![Infants Adults Elderly
Gastric pH High Normal[2 -3] High
Intestinal
surface area
Low More Low
Blood flow to
GIT
Low Normal Low
Enzyme activity Lower Normal Low
Bile acids &
Lipase
Low Normal Low
Absorption Altered pattern Normal Impaired
2. Gastrointestinal Function](https://image.slidesharecdn.com/druguseinpaediatricgeriatricpatients-171206044541/85/Drug-use-in-paediatric-amp-geriatric-patients-7-320.jpg)
Drug use in paediatric & geriatric patients
- 1. Drug use in paediatric & geriatric patients Dr Shinde Viraj Ashok Junior Resident – 2 Department of Pharmacology GMC Nagpur Guided by Dr V. M. Motghare Professor & Head Dept of Pharmacology GMC Nagpur Dr S. Pimpalkhute Lecturer Dept of Pharmacology GMC Nagpur
- 2. Introduction • Pharmacokinetics • Pharmacodynamics • Calculation of drug dose • Adverse drug reaction • a Drug use in paediatric • Pharmacokinetics • Pharmacodynamics • Main drug groups • Adverse drug reaction • Special aspects of geriatric pharmacology Drug use in geriatric
- 3. • Infancy and childhood are rapid stages of development , various organs, enzymes and body systems that handle the drugs and dosage are differ in time. • Important changes in responses to some drugs occur with increasing age in many individuals. Among these changes are increased incidence with advancing age of Several simultaneous diseases Nutritional problems Reduced financial sources
- 5. Drug Absorption 1. Blood Flow at the Site of Administration 2. Gastrointestinal Function 3. Rectal absorption 4. Transdermal absorption
- 6. 1. Blood Flow at the Site of Administration • Absorption from IM or SC injection in neonates - rate of blood flow to the muscle or subcutaneous area injected. • Physiologic conditions - reduce blood flow • Cardiovascular shock • Vasoconstriction due to sympathomimetic agents • Sick preterm infants - very little muscle mass. Complicated by - diminished peripheral perfusion to these areas. • Examples of drugs especially hazardous in such situations are • Cardiac glycosides • Aminoglycoside antibiotics • Anticonvulsants
- 7. Infants Adults Elderly Gastric pH High Normal[2 -3] High Intestinal surface area Low More Low Blood flow to GIT Low Normal Low Enzyme activity Lower Normal Low Bile acids & Lipase Low Normal Low Absorption Altered pattern Normal Impaired 2. Gastrointestinal Function
- 8. 3 Rectal absorption • Faster & more predictable • Diazepam solution is given rectally to control febrile seizures in children < 5yrs 4 Transdermal absorption • Faster • Skin is thin & more permeable
- 9. Drug Distribution • As body composition changes with development, the distribution volumes of drugs are also changed. • Preterm infants (1% of total body weight) - less fat than full-term infants (15% of total body weight). • Major factor determining drug distribution is drug binding to plasma proteins. • Albumin is the plasma protein with the greatest binding capacity.
- 10. Drug Distribution • Protein binding of drugs - reduced in the neonate. • Local anaesthetic drugs • Diazepam • Phenytoin • Ampicillin • Phenobarbital • Drugs given to a neonate with jaundice can displace bilirubin from albumin. Because of the greater permeability of the neonatal blood-brain barrier, substantial amounts of bilirubin may enter the brain and cause kernicterus. Example – sulfonamides • Bilirubin can displace a drug from albumin - raise the free drug concentration - would result in greater therapeutic effect or toxicity at normal concentrations. Example- phenytoin
- 11. Drug Metabolism • Metabolism of most drugs occurs in the liver . • Drug-metabolizing activities - cytochrome P450 dependent mixed-function oxidases and the conjugating enzymes - 50% of adult values in early neonatal life than later. • Neonates decreased ability to metabolize drugs - many drugs have slow clearance rates and prolonged elimination half-lives. • Example - Chloramphenicol can produce grey baby syndrome
- 12. Comparison of elimination half-lives of various drugs in neonates and adults.
