PEDIATRIC THERAPEUTICS

3.2
11/28/16
Dean Angeline Alabastro, MD
“Kindness alone can’t save people! You need knowledge and medical skills to go along with it! Without it, you can’t save a single
201 8 person!”– Dr. Kureha, One Piece Chapter 144

OUTLINE: Questions:
I. Influence of Age on Drug Therapy
II. Pharmacokinetics 1. What condition will you consider?
A) Factors which Affect Drug Absorption  Respiratory Distress Syndrome (RDS)
1) Blood Flow at Site of Administration  Pneumonia
2) Gastrointestinal Function  SEPSIS NEONATORUM - systemic
(a) Gastric Acid Secretion
2. Next step?
(b) Gastric Emptying Time
 Do diagnostics to get the Dx
(c) Intestinal Mobility
3. What will you give?
(d) Biliary Function
(e) Microbial Flora  Antibiotics: Ampicillin + Gentamicin
3) Effects of Dosage on Forms of Absorption  Note: No oral prep Gentamicin
4) Parenteral Drugs 4. ROA?
5) Effects of Other Routes of Administration  Intravenous (IV)
(a) Transdermal 5. Dose?
(b) Transrectal  Ampicillin: 50-100 mg/kg
(c) Inhalation  Gentamicin: 2.5 mg/kg/BW
B) Factors which Affect Drug Distribution 6. Frequency of Administration?
1) Vascular Perfusion  q 6 hours
2) Body Composition
3) Tissue Bindin Characteristics Case 2:
4) Physiochemical Properties of Drugs A previously healthy 4 year old boy is brought to an urgent care center by
5) Plasma Protein Binding his mother for difficulty breathing for one day. 3 days prior he had
6) Route of Administration developed a runny nose, cough, and low grade fevers with a temperature
C) Clearance (Metabolism) maximum of 101 degrees F (38.3 degrees C). He continued to take liquids
D) Factors Affecting Drug Excretion well, but his solid intake has decreased. His temperature this morning was
1) Functional Ability of Glomerulus 103 degrees F (39.4 degrees C) and he was breathing fast and working hard
2) Tubular Secretion to breathe. He does not have any ill contacts.
3) Integrity of Renal Blood Flow
4) Extent of Protein Binding He has never been hospitalized or had any surgeries. He was born at term
III. Factors Considered when Prescribing a Drug without any complications. He is not taking medications other than
IV. Drug – Drug Interactions acetaminophen. His immunizations are up to date for his age (except he had
V. Drug Interactions not received the pneumococcal conjugate vaccine). His parents and 10 year
A) Oral Bioavailability
old sister are healthy and the remainder of his family history is non-
B) Protein Binding
contributory. There are no smokers in the household, and he has not
C) Biotransformation
traveled recently. He does not have a history of choking or vomiting. He has
D) Altered Renal Function
not had frequent ear or skin infections. He does not have a history of foul-
VI. Risks for Adverse Drug Reactions
smelling stools.
VII. Causes of Non-Adherence to Drug
VIII. Compliance
Exam: VS T 40 degrees C (104 degrees F), P 130, RR 40, BP 100/70, oxygen
A) Compliance Issues
IX. Therapeutic Drug Monitoring saturation 87% in room air. His height and weight are in the 50th percentile
for his age. He is awake and alert, in moderate distress. His conjunctiva and
X. Summary
TMs are normal. His nasal mucosa is erythematous with yellowish
Cambria – Previous transes and Cases from Doc Alabastro’s Lec
Arial – doc’s lecture and others.. =) discharge. His lips and mucous membranes are dry. His neck is supple, with
several small anterior cervical lymph nodes. Lungs: Moderate subcostal,
intercostal, and supraclavicular retractions, symmetric expansion, dullness
INFLUENCE OF AGE ON DRUG THERAPY to percussion at the right base, increased vocal fremitus over the right base,
 Pharmacokinetic, pharmacodynamic and psychosocial decreased air entry over right lower lobe with crackles, no wheezes. Heart:
changes occur Tachycardia, regular rhythm without murmur. Pulses are 2+, and capillary
 Three groups: refill time is 3 seconds. His abdomen, skin, and neurological examinations
1. Premature infants: Mature to term are unremarkable.
 The transition from preterm to term Questions:
st
2. Mature during 1 few years of life
 Pharmacokinetics must be paid attention because 1. What condition will you consider?
