Geriatric & Pediatrics Pharmacology

Geriatric & Pediatrics Pharmacology

1. Geriatric & Pediatrics Pharmacology Pediatrics Pharmacology

2. Pediatrics age NEONATE First 4 week of life INFANCY Up to 1 year of age TODDLER 1-3 year of age PRESCHOL 3-6 years of age SCHOLE AGE OF CHILDERN 6-12 years of age ADOLESCENTS 12-18 years of age

3. Drug therapy in Pediatrics Pharmacokinetic process Absorption Distribution Biotransformation Elimination Pharmacodynamic Pediatric dosage forms and compliance

4. Pharmacokinetic process in pediatric patients Absorption: GI factors altering drug absorption: Prolonged gastric emptying time and irregular gut motility interfere with achievement of peak plasma conc of drug. Reduced transit time in upper intestine Presence of food decreases absorption of penicillin, paracetamol and ampicillin . High protein diet and low carbohydrate diet increases clearance of theophylline. Absorption of lipid soluble drugs reduced in infants as they have low conc of lipase and bile acid.

5. Oral absorption of various drugs in neonate compared with older children & adults Drugs Acetaminophen Ampicillin Diazepam Digoxin Penicillin G Sulfonamides Phenobarbital Phenytoin Oral absorption Decreased Increased Normal Normal Increased Normal Decreased Decreased

6. DISTRIBUTION The reversible transfer of drug from one location to another within the body (or) which involves reversible transfer of a drug between compartments.

7. FACTORS AFFECTING DRUGS DISTRIBUTION 1) Physicochemical properties of the drug Molecular size Oil water partition coefficient ( Kow ) Degree of ionization that depends on pKa 2) Physiological factors Organ or tissue size Blood flow rate Physiological barriers to the diffusion of drugs blood capillary membrane

8. . cell membrane specialized barriers blood brain barrier blood cerebrospinal fluid barrier placental barrier blood testis barrier 3) Drug binding in the blood 4) Drug binding to the tissue and other macromolecules 5) Miscellaneous factors related in mother e.g. Age Pregnancy Obesity Diet Disease states Drug interactions

9. Plasma protein binding Albumin α-glycoprotein and lipoproteins. Higher fraction of unbound (free) drug due to: Reduced concentration of plasma proteins in infancy Decreased affinity for drug binding e.g. digoxin , theophylline, High conc of endogenous compounds such as bilirubin , hormones transferred through placenta Reduced plasma proteins e.g. PEM, nephritic syndrome. Decreased binding of drugs in disease states.

10. Blood brain barrier In predicts Blood brain barrier is not well developed, so drug penetration is more in CNS e.g. bilirubin , lipid soluble drugs, morphine etc. Disease states in newborn & infants confound enhanced penetration e.g. Acidosis, hypoxia, hypothermia and hypoglycemia.

11. Biotransformation of drugs Drug metabolizing enzymes & immature in neonates, so drug metabolizing capacity limited. Phase 1 oxidation reaction & glucoronidation are immature at birth hence increased toxicity e.g. chloramphenicol produces gray baby syndrome. Plasma esterase reduced in infants leading to prolonged apnoea due to succinylcholine . Sulfat reaction more active in infants & children leading to more toxic metabolite of paracetamol . M etabolism is faster for certain drugs after 1st year so reduced t½. E.g. theophylline, phenytoin , carbamazapine , phenobarbitone .

12.  Elimination GFR is low and tubular transport not fully developed D rugs eliminated by kidney should be reduced in infants e.g. aminoglycosides , diuretics. t 1/2 of theophylline and prednisolone & reduced due to high plasma clearance. t 1/2 of ampicllin , digoxin & certain increased due to reduced renal clearance In patients with renal insufficiency dosage guides are based on serum creatinine levels.

13. Pediatric drug dosage Dose calculation on the basis of age, surface area and weight Based on age (young’s rule) Dose = Adult dose x Age ( years) Age +12 Based on weight Dose = Adult dose x weight(kg) 150

14. Pediatric dosing is commonly based on body surface area (BSA) Approximate dosage for a child = Body surface area of the child × adult dose 1.73 m² Dose Approximation based on Body Surface Area

15. Drug Therapy in Pediatric Patients: Promoting Adherence to a Medication Regimen Patient/ caregiver/ family need to know: Name of medication Purpose of medication Dosage size and timing (r/t meals, other meds, time of day, symptom onset, and so forth) Administration route and technique Special considerations Treatment duration Drug storage- safety for children in household Nature and time course of desired responses Nature and time course of adverse effects.

