Phartherinfelderly-2013 BW PDF

PHARMAKOTHERAPY
IN INFANTS AND ELDERLY
Ngatidjan
Department of Pharmacology and Therapy

Faculty of Medicine UGM
Lecturer in the Faculty of Medicine MUY
1
Processes in Drug Therapy
Pharmaceutical Process
Pharmacokinetic Process
Pharmacodynamic Process
Therapeutical Process
Ngatidjan PHARTHERINFOLD-2013 2
PHARMACEUTIC PROCESS
Determinators
Drug composition and preparation
drug pharmacokinetics pharmacodynamics
it is designed to be easy absorbed, to be used orally (tablet,
capsule, caplet, film coated tablet, sugar coated tablet, suspension,
solution etc.), intramuscularly, intravenously, sublingual (tablet),
rectally (suppository, enema), etc.
it is designed to be uneasy absorbed or unabsorbed (procaine
adrenaline local anesthetics, etc.)
Drug performance patient compliance

drug color, smell, taste, shape, dimension, drug preparation.
(Graham-Smith & Aronson, 2003)
DRUG
inhalation orally intramuscularly intravenously
mucous membrane cells
endothelial cell
portal vein
liver
endothelial cell
systemic circulating blood
site of action other tissues liver kidney

(metabolism) (excretion)
effects feses urine 4
drug administration
(dose, route / methods, frequency)
absorption, first pass metabolism, bioavailability, distribution, elimination
plasma drug / metabolite concentration
drug concentration at the site of action
therapeutical / adverse effect

Ngatidjan 5
(Graham-Smith & Aronson, 2003)
Pharmaceutical process Drug in dose form
is the drug getting into the patient?
Gastrointestinal form Parenteral
First pass
Hepatic
metabolism
Pharmacokinetic process
is the drug getting to its site of action?
Extracellular fluid
eliminasi
Tissue
site of drug
action
Pharmacodynamic process
is the drug producing the required Pharrmacological effects
pharmacological effects
Therapeutic process
is the pharmacological effet being
translated into a therapeutic effect?
Therapeutic / adverse effects 6
DRUGS USE ON INFANTS
AND CHILDREN
Infants and Children
Neonate
Infancy
The toddler
Young child
Drugs use on infants and chlidren
1. Infants and children are not just little adults,
pharmacokinetic-pharmacodynamic differences.
2. Organ function development ,
drug distribution, metabolism and elimination drug pharmacokinetics effects.
3. Special methods of drug administration are needed,
orally, rectally, inhalation, or injection dose calculation.
4. The pediatric medication process is complex and error-prone,
multiple steps required in calculating, verifying, preparing, and administering doses.
5. The myth that neonates and young infants do not experience pain,
leads to inadequate pain management.
6. Concomitant diseases may occurred,
dosage requirements to achieve a targeted effect for a specific disease.
Neonate, infants and children vs. adult
Pharmaceutical aspect
they dont like injection differ in drug administration
most of them like syrup preparation differ in drug kinetics
Pharmacokinetic aspect
neonate may slow in metabolism differ in drug dose
Pharmacodynamic aspect
differ in drug sensitivity differ choosing of the kind of drug
Therapeutical aspect
prevention / prophylactic or curative
Neonate
Rapid growth
Variable alteration of drug metabolism

and elimination
Lower tolerance to adverse drug effects

higher incidence of therapeutic error
higher incidence of adverse drug effect
Infancy
An extension of early (first) stage
differ from the adult and elderly

need adjustment of the therapy.
Body weigh gain and water composition change

rapidly
need to adjust the dose
The toddler
Associated with recurrent minor illness
multiple short course of therapy
some problems in taking medicines drug preparation
Motor skill and curiosity developed faster

most likely to be suffering from poisoned intoxicated
Drug preparation and dose calculation are the

important aspect
Young child
Enhance of metabolism and
excretion capacity of some drugs
The capacity of metabolism and

excretion are change rapidly
most likely to be intoxicated
Pharmaceutical factors
Most children do not like injection
oral route is most suitable in vomiting?
Oral route
are not as tablets, capsule or caplet
mostly liquid form are preferable
sweetened medicine? tend to cause carries
Precise dose is hard to be achieved approximate

C. (cochlea) adult spoon : 15 ml
cp. (cochlea pultis) soup spoon : 8 10 ml
cth. (cochlea tea) tea spoon : 5 ml
DOSE CALCULATION
Depends on age (Youngs rule)
Dose = adult dose x [age in years : (age + 12)]
Depends on body weight (Clarks rule)

more precise
Dose = adult dose x (weight in kg : 70)
Dose = adult dose x (weight in pound : 150)
Depends on surface area

Dose = percentage (surface area rule) to adult dose
DRUG DOSE AND SURFACE AREA
Weight
Approximate Surface are Percentage of
in kg in lb / pound age (m2) adult dose
3 6.6 newborn 0.2 12

