PADIATRIC AND GERIATRIC

MEDICATION

Presented By:

Nirav VachhaniM.Pharm (Sem III)

Guided By:

Mr. Pinakin JadadvAssistant Professor

Deparment of Pharmacology,S. J. Thakkar Pharmacy Collrge,

Rajkot.

PEDIATRIC MEDICATION

Presented By:

Nirav VachhaniM.Pharm (Sem III)

Guided By:

Mr. Pinakin JadadvAssistant Professor

Deparment of Pharmacology,S. J. Thakkar Pharmacy Collrge,

Rajkot.

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Con

ten

ts

• Introduction• Importance Of Pediatric Drug Handling• The Normal Child

Pharmacokinetic of Children A, D, M, E Monitoring Parameters

Drug Therapy in Children Dose Calculation Appropriate Dosage form and route Diseases condition Adverse reaction in Therapy Counseling

• Summary• References

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Introduction• Pediatric means..• As per ICH (2000) ,Childhood is divided in..

• Topics will cover information on P’kinetic parameters, Choice of Drug dosage and its form and aspects on adverse reaction.

Age:- Up to 28 days

(Neonate)

Age:- 2- 11 years

(Children)

Age:- 1- 24 months(Infants)

Age:- 12-18 years

(Adolescents)

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Importance of drug handling: Lack of data on important pharmacokinetic and

pharmacodynamic differences has led to several terrible situations in pediatric care. One is an ethical issue, the inability to obtain true

informed consent. The second obstacle is inherent to children; they

grow and change rapidly. Infancy and childhood is rapid stage of development

and various organs, enzymes and body systems that handle drugs and their dosage are different in time. So, Drug studies must be performed on children at each stage of their development to determine appropriate usage.

Highly Critical aspects in child treatment are P’kinetic parameters Method of drug administration Dose & dosage forms

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The Normal Child:

• Growth and development are important indicators of a child’s general well-being and pediatric practitioners should be aware of the normal development milestones in childhood.

• The World Health Organization (WHO) has publised the widely used growth charts.

• Three important tools in developmental assessment.– Height– Weight– Head circumference

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• In addition to the above, assessments of hearing, vision, motor development and speech are undertaken at the child health clinics.

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Pharmacokinetics:• There is high importance of clinical

pharmacokinetics in optimization of drug therapy.• Drugs that are safe and effective in one group of

pediatric patients may be ineffective or toxic in another, so an understanding of variability in drug disposition is essential if children are to receive rational and appropriate drug therapy.

AD

MEABSORBTION

DISTRIBUTION

METABOLISM

EXCRETION

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• Two factors affecting the absorption of drugs from the G.I. tract are pH-dependent passive diffusion and gastric emptying time. Other is G.I. tract enzyme activity.

PH• Premature Infants- Elevated pH (More than Infant)• Infant- Range from 6-8

Gastric Emptying

• Infants/Noenate:- Prolonged gastric emptying time. But lower peristaltic movement than older child and adults.

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• In premature infants, higher serum concentrations of acid-labile drugs—such as penicillin, ampicillin and nafcillin—and lower serum concentrations of a weak acid such as phenobarbital can be explained by higher gastric pH.

• Gastric emptying time:-– Gastric emptying time is delayed in infants and

reaches adult levels by 6 to 8 months of age.– Drugs that are absorbed primarily in the stomach

may be absorbed more completely than anticipated. In the case of drugs absorbed in the small intestine, therapeutic effect may be delayed. Peristalsis in the neonate is irregular and may be slow.

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• Gastrointestinal enzyme activities:-– It is lower in the newborn than in the adult.

Activities of amylase and lipase, beta-glucuronidase, and glutathione peroxidase enzymes are low in infants up to 4 months of age. Neonates also have low concentrations of bile acids and lipase, which may decrease the absorption of lipid-soluble drugs.

• Absorption from Intramuscular route:-– less predictable absorption in infant– Examples like Diazepam Rapid Absorption ,

Phenobarbital Poor absorption

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• Absorption from Skin :-– Percutaneous absorption may be increased in

neonate because of an underdeveloped epidermal barrier (stratum corneum) and increased skin hydration.

• Absorption from Rectal route :-– The rectal route of administration can be

useful in infants or children who are unable to take oral medication.

– The mechanism of rectal route absorption is probably similar to that of the upper part of GI tract, despite differences in pH, surface area and fluid content.

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• Drug distribution is determined by– Physicochemical properties of the drug

itself (pKa, molecular weight, partition coefficient,etc…)

– Physiologic factors specific to the patient.

