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Pharmacy Notes

General Prescribing Guidelines for Pediatrics

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Detailed insights into pediatric patient classification, drug absorption, metabolism, safety challenges, historical drug tragedies, and tailored pharmacotherapy for children.

  • pediatric pharmacotherapy
  • drug dosing
  • children
  • drug safety
  • pharmacokinetics

By Dr. Ayesha Fatima

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  1. Page 1. PEDIATRICS Pediatric Patients: Pediatric patients are individuals younger than 18 years of age. They are classified according to age: Age Group Definition Physiological Characteristics Premature Infants Babies born before 37 weeks of gestation Immature liver, kidneys, lungs, and GI tract Poor drug metabolism and excretion Increased sensitivity to medications Neonates 1 day to 1 month of age Immature liver enzymes Reduced kidney function Slow gastric emptying Increased permeability of the blood-brain barrier Infants 1 month to 1 year of age Rapid maturation of liver and kidney function Increasing drug metabolism Rapid growth with doubling/tripling of body weight during the first year Children 1 to 11 years of age Liver enzyme activity may be higher than in adults Faster metabolism of some drugs Improved immune function and steady growth Adolescents 12 to 16 years of age Hormonal changes associated with puberty Changes in body composition (fat and muscle mass) Drug handling gradually approaches that of adults Physiological changes at each developmental stage influence drug absorption, distribution, metabolism, and excretion (ADME). Therefore, pediatric drug therapy must be individualized according to the patient's age and developmental stage. INFANT MORTALITY AND IT’S IMPROVEMENT Infant mortality refers to the number of infants who die before reaching one year of age per 1,000 live births. Historically:  During the 19th century, nearly 200 infants died for every 1,000 births.
  2. Page 2.  This means that many medications prescribed for children are used off-label, where physicians rely on available scientific evidence and clinical experience rather than formal pediatric approval. Why is Pediatric Pharmacotherapy Challenging? One of the biggest challenges in pediatric medicine is the lack of sufficient clinical data. For many drugs, there is limited information regarding: 1. Pharmacokinetics : This refers to what the body does to the drug , including: ADME Parameters of drugs 2. Pharmacodynamics: This refers to what the drug does to the body , including: Therapeutic effects, Adverse effects 3. Drug Efficacy: A drug that is effective in adults may not produce the same effect in newborns or infants because receptor sensitivity and organ function differ. 4. Drug Safety: Children are much more susceptible to adverse drug reactions because many of their organs are still developing. Therefore, medications must always be prescribed with extreme caution. Historical Drug Disasters in Pediatrics Because of insufficient knowledge of pediatric pharmacology, several serious drug-related tragedies occurred. Drug/Condition Cause/Mechanism Clinical Features/Effects Lesson Learned Gray Baby Syndrome (Chloramphenicol) High doses of chloramphenicol (100–300 mg/kg/day) administered to neonates. Immature liver enzymes (deficient glucuronidation) and reduced renal excretion cause drug accumulation, leading to toxic serum concentrations. Abdominal distension Vomiting, Diarrhea, Ref
  3. Page 3. brain, causing bilirubin encephalopathy (kernicterus). loss, Cerebral palsy, Death in severe cases function, reduced protein binding, and an underdeveloped blood- brain barrier. Special Considerations in Pediatric Drug Therapy 1. Dosage Regimen 1. Children are not small adults. 2. Pediatric doses should not be calculated by simply reducing the adult dose based on body weight (mg/kg) or body surface area (mg/m²). 3. Drug dosing should also consider age, organ maturity, developmental stage, and disease condition. 4. Individualized dosing helps achieve effective treatment and prevents toxicity. 