PHARMACOLOGY

OF
PEDIATRICS
&
GERIATRICS

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 INTRODUCTION

Many drugs have not been adequately

evaluated in infants in terms of their
pharmacokinetic & pharmacodynamic
properties.

Pediatric drug data are not readily available

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DRUG THERAPHY IN INFANTS

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PHARMACOKINETICS
• Absorption and Bioavailability.

• Protein binding and Drug

distribution.

• Metabolism and excretion.

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 Absorption
• From the GI tract .

• Transdermal absorption .

• Transrectal drug therapy .

• Absorption of drugs from the

lung .

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Absorption from the GI tract

 It is affected by :

• Gastric acid secretion

• Bile salt formation
• Gastric emptying time
• Intestinal motility
• Bowel length and effective
absorptive surface
• Microbial flora

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 Reduced gastric acid secretion

Increases bioavailability decreases bioavailability of

of acid-labile drugs  weakly acidic drugs
eg, phenobarbital
eg, penicillin

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Injected drugs are often
erratically absorbed because of

• Variability in muscle mass among

children

• Illness (eg, compromised

circulatory status)

• Differences in absorption by site of

injection

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• IM injections are generally avoided
in children .

• Transdermal absorption may be

enhanced in neonates and young
infants because the stratum
corneum is thin .

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 Distribution

• The volume of distribution of drugs changes

in children with aging.

• These age-related changes are due to

changes in body composition and plasma
protein binding.

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Changes in body proportions of body
composition with growth and aging.

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Metabolism and elimination

• Drug metabolism and elimination vary with

age and depend on the substrate or drug .

• The cytochrome P-450 (CYP450) enzyme

system in the small bowel and liver is the
most important known system for drug
metabolism.

• The neonatal liver has less capacity for

oxidation and conjugation reactions.

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 Pharmacodynamics
• It is assumed that the MOA is similar in infants
and adults.

• But ,immaturity in receptor or neurotransmitter

development may contribute to age-dependent
differences in drug responses.

• Appropriate use of drugs have increased the

survival of neonates with severe abnormalities
who would otherwise die within days or weeks
after birth.

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 Adverse Effects
• Some Adverse effects are peculiar to
neonates and infants due to immaturity
• Some of the documented toxicities are :

Ototoxicity with Aminoglycosides.

Tetracyclines : Tooth discolouration
Delayed bone growth
Hepatoxicity with asprin or paractamaol
Stunted growth with Corticosteroids

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 Dosage
Calculations
• Ideally the dosage for neonates and infants
should be individualized, taking into
consideration age, weight, body surface area
and pharmacokinetic realities.

• Doses based on body surface area are

possibly the best way to scale down adult
doses for infants and young children.

• This method is not reliable for prematures.

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 Paediatric doses can be
calculated from one of the
following methods:

• 1.Dosage based on weight (Clark’s rule )

Dose = Adult dose * Weight (kg)/60.

2.Dosage based on age (Young’s rule)

Dose = Adult dose * Age (yrs)/Age +12

3.Dose based on surface area.

Dose =Adult dose * Body surface area(m2) /Adult body

surface area

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CONTRAINDICATED DRUGS

• Asprin.
• Ampicillin.
• Cephalexin.
• Phenytoin.
• Vitamin K or Novobiocin
Chloromphenical

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DRUG THERAPHY IN GERAITRICS

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 Absorption
• The conditions which alter the rate of
absorption at aging are:

1.Altered nutritional habits.

2.Greater consumption of non-prescription

drugs

3.Changes in gastric emptying time

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 Distribution

• Compared to young adults, the elderly have:

1.reduced lean body mass,
2.reduced total and percentage
body water,
3.increase in fat as a percentage of body mass

There is a decrease in serum albumin

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 Metabolism
• The capacity of the liver to metabolize drugs
does not appear to decline consistently with
age for all drugs.
• The greatest changes are in phase I
reactions
• These changes may be caused by
decreased liver blood flow an important
variable in the clearance of drugs.
• In addition, there is a decline of the liver's
ability to recover from injury.

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Effects of Age on Hepatic
Clearance of Some Drugs
• Age-Related • No Age-Related
Decrease in Hepatic Difference Found
Clearance Found

• Alprazolam • Nitrazepam
• Barbiturates • Oxazepam
• Diazepam • Prazosin
• Propranolol • Salicylate
• Quinidine, quinine • Ethanol

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 Elimination
• Since kidney is the major organ for
clearance of drugs from the body, there is a
decline in the renal functional capacity.

• Decreased renal functions include :

– decreased blood flow to the kidneys
– decreased glomerular filtration
– decreased tubular secretion
– decline in creatinine clearance

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• Dosing recommendations should
be done for the elderly people.

