Drug use in the elderly

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Drug use in the elderly
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Assessing Older Adults
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Assessing Older Adults
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Assessing Older Adults
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Assessing Older Adults
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Assessing Older Adults
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• Causes of Alteration of
• Drug Response in the Elderly
• Pharmacokinetic
• - Absorption
• - Distribution
• - Metabolism
• - Excretion
• Pharmacodynamic
• Drug interactions

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Oral administration
ELIMINATION
Intravenous administration
INTESTINE
BILE
Drug and
SYSTEMIC CIRCULATION
LIVER
BOUND
FREE
Metabolites
TISSUES
Pharmacokinetic
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Altered Drug Action with Aging

• Pharmacokinetics
• What the body does to the drug
• - Absorption of the drug
• - Distribution of the drug to various organs
  and tissues in the body
• - Metabolism of the drug
• - Renal excretion

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Absorption
Altered Drug Action with Aging

• The gastrointestinal tract undergoes both
  physiologic and anatomic changes with aging
• about 30 decrease in mucosal absorption surface
  in the small bowel and GI motility
• 40 reduction in small intestine blood flow
• galactose, calcium, thiamine, iron

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Altered Drug Action with Aging

• Absorption
• Most frequently does not result in clinically
  relevant changes in drug absorption after oral
  administration
• Factors that can alter drug absorption
• - swallowing difficulties
• - poor nutritional status
• - interaction with other prescription and
• non prescription medications

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Distribution
Altered Drug Action with Aging

• The body composition is altered by aging
• decrease in total body mass
• decrease in total body water
• decrease in lean body mass
• decrease in liver mass
• increase in total body fat

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Distribution
Altered Drug Action with Aging

• Volume of distribution (Vd) of lipophilic drug is
  increased in the elderly
• t 1/2 0.693xVd
• plasma clearance

• Prolong half life (t ½ )

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Altered Drug Action with Aging
Distribution

• Alteration in protein binding of drugs.
• (decrease of albumin).
• acidic drugs and high protein binding drugs eg.
  phenytoin, phenylbutazone, warfarin may increase
  free drug concentration.

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Metabolism The effect of age on hepatic
clearance of drugs
Altered Drug Action with Aging

• Hepatic clearance of drugs is determined by
• 1.Intrinsic ability of the liver to metabolize
  drugs
• phase I reaction by the microsomal mixed
  function oxidase system. Aging decrease phase I
  reaction
• phase II conjugation not affected by
  aging
• 2.Liver blood flow is reduced in the elderly

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Case 1

• ???? 73 ??
• ????? ???????????????? ???????????
• 4 ??????? admitted ??????????? ?????
• ??????? HT 12 ?? ?? minor stroke left
  hemiparesis, good recovery
• Dx Pneumonia
• Rx Antibiotic, hydration, oxygenation

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Case 1

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  ???????????????????????????????? ?????????????
  ?????????????????????????????????
  ?????????????????????
• Rx Diazepam 5 mg oral and physical restrain

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Case 1

• In the next morning the patient was well,
  refused any problem last night.
• Next night at 2 AM. She confused and agitated
  again. Diazepam 10 mg given orally and she slept
  for over 24 hr.

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Case 1

• When she woke up, brought to bathroom in wheel
  chair and fell in the bathroom. Bruise over her
  left face.
• Please discuss about her agitation and proper
  management

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MEAN ELIMINATION HALF - LIFE (HOURS)
Drug Young Old Diazepam 24 75
Chlordiazepoxide 10 30 Oxazepam 10 10
Lorazepam 12 12 Alprazolam 10 17
Imipramine 19 24 Amitriptyline 16 22
Desipramine 34 75 Nortriptyline 27 40
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Distribution
Altered Drug Action with Aging

• The body composition is altered by aging
• decrease in total body mass
• decrease in total body water
• decrease in lean body mass
• decrease in liver mass
• increase in total body fat

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Oral administration
ELIMINATION
Intravenous administration
INTESTINE
BILE
Drug and
SYSTEMIC CIRCULATION
LIVER
BOUND
FREE
Metabolites
TISSUES
Pharmacokinetic
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DRUGS
ORAL ADMINISTRATION
CIRCULATION
BOUND
FREE
ABSORPTION
young
TISSUE
fat
elderly
Vd
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Benzodiazepines

