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 don’t 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 (Young’s rule)
 Dose = adult dose x [age in years : (age + 12)]
 Depends on body weight (Clark’s 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
17
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
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PHARMACOKINETIC FACTORS
• Drug distribution
 protein binding
some drugs (i.e. sulfonamide) may cause Kern’s 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) 2–7
Children 1- 15 years 2 – 20
Adult 20 – 30
24
(Lüllmann 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  Reye’s 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
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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 (Clark’s 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

Infant (1 months) 2–7

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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