6 13.2 3 months 0.3 18
10 22.0 1 year 0.45 28
20 44.0 5.5 years 0.8 48
30 66.0 9 years 1.0 60
40 88.0 12 years 1.3 78
50 110.0 14 years 1.5 90
60 132.0 adult 1.7 102
70 154.0 adult 1.76 103
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PHARMACOKINETIC FACTORS
Drug absorption
neonate low gastric acid secretion
drug absorption differ from adult
weak acid drugs is absorbed less
than those of adult
weak base drugs is absorbed more
than those of adult
older children almost the same to adult

DRUG DISTRIBUTION
Age group Total body Extracellular Intracellular Fat
water (%) fluid (%) fluid (%) (%of weight)
Premature baby 85 50 35 1
Fullterm neonate 70 40 30 15
Infant (6 months) 70 35 35 15
Child 65 25 40 15
Young adult 60 15 45 20
Elderly adult 45 10 35 10
19
PHARMACOKINETIC FACTORS
Drug distribution
protein binding
some drugs (i.e. sulfonamide) may cause Kerns icterus
interaction to bilirubin
sulfonamides displace bilirubun from plasma albumin
bilirubin
albumin
drug
Pharmacokinetic factors
Drug elimination
metabolism in neonate is lower than adult
GFR and tubular function (excretion)
is lower than those of adult
half life
tend to accumulate drug and its metabolites

DRUG ELIMINATION
Age group Half life of diazepam (hours)
Premature baby 38 120
Fullterm neonate 22 46
Infant (1 months) 10 12
Children 1- 15 years 15 21
Adult 24 48
23
DRUG ELIMINATION
Age group Half life of phenytoin (hours)
Neonate 30 60
Infant (1 months) 27
Children 1- 15 years 2 20
Adult 20 30
24
(Lllmann et al., 2005)
Drug usage
in nourishing woman
What aspect have to be considered?
Is there any benefit if someone give
drug for infant by mean of giving the
drug to the nourished mother?
in nourished mother
some drugs may appear in breast milk
cause infant intoxication? no
cause any other risk for infants? yes it is allergy
therapy for the infant,
does mother have to take the drugs ?
irrational ?
27
ANTIBIOTIC IN BREAST MILK
Infant / maternal (50-100%) Infant / maternal (30-50%) Infant / maternal (0-30%)
ampicillin cefamandole amikain
carbenicillin cephalotin cefazolin
methicillin streptomisin dicloxacillin
chloramphenicol clindamycin eritromisin
sulfonamide gentamisin nafcillin
trimethoprim kanamisin oxacillin
tetrasiklin tobramicin
Penicillin G 28
Pharmacodynamic factors
Drug target
- receptors,
- ion channels,
- enzyme system
drug effects
- therapeutic effects
- side effects
- toxic effects
is any differences from those of adult?
Analgesics - antipyretics
- paracetamol is safe,
- acetosal Reyes syndrome,
- NSAIDs side effects
(gastrointestinal, etc.)
Antibiotics - chemotherapeutics
- penicillin derivatives is more safe,
- tetracycline tooth coloration,
- aminoglycosides deafness
- atropine hyperthermia
Cold remedy?
- paracetamol is safe analgesic antipyretics,
- sympathomimetics nasal obstruction,
- dextromethorphane antitusive?
- antihistamines any benefit?

Drug preparation
drug kinetics (liquid > tablet > enteric tab)
drug concentration in the site of action
drug effect therapeutical effect
side / toxicological effect

DRUGS USE ON ELDERLY
Leading cause of death in elderly (DiPiro et al, 2012)
35
drug administration
(dose, route / methods, frequency)
absorption, first pass metabolism, bioavailability, distribution, elimination
plasma drug / metabolite concentration
drug concentration at the site of action
therapeutical / adverse effect

Pharmacotherapy in elderly
The population of elderly (aged > 65 years) is increasing.
Age-related changes in physiology may affect the PKD
(pharmacokinetics and pharmacodynamics) of some drugs.
Improving and maintaining functional status (physiological) is
important in care for elderly.
Drug-related problems in elderly are common and may cause
considerable morbidity.
It is important to optimize drug therapy and prevent drug
related problems in older elderly.
Relevant changes in ageing and pharmacology
Pharmacological Age-related changes Clinical effect
parameter
Tissue sensitivity Alterations in receptor number, Patients are more sensitive or less
and affinity, or other site of drug sensitive to a given medication
action
Absorption Decrease in splanchnic blood Minimal changes associated with

flow and absorptive surface ageing
gastrointestinal motility
Increased gastric pH
Distribution Decrease in total body water, Higher concentration of drugs

serum albumin and lean body Longer elimination half-life of lipid
mass soluble drugs
Increased fat
Metabolism Decreased liver blood flow Decreased biotransformation and

and enzyme activity first-pass metabolism
Excretion Decreased renal perfusion, Decreased renal elimination

GFR and tubular secretion of drug
rate and tubular secretion
(Oscar et al, 2012)
Elderly people versus adult
Pharmaceutical aspect
difficult to swallow differ in drug administration
Pharmacokinetic aspect
elimination lower than adult differ in drug dose
Pharmacodynamic aspect
sensitivity differ from adult choosing of drug
Therapeutical aspect
differ in drug use for therapeutic purpose
Pharmaceutical factors
Most elderly people difficult to swallow drugs
oral route is suitable but in non-solid form
Oral route
are not as tablets, capsule or caplet
mostly liquid form are preferable
dose problems (drug concentration)?
Precise dose is hard to be achieved approximate

