Drugs used

at
extremes

Extremes of age
Embryo:
Fetus
Neonate
Infant
Toddler
Child
Adolescent
Adult
Senior citizen

Drugs at extremes of age

are not different
Difference is in PK-PD at
the extremes of age

Pediatric medicine
Need for a special approach
1. Differences in physiology & rapid changes

of growth - PK,PD features, ADRs

2. Inability of child to express
3. Drugs given to lactating women
Individualized therapy for the child

Remember

"Pediatric does not deal with miniature men and women, with reduced
doses and the same class of disease in smaller bodies, but . . . has
its own independent range and horizon = Dr. Abraham Jacobi

Geriatric medicine
Need for a special approach
Low physiological reserve
Several comorbid conditions and concomitant

medication
Easy toxicity of drugs
Decreased dosing compliance
General problems in elderly nutritional,
financial, behavioural,

Pediatric
Pharmacology

Classifying Pediatric population

Paediatric patients: 0-18 yrs. of age
Classifying them-

Preterm: <37 wks

Term: 38- 42 wks
Neonate: <1 month
Infant: 1- 12 months
Toddler: 1- 3 yrs
Children: 3- 12 yrs
Adolescents: 12- 18 yrs

Oral Absorption
Gastric acid secretion
Premature infants- Gastric Acid reaches to

highest level on 4th day of life

Application
weak bases are less ionized and have

greater bio availability e.g. ampicillin,

erythromycin, penicillins

weakly acidic drugs-decreased bio

availability e.g. phenobarbitone

Gastric emptying
Gastric emptying- prolonged and does not

reach adult value till 6-8 months

Application:
Drugs absorbed in stomach: increased

e.g. salicylates, barbiturates

drugs absorbed in small intestine: effect
delayed e.g. morphine, quinine

Peristalsis
Irregular & slow, hence absorption unpredictable

GI enzyme activity
GI enzyme activities are lower in new born

Application
low concentration of bile acids, lipase may decrease

absorption of lipid soluble drugs e.g. vitamins A, D, E

(so water soluble forms need to be administered)
Intestinal micro flora is not developed, so entero
hepatic cycling of some drugs does not occur e.g.
diazepam

Rectal absorption
It is quite erratic
But rapid and efficient absorption with proper

drug & dosage forms

e.g. rectal administration of diazepam
solution is important in neonates with seizures
in whom rapid i.v. access is not available,
acetaminophen

Intra muscular absorption

In neonates, premature and term babies -

both rate & amount is reduced due toa. decreased muscle mass and blood flow
b. higher water content in muscles
c. diminished muscular contractions
Aminoglycosides, anticonvulsants
Infants and children perfusion improves

Percutaneous absorption
Increased in neonates (up to 3 times than

adults) due toa. decreased thickness of stratum corneum

b. increased skin hydration
c. increased surface area per kg of body wt.
Application: neonates prone to toxicity of
topical drugs such as bacitracin, neomycin,
polymyxin B, salicylic acid, glucocorticoids etc.

Distribution
Increased Vd
70-75% is water content
Increased ECF 40%

Application:
Gentamicin is water soluble and gets
distributed to ECF hence, higher doses are
needed

Plasma protein binding

Reduced in infants
Increase free drug conc - toxicity increases
Drugs compete with serum bilirubin for binding to

albumin, can cause displacement of bilirubin

kernicterus. Eg:- sulfonamides, cephalosporins
Conversely bilirubin can displace some drugs
causing their toxicity. Eg:- phenytoin.

Drug Metabolism
enzymes are deficient in the new born especially

premature.
deficit is made up in first few months
decreased metabolism: t1/2 of drugs in increased
Drugs accumulate and predispose to adverse
effects.
Application
chloramphenicol- in premature new born -- grey
baby
syndrome.

Excretion-GFR - adult value by 6- 12 months

Tubular transport mechanisms are also immature in

new born so t is prolonged to 3-5 times.

Tubular secretion reaches adult rates by 7 months.
Eg:- dose of Ampicillin in neonates
<7 days old- 50-100mg/kg/day in 2 doses at 12hrs
interval.
>7 days old- 100-200mg/kg/day in 3 doses at 8 hrs
interval
Toddlerhood - high dose / kg BW for digoxin,
theophylline

Pediatric drug dosage

Approximation of dosage can be made by several

methods based on age, weight, surface area.

