Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5910_Библиотеки_им_академика_М_И_Перельмана
.pdf
462
A. R. Mair et al.
Polypharmacy
Metabolism:
hepatic blood
flow, size and
enyzme function
Distribution:
muscle, fat,
albumin
Fig. 20.1 Common pharmacokinetic changes in drug use, absorption, distribution, metabolism, and excretion in old age
pharmacokinetics and pharmacodynamics [15,
16]. There is limited research characterizing the
effects of frailty as a source of variability in pharmacokinetics and pharmacodynamics among
older people [17].
Digoxin provides an example of the complexity of pharmacokinetics and pharmacodynamics
in old age. Clearance of digoxin, which is predominantly excreted unchanged by the kidneys,
is reduced by age-related decline in glomerular
ltration and tubular secretion, compounded by
the effects of common chronic diseases in old
age such as diabetes, hypertension, and cardiovascular disease, and exacerbated by acute renal
failure during acute illness or injury. Drug interactions may occur by blockage of renal transporters involved in active secretion of digoxin by
commonly used drugs in older people, such as
erythromycin or verapamil, resulting in digoxin
toxicity. Pharmacodynamically, the most serious
adverse effects of digoxin are cardiac arrhythmias. Susceptibility to these is likely to be
increased with the increased prevalence of
underlying cardiovascular disease in old age and
the increased prevalence of hypokalemia and
hypomagnesemia, which are very common with
concurrent use of diuretics or proton pump
inhibitors. Even the less serious adverse effects
of digoxin, such as nausea, can precipitate serious malnutrition in an older person. Safe use of a
narrow therapeutic index drug like digoxin
requires constant vigilance with frequent clinical
and therapeutic drug monitoring and proactive
dose adjustment.
Absorption:
Passive – slower, complete
Active – impaired transporters
Excretion:
renal function
20 Safe Prescribing and Monitoring in the Older Person
463
5 Aging, Medication-Related
Harm, and
Pharmacovigilance
One of the consequences of polypharmacy in
older adults is medication-related harm, which
can include harm from adverse drug reactions (ADRs), nonadherence, and medication
errors. Factors such as age-related changes in
pharmacokinetics and pharmacodynamics,
reduced physiological reserve, and a higher prevalence of cognitive impairment can predispose
older adults to medication-related harm.
Between 1988 and 2021, 250,000 hospital
admissions in Australia were medication-related,
with an associated cost of AUD$1.4 (€920) billion annually [18]. Importantly, two-thirds of the
medication-related hospitalizations were potentially preventable. In the UK, it was estimated
that there are 237 million medication errors in
England over a year period [19], and preventable
ADRs were estimated to cost the National Health
Service (NHS) £98.5 (€115) million perannum,
consume 181,626 bed days, and cause/contribute
to 1708 deaths during initial hospitalization.
Additionally, certain environments may increase
patients’ risks of developing medication-related
problems. These include transitions of care, such
as transition from hospital to the home or residential care, due to changes in medications, poor
communication between transition, and problems
with medication adherence. A systematic review
found that 17–51% of community dwelling
patients discharged from hospital within 30days
experienced medication-related harm [20]. The
effects of medication-related harm include
disability, hospitalization, and death [20]. It is
estimated that in the USA, adverse drug events
will be responsible for at least 4.6-million hospitalizations of older people and as many as
150,000 premature deaths over the next decade,
with economic cost of medical care to treat
adverse drug events about $62billion [21]. The
Organisation for Economic Cooperation and
Development (OECD) found older people in
long-term care settings were at an increased risk
of medication-related harm [4]. Interestingly, a
Norwegian study reported that more medication-
related problems were found for patients who
were frail, receiving nursing home care in their
own homes, rather than those residents in nursing
homes [22].
