IMM 23 and 29: Introduction to Geriatrics Flashcards
Categories of Older Adults
- middle-aged (45-64)
- young-old (65-74)
- old (75-84)
- old-old (85-99)
- oldest old (100+)
Generations of Older Adults
- octogenarian
- nonagenarian
- centenarian
Men vs. Women 65+
compared to men the same age, women are generally more likely to have various chronic medical conditions
List 10 of the common chronic diseases seen in older adults.
- hypertension
- periodontal disease
- osteoarthritis
- ischemic heart disease
- diabetes
- osteoporosis
- cancer
- COPD
- asthma
- mood and anxiety disorders
What is pharmacokinetics?
the science of how the body affects the drug
What is pharmacodynamics?
the science of how the drug interacts with the body
What PK parameters are impacted by aging? (4)
- absorption
- distribution
- hepatic metabolism
- renal excretion
What PD parameters are impacted by aging? (2)
- target organ changes
- homeostasis
What are the physiologic changes of aging? (11)
- ↓ brain size and synaptic activity
- ↓ levels of neurotransmitters
- ↑ permeability of blood brain barrier
- ↓ muscle mass and perfusion
- ↓ bone density
- ↑ adipose tissue
- ↓ skin integrity and perfusion
- ↓ gastric acid production and blood flow
- ↓ hepatic mass and blood flow
- ↓ function of some hepatic enzymes
- ↓ renal size, blood flow and function
Physiologic Factors Impacting Absorption
Describe the absorption of oral medications.
conflicting evidence of clinical relevance, but may impact rate and extent of absorption of oral medications
- ↓ gastric acid production (↑ gastric pH)
- ↓ gastrointestinal motility
- ↓ gastrointestinal tract blood flow
Physiologic Factors Impacting Absorption
Describe the absorption of IV administration.
no impact
Physiologic Factors Impacting Absorption
Describe the absorption of subcutaneous and intramuscular administration.
- DECREASED tissue perfusion in older adults can result in DECREASED RATE of absorption for subcutaneous and intramuscular injections
- may DECREASE maximum concentration (Cmax) and INCREASE time to maximal concentration (Tmax)
- no impact on EXTENT of absorption
Physiologic Factors Impacting Absorption
Describe the absorption of topical administration.
little evidence that age-related skin changes will impact transdermal absorption, but may contribute to increased skin irritation
- DECREASED epidermal and dermal thickness
- DECREASED elasticity
- DECREASED blood flow to the skin
- DECREASED water content of skin
Physiologic Factors Impacting Distribution
Describe how body composition affects distribution.
older adults have:
- ↓ total body water
- ↓ muscle mass/lean body weight
- ↑ adipose tissue
which can result in :
- hydrophilic drugs may have a decreased volume of distribution
- lipophilic drugs may have an increased volume of distribution
and because of the changes in Vd:
- half-life for hydrophilic drugs may decrease
- half-life for lipophilic drugs may increase
Physiologic Factors Impacting Distribution
Describe how plasma protein binding affects distribution.
- drugs highly bound to ALBUMIN most effected – albumin levels ~ 20% lower in older adults than younger adults, therefore may have HIGHER free fraction of drugs highly bound to albumin
- drugs highly bound to ⍺-1-acid glycoprotein levels NOT SIGNIFICANTLY effected – no significant changes to ⍺-1-acid glycoprotein levels in older adults
How does hepatic metabolism change?
- ↓ hepatic blood flow
- ↓ hepatic mass
↓ first pass metabolism
Physiologic Factors Impacting Clearance
How are hepatically-eliminated drugs affected?
action of Phase I Enzymes (ie. cytochrome P450 system) may be DECREASED
- reduced clearance of drugs metabolized by cytochrome P450 system
- because of the change in Cl, half-life of medications metabolized by CYP P450 may be increase
action of Phase II Enzymes (conjugation, glucuronidation) NOT SIGNIFICANTLY impacted by aging
Physiologic Factors Impacting Clearance
How is renal elimination affected?
drugs undergoing renal clearance may have DECREASED renal clearance in older adults due to:
- ↓ renal size
- ↓ renal blood flow
- ↓ glomerular filtration
- ↓ tubular secretion
because of the change in Cl, the half-life of medications cleared renally may be increased
Physiologic Factors Impacting Pharmacokinetics
What processes do most medication have a potential change in?
- absorption
- distribution
Physiologic Factors Impacting Pharmacokinetics
Why do oral medications have a potential change in absorption?
- ↑ gastric pH
- ↓ motility
- ↓ blood flow
- ↓ first pass metabolism
Physiologic Factors Impacting Pharmacokinetics
Why do subcutaneous or intramuscular medications have a potential change in absorption?
↓ tissue perfusion
Physiologic Factors Impacting Pharmacokinetics
Why do medications have a potential change in distribution?
- change in body composition
- ↓ albumin levels, and therefore drugs bound to albumin
Pharmacodynamic Changes
What are the target organ physiologic changes? (3)
- ↑ permeability of blood brain barrier
- ↓ number and activity of receptors
- ↓ levels of hormones and neurotransmitters (epinephrine, dopamine, acetylcholine)
Pharmacodynamic Changes
What are the homeostatic changes? (1)
↓ ability of body to respond to physiologic challenges (ie. impaired baroreceptor reflex)
Physiologic Factors Impacting Pharmacodynamics
What are the changes to the central nervous system?
