FARMAKOLOGI GERIATRI

Oleh :
P. Santoso,S.Si.,M.Biomed,Apt
 Who is old?
60+, 70+, 80+, 90+…?

We are born as copies and die as

originals
Bo G Eriksson
TERAPI FARMAKOLOGI PADA
GERIATRI
 Who is old?
60+, 70+, 80+, 90+…?

We are born as copies and die as

originals
Bo G Eriksson
 Elderly more sensitive to drugs
because (1)
• Reduced amount of water in the body -fat soluble drugs
remain longer in the body with prolonged effects – of
importance for some sedatives and anxiolytics
• Reduced kidney function - decreased excretion of some
cardiovascular drugs, some antibiotics, diabetic drugs,
antiinflammatory drugs – need to reduce dosage
• Reduced liver function – decreases metabolism of opioids,
bensodiazepines and some antidepressive drugs
• Brain and nervous system more sensitive to psychotropic and
analgesic drugs – dizziness, confusion
 Elderly more sensitive to drugs
because (2)
• Decreased capacity to regulate blood pressure
– blood pressure fall, fainting, vertigo when
using drugs for hypertension
• Gastrointestinal sensitivity to anti-
inflammatory drugs - bleeding
 Drug safety in the elderly
Do we have a problem? Yes!
Top ten medicines reported by the EU member states
to WHO in 2010 - women and men 80+

1. Acetylsalicycic acid 6. Enalapril

2. Warfarin 7. Rovecoxib
3. Lefloxacin 8.Digoxin
4. Furosemide 9. Clopidogrel
5. Acenocoumarol 10. Ciprofloxacin
– Geriatri ≥ 65 tahun, 75 s/d 85 (Old old), ≥ 85 tahun(
Oldest old),
– Cabang kedokteran yg konsen thd aging proses:
• Pencegahan, diagnosis dan terapi.
– Objektif:
• Pengaruh usia thd farmakokinetik dan
farmakodinamik
• Memahami prinsip-prinsip peresepan obat pd orang
tua
• Multiple comorbid state
• Polifarmasi
• Resiko adverse drug events
• Tingkat kepatuhan minum obat
• Biaya
 Fakta berkaitan dgn geriatri

 Pasien berumur 65 th atau lebih

mencakup 13% dari populasi dan
membelanjakan 33% obat-obatan yg
diresepkan.

 Tahun 2040, geriatri mencakup 25%

populasi dan membelanjakan 50% obat-
obat yg diresepkan.
 Biggest errors made in
prescribing for elderly people
• Polypharmacy - a drug for every complaint and elderly
people have lots of aches and pains, circulation and
breathing difficulties etc
• Side effects are missed because they are misinterpreted as
part of getting old - particularly senility - hearing loss etc
• Elderly people often see a different doctor every time and
the next doctor does not realize that the patient was clever
and active a week ago.
• Physicians often assume that the patient is ill because they
are not taking their medications when in fact they are taking
them and the amount prescribed for them too much.
Perubahan Fisiologi Pada Lansia

 Adanya penurunan fungsional progresif

dalam banyak sistem organ dengan
bertambahnya umur, perubahan tersebut
mempengaruhi farmakoterapi
Some changes related to aging that affect pharmacokinetics of drugs

Variable Young Adult Older Adult

Body Water 61 53

Learn Body Mass 19 12

Body fat (% of body weight) 26 – 33 women 38 – 45

18 – 20 Men 36 - 38
Serum Albumin (g/dL) 4,7 3,8

Kidney Weight (% of young adult) 100 80

Hepatic flow (% of young adult) 100 50 - 60

Physiologic changes with Aging
Physiologic changes with Aging
Physiologic changes with Aging
 Perubahan Farmakokinetik
Sebagai akibat banyak perubahan fisiologi
secara teoritis berpengaruh pada :
1. Absorbsi
2. Distribusi
3. Metabolisme
4. Ekskresi
 Effects of Aging on Absorption

• Rate of absorption may be

delayed
– Lower peak concentration
– Delayed time to peak
concentration
• Overall amount absorbed
(bioavailability) is
unchanged
 Drug distribution changes in
the elderly
fluid and tissue compartments
• decrease in total body water
• increase in fat compartment
• decrease in muscle mass
plasma drug-binding proteins (rarely significant clinically)
• decrease in serum albumin levels
• no change in -acid glycoprotein levels
 Effects of Aging on Volume of Distribution
(Vd)
Aging Effect Vd Effect Examples

 body water  Vd for hydrophilic ethanol, lithium

drugs
 lean body mass  Vd for for drugs digoxin
that bind to muscle
 fat stores  Vd for lipophilic diazepam, trazodone
drugs
 plasma protein  % of unbound or diazepam, valproic acid,
(albumin) free drug (active) phenytoin, warfarin
 plasma protein  % of unbound or quinidine, propranolol,
free drug (active) erythromycin, amitriptyline
(1-acid glycoprotein)
 Aging Effects on Hepatic Metabolism

• Metabolic clearance of drugs by the liver may

be reduced due to:
– decreased hepatic blood flow
– decreased liver size and mass
• Examples: morphine, meperidine, metoprolol,
propranolol, verapamil, amitryptyline,
nortriptyline
 Effect of Aging on Drug
Metabolism and Elimination
Catagori or Class Decrease Hepatic Metabolism Decrease Renal Elimination

