 1 amp
Fluimucil 2 dd 500 mg tab
promethazin 2 dd 25 mg
triamtereen 1 dd 50 mg
nitrostat z.n.
verapamil ret. 1 dd 180 mg
magnesiumoxide 4 dd 1000
mg

paracetamol/coden 8 dd
500-20 mg

diazepam 2 dd 10 mg

calciumcarbonaat 1 dd 1000
mg

colecalciferol 1 dd 400 IE

temazepam 1 dd 20 mg a.n.

omeprazol 3 dd 40 mg

ferrofumarate 3 dd 200 mg

acetylic acid 1 dd 38 mg

bisacodyl 3 dd 15 mg

atorvastatin 1 dd 40 mg

bumetanide 1 dd 3 mg

Functional decline and not feeling well since 6 months

Multimorbidity = (too) many specialists involved

Geriatric Pharmacology

2008; diagnostics and/or therapy by:

Gasteroenterology: endoscopy

Orthopaedics: hip pain e.c.i.

Anaesthesiology: hip pain e.c.i.

Pulmonology: asthma?

Geriatrics: DM, polypharmacy, heart failure

Rehabilitation medicine: hip pain e.c.i.

Ophthalmology: cataract, retinopathy

Plastic surgery: abdominal fat reduction?

Geriatric Pharmacology

What to do??????

Geriatric Pharmacology

Do we have a problem?
Geriatric Pharmacology

65 and older: >40% of

extramural prescription drugs
( 16% of the Dutch
population)

65 and older:

40%: no medication
20%: 1 drug
40%: 2 drugs
On average 3 different drugs
a day

Characteristics of medication use in the elderly

Geriatric Pharmacology

80% of all prescriptions for elderly is a repeat

order

10-15% of hospital admissions in the elderly
caused by medication use

Top 5 drugs in the elderly (NL 2010)

Geriatric Pharmacology

acetylsalicylate
metoprolol
simvastatin
omeprazol
furosemide

 4 generic drugs (%)

Geriatric Pharmacology

Polypharmacy
Geriatric Pharmacology

More adverse events

Reduced adherence
More inappropriate medication
More morbidity, loss of function and mortality
More costs

Exclusion criteria in 283 RCTs

Geriatric Pharmacology

Exclusion criteria

No (%) of trials

Inability to give
informed consent
Age > 65

85.5
38.5

Related to gender:
Male
Female
Co-morbidities

7.8
39.2
81.3

Medication related

54.1

JAMA. 2007;297(11):1233-40.

Influence of pharmaceutical companies

Geriatric Pharmacology

Study design: new drug compared to inferior drug or too

low dose

Selection bias: study population does not represent a
relevant population

Publication bias: negative resultats are not published or
not released for meta-analyses

Evidence based medicine

Geriatric Pharmacology

Conflict of interest and positive conclusions

of meta-analyses
Geriatric Pharmacology

Sponsoring by 1 company:

55% favorable outcome

92% favorable conclusion

Sponsoring by 2 or more companies:

57% favorable outcome

79% favorable conclusion

Non profit sponsoring:

No difference between outcome and conclusion

Yank V. et al. BMJ 2007;335:1202-5

Geriatric Pharmacology

What if doctors, like Nascar drivers, wore their sponsor logos?

New Yorker Magazine (2011)

Geriatric Pharmacology

Study population:

age 71 jr (SD 5 yr)

GFR < 50ml: 1-2%

Diabetes Obes Metab. 2009;11:804-12.

Geriatric Pharmacology

Pharmacodynamical changes in
the elderly

(what does the substance to the body?)

Farmacodynamics II
Geriatric Pharmacology

Relevance:

Central nervous system:

increased central parasympatic responsiveness.
For example: anticholinergics

Cardiovascular:

decrease -adrenergic responsiveness and baroreceptor
reflex.
For example: -blocking agents, vasodilating agents, digoxin

Drugs with a strong anticholinergic effect

Geriatric Pharmacology

Anti-aritmics: disopyramide
Anti-emetics: cyclizine, dimenhydrinate, meclozine
Antihistaminics: clemastine, meclozine, promethazine
Anti-Parkinson drugs: biperideen, pergolide, orfenadrine, levodopa
Classic antipsychotics: chloorpromazine, haloperidol, cisordinol
Atypical antipsychotics: clozapine, olanzapine
Spasmolytics: atropine, oxybutynine, tolterodine
Tricyclische antidepressive drugs
Anaesthetics: e.g. propofol

Anticholinergic activity of some

much prescribed drugs
Geriatric Pharmacology

Medication
captopril
coden
dipyridamol
isosorbidedinitrate
furosemide
nifedipine
ranitidine
digoxin
theofyllin
prednisolon
cimetidine

Anticholinergic activity
(in atropine equivalent)
0,02
0,11
0,11
0,15
0,22
0,22
0,22
0,25
0,44
0,55
0,86

Tune L et al. Am J Psychiatry 1992; 149: 1393-1394.

