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EAHP 2012 Report – Drug safety in geriatric patients
by Zara Qadir reporting on the presentation by Professor Petra Thürmann (pictured) from the Philipp Klee-Institute of Clinical Pharmacology at the HELIOS Klinikum Wuppertal in Germany.
Understanding the pharmacokinetic parameters differences in the elderly compared to young patients is increasingly important for hospital pharmacists as our population ages. In 2002, the USP MEDMARX 2002 report showed that more than one third of hospital medication errors involved geriatric patients.Closing the EAHP Congress was Professor Petra Thürmann from the Philipp Klee-Institute of Clinical Pharmacology at the HELIOS Klinikum Wuppertal in Germany, who offered delegates expert guidance in the safe management of drugs in the elderly patient.
“We know that drugs are differently metabolised and eliminated in old age, and there is an altered pharmacokinetic profile. Also, elderly people who have multiple morbidities are exposed to more adverse drug interactions than younger people. For some drugs, we have to weigh up whether they have the same benefit/risk ratio in elderly people as they do in younger people,” emphasised Professor Thürmann.
Defining ‘old age’ by calendar (for example above aged 65 years) is not always appropriate as older patients exhibit a wide inter-individual variability. Ageing can be defined physiologically as ‘the gradual biological impairment of normal function as a result of changes to cells and structural components, which have a direct impact on organ function’1.
‘Frailty’ is an important concept, as frail elderly individuals will have a decline in their physiological function, which can increase their vulnerability to adverse events2. A number of functional parameters and tests examine and characterise fragility (e.g. Charlson Index, Functional Comorbidity Index3, Handgrip Test, Timed up and go-Test etc.), which are being adopted in clinical trials.
Polypharmacy becomes increasingly common in individuals as they approach the ninth decade of their lives. Professor Thürmann described a study of drug-intake amongst a fit and healthy ABI-cohort4 of community–dwelling German seniors (n= 1937, 78,2 +/- 4,2 years, 53.3% females). Even though the individuals were reasonably healthy for their age, around 64% of patients were on five drugs per day or more5.
A ‘pharmacologically unhappy triad’ and the renal system
One system that is very sensitive in old age is renal function. ‘A pharmacological unhappy triad’, can occur with certain drug combinations in elderly patients: (high dose) diuretics, NSAIDs and inhibitors of the renin-angiotensin-aldosterone-system RAAS (ACE-inhibitor, AT1-Blocker, renin-inhibitor). These drug interactions can cause an increase in blood pressure and in the worst-case scenario − renal failure. Research has shown that preventable drug-related hospital admissions are a result of this particular combination6.
As people age, their renal function declines dramatically. One third of patients over 85 years have a low creatinine clearance (eGFR of under 30 ml/min)7,8. This is problematic, and a recent study has shown that one third of patients with decreased renal function are not recognised and treated as such by their primary care physician9. Furthermore, one third of prescriptions of renally excreted drugs are not dose-adapted according to renal function of the individual patient9,10.
“Even in most recent drug development, the relevance of age and renal function appears to be underestimated [example of RELY study11]. Dosing recommendations are derived from subgroup analysis,” commented Professor Thürmann, who advised closer monitoring of renal function for elderly patients. Serum creatinine should be checked at least once a year and adjusted. Hospital pharmacists can also flag patients with creatinine-clearance under 60 ml/min in hospital and primary care.
Pharmacodynamics in the elderly
Unfortunately, there is a shortage of studies performed in elderly patients that address pharmacodynamics. Changes in receptor density, affinity signal transduction and cellular response occur with ageing. Thürmann highlighted an array of changes and vulnerabilities occurring in the elderly person. “Reflex response is decreased which make elderly people more vulnerable to acute or rapid changes such as high temperatures. The central nervous system suffers from decreased perfusion and function, which make elderly patients vulnerable to delirium states after surgery.” One recent study12 showed that benzodiazephines slow down reaction time by half (increasing sedation, delirium and reducing cognitive function).
Potentially inappropriate medications (PIMS)
Some drugs are classified as potentially inappropriate medications (PIMS) for the elderly. For example, drugs with anticholinergic side effects can cause problems [see Table 1]. In the Three-Cities Study13, there was a decline in cognitive functions associated with anticholinergic drugs over four years [see Table 2].
PIMs are defined as medications for which the risk of an adverse event outweighs the clinical benefit, particularly when there is evidence in favour of safer or more effective alternative therapy for the same condition14. Specific recommendations (e.g. dose-adjustment) are useful to avoid adverse events15. Most PIMS are drugs that have anticholinergic effects (e.g. some urological antispasmodics, tricyclic antidepressants) or are drugs that may increase the risk of falls (e.g. short acting nifedipine, doxazosin or long-acting benzodiazephines).