2. Bioavailability 1. Bioavailability is the amount of drug that reaches the bloodstream after administration. 2. In children, bioavailability differs because the gastrointestinal tract is still developing. 3. Drug absorption may be higher or lower than in adults. 4. These differences can alter the therapeutic effect of the drug. 3. Pharmacokinetics (PK) 1. Pharmacokinetics includes Absorption, Distribution, Metabolism, and Elimination (ADME). 2. These processes vary between premature infants, neonates, infants, children, and adults. 3. Drug dose, dosing interval, and route of administration should be adjusted according to age. 4. Individualization improves drug efficacy and safety. 4. Pharmacodynamics (PD) 1. Pharmacodynamics refers to how the drug affects the body. 2. Children's receptors and organs may respond differently to drugs than those of adults. 3. The same drug concentration ma
  4. Page 4. 4. These preparations help infants and young children take medicines more easily. 8. Modification of Adult Formulations 1. Adult injectable medicines are often diluted to provide small pediatric doses. 2. Examples include aminophylline, methylprednisolone, morphine, and phenobarbital. 3. Improper dilution may affect drug stability, compatibility, and bioavailability. 4. Accurate preparation is essential for safe treatment. 9. Intravenous (IV) Drug Administration 1. Infants have small and fragile veins. 2. They can tolerate only small volumes of IV fluids. 3. Accurate infusion pumps and dosing devices should be used. 4. Careful administration reduces medication errors. 10. Oral Drug Administration 1. Young children often have difficulty swallowing tablets or capsules. 2. Poor taste may lead to refusal of medication. 3. Liquid formulations or taste-masking techniques may improve acceptance. 4. Proper administration techniques improve treatment success. 11. Medication Adherence 1. Children depend on parents or caregivers to receive medicines correctly. 2. Missed doses or incorrect administration can reduce treatment effectiveness. 3. Parents and caregivers should receive proper counseling. 4. Good adherence improves therapeutic outcomes. 12. Ethical Considerations 1. Children cannot legally provide informed consent for research. 2. Parents or legal guardians provide consent on their behalf. 3. Pediatric clinical studies require strict ethical review. 4. The benefits of research
  5. Page 5. o Rate of absorption Extent of absorption (bioavailability)  Drug therapy should therefore always be individualized according to: o Age o Weight o Gestational age o Organ maturity o Disease condition 1. Oral (Gastrointestinal) Absorption Oral administration is the most common route in children. However, gastrointestinal physiology changes markedly during infancy, making drug absorption unpredictable. A. Gastric pH Developmental Changes 1. Full-term newborn: Gastric pH = 6–8 (nearly neutral) 2. Within 24 hours: Gastric pH falls to 1–3 3. Premature infants maintain higher gastric pH longer because acid secretion is immature. 4. Adult acid secretion develops by approximately 2 years of age . Effect on Drug Absorption Higher gastric pH means: 1. Acid-labile drugs are protected from acid degradation. 2. Weak acidic drugs remain less ionized and are absorbed less efficiently. Clinical Examples Increased absorption  Penicillin , Ampicillin , Nafcillin  These antibiotics are destroyed by gastric acid in adults but survive better in neonates. Decreased absorption  Phenobarbital  Other weak acidic drugs B. Gastric Acid Secretion Development  Immature at birth  Gradually increases  Adult secretion reached by about 2 years Clinical Importance Gastric acid determines:  Drug dissolution  Drug ionization  Stability  Bioavailability Some drugs require acidic environments for optimal absorption. C. Gastric Emptying Development Neonates have:  Delayed gastric emptying  Particular