• Depressogenic
• Ataxia --- leading to falls and fractures
• Confusion
• Disinhibition -- aggression sexually
  inappropriate behaviour
• Withdrawal symptoms
• AVOID long acting Benzos such as diazepam and
  flurazepam (except may be in alcohol withdrawal)

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Benzodiazepines

• Short and intermediate acting preferred
• Used as adjunctive therapy mostly (potentiating
  agent)
• Sometimes indicated as a hypnotic after organic
  and other psychiatric disorders have been ruled
  out

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Sedative-Hypnoticand Anxiolytic Drugs in the
Elderly
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Sedative-Hypnotic and Anxiolytic Drugs in the
Elderly
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Case 2
???? 75 ?? BW 45 Kg. CC N/V 2 ??? PI case
angina pectoris Rx Propanolol and ASA gr V 9
??????? ?? chest pain ???? Atrial fibrillation
(rate 126/m) Lab Cr 0.9 mg
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Case 2
Rx Digoxin (0.25 mg V x 3 ??? 2 ??. ) HR
94/min ?????? D/C home ?? Digoxin (0.25) 1 tab
OD ??????????? 2 ??? ?????????? ????????
??????? PE P 42/min irregular, BP 90/60
mmHg ???? ? ???? ??????????????????????????
?
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Case 2
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Estimating Renal Function

• Creatinine clearance(Clcr) is used to assess
  renal function, and can be estimated by the
  Cockroft and Gault equation
• Clcr (140-Age)(Wt) S
• (72)(Scr)
• where Clcr is the creatinine clearance in mL/min
• Age is in years
• Wt is the lean or ideal body weight in kg
• Scr is the serum creatinine concentration in
  mg/dL
• S 1.0 for males and 0.85 for females

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Estimating Renal Function

• It is important to recognize that due to
  age-dependent declines in renal function, elderly
  patients with normal serum creatinines may have
  Clcr requiring dosage adjustment
• A. 60 kg, 30-year-old man with serum
  creatinine 1 mg/dL
• Clcr (140-30)(60) 1 91.66
  mL/min
• (72)(1)
• B. 60 kg, 70-year-old man with serum
  creatinine 1 mg/dL
• Clcr (140-70)(60) 1 58.33
  mL/min
• (72)(1)

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Cardio-vascular drugs

• Digoxin
• High incidence of ADRs
• (digoxin toxicity nausea, vomitting,
  anorexia,
• cardiac arrhythmia, dead)
• Plasma digoxin levels
• Half-life of digoxin increase with aging

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Digoxin

• Special consideration
• Subacute toxicity of anorexia with weight loss
  more common initial sign than other GI of
  cardiovascular effects
• Baseline an follow up ECG essential
• Dose on lean body weight and creatinine
  clearance with attention to electrolyte and
  thyroid status

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Digoxin

• Adjust dose with Renal impairment and aged
  patients.
• Older adults may develop exaggerated serum/tissue
  concentration due to
• Decreased lean body mass
• Decreased total body water
• Age related reduction in renal function
• Drug Interactions
• Most common K wasting diuretic
• amiodarone

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Case 3

• ??? 78 ?? ?????????????? ?????? ???????????????
• 1 ???????
• Case HT 10 ??
• AF 4 ??
• On Atenolol 50 mg OD
• Amlodipine 10 mg OD
• Warfarin 3 mg ?????? ??? ?????
• 1.5 mg ???????????

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Case 3

• FU ???????????? 8 ??? ???????????????
• INR 2.46
• Complaint ??? ?? ??????
• Dx. Pharyngitis
• Rx. Clarithromycin added
• (Hx of penicillin allergy)

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Case 3

• ????????????????????? ????????????? ?????
  ???????????? ?????? ?????????????????
• PE coma,
• pupil dilated left side 4 mm.
• sluggish react to light
• right 3 mm.
• decorticate posture

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Problem

• Coma acute cerebral hemorrhage
• Underlying DM, HT
• Atrial fibrillation with anticoagulant

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Anticoagulants

• Heparin
• Special consideration
• Increase risk of bleeding with age
• Warfarin
• Strongly protein - bound and metabolized by the
  liver
• Dose required for proper anticoagulation is
  lower in elderly

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Drug Interactions

• Significance Rating
• A number 1 through 5 will be assigned to each
  interaction monograph, based on the Editorial
  Groups assessment of the interactions Severity
  and Documentation (defined below)
• is a severe and well documented interaction.
• is an interaction of no more than unlikely or
  possible documentation.
• Major The effects are potentially
  life-threatening or capable of causing permanent
  damage

