Meds in elder

• Frailty


  Increased vulnerability due to ageing and associated with a decrease in the body's physical and psychological reserves
• Frailty syndromes


  1. Progressive loss of functional capabilities of most body organs

  2. Changes in responses to various stimulation

  3. Decrease in homeostatic or counter-regulatory mechanisms
• Pharmacokinetic and pharmacodynamic changes slowly occur and become clinically significant when people reach around 75 years
• Absorption


  • Extent of drug absorption is largely unchanged (AUC) - except for first-pass metabolism
  • Absorption rate may be slowed down - decreased Cmax and Tmax
• Distribution


  • Decrease in total body water and muscle mass and increase in body fat mass
  • Changes in body composition have a significant effect on distribution
  • Water soluble drugs - decreased Vd - increased plasma concentration e.g. digoxin (decreased dose)
  • Lipid soluble drugs - increased Vd - decreased plasma concentration e.g. diazepam, amitriptyline - don't increase dose due to pharmacokinetics (poor perfusion of fatty tissues decreases drug clearance) - prolonged effect
• Metabolism


  • Decreased hepatic mass, metabolism, and blood flow to the liver with age
  • Affects drugs with extensive first-pass metabolism e.g. propranolol, metoclopramide - decreased dose
  • Drugs metabolised by CYP enzymes e.g. warfarin, diazepam, barbiturates, phenytoin, theophylline
• Elimination


  • Decreased renal drug clearance - accumulation of some drugs
  • Decreased renal blood flow by 10% per decade and renal plasma flow decreases by 50%
  • Problem for drugs mainly excreted unchanged by kidneys + narrow therapeutic index e.g. digoxin - decreased dose, e.g. lithium - decreased dose, DOACs (rivaroxaban, apixaban, edoxaban)
• Pharmacodynamics


  • Significantly altered with increased age due to changes in responsiveness of target organs
  • Generally, older people have increased sensitivity and altered homeostatic mechanisms
  • May be due to a change in receptor binding, decreased receptor number, or altered translation of a receptor-initiated cellular response into a biochemical reaction
• Drug sensitivity


  • Older people are more sensitive to benzodiazepines - accumulate in fatty tissue
  • Warfarin requirements 25% decreased in older people to achieve target INR
  • Increased susceptibility to anticholinergic effects of drugs e.g. tricyclic antidepressants - drowsiness, dizziness, confusion
  • Beta-1, beta-2, and alpha-receptor responsiveness decreased
• Drug-related harm in the elderly is one of the most challenging public health issues globally
• Older people are more vulnerable to morbidity/mortality secondary to drug-related harms due to age-related changes and pathologies
• 80% of patients over 75 take a prescription medicine
• 36% of these patients take more than 4 medicines
• Approximately 50% of older adults take 1 or more medications that aren't medically necessary
• Prescribing cascade


  1. Ramipril - common first dose hypotension -> dizziness -> GP: mistaken for vertigo - prochlorperazine added -> more dizziness -> fall -> A&E admission

  2. Take at night to avoid daytime dizziness

  3. Hypotension subsides after a few days

  4. Amlodipine - common side effect ankle edema -> GP: adds furosemide -> hypokalaemia -> muscle weakness & falls -> Elevate feet
• Reasons for inappropriate prescribing

  • Increased incidence of adverse drug events: hazardous interactions
  • Side effects treated with other medications rather than non-pharmacological intervention
  • Lack of medication review
• Misprescribing (PIMs)


  • Refers to prescription of a medication that significantly increases the risk of an adverse drug event
  • Also - potentially inappropriate medicines (PIMs)
• Misprescribing (PIMs)


  • Tramadol in epilepsy
  • NSAID in renal failure
  • Sildenafil+nitrates
• Overprescribing (PIMs)


  Prescription of medications for which no clear clinical indication exists
• Under-prescribing (PPOs)


  Omission of potentially beneficial medications that are clinically indicated for treatment or prevention of a disease
• Under-prescribing (PPOs)


  • Laxative with morphine sulfate
  • Folic acid in rheumatoid arthritis with methotrexate
  • Osteoporosis - calcium and vitamin D / bisphosphonate after 5 years - >5 years fragility fracture
  • Vaccines - Flu/Covid/Pneumococcal/Shingles
• Medication Appropriateness Index (MAI)


  • Assesses prescribing appropriateness using 10 implicit criteria
  • Encompasses elements of drug prescribing that are applicable to any medication and any clinical condition in any clinical setting
  • Comprehensive clinical details, medical knowledge and clinical judgement are required to implement MAI criteria
  • Does not address under-prescribing
  • Time consuming to use
• Beer's Criteria


  • 34 medications / medication classes to be avoided in older adults e.g. first generation antihistamines
  • Medications to be avoided specifically in 14 listed diseases and conditions e.g. NSAIDs in heart failure
  • 5 medications to be used with caution in older adults e.g. dabigatran in ≥ 75 years old
  • Concise explanation of inappropriateness
  • Severity rating of adverse outcomes
  • Can be used by computerized clinical information systems
  • Several drugs unavailable outside North America
  • Many drugs not prescribed in older people
  • No drug-drug interactions
  • Does not consider duplicate drugs
  • Under-prescribing not considered
  • Poor structure/presentation
• STOPP/START Criteria


  • STOPP - 130 explicit criteria and 3 implicit criteria for potentially inappropriate prescriptions in ≥ 65 years
  • START - 57 explicit criteria and 1 implicit criteria for potential prescribing omissions in ≥ 65 years with a specific condition, where no contraindication exists
  • Concise explanation of inappropriateness
  • Organized by physiological systems
  • Includes drug-drug and drug-disease interactions
  • Includes drug duplication
  • Considers under-prescribing
  • Does not suggest safer alternatives to inappropriate drugs
  • Does not address certain domains of prescribing appropriateness, e.g. indication, formulation and cost
• Deprescribing


  Process of withdrawal of an inappropriate medication, supervised by a healthcare professional with the goal of managing polypharmacy and improving outcomes

  
• Barriers to deprescribing


  • Easier to maintain status quo
  • Easier to start than stop medicines
  • Little evidence on how best to safely stop
  • Withdrawing medicines can be unpredictable
  • Time consuming
  • Prescriber reluctance
  • Consent and capacity issues
• Approach to stopping medications

  1. Must involve patients, carers, multidisciplinary team

  2. Many challenges and barriers

  3. Clinical and communication skills vital

  4. Sequential over time - patience

  5. Takes time, frequent monitoring and review

  6. Structured approach is best - use tools available
• Outcomes of deprescribing


  • No obvious change in clinical status
  • Resolution of specific adverse drug reactions - 5 half-lives for complete elimination
  • Improvement in function, quality of life and safety: decreased medication errors, risk of falls, and increased cognition and adherence to other medications
  • Withdrawal syndromes: SSRIs, hypnotics, benzodiazepines, opioids - taper
  • Rebound syndromes: PPI (rebound acid secretion); zopiclone (rebound insomnia) - reintroduce at decreased dose
  • Unmasking drug interactions
  • Reappearance of symptoms of original disease/risk factors