• If dosage is not reduced in size

or frequency there is a possibility
of accumulation to toxic levels

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 Pharmacodynamics
• Physiological changes in elderly patients
affecting pharmcodynamics

Target organ physiological changes

• increased sensitivity to pharmacological agents
• decreased desirable effects of pharmacotherapy
• increased adverse effects
Homeostasis changes
• decreased capacity to respond to physiological
challenges and the adverse side effects of drug
therapy

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MAJOR DRUG GROUPS FOR
GERIATRICS

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 CENTRAL NERVOUS YSTEM
SEDATIVE-HYPNOTICS

• The half-lives of many benzodiazepines

and barbiturates increase 50–150%
between age 30 and age 70.
• For many of the benzodiazepines, both the
parent molecule and its metabolites are
pharmacologically active
• Since decline in renal function and liver
disease, if present, both contribute to the
reduction in elimination of these
compounds.

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• Therefore due to toxicities of
these drugs, ataxia and other
aspects of motor impairment
should be particularly watched for
in order to avoid accidents

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ANALGESICS

The opioid analgesics show variable changes

in pharmacokinetics with age.

• Therefore, this group of drugs should be

used with caution until the sensitivity of the
particular patient has been evaluated, and
the patient should then be dosed
appropriately for full effect

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ANTIPSYCHOTIC & ANTIDEPRESSANT

The antipsychotic agents have been

very heavily used in the management
of a variety of psychiatric diseases in
the elderly people.
eg., phenothiazines and haloperidol

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 CARDIOVASCULAR DRUGS

Antiarrhythmic Agents

• The treatment of arrhythmias in the elderly is

particularly challenging because of the lack of
good hemodynamic reserve.
• The clearances of quinidine and procainamide
decrease and their half-lives increase with age.
• Disopyramide should probably be avoided due
to major toxicities.

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Anti-Inflammatory Drugs

Osteoarthritis is a very common disease of the

elderly.
• The nonsteroidal anti-inflammatory agents must
be used with special care in the geriatric patient
because they cause toxicities to which the
elderly are very susceptible
• In the case of aspirin, the most important is
gastrointestinal irritation and bleeding
• In the case of the newer NSAIDs, the most
important is renal damage, which may be
irreversible

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 Adverse Drug Reactions
The elderly are 2-3 times more at risk for
adverse drug reactions due to:

1. reduced stature.
2. reduced renal and hepatic functions.
3. cumulative insults to the body (eg., disease,
diet, drug abuse)
4. multiple and potent medications.
5. altered pharmacokinetics.
6. noncompliance.

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 ADR: Anticoagulants
• Elderly patients are more sensitive to the
effects of anticoagulants

• Pharmacodynamic changes: vitamin K-

dependent clotting factors deficiency
• Pharmacokinetic changes: anticoagulants such
as
warfarin have a very narrow therapeutic value and
are highly protein bound
• drug interactions (eg., phenytoin)
• adverse effect: excessive internal bleeding
• Frequent monitoring by primary care physician

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 ADR: NSAIDs
• Non-Steroidal Anti-Inflammatory Drugs are
frequently prescribed in the elderly patients

• Pronounced adverse gastrointestinal side

effects
• Other adverse drug reactions in the kidney
and CNS have also been associated with
chronic NSAID therapy in the elderly

• Alternate therapies:
– acetaminophen (Tylenol) for analgesia
– new COX-2 inhibitors for anti-inflammatory
actions

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 ADR: Cardiovascular Agents
• congestive heart failure is a common age-
related condition

• Digoxin used to be the drug of choice for

congestive heart failure
– drug elimination is reduced in the elderly;
– often worsens cardiac symptoms

• Replaced by newer therapeutic agents:

betaaderenergic receptor blocker and
angiotensinconverting enzyme inhibitors

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Commonly used medications best avoided
in the elderly

• Anticholinergic preparations

– diphenhydramine (Benadryl)
– doxepin (Sinequan)
– dicyclomine (Bentyl)

• Benzodiazepines with active metabolites

– diazepam (Valium)
– flurazepam (Dalmane)

• Central acting CNS agents

– alpha methyldopa (Aldomet)
– clonidine (Catapres)

• Analgesics

– propoxyphene (Darvon)
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– indomethacin (Indocin)
CONCLUSION

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References
• Pharmacology 2nd edition, Bhattacharya, pg no
501-514.

• Katzung : Clinical pharmacology.

• www.merk&co.in

• http://www.med.yale.edu/library/heartbk/23.pdf

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THANK YOU

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