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Medicines and falls Assessing the impact of medicine on falls risk Presenter notes: This presentation is designed for registered nurses, but may be applicable to all nursing staff at the aged care facility. It is part of a series of four presentations on medicine and falls. The first presentation examined common causes of falls, and the impact and cost of falls on the individual and the community. This second presentation will discuss medicines that increase the risk of falls. The third presentation will identify intervention strategies to reduce medication related falls. The final presentation looks at the role of the pharmacist in preventing falls. Medicines have been shown to contribute to an increased risk of falling in a number of epidemiological studies. The risk may be increased by medication interaction, unwanted side effects (such as dizziness) or the desired effects of medicines such as sedation. Residential aged care facilities (RACFs) staff and the whole health care team need to recognise that pharmacological changes that occur with ageing may lead to potentially avoidable events in older people, including falls and fractures. This presentation will discuss the use of multiple medicines, including psychoactive medicines, and the contribution they make to the resident’s risk of falling. Reference Preventing Falls and Harm From Falls in Older People. Best Practice Guidelines for Australian Residential Aged Care Facilities 2009 www.safetyandquality.gov.au/internet/safety/publishing.nsf/content/compubs_FallsGuidelines/$File/Guidelines-RACF.PDF 1 Learning objectives • Recognise the causes, impact and cost of falls • Identify the effects of medicine that may result in a fall • List medicines that may be a falls risk • Understand possible falls prevention strategies and changes to medication regimens and dosage forms that can be made to minimise the risk of falls • Describe the role of the pharmacist in falls minimisation Presenter notes: All the learning objectives for the four presentations of Medicines and falls are listed on the slide. This presentation will focus on identifying the causes of falls, the effects of medicine that may result in a fall and listing those medicines that may be a falls risk. 2 Medication and falls in RCFs • Medication use is common in residential care facilities (RCF) – 98% of residents take at least one medicine – 63% take >4 medicines • Medication use is associated with falls, with one study finding increase relative risk of falling; – 1.4 times greater with 1 medicine – 2.2 fold greater for 2 medicines – 2.4 fold greater for >3 medicines Presenter notes: The use of medicines and the risk of falls is an important consideration for residential care facilities (RCF) staff. Medication use, in particular use of multiple medicines, is commonplace in RCFs with 63% of residents taking more than 4 medicines. The use of medicines has been associated with increased risk of falls. Compared to residents who are not using medicines, the risk of falling is • 1.4 times greater with 1 medicine used • 2.2 fold greater for 2 medicines used • 2.4 fold greater for >3 medicines used Reference: Preventing Falls and Harm From Falls in Older People. Best Practice Guidelines for Australian Residential Aged Care Facilities 2009. Available at www.safetyandquality.gov.au/internet/safety/publishing.nsf/content/compubs_FallsGuidelines/$File/Guidelines-RACF.PDF 3 Risk Factors for medication related falls • Taking 4 or more medicines • Starting or stopping a medicine • Dose changes • Having trouble remembering to take medicine leading to missed doses or doubling up • Alcohol consumption Presenter notes: Certain factors may increase the risk of medication related falls in RCF residents. Evidence has shown that elderly people taking four or more medicines are at high risk of falling, and as we have seen earlier up to 63% of RCF residents take >4 medicines. The risk of adverse (unwanted) drug effects and interactions with other drugs increases with number of medicines taken, and this may contribute to the increased risk of falls. The risk of falls is also increased when starting or stopping a medicine, or after a dose change. A new medicine or lowering/increasing a dose of a medicine can alter the way a person feels e.g. dizziness, sedation, therefore extra care is indicated to prevent a fall. Missing doses and getting mixed up with which medicine to take at what time can also cause a fall. Alcohol has also been shown to be a risk factor for a fall as it can also interact with the medicines that a person is taking. Care notes Any resident who is taking four or more medicines and is self-medicating is a potential falls risk. Monitor this resident closely. Care should be taken if the resident has a number of different healthcare providers e.g. a GP, a medical specialist, a hospital doctor, to ensure each medicine prescribed is indicated and appropriate. The pharmacist can assist in reviewing a residents medication via a RMMR. Reference: Tinetti ME. Preventing Falls in Elderly Persons. New England Journal of Medicine. 