Age:
Youngs formula: child dose = age x adult dose.
(age+12)
Dillings formula: child dose=

age x adult dose.

20

PEDIATRIC drug dosage

Body weight: individual dose = BW ( kg ) x

avg.

70

adult dose

BSA: individual dose = BSA (sq.m ) x avg.

adult dose.
1.7

Pharmacodynamics
consideration.Examples
Lack of efficacy of some antidepressants in

children.
Paradoxical seizures after exposure to
benzodiazepines
Increased expression of opioid receptors
increased sensitivity in neonates
Patent Ductus Arteriosus - Indomethacin &
PGE1.

A Short Question break.

1. Complete the statement
Tetracyclines are contraindicated in pregnant women and
____________________ and Justify.
_____ is contraindicated for control of seizures in children below
2 years of age.
2. State T / F
Aspirin can be prescribed to a 10 year old child for fever and
headache due to viral infection.
-------- is not used for dewarming in children below 2 years of
age. Instead ______ is preferred.

Drugs in breast milk

If medication in nursing mother is required
30-60
3-4

min after nursing.

hours before next feeding.

Antimicrobials
Chloramphenicol:- grey baby syndrome,

diarrhoea,
BM depression.
Tetracycline:- permanent staining of teeth.
Decreased bone growth
Sulphonamides:- kernicterus.
Metronidazole:-may make milk taste bitter.
FQ- Possible risk of arthropathy
Chloroquine- Retinal damage in newborn infants

Analgesics
Aspirin:
- Reyes syndrome
CNS effects, convulsions
Opioids
Infants are more susceptible to respiratory
depressant action of morphine.

AMIODARONE
Possible effects of released iodine on neonatal

thyroid.
Risk of hypothyroidism.
radio- iodine thyroid suppression in infants.
Diazepam
Sedative effect on nursing infants long half
life drug accumulation
Barbiturates
Lethargy, sedation, poor suck reflexes.

Problems with pediatric drug

therapy
Postnatal period
Administration:
oral route may cause aspiration
IM route : sciatic nerve damage
preferred site will be lateral aspect of thigh
Regimen : renal and hepatic considerations
Drugs given to mother during labour and
lactation period

Problems.
General

Taste of the medicine compliance

Accidental overdose - Toddlers
Prone to get recurrent infections----OTC
medications

Principles of pediatric drug

prescribing
Parents role : clear instructions
Measuring errors
Spilling
Spitting
Disappearance of symptoms
Warning / worsening signs
Use of calibrated measurement spoon/syringe
pill containers
random pill count and measurement of serum conc.

Principles of pediatric drug

prescribing
Review the need of drug therapy
Reassure parents
Selection of Practical and convenient dosage forms

and dosing schedules

Prefer palatable syrups, use of chasers
liquid formulations SUSPENSIONS

thorough shaking. Eg. Phenytoin

Emphasis on completion of the course of

antimicrobials
Avoid OTC / previously used medicines

Aging
Progressive, universal decline first in
functional reserve and then in function that
occurs in organisms over time.

The biochemical composition of tissues

changes
Physiologic capacity
Homeostasis
Vulnerability to disease processes

Geriatric Age group

According to the WHO, generally accepted age is
>65 years.
TheNational Policy of Older Personsrecognizes a
person who is 60 years of age and above as a
Senior Citizen.
http://www.who.int/healthinfo/survey/ageingdefnolder/en/index.html,
http://india.gov.in/citizen/senior_citizen/general.php#q2 accessed on 8/05/12

Ageing Population Figures

-India

Drug Consumption amongst

the elderly
> 65 yrs constitute about 8 % of the
population and consume 31% of prescribed
drugs.
40% of all OTC drugs.
Average of 4 - 6 medications at any one time.
Average of 13 to 15 prescriptions per year.

