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Drug therapy in pediatric and geriatric age groups

The document discusses the principles and challenges of drug therapy in pediatric and geriatric populations, highlighting pharmacokinetic and pharmacodynamic differences between these age groups. It outlines the importance of careful dose calculation, compliance issues, and specific adverse drug reactions associated with different age groups. Additionally, it emphasizes the necessity for thoughtful prescribing practices to minimize potential drug-related complications.

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Drug Therapy In Pediatric & Geriatric Age Groups Dr Naser Tadvi
Objectives • Discuss the principles of prescribing in pediatric and geriatric age groups. • Discuss the pharmacokinetic and pharmacodynamics differences in pediatric, geriatric and adult age groups. • Describe different paediatric dosage forms & compliance in children. • Discuss important adverse drug reactions occurring in geriatric & pediatric age groups.
Pharmacokinetic differences in children (Absorption) • Gastro-intestinal(GI) absorption slower in infancy, but absorption from intra-muscular injection is faster. • In neonates common practice to use iv preparations • Infant skin is thin and percutaneous absorption can cause systemic toxicity (example if potent steroids are applied too extensively)
• Body fat content in infants low, water content is high • Lower Vd of fat soluble drugs (diazepam) in infants • ↓Plasma protein binding of drugs in neonates (Kernicterus due to displacement of Bilirubin by sulfonamides) • Blood–brain barrier is more permeable in neonates and young children, leading to an ↑risk of CNS adverse effects. Pharmacokinetic differences in children (Distribution )
• At birth, the hepatic microsomal enzyme system is relatively immature particularly in preterm infant but after first four weeks it matures rapidly • Conversely hepatic drug metabolism increased in older infants and children • Phenobarbitone metabolism faster in children than adults • Drugs administered to the mother can induce neonatal enzyme activity (e.g. barbiturates). Pharmacokinetic differences in children (Metabolism )
Comparison of elimination half lives of various drugs in neonates and adults
Clinical significance • Phenobarbital, when given to pregnant women near term, can induce fetal hepatic enzymes responsible for the glucuronidation of bilirubin. • Chloramphenicol can produce grey baby syndrome in neonates
• All renal mechanisms (filtration, secretion and reabsorption) are reduced in neonates. • Renal excretion of drugs relatively reduced in new born Pharmacokinetic differences in children (Excretion )
Pharmacodynamics • Paradoxical effects of some drugs – Hyperkinesia with phenobarbitone – Sedation of hyperactive children with amphetamine • Augmented responses to warfarin in prepubertal patients
Principles of prescribing in children  Calculate doses for drugs based on weight of patients.  Use well established drugs  Give proper instructions to parents  Keep all drugs out of reach of children  Use antibiotics sparingly and only when required.  Avoid prolonged treatment with drugs that have delayed complications (Steroids).  use suitable dosage forms  Keep in mind PK & PD differences
How to calculate pediatric dose
Pediatric dosage form and compliance  Children < 5 years may have difficulty in swallowing even small tablets, and hence oral preparations which taste pleasant are often necessary to improve compliance.  Pressurized aerosols (e.g. salbutamol inhaler) are only practicable in children over the age of ten years. Nebulizers may be used.  Children find iv infusions uncomfortable.  Rectal administration is convenient alternative (e.g. metronidazole to treat anaerobic infections). Rectal diazepam is particularly valuable in the treatment of status epilepticus. Rectal administration should also be considered if the child is vomiting.
Important Adverse effects in children • With a few notable exceptions, drugs in children generally have a similar adverse effect profile to those in adults. • Examples of Some specific ADR 1. chronic corticosteroid use: inhibit growth 2. Tetracyclines : staining and occasionally dental hypoplasia 3. Fluoroquinolone(ciprofloxacin): damage growing cartilage 4. Metoclopramide: Dystonias more frequently than in adults 5. Valproate : hepatotoxicity is increased in young children 6. Aspirin: Reye’s syndrome
Geriatric Age group • Let us then rejoice, • While we are young. • After the pleasures of youth • And the tiresomeness of old age • Earth will hold us.