C. (cochlea) adult spoon : 15 ml
cp. (cochlea pultis) soup spoon : 8 10 ml
cth. (cochlea tea) tea spoon : 5 ml
Pharmacokinetic factors
Drug elimination
metabolism in elderly is lower than adult
GFR and tubular function (excretion)
is lower than those of adult
half life
tend to accumulate drug and its metabolites

Medications with decreased renal excretion
Triamterene Atenolol
Sotalol Amantadine
Procainamide Ampicillin
Ranitidine Cimetidine
Pancuronium Cephradine
Phenobarbital Ceftriaxone
Penicillin Digoxin
Lithium Furosemide
Kanamycin Doxycycline
Hydrochlorothiazide Gentamicin
(Cepeda & Morley, 2012)
Drug target
- receptors,
- ion channels,
- enzyme system
drug effects
- therapeutic effects
- side effects
- toxic effects
is any differences from those of adult?
Some drugs are needed
Vitamine and nutrition supplements
Minerals
Enzymes
Hormones
Analgesics-antiinflammatory agents
Etc.
Analgesics - antipyretics
- paracetamol is safe,
- acetosal g.i. bleeding,
- NSAIDs side effects
Antibiotics - chemotherapeutics
- penicillin derivatives is more safe,
- tetracycline tooth coloration,
- aminoglycosides deafness
- erythromycin g.i. colic

Antithrombotic
(low dose ASA),
- may cause g.i. bleeding melena,
- change with other antithrombus
then back to low dose ASA

Antitusive
(do not give codeine),
- may cause constipation,
scibala (hard feces)
- is there any benefit to give cathartics
(yes but it may cause rebound phenomenon)
Guideline for monitoring of drug uses in elderly
Acetaminophen (>4 g/day) Hepatic function tests
Aminoglycosides Serum creatinine, drug levels
Hypoglycemic agents Blood sugar levels
Antiepileptic agents (older) Drug levels
ACEH (captopril, lisinopril etc.) Potassium levels
Antipsychotic agents Extrapyramidal adverse effects
Appetite stimulants Weight, appetite
Digoxin Serum creatinine, drug levels
Diuretic Potassium levels
Erythropoiesis stimulants Blood pressure, iron and ferritin
levels, complete, blood count
51
Guideline for monitoring of drug uses in elderly
Fibrates Hepatic function test, complete
blood count
Iron Iron and ferritin levels, complete
blood count
Lithium Drug levels
Niacin Blood sugar levels, hepatic
function tests
Statins Hepatic function tests
Theophylline Drug levels
Thyroid replacement Thyroid function tests
Warfarin Prothrombin time/international
normalized ratio
52

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PHARMAKOTHERAPY

IN INFANTS AND ELDERLY

Department of Pharmacology and Therapy

Drug performance patient compliance

inhalation orally intramuscularly intravenously

mucous membrane cells

systemic circulating blood

site of action other tissues liver kidney

absorption, first pass metabolism, bioavailability, distribution, elimination

plasma drug / metabolite concentration

drug concentration at the site of action

therapeutical / adverse effect

Gastrointestinal form Parenteral

Variable alteration of drug metabolism

Lower tolerance to adverse drug effects

differ from the adult and elderly

Body weigh gain and water composition change

Motor skill and curiosity developed faster

Drug preparation and dose calculation are the

The capacity of metabolism and

Precise dose is hard to be achieved approximate

Depends on body weight (Clarks rule)

Depends on surface area

3 6.6 newborn 0.2 12

older children almost the same to adult

GFR and tubular function (excretion)

is lower than those of adult

tend to accumulate drug and its metabolites

Premature baby 38 120

ampicillin cefamandole amikain

carbenicillin cephalotin cefazolin

methicillin streptomisin dicloxacillin

chloramphenicol clindamycin eritromisin

sulfonamide gentamisin nafcillin

trimethoprim kanamisin oxacillin

- tetracycline tooth coloration,

- sympathomimetics nasal obstruction,

- antihistamines any benefit?

drug concentration in the site of action

drug effect therapeutical effect

side / toxicological effect

absorption, first pass metabolism, bioavailability, distribution, elimination

plasma drug / metabolite concentration

drug concentration at the site of action

therapeutical / adverse effect

Absorption Decrease in splanchnic blood Minimal changes associated with

Distribution Decrease in total body water, Higher concentration of drugs

Metabolism Decreased liver blood flow Decreased biotransformation and

Excretion Decreased renal perfusion, Decreased renal elimination

Precise dose is hard to be achieved approximate

GFR and tubular function (excretion)

is lower than those of adult

tend to accumulate drug and its metabolites

- acetosal g.i. bleeding,

- NSAIDs side effects

- tetracycline tooth coloration,

- erythromycin g.i. colic

- may cause g.i. bleeding melena,

- change with other antithrombus

then back to low dose ASA

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