• So, variable aspect is the physiologic functions such as– Total Body Water– Plasma Protein binding of drug– Volume of Distribution

D

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DTotal Body Water

• 94% in the fetus, 85% in premature infants, 78% in full-term infants, and 60% in adults.

Plasma Protein Binding

• Less in Newborn and infants • Reasons• Examples

VD

• The decrease in plasma protein binding of drugs can increase their apparent volumes of distribution

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• Drug metabolism is substantially slower in infants compared with older children and adults.

• Less maturation of various pathways of metabolism within a infant.

• E.g. :- sulfation pathway is well developed but the glucuronidation pathway is undeveloped in infants.

• The cause of the tragic chloramphenicol-induced gray baby syndrome in newborn infants is a decreased metabolism of chloramphenicol by glucuronyl transferases to the inactive glucuronide metabolite.

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• Because of decreased metabolism, doses of such drugs as theophylline, phenobarbital, phenytoin, and diazepam should be decreased in premature infants.

• Particular Microsomal enzymes such as CYP2C9, CYP2C19, CYP1A2 are variant in their function.

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• The processes of glomerular filtration, tubular secretion, and tubular reabsorption determine the efficiency of renal excretion. These processes may take several weeks to 1 year after birth to develop fully.

• Glomerular filtration rate is about 2–4 mL/min per 1.73 m2 in term infants.

• In infants, if possible then avoid Chloramphenicol and Amino glycoside, because their metabolites are accumulated due to immature function of kidney. Especially Cloramphenicol metabolites are highly accumulated due to less developed glucuronidation pathway, which convert the cholamphenicol in highly water soluble moiety.

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Monitoring parameters• Pediatric vital signs, Biochemical and

Hematology parameters change throughout childhood.

• It gives idea about therapy management in prolonged treatment.

VITAL SIGNS

Parameters Age (2-5 years) Age (5-12) years

Heart rates (beats/ min)

100-120 80-100

Systolic Blood pressure (mmHg)

80-90 90-110

Respiratory rates (beats/ min)

25-30 16-25

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Biochemical ParametersParameters Age (2-12

years)Age (>18

years)

Albumin (g/L) 30-50 35-55

Bilirubin (microM/L)

<15 <17

Creatinine(microM/L)

30-80 50-120

Hemoglobin(g/dL)

11-14 13.5-18(male)12-16(female)

WBC (*109/L) 5-14 3.5-11

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Drug therapy in pediatrics

1. Dose calculation2. Choice of dosage form3. Disease Condition4. Adverse reaction5. Counseling

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1. Dose calculation :-• Height and Wt growth are rapidly changing

factors in childhood, which also influence significantly some p’kinetic parameters. So, this factors should be considered during therapy. So dose calculation is needed.

• Doses should be obtained from pediatric book for children.. For example, In india IAP-Drug formulary is reliable source for pediatric practice and their important drugs.

• For many years, pediatric dosage calculations used pediatric formulas such as Fried’s rule, Young’s rule, and Clark’s rule. These formulas are based on the weight of the child in pounds, or on the age of the child in months, and the normal adult dose of a specific drug.

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1) Young’s Rule :- (based on age)Pediatric dose =

2) Fried’s Rule :- (Age adjustment for infants)Infant Dose =

3) Clark’s Rule :- (based on body weight)Pediatric Dose =

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• Other routes like….

2. Choice of Dosage form :-

Oral Route• Tablets are less convenient• Liquid preparation are easy to administer in

accurate dose and to form in desirable dose by dilution

Parenteral Route:- • Site of Access• Safety from fluid overload• Aware about Excipients

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• Dose regimrn selection :-Factors to be considered when

selecting a drug regimen or rout of administration for a pediatric patient are…

– Age/Weight/Surface area– Assess the appropriate dose– Assess the most appropriate interval– Assess the route of administration– Consider the expected response and

monitoring parameters– Interactions– Legal consideration

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3. Diseases condition :-

Cystic fibrosis

Renal disorder

Liver

disease

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Liver disease :-• Drugs with a high hepatic extraction ratio

(>0.7; such drugs include morphine, meperidine, lidocaine, and propranolol).

• Clearance of these drugs is affected by hepatic blood flow. A decreased hepatic blood flow in the presence of such disease states as cirrhosis and congestive heart failure is expected to decrease the clearance of drugs with high extraction ratios.

• Theophylline clearance may decrease by 45% in a child with acute viral hepatitis.

• Because of a lack of specific data on dosage adjustment in liver disease, drug therapy should be monitored closely in pediatric patients to avoid potential toxicity from excessive doses.

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• Renal failure decreases the dosage requirement of drugs eliminated by the kidney. Once again, because of limited studies, dosage adjustments in pediatric patients are based largely on data obtained in adults.