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Key Elements of Patient Education Regarding
Warfarin

• Identification of generic and brand names
• Purpose of therapy
• Expected duration of therapy
• Dosing and administration
• Visual recognition of drug and tablet strength
• What to do if a dose is missed
• Importance of prothrombin time/INR monitoring
• Recognition of signs and symptoms of bleeding
• What to do if bleeding occurs

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Ten Most Common Drug-Drug Interactions in the
Elderly
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Ten Most Common Drug-Drug Interactions in the
Elderly
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Case 4

• ??? 72 ??
• high fever and chill 3 hrs PTA
• Underlying DM, HT for 10 years
• Recent history of ischemic stroke with right
  hemiparesis 6 month ago.

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Case 4

• On the last visit 1 mo ago, the family
• reported frequent crying with desire to
• death because of dependency.
• Nortriptaline 10 mg was added to drug
• regiment. The patient seemed less crying

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Case 4

• History of frequent urination for 1 wk. and
  drowsy with low grade fever
• PE full urinary bladder up to umbilicus

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Problem

• Urosepsis
• Acute urinary retention
• Underlying DM, HT and ischemic stroke
• Post stroke depression

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2002 Criteria for potentially inappropriate
medication use in older adults Considering
diagnoses or conditions
Beers Criteria
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2002 Criteria for potentially inappropriate
medication use in older adults Considering
diagnoses or conditions
Beers Criteria
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2002 Criteria for potentially inappropriate
medication use in older adults Considering
diagnoses or conditions
Beers Criteria
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2002 Criteria for potentially inappropriate
medication use in older adults Considering
diagnoses or conditions
Beers Criteria
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HOW TO PRESCRIBE APPROPRIATELY

• Obtain a complete drug history.
• previous treatments and responses
• allergies
• OTC drugs
• nutritional supplements
• alternative medications
• alcohol, tobacco, caffeine, and recreational
  drugs.
• Avoid prescribing before a diagnosis is made.
• Review medications regularly and before
  prescribing a new medication.
• D/C medications ? no longer needed.
• Monitor the use of prn and OTC drugs.

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HOW TO PRESCRIBE APPROPRIATELY

• Know the actions, adverse effects, and toxicity
  profiles of the medications you prescribe.
  Consider how these might interact or complement
  existing drug therapy.
• Start chronic drug therapy at a low dose and
  titrate dose on the basis of tolerability and
  response.
• Use drug levels when available.
• Attempt to reach a therapeutic dose before
  switching or adding another drug.

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HOW TO PRESCRIBE APPROPRIATELY

• Educate patient and/or caregiver about each
  medication.
• regimen
• therapeutic goal
• cost
• potential adverse effects
• drug interactions
• written instructions.
• Avoid using one drug to treat the adverse events
  caused by another
• Attempt to use one drug to treat two or more
  conditions.

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HOW TO PRESCRIBE APPROPRIATELY

• Use combination products cautiously.
• Establish need for more than one drug.
• Titrate individual drugs to therapeutic doses
• switch to combinations if appropriate.
• Communicate with other prescribers.
• Don't assume patients willthey assume you do!
• Avoid using drugs from the same class or with
  similar actions
• eg. alprazolam and zolpidem

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CRITERIA FOR DRUGS OF CHOICE FOR OLDER ADULTS

• Established efficacy
• Compatible safety and adverse-event profile
• Low risk of drug or nutrient interactions
• Half-life lt24 h with no active metabolites
• Elimination does not change with age or known
  dose adjustments for renal or hepatic function
• Convenient dosing single or twice daily
• Strength and dosage forms match recommended doses
  for older adults
• Affordable to the patient

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WAYS TO REDUCE MEDICATION ERRORS

• Be knowledgeable about the medication's dose,
  adverse events, interactions, and monitoring.
• Write legibly
• to avoid misreading of the drug name (Celexa
  versus Celebrex).
• Write out the directions, strength, route,
  quantity, and number of refills.
• Always precede a decimal expression of lt1 with a
  zero (0)
• never use a zero after a decimal.

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WAYS TO REDUCE MEDICATION ERRORS

• Avoid abbreviations, esp easily confused ones (qd
  and qid).
• Do not use ambiguous directions, eg, as directed
  (ud) or as needed.
• Include the medication's purpose
• in the directions (eg, for high blood pressure).
  
