Paediatric drugs, its dose and dosage forms

discuss about the need for pediatric pharmacists. explains about the pharmacological and physiological factors such as dose of drug, dosage forms, weight of child, age of child, BSA of child that have to be considered on prescribing a pediatric patient

1. Paediatric Pharmacy Practice 1

2.  20 to 25% of total world population  Poorly developed organ functions and highest risk of toxicity and poor clinical response.  Sulphanilamide elixir- death: Thalidomide tragedy. Taste of Raspberries, Taste of Death The 1937 Elixir Sulfanilamide Incident 2

3. Why Do We Need Paediatric Pharmacists?  Children are at increased risk of adverse drug events (ADE’s)  Pharmacologic factors •Age-based variability in absorption, distribution, metabolism, and excretion of drugs  Physiologic factors •Weight and/or body surface area (BSA) need to be considered for each drug for each patient 3

4.  Process factors •Individualized dilution of stock medications and fluids •Multiple concentrations of same drug • Dilution errors  Environmental factors •ICU setting  Weight-based dosing  Error dosing rate  Error rates inversely related to size or weight of patient 4

5. Paediatric medication orders are more prone to errors than adult orders  Doses are not standard  Math errors can occur when calculating the dose  Suspensions often have to be compounded  Tablets may have to be cut  Dilutions need to be made to make amounts that are measurable  However, children have less tolerance for errors 5

6. Preemie <37 weeks gestation (gestational age is the time from conception until Birth) Full Term 37-42 weeks gestation Neonate First 30 days of life Infant First year of life Toddler From 1 to 2 years of life Child Age 3-11 Adolescent Age Age 12 on Definition of a child is based on age 6

7. Special Challenges of Practicing in Pediatrics  Lack of published information on therapeutic uses and monitoring of drugs  Lack of FDA approval for many drugs used in pediatrics  Lack of appropriate commercially available dosage forms and concentrations of commonly used medications  Inability of patients to communicate with caregivers  Interacting with parents 7

8. Skills Necessary  Dosage calculations  Dosage-form selection  Specialized drug preparation and administration techniques  Understanding of PK/PD changes occurring with age  Understanding of disease-specific conditions affecting drug choice or dose  Understanding nature of medication errors in pediatric patients 8

9. Role of the Paediatric Pharmacist Ensure the patient receives the necessary drug in a manner that allows the intended therapeutic effect to be realized. 9

10.  Patient interviews  Medication history •Inquiring about OTC and herbal medications  Allergy history •True allergic reaction?  Immunization history •Can make recommendations to MD if patient is not up-to-date on immunizations 10

11.  Discharge counselling  Administration & use of appropriate measuring device dosage  Preparation of form at home, if necessary  Attention to taste of liquid medications  Prevention of accidental ingestions  School / day-care issues directed at patient and/or caregiver 11

12. Drug Information  Influence selection of drug therapy in initial phase of patient care •Consult with physician and patient  Provide current, unbiased and relevant drug information  Assist with finding literature supporting use of drugs for unlabeled indications 12

13.  Therapeutic Drug Monitoring  Understanding timing / indication of monitoring to prevent unnecessary blood draws on children  Account for age-related differences in dosage  Documentation in patient chart  Monitor steps of the medication use process  Reduce drug costs Avoidance of medication errors resulting from over- or underdosing 13

14.  Reduce Medication Errors  Report medication errors  Encourage others to report medication errors or suspected ADE’s  Participation in quality-improvement committees  Develop and enforce policies and procedures for safe medication practices 14

15.  Drug Use Evaluation  Low therapeutic index drugs  Those responsible for serious medication errors  High frequency of preventable adverse drug reactions  Expensive medications  Education  Patients  Nursing unit staff  Physicians  Pharmacy students and residents 15

16.  Research  Pediatric patients are “therapeutic orphans”  Insufficient research in pediatric patients  Expansion of adult diseases into the pediatric population (i.e. AIDS)  Use of therapeutic agents in children without FDA approval 16

17. Pharmacokinetic considerations 17

18. Absorption – Gastrointestinal  pH- gastric acid output maturity is related to postnatal age and approaches adult values by 3 months of age  GI motility- neonates have a delay in gastric emptying time, adult values are reached at 6-8 months of age  GI contents- d e velops rapidly within the first year of life, underdeveloped flora can increase absorption of drugs ( digoxin ) – 18

19. 19 Percutaneous  Absorption is increased in the newborn due to immature epidermal barrier and increased skin hydration during the first 2 weeks of life  Increased surface area to weight ratio increases percutaneous absorption

20. Distribution – Body Water • Neonates are 80 % body water compared to 55% in adults • Vd is increased for drugs that distribute to aqueous parts of the body ( aminoglycosides ) • Total body fat is 1% in a 29 wk neonate • Total body fat is 15% in a full term baby • Total body fat is 20-25% in 2yo toddler • Fat content tends to increase between 5-10 years followed by a decrease through age 17 • Vd is increased for drugs that are highly lipid soluble 20

21. – Plasma Protein Binding • Neonates have decreased plasma protein which increases unbound concentrations (ex: Phenytoin may only be 70% bound in a neonate compared to 90% in an adult) – Blood Brain Barrier • An immature BBB due to incomplete CNS myelination results in increased CNS drug penetration 21

22. Metabolism – Neonates have decreased activity of many enzyme pathways, that is why drug dosages are decreased for neonates  P450 activity is 50% of adult levels  Decreased hydroxylation activity leads to decreased metabolism of phenobarbital , phenytoin , lidocaine  Children have increased hepatic enzyme activity between 2-4 years of age. This may be due to large liver size compared to total body weight. Doses are increased during this time for theophylline , phenytoin , and phenobarbital . 22

23.  At birth, kidney function is decreased, GFR matures first, then tubular secretion, and lastly tubular reabsorption  GFR at birth is 2-4 ml/min, which is 0.5% of an adult level  After the first week of life, a significant increase in GFR is seen, this explains why recommended doses change after 7 days of life  At 1 year, GFR reaches 70 ml/min/m2  Around 12-24 month of age, GFR and tubular secretion are more mature than tubular reabsorption and cause an increased renal clearance of drugs ( digoxin ) Excretion 23

24. Administering Medications to Children 24

25. •  Safe pediatric dosages calculated by: –  Body weight •  Measured in mg per kg, mcg per kg, etc. –  Body surface area (BSA) •  Measured in m 2 Remember  1 kg = 2.2 lb –  When converting pounds to kilograms, round kilogram weight to one decimal place •  Tenths  1 lb = 16 oz 25

26. Dosage is optimally calculated by using the child’s body weight or mass and the appropriate dose in milligrams per kilogram (mg/kg). A. Fried’s rule for infants age (in months) X adult dose ............................ = dose for infant 150 26

27. age (in years) ............................. X adult dose = age (in years) + 12 dose for child Young’s rule for children 2 years old or older weight (lb) X adult dose ........................................ = dose for child 150 lb ( avg wt of adult) Clark’s rule 27

28. BSA of child (m) 2 X adult dose ............................................... = 1.73 m 2 ( avg adult BSA) approximate dose for child Child’s dosage based on body surface area (BSA) In the case of some drugs, such as chemotherapy, doses are based on body surface area (BSA). This value can be determined from the patient’s height and weight, using either a nomogram or the following equation: height (cm) X weight (kg) BSA (m) 2 = ....................................... 3600 28

29. Although the total body water content of an adult accounts for approximately 60% of body weight, the total body water content of a healthy newborn is (A) 40%. (B) 50%. (C) 70%. (D) 80%. (E) 90%. 29

30. THANK YOU 30