  6. Page 6. D. Gastric Transit Time Development Food and drugs remain longer in the stomach. Effect  Delays movement into small intestine.  Slower onset of absorption. Clinical Importance Emergency medications given orally may act later than expected . E. Intestinal Transit Time Development Intestinal motility is slower during infancy. Effect Drugs remain longer in the intestine, leading to:  Slower absorption  Sometimes greater total absorption F. Gastrointestinal pH The pH differs throughout infancy. This influences:  Drug ionization  Drug dissolution  Drug stability The effect depends entirely on the drug. G. Passive Diffusion and Active Transport Passive Diffusion Develops early. Most drugs cross intestinal membranes by passive diffusion. Active Transport Carrier-mediated transport matures around 4 months . Examples include:  Vitamins  Amino acids  Certain antibiotics Clinical Significance Drug absorption becomes more predictable after infancy. H. Effect of Food Milk Formula Breastfeeding Solid food can all alter absorption. Mechanisms Food may:  Delay gastric emptying  Bind drugs  Alter gastric pH Examples Some antibiotics should not be taken with milk because calcium binds the drug and reduces absorption. I. Posture Infants lying flat may have slower gastric emptying. This may alter drug absorption slightly. Especially important in hospitalized neonates. J. Disease States Conditions affecting GI absorption include:  Vomiting  Diarrhea  Malabsorption  Intestinal inf
  7. Page 7. Effect Drug absorption becomes:  Reduced  Delayed  Highly unpredictable Dose adjustment may be necessary. K. Therapeutic Interventions Examples include:  Nasogastric suction  Continuous feeding  Acid-suppressing drugs These interfere with oral drug absorption. 2. Intramuscular (IM) Absorption IM absorption is highly variable in newborns. Developmental Factors Premature infants have:  Less muscle mass  Poor muscle perfusion  Weak muscle contractions  Vasomotor instability Effect Drug reaches circulation slowly and unpredictably. Drug Examples Phenobarbital Rapidly absorbed. Diazepam Poorly absorbed from muscle. Demonstrates that IM absorption is drug dependent. Clinical Importance As infants grow:  Muscle mass increases.  Blood flow improves.  IM absorption approaches adult values. Limitations IM injections are:  Painful  Stressful  Difficult in small infants Therefore:  Avoid IM injections whenever possible.  Reserve IM administration for emergencies or when IV access is unavailable. 3. Intraosseous (IO) Absorption Principle When IV access cannot be established during emergencies: A needle is inserted into the bone marrow cavity (usually proximal tibia). Bone marrow has:  Rich vascular supply  Venous sinusoids Drug rapidly enters systemic circulation. Clinical Uses Preferred during:  Pediatric cardiac arrest  Shock  Severe dehydration  Trauma Almost all emergency medications can be administered by the IO route. 4. Skin (Topical/Percutaneous) Absorption
  8. Page 8. A. Thin Stratum Corneum The outer skin barrier is immature. Drug passes through more easily. B. Increased Skin Hydration Infant skin contains more water. Hydrated skin absorbs drugs faster. C. High Body Surface Area (BSA) Infants have:  Larger BSA relative to body weight. Therefore: A small amount of topical drug may produce significant systemic exposure. D. Underdeveloped Epidermal Barrier Drug penetrates deeper layers more easily. Higher risk of toxicity. Clinical Examples Systemic toxicity has occurred with:  Hexachlorophene  Salicylic acid  Rubbing alcohol Topical Corticosteroids Infants absorb more steroid. May develop:  Growth suppression  Adrenal suppression  Cushing syndrome Topical Theophylline Used experimentally in premature infants for neonatal apnea. Can produce therapeutic blood concentrations. Transdermal Patches Methylphenidate Approved in children aged 6–12 years . Patch remains effective during:  Bathing  Swimming  Exercise Hyoscine Patch Used for:  Excessive drooling Fentanyl Patch Provides:  Continuous opioid analgesia  Used only for chronic pain in opioid-tolerant patients (not opioid- naïve children) EMLA Cream Contains:  Lidocaine  Prilocaine Avoid in premature infants because excess prilocaine absorption may cause methemoglobinemia . Needle-Free Jet Injectors Deliver drugs subcutaneously without needles. Used for:  Growth hormone  Insulin  Vaccines  Sedation Advantages:  Reduced needle phobia  Comparable absorption to SC injection
