Pitfalls in Prescribing for older people

Christopher PattersonMcMaster University,

Hamilton, OntarioCanada

Objectives

• Pharmacokinetic changes with age

• Pharmacodynamic changes

• Polypharmacy and interactions

• Underprescribing

• Medication errors

Pharmacokinetics and aging

• Absorption

• Distribution

• Metabolism

• Excretion

• And…therapeutic effect at receptor level

Absorption

• Changes in gastric pH (higher with aging)

• Changes in GI transit time (increased with aging)

• Changes in intestinal absorptive area (reduced)

BUT

Very little change in absorption of drugs

Absorption

• Type of preparation often more important e.g. absorption of phenytoin:

liquid>tablet>capsule

• Interactions important e.g. calcium and levothyroxine

Distribution

• Chronic illness associated with lower levels of serum albumin

• Highly protein bound drugs may be affected by acute displacement eg. Warfarin and sulphonyureas

• Acid 1 alpha glycoprotein elevated in acute illness may affect binding e.g.amitriptyline

Changes in body composition with aging

Water soluble vs. fat soluble drugs

H2O soluble-hydrophilic• Atenolol• Hydrochlorthiazide• Sotalol• Theophylline• Triazolam• Aminoglycosides

Fat soluble-lipophylic• Amiodarone• Diazepam• Haloperidol

Phenytoin: zero order kinetics saturation of protein binding sites

Metabolism

• Mostly in liver• Phase 1 Oxidation, reduction, hydrolysis Most affected by aging• Phase 2 Acetylation, glucuronidation, sulfation,

glycineMostly unaffected by aging

Metabolism

Changes in hepatic metabolism with age

Serum t ½ (hours) and agePhase 1 metabolism

Young Old

Amitriptyline 14.7 27.2

Diltiazem 3.8 4.2

Diazepam 20 75

Warfarin 3.7 4.4

Serum t ½ unchanged:phase 2 metabolism

Glucuronidation • Oxazepam• Temazepam• Lorazepam Oxidation • Metoprolol Acetylation• Hydralazine

Elimination

• Elimination represents clearance of drug from the body

• May be predominantly renal (water soluble drugs and metabolytes)

• Biliary (e.g. some metabolytes of digoxin)

• Other

Renal function and aging

Drugs predominantly eliminated via renal route

• Digoxin

• Aminoglycoside antibiotics

• Lithium

• Spironolactone

• Vancomycin

Calculation of creatinine clearanceCockcroft-Galt equation

Pharmacodynamic changes with aging

Increased receptor sensitivity

• Opioids

• Some benzodiazepines (e.g. nitrazepam)

Reduced response to β adrenergic receptors

• Isuproteronol

Impaired homeostasis

• Antihypertensives (e.g. prazosin)

Adverse Drug Reaction

Idiosyncratic

• Unpredictable

Exaggeration of pharmacological effects

• Predictable

• Start low, go slow!

Incidence of Preventable AEs(Thomas & Brennan BMJ 2000;320:741)

Event type Incidence ages

16-64

Incidence age >65

Diagnostic 0.22 0.27

Operative 0.76 0.99

Procedure 0.13 0.69*

Drug 0.17 0.63*

Fall 0.01 0.10*

Drug interactions

Absorption

• Calcium and iron salts

Metabolism

• Warfarin plus metronidazole

Pharmacodynamic

• E.g. Glyceryl trinitrate and sildanefil

Conditions that affect drug metabolism or action

• Malnutrition

• Heart failure

• Hepatic dysfunction (especially parenchymal disease cirrhosis)

• Renal impairment or failure

• And many others

Some drugs to be used with extreme caution in older people

• Anticholinergic drugs (antihistamine H1, tricyclic antidepressants etc.)

• Long acting benzodiazepines (diazepam, chlordiazepoxide )

• Theopylline

• NSAIDs (indomethacin, )

• Some opiates (pethidine, meperidine)

• Antipsychotics

Antipsychotics and sudden death

Ray W et al N Engl J Med 2009; 360: 225

SUMMARY

• Changes in pharmacokinetics important• Especially renal changes (do calculate

Cr/cl)• Pharmacodynamic changes not always

pedictable• Watch for drug interactions and side

effects• Do not overlook effects of illness plus

aging

Serum t ½ (hours) and age

Young Old

Amitriptyline 14.7 27.2

Diltiazem 3.8 4.2

Sotalol 7.1 11.4

Warfarin 3.7 4.4

Undertreatment (Grymonpre & Patterson CPS 2006)

Medication class Percent of optimal

ASA in ischemic heart disease

50

Beta blockers after MI 50

Hypertension 50

Warfarin for atrial fibrillation 15-44

Antidepressants 10-30

Osteoporosis after hip # 10

Adverse Event

• “An unintended injury or complication which results in disability, death or prolonged hospital stay and is caused by health care management”

• Wilson R et al Med J Aus 1995;163:458

Adverse Events

• Incidence in hospital 2.9-16.6%

• Meta analysis of incidence 6.7%

• Adverse drug events 50%

• Operative complications 30%

• Nosocomial infections 20%

• Preventable 30-60%

Medication Errors

• Sins of commission: wrong drug, wrong dose, wrong patient, wrong time, or wrong route

• Sins of omission: not providing appropriate medication

• Many errors do not cause adverse events (we are a very resilient species…)

Detection of Adverse Events

• Voluntary reporting 0.7%

• Computer monitoring 9.6%

• Chart review 13.3%

• Direct observation Higher

Jha K et al J Am Med Informatics Assoc; 5:305

Why won’t people report errors or near misses?

• Not aware of error• Not aware of need to report• Patient apparently unharmed• Fear of disciplinary action or litigation• Unfamiliar with reporting mechanisms• Loss of self esteem• Too busy• Lack of feed back when errors are reported

Near Misses: unique opportunities

• Occur 3-300 times more often than errors• Fewer barriers to data collection• Higher incidence allows quantitative

analysis• Proactive intervention• Reduces blame• Hindsight bias reduced Barach P & Small S BMJ 2000;320:759

Prescribing Problems

• Illegible handwriting

• Wrong drug

• Wrong dose

• Wrong frequency

• Wrong route

• Wrong patient

• Name confusion

Name Confusion

• Losec• amiloride• Fluoxetine• hydralazine• carbamazepine • chlorpropamide • thyroxine

• Lasix• amlodipine• Paroxetine• hydroxyzine• carbimazole• chlorpromazine• thioridazine

Inappropriate Abbreviations

• AZT• CPZ• HCl• HCT• MSO4• MTX• PIT• D/C• SC

• >,<• @• +• ug• AU• HS• IU• OS• OD