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LETTER TO THE EDITOR |
Section of Geriatric Medicine Department of Internal Medicine Erasmus Medical Center and Harbour Hospital Rotterdam The Netherlands
Address correspondence to Tischa J. M. van der Cammen, MD, PhD, Section of Geriatric Medicine, Erasmus Medical Center, P.O. Box 2040, NL-3000 CA Rotterdam, The Netherlands. E-mail: t.vandercammen{at}erasmusmc.nl
To the Editor:
Falls are among the most common and serious problems facing older persons and are associated with considerable morbidity and mortality (1). In this letter, we discuss drug-induced falls by presenting three cases from our Falls Clinic in whom falls stopped after a change in their drug regimen. Data on drug-induced falls are limited, but there is a consistent association between use of psychotropic drugs and falls in older persons (2,3). In addition, an increased fall risk has been demonstrated for certain cardiovascular drugs and for polypharmacy, defined as the use of three or more prescribed medications (4). Also, a fall before hospital admission has been shown to be a risk indicator for a severe adverse drug reaction (5).
Case 1
An 89-year-old woman complained of weekly fainting spells and falls, sometimes upon standing up, for the past 3 years. She had a history of hypothyroidism, glaucoma, and pulmonary embolism. She used thyroxin 0.1 mg once daily, aspirin 38 mg once daily, and timolol eyedrops 0.25% in both eyes once daily. On physical examination, blood pressure supine was 160/80 mmHg and regular pulse rate was 76 bpm. The lowest blood pressure after a half minute, 1 minute, 2 minutes, and 3 minutes of standing was 145/80 mmHg; pulse rate 92 bpm. Further physical examination was normal. Laboratory work yielded normal blood count, electrolytes, renal and liver profiles, thyroid-stimulating hormone, and free thyroxin. The electrocardiogram (ECG) showed sinus rhythm, first degree atrioventricular block, and left bundle branch block.
Systolic orthostatic hypotension induced by the systemic effect of the ocular beta-blocker was suspected. Her eyedrops were therefore changed to latanoprost. Follow-up for 9 months revealed that, after the change of her eyedrops, syncope, dizziness, and falls ceased, confirming the diagnosis.
Case 2
A 74-year-old woman complained of frequent falls for the past 3 months, mainly at night. Her medical history revealed a hip fracture, percutaneous transluminal coronary angiography, heart failure, diabetes mellitus, and urinary incontinence. Her medication consisted of perindopril 4 mg once daily, furosemide 40 mg once daily, metoprolol slow-release 100 mg once daily, aspirin 100 mg once daily, simvastatin 20 mg once daily, metformin 500 mg twice daily, and colecalciferol 400 I.U. once daily. Three months earlier, tolterodine 4 mg once daily had been added because of urinary incontinence. On physical examination, she had diastolic orthostatic hypotension, her blood pressure supine was 130/75 mmHg, and regular pulse rate 68 bpm. The lowest blood pressure after a half minute, 1 minute, 2 minutes, and 3 minutes of standing was 130/65 mmHg; pulse rate 72 bpm. Except for a trace of pitting edema at both ankles, physical examination was normal. Laboratory work yielded normal blood count, electrolytes, and renal and liver profiles. Nonfasting glucose was 9.5 mmol/l; HbA1c 8.5%. ECG showed sinus rhythm and left axis deviation. Because the falls had started around the time of the addition of tolterodine, this drug was thought to be the most probable cause of the falls, as its anticholinergic properties can induce orthostatic hypotension. Therefore, tolterodine was stopped. Metoprolol was halved because of the relatively high dosage. Follow-up for 1 year revealed that falls had stopped after this change of medication, confirming the diagnosis. The urinary problems had remained unchanged.