Absorption
Condition associated with age altering rate of

absorption
Altered nutritional habits
Increased consumption of non prescription
drugs(laxatives, antacids)
Slow gastric emptying esp. diabetics

Distribution
Decrease total body water
Decrease lean body mass and increase in fat

content
Decrease Blood flow
Alteration in Size & composition of compartments
of the body.
Decrease in albumin causes altered bound: free
drug ratio - alter loading dose,
Decrease loading and maintenance dose
Eg:- digoxin- early CHF decrease apparent Vd &
clearance - decrease loading dose & maintenance dose

Metabolism
decrease in hepatic blood flow- thickening

& defenestration of sinusoidal

endothelium.
Decrease capacity of the enzymes
Decrease ability to recover
Decrease clearance of drugs with high
hepatic extraction ratio
Effect of liver / comorbid conditions

Hepatic metabolism can be of two

types :
1. Flow-limited metabolism: Highly extracted
substrates
Decreases for: Pethidine, Morphine,
Propranolol, Amitriptyline, Verapamil, Imipramine,
Lignocaine.

2. Capacity-limited metabolism: Poorly extracted

medications & in some cases, protein bound drugs.

Excretion
Decrease in renal plasma flow, GFR, tubular secretion
Dose on basis of creatinine clearance

Cockcroft Gault formula

creatinine clearance(ml/min)= (140-age) x wt (in kg)
72 x serum
creatinine(mg/dl).
For women the result should be multiplied by 0.85
Reduced lung volumes & comorbid disorders
Elimination, eg. , Inhalational anaesthetics not used

Increase in pharmacological
response
Seen with benzodiazepines,
barbiturates, opioid analgesics,
halothane; anticoagulants, thrombolytic
therapy.

Drugs acting on -adrenergic receptors :

asthma, HTN.

Pharmacodynamics
Postural hypotension
Occurs in-20% of ambulatory patients >65years
of age & 30% in patients>75 years of age
Mechanism
a)Impaired baro receptor function
b)Failure of cerebral blood flow autoregulation
E.g. Drugs with sympatholytic activity
Alpha blockers , Phenothiazines, TCA
Volume depleting-Diuretics
Vasodilator-Nitrates & Alcohol

Pharmacodynamics
Receptor sensitivity
Selective decline in cholinergic system in
neocortex & hippocampus.
Increase in MAO
Decrease in sensitivity of adrenergic
receptors particularly beta receptors.

Which of the following drug classes is most often

associated with cognitive decline in elderly
patients?
A. Diuretics
C. Antidepressants
B. Benzodiazepines D. Antiarrhythmics
Which of the following drugs can lower the
seizure threshold?
A. Ciprofloxacin
C. Clozapine
B. Bupropion
D. All of the above

ADRs
Incidences of ADR is high in
Polypharmacy
Comorbid conditions
Personal errors decrease in cognitive

functions
Use of OTC drugs
PD & PK

Common ADRs
Postural Hypotension
Constipation
Incontinence
Parkinsonism
Depression
Confusional state
Loss of postural
reflexes

Drugs common ADR

Atropine: Urinary retention
Aspirin: G I irritation and bleeding

NSAIDS: Irreversible renal damage

Cumulation of NSAIDS->More renal damage
Corticosteroids: Osteoporosis
BZD & Barbiturates: pshycomotor effects
Opioids: respiratory depression & urinary
retention
Haloperidol - causes EPR

Precautions to avoid ADR

Drug selection and administration.
Start low go slow
Final dosage schedule with min. no of pills
History of OTC
Regular follow up

Non-adherence to
medication

Non-adherence to
medication
Multiple drugs
Multiple daily dosages
Frequently changing drug regimens
Expensive drugs
ADRs
Dependence on others
Progressively diminishing cognition, vision, dexterity,
mobility.
Social factors: loneliness, economical stress, loss of
spouse, social and familial neglect
Intentional/ intelligent non-adherence.

Improving Drug Compliance

Health Buddy

Pill Organizer

BLISTER PACK!!!

Principles of drug
prescribing
Simplifying drug regimens
1.
2.
3.
4.

5.
6.
7.

Cheaper alternative therapy

Use drugs needing less frequent administration
Link it with meals
Use of similar schedules, No frequent change in
schedules
Easy handling: easy opening bottles
Large label: large/ boldly written instruction
Elicit intelligent non-compliance and improve

Principles of drug
prescribing
Patient education and counseling
1.
2.
3.
4.

Respectful communication with patients

Discourage self-prescription, doctor shopping
ensure compliance
Social & financial support