↑ permeability of BLOOD BRAIN BARRIER, resulting in:
- more medication crossing blood brain barrier/greater concentration of medication in brain in older adults compared to younger adults
- therapeutic effects potentially seen at LOWER doses
- INCREASED risk of CNS-related adverse effects (ie. confusion, sedation)
↓ number of neurons/receptors PLUS ↓ levels of neurotransmitters
- often an INCREASED susceptibility to effects of medications impacting neurotransmitter
- ie. older adults have ↓ dopaminergic neurons/dopamine receptors and ↓ dopamine levels in the brain – RESULT: increased susceptibility to adverse effects from dopamine antagonist (ie. antipsychotics)
- ie. older adults have ↓ GABA levels in the brain – RESULT: enhanced response to benzodiazepines (GABA agonist) at lower dose and HIGHER adverse effects
Physiologic Factors Impacting Pharmacodynamics
What are the changes to the cardiovascular system?
- ↓ number of β1 receptors PLUS ↓ post-receptor activation from β1 receptors
- DECREASED response to drugs that are agonists or antagonists of β1 receptors
- ie. older adults have decreased antihypertensive effects β1 blockers and as a result, this class of medications is not recommended for managing blood pressure in older adults
Physiologic Factors Impacting Pharmacodynamics
What does the baroreceptor reflex normally cause?
an increased heart rate in response to low blood pressure
- this prevents orthostatic hypotension (drop in blood pressure upon standing)
Physiologic Factors Impacting Pharmacodynamics
Describe the baroreceptor in older adults?
decreased baroreceptor, resulting in;
- increased response to anti-hypertensives
- increased risk of orthostatic hypotension
What is an adverse drug reaction (ADR)?
adverse effects of a drug that was properly administered in the correct dose, for therapeutic or prophylactic use
Describe the prevalence of ADRs in older adults.
- account for 57.6% of all ADR-related hospitalizations
- 48% of older adults ADR-related hospitalizations occur in aged ≥ 80 years
- ADR’s account for 2.7% of all hospitalizations in older adults (vs. 1% for younger individuals)
What are the risk factors for adverse drug reactions? (9)
- older age
- male
- polypharmacy
- ↑ number comorbidities
- ↑ number of prescribers
- ↑ number of pharmacies
- previous hospitalizations in past year
- newly started medications
- poor kidney function
Physiologic Changes of aging and ADRs
Pharmacokinetic Factors
- plasma protein binding: ↑ free fraction (↓ albumin)
- volume of distribution: ↓Vd (hydrophilic drugs) = ↑ concentration
- volume of distribution: ↑ Vd (lipophilic drugs) = ↑ duration of action
- ↓ phase 1 enzymatic reactions = ↓ hepatic metabolism and ↑ drug accumulation
- ↓ Renal Elimination = ↑ Drug accumulation
Physiologic Changes of aging and ADRs
Pharmacodynamic Factors
- ↑ permeability of blood brain barrier = ↑ risk of CNS ADRs
- ↓ receptors and neurotransmitters = ↑ susceptibility of ADRs
What is a common cause of ADRs in elderly?
anticholinergic medications
- allergy medications
- anti-nauseants
- antidepressants
- antipsychotics
- incontinence medications
- sleeping pills
- muscle relaxants
- cough and cold medications
What are some common side effects from anticholinergic medications?
- eyes: blurred vision, dry eyes
- mouth: dry mouth
- bowel: constipation
- skin: skin-flushing, unable to sweat, overheating
- bladder: urine retention (unable to empty bladder)
- heart: rapid heart rate
- brain: drowsiness, dizziness, confusion, hallucinations
What are some common ADRs in older adults?
- mental status changes
- orthostatic hypotension
- gastrointestinal/genitourinary disturbances
What is polypharmacy?
broadly defined as the use of multiple medications
How is polypharmacy categorized? (2)
traditionally defined numerically:
- polypharmacy: ≥ 5 medications
- hyper-polypharmacy: ≥ 10 medications
may also be categorized based on chronicity of use or appropriateness of therapy
What is the most common definition of polypharmacy?
taking at least 5 or more prescription medications concurrently
What are the consequences of polypharmacy?
↑ risk of:
- mortality
- emergency department visits and hospitalizations
- adverse drug events
- drug interactions
- cognitive and functional impairment
- falls
- frailty
- admission to long term care facility
- medication non-adherence
- prescribing cascades
↓ quality of life
What are the patient risk factors for polypharmacy?
- older age
- ale
- ↑ number comorbidities
- ↑ number of pharmacies
- ↑ number of prescribers
- mental health conditions
- residing in long-term care facility
What are the health care system risk factors for polypharmacy?
- lack of primary care physician
- poor medical record keeping
- poor transitions of care
- prescribing to meet disease-specific quality metrics
- use of automated refill systems
What is a prescribing cascade?
- adverse effect from one medication is misinterpreted as a new condition, and a new treatment (drug or medical device) is used to treat the adverse effect
- adverse effect from a drug is anticipated and a new drug prophylactically prescribed
Describe the approach to prescribing cascades.
- is one of the patient’s current medications causing the signs/symptoms that new medication is being prescribed to treat
- is the medication causing the reaction necessary, can it be stopped or substituted for something else
- what are the risks and benefits of continuing the medication that led to the cascade
What are the 3 types of potentially inappropriate prescribing (PIP)?
- mis-prescribing
- over-prescribing
- under-prescribing
What is mis-prescribing?
use of medication where there is increased risk of adverse drug events