- 13. Drug Metabolism • If Mother has received drugs (eg phenobarbital) that can induce early maturation of foetal hepatic enzymes. • Ability of the neonate to metabolize certain drugs will be greater than expected • During toddlerhood - metabolic rate of many drugs exceeds adult values, necessitating larger doses per kilogram than later in life. Example – Theophylline , phenytoin & carbamazepine. Less therapeutic effect And Lower plasma drug concentrations
- 14. Drug Excretion Glomerular Filtration Rate 1. Lower in neonates born before 34 weeks of gestation . 2. End of the third week – GFR is 50% of the adult value. 3. By 6 -12 months – GFR reaches adult Values (per unit surface area). • Example – Gentamicin & penicillin t½ is prolonged by 3 – 5 times t1/2 of drugs is increased
- 15. • Drugs that depend on renal function for elimination are cleared from the body very slowly in the first weeks of life. • During toddlerhood GFR exceeds adult values Example - Digoxin Larger doses per kilogram than in adults
- 16. Special Pharmacodynamic Features in the Neonate 1. Administration of indomethacin - Rapid closure of a patent ductus arteriosus 2. Infusion of prostaglandin E - Ductus to remain open, which can be lifesaving in an infant with transposition of the great vessels or tetralogy of Fallot (caused antral hyperplasia with gastric outlet obstruction) 3. Neonates - More sensitive to central depressant effects of opioids than are older children and adults - Necessitating extra caution when they are exposed to some narcotics (eg, codeine) through breast milk.
- 17. Elixirs Suspensions Flavoured solutions of drug in sugar syrup or glycerol along with higher proportion of alcohol Liquid medicament containing insoluble substances which are homogenously distributed throughout vehicle with or without help of suspending agents. Drug molecules are dissolved and evenly distributed. Undissolved particles and uneven distribution Shaking not required Shaking required First dose from the bottle and the last dose should contain equivalent amounts of drug First doses from the bottle may contain less drug than the last doses, with the result that less than the expected plasma concentration or effect of the drug may be achieved early in the course of therapy. e.g. vit B -complex elixir, lanoxin elixir e.g. milk of magnesia, phenytoin suspension
- 18. Reasons for non compliance • Measuring errors • Spilling • Spitting out • Discontinuation of antibiotics after feeling better
- 19. How to check compliance ?? 1. Random pill counts 2. Measurement of serum concentrations 3. Use of computerized pill containers
- 20. paediatric drug dose & its calculation 1. Most reliable paediatric dose information - provided by the manufacturer in the package insert. 2. In absence of explicit paediatric dose recommendations , an approximation can be made by methods based on age, weight or surface area. 3. Rules regarding this aren’t precise and should not be used if the manufacturer provides a paediatric dose. 4. When paediatric doses are calculated (either from one of the methods set forth below or from a manufacturers dose), the paediatric dose should never exceed the adult dose.
- 21. Surface Area, Age, & Weight • Calculations of dosage based on age or weight are conservative and tend to underestimate the required dose. • Doses based on surface area are more likely to be adequate. Age (youngs formula) Dose = Adult dose x Age(years) Age+ 12
- 22. Determination of drug dosage from surface area.
- 23. • Weight ( Clarks rule): OR Dose =Adult dose x Weight (kg) 70 Dose = Adult dose x Weight (lb) 150
- 24. Adverse drug reaction Children are growing and are more susceptible to adverse effects of drugs like 1. Corticosteroids – Suppression of growth 2. Androgens – Early fusion of epiphysis ( stunting of growth) 3. Tetracyclines - Discolouration & deformation of teeth 4. Phenothiazines - Dystonic reactions
- 26. Duniya bhi ajab sara –e - faani dekhi Har cheez yahaa'n ki aani jaani dekhi Jo aa ke na jaaye wo budhaapa dekha Jo jaa ke na aaye wo jawaani dekhi Meer Babar Ali Anees World is like a mortal motel everything here is sure fatal (But) saw never ending oldhood and forever gone young puerile
- 27. Pharmacologic changes Associated with aging Pharmacokinetics 1. Absorption Conditions associated with age that may alter the rate of absorption of drugs - 1. Altered nutritional habits 2. Greater consumption of non prescription drugs (eg, antacids and laxatives) 3. Changes in gastric emptying- slower in older persons (older diabetics)
- 28. 2. Distribution Elderly have ( compared to young adults) Reduced lean body mass Reduced body water ↑ fat as a percentage of body mass ↓ serum albumin ↑ serum orosomucoid (a-acid glycoprotein) Loading dose - Alteration Maintenance dose - Reduced because of reduced clearance of the drug.