Specic to the older person, there are many
challenges prescribers face that can impede
appropriate prescribing, especially with multiple prescribers and multiple patient comorbidities. Avoiding the “prescribing cascade” is one
such challenge—when a new medicine is prescribed to “treat” a side effect of another medicine, in the mistaken belief that a new medical
condition requiring treatment has developed
[23]. In younger individuals, side effects may be
easier to differentiate; however, given the complexities of older adults, multimorbidity and
polypharmacy, a side effect can be misdiagnosed as a new condition. For example, dihydropyridine calcium channel blockers, such as
amlodipine, are commonly prescribed for
hypertension and can often result in peripheral
edema in the individual. Treatment of peripheral
edema with loop diuretics, such as furosemide,
can increase the risk of adverse events such as
falls and hospitalization, and can potentially
decrease quality of life [24]. A simpler solution
for addressing the peripheral edema would be to
reduce the dose ofamlodipine, while monitoring for side effects and blood pressure goals,
considering if an alternative medication should
be prescribed in place.
Identifying medications that may predispose
an older person to medication-related harm can
be challenging for healthcare practitioners.
Several tools have been developed to identify
high-risk or potentially inappropriate medications, and these include explicit and implicit criteria, such as The Beers Criteria [25] and the
Screening Tool of Older Person’s Prescriptions/
Screening Tool to Alert Doctors to the Right
Treatment (STOPP/START) [26]. These criteria
have been studied extensively in older people to
evaluate their effects on medication-related harm
and ADRs [27, 28]. Other tools such as The Drug
Burden Index (DBI); a measure of the cumulative
exposure to anticholinergic and sedative medications in an older person can be used to estimate
the impact of high-risk medications on clinical
464
A. R. Mair et al.
measures such as physical function [29]. In practice, these measures are all potentially useful
clinical risk assessment and screening tools.
However, clinical decisions require assessment
of the risk of harm in the individual (which is
variable) and the potential benet of treatment.
Case study 2 discusses about an older person
with high anticholinergic and sedative burden to
understand the contribution of multimorbidity
and polypharmacy on medication-related harm
and the role of pharmacovigilance in reducing
it.
6 Undertaking Person-
Centered Medication Review
When undertaking medication reviews, it is
important to involve the older person and their
carer in the decision-making about the medications they are taking, considering “what
matters to you.” One example is the seven-step
approach taken to review medication [30]
(Fig. 20.2: Seven steps to appropriate poly-
pharmacy). The seven- step approach starts by
matching therapeutic objectives to current life
priorities with the patient. This initial discussion guides decision- making in subsequent
steps that consider medication need, effectiveness, and safety before a therapeutic plan and
follow-up strategy are agreed upon.
Determining the therapeutic objectives with
the patient’s current life priorities (step 1)
allows decision about whether the right medication has been chosen, followed by assessing
whether the medicines are essential (step 2) or
unnecessary (step 3), whether therapeutic
objectives that matter to the patient are achieved
(step 4), which medicines are too risky or cause
unacceptable adverse effects (step 5), which
medicines are not cost-effectiveor more harmful to the environment (step 6), and whether the
patient is willing and able to manage their medicines in a way that avoids harm and maximizes
benet (step 7).
Medication reviews can be conducted in multiple settings, such as within the home, residential
aged care facility, or hospital, and by multiple
practitioners, including pharmacists, general prac-
titioners, and specialist physicians. There are various models of medication review service provision
internationally. In the USA, the Medication
Therapy Management (MTM) service aims to
ensure the best therapeutic outcomes for patients
and includes ve elements: medication therapy
review, a personal medication record, a medicationrelated action plan, intervention or referral, and
documentation and follow-up [31]. In a study that
evaluated the collaboration between physicians
and pharmacists providing the MTM service for
150 patients, physicians accepted 47–50% of recommendations made by pharmacists to stop or
change medications for patients with polypharmacy and demonstrated that patients beneted
from collaboration between physicians and pharmacists [32]. The Home Medicines Review
(HMR) and Residential Medication Management
Review (RMMR) are two established, government-funded pharmacist- led medication review
services available in Australia [33]. A study that
aimed to evaluate RMMRs on medication use
appropriateness in 223 aged care residents demonstrated a reduction in inappropriate prescribing
among aged care residents [34]. Across the UK
health services, there are GP practice pharmacists
who are working as part of the multidisciplinary
teams, and part of their roles will be to undertake
medication reviews. In Scotland, in 2012, policy
was introduced for pharmacists to work as part of
the multidisciplinary teams to undertake polypharmacy reviews using the seven-step process, and
was also introduced as part of the GP contract for
those patients who needed anticipatory care plans
[35]. Many pharmacists across the UK are independent prescribers, which allows for the prescribed medications to be altered and amended by
the reviewing pharmacist. Across England, medicines optimization services have been developed
for pharmacists to deliver structured medication
reviews as part of contracted enhanced services
[36].