• Write dosages for thyroid replacement therapy in
  µg not mg.
• Always re-read what you've written.

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Age-Associated Changes in Pharmacokinetics and
Pharmacodynamics
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COMPLICATING FACTORS

• Physical Interactions
• Mg, Ca, Fe, Al, or zinc can lower oral
  absorption of levothyroxine and some quinolone
  antibiotics.
• Tube feedings decrease absorption of oral
  phenytoin and levothyroxine.

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COMPLICATING FACTORS

• Decreased Drug Effect
• Warfarin and vitamin K-containing foods (eg,
  green leafy vegetables, broccoli, brussels
  sprouts, greens, cabbage)
• Decreased Oral Intake or Appetite
• alter the taste of food (dysgeusia)
• decrease saliva production (xerostomia)
• making mastication and swallowing difficult.
• dysgeusia include captopril and clarithromycin.
• cause xerostomia include antihistamines,
  antidepressants, antipsychotics, clonidine, and
  diuretics.

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COMPLICATING FACTORS

• Drug-Drug Interactions
• impaired absorption
• eg, sucralfate and ciprofloxacin
• displacement from protein-binding sites
• eg, warfarin and sulfonamides
• inhibition or induction of metabolic enzymes
• two or more drugs have a similar pharmacologic
  effect
• eg, potassium-sparing diuretics, potassium
  supplements, and ACE inhibitors

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COMPLICATING FACTORS

• Drug-Drug Interactions Digoxin
• increase digoxin concentration or effect, or
  both
• amiodarone
• diltiazem
• erythromycin
• esmolol flecainide
• hydroxychloroquine
• Ibuprofen
• indomethacin
• decrease digoxin concentration or effect, or
  both
• aminosalicylic acid
• antacids a
• ntineoplastics
• cholestyramine
• colestipol

• nifedipine
• quinidine
• quinine
• spironolactone
• tetracycline
• tolbutamide
• verapamil

• kaolin
• pectin
• metoclopramide
• psyllium
• sulfasalazine
• St. John's wort

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Enzyme Inhibitors and Inducers

• Selected CYP Isozyme Substrates, Inducers, and
  Inhibitors

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Enzyme Inhibitors and Inducers

• Selected CYP Isozyme Substrates, Inducers, and
  Inhibitors

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Enzyme Inhibitors and Inducers

• Selected CYP Isozyme Substrates, Inducers, and
  Inhibitors

CYP2D6
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Medication Review for the 10-Minute Consultation
The NO TEARS Tool

• Need/indication
• Open questions
• Tests
• Evidence
• Adverse effects
• Risk reduction
• Simplification/switches

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Age-related factors can change drug metabolism

• 4 major age-related pharmacokinetic alterations
• decreased elimination
• decreased hepatic metabolism
• altered distribution in various body compartments
  
• altered absorption

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Age-related factors can change drug metabolism

• Drug absorption
• affected by alterations in gastric pH and
  gastrointestinal motility
• may delay or increase the absorption of drugs.
• Distribution
• affected by the alterations in protein binding
• decreased protein-rich lean body mass or low
  serum albumin levels
• drugs compete for the same protein-binding sites

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Polypharmacy
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Polypharmacy

• The administration of numerous medicines, often
  for multiple indications, at the same time.

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Polypharmacy

• The administration of numerous medicines, often
  for multiple indications, at the same time.
• Derogatory sense
• The probability of adverse drug events increases
  with the number of drugs prescribed

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Polypharmacy

• Six adverse consequences of polypharmacy
• Nonadherence
• (probability increases with complexity of the
  drug regimen)
• Adverse drug reactions
• Drug-drug interactions
• risk of hospitalizations
• Medication errors
• (e.g., taking too much of one drug not enough
  of another)
• costs, from treatment of adverse events

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Adverse Reactions to Common Drugs

• drug-drug interactions drug-nutrient or
  drug-food interactions drug-disease state
  interactions drug-laboratory test interactions

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Adverse Reactions to Common Drugs

• Digoxin Diuretics ß-Adrenergic receptor
  blockers (propranolol) Autonomic Nervous System
  (ANS) Antihypertensive Drugs Anticoagulants
  Theophylline Analgesics Sedative-hypnotic
  agents Tricyclic antidepressants and
  antipsychotic drugs Antiparkinsonian drugs

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Adverse Reactions to Common Drugs

• Digoxin

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Nutrition