physiologic processes that influence PK variables in  Pneumonia (Bacterial)
infant change significantly in the first year of life 2. Next step?
especially in first few months  Do diagnostics to get the Dx
3. Children reaching puberty and adolescence 3. What will you give?
 Adolescents are already considered to have  Antibiotics: Amoxicillin
pharmacokinetics and pharmacodynamics similar to 4. ROA?
 Oral
an adult
5. Dose?
 Different formulations needed for drug delivery affects
absorption and disposition  40 mg/kg
6. Frequency of Administration?
o Children and infants cannot be given solid medications—  q 8 hours
only liquids or IV so absorption is usually affected.
 Psychosocial issue influence compliance, timing of drug
administration and drug reactions to drug use PHARMACOKINETICS
o Children are dependent on their caretakers FACTORS WHICH AFFECT DRUG ABSORPTION
o Their intake of drugs is affected by the schedule of the  Follows same general principles in adults
caretaker or by their schooling Unique factors:
Case 1:
a. Blood flow at site of administration as determined by
This is a 3000 g, 35 weeks newborn, female, delivered via normal
physiologic status of the child
spontaneous vaginal delivery to a 25 year old G1P0 with early preeclampsia b. GI function (for oral drugs) which changes rapidly during the
and rupture of membranes which occurred 20 hours prior to delivery with first few days after birth
clear fluid. There was no maternal fever. Apgars were 8 and 9.
BLOOD FLOW AT SITE OF ADMINISTRATION
In the NB surgery, on the 2nd day:  Absorption after IM or SQ injection depends mainly on rate of
VS: HR 140, T 37, BP 47/39, RR 54. Oxygen saturation is 98-100% in room blood flow to the area injected
air.  Conditions that might reduce blood flow:
o CV shock
Infant appears slightly pale and mottled. She is centrally pink with
o Vasoconstriction due to sympathomimetic agents
persistent grunting, shallow respirations, and lethargy. Her fontanelle is soft
and flat. Heart exam is normal. Lungs show good aeration. Abdomen is soft o Heart failure
and without masses. Pulses are 1+ throughout with 3-4 sec capillary refill.
Neuro exam shows decreased tone and a weak, intermittent cry.
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TRANSCRIBERS: RxMen: Magaoay, Manio, Meneses, Ordoña, Villadolid
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PEDIATRIC PHARMACOLOGY

 If there is decreased perfusion (or thin muscle mass), the drug Phenytoin Decreased
remains in the muscle and is absorbed slowly Sulfonamide No Change
 If perfusion suddenly improves  sudden unpredictable increase
in drug concentration in circulation  may be toxic
GASTRIC EMPTYING TIME
o Cardiac glycosides
 Delayed by 6-8 hours until 6th to 8th month
o Aminoglycoside antibiotics
 Delay is offset by decreased gastric absorptive surface of GIT
o Anticonvulsant
in neonates
o Can result in regurgitation of oral medications
ORAL PREPARATION o Increase time it takes to reach therapeutic concentration in
 Variable gastric and intestinal transit time: infants < 3 months
o In young infants – Gastric emptying time is prolonged and o Acetaminophen, penicillin, phenobarbital, phenytoin
only approaches adult values at around 6 months of age.