- 29. Effect on plasma protein binding Plasma protein binding reduced due to Reduction in plasma albumin levels Changes in binding affinity due to ageing. Dose should be ↓ ↓
- 30. Drugs whose reduced protein binding in elderly leads to adverse reactions • Warfarin • Diazepam • Lorazepam • Phenytoin • Phenylbutazone • Tolbutamide
- 31. Effects of Aging on Volume of Distribution (Vd) Aging Effect Vd Effect Examples body water Vd for hydrophilic drugs ethanol, lithium lean body mass Vd for for drugs that bind to muscle digoxin fat stores Vd for lipophilic drugs diazepam, trazodone plasma protein (albumin) % of unbound or free drug (active) diazepam, valproic acid, phenytoin, warfarin plasma protein (1-acid glycoprotein) % of unbound or free drug (active) quinidine, propranolol, erythromycin, amitriptyline
- 32. • Examples: Water soluble drugs like digoxin: in elderly the Vd of digoxin is reduced so smaller dose in required to provide adequate digitalization. Lipid soluble drugs (lignocaine, thiopentone), Vd rises leading to increased half life of a drug: increase drug effect and toxicity. So dose should be reduced.
- 33. 3. Metabolism 1. ↓ in hepatic microsomal drug metabolising activity 2. ↓ hepatic blood flow 3. Heart failure - Alter the ability of the liver to metabolize drugs - By Reducing hepatic blood flow.
- 34. 3. Elimination • Age related decline of renal functional capacity is very important • Decline in creatinine clearance occurs in about two thirds of the population. • Serum creatinine alone is not an adequate measure of renal function. • Practical result Marked prolongation - half-life of many drugs eg - atenolol, gabapentin, digoxin, quinolones, lithium, aminoglycosides. Possibility of accumulation to toxic levels if dosage is not reduced in size or frequency.
- 35. • Rough correction can be made by using Patients from ages 40 through 80: • For women, the result should be multiplied by 0.85 (because of reduced muscle mass). Creatinine clearance (mL/min) = (140 -Age) x (Weight in kg) 72 xSerum creatinine in mg/dL
- 36. Lungs are important for the excretion of volatile drugs. ↓ respiratory capacity ↑ incidence of active pulmonary disease in the elderly Use of inhalation anaesthesia is less common and parenteral agents more common in this age group
- 37. Pharmacodynamic Changes • It was long believed that geriatric patients were much more sensitive to the action of many drugs, implying a change in the pharmacodynamic interaction of the drugs with their receptors • Most apparent changes Altered pharmacokinetics Diminished homeostatic responses. • Some data from animal studies suggest actual changes with age in the characteristics or numbers of a few receptors. • The most extensive studies suggest a decrease in responsiveness to ß-adrenoceptor agonists.
- 38. Diminished homeostatic responses are 1. Average blood pressure goes up - age Incidence of symptomatic orthostatic hypotension - Increases markedly. 2. Average 2- hour postprandial blood glucose level increases - 1 mg/dL for each year of age above 50. 3. Temperature regulation – impaired Hypothermia - Poorly tolerated by the elderly.
- 39. Behavioral & Lifestyle Changes Forgetting to take ones pills Result of cognitive changes.
- 40. Cns drugs Drugs to be avoided Reasons Safer alternatives a) Sedatives & hypnotics – antianxiety drugs -Diazepam -Barbiturates -Clorazepate -Prolongation of half life -highly sensitive leading to ataxia , loss of postural reflex and fall Oxazepam, lorazepam –do not form active metabolites -have short half life -less sedating b)Analgesics 1)Opioids Elderly very sensitive to respiratory depressant effects Pentazocine be avoided -Codeine , meperidine, morphine. -Titrate optimum dose and frequency of administration. 2)NSAIDs -Used very carefully may cause GIT bleeding and analgesic nephropathy -Indomethacin avoided due to CNS side effects. -Ibuprofen , nimesulide -Corticosteroids may be used along with calcium and Vit-D supplements.
