Medicines, etc.

Disclaimer

The following narrative is for purposes of information only and offers no specific practical advice on the care or management of patients beyond that which is advised by a trained healthcare professional.

Never stop taking prescribed medicines without the advice of your doctor (or nurse, or pharmacist).

Introduction

When I was at medical school, I am not sure if polypharmacy had been invented, or, if it had, it wasn’t something we discussed much. If you haven’t heard the word, you can probably work-out what it means – ‘poly’ – lots, ‘pharmacy’ – medicines; as to what lots of medicines means is less clear