  9. Page 9. Indications  Vomiting  Unconsciousness  Seizures  Refusal to swallow Characteristics Absorption is:  Variable  Drug dependent  Sometimes rapid Example Rectal diazepam:  Rapidly terminates seizures  Can be administered by parents at home during emergencies 7. Buccal Absorption The buccal mucosa is:  Thin  Highly vascular Drugs absorbed here enter systemic circulation directly, bypassing much of the first-pass hepatic metabolism. Advantages  Rapid onset  No swallowing required  Useful in postoperative patients  Useful in nausea and vomiting Highly Lipophilic Drugs Absorbed rapidly:  Fentanyl  Midazolam Buccal Midazolam Preferred over rectal diazepam for:  Acute seizures Reasons:  Faster  Easier administration  More socially acceptable Fentanyl Lozenges Used for:  Painful procedures  Breakthrough cancer pain Not licensed for routine pediatric use. Melt/Wafer Formulations Examples:  Ondansetron  Piroxicam Although they dissolve in the mouth, they are swallowed and absorbed from the GI tract rather than the buccal mucosa. Buccal Desmopressin Higher bioavailability than tablets. 120 μg buccal ≈ 200 μg oral 8. Intranasal Absorption The nasal mucosa has an extensive blood supply, allowing rapid systemic drug absorption. Uses Local Therapy Examples:  Nasal decongestants  Corticosteroid nasal sprays Systemic Therapy Examples:  Desmopressin for diabetes insipidus  Midazolam for seizures and procedural sedation  Fentanyl for rapid analgesia  Diamorphine for
  10. Page 10.  Mucociliary clearance Adverse Effects Excessive absorption of intranasal corticosteroids may lead to:  Adrenal suppression  Growth retardation  Cushingoid features 9. Inhalational Absorption Drugs are delivered directly into the lungs, providing a rapid onset of action because of the lungs' large surface area and rich blood supply. Advantages  High drug concentration at the site of action (lungs)  Reduced systemic exposure  Rapid onset  Lower doses required than systemic therapy Clinical Uses  Mainstay of asthma management  Bronchodilators (e.g., salbutamol)  Inhaled corticosteroids for long-term control Factors Affecting Pulmonary Absorption Drug absorption depends on:  Airway size  Lung maturity  Pulmonary blood flow  Breathing pattern  Correct inhaler technique  Appropriate spacer use in young children Systemic Absorption Long-term use of high-dose inhaled corticosteroids may result in:  Adrenal suppression  Growth retardation  Reduced bone mineral density (rare) Therefore, the lowest effective dose should be used and growth should be monitored. Distribution Distribution is the reversible movement of a drug from the bloodstream to body tissues and organs after absorption. In children, especially premature infants and neonates, drug distribution differs significantly from adults because of developmental changes in body composition and physiology. Premature infants, neonates, infants, children, and adolescents all have different distribution patterns. Th
  11. Page 11. a. pKa (Degree of Ionization) Determines whether a drug is ionized or non-ionized. Non-ionized drugs cross cell membranes more easily. Influences tissue penetration. b. Molecular Weight Small molecules distribute more rapidly. Large molecules remain mainly within the vascular compartment. c. Lipid Solubility (Partition Coefficient) Lipid-soluble drugs easily cross cell membranes. Water-soluble drugs remain mainly in extracellular fluid. Important Clinical Point 2. Patient-Specific Physiological Factors These undergo significant maturation after birth and are the major determinants of pediatric drug distribution. They include: 1. Organ blood flow (vascular perfusion) 2. Body composition 3. Plasma protein binding 4. Tissue binding 5. Disease states A. Vascular Perfusion : Vascular perfusion refers to the amount of blood reaching various organs. Developmental Changes Immediately after birth: Blood flow distribution differs from adults. Organ perfusion gradually matures during infancy. Highly perfused organs include: Brain, Heart, Liver, Kidneys These organs receive drugs first. Effect on Drug Distribution Initially: Drug rapidly reaches highly perfused organs. Later: Drug redistributes into: Muscle, Fat, Skin As circulation matures, distribution becomes similar to adults. Clinical Significance: Rapid CNS drug delivery may occur in neonates because: Brain receives a larger proportion of cardiac output. Blood–brain barrier is relatively immature. B. Body Composition: One of the mo
