EMAN SUTRISNA

DEPARTMENT OF PHARMACOLOGY AND THERAPEUTIC

MEDICAL FACULTY JENDERAL SOEDIRMAN UNIVERSITY

BABY-CHILDREN

ELDERLY

SPECIAL AGE
GROUPS

SPECIAL
CONDITIONS

PREGNANCYLACTATION

HEPATIC DISEASE

RENAL DISEASE

ELDERLY

NORMAL/NATURA
L

WITH DISEASES

RENAL DISEASE

HEPATIC DISEASE

NORMAL AGING
Physiologic function

homeostatic reserve

Phkinetic phdynamic
changes

Altered-drug response

Adverse drug event/toxicity

Multiple disease
Multiple medication

drug interaction

Medication-Related Problems
Why the elderly are at risk

Physiologic Variable

Adults

Elderly

ABSORPTION
Esophageal motility
Gastric emptying time (half
time, min)
Function of Digestive Enzymes

47

123

Physiologic Variable

Adults

Elderly

DISTRIBUTION
Serum albumin
Total body water (L/kg weight)

4.7
.50

3.8
.47

18
33

36
45

Adipose tissue (% total body weight)

Male
Female

Physiologic Variable

Adults

ELDERLY

Metabolism
Liver weight (gm/kg body weight)
Hepatic blood flow (mL/min)
Antipyrine clearance (mL/hr/kg)

25
1400
47

20
800
28

122
1100

85
600

Elimination
Glomerular filtration rate
Renal blood flow (mL/min/1.73m2)

Changes in Pharmacokinetics
Age-associated changes in physiology

and organ function result in changes in

pharmacokinetics
No significant changes in absorption

2004: Cusack, Amer. J of Geriatric Pharmacotherapy

Plasma Half-Lives in Young and

Old
Drug
Young (20-30) Elderly (65-80)
Penicillin G
Tetracycline
Digoxin
Diazepam
Lidocaine
Chlordiazepoxide
Phenobarbital
Warfarin

20.7 min
3.5 hr
51 hr
20 hr
80.6 hr
8.9 hr
71 hr
37 hr

39.1 min
4.5 hr
73 hr
80 hr
139.6 hr
16.7 hr
107 hr
44 hr

Volume of Distribution
(Vd)
Extent of distribution in the plasma
relative to the amount in the body.
The elderly have an increased
proportion body fat and decreased
muscle mass

Increased volume of distribution for fat

soluble drugs increases longer half life-e.g.,

diazepam
Decreased volume of distribution for
water soluble drugs increases drug plasma
concentration e.g., ethanol

Protein Binding
Decreased albumin a higher

proportion of free drugs.

Drugs that bind to albumin :

Cephalosporines : Ceftriaxone,

ect
Diazepam
Phenytoin
Warfarin, ect...

Hepatic Metabolism
Regional blood flow to the liver at age 65 is

reduce by 40-45% compared to a 25 year old

Decreased liver size and hepatic blood
flow.
Metabolic clearance of drugs by the liver may be

reduced Accumulation active drug (repeated

administration), increasing drug half-life
Increase pharmacologic response (intensity and
time of action
Increase risk of toxicity

Environmental effects: smoking stimulates

peroxydase enzymes ROS

Elimination
Even in the absence of kidney disease

renal clearance may be reduced 3550%.

Decreased renal function results in
Decreased elimination of drugs
Reduced renal clearance of active

metabolites may enhance therapeutic

effect BUT also increase risk of toxicity.

Need to dose management

reduce dose and/or increase dosing
intervals.

Pharmacodynamics Change
Receptor alteration
with age best documented for adrenergic

receptors and autonomic nervous system.

Increased drug sensitivity

to sedation, hypotensive (side) effects
Diminished adaptive capacity most

manifested as increased occurrence of

adverse events with medications.

% of people taking a drug

Adverse Drug
reactions more
common in the
elderly

7 times more
common in the
elderly

= authors of studies

Factors that Predispose

Elderly to ADRs
Drug accumulation secondary to

reduced renal function

Polypharmacy
Greater use of drugs with a low
therapeutic index ( i.e. digoxin)
Inadequate supervision of long-term
therapy
Poor patient adherence

Factors Attributing to Poor

Drug Adherence
Multiple chronic disorders
Multiple prescriptions
Multiple doses
Change in daily drug regimen
Cognitive or physical impairment
Living alone
Inability to pay for drugs
Presence of side effects

Attention to DRUGS INDUCE

DISEASE
Ototoxic reaction (aminoglicoside)
Nephrotoxic reaction (aminoglicoside, beta

lactam, NSAIDs)
Hepatotoxic reaction (Parasetamol, steroid,
OAT, hypnotic sedative)
Periperal neurophaty (INH, nitrofurantoin)
Hypoglycemic (Sulfonil urea)
Cardiotoxic (digitalis, blocker)

i
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t
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EEffeekk toks

Hepatitis
Hepatitis akut:paracetamol
akut:paracetamol

(Acetaminophen)
(Acetaminophen)
,tetrasiklin,Isoniazid,salisilat,
,tetrasiklin,Isoniazid,salisilat, ethanol,
ethanol,
ferrosulfas.
ferrosulfas.