INTESTINAL MOBILITY
PARENTERAL DRUGS  Both neonates and infants have irregular peristalsis, enhancing
(Erratically Absorbed) absorption
 Type of feeding affect intestinal transit time:
Patient Characteristics Drug Properties o Greater in breast-fed
 Blood flow to  Solubility (water, lipid)  Greater relative size of duodenum:
muscle  pH of extracellular fluid o Enhances drug absorption
 Muscle mass  ease in crossing
 Muscle tone capillary membranes BILIARY FUNCTION
 Activity/illness  amount of drug Decreased bile salts and bile acid (α-amylase and pancreatic
administration
enzymes) until approximately 4 months of age
 Variability in chemical properties o Decreased bioavailability/absorption of lipid-soluble drugs
 Differences in absorption by site of injection: IV, IM, SC o E.g. Diazepam, Vitamin E
 IV is most dependable but you have to consider:
o Binding to tubing MICROBIAL FLORA
o Unintended bolus infusion
Change in bacterial flora during neonatal period:
o Delayed delivery
o Vitamin K and Lipid Soluble Vitamins: More rapid
o Occlusion of IV
development of flora in breast-fed infants
o Know which drugs are given by fast or slow IV to avoid
Diseased conditions such as diarrhea and giardiasis:
irritation at the site of injection and always test the patency
o Decreased absorption
of the IV line before giving the drug.
 IM administration problems:
o Variability in muscle mass among children EFFECTS OF DOSAGE ON FORMS OF ABSORPTION
o IM is avoided because of pain and possible tissue damage  Taste:
 Presence of illness (e.g. Compensated circulatory status) usually o Spitting of foul tasting medication
renders the patient difficult to insert IV lines especially if the o Old liquid formulations
patient is acidotic (Manipis ang veins)  Solid form must dissolve in solution before it can be absorbed
 Faster after liquid dosing (Liquid > Suspension)
GASTROINTESTINAL FUNCTION  Caplet ≥ Tablet > Sustained/delayed release
Table 1. Physiologic Factors that influence oral absorption  Drug interactions with concurrent medications or dietary intake
FACTOR NEONATE INFANT CHILD o Do not give too many drugs to relieve numerous symptoms
Gastric Acid Reduced Normal Normal
o Target the specific illness in giving medications to prevent the
Secretion
occurrence of polypharmacy
Gastric Emptying Decreased Increased Increased
Time EFFECTS ON OTHER ROUTES OF ADMINISTRATION
Intestinal Reduced Normal Normal TRANSRECTAL
Mobility  Only used in emergencies (when no IV lines can be found)
Biliary Function Reduced Normal Normal
o Drug is absorbed by the hemorrhoidal veins
o Avoids first-pass hepatic elimination and infants
Microbial Flora Acquired Adult pattern Adult pattern
o Drug erratically and incompletely absorbed
Difference in venous drainage system
GASTRIC ACID SECRETION Expulsion of drug
Age pH  Hold buttock area to prevent the expulsion of the
At Birth  6-8 drug until it is already absorbed
Feces in rectum
24 Hours After Birth  1-3
Frequent bowel movements in neonates
9-12 Days of Age  Starts to increase o Lack of anal sphincter muscle
About 3 Years Old  Declines slowly until o Diazepam, midazolam, atropine, barbiturates, valproic acid
reaching 2-3
 In preterm infants, secretion of acid occurs more slowly
th INHALATION
(highest concentration in 4 day of life)
 Significance in neonates and infants:  Varies less by physiologic parameters
 Varies more by the reliability of the delivery device and
↓ Acid secretion
technique
↓
 Drug considerations
↑ Bioavailability of acid ↓ Bioavailability of weakly o Particle size (Small: deposited in lower airways)
labile drugs (e.g. acidic drugs o Lipid solubility (More soluble: deposited in lower airways)
Penicillin & (Phenobarbital) o Protein binding
Ampicillin) o Drug metabolism in the lungs
o Mucociliary transport
Table 2. List of some commonly prescribed oral drugs and effects of  Pediatric characteristics
gastric acid secretion o Lower tidal volumes
DRUG ORAL ABSORPTION o Increased respiratory rates especially when crying
Acetaminophen Decreased o Reduces drug delivery and absorption
Ampicillin Increased
Diazepam No Change TRANSDERMAL
