PHARM 401 Geriatrics Toxicology and Medication Safety Flashcards
Demographics - Canada
Medication Use Among Older
Canadians
Canada July 2022
* 18.8 % of
population age ≥65
Alberta age ≥65
* 2010 = 10.7%
* 2019 = 13.2%
* 2022 = 14.8%
* 2036 = 18%
(AH projection)
- 17% of the
population - 40% of Canada’s
spending on
prescribed drugs - 55% of public
drug spending
Top 10 in Seniors - Canada
Rank Drug class Rate of use Chronic rate of
use
1 HMG-CoA reductase inhibitors 51.5% 46.7%
2 Proton pump inhibitors 32.1% 23.3%
3 Dihydropyridine derivatives 24% 20.6%
4 ACE-I, plain 22.8% 20%
5 Beta-blockers 22% 19.3%
6 Thyroid hormones 18.4% 17.3%
7 Angiotensin II antagonists, plain 16.6% 14.6%
8 Biguanides 14.4% 12.4%
9 Other antidepressants 12.6% 9%
10 SSRI 11.2% 9%
Medication Safety
Adverse Drug Reactions/Events
- Medication errors $42B US
- Goal:
- reduce severe, avoidable
medication-related harm by 50%
over 5 years - Priority Actions:
- High risk situations
- Includes children, older adults
- Polypharmacy
- Transitions in care
- ADR: a noxious, unintended effect of a drug that
occurs in doses normally used in humans for the
diagnosis, prophylaxis, or treatment of disease. - ADE: An untoward occurrence after exposure to a
drug that is not necessarily caused by the drug.
Types of ADR
Adverse Drug Events
slide 13
- Age >65 years = up to 25% of hospital admissions and
ER visits - Vs only 1-4% of ER visits for rest of the population
- Seniors have the highest mortality rate from toxicologic
exposures - 4% of exposures, 23% of deaths
- ER visits and hospitalizations for ADR cost $36B for
seniors in Canada - up to 1/3 of elderly who experience an ADE never fully
recover - estimates of 30-80% of ADE in elderly are preventable
a disproportionate number of older adults who end up dying from toxic exposures. In contrast to children, there’s obviously high number of toxic exposures in children, but we tend to act on them very quickly, and they tend to be different in terms of context.
and so children tend to have much lower mortality when it comes to toxic exposures, older adults, much more mortality.
ADR – Risk Factors
- Age (especially if >85 years)
- Co-morbidities
- Caregiving (dependent)
- # of medications (especially 15 or more) and doses/day
- MRCI (complexity)
- High risk medications
- Non-adherence
- Recent start of a new medication
- Number of pharmacies used
- Number of prescribers involved
- Recent hospitalization in past year
ADR – Who is at risk
- People with multiple chronic conditions
- Women
- People over the age of 65
In 2016 in Canada:
* 0.7% of seniors (= 41,300 seniors) were
hospitalized due to an adverse drug reaction
* 1 in 143 seniors are hospitalized due to
harmful effects of their medication.
there are some studies showing women, or at higher risk for AD restrictions across all age groups, because we have less research in women
for medications, but in some studies and older adults it’s sometimes men. So it it could be both men or women depending on the literature you’re looking at.
there might be different reasons for women. It’s because we Don’t study drugs enough. In the early stages. In women we mostly have men enrolled in some of the early studies.
and we also are not dose adjusting appropriately for women,
older men who require caregiving are at higher risk as well. So there might be different factors, but both male female are are at risk.
- Often it’s the spouse.
their female spouse, who is helping them take medications. So if they are widowed, for instance, or require another caregiver. There tends to be more errors
System Considerations
Geriatricians/Specialty Services
* In 2018, 304 board certified geriatrics in Canada
* Estimated need >700
* Evidence base
* Selection of ‘clean’ patients in trials
* Bias against age, multimorbidity
* Prescribing patterns
* Influence of pharma and new drugs
* Tendency to maintain Rx vs review
* Tendency to prescribe meds in patient interactions
Multimorbidity
Polypharmacy
- Associated with age
- Linear association with # medications
- Literal definition
– 2 or more medications - Most commonly accepted definition in practice:
– 5 or more medications (Rx or OTC) - Proposed definitions if the focus is on numbers
– The use of 2 or more drugs without indications or for the
same purpose.
– The use of a drug to treat the adverse reactions of another
drug.
– The use of 2 or more drugs from the same class to treat
different indications. - Clinically meaningful
– When a medication is not needed
Polypharmacy
Prescribing Cascades
- Use of one drug to treat the adverse effects of
another
see slide 20
One reason we’ve gotten into poly pharmacy is prescribing cascades. So people are started on medications. They have a side effect. We treat the side effect with another medication, then that causes a side effect,
if we stop the first medication we could address this entire cascade.