16. Geriatric Pharmacology

17. Geriatric Pharmacology Elderly people means older people age >65 years. 20% of hospitalizations due to medications they’re taking.

18. . Alzheimer`s disease Parkinsonism Stroke Vascular dementia Visual impairment specially cataracts and macular degeneration Atherosclerosis Arthritis Fractures Cancer Diabetes Heart failure

19. Drugs selection in Geriatric Pharmacokinetic process Pharmacodynamic

20. Effects of Absorption in geriatric Physiologic change Decreased gastric acidity Decreased gastrointestinal blood flow Delayed gastric emptying Slowed intestinal transit time General clinical effect Passive diffusion: for most drugs decreased Decreased active transport: Decreased bioavailability for some drugs Decreased first-pass effect: Increased bioavailability for some drugs

21. Effects of Distribution in geriatric Decreased Total body water Increased Plasma Conc. of water soluble drugs Lower doses are required: Lithium, digoxin , ethanol, etc Decreased Lean body mass Increased Volume Distribution, Longer (t½) of water soluble drugs Accumulation into fat of lipid soluble drugs Decreased Serum Albumin Increased unbound fraction of highly protein bound drugs Binds acidic drugs: warfarin , phenytoin , digitalis, etc Decreased Alpha1 Acid glycoprotein Increased unbound fraction of highly protein bound drugs Binds basic drugs: lidocaine and propranolol , etc

22. Effects of metabolisms in geriatric Difficult to predict, depends on General health & nutritional status Use of alcohol, medications Long term exposure to environmental toxins/pollutants Decreased liver mass/ hepatic blood flow Delayed/reduced metabolism of drugs Higher plasma levels Changes in phase 1 reaction those carry out microsomal p450 Decline in liver ability to recover from injury Lower serum protein levels Loss of protein binding

23. Effects of elimination in geriatric Physiologic change Decreased GFR Decreased renal blood flow Decreased renal mass General clinical effect Decreased clearance Increased (t½) of renal eliminated drugs

24. Pharmacodynamic changes in the elderly Changes in receptor affinity Changes in receptor number Post-receptor alteration Age-related impairment of homeostatic mechanisms Example: decreased baro -receptor reflexes

25. Age-related changes: Sensitivity to sedation and psychomotor impairment with benzodiazepines Level and duration of pain relief with narcotic agents Drowsiness with alcohol Sensitivity to anti-cholinergic agents Cardiac sensitivity to digoxin

26. Behaviour and lifestyle change Cognitive changes associated with vascular and other pathology Economic stresses with reduced income or due increased expenses of illness Loss of spouse

27. Major adverse drugs reactions in elderly Positive relationship between number of drugs taken and incidence Prescribing errors Polypharmacy Drug interactions with other prescriptions Unawareness of age related physiologic changes Drug usage errors OTC

28. Factor contribute adverse drugs reactions Polypharmacy How many prescription medications are too many? >4 or >5 Many elderly people receive 10 - 12 medications per day Heart Kidney Liver Thyroid

29. Economic factors Choose between food and medications OTC instead of expensive doctor visits Use of outdated medications Use of home remedies Share medications Nutritional supplements may affect how body metabolizes of medications

30. Polypharmacy Use of multiple medications Consume 30% of all prescription drugs [average person takes 4-5 prescription meds] Consume 40% of OTC Excessive use of drugs Overdose of a drug

31. Risks of problems: Polypharmacy primary reason for adverse reactions Medication errors Wrong drug, time, route Adverse effects from each drug Adverse interactions between drugs

32. Major group drugs reactions Sedative and hypnotic drugs Half life of many drugs benzodiazepine & barbiturates increases 50% between age 40 - 70 Adverse reactions like Ataxia & motor impairment mostly present

33. Narcotic analgesics Respiratory depression Constipation Urinary retention Hypotension Dizziness Confusion

34. Anti-pyretic and antidepressant Delirium Dementia Agitation Sedative effects Orthostatic Hypotension

35. Antipsychotics Jaundice Extra pyramidal symptoms Sedation, dizziness (can lead to falls) Orthostatic Hypotension Scaling skin on exposure to sunlight ( phenothiazines )