While undertaking medication reviews, it is
important to consider the older person’s goals
and preferences, together with their current medical conditions and medications. Shared decisionmaking during medication review can open the
conversation with older people, allowing them to
express their preferences and improve patient
20 Safe Prescribing and Monitoring in the Older Person
465
Fig. 20.2 Seven-step process to person-centered approach for appropriate prescribing (reproduced with permission
from Scottish Government, Effective Prescribing and Therapeutics Division [30])
autonomy, which is important for all decisions
including deprescribing [37]. A recently developed tool called the PREparing Patients for
6.1 Monitoring andReview
ofHigh-Risk Medicines
inOlder People
Active Involvement in medication Review
(PREPAIR) can support active involvement of
patients during medication review within general
practice [38].
Case studies 1 and 2 discuss the importance of
undertaking person-centered medication review.
In the earlier sections of this chapter, we have
considered the changes in physiology that predispose the older person to increased medicationrelated harm. Incidence of frailty further
complicates this issue, and particular attention
needs to be given to the groups of medication
466
A. R. Mair et al.
where additional factors in prescribing and monitoring need to be considered.
The highest prevalence of preventable harm is
seen in the older person, with high comorbidity
and polypharmacy. The risk of harm is generally
higher in older people with multimorbidity than
in younger patients due to their reduced ability to
clear drugs (e.g., due to renal and/or hepatic
impairment) and increased vulnerability to drugs’
adverse effects (due to general frailty and drug–
drug and drug–disease interactions) and medication burden [39, 40]. However, the increased risk
of harm is not always offset by increased benets,
and for many preventive medicines, such benets
may never be realized due to a shortened life
expectancy.
When reviewing medications for older people,
it is important to consider areas of prescribing
where monitoring would need to be done to minimize harm. A rapid systematic review identied
that medicines implicated in causing the most harm
in older people found to be at increased risk of
harm [41]. Table 20.1 describes monitoring that
should be undertaken to assess the efcacy and
safety of these medicines. The table is not exhaustive but covers a few areas for consideration of
some of the high-risk medications, especially when
the older person is taking multiple medications
[42].
6.2 Quality Indicators
Several countries have developed inappropriate
prescribing indicators that might be related to
either the number of medications used, specicmedications, or specic medication combinationsused for older persons [30, 43–45]. Some
jurisdictions also have indicators for identication of medication-related harm and process indicators for medication review [45, 46]. The use of
quality indicators is helpful to establish benchmarks but then to also drive improvement and
sustain change.
These indicators should be chosen to address
country-specic prescribing challenges that need
addressing for the older person. National prescribing data or national pharmacovigilance reporting
and learning systems may help identify key areas
to address. One example of a quality indicator
would be the inappropriate use of antipsychotics in
people with dementia. Antipsychotics have an
adverse prole on cardiovascular health and can
cause extrapyramidal symptoms, sedation, and
falls. The chart in Fig.20.3 shows the use of antipsychotics across different regions of Scotland.
6.3 Factors Aecting Patient
Decision-Making
andInvolvement
Patient involvement is crucial for making effective and safe medical plans, including optimizing
medication regimens. This may be direct (discussion with patient), informed (through previous
documentation of goals, values, and wishes), or
indirect (what family and friends recommend).
This will ensure that rather than an unbalanced
snapshot view, factors affecting the older person’s daily life are taken into consideration.