Cirrhosis:
Cirrhosis: MTX,
MTX, arsen,
arsen, ethanol.
ethanol.

Cholestasis:Estrogen.
Cholestasis:Estrogen.

Neoplasma:kontrasepsi
Neoplasma:kontrasepsi oral
oral ,,
kortikosteroid
kortikosteroid

Drugs Causing ADR

Most frequent drug class causing
ADR

Cardiovascular active agents

Analgesics
Antibiotics
Hypoglycemic agents
Psychotropic agents
Anticoagulants
Others

34
18
15
10
7
5
12

Appropriate Prescribing for

Geriatric Patients
Obtain a complete drug history
Avoid prescribing before a diagnosis is made
Review medications regularly and before

prescribing a new medication

Know the actions, adverse effects, and
toxicity profiles of he medications you
prescribe
Start low dose and titrate dose based on
tolerability and response

Prescribing to Reduce ADRs

hepatic and renal disease may impair

clearance of drugs so smaller doses may

be needed.
Prescribe as few drugs as possible and

give clear instructions to patients and carers

If serious ADRs are liable to occur warn

the patient
Where possible use familiar drugs. .

Principle of Geriatric Drug Use

Start low and go slow

HAPPY
OMA-OPA

Contoh Model
PENYESUAIAN DOSIS PADA
PENDERITA PENYAKIT GINJAL
TERUTAMA PADA OBAT

INDEKS
TERAPI SEMPIT
DENGAN

Creatinine
Creatinine clearance(mL/min)=
clearance(mL/min)=
(140-umur)
(140-umur) xx Berat
Berat badan
badan (kg)
(kg)
------------------------------------------------------------------------------------72
72 xx kadar
kadar creatinine
creatinine serum
serum
(( mg/dL)
mg/dL)
Koreksi
Koreksi pada
pada wanita:
wanita: kali
kali 0.85
0.85

Tentukan
Tentukan dosis
dosis berdasarkan
berdasarkan dosis
dosis pada
pada ginjal
ginjal
normal.
normal.
Tentuan
Tentuan fraksi
fraksi obat
obat utuh
utuh atau
atau metabolit
metabolit aktip
aktip
yg
yg diekskresi
diekskresi lewat
lewat ginjal.
ginjal.
Hitung
Hitung fungsi
fungsi clearance
clearance ginjal
ginjal atau
atau dg
dg formula
formula
Cockroft-Gault.
Cockroft-Gault.
Hitung
Hitung dosage-ajustment
dosage-ajustment factor
factor ::
_________1_________
_________1_________
FF (( kf
kf 11 )) +
+ 11
F=fraksi
F=fraksi obat
obat utuh
utuh dlm
dlm urine(
urine( %)
%)
kf=
kf= fungsi
fungsi ginjal
ginjal relatip=clearance
relatip=clearance
kreatinin:120
kreatinin:120 ml/min
ml/min

PILIH
PILIH MANA
MANA YANG
YANG DISUKAI
DISUKAI ::
Dosis
Dosis pada
pada ginjal
ginjal normal
normal dibagi
dibagi
ajustment
ajustment factor,
factor, teruskan
teruskan dengan
dengan
interval
interval pemberian
pemberian seperti
seperti biasa
biasa ,, atau:
atau:
Dosis
Dosis seperti
seperti normal
normal tetapi
tetapi
intervalnya
intervalnya merupakan
merupakan perkalian
perkalian
antara
antara ajustment-factor
ajustment-factor dengan
dengan
interval
interval normal
normal ,atau:
,atau:
Kurangi
Kurangi dosis
dosis dan
dan perpanjang
perpanjang
interval.
interval.

Contoh:
Contoh: Perhitungan
Perhitungan Dosis
Dosis
Digoxin
Digoxin
FF digoxin=0.75
digoxin=0.75 (75%
(75% diexcresi
diexcresi sbg
sbg
bentuk
bentuk utuh
utuh dlm
dlm urine).Bila
urine).Bila dosis
dosis
lazim(ginjal
lazim(ginjal normal)
normal) 0.25
0.25 mg,
mg,
clearance
clearance creatinin
creatinin 60
60 ml/menit,
ml/menit, maka
maka
11
Dose-ajustment
Dose-ajustment factor=
factor=
----------------------------------------------0.75
0.75 (60/120
(60/120 1)
1)
+
+ 11
=
= 1.6
1.6
Dosis
Dosis penyesuaian=
penyesuaian= 0.25mg
0.25mg // 1.6
1.6 =
=