- 41. Cns drugs Drugs to be avoided Reasons Safer alternatives c)Antipsychotics -Phenothiazine analogues -Haloperidol analogues Avoided -greater risk of extrapyramidal side effects and postural hypotension -Elderly very sensitive to their anticholinergic side effects Thioridazine , olanzapine , risperidone , ziprasidone are safe. d) Antidepressants -Tricyclic antidepressants -due to postural hypotension & anticholinergic side effects -SSRIs -elimination not affected with ageing. e)Antimania -Lithium -Renal toxicity -carbamazepine or valproic acid.
- 42. Cns drugs Drugs to be avoided Reasons Safer alternatives f) General anaesthetics -Halothane -Thiopental -more sensitive to halothane more prone to its hepatotoxicity -very sensitive to thiopental -midazolam , propofol -isoflurane - expensive g)Drugs for Alzheimer’s disease -Tacrine -sensitive to CNS toxicity having anti- cholinergic effects -hepatotoxicity -Donepezil , memantine , galantamine are preferred , being safer.
- 43. CVS drugs Drugs to be avoided Reasons Safer alternatives a) Cardiac glycosides -Digoxin -increase sensitivity to toxic arrhythmogenic actions of digoxin -loading dose=reduced -maintenance dose=reduced. b) Antiarrhythmic drugs -Disopyramide -Quinidine -Quinidine clearance decreased and half life prolonged -Disopyramide avoided =its anti- muscarinic effects -dose must be reduced. c) Platelete inhibitors -Dipyridamole -postural hypotension, coronary steal -clopidogrel or aspirin
- 44. Antihypertensive Drugs 1. Hypertension - Treated vigorously in the elderly. 2. Thiazides - First step in drug therapy 3. Hypokalemia , hyperglycemia, and hyperuricemia caused by these agents are more relevant in the elderly because of the higher incidence in these patients of arrhythmias, type 2 diabetes, and gout. 4. Calcium channel blockers – Effective and safe if titrated to the appropriate response Useful in patients who also have atherosclerotic angina. 5. Beta blockers - potentially hazardous in patients with obstructive airway disease - considered less useful than calcium channel blockers in older patients unless heart Failure is present.
- 45. Drugs for Respiratory Diseases Drugs to be avoided Reasons Safer alternatives -Ephedrine -Isoproterenol -Theophylline -high BP, tachycardia -tremors -CNS stimulants -Salbutamol , beclomethasone Antibiotics Drugs to be avoided Reasons Safer alternatives -Penicillins -Cephalosporins -Fluoroquinolones -decline in renal function -sensitive to peripheral neuritis -Ceftriaxone or cefoperazone excreted through bile
- 46. Anti-diabetic drugs Drugs to be avoided Reasons Safer alternatives -Chlorpropamide -Glibenclamide -half lives increased in elderly -serious hypoglycaemic episodes -fluid retention -Glipizide , gliclazide And natiglinide + metformin may be used
- 47. Adverse drug reactions in elderly • Single drug – 10 % chances of ADR Ten drug – nearly 100 % chances of ADR • Patients may see several different practitioners for different conditions and accumulate multiple prescriptions for drugs with overlapping actions. • Reasons for high incidence of ADR include • Errors in prescribing on the part of the practitioner. • Errors in drug usage by the patient.
- 48. Adverse drug reactions elderly • It is useful to Conduct a brown bag analysis in such patients. • Brown bag analysis consists of asking the patient to bring to the practitioner a bag containing all the medications, supplements, vitamins, etc, that he or she is currently taking
- 49. Practical aspects of geriatric pharmacology • Quality of life in elderly patients can be greatly improved and life span can be prolonged by the intelligent use of drugs. • Expense of drugs can be a major disincentive in patients receiving marginal retirement incomes who are not covered or inadequately covered by health insurance. • Nonadherence may result from forgetfulness or confusion, especially if the patient has several prescriptions and different dosing intervals.
- 50. Practical aspects of geriatric pharmacology • Prescriptions written by several Different practitioners - no attempt to design integrated regimens that use drugs with similar dosing Intervals for the conditions being treated. • Non adherence may also be deliberate. A decision not to take a drug may be based on prior experience with it.