2003;348(1):42-49. 4 Falls - medicine and age • Age-related changes – Renal function decline – Increased sensitivity to drug effects • Poly-pharmacy • Non-compliance due to: – Regimen complexity – Language difficulties – Swallowing difficulties – Attempt to minimise adverse effects – Potential cost saving Presenter notes: The elderly are often more susceptible to medicine-related falls due to age-related changes. Medication problems can be associated with: • • • • Pharmacokinetic changes (how the body absorbs, distributes, metabolises and excretes drugs) - most important effect of ageing is reduction in renal function which results in reduced elimination of both renally excreted drugs and active drug metabolites. If a dose is not altered to reflect a reduction in renal function, adverse drug effects may occur potentially causing a fall; Pharmacodynamic changes (the effect of drugs on cellular and organ function) sensitivity to the effect of drugs changes with age as drug receptors and target organ responses can change. This may be seen by increased central nervous system (CNS) effects of psychoactive medicines such as benzodiazepines and opioids which can result in falls amongst other effects. The body’s compensatory mechanisms may be affected by age resulting in drug adverse effects e.g. orthostatic (postural) hypotension may occur with diuretics or tricyclic antidepressants (TCAs) causing a person to fall; Poly-pharmacy - elderly patients often take many medicines increasing the risk of adverse drug effects and interactions. Residents may have both a GP and specialist(s) who prescribe drugs as well as drugs brought in from hospital stays and family. They also may be taking over-the-counter(OTC) medicines, drugs for a previous illness, or even drugs prescribed for another person. A medication review by an accredited pharmacist may be necessary to confirm exactly what is being taken; and Non-compliance – may be unintentional as a result of confusion or forgetfulness. This can occur due to regimen complexity, language difficulties, swallowing difficulties. 5 Intentional non-compliance can occur in an attempt to minimise adverse effects or to save money. This will be more common for residents who self-administer. The use of drugs in the elderly must be carefully planned and monitored because age-related changes in pharmacokinetics and pharmacodynamics, as well as the risks of polypharmacy and non-compliance, predispose the elderly to adverse drug reactions. Care notes Residents in residential aged care services have the right to administer some, or all, of their own medicine. In order to meet duty of care and accreditation requirements and to optimise resident care, it is recommended that RACF maintain some form of record of these medicines. This may be in the form of a medication record indicating that the resident is self-administering, or a card, which is updated as medicine changes occur. The medicine advisory committee (MAC) should develop a policy regarding the procedures to be used when a resident chooses to selfadminister medicine. A resident who is self-administering should be regularly assessed. References: • Rossi S. Australian Medical Handbook [online] Prescribing for the elderly 2012 • Preventing Falls and Harm From Falls in Older People. Best Practice Guidelines for Australian Residential Aged Care Facilities 2009. Available at www.safetyandquality.gov.au/internet/safety/publishing.nsf/content/compubs_FallsGuidelines/$File/Guidelines-RACF.PDF • Resource Kit to enable implementation of the APAC Guidelines for Medication Management in Residential Aged Care Facilities. Guidelines for management of residents who administer their own medicines (self-administration). www.health.vic.gov.au/dpu/resource-kit.htm 6 Causes of medicine related falls • • • • • • • • • Agitation Balance problems Blurred vision Confusion Dizziness Drowsiness Gait problems Syncope Urgency Presenter notes: Some medicines cause effects that have been implicated in falls either as an intentional effect (e.g. sedation) or as an adverse drug effect (e.g. dizziness). Listed on the slide are some effects of medicines that may cause a patient to fall while taking certain medicines. (Syncope - temporary loss of consciousness caused