Geriatric Pharmacology

Pharmacokinetical changes in
the elderly
(what does the body to the substance?)

Pharmacokinetical changes in old age

Geriatric Pharmacology

factor

difference

clinical effect

example

Resorption

acidity
intestinal
resorption

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

Diazepam
Ethanol
Digoxin

Metabolism

CYP-450

T1/2 fase 1 drugs

Interactions!

Elimination

renal blood flow

glomeric filtration

T1/2 renally
cleared drugs

Digoxin, lithium,
aminoglycosides

Pharmacokinetical changes in old age

Geriatric Pharmacology

factor

difference

clinical effect

example

Resorption

acidity
intestinal
resorption

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

Diazepam
Ethanol
Digoxin

Metabolism

CYP-450

T1/2 fase 1 drugs

Interactions!

Elimination

renal blood flow

glomeric filtration

T1/2 renally
cleared drugs

Digoxin, lithium,
aminoglycosides

Cytochrome P450
Geriatric Pharmacology

CYP
family

substrate

Inhibitor

Inductor

1A2

clozapine
theofylline

cimetidine
ciprofloxacin
fluvoxamine

carbamazepine
phenytoin
rifampicin
smoking

2C9

tolbutamide
phenytone
warfarin

amiodaron
cimetidine
fluconazol
miconazol
fluvoxamine

carbamazepine
phenytoin
rifampicine
phenobarbital

2C19

diazepam
citalopram
clopidogrel
PPIs

co-trimoxazole
fluvoxamin
fluoxetine
esomeprazol

carbamazepine
phenytoin
rifampicine
ethanol

Cytochrome P450
Geriatric Pharmacology

CYP
substrate
family

Inhibitor

Inductor

2D6

tricyclische
antidepressive
antipsychotics
metoprolol
propranolol

fluoxetine
paroxetine
ritonavir
kinidine
sertraline

dexamethason
rifampicin

3A4

calcium
antagonists
carbamazepine
cisapride
fentanyl
terfenadine
simvastatin

calcium
antagonists
amiodaron
imidazoles
macrolides
Protease inhibitors
SSRIs

rifampicin
carbamazepine
phenytoin
glucocorticoids

Pharmacokinetical changes in old age

Geriatric Pharmacology

factor

difference

clinical effect

example

Resorption

acidity
intestinal
resorption

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

Diazepam
Ethanol
Digoxin

Metabolism

CYP-450

T1/2 fase 1 drugs

Interactions!

Elimination

renal blood flow

glomeric filtration

T1/2 renally
cleared drugs

Digoxin, lithium,
aminoglycosides

Geriatric Pharmacology

Evaluate medication periodically!

Geriatric Pharmacology

Qualitative: Medication Apropriateness Index (MAI)

Indication
Effectiveness
Dosage
Practical instructions

Drug-drug interaction
Drug-disease interaction
Duplication
Duration

Fitzgerald LS, Hanlon JT, et al. Ann Pharmacother. 1997;31:543-8.

Evaluate medication periodically!

Geriatric Pharmacology

Qualitative: Medication Apropriateness Index (MAI)

What should be added?

Indication
Effectiveness
Dosage
Practical instructions

Drug-drug interaction
Drug-disease interaction
Duplication
Duration

Fitzgerald LS, Hanlon JT, et al. Ann Pharmacother. 1997;31:543-8.

Periodical drug regimen evaluation (2)

Geriatric Pharmacology

Explicit:

Updated Beers criteria
J Am Geriatr Soc. 2012;60:616-31.

STOPP (Screening Tool of Older Peoples potentially

inappropriate Prescriptions) and START (Screening
Tool to Alert doctors to the Right Treatment) criteria
Barry JP et al. Age Ageing. 2007;36:632-638.

Take home question

Geriatric Pharmacology

Is this drug really beneficial for my geriatric patient?