36. Tricyclic antidepressants Dry mouth Constipation Blurred vision Postural hypotension Dizziness Tachycardia Urinary retention

37. Cardiovascular drugs Dizziness Orthostatic Hypotension Hallucinations Bradycardia Arrhythmias

38. Diuretics Fluid/electrolyte disorders Dehydration Hypotension Thiazide diuretics can increase blood glucose levels (more insulin for diabetics ) Fatigue Loss of appetite Nausea Vomiting Visual disturbances Nightmares Nervousness Hallucinations Bradycardia Arrhythmias

39. Ant arrhythmias drugs Treatment of arrhythmias in elderly is particularly challenging due to Lack of good hemodynamic reserves Frequency of electrolyte disturbance High prevalence of coronary disease Confusion Slurred speech Light-headedness, seizures Hypotension

40. NSAIDs Gastric discomfort Bleeding Increased risk of toxicity Corticosteriods Sodium retention (may worsen HTN & CHF) Insomnia Psychotic behavior Osteoporosis (with impaired renal function)

41. Drugs use in Alzheimer's disease Progressive impairment of memory and cognitive function, Prevalence increases with age Pathological changes includes increased deposits of myeloid beta peptide in cerebral cortex due to progressive loss of neurons especially cholinergic neurons

42. Drugs use in glaucoma and mucosa dermatitis Cholinomimetics drugs because of evidence of loss of cholinergic neurons Tacrine , donepezil , rivastigmine & galantamine are used as these are cholinesterase inhibitors ADRs nausea, vomiting & peripheral cholinomimetics effects

43. Optimal pharmacotherapy Balance between overprescribing and under prescribing Correct drug Correct dose Targets appropriate condition for the patient Avoid “a pill for every ill” Always consider non-pharmacologic therapy

44. Patients factors of ADEs Polypharmacy Multiple co-morbid conditions Prior adverse drug event Low body weight or body mass index Age > 85 years Estimated CrCl <50 mL /min

45. Drug - drug interactions Absorption may be increased or decreased Drugs with similar effects can result additive effects Drugs with opposite effects can antagonize each other Drug metabolism may be inhibited or induced

46. Common Drug - drug interactions Combination Risk ACE inhibitor + potassium Hyperkalemia ACE inhibitor + K sparing diuretic Hyperkalemia , hypotension Digoxin + antiarrhythmic Bradycardia , arrhythmia Digoxin + diuretic Electrolyte imbalance; arrhythmia Diuretic + diuretic Electrolyte imbalance; dehydration Benzodiazepine + antidepressant Benzodiazepine + antipsychotic Sedation; confusion; falls CCB/nitrate/vasodilator/diuretic Hypotension

47. Common Drugs disease interaction Combination Risk NSAIDs + CHF Fluid retention Narcotics + constipation CHF exacerbation Anticholinergics + constipation Urinary retention Metformin + CHF Hypoxia, increased risk of lactic acidosis NSAIDs + gastropathy Increased ulcer and bleeding risk NSAIDs + HTN Fluid retention; decreased effectiveness of diuretics

48. Principles of drugs prescribing in elderly Avoid prescribing prior to diagnosis Start with a low dose Avoid starting 2 agents at the same time Reach therapeutic dose before switching or adding agents Consider non-pharmacologic agents

49. Preventing Polypharmacy Review medications regularly & each time a new medication started or dose is changed Maintain accurate medication records (include vitamins, OTC & herbals)

50. Client taking meds regulatory Suggest physician prescribe combination drugs or long-acting forms Fewer pills to remember Suggest re-evaluation of medications periodically Encourage client to use one pharmacy New medications Good information Encourage follow up

51. Compliance Prescriber must recognize Forgetfulness Prior experience Physical disabilities Recommendations to improve compliance Take careful drug history Prescribe only for a specific & rational indication Define goal of drug therapy High index of suspicion regarding drug reactions & food interactions Simplify drug regimen

52. Enhancing Medication Advance Avoid newer, more expensive medications Prescribe less expensive, generic drugs Simplify the regimen Utilize pill organizers or drug calendars Educate patient on medication purpose, benefits, safety & potential ADEs

53. Therapeutic drugs monitoring Most drugs have narrow therapeutic windows and thus toxicity is unlikely at 'normal doses'. Phenytoin Phenobarbital Warfarin Carbamazepine Gentamicin Vancomycin Digoxin Theophylline