  12. Page 12. Extracellular Fluid (ECF): Development Age Extracellular Fluid Premature infant 50% 4–6 months 35% 1 year 25% Adult 19% Effect  Many water-soluble drugs remain primarily in extracellular fluid.  Since neonates possess a much larger extracellular compartment:  Drug distributes more extensively.  Clinical Significance: Larger loading doses are required.  Water-Soluble Drugs Examples:, Gentamicin, Tobramycin, Amikacin Distribution volume is: Highest in Extremely premature infants Gradually decreases as: Gestational age increase, Birth weight increases C. Plasma Protein Binding Many drugs circulate bound to plasma proteins. Only free (unbound) drug is pharmacologically active. Developmental Changes Neonates have: 1. Lower albumin concentration 2. Lower globulin concentration 3. Reduced protein- binding capacity 4. Reduced protein- binding affinity 5. Higher concentrations of: Bilirubin, Free fatty acids  compete for protein-binding sites. Effect Less drug binds to plasma proteins. More drug remains free. Clinical Consequences Free drug: efficacy and toxicity increase 1. Produces therapeutic effects 2. Produces adverse effects 3. Crosses membranes 4. Is filtered by kidneys Albumin Albumin mainly binds: Acidic drugs. Examples: Phenytoin Phenobarbital Salicylates Warfarin Because albumin concentration is reduced: More free drug circulates. Globulins Basic drugs bind more to globulins. Globulin concentration is also lower in neonates. Result: Higher free concentrations. Age-Rel
  13. Page 13. 3. Clinical Importance As children grow: o Tissue composition changes. o Drug storage and release become more predictable. o Distribution patterns gradually resemble those of adults. Disease States: Disease may have a greater impact on drug distribution than normal developmental changes. Examples include: 1. Renal impairment 2. Liver disease 3. Hypoalbuminemia 4. Severe burns 5. Edema 6. Dehydration 7. Sepsis Disease may: 1. Reduce protein binding 2. Alter tissue perfusion 3. Change body water distribution 4. Increase or decrease volume of distribution Clinical Significance: Drug doses often need adjustment based on the child's clinical condition, not just age. Distribution into Breast Milk Many medications taken by lactating mothers pass into breast milk. Drug transfer depends on: 1. Lipid solubility 2. Molecular weight 3. Protein binding 4. Ionization 5. Maternal plasma concentration Clinical Importance: Breastfed infants may receive clinically significant drug exposure. The risk is greatest in 1. Premature infants 2. Neonates 3. Infants with renal or hepatic impairment Metabolism 1. Drug metabolism (biotransformation) is the enzymatic conversion of drugs into more water- soluble compounds , making them easier to eliminate from the body. 2. The liver is the principal organ responsible for drug metabolism, although metabolism also occurs in the intestines, kidneys, lungs, and plasma. 3. Drug metabolism in children is not constant throughout childhood . 4. The capacity to met
  14. Page 14.  Older children often metabolize drugs faster than adults.  Pediatric doses should be individualized according to age and developmental stage. Development of Hepatic Drug Metabolism The metabolic capacity of the liver changes throughout childhood. Age Metabolic Capacity Premature infant Very low Neonate Low Infant Rapidly increasing Young child (1–9 years) Higher than adults Adolescent Similar to adults Clinical Importance Drug clearance changes with age. Therefore:  Neonates often require lower maintenance doses .  Young children may require higher mg/kg doses .  Adolescents generally receive adult-equivalent doses. Phases of Drug Metabolism Drug metabolism occurs in two phases . Phase I Reactions (Functionalization)/ Cytochrome P450 System) These reactions introduce or expose functional groups on the drug molecule. Types  Oxidation (most common)  Reduction  Hydrolysis Most Phase I reactions are catalyzed by the Cytochrome P450 (CYP450) enzyme system . Development Most CYP enzymes are:  Immature at birth.  Increase rapidly after birth.  Reach or exceed adult activity during childhood.  Decline to adult levels during adolescence. Effect Reduced CYP activity causes:  Slow drug metabolism.  Drug accumulation.  Longer elimination half-life. Example: Phenobarbital Phenobarbital undergoes oxidative metabolism. Neonates Oxidative metabolism is poor. Drug clearance is reduced. Half-life is prolonged. Clinical Significance  Lower daily doses are required in premature