- 51. Errors in drug taking are caused by physical disabilities. 1. Arthritis 2. Tremor 3. Visual problems may all contribute. 4. Liquid medications that are to be measured by the spoonful are especially inappropriate for patients with any type of tremor or motor disability. Practical aspects of geriatric pharmacology
- 52. • Cataracts and macular degeneration occur in a large number of patients over 70 Labels on prescription bottles should be large enough for the patient with diminished vision to read or Colour coded if the patient can see but can no longer read Practical aspects of geriatric pharmacology
- 53. Drug therapy has considerable potential for both helpful and harmful effects in the geriatric patient. The balance may be tipped in the right direction by adherence to a few principles: 1. Take a careful drug history. 2. Prescribe only for a specific and rational indication. Do not prescribe omeprazole for dyspepsia. 3. Define - Goal of drug therapy. 4. Maintain a high index of suspicion regarding drug reactions and interactions. 5. Simplify the regimen as much as possible.
- 54. Conclusion Special caution should be taken while prescribing to paediatric and elderly age group taking in to consideration their altered pharmacokinetic and pharmacodynamics parameters Elderly patients are generally taking medicines for two or three associated chronic diseases (hypertension, diabetes , psychiatric illness etc) possibility of drug drug interaction should be given due attention while prescribing to them. Paediatric patients should not be treated as if they are mini adults ( simply modifying dose using body weight or surface area formula is not sufficient).
- 55. References • Katzungs basic & clinical pharmacology 12th edition • Principle of pharmacology ,S.K Sharma 2nd edition • Pharmacology & pharmacotherapeutics, Satoskar 23rd edition
- 57. B. Gastrointestinal Function • In full-term infants, gastric acid secretion begins soon after birth and increases gradually over Several hours. • In preterm infants, the secretion of gastric acid occurs more slowly, with the highest concentrations appearing on the fourth day of life. Therefore, drugs that are usually partially or totally inactivated by the low pH of gastric contents should not be administered orally. • Gastric emptying time is prolonged (up to 6 or 8 hours) in the first day or so after delivery - drugs absorbed primarily in stomach may be absorbed more completely than anticipated. • Drugs absorbed in the small intestine, therapeutic effect may be delayed • amount of drug absorbed in the small intestine - unpredictable; . Peristalsis in the neonate is irregular and may be slow. • more than the usual amount of drug may be absorbed if peristalsis is slowed, and this could result in potential toxicity from an otherwise standard dose.
- 58. • An increase in peristalsis, as in diarrheal conditions, tends to decrease the extent of absorption, because contact time with the large absorptive surface of the intestine is decreased. • Gastrointestinal enzyme activities - lower in the newborn than in the adult. • Activities of a-amylase and other pancreatic enzymes in the duodenum are Low in infants up to 4 months Of age. • Neonates low concentrations of bile acids and lipase -decrease the absorption of lipid-soluble drugs.
- 59. Paediatric dosage forms & compliance • Elixirs - alcoholic solutions - drug molecules are dissolved and evenly distributed. No shaking is required, and unless some of the vehicle has evaporated , the first dose from the bottle and the last dose should contain equivalent amounts of drug. • Suspensions - undissolved particles of drug that must be distributed throughout the vehicle by shaking. If shaking is not thorough each time a dose is given , the first doses from the bottle may contain less drug than the last doses, with the result that less than the expected plasma concentration or effect of the drug may be achieved early in the course of therapy. Conversely, Toxicity may occur late in the course of therapy , when it is not expected.
- 60. • Uneven distribution is a potential cause of inefficacy or toxicity in children taking phenytoin suspensions . • Compliance may be more difficult to achieve in paediatric practice than otherwise, since it involves not only the parents conscientious effort to follow directions but also such practical matters as measuring errors , spilling, and spitting out. For example, the measured Volume of teaspoons ranges from2.5 to 7.8 mL . • Parents should obtain a calibrated medicine spoon or syringe from the pharmacy. These devices improve the accuracy of dose measurements and simplify administration of drugs to children.