Patients may access treatment across different
care settings, and this can result in siloed care for
the older person that should be ideally coordinated so that it is integrated [47]. These problems
can be exacerbated when patients access services
from acute hospital services instead of primary
care and were observed during the COVID-19
pandemic [48]. While options such as remote
consultation may be effective, some older people
may nd this approach more challenging [49].
Under these challenges, patients may be given
prescriptions inappropriately.
There are several mechanisms that can help
instigate involvement of older patients in the
acute setting to ensure optimal, safe patient decisions [50]:
– Ensure involvement of the multidisciplinary
team to assess frailty and function prior to
acute illness and aim to restore patient to this
level of function if possible.
– Involve pharmacists to help assess appropri-
ateness of medication by obtaining the best
possible medication history and medication
review, to avoid inappropriate polypharmacy
20 Safe Prescribing and Monitoring in the Older Person
467
Table 20.1
monitoring that should be undertaken to optimize safety and effectiveness of treatment
Medication class with
potential to cause harm
Simple analgesics (e.g.,
acetaminophen/
paracetamol)
Commonly used antibiotics
For example: piperacillin/
tazobactam, amoxicillin/
clavulanic acid, gentamicin,
ciprooxacin
Antithrombotics including
aspirin, clopidogrel, and
other antiplatelet drugs,
Factor Xa inhibitors, low
molecular weight heparin,
warfarin
Anti-inammatory
(NSAIDs)
Antidepressants Begin with a low dose, increasing
Common medication classes that have the potential to cause harm in the older person and a summary of
Monitoring to be done to assess
efcacy
Onset of pain relief is
approximately 30min after oral
administration and 5–10min after
IV infusion
Chronic pain can take up to
3months to control
Systemic (e.g., fever, white cell
count, and inammatory markers)
and local evidence (e.g., wound)
of bacterial infection
Relevant coagulation measure
(e.g., INR for warfarin), clinical
conditions (vessel imaging may
be required), patient status
Check the impact on pain relief/
symptoms after initiating the
treatment
gradually over 2–4weeks as
tolerated
Full effect may take 6–8weeks,
but improvement is often seen
within 1–3weeks. “Start low and
go slow” with frequent
consultations to monitor for
efcacy
Monitoring that should be done to avoid and
detect harm (with comments)
• Elevated aminotransferases
• Factors thatmay predispose to hepatotoxicity:
prolonged fasting or malnutrition, hepatic
enzyme inducers, severe renal/liver impairment,
chronic alcohol intake
• Adherence/medication error contributes to
toxicity in old age, with cumulative exposure
from different formulations available over the
counter
• Liver and renal function—inform dose and may
be signs of toxicity
• Other toxic effects—ototoxicity, gastrointestinal
side effects (e.g., Clostridium difcile)
• Antibiotic allergy: immediate (e.g., urticaria,
angioedema, anaphylaxis) or delayed (e.g.,
Stevens–Johnson syndrome)
• Use as per local antimicrobial formulary with
reference to local resistance patterns and take in
depth drug allergy history
• Renal function, liver function
• Consider pharmacokinetic and
pharmacodynamic drug interactions
• Note an increased risk of hemorrhage with
multiple antithrombotics, e.g., combination of
aspirin and clopidogrel
• Risk of gastrointestinal bleeding is exacerbated
by a history of peptic ulcer disease and the
pharmacodynamic interactions of several
medicines, including other NSAIDs,
antiplatelets, anticoagulants, corticosteroids, and
selective serotonin reuptake inhibitors
• Decisions to use NSAIDs in older patients, alone
or in combination, should be restricted to
scenarios where there are no alternatives. When
unavoidable, consider gastroprotection:
• May increase cardiovascular risk
• Consider topical preparation
• Older people may have slow response to
treatment with a higher risk of recurrence
• Hypernatremia, falls, and anticholinergic effects
are common adverse effects of antidepressants in
old age
• Older adults are at increased risk of long QT
syndrome
• Mirtazapine and sertraline seem ineffective for
depression in people with dementia
• Optimize nonpharmacological interventions
(continued)