Digoxin No Change  Enhanced in neonates and young infants
 Absorption inversely related to the thickness of stratum
Penicillin Increased corneum
Phenobarbital Decreased o Thin in neonates

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o Side effects may be seen earlier due to enhanced  Morphine

absorption  Phenobarbital
 Absorption directly related to the hydration of the skin  Phenytoin
 Ratio of surface area related to weight greater than of older o Examples:
children  Sulfonamide antibiotics were given as prophylaxis
 Skin disruptions (abrasions, eczema, burns) increase against sepsis in neonates, it displaced bilirubin
absorption in any age bound in albumin  bilirubin pass through BBB 
o Do not give directly in areas of disruptions except in Kernicterus
eczema  Conversely, phenytoin is bound to albumin, however
when serum bilirubin rises, phenytoin is displaced
and free drug concentration is increased
FACTORS WHICH AFFECT DRUG DISTRIBUTION IN
CHILDREN
VASCULAR PERFUSION METABOLISM
 Neonatal RDS and post-asphyxia Prof Notes:
o A R-L vascular shunt occurs and diverts blood from the  Enzyme system mature at different times and may be absent
lungs to the tissues and organs at birth or present …. reduced amount
 Altered metabolic pathways – except from some drugs
 Metabolic rate – increased dramatically in children and greater
BODY COMPOSITION (EXTRACELLULAR & TOTAL BODY than adults
WATER SPACES)
CLEARANCE
 Total body compartment relatively larger among premature
 Hepatic drug metabolism
infants than in full-terms
o Phase 1 reactions or Non-synthetic
o Adult: 50-60% of its body weight in form of water
 Achieve maturity at 6 mos of age
o Full term neonate: 70%
 Attain adult rate by late puberty
o Preterm neonate: 85%
o Phase 2 reactions or Synthetic
 Extracellular water compartment higher in neonate than in
adults (20% in adult, 40% in neonates)  Lower in neonatal life
o Most neonates have diuresis in first 24-48h of life o Glucoronide formation fully matured between the 3rd and
o Increase extracellular compartment--- increase water 4th year of life
compartment--- increase distribution o Decreased ability of neonates to metabolize drugs results in
 Drugs mainly distributed in body water will have greater volume slow clearance rates and prolonged elimination half-lives
of distribution (Sulfonamides)  Barbiturates
 Total body fat lower in prematures (1%) than in full terms  Analgesics
(15%)  Glycosides
o Lipophilic drugs will have lower volume of distribution  So if a child has liver disease, drugs remain there
o Higher doses of water-soluble drugs required in younger  Use with caution, antibiotics excreted in the liver
children rather than fat soluble drugs (Ceftriaxone and rifampicin)
o Consequential drug toxicities
TISSUE BINDING CHARACTERISTICS
 CYP 45O system is the most studied of the oxidase
 Drugs extensively bound to tissues exhibit increased “free” blood systems
levels when the mass tissue is reduced  Phase 2 less well studied
o Disease  Glucoronidation pathways deficient in neonates and
o Degeneration infants (Acetaminophen)
o Immaturity  At birth, concentration of drug-oxidizing enzymes similar to that
PHYSIOCHEMICAL PROPERTIES OF DRUG in adult but activity is reduced
 Lipid solubility and molecular configuration o Reflected by prolonged body eliminations of drugs
o Affect the ability of a drug to move across membranes (Phenytoin, caffeine, diazepam)
into target cells and tissues  Metabolic activity achieved at 6-12 months
 Drugs that display favorable properties for absorption may o Activity of certain hydrolytic enzymes including esterases
pose a great risk for toxicity in neonates reduced during neonatal period
 Important for metabolic clearance of cocaine
PLASMA PROTEIN BINDING o Elimination of metabolites reduced in the newborn (N-
 Albumin binds acidic drugs, fatty acids and bilirubin methylation of theophylline to caffeine)
o Albumin is the plasma protein with the greatest binding o Ultimate ability to metabolize drugs is genetically
capacity modulated
 In general: protein binding of drugs is reduced in neonates