Physiological changes in elderly Variables Physiological change Body composition ↓Total body water ↓ Lean body mass ↑ Body fat ↓ Plasma albumin ↑ α1 acid glycoprotein Renal ↓ GFR ↓ Renal blood flow ↓ tubular secretion
Pharmacokinetic changes in elderly Pharmacokinetic parameters Pharmacokinetic changes Absorption •↓ first pass metabolism so increased bioavailability of propranolol & morphine •↓ absorption by sublingual route due to reduced blood supply to oral mucosa
Pharmacokinetic parameters Pharmacokinetic changes Distribution •↓ serum albumin: ↑ free drug conc of acidic drugs •↑α1 acid glycoprotein : ↓ free fraction of basic drugs • ↓ Vd of water soluble drugs (acetaminophen, ethanol) • ↑ Vd of lipid soluble drugs (diazepam, lidocaine)
Drugs bound to albumin Drugs bound to alpha1 acid glycoprotein Barbiturates, benzodiazepines Quinidine , verapamil, lidocaine , di-isopyramide Valproic acid , phenytoin Bupivacaine Penicillins, sulfonamides , tetracyclines B- blockers, methadone , prazosin NSAIDS Imipramine Tolbutamide Warfarin
Pharmacokinetic parameters Pharmacokinetic changes Metabolism •↓ Phase I oxidative pathways phase II conjugation pathways : no change •↓ drug clearance & ↑ t1/2 of oxidatively metabolized drugs (Diazepam, piroxicam, theophylline, quinidine) • Phase II metabolism of drugs like oxazepam, lorazepam is unaffected
↓ Pharmacokinetic parameters Pharmacokinetic changes Excretion •↓ Renal clearance of drugs •↑ t1/2 • Creatinine clearance as guide to dose adjustment • ↓ respiratory capacity & ↑ incidence of pulmonary diseases use of IV rather than inhalational anaesthetics preferred
Some drugs with reduced renal elimination in elderly • Penicillins, Tetracyclines , Aminoglycosides • Cimetidine • Digoxin • Atenolol • Lithium • Diuretics • Clonidine , captopril, enalapril
Dose calculation • Cockroft gault formula: – For females multiply above value by 0.85 • Corrected dose = Normal dose x pt CrCl Normal CrCl CrCl = (140-age) x weight [kg] (sCr x 72)
Pharmacodynamic Changes: • Greater sensitivity to medications affecting the CNS (benzodiazepines and opioids) • More confusion with cimetidine • Increased incidence of postural hypotension • Reduced clotting factor synthesis: require reduced dose of warfarin • Increased toxicity from NSAIDS • Increased incidence of allergic reactions
General principles for prescribing in elderly o Think about the necessity for drugs. o Avoid drugs with negligible or doubtful benefits. o Think about the dose. o Think about drug formulation. o Assume any new symptoms may be due to drug side- effects. o Take a careful drug history. o Use fixed combinations of drugs rarely. o Check Compliance. o Think before adding a new drug to the regimen. o Stopping is as important as Starting.
Geriatric Prescribing - ADRs ADRs and Age o Incidence of ADR increases with age o Elderly receive more medicines o Incidence of ADR increases the more prescribed medicines taken o For patients aged>50 yrs o ADR rates – 5% for 1 or 2 medicines o Increased to 20% when >5 medicines Most frequent drug classes causing ADRs o Cardiovascular Drugs o Analgesics (opioid mainly) o Antibiotics o Hypoglycemic agents o Psychotropic agents o Anticoagulants
• Attempt to prescribe a drug that will treat more than one existing problem Examples: – calcium channel blocker or beta blocker to treat both hypertension and angina pectoris – ACE-inhibitor to treat both hypertension, heart failure, and or for renal protection in diabetes – Alpha-blocker to treat both hypertension and prostatism Prescribing Pearls
Golden rule for drug therapy in elderly • Smallest number of drugs • In lowest possible doses • For shortest possible time • In simplest regimen
Summary • principles of prescribing in pediatric and geriatric age groups. • pharmacokinetic and pharmacodynamics differences in pediatric, geriatric and adult age groups. • Paediatric dosage forms & compliance in children. • Important adverse drug reactions occurring in geriatric & pediatric age groups.
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