- 61. • Parents may not always be able to say with confidence how much of a dose the child actually received. • Parents must be told whether or not to wake the infant for its every- 6-hour dose day or night. • Matters should be discussed and made clear, and no assumptions should be made about what the parents may or may not do • Noncompliance frequently occurs when antibiotics are prescribed to treat otitis media or urinary tract infections and the child feels well after 4 or 5 days of therapy. • Parents may not feel there is any reason to continue giving the medicine even though it was prescribed for 10 or 14 days. This common situation should be anticipated so the parents can be told why it is important to continue giving the medicine for the prescribed period even if the child seems to be cured.・
- 62. • Practical and convenient dosage forms and dosing schedules should be chosen to the extent possible. • Whenever a drug does not achieve its therapeutic effect, the possibility of noncompliance should be considered.
- 63. Challenges of Geriatric Pharmacotherapy • New drugs available each year • Advanced understanding of drug-drug interactions • Multiple co-morbid states • Polypharmacy • Medication compliance • Effects of aging physiology on drug therapy • Medication cost
- 64. Some potential strategies for the prevention or treatment of Alzheimer’s disease.
- 65. Major drug groups CENTRAL NERVOUS SYSTEM DRUGS Sedatives & hypnotics • Half lives of many benzodiazepines and barbiturates increase by 50 - 150% between ages 30 and 70 change occurs during the decade from 60 to 70. • Toxicities of these drugs, ataxia and other signs of motor impairment should be particularly watched for in order to avoid accidents.
- 66. Analgesics • Opioid analgesics show variable changes in pharmacokinetics with age. • Elderly - more sensitive to respiratory effects of these agents because of age-related changes in respiratory function.
- 67. Antipsychotic & Antidepressant Drugs • Traditional antipsychotic agents (phenothiazines and haloperidol) Have been very heavily used (and probably misused) in the management of a variety of psychiatric diseases in the elderly.
- 68. Drugs Used in Alzheimer’s Disease • Memantine binds to NMDA receptor channels in a use-dependent manner and produces a non competitive blockade. • Drug appears to be better tolerated and less Toxic than the cholinesterase inhibitors. • Memantine is available As Namenda in 5 and 10 mg oral tablets.
- 69. • Positive Inotropic Agents 1. Heart failure is a common and particularly lethal disease in the elderly. 2. Toxic effects of digoxin - dangerous in the geriatric population- elderly are more susceptible to arrhythmias. 3. Because the drug is cleared mostly by the kidneys, renal function must be considered in designing a dosage regimen. 4. Hypokalemia, hypomagnesemia, hypoxemia (from pulmonary disease), and coronary atherosclerosis all contribute to the high incidence of digitalis-induced arrhythmias in geriatric patients.
- 70. Antiarrhythmic Agents 1. Treatment of arrhythmias in the elderly is challenging because of the lack of good hemodynamic reserve. 2. The Frequency of electrolyte disturbances, and the high prevalence Of Severe coronary disease. 3. Clearances of quinidine and procainamide decrease and their half-lives increase with age. 4. Disopyramide should probably be avoided in the geriatric population because its major toxicities antimuscarinic action, 1. leading to voiding problems in men 2. negative inotropic cardiac effects, leading to heart failure 5. Measures (such as anticoagulant drugs) should be taken to reduce the risk of thromboembolism in chronic atrial fibrillation.
- 71. Antimicrobial drugs • Age-related changes contribute to the high incidence of infections in geriatric patients. • In lungs, a major age and tobacco dependent decrease in mucociliary clearance significantly increases susceptibility to infection. • In urinary tract, the incidence of serious infection is greatly increased by urinary retention and catheterization in men. • Decreased renal function; because most of the ß-lactam, aminoglycoside, and fluoroquinolone antibiotics are excreted by this route, important changes in half-life may be expected. • Aminoglycosides cause concentration- and time-dependent toxicity in the kidney and in other organs.
- 72. Anti-inflammatory drugs • Osteoarthritis is a very common disease of the elderly. • Nonsteroidal anti-inflammatory agents (NSAIDs) - used with special care in geriatric patients because they cause toxicities to which the elderly are very susceptible. • Aspirin - gastrointestinal irritation and bleeding. • Newer NSAIDs - renal damage may be irreversible. • Corticosteroids are extremely useful in elderly patients who cannot tolerate full doses of NSAIDs - but they consistently cause a dose- and duration- related increase in osteoporosis.
- 73. Ophthalmic drugs Macular Degeneration • Age-related macular degeneration (AMD) is the most common cause of blindness in the elderly in the developed world.