 α1-acidic glycoprotein and lipoproteins, binds alkaline drugs Table 3. Drugs Subject to Phase 1 and Phase 2 Reactions
 Albumin and total protein concentrations PHASE 1 PHASE 2
o Lower in neonate and approach adult levels by 10-12 Phenytoin Acetaminophen
months Ibuprofen Morphine
 Lower in preterms Codeine Corticosteroids
o Decreased binding proteins increased free drug  Diazepam Dopamine
toxicity in lower doses Naloxone Sulphonamides
o Reduced protein binding in infants – Ampicillin and Methylphenidate Isoniazid
nafcillin Indomethacin Digoxin
o Example: Succinylcholine Diazepam
 Diazepam with total plasma concentration of  Another consideration is whether the mother was receiving
300mcg/L. drugs (e.g. Phenobarbital) that can induce early maturation of
 In adult, it has plasma protein binding of 98%  fetal hepatic enzymes  the ability of the neonate to
6mcg/L free drug metabolize certain drugs will be greater, less therapeutic effect
 In neonates, it has PPB of 90%  30mcg/L or and lower plasma concentration
higher
 Although, higher free concentration may result in
faster elimination, this concentration may be quite FACTORS AFFECTING DRUG EXCRETION
toxic initially FUNCTIONAL ABILITY of the GLOMERULUS
 Competitive binding (Bilirubin and free fatty acids)  GFR
o Higher in neonates and infants o In full term (2-4 mL/min) increases to 8-20 mL/min by 2-3
o Net result: increase free drug concentration, greater drug days
availability at receptor sites; pharmacological effects and o Approaches adult value at 3-5 months
adverse reactions occur at lower drug (That is why drugs o Adult values at 3 years
are computed per kilogram of the child’s body weight)  GFR in preterms (before 34 weeks AOG) is markedly reduced
o Higher ratio for free to total drug for: and increases more slowly than in term infants (So compute
 Salicylates in terms of weight)
 Sulfonamides o Neonate has only 30-40% GFR of the adult value

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o At end of first week, it improves, increased by 50%  Other problems need to be considered.
o In the first day of life, antibiotics should be given every 12 o For example: Calculation by BW in the overweight child may
hours then at 1 week old it is adjusted to every 8 hours result in higher doses being administered than necessary.
due to GFR considerations in drug excretion o In such cases, dose should be calculated from ideal weight,
o Example: related to height and age.
 Penicillins dose for neonates <7 days is 50-100 Para may idea paano kunin ang BSA: =)
mg/kg/d in 2-doses at 12h interval. In >7 days old, 100-
200 mg/kg/d in 3-doses at 8h interval
 Aminoglycosides have a narrow therapeutic window
so always compute for the drug dosage appropriate for
the child’s weight.
TUBULAR SECRETION
 Decreased by 70-80%
 Tubular absorption of Na, Cl, amino acids and glucose is  BSA estimates and more accurate
increased in newborns o mg/kg – e.g. Lasix
 Adult values reached at 5-7 months of age o mcg/kg. – Fentanyl
INTEGRITY OF RENAL BLOOD FLOW o units/kg – Heparin
 Renal blood flow at birth is 12 mL/min
 Approaches adult value at 5-12 months Example: Calculate.
EXTENT OF PROTEIN BINDING
 Amount of drug filtered is inversely related to protein binding Case 1: Wt = 3000g  3kg
  Protein binding   Drug filtered A. Ampicillin: 100 mg/kg/day
Dose: 100 mg/ kg x 3 kg = 300 mg/day
Table 4. Changes in Elimination Half-life during Development (Hours) Divide to 2 doses (q12)
o
DRUG NEWBORN INFANT CHILD ADULT = 150 mg q 12 , IV (push)
Acetaminophen 4.9 4.5 3.6 B. Gentamicin: 2.5 mg/kg
Amikacin 5-6.5 1.6 2.3 Stock Dose: 10mg/ml in 2ml ampule
Amoxicillin 3.7 0.9-1.9 0.6-1.5 Dose: 2.5 mg/kg x 3 kg = 3.75 ml
Cefuroxime 5.5 1.5 1.2 1.5
Diazepam 30 10 25 30 Case 2: Wt: 16 kg
Digoxin 18-33 37 30-50 Amoxicillin: 40 mg/kg
Gentamicin 4.0 2.6 1.2 2-3 Stock Dose: 250mg/5ml
Theophylline 30 6.9 3.4 8.1 Dose: 40mg/kg x 16kg = 640 mg/kg
Vancomycin 4.1-9.1 2.2-2.4 5.6 Divided into 3 doses
o
*Note that elimination half-lives are generally higher in the newborn period thus mas = 213.33 mg, q8
matagal ang drug umiikot sa katawan which means there is a greater risk for toxicity.