468
A. R. Mair et al.
T
able 20.1
Medication class with
potential to cause harm
Antiepileptics “Start low and go slow” with
Antipsychotics Antipsychotic response may
Cardiovascular:
antiarrhythmics (e.g.,
atenolol, bisoprolol)
Corticosteroids Review of clinical condition and
Hypnotics Monitor effects on sleep
(continued)
Monitoring to be done to assess
efcacy
frequent consultations to monitor
for clinical efcacy
Tailor the dose of all antiepileptic
drugs to clinical response. With
some agents (e.g., phenytoin,
carbamazepine), monitoring
plasma concentrations may be
useful
occur in 1–2weeks; however,
allow 2–3months for full trial
“Start low and go slow” because
of greater risk for adverse effects
(e.g., hypotension, confusion,
anticholinergic effects, and acute
Extra Pyramidal Side
[EPS]effects)
Review response to medication
after initiation in terms of
cardiovascular symptoms,
HeartRate, BP, and ECG/ 24-h
ECG monitoring as appropriate
for indication
whether there is ongoing
indication for prolonged therapy
of oral (e.g., >7.5mg daily of
prednisolone or equivalent for
>3months) and inhaled forms
Tolerance develops to the
hypnotic effects of
benzodiazepines in weeks
Monitoring that should be done to avoid and
detect harm (with comments)
• For seizure-free older patients, altering the dose
to bring apparently subtherapeutic plasma
concentrations into the therapeutic range can
induce toxicity
• Falls and fracture risk may be increased by CNS
adverse effects
• Hyponatremia is common with carbamazepine
and oxcarbazepineand hypernatremia is
common with phenytoin
• Can be used for neuropathic pain and should not
be used for generalized pain—evaluate
appropriateness
• Associated with increased risk of stroke and
death (increased risk with higher doses and
rst-generation antipsychotics)
• Treat for the shortest possible time to minimize
the risk of tardive dyskinesia and death
• Avoid if possible, in people with dementia
• Falls and anticholinergic effects are common
adverse effects of antipsychotics in old age
• Older adults are at increased risk of long QT
syndrome
• Be aware of drug–drug interactions that may
precipitate heart block (e.g., other
antiarrhythmics, cholinesterase inhibitors)
• Consider cardiovascular disease or drug side
effects with falls, syncope, and breathlessness
Prolonged corticosteroid therapy can lead to
osteoporosis, glaucoma, and cataracts; increased
infections; and changes in blood chemistry/
physiology, blood sugar, and blood pressure
(Cushing’s-like syndrome)
Acute corticosteroid therapy can precipitate
delirium in older people
• The pharmacological action of benzodiazepines,
through positive allosteric modulation of the
GABA-A receptors increasing GABAergic
transmission, impair memory, increase sedation,
cause inattentiveness, ataxia, and motor
impairment, providing a pathway for their
association with dementia, delirium, and falls
• Multidisciplinary review of falls prevention
interventions to minimize impact of druginduced falls
(continued)
4
Percentage of patients (%)
Source: Prescribing Information System Scotland, PHS, NSS.