  15. Page 15.  Methylation  Glutathione conjugation Phase II Metabolism – Sulfation Development Unlike glucuronidation: The sulfation pathway is well developed even in premature infants and newborns . Importance Sulfation acts as an alternative metabolic pathway when glucuronidation is immature. Clinical Significance Neonates can metabolize several drugs adequately through sulfation despite immature liver function. Phase II Metabolism – Glucuronidation Development Glucuronidation is:  Poorly developed at birth.  Gradually matures over the first several months to approximately 1 year of life. The enzyme responsible is UDP- glucuronosyltransferase (UGT) . Effect Reduced glucuronidation causes:  Slower metabolism  Drug accumulation  Longer half-life  Increased toxicity Clinical Importance Many drugs depend on glucuronidation for elimination. Neonates metabolize these drugs much more slowly than adults. Example: Paracetamol (Acetaminophen) Adults Approximately 70% of paracetamol is metabolized by glucuronidation . Newborns Less than 20% undergoes glucuronidation. Instead, Most metabolism occurs through sulfation . Clinical Significance Children are generally less susceptible to paracetamol toxicity than adults because:  Sulfation is efficient.  Less drug is converted to the toxic metabolite NAPQI . However, overdose can still cause severe hepatotoxicity. Example: Chloramphenicol Chloramphenicol requires glucuronidation for detoxification. Neonates Deficiency of glucuronyltransferase
  16. Page 16. Because hepatic metabolism is reduced: The following drugs often require lower maintenance doses or longer dosing intervals:  Theophylline  Phenobarbital  Phenytoin  Diazepam Compensatory Metabolic Pathways Children may rely on alternative metabolic pathways when a major pathway is immature. Example Paracetamol: Adults: Main pathway: Glucuronidation ↓ Neonates: Main pathway: Sulfation Compensatory sulfation prevents excessive accumulation of paracetamol. Pharmacogenetics and Pharmacogenomics Not all children metabolize drugs at the same rate. Inherited genetic variations influence:  Drug metabolism  Drug efficacy  Drug toxicity Genetic testing helps individualize drug therapy and improve safety, especially for drugs with a narrow therapeutic index. Elimination 1. Drug elimination is the process by which a drug and its metabolites are removed from the body, primarily through the kidneys (urine) and, to a lesser extent, through the bile, feces, lungs, sweat, saliva, and breast milk. 2. In pediatric patients, renal excretion is the major factor affecting elimination of many drugs , and renal function changes dramatically during infancy. 3. The kidneys are the primary organs responsible for eliminating many drugs and their metabolites. 4. Renal function is immature at birth , especially in premature infants  Drug elimination is therefore much slower in premature infants and neonates than in older children and adults  Slower elimination leads to: Drug accumulation , Prolo
  17. Page 17. Glomerular Filtration Rate (GFR): Glomerular filtration is the passive filtration of plasma and drugs from the glomerular capillaries into the renal tubules . Only: Free (unbound) and Small molecular weight drugs are filtered. Developmental Changes Approximate GFR: Age GFR (mL/min/1.73 m²) Preterm infant 0.6–0.8 Full-term infant 2–4 Adult 120–130 Thus, neonatal GFR is only a small fraction of adult values. Effect Low GFR causes:  Reduced filtration  Reduced renal clearance  Prolonged elimination  Longer drug half-life Clinical Significance Drugs eliminated primarily by filtration require:  Lower doses  Longer dosing intervals Examples:  Gentamicin  Tobramycin  Vancomycin Three Processes of Renal Drug Elimination  All three are immature at birth Renal elimination depends on three physiological processes : 1. Glomerular filtration 2. Tubular secretion 3. Tubular reabsorption 1. Glomerular Filtration Development  Significantly reduced at birth.  