FACTORS CONSIDRED WHEN PRESCRIBING A DRUG
ROUTE OF ADMINISTRATION and DRUG REGIMEN  Risk and benefits
 If orally, liver becomes primary distribution site  Long term effects
o Extensive hepatic metabolism  Dosage form
 Reduces amount of circulating active drug  Route of administration
 Limits its effects  Frequency of administration
 Dosage higher than IV  Pharmacogenetics
 If IV, heart and lungs become the primary distribution sites DRUG-DRUG INTERACTIONS
a. Factors facilitating passage of drug to blood brain barrier Pharmaceutic
o Incomplete anatomic development of the barriers o Drug inactivation when compounds are mixed together
o Increased permeability of the membranes physically prior to patient administration
o Incomplete myelinization in the brain o E.g. Syringes, infusion tubing, parenteral fluid preparation
o Acidosis o Do not give drug combinations in a single syringe
o Hypoglycemia Pharmacokinetic
b. Toxicity of drugs in neonates aggravated by great passage of o Disposition characteristics of one compound are influenced
most drugs to the BBB by those of another
o Exception: CNS infection (meningitis) in older children and o Absorption, distribution, metabolism, excretion
adults. This allows the BBB to accept the drug given. Pharmacodynamics
Penicillin (a drug commonly used for the treatment of o Compounds compete for the same receptor or physiologic
meningitis) is always given at a meningitic dose of system
200,000 IU Pen G than usual dose of 100,000 IU to Combination of drugs
increase the amount of drug going to the brain
This is because as the person heals or gets better, the
BBB will recover its function of stopping drugs from DRUG INTERACTIONS
crossing ORAL BIOAVAILABILITY
The meningitic dose will ensure that the therapeutic  Decreased oral bioavailability of index drug
dose of the medication will reach the brain and o Tetracycline with calcium, magnesium, or iron
eventually exert its effect  Drugs that damage the intestinal absorptive surface decrease
absorption
Additional Notes Prof. Lec: o Anti-neoplastic agents
 Compliance in children is influenced by formulation, taste, o Neomycin
appearance, ease of administration of preparation  Enhancement of gastric emptying affects rate
 Prescribed regimen should be tailored to the child’s daily o Metoclopramide
routine where possible treatment goals should be set in o Domperidone
with child  Delayed gastric emptying affects rate
 Whenever possible, the use of products which avoid the o Morphine
need for administration during school hours should be…. o Antacids
(e.g. modified-release preparation or drugs with long T o Anti-cholinergics
½)  Drugs with extensive first pass (lidocaine, morphine)
 Most schools will request written permission from parents combined with drugs that decrease hepatic blood flow
to administer the medication, or may ask parent’s to (cimetidine, beta blockers) will raise steady state
return to school to give the meds themselves concentration
PROTEIN BINDING
DOSE CALCULATION  Drugs that are highly bound to proteins are subject to
 Children doses may be calculated from adult dose, by using displacement by other drugs with higher affinity to the same
Age, Birth Weight, or Body Surface Area, or by combination protein- binding site
of these factors. The most reliable are based on BSA.