Analgesic and anti inflamatory Ibuprofen, morphin, naproxen,

dextropropoxiphen, meperidin

Antibiotics Amikacin , Ciprofloxacin,

gentamycin, streptomicin
Nitrofurantoin, tobramicin

Cardiovascular drugs Amlodipine, Diltiazem Captopril , digoxin

Enalapril , lisinopril
Nifedipine, Lidocaine Prokainamide
 Effect of Aging on Drug
Metabolism and Elimination
Catagori or Class Decrease Hepatic Metabolism Decrease Renal Elimination

Diuretics Furosemide
Amiloride
Hydrochlorothiazide
Triamterene

Psychoactive drugs Alprazolam

Chlordiazepoxide
Desipramine
Diazepam
Imipramine
Nortriptyline
 Concepts in Drug Elimination
• Half-life
– time for serum concentration of drug to decline
by 50% (expressed in hours)
• Clearance
– volume of serum from which the drug is removed
per unit of time (mL/min or L/hr)
• Reduced elimination  drug accumulation
and toxicity
ELIMINASI
 Ekskresi ginjal merupakan rute utama eliminasi untuk
banyak obat.
Pengurangan kecepatan eliminasi dipengaruhi oleh
umur, baik fungsi glomerulus maupun tubulus.
 Kecepatan filtrasi glomerulus (GFR) diukur melalui
inulin atau kliren creatinin
 Pada umumnya obat-obat yang secara signifikan di
eksresi melalui ginjal pada usia lansia akan menurun
klirens creatininnya.
 Obat-obat yang mempunyai potensi toxic serius
seperti aminoglikosida, amantadine, lithium, digoxin,
procainamide, chlorpropamide, cimetidin dan
beberapa NSAID
 Drug elimination changes in
the elderly
decrease in renal functions
• decreased blood flow to
the kidneys
• decreased glomerular
filtration
• decreased tubular
secretion
• decline in creatinine
clearance
 Effects of Aging on the Kidney
• Decreased kidney size
• Decreased renal blood flow
• Decreased number of functional nephrons
• Decreased tubular secretion
• Result:  glomerular filtration rate (GFR)
• Decreased drug clearance: atenolol,
gabapentin, H2 blockers, digoxin,
allopurinol, quinolones
Creatinin clearance mL/min =
(140 – Age) X (Weight in kg)
72 X Serum creatinine in mg/dL
Rumus Cokcroft-Gault yg dpt diterapkan
pada pasien berumur 40 - 80 thn
Example: Creatinine Clearance vs.
Age in a 5’5”, 55 kg Woman

Age Scr CrCl

30 1.1 65

50 1.1 53

70 1.1 41

90 1.1 30
 FARMAKODINAMIKA
Ada beberapa bukti pada usia lanjut respon terhadap
obat berubah atau ". sensitivitas"
Empat mekanisme :
(1) perubahan dalam jumlah reseptor
(2) perubahan afinitas reseptor,
(3) perubahan postreceptor dan
(4) mekanisme penurunan homeostatik
Sebagai contoh, muscarinic, hormon paratiroid, β-
adrenergik, α1-adrenergik, dan reseptor μ-opioid
 Pharmacodynamics (PD)
• Definition: the time course and intensity of
pharmacologic effect of a drug
• Age-related changes:
–  sensitivity to sedation and psychomotor impairment
with benzodiazepines
–  level and duration of pain relief with narcotic agents
–  drowsiness and lateral sway with alcohol
–  HR response to beta-blockers
–  sensitivity to anti-cholinergic agents
–  cardiac sensitivity to digoxin
 PK and PD Summary
• PK and PD changes generally result in
decreased clearance and increased sensitivity
to medications in older adults
• Use of lower doses, longer intervals, slower
titration are helpful in decreasing the risk of
drug intolerance and toxicity
• Careful monitoring is necessary to ensure
successful outcomes
Most Common Medications Associated
with ADEs in the Elderly

• Opioid analgesics
• NSAIDs
• Anticholinergics
• Benzodiazepines
• Also: cardiovascular agents, CNS agents, and
musculoskeletal agents
Adverse Drug Reaction Risk Factors in Older Outpatients. Am J Ger Pharmacotherapy 2003;1(2):82-89.
 Considerations for pharmacotherapy in the elderly
• Is drug therapy required?
• choice of appropriate
drug and preparation
• dosage regimen to
accommodate changes in
physiology
• detailed monitoring and
periodic re-evaluation of
drug therapy
• clear and simple
instructions
 Summary
• changes in the physiology of the elderly alter
responses to drug therapy
• pharmacokinetic changes affect the effective
concentration of drug in the body
• pharmacodynamic changes alter the body’s response
to the drug therapy
• adverse drug reactions are more common in the
elderly and can be avoided with better primary care
 Principles of Prescribing in the Elderly
 Balance between overprescribing and
underprescribing
 Start with a low dose and titrate slowly
 Correct drug
 Correct dose
 Targets appropriate condition
 Is appropriate for the patient

Avoid “a pill for every ill”

Always consider non-pharmacologic therapy
Terimakasih