20 Safe Prescribing and Monitoring in the Older Person
469
T
able 20.1
Medication class with
potential to cause harm
Centrally acting analgesics:
e.g., opioids, gabapentinoids
(continued)
Monitoring to be done to assess
efcacy
Review indication regularly:
avoid long-term use of opioids
for chronic noncancer pain
Monitor pain and be aware of
tolerance
Check that simple analgesics are
used optimally
Set realistic goals regarding pain
management and ensure use of
multidisciplinary interventions
Diuretics Onset of action following oral
administration is 4–6h
Monitor uid balance (e.g.,
weight) and symptoms/signs
(e.g., peripheral or pulmonary
edema)
Respiratory: prednisolone
and inhaled corticosteroids;
inhaled beta-agonists;
inhaled anticholinergics
Review of clinical condition with
examination and use of
investigation such as peak
owand spirometry
Monitoring that should be done to avoid and
detect harm (with comments)
• Monitor for potential dependency and
withdrawal reaction (while dose is being
reduced)
• Monitor people taking opioids for constipation
and prevent with aperients (bulk-forming
laxatives)
• Review multidisciplinary falls prevention
interventions to minimize impact of druginduced falls
• Older adults are more susceptible to electrolyte
imbalance, orthostatic hypotension, and urinary
incontinence with diuretics. Urinary
incontinence may reduce adherence
• If deprescribed, then wean slowly to prevent
rebound uid retention and heart failure
• Review inhaler technique to avoid oral thrush
and ensure effectiveness
• Review side effects of steroids (as above) and
encourage patient education for adherence and
appropriate weaning regimens
• Consider beta agonist effect in patients with
tachycardia or palpitations
• Side effects of long-acting muscarinic receptor
antagonists (LAMA), e.g., glaucoma
3.5
3
2.5
2
1. 5
1
0.5
0
Mar
2018
Fig. 20.3 Proportion of people aged 75 years and over prescribed an antipsychotic medication as a percentage of all
people aged 75 years and over (from Mar 2018 to Sept 2022)
Sep
2018
Mar
2019
Sep
2019
Mar
2020
Sep
2020
Mar
2021
Sep
2021
NHS BOARDS
SCOTLAND
Mar
2022
Sep
2022
470
A. R. Mair et al.
as well as ensure crucial medications are not
being missed [30, 51, 52].
– One way to avoid harm is to have prearranged
emergency healthcare plans (anticipatory care
plans) in place, which are documents detailing
patient goals and wishes and past medical history [51]. It is also important to consider any
legal documents that may have been put in
place to support the older person and avoid
unnecessary hospital prescriptions and potential admissions. This would have a dual effect
in optimizing patient care and reducing the
burden on hospital services.
– Appropriately direct patients to the most rele-
vant care service to help ensure best practice
treatment and most effective continuity of
care, e.g., clinical pharmacists supporting
review of prescribing.
– Empower patients to become their own health-
care champion to help alleviate the strain built
up due to service provision. For example, having an accurate medication list held by the
patient or a “health passport” can enhance the
medication history that should be integrated as
part of every consultation.
– Conduct a thorough medication review that
includes reconciliation when the patient
crosses care transitions to enable safer medication prescribing.
– Enhanced, streamlined documentation, online
prescribing, shared access to notes between
primary and secondary care, as well as patient
involvement documented clearly allow primary and secondary care to efciently communicate and ensure safe medication-related
decisions are made while considering patient
views.
6.4 Impact ofMedicines
onHealthy Aging
Successful aging focuses on expanding healthy,
functional years of life [53]. This includes avoiding disease and disability, having high cognitive
and physical function, high social engagement, a
positive mood, and feeling in control. Currently
available therapeutic drugs play important roles
in prevention and management of disease.
Pharmacovigilance studies suggest that medications can affect healthy aging in either direction.
Some medicines (e.g., those with anticholinergic
and sedative effects) have negative impacts on
cognitive, mental, and physical function [29].
Medicines may also affect social engagement, for
example, people may avoid outings because of
incontinence precipitated by diuretics, or be better able to interact socially because their breathlessness is well controlled by medicines treating
chronic cardiac or respiratory disease, allowing
them to talk more easily.
Internationally, development or repurposing of
medicines that target aging biology itself to
improve health span is underway, with the emergence of geroscience research [54]. Geroscience
investigates the effects of interventions, including
licensed therapeutic medications, on modifying
the hallmarks of aging, such as DNA instability,
telomere attrition, epigenetic alterations, loss of
proteostasis, deregulated nutrient- sensing, mitochondrial dysfunction, cellular senescence, stem
cell exhaustion, and altered intercellular communication [55]. For example, in preclinical studies,
metformin and rapamycin have shown some
effects on some of these hallmarks and have
reduced the incidence of age- related disease and
increased some measures of healthspan. In the
absence of rigorous clinical data and of a regulatory framework, no medications are currently recommended to target healthy aging. Some older
people already take medications and/or supplements in the hope that they may improve healthspan. It is important to ask patients about these
since they may interact with the patient’s medications and medical conditions. The future use of
effective therapies that target healthy aging will
need to consider all issues in safe prescribing for
older adults discussed in this chapter and ultimately may impact on the prevalence of multimorbidity and polypharmacy in old age.