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 Results in the transient increase in the concentration of the  Forgetting to take doses and stopping after some improvement
index drug but before completing full course
BIOTRANSFORMATION  Inability to obtain drug due to lack of financial resources
 Drugs are metabolized by a number of different pathways and the use of dosing schedule not compatible with the
o Quantitative fraction of each pathway is difficult to evaluate family’s routine
 Drugs with inhibitory effects on hepatic metabolism
(cimetidine, erythromycin, ciprofloxacin, omeprazole) when THERAPEUTIC DRUG MONITORING
combined with a drug with a narrow therapeutic index  Measurement of drug concentration and the use of
(theophylline) results in increased concentration and potential pharmacokinetic principles to individualize drug dosing in an
toxicity attempt to maximize the therapeutic efficacy while minimizing
 Enzyme induction enhances clearance of index drugs leading the potential toxicity
to a decrease or loss of efficacy o Usually antibiotics have an effect within 48 hours
o Rifampicin o Know how soon the effects of the drug will occur so that
o Prednisone you will know when to follow-up with the patient or if you
o Oral contraceptives have given the right drug or treated the right disease
o Phenytoin  Applicable for medications with narrow therapeutic indices and
o Theophylline for agents that demonstrate a good correlation between
o Digoxin serum concentrations and pharmacologic effects
o Chloramphenicol  Appropriate timing of drug concentration measurement is
o Doxycycline crucial for accurate therapeutic drug monitoring
o Metronidazole o Sabi ni doc 5 times the half-life of the drug bago
o Propranolol magmeasure
o Opioid analgesics o Example
 In case of induction interaction, index drug should be increased  Ang half-life ng drug A mo ay 10 hr x 5 = 50 hr
 Measure drug concentration after 50 hours nagstart
ALTERED RENAL FUNCTION
 Drugs excreted entirely by GFR unlikely to be affected by SUMMARY
other drugs
 A child is not a “miniature adult”
 Drugs actively secreted into the tubular lumen can be  Consider the physiology of a neonate, an infant and an older
inhibited by other drugs child
o Methotrexate toxicity enhanced by inhibition of tubular  Pharmacokinetic principles apply to pediatric patients in the
secretion by salicylates
context of unique characteristics of a neonate, infant, and a
o Lithium reduced with thiazides child
o Probenecid reduces excretion of penicillin  Important to understand the influence of age of drug disposition
and resulting effects on drug activity
RISK FOR ADVERSE DRUG REACTIONS
 Different and changing pK parameters between patients of
Exercise:
various ages and stages
Dose Calculation.
 Need for calculation of individualized doses based on age,
weight, BSA, clinical condition 1. Calculate the dose of amoxicillin suspension in ml for otitis media
 Lack of available dosage forms and concentrations for 1 year old child weighing 22lbs. Dose referred is 40 mg.kg divided
 Need for precise dose measurement and appropriate drug BID and suspension comes in concentration of 400mg/5ml.
delivery systems
• Lack of published information and FDA approved labeling 2. Calculate the dose of ceftriaxone in mls for meningitis for 5 y/o
weighing 18 kg. Dose referred is 100 mg/kg/day IV once daily and
dosing comes prediluted in concentration of 40 mg/kg.
CAUSES OF NON-ADHERENCE TO DRUG
RECOMMENDATIONS 3. Calculate the dose of vincristine in mls for a 4 y/o with leukemia
weighing 37 lbs and 97 cm tall. The dose regimen is 2 mg/m2 and
 Cost drug comes in 1mg/ml concentration.
o Pag sobrang mahal baka hindi na bilhin ng nanay o di na
magrefill
o Baka mag-imbento si mommy ng mas maliit na dosage
para tipid
 Painful or inconvenient administration It’s GREEN in 3Beeeeee!!
 Need for frequent regimens
 Complex regimens
o Kailangan mag-effort talaga sa pag-explain
 Children below 6 years
13 days to Go!
o Difficulty swallowing pills
o Bad taste
o Parents partially remember or understand rationale for
taking the drug
 Older children
o Need to leave classes or activities (insulin metered dose
inhalers)
o Rebellion (adolescence)

COMPLIANCE
 Time to explain nature of illness
 Action of medication prescribed
 Precise instructions for carrying out treatment
 Specific instructions regarding dosage written down clearly and
in detail
 Regimen results in minimal interference with the daily living
schedule particularly sleeping habits
o Take drug 1 hour before sleeping
 Collaboration between prescribing physician and dispersing
pharmacist

Compliance Issues:
 Preparing correct doses in an acceptable dosage formulation
 Poorest compliance in asthma and epilepsy

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