Drug Interactions
- Approximately 50% of drug interactions lead to an
adverse event - Drug-disease interactions are 2-3 times more
common than drug-drug interactions - Manifestations in older adults:
- Neuropsychologic impairment
- Hypotension
- Renal failure
Drug Intx – Risk Factors
Patient factors
* PK/PD changes
* Decreased organ system reserve
* Nutrition status
* Co-morbidities
* Aged heterogeneity (lifelong habits, environment,
genetics)
* Atypical disease presentation, or assumption that it is an
aging problem, masks detection of interactions
* Communication (e.g. not informing providers of
medications taken)
Prescriber factors
* Number of prescribers
* Inadequate medication histories
* Use of evidence-based medicine
* Attitudes (e.g. ageism)
Regimen factors
* Number of medications
* if 8 medications, then risk of interaction almost 100%
* Types of medications (e.g. warfarin)
Health care system factors
* Communications (with patient, other providers)
* Inadequate medication histories
* Use of 70 kg male as research prototype
Drug Intx - Interventions
- Review by pharmacist
- Technology to flag interactions
- Medication reviews for medications with significant
interactions - e.g. warfarin, phenytoin
- Thresholds for medication review
- e.g. 5 or more meds, 5 or more comorbidities
ADR – Common Examples
- Drugs Most Commonly Implicated
- Antibiotics
- Anticoagulants
- Antineoplastic agents
- NSAIDs
- Analgesics
- Note: variations by study, drug use patterns
consistently it’s antibiotics, and that’s because
we throw something in just for days or a week or 2, and
it’s usually something that we think is necessary, like if someone has a uti. If someone has a pneumonia, we decide we want to treat that.
and so sometimes we don’t make adjustments as well in the other medications. and we don’t take into account how we could adjust the actual antibiotic, so we end up causing harm
Potentially
Inappropriate
Medications
Also identified as “PIM”
* A medication or medication class
where harm outweighs the benefit,
and there are safer alternatives
available.
* The Beers Criteria are explicit
* The Beers Criteria are used by
CIHI to identify PIM
Benzodiazepines
All antipsychotics
Tricyclic antidepressants
Amitriptyline
Imipramine
1 st generation antihistamines
Cardiovascular/diuretic agents
Amiodarone
Digoxin > 0.125 mg/day
Non-benzodiazepine sedative hypnotics
Sulfonylurea oral hypoglycemics
PIM Impact
The cost of (potentially) inappropriate
medication - PIM
- ADR
- Hospitalization
- functional decline
- System costs
$419 million
Canadians spend $419M
per year on potentially
harmful prescription
medications. This does
not include hospital
costs.
$1.4 billion
Canadians spend $1.4B per year
in health care costs to treat
harmful effects from
medications, including fainting,
falls, fractures and
hospitalizations.
Why are ADR/ADE so common yet
undetected in older adults?
- Lack of recognition
- Health professionals
- Patients
- Type of exposure
- Attitudes/Ageism
- “Atypical” presentation
- Physiologic changes,
PK/PD changes
Aging
Forms of aging
- Chronological aging
- Physiologic aging
- Social age
- Legal age
- Functional age
- Is NOT synonymous with disease
- Changes are experienced by all human beings
- Some changes may be due to lifestyle choices, social
determinants of health, exposure to particular
chemicals, etc.
Physiologic Aging
- Each organ system has changes associated with
aging, which often start in the 5th decade - Implications of these changes include:
- Reduced tissue/organ function
- Functional decline
- Increased susceptibility to disease
- Change in behaviour
- Differences in PK and PD
Sensory Changes
Taste
* Loss of lingual papillae
* Diminution of ability to taste
* Salivation decreases
* Use of dentures
* Decreased interest in food
* Decreased taste of salt – may use NaCl excessively
- Hearing Loss
- Stria vascularis highly vascular tissue; greater O2 demand than the brain
- 65% of seniors ≥85y have presbycusis
- Vision
- Decreased ability to adapt to light
- Reduced depth perception
- Increased sensitivity to glare
- Consider: Lighting in counseling area, size of print, colours/shades, glossiness of
paper
Physiological Changes
Body composition - ↑fat
* CV - ↓ cardiac output, ↓ beta sensitivity
* Renal - ↓ GFR, ↓ nephrons
* GI - ↓ H+
, ↑ gastric emptying time
* Hepatic - ↓ size, ↓ blood flow
* Nervous - ↓ blood flow to CNS
* Pulmonary - ↓ cilia
* Endocrine - ↓ hormonal secretions
Body Composition
- Loss of muscle mass
- starts ~ age 40
- accelerates in 6th decade (i.e. 50’s)
- By age 90, a person has half their muscle mass
- Some changes may be due to inactivity vs physiologic
aging - Function and quality of muscle changes, along with
neural stimulation, which slows - Fat mass increases
Absorption - GI
- Physiologic Change
- ↑ gastric pH
- ↓ gastric acid secretion
- ↓ GI blood flow
- ↓ gastric surface area
- ↓ GI motility
- PK Implication
- Potential for delay in
absorption - Minimal impact on
extent of absorption of
passively absorbed
drugs - Active transport (e.g.