Increases rapidly after birth.  Remains below adult levels until approximately 3–6 months of age. Effect Reduced filtration delays elimination of drugs cleared mainly by the glomerulus. Clinical Examples Examples of drugs cleared mainly by glomerular filtration include:  Aminoglycosides  Vancomycin  Digoxin (partially) 2. Tubular Secretion Definition Tubular secretion is an active transport process that moves drugs from the blood into the renal tubules. Development At birth:  Tubular secretion is poorly developed.  Tran
  18. Page 18. Development Tubular reabsorption is:  Relatively reduced in infants.  Matures later than glomerular filtration. Effect Reduced reabsorption allows more drug to remain in the urine. This partially compensates for the reduced GFR. However, because filtration and secretion are also immature, overall renal elimination remains reduced . Maturation of Renal Function Both glomerular and tubular functions mature progressively after birth.  Rapid improvement during the first weeks and months of life.  Most renal functions reach near-adult levels by approximately 6–8 months of age . Clinical Significance As renal function matures:  Drug clearance increases.  Drug half-life decreases.  Dose requirements increase. Frequent dose adjustments are necessary during infancy. Combined Effect of Immature Metabolism and Elimination Premature infants have:  Poor glucuronidation (hepatic metabolism)  Poor renal elimination Both processes contribute to chloramphenicol accumulation. Clinical Outcome Development of Gray Baby Syndrome . This illustrates how impaired metabolism and impaired elimination can together produce severe toxicity. Dose Adjustment Because renal clearance changes rapidly during infancy: Drug doses should always be adjusted according to:  Gestational age  Postnatal age  Current renal function  Clinical response Other Factors Affecting Drug Elimination Besides age, several additional factors influence renal drug elimination. Nutritional Status Malnutrition may alter: 
  19. Page 19. Pharmacodynamics In pediatric patients, pharmacodynamic responses differ from adults because of: 1. Developing organs 2. Immature receptors 3. Ongoing growth 4. Disease-specific physiological changes 5. Developmental changes in body systems Therefore, the same drug may produce: 1. Different therapeutic effects 2. Different adverse effects 3. Different dose requirements in children compared to adults. While prescribing drugs for children, physician should consider: 1. Drug efficacy 2. Drug toxicity 3. Developmental physiology 4. Disease-specific changes 5. Organ maturity 6. Long-term safety 7. Age-related adverse effects Failure to consider these factors may result in: 1. Therapeutic failure 2. Drug toxicity 3. Permanent developmental abnormalities 4. Growth impairment 5. Increased morbidity and mortality Physiological differences alter drug response. 1. Immature receptor systems 2. Different receptor sensitivity 3. Different receptor number 4. Immature nervous system 5. Immature endocrine system 6. Developing immune system 7. Rapid growth 8. Organ maturation 9. Disease-specific physiological differences Pathophysiological Differences Affect Drug Response Certain diseases behave differently in children than adults. These disease-specific differences alter: 1. Drug efficacy 2. Drug selection 3. Drug dosage 4. Therapeutic outcome Example 1: Asthma Children Adults Mostly reversible extrinsic (allergic) asthma Non-specific intrinsic bronchial hyperreactivity Respond well to allerg