Pharmacovigilance is a key tool for identication of associations between drug use and markers of successful aging [56]. It is important to test
the effects of real-world drug use in complex
20 Safe Prescribing and Monitoring in the Older Person
471
older people on not only lifespan but also health
span. This can be done with cross-sectional and
longitudinal pharmacoepidemiology studies,
analyzing data on drug use and on components of
successful aging, including incident diagnoses of
chronic disease, objective functional measures,
measures of social activity and mood. For example, among people with diabetes, metformin,
which acts on key pathways in the biology of
aging, is associated with slower cognitive decline
and reduced risk of dementia [57].
6.4.1 Geriatric Syndromes
Geriatric syndromes are nonspecic, multifactorial conditions and are common presentations
among older people (e.g., cognitive impairment,
frailty, falls, incontinence). Geriatric syndromes
have a bidirectional relationship with medication-related problems. The most reversible causes
of geriatric syndromes are ADRs. Therefore, it is
important to consider this possibility when older
people present with conditions such as cognitive
impairment, falls, incontinence, and frailty. A
medication is more likely to cause an acute presentation when there has been a change in prescribing (new drug or dose, affecting person
directly or indirectly through drug interaction) or
an acute increase in concentration (e.g., acute
renal or hepatic failure, reducing clearance).
Geriatric syndromes also increase the risk of
non-adherence, medication errors, and adverse
drug effects. For example, people with cognitive
impairment may have difculty remembering and
following medication regimens, and medication
management may involve formal and/or informal
carers. Frail older people with multimorbidity are
more likely to have multiple prescribers, which
can result in a lack of care co-ordination, unrecognized drug–drug and drug–disease interactions,
and complex management regimens. Various
tools are available to assess frailty, for example
the Rockwood Frailty Index [58] including electronic versions available at the point of care [59],
which measure accumulation of age-associated
decits across multiple domains. These are helpful to inform anticipatory or emergency care planning and have conversations about patients’
objectives and priorities for treatment, as well as
raising awareness of additional care required to
treat these complex, vulnerable people, who are at
increased risk of severe adverse drug effects.
Much of the evidence on the association
between medication use and geriatric syndromes
comes from pharmacovigilance [56]. This
includes spontaneous case reporting and pharmacoepidemiologic studies of associations between
medication use and these outcomes. There are
also observational studies demonstrating differences between people with and without geriatric
syndromes in adherence with single disease treatment guidelines [60] and prevalence of drug
interactions [61].
The signals from these pharmacovigilance
studies are supported by mechanistic pharmacological data and interventional studies.
Mechanistically, medications with anticholinergic and sedative actions have well-studied pharmacological mechanisms that explain the
observed associations of the use of these medication classes with geriatric syndromes. Shortterm interventional studies of treatment with
single drugs demonstrate direct drug effects relevant to geriatric syndromes. For example, single-dose studies of tricyclic antidepressants,
which have anticholinergic properties, result in
decits in attention and reaction time, although
these effects may vary with dose, with development of tolerance during long-term treatment
[62]. These effects may be cumulative when
multiple anticholinergic drugs are administered
together [63].
For some medication classes, interventional
studies have demonstrated a reduction in these
syndromes when medications are withdrawn and
ceased (deprescribed) [46]. For example, a randomized trial demonstrated that withdrawal of
psychotropic drugs reduced the risk of falling in
older people [64].
The combined data from pharmacovigilance,
mechanistic, and interventional studies are used
to inform clinical assessment. If a patient presents with a geriatric syndrome, it is important to
look for a potentially reversible drug-related
cause.
Соседние файлы в папке Библиотека им академика М.И. Перельмана