• Serum drug concentrations should be monitored for drugs with narrow therapeutic index and eliminated largely by the kidney (e.g., aminoglycosides and vancomycin) to optimize therapy in pediatric patients with renal dysfunction.

• For drugs with wide therapeutic ranges (e.g., penicillins and cephalosporins), dosage adjustment may be necessary only in moderate to severe renal failure.

• Renal clearance or rate of elimination is directly proportional to the glomerular filtration rate, as measured by endogenous renal creatinine clearance.

Renal disease :-

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• Drug therapy in pediatric patients with cystic fibrosis has been reviewed. For unknown reasons, these patients require increased doses of certain drugs.

• Studies have reported a higher clearance of such drugs as gentamicin, tobramycin, netilmicin, amikacin, dicloxacillin, cloxacillin, azlocillin, piperacillin, and theophylline.

• Reason : Variations in hepatic metabolic activity or in phenotypic distribution of metabolic polymorphisms may explain some pharmacokinetic differences in CF.

Cystic Fibrosis:-

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• Mechanism is not cleared in adverse effect of many drugs in child. But it may be due to immature p’kinetic parameters and some medication errors.

• Some well known adverse effect• Tetracycline Teeth brown coloration• Corticosteroids Growth suppression in

Prepubertal child.• Paradoxical hyperactivity in child with

phenobarbital treatment• Aspirin treatment Reye’s syndrom

4. Adverse reaction in therapy :-

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• Medication errors are also considered as an important cause of ADRs and should always be considered as a possible causative factor in any unexplained situation.

• The incidence of medication errors and the risk of serious errors occurring in children are significantly greater than in adults.

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• Parents are often responsible for the administration of medicines to their children and therefore the concordance and adherence of both parties must be considered.

• Non-adherence may be caused by several factors such as patient resistance to taking the medicine, complicated dosage regimens, misunderstanding of instructions and apparent ineffectiveness or side effects of treatment.

• Several general principles should be considered in an attempt to improve adherence.

5. Counseling adherence and concordance

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• Attention should be given to the formulation, taste, appearance and ease of administration of treatment.

• The regimen should be simple and tailored to the child’s walking day.

• Many health professionals often counsel the parents only, rather than involving the child in the counseling process.

• Where possible, treatment goals should be set in collaboration with the child.

• Studies have shown that parents consider the 8-10 year age groups the most appropriate at which to start including the child in the counseling process.

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Su

mm

ary

• Main key Points covered in topic…..– Children are not small adults– Patient details such as age, weight and

surface area need to be ensure appropriate dosing

– Weight and surface area may change significantly in a relatively short time period

– Pharmacokinetic changes in childhood are important and have a significant influence on drug handling and need to considered when choosing an appropriate dosing regimen for a child

– The use of an unlicensed medicine in children is not illegal although it must be ensured that the choice of drug and dose is appropriate.

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1) Parthasarthi G, Hausen KN and Nahata MC. Pediatric pharmacy practice. In parthasarthi G, Hausen KN and Nahata MC edited A textbook of clinical pharmacy practice, 1st Edition. Universities Press Private Ltd, 2008; 160-189.

2) EMEA 2005 Reflection paper: formulations of choice for the paediatric population. European Medicines Evaluation Agency, London. Available online at: www.eniea.eu.int/pdfs/human/peg/19481005en.pdf

3) International Committee on Harmonization 2000 Note for guidance on clinical investigation of medicinal products in the paediatric population. European Agency for the Evaluation of Medicinal Products, London

4) McIntyre J. Conroy S. Avery A et at 2000 Unlicensed and off label prescribing of drugs in general practice. Archives of Disease in Childhood 83: 498-501R

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5) National Institute for Clinical Excellence 2000 Guidance on the use of inhaler systems (devices) in children under the age of 5 years with chronic asthma. Technology Appraisal No 10. National Institute for Clinical Excellence. London

6) National Institute for Clinical Excellence 2002 Asthma-inhaler devices for older children. Technology Appraisal No 38. National Institute for Clinical Excellence, London

7) Scott E, Swanton J, McElnay Jet al 1995 Pharmacists and child health. Centre for Pharmacy Postgraduate Education/HMSO, London

8) Turners. Longworth A, Nunn A J et al 1998 Unlicensed and off-label drug use in paediatric wards: prospective study. British Medical Journal 316:343-345

9) Yeung S C, Ensom M H 2000 Phenytoin and enteral feedings: does evidence support an interaction? Annals of Pharmacotherapy 3(7-8): 896-905

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Thank You