  20. Page 20. Although infants are smaller, they require relatively higher maintenance doses than adults. Example 3: Insulin Insulin requirements are highest during adolescence. 1. Rapid body growth 2. Puberty 3. Increased growth hormone 4. Increased insulin resistance during adolescence Clinical significance Insulin doses should be adjusted frequently during puberty. Drug Toxicity in Pediatric Patients Drug toxicity varies according to age. Some adverse effects:  Occur only in newborns  Occur only in infants  Appear many years later  Affect growth and development Therefore, Long-term medication safety must always be considered in pediatric patients. Drug Pediatric Toxicity Reason Promethazine Severe respiratory depression Immature respiratory center Chloramphenicol Increased toxicity (Gray baby syndrome risk) Immature hepatic metabolism Codeine Respiratory depression and death CYP2D6 ultra-rapid metabolism Propylene glycol Hyperosmolality Poor metabolism in infants Benzyl alcohol Gasping syndrome Immature detoxification Ethanol-containing formulations CNS depression Immature metabolism Sorbitol GI disturbances Osmotic effects Cold medications Serious toxicity Lack of proven efficacy Tetracyclines Teeth staining and bone growth inhibition Calcium chelation Toxicity of Pharmaceutical Excipients Inactive ingredients may produce toxicity in children. Excipient Toxic Effect Propylene glycol Hyperosmolality Benzyl alcohol Gasping syndrome Ethanol CNS depression Sorbitol Osmotic diarrhea Fac
  21. Page 21. Factor Effect on Drug Therapy Examples Hepatic (Liver) Disease Decreases drug metabolism and increases toxicity Morphine, Propranolol, Theophylline Renal (Kidney) Disease Decreases drug excretion, causing drug accumulation Gentamicin, Vancomycin Cystic Fibrosis Increases drug clearance, requiring higher doses Tobramycin, Amikacin Obesity Alters drug distribution and dosing Vancomycin, Chemotherapy drugs Gastrointestinal Disease Reduces drug absorption Oral medications Hypoxemia Slows elimination of some drugs Amikacin Critical Illness Changes drug metabolism and clearance Phenytoin DRUG THERAPY IN CHILDREN (DOSAGE AND DOSE REGIMEN SELECTION) Drug therapy in children is more complex than in adults because children are continuously growing and developing. Drug doses must be individualized based on physiological factors such as age, body weight, body surface area (BSA), organ maturity, and disease state. Extrapolating adult doses to children can lead to underdosing or toxicity. 1. DRUG THERAPY IN CHILDREN General Principles of Pediatric Drug Therapy 1. Children are not small adults. 2. Drug doses should never be extrapolated directly from adult doses. 3. Pediatric dosing recommendations should always be obtained from a pediatric dosage handbook or pediatric formulary (e.g., BNF-C). 4. Pediatric formularies include: 1. Licensed drug use 2. Unlicensed drug use 3. Off-label drug use 4. Prescribing guidelines 5. Drug monographs METHODS OF PEDIATRIC DOSE CALCULATION (PPT of calculati
  22. Page 22. Dosing Interval Consider clearance, disease, and the child’s waking schedule Route/Formulation Choose the safest and most practical route; avoid unsuitable excipients Monitoring Assess efficacy, toxicity, growth, and therapeutic drug levels where indicated Drug Interactions Evaluate drug–drug and drug–food (especially milk) interactions Legal Considerations Check licensed, off-label, or unlicensed use and ensure evidence supports therapy ISSUES IN PEDIATRIC DRUG THERAPY Issue Key Points Pain Management Assess and treat pain using medicines and non-drug methods. Drug Administration Accurate dose measurement and safe administration are essential. Alteration of Dosage Forms Child-friendly formulations may require preparation or modification. Medication Adherence Ensure children and caregivers follow the prescribed treatment correctly. Dose Requirements Calculate doses based on weight or body surface area; avoid using adult doses directly. Drug Interactions Consider interactions with drugs, food, milk, and herbal products. Complementary Medicine Herbal medicines may interact with prescribed drugs; inform healthcare providers. Medication Safety Prevent errors through careful calculation, monitoring, and use of pediatric formulations. Adverse Drug Reactions Monitor for age-specific side effects and report suspected ADRs. Medication Errors Prevent errors through proper calculations, verification, and standardized procedures.

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