by a fall in blood pressure) References: • Ruddock B. Medications and Falls. CPJ/RPC 2004;137(6):17-18. • Preventing Falls and Harm From Falls in Older People. Best Practice Guidelines for Australian Residential Aged Care Facilities 2009 www.safetyandquality.gov.au/internet/safety/publishing.nsf/content/compubs_FallsGuidelines/$File/Guidelines-RACF.PDF 7 Medicines that increase the risk of falls Effect of medicine Medicine Agitation antidepressants, antipsychotics, stimulants Balance anticonvulsants, antipsychotics, prochlorperazine Blurred vision eye drops, anticholinergics, any drug with anticholinergic effects Confusion opioids, psychotropics, any drug with anticholinergic effects Dizziness blood pressure medications, diuretics, any drug with anticholinergic effects Drowsiness psychotropics, anticonvulsants, any drug with anticholinergic effects Gait abnormalities antidepressants, antipsychotics, metoclopramide Syncope blood pressure medications, vasodilators Urgency diuretics Presenter notes: Which medicines can cause these effects? There has been a number of studies that have shown an association between medication use and falls in older people. Some medicines have been studied more than others. Although many medicines are suggested as implicated in falls, strong evidence only exists to suggest that psychotropic medicines (e.g hypnotics, anxiolytics, antidepressants and antipsychotics) are involved. There is less evidence for those medications lowering blood pressure. It is suspected other medicines such as anticonvulsants, opiate pain medicines and those medicines with anticholinergic side effects such as blurred vision, confusion, dizziness and drowsiness are also implicated. A variety of medication categories may predispose an individual to falls. Some examples are: • Antidepressants may cause side effects such as sedation, lethargy, confusion, double vision, motor incoordination, dizziness, and weakness; • Medicines that have significant anticholinergic effects such as antihistamines, metoclopramide, promethazine, muscle relaxants, and medicines used to treat urinary incontinence (oxybutynin and tolterodine) may cause sedation, confusion, a lack of coordination, or dizziness; • Many anti-parkinson’s agents may result in dyskinesia, confusion, and delirium, which can increase the risk of falling; • Medicines used chronically to treat hypertension, parkinson’s disease, and angina can result in orthostatic hypotension-related falls; 8 • • • Psychotropic drugs (hypnotics, anxiolytics, antidepressants, antipsychotics) have been shown to increase the risk of falls particularly in older adult patients; Analgesics, including both opioid and nonsteroidal anti-inflammatory drugs (nsaids); and Anticonvulsants. In this presentation we are going to focus on drugs with anticholinergic effects, benzodiazepines, antidepressants, diuretics, blood pressure medicine and alcohol. Care notes Since many medicines may exert an effect that could result in a fall, ensure there is a list of these medicines is displayed. Residents who self-administer their medicines need to be educated on the effects of their medicines to avoid a fall. References: • Lindsey P. Psychotropic Medication Use among Older Adults: What All Nurses Need to Know 2009 [accessed online] www.ncbi.nlm.nih.gov/pmc/articles/PMC3128509/ • Preventing Falls and Harm From Falls in Older People. Best Practice Guidelines for Australian Residential Aged Care Facilities 2009 www.safetyandquality.gov.au/internet/safety/publishing.nsf/content/compubs_FallsGuidelines/$File/Guidelines-RACF.PDF 9 Drugs with anticholinergic effects Anticholinergic effects Drugs that exert anticholinergic effects Blurred vision with dilation of pupils •Drugs for urinary incontinence Dry mouth •Antispasmodics and antidiarrhoeals Constipation •Antipsychotics Delirium or central excitation •Tricyclic antidepressants Dizziness •Drugs for Parkinson's disease and to treat Glaucoma worsening extrapyramidal side effects Hallucinations or euphoria •Bronchodilators Hyperpyrexia •Drugs for eye examinations Urinary hesitancy or obstruction •Other drugs such as disopyramide, mianserin, •Antihistamines pizotifen, prochlorperazine Presenter notes: Let’s start with drugs that exert an anticholinergic effect. Anticholinergic effects are physical symptoms that result from medicine that opposes the action of acetylcholine, a neurotransmitter (chemical within the nervous system). These anticholinergic effects typically act peripherally and centrally and are dose related. Medicines that have significant anticholinergic effects, such as antihistamines, promethazine, muscle relaxants, and medications used to treat urinary incontinence (oxybutynin and tolterodine) may cause both peripheral and central effects. Peripheral effects: dryness of mouth, dilatation of pupils, flushing, worsening of glaucoma, urinary hesitancy or obstruction, constipation, paralytic ileus, nausea and blurred vision. Central effects: dizziness, hallucinations, euphoria, hyperpyrexia and central excitation. Older people are more susceptible to central adverse effects such as delirium. All of these effects may contribute to an increased risk of falls. Examples of drugs that exert anticholinergic effects Drugs for urinary incontinence - darifenacin, oxybutynin, propantheline, solifenacin, tolterodine Antihistamines - brompheniramine, chlorpheniramine, dexchlorpheniramine, dimenhydrinate, diphenhydramine, pheniramine, promethazine, trimeprazine Antispasmodics and antidiarrhoeals - belladonna alkaloids, hyoscine (butylbromide or hydrobromide), loperamide Antipsychotics - chlorpromazine, clozapine, fluphenazine, olanzapine, pericyazine, trifluoperazine Tricyclic antidepressants - amitriptyline, clomipramine, dothiepin, doxepin, imipramine, nortriptyline[E], trimipramine 10 Drugs for Parkinson's disease and extrapyramidal disorders - amantadine, benzhexol, benztropine, biperiden, orphenadrine Bronchodilators - ipratropium (nebulised), tiotropium Drugs for eye examinations - atropine, cyclopentolate, homatropine, tropicamide Other - disopyramide, mianserin, pizotifen, prochlorperazine References: • Therapeutic Guidelines Psychotropic Drugs 2003 [update 2006 Apr] • National Prescribing Service. NPS News 59: Drugs used in dementia in the elderly. www.nps.org.au/health_professionals/publications/nps_news/current/nps_news_59_dru gs_used_in_dementia_in_the_elderly 11 Benzodiazepines Drug name Product name Duration of action Alprazolam Alprax, Kalma, Ralozam, Xanax short acting Diazepam Atenex, Ranzepam, Valium, Valpam long acting Flunitrazepam Hypnodorm long acting Lorazepam Ativan, Lorazepam medium acting Nitrazepam Alodorm, Mogadon long acting Oxazepam Alepam, Murelax, Serepax short acting Temazepam Normison, Temtabs, Temaze short acting Presenter notes: Benzodiazepines are another group of drugs where use is a consistently reported risk factor for falls and fractures in older people, both after a new prescription and over the long term. They affect cognition, gait and balance. Benzodiazepines are most commonly prescribed for anxiety disorders or symptoms (known as anxiolytics). Because of the increased susceptibility to oversedation and memory and psychomotor impairment, elderly patients who take benzodiazepines are more at risk for falls and skeletal fractures. Medicines in this class have varying onset of action and duration as summarised below: Very short acting (half-life <6 hours) — midazolam, triazolam. Short acting (half-life 6–12 hours) — alprazolam, oxazepam, temazepam Medium acting (half-life 12–24 hours) — lorazepam, bromazepam. Long acting (half-life >24 hours) — clobazam, clonazepam, diazepam, flunitrazepam, nitrazepam. Rapid onset (<1 hour after oral administration) — alprazolam, diazepam, flunitrazepam, midazolam, temazepam, triazolam. Shorter acting agents (particularly those with rapid onset of action) are more likely to lead to acute withdrawal symptoms. Diazepam's rapid onset of action and long half-life mean it is associated with less withdrawal. Long acting agents, e.g diazepam, clonazepam, are preferred when using benzodiazepines as prophylaxis against withdrawal from alcohol, barbiturates or other benzodiazepines. 12 Care notes Resident’s using short acting agents for sleep should be discouraged from rising from bed after dose has been taken. Reference: • Rossi,S. Australian Medical Handbook [online] 2012 • Preventing Falls and Harm From Falls in Older People. Best Practice Guidelines for Australian Residential Aged Care Facilities 2009 www.safetyandquality.gov.au/internet/safety/publishing.nsf/content/compubs_FallsGuidelines/$File/Guidelines-RACF.PDF 13 Antidepressants Class Drug name MAO-I phenelzine, tranalcypromine, moclobemide SSRIs citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline TCAs amitriptyline, clomipramine, dothiepin, doxepin, imipramine, nortriptyline Others lithium , mianserin, mirtazapine, reboxetine, duloxetine, desvenlafaxine , venlafaxine Presenter notes: Antidepressants are associated with higher falls risk specifically specific serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) classes. However, the risk appears to be dose related. They may cause side effects such as sedation, lethargy, confusion, double vision, motor incoordination, dizziness, and weakness. All these effects can contribute to the risk of falls. Monoamine oxidase inhibitors (MAO-I) - used as a second line treatment for both major depression and some anxiety disorders, including phobic disorders and panic disorder. They must be used with caution in the elderly because of drug interactions and potential adverse cardiovascular effects (particularly orthostatic hypotension). Serotonin selective reuptake inhibitors (SSRIs) - a newer generation of this class of medicine, have become the preferred first-line treatment for depression in older adults, as these drugs have more benign side effects than other antidepressant agents. Side effects common to SSRIs include headache, gastrointestinal disturbances, increased sweating, and sexual dysfunction. Unlike other antidepressant drugs, SSRIs have fewer anticholinergic or cardiovascular effects. However, older adults have increased sensitivity to SSRI adverse effects than do younger patients. Tricyclic antidepressant drugs (TCAs) - an older generation of antidepressant medicine, have a number of side effects that increase elderly patients' risk for falls. These include sedation, psychomotor retardation, postural hypotension, and anticholinergic effects, which may cause blurred vision and cognitive impairment. Fall risk is the greatest during the first 90 days of treatment, when dosages are being adjusted and before physiological adjustment has taken place. 14 A recent study found that residents in aged care facilities who have dementia and take antidepressants are significantly more likely to suffer an injury as a result of a fall compared to residents who do not take these drugs. This risk of a fall is present even if the patient is only taking low or moderate doses of the drugs. According to Dutch researchers, many people in aged care facilities with dementia also have depression and so are treated with antidepressants. References: • Rossi, s. Australian Medical handbook [online] 2012. • Preventing Falls and Harm From Falls in Older People. Best Practice Guidelines for Australian Residential Aged Care Facilities 2009 www.safetyandquality.gov.au/internet/safety/publishing.nsf/content/compubs_FallsGuidelines/$File/Guidelines-RACF.PDF • Dose-response relationship between Selective Serotonin Reuptake Inhibitors and Injurious Falls: A study in Nursing Home Residents with Dementia Sterke C et al. British Journal of Clinical Pharmacology. www.irishhealth.com/article.html?id=20259acobson et al., 2007). 15 Diuretics • Weakly associated with falls • Can cause orthostatic hypotension by: - lowering blood pressure - volume depletion Drug name Product name Frusemide Frusid, Lasix, Uremide, Urex Hydrochlorothiazide Dithiazide, Hydrene (with triamterene), Moduretic (with amiloride) Presenter notes: Diuretics are weakly associated with an increased risk of falls. Diuretics can have a direct effect on blood pressure and can also cause volume depletion, which in itself can cause orthostatic (postural) hypotension. Counsel the patient that they may feel dizzy on standing when taking this medicine. Encourage the patient to get up gradually from sitting or lying to minimise this effect; sit or lie down if you become dizzy. This is an incomplete list of medicines for high blood pressure. The slide is intended for discussion only. References: Rossi, S. Australian Medical handbook [online] 2012. 16 Blood pressure medicines • Used to treat hypertension • Elderly may experience first dose effect • Adverse effects are hypotension, dizziness, fatigue Drug class Example ACE inhibitors Perindopril (Coversyl) Ramipril (Ramace, Tritace, Prilace, Tryzan) Beta blockers Atenolol (Noten, Tenormin, Tensig) Presenter notes: Drugs used to treat hypertension may predisposed elderly patients to first dose hypotension. Adverse effects of antihypertensives that may increase falls risk include hypotension, dizziness, fatigue. Advise the patient to get up gradually from sitting or lying to minimise this effect; sit or lie down if you become dizzy or light-headed. Medications and volume depletion are the two most common causes of postural hypotension in older people. Although medicine commonly associated with postural hypotension include the antihypertensive agents, you should also be aware that antianginals, antidepressants, antipsychotics and antiparkinsonian medications and diuretics can all cause postural hypotension possibly resulting in falls. References: • Rossi, S. Australian Medical handbook [online] 2012. • Preventing Falls and Harm From Falls in Older People. Best Practice Guidelines for Australian Residential Aged Care Facilities 2009 www.safetyandquality.gov.au/internet/safety/publishing.nsf/content/compubs_FallsGuidelines/$File/Guidelines-RACF.PDF 17 Other drugs of concern • Corticosteroids – Bone weakness • Anti-coagulants – Risk of haemorrhage • Lithium – Tremor, vertigo Presenter notes: These are some of the other drugs mentioned in the literature which are associated with falls. Examples are: • Corticosteroids: bone weakness can occur from prolonged corticosteroid use would cause a potential injury risk if a fall occurs. • Anticoagulants: may increase risk of haemorrhage if fall occurs, but studies show these patients do not fall more than others. • Lithium: common adverse effects of tremor and vertigo may contribute to risk of falling. References: Rossi, S. Australian Medical handbook [online] 2012. 