For reference purposes, several PIM lists have been developed including the recently updated Beers list15,16, a Canadian criteria list17 and a GermanPRISCUS18 list.
In Europe, 20% of elderly patients (over 65-years) receive one prescription with at least one potentially inappropriate drug19. Several studies have shown that PIMs are associated with increased risk of hospitalisations20, increased fall-risk21 and an increase in number of office visits22. Conversely, other studies have shown contradictory results23,24,25. Unfortunately, there are still no randomised control studies that prove an association between PIM reduction (feasibility and safety of alternatives) and reduction in the number of adverse events. However, retrospective data from the German ABI-Cohort does show polypharmacy-treated patients have a higher risk for five or more consultations per month and a higher risk of 2 or more falls26.
PIMs lists can be used to check drug-to-drug interactions, duplication of treatment (unnecessary therapies) and monitoring of drug therapy. Pharmacists can also analyse the prescription databases against known risk factors.
Is this an adverse effect of medication or a new disease?
When a patient is hospitalised exhibiting new symptoms, health care practitioners should question whether the symptom is indicative of a new disease, or is if it is an adverse effect of existing medication regime. In some circumstances, a prescribing cascade can develop [see Figure 1]. “When recording symptoms, you should look out for falls, cognitive function and gastrointestinal symptoms,” advised Thürmann. Pharmacists and clinicians should check whether a patient has been newly described a drug. Every new symptom could potentially be a side effect [see Figure 2].
Adverse drug-drug interactions with polypharmacy
In the German getABI-Cohort4, over a fifth of patients (n=426) had serious or a contraindicated drug-drug interaction (n=16)5. The German researchers have also been collecting adverse event data27 and have found that about 5% of hospitalisations were drug related. In the over 70 years old age group, patients had five conditions (4,8+/- 2,0, <0.001) and took 6 drugs per day (6,4 +/- 2,8, <0,001). Over half of the drug problems were from drug-drug interactions (see Figure 3).
“Drug-drug interactions is something we could prevent either by electronic prescribing or having pharmacists checking for possible interactions,” stressed Thürmann. However, studies are still unclear as to whether electronic prescribing reduces adverse events28 and there is a lack of prospective studies.
To combat drug-drug interactions, medication reconciliation by pharmacists has been shown to be useful29. Professor Thürmann urged hospital pharmacists to be involved in assessing the case of vulnerable elderly patients using AVOVE Quality Indiciators30. Another useful screening tool is STOPP (Screening Tool of Older Person’s Potentially Inappropriate Prescriptions)/START31 (Screening Tool to Alert doctors to the Right i.e. appropriate, indicated Treatment).
ACOVE Quality Indicators30:
- Updated medication list, annual drug review
- Proper instructions about drugs
- Documentation of drug responses
- Check for drug interaction and PIMs
Concluding remarks
“We need proper data on drug safety and efficacy in elderly patients because frequently nowadays elderly patients are not involved in clinical trials. We also have to properly characterise the patients according to function, cognition, and their preferences. We will never have a guideline (and clinical trials) for all combinations of multi-morbidity so it will always be an individualised drug therapy according to the needs of the individual patient. Our seniors require and deserve support and this must be a multi-professional approach from physicians, pharmacists, nurses, and social workers.”
References:
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2. Rockwood K. et al., 2005. What would make a definition of frailty successful? Age Aging 34(5): 432-434
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4. Diehm C et al. Circulation 2009; 120:2053-2061.
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9. Harder et al. 2009
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14. Laroche et al. Clin Pharmacol ther 2009
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18. Holt et al. Dtsch Arztebl Int 2010
19. Fialova et al, JAMA 2005
20. Jam & Asparasu, Ann Pharmacother 2007
21. Berdot et al, BMC Geriatrics 2009
22. Fick et al. J Med Care Pharm 2001
23. Page and Ruscin Am J Geratr Pharmacother 2006
24. Laroche et al. br J Clin Pharm 2007
25. Hanlon et al. med care 2002
26. Holt R., 2010
27. Schmiedl S. basic Clin Pharmacol toxicol 2007 101: (5) 339
28. Health Technology Assessment, DIMDI, Germany, 2009 (http://www.dimdi.de/static/en/hta/)
29. Kaboli P.J., Arch Intern Med 2006;166:955-964
30. Gallagher P.F., Int J Clin Pharmacol Ther 2008; 46: 72-83.
