DRUG DOSING IN ELDERLY

1. DRUG DOSING IN ELDERLY K.P. ARUN LECTURER DEPARTMENT OF PHARMACY PRACTICE JSS COLLEGE OF PHARMACY OOTY

2. INTRODUCTION • Ever increasing population of aged people (>65yrs) • Elderly have multiple disorders and complaints partly due to aging and partly due to disease process and consume more medicine than the rest of the population (about 3 time the normal adult) • About at half of all drugs used are for the elderly • ADRs are more common in elderly • Advancing age accompanied by PK & PD changes which together with impairment of feed back mechanismsand coexisting disease contribute to an increased sensitivity to a particular drug and corresponding increase in adverse drug reactions

3. INTRODUCTION… • Cellular mass decreased by about 30% during aging which are irreversible, inevitable and additive leading distinct physiological changes • PK changes in ADME • PD – for most drugs receptors sensitivity ↑ in advancing age, whereas ↓ in number of receptor • Coexisting diseases • Poly pharmacy • Compliance

4. INTRODUCTION… SPECIAL CONSIDERATIONS OF THE ELDERLY AS UNIQUE GROUP WITHIN THE POPULATION

5. ABSORPTION • The component less affected by age • ↓ in gastric acid secretion, GI blood flow, pancreatic trypsin, GI motility and number of absorbing cells → altered dissolution rate , possible decrease in absorption rate, long time for onset on effect of drug • Vitamin, mineral and nutrient deficiencies common due to active absorption of these compounds • Drugs mostly absorbed passively • Active absorption is affected

6. DISTRIBUTION • Reduction in • Mean body mass • Total body water • Plasma albumin • Total protein concentration remains same • Increase in body fat leading to increase in Vd of lipid soluble drugs and decrease in Vd of hydrophilic drugs • Delayed onset followed by accumulation and overdosing in multiple dosing situations • Increase in free fraction of highly bound acidic drugs and possible decrease in free fraction of basic drugs • Theophylline, Warfarin, Phenytoin, Diazepam, Barbiturates show increase in t1/2 • Digoxin, Lithium and Cimetidine show increased plasma level

7. METABOLISM • Decrease in hepatic cell mass (28 % and 44 % in men and women by the age of 91) • Decrease in hepatic blood flow for about 35 % • Possible decrease in enzyme inducibility, Acetylation, Glucuronitation • Apparently decreased metabolism and clearance of certain drugs (Propranolol, Labetalol, Verapamil, Metoclopramide, Opioids, Diazepam) • Other factors like, smoking, alcohol, disease conditions, co administered drugs like erythromycin can can inhibit the metabolism still further

8. EXCRETION • When compared to 10 years, at the age of 40 years GFR reduced by 10% and 6-10% is reduced in every 10 years after this age • At the age of 90 years about 30-40% reduction in GFR occur • ↓ in renal plasma flow and active secretion • ↓ in excretion of renally cleared drugs (Digoxin, Penicillin, Vancomycin, Lithium, Amino glycosides) • Coexisting diseases like HT, DM include renal compromise • Creatinine Clearance (ml/min) For male = 140 – age(years) x Weight(Kg) / 72 x Serum Cr (mg/dL) For female = 140 – age(years) x Weight(Kg) / 85 x Serum Cr (mg/dL)

9. PHARMACODYNAMICS • Change in receptor binding decrease in number of receptors or mechanisms • Organ specific age change • Changes in CNS enzyme activity • Possible altered second messenger function • Reduction in baroreceptor reflex sensitivity • ↓ receptor response (β – adrenergic agonists blockers) • ↑ receptor response (Morphine, Diazepam)

10. SUMMARY OF PHYSIOLOGIC AND PATHOLOGIC CHANGES AND THEIR PK AND THERAPEUTIC CONSEQUENCES IN THE GERIATRIC PATIENTS

13. SUMMARY… • The interrelated factors and the relationship that exists among them can be described mathematically Effect αf CtαCP αF D (t1/2) / Vss f = Sensitivity of receptor Ct = Concentration of drug at the site of action Cp = Concentration of drug in plasma FD = Bioavailability t1/2 = half life Vss = Vd at Steady state

14. ADVERSE DRUG REACTIONS • ADR are more common in elderly (20-25% more then in the young) • They are mostly dose related rather than idiosyncratic • Drugs that causes postural hypotension (antihypertensive) ataxia (benzodiazepines) volume and electrolyte imbalances (diuretics) are more prone to cause ADR in elderly • Poly pharmacy results in increase drug interaction, ADR and non compliance • Increase in number of drugs predisposes the patients to drug disease interaction • Β – blocker eye drops for glaucoma may lead to a worsening of asthma or CCF also called the prescribing cascade

15. COMPLIANCE • The extent to which a person behavior coincides with medical advice • Types: • Not having prescription filled • Taking the wrong dose • Incorrect time • Forgetting to take a medication • Intentional noncompliance • Ceasing medication so soon DRUGS TO LOOK OUT FOR IN ELDERLY: • Cardiovascular drugs • Antihypertensive drugs (Thiazides ,β – blockers, CCBs, ACE inhibitors) • NSAIDs • Benzodiazepines

16. THE PHARMACIST • The pharmacists are in a unique position to influence appropriate medication at both the prescriber and patient level • Patient counseling and monitoring • Use his skills during refilling to assess the effects of the medication and inform the physician • Enhance compliance • A multi-disciplinary approach required

17. GUIDELINES FOR PRESCRIBING FOR ELDER PEOPLE • Appropriate treatment requires adequate clinical assessment and accurate diagnosis • Problem oriented prescribing i.e., treat only the disorder that need to be treated • Keep drug regimens simple • Use low doses and increase slowly • Avoid polypharmacy • Consider potential drug interactions • Provide patients with clear instructions both verbal and in writing • Review patients and their medications regularly • If in doubt, don’t prescribe