18 Alcohol • Drinking alcohol increases the risk of falls and injuries • Alcohol dependence may be mistaken for depression, insomnia, poor nutrition and frequent falls • Remember a standard drink contains 10gm of alcohol – = 100ml glass of wine – = 30ml of spirits – = 375ml of mid-strength beer Presenter notes: For some older adults, drinking alcohol increases the risk of falls and injuries, as well as some chronic conditions. Population-based studies estimate that approximately 40 per cent of males and 30 per cent of females aged over 60 years drink at a moderate level. The decline in alcohol consumption in the older population is primarily associated with the onset of health problems. Alcohol dependence may also be mistaken for medical or psychiatric conditions such as depression, insomnia, poor nutrition and frequent falls. Also consider potential interactions with medications. A standard drink is any drink containing 10 grams of alcohol. One standard drink always contains the same amount of alcohol regardless of container size or alcohol type (i.e. beer, wine, or spirit). Australian Guidelines to Reduce Health Risks from Drinking Alcohol : Guidelines 1 and 2 (total of 4) Guideline 1: Reducing the risk of alcohol-related harm over a lifetime: The lifetime risk of harm from drinking alcohol increases with the amount consumed. For healthy men and women, drinking no more than two standard drinks on any day reduces the lifetime risk of harm from alcohol-related disease or injury. Guideline 2: Reducing the risk of injury on a single occasion of drinking: On a single occasion of drinking, the risk of alcohol-related injury increases with the amount consumed. For healthy men and women, drinking no more than four standard drinks on a single occasion reduces the risk of alcohol-related injury arising from that occasion. 19 References • Australian Government. National Health and Medical Research Council. www.nhmrc.gov.au/your-health/alcohol-guidelines Appendix 1[2011 July 13; cited 2012 Feb 2] • The Australian Government – Department of Health and Ageing. www.health.gov.au/internet/alcohol/publishing.nsf/Content/guidelines • Australian Government. National Health and Medical Research Councilwww.nhmrc.gov.au/_files_nhmrc/publications/attachments/ds10-alcoholqa.pdf [2011 July 13; cited 2012 Feb 2] • Australian Government. National Health and Medical Research Councilwww.nhmrc.gov.au/your-health/alcohol-guidelines [2011 July 13; cited 2012 Feb 2] • The Australian Government – Department of Health and Ageing. www.health.gov.au/internet/alcohol/publishing.nsf/Content/standard Department of Health and Ageing. The Australian Standard Drink [2009 Oct 21; cited 2012 Feb 02] 20 Mrs Sharpe Prescribed medicines: • Oxazepam 30mg 1 four times daily • Zolpidem 10mg ½ tab at night • Ramipril 10mg 1 morning • Metformin 500mg 4 at night • Crestor 5mg 1 night 15 Presenter notes: Mrs Sharp is 86 and has recently been admitted to your RACF after the death of her husband. She is unsteady when walking and her balance appears impaired. Ask the group to: • Review Mrs Sharpe’s medicines. Do any of the medicines pose a falls risk for Mrs Sharpe? Note: Mrs Sharpe is taking more than four medicines making her a falls risk; she is taking Oxazepam 300mg 1 four times daily for anxiety and Zolpidem ½ tablets night for insomnia. The concurrent use of multiple benzodiazepines or benzodiazepine-like drugs (e.g. zolpidem) makes Mrs Sharpe a falls risk. • What would you do now? Note: Undertake a falls risk assessment; suggest a residential medication management review. 21 Summary • Residents using medicines, particularly > 4 medicines are at increased risk of falls • Medicine that increase falls risk are: – Psychotropic drugs: hypnotics, anxiolytics, antidepressants, antipsychotics – Drugs which exert anticholinergic effects – Antihypertensives – Analgesics – Anticonvulsants – Others – corticosteroids, anticoagulants, alcohol 16 Presenter notes: Be aware that certain classes of medicine are more likely to increase the risk of falls in older people. 22 Any questions? 17 17 23