B12, iron, calcium) may
be reduced
Absorption – IM, topical
Absorption – Summary
* Most drugs are well absorbed in older adults
* Rate of absorption may be delayed in some
patients
* This is relevant for some treatments, e.g. immediate
release levodopa, analgesia
* Drug absorption can also be affected by other
conditions or medications
Physiologic Change
* ↓ in blood flow
* ↓ skin hydration
- PK Implication
- Slower , erratic, or
lower absorption (e.g.
antibiotics) - NB in immobile patients
- Higher absorption of
topical steroids - NB if occlusive dressings
Distribution
Aging Vd effect Example
↓ body water ↓ Vd for hydrophilic drugs Ethanol, lithium
↓ lean mass ↓ Vd for drugs that bind to muscle,
or are water soluble
Digoxin
↑ fat stores ↑ Vd for lipophilic drugs Diazepam, anaesthetics
↓ albumin ↑ % unbound or free drug Valproic acid, phenytoin,
warfarin
- Distribution can be altered by aging or other
disease states - Lipid soluble drugs show an increase in Vd
- Protein changes with aging are insignificant and
rarely have an impact on drug therapy - Protein changes often occur with concurrent
illness, not aging
Metabolism
- Physiologic Change
- ↓ hepatic mass
- ↓ hepatic blood flow
- ↓ CYP P450 content
- PK Implication
- ↓ first pass metabolism
- ↓ phase 1 metabolism
- ↓ phase 2 metabolism
if frail older adult
see slide 45 for table
MetabolismMetabolism – Summary
- Drugs metabolized by Phase 2 are preferred
- For medications oxidatively metabolized, reduce
dose - Multiple medications can have more dramatic drug
interactions if impacting CYP P450
High hepatic extraction ratio: decrease dose
* Rationale: medications are affected by blood flow to the
liver, which decreases with age. Less medication will be
removed, leading to higher concentrations and longer t1/2
than expected.
* Examples: Morphine, propranolol, verapamil
Low hepatic extraction ratio: decrease dose
* Rationale: medications are affected by enzyme capacity,
and if the medication requires ox/redox (e.g. CYP P450)
enzymes this could lead to reduced metabolism.
* Examples: warfarin, phenytoin
Conjugation: no change in dose
- Metabolism can be dramatically affected by illness,
particularly acute illness - Other factors affecting metabolism include chronic
illness, genetics, diet, smoking, EtOH use
Elimination
Elimination – Summary
- Physiologic Change
- ↓ renal blood flow
- ↓ GFR
- ↓ tubular secretion
- PK Implication
- renally eliminated
drugs are delayed - Longer t1/2 of renally
eliminated drugs
Decreased renal elimination of drugs is the single
most clinically significant change in PK due to aging
* The majority of drug dosage adjustments in older
adults are due to renal function
* Note: decreased muscle mass in frail older adults
* CrCl is an estimate
Pharmacodynamics
- Altered homeostatic balance manifested in a stress
environment. - Change in homeostatic regulation
- Change in receptor responsiveness
- Change in receptor density
- Change in receptor affinity
- Post-receptor changes
- Change in negative feedback
- Implications
- Increased sensitivity to drugs
Pharmacodynamic Changes
- Paradox of exposure
- Examples:
- Postural control
- Orthostasis
- Thermoregulation
- Visceral muscle function
- Cognition
- Anticoagulation
- Tardive dyskinesia
- Arrhythmias
Pharmacodynamic - CNS
Pharmacodynamic - Postural
- Higher cognitive function
- Mechanism:
- Neuronal loss
- Receptor downregulation
- Examples
- Central anticholinergics
- Stimulants
- Postural control
- Mechanism:
- Fewer dopamine (D2) receptors in striatum
- Examples
- Antipsychotics
- Metoclopramide
Pharmacodynamic - Movement
- Tardive dyskinesia
- Mechanism:
- Impaired or decreased dopamine synthesizing neurons
- Examples:
- antipsychotics\
\ - Orthostasis
- Mechanism:
- blunting of β response
- receptor down-regulation
- changes in vascular tree and autonomic nervous system
- Examples
- BP meds
- TCA
- Antipsychotics
- Diuretics
Pharmacodynamic - CV
Pharmacodynamic - Coagulation
- Arrhythmias
- Mechanism:
- Cardiac hypersensitivity
- Examples:
- Antiarrhythmic medication
Anticoagulation
* Mechanism:
* Poor hepatic production of coagulation factors
* Dietary intake
* Examples
* Anticoagulants
* Thrombolytics
Pharmacodynamic - Visceral
Temperature
- Visceral muscle
- Mechanism:
- visual disturbances (pupillary autonomic responses)
- bladder instability (detrusor contractions)
- intestinal motility decreased
- Examples
- Anticholinergics`
- Thermoregulation * Mechanism: * Poor temperature regulating
mechanisms: (e.g. shivering, metabolic rate,
vasoconstriction,
thirst
response ,
awareness of T) - Examples * Meds affecting awareness,
mobility, muscular activity,
vasoconstrictor mechanisms - CNS meds (e.g.
phenothiazines, barbiturates,
BZD, narcotics, EtOH)
Temperature