Case 3
An 81-year-old man complained of dizziness upon standing up, frequently associated with falls, for several months. He had a history of paroxysmal atrial fibrillation, presbyacusis, and bilateral cataract extraction. He used aspirin 100 mg once daily and flecainide 50 mg twice daily for several years. On physical examination, blood pressure supine was 200/90 mmHg, and regular pulse rate was 56 bpm. The lowest blood pressure after a half minute, 1 minute, 2 minutes, and 3 minutes of standing was 120/60 mmHg; pulse rate was 64 bpm. Further physical examination was normal. Laboratory testing showed a normal blood count, serum creatinine level of 104 micromol/l, serum ureum 9 mmol/l, and normal electrolytes. Creatinine clearance according to the Cockroft and Gault formula was 38.7 ml/min. Repeated ECGs showed a sinus rhythm with left axis deviation and left anterior fascicular block.
Tilt-table testing showed autonomic insufficiency with an inappropriate catecholamine response. The most probable diagnosis was orthostatic hypotension induced by a negative inotropic cardiac drug (flecainide), superimposed on preexisting autonomic insufficiency. Therefore, flecainide was stopped. Frequent follow-up for 1 year showed that the patient remained in sinus rhythm and falls ceased, confirming the diagnosis.
Discussion
In these three patients, we were able to prevent further falls by modifying their drug regimen, despite abundant comorbidity. Case 1 had typical complaints of orthostatic hypotension even though we could not confirm this on testing (systolic drop did not reach 20 mmHg). As the prevalence of orthostatic hypotension changes according to the time of day and may not be detectable at the time of measurement (6), we decided to be practical and treat the typical symptoms. Timolol is a nonselective lipophilic beta-blocker, which, even when used as eyedrops, can have systemic effects (7,8). It usually can be safely changed to latanoprost, a selective prostanoid-FP-receptor agonist, which does not have these side effects.
Case 2 had proven diastolic orthostatic hypotension (defined as a drop in diastolic blood pressure of 10 mmHg or more) and obvious polypharmacy. There were a number of drugs that could have caused her symptoms, such as tolterodine, metoprolol, furosemide, and perhaps perindopril, although angiotensin-converting enzyme inhibitors are thought to give less rise to orthostatic hypotension than other antihypertensive drugs (9). Since the patient's falls began around the time that tolterodine was added, we reasoned that it most likely gave rise to her symptoms and we withdrew it; because of the relatively high dose of metoprolol, we decided to halve this drug at the same time. Furosemide was continued because of the patient's reduced cardiac function and the risk of recurrence of heart failure. Perindopril was continued because it was less likely to give rise to orthostatic hypotension than other antihypertensive drugs and it was needed to reduce the risk of recurrence of heart failure.
The relationship between anticholinergic drugs and falls has not been studied in larger series, but anticholinergics can cause orthostatic hypotension and falls (10). Since metoprolol, a selective lipophilic betablocker, was used in a relatively high dose, it was thought to be partly responsible for the orthostatic response in case 2.
Case 3 was on flecainide, a class Ic anti-arrhythmic drug with a negative inotropic action, because of paroxysmal atrial fibrillation. Tilt-table testing revealed an autonomic insufficiency, which can be primary, secondary, or a combination of the two. Primary autonomic insufficiency in old age is thought to be due to increased baroreceptor sensitivity. One of the causes of secondary autonomic insufficiency is the use of certain drugs, in this case, flecainide. After stopping this drug, the orthostatic hypotension lessened to an extent where the patient did not experience any more falls. He also remained in sinus rhythm. A study on drug withdrawal in a Falls Clinic held in 2001 showed that chronic cardiovascular medication could often be withdrawn safely. After stopping anti-arrhythmic drugs because of falls, renewal of these drugs was not necessary in 36% of cases; for anti-anginal drugs, renewal was not necessary in 77% of cases; for antihypertensives, no renewal was necessary in 69% of cases (11).
This case series demonstrates that, in older patients with frequent falls, an adverse drug reaction should be considered. If a suspected drug can be defined, this should be stopped or reduced. In the case of polypharmacy in a patient with falls, it is worth the effort to try and limit the amount of prescribed drugs, or at least reduce the doses to the lowest effective level. Even if underlying pathology is present, drug withdrawal may stop the symptoms.
Acknowledgments
This case series was presented as a poster at the 4th National Conference on Falls and Postural Stability of the British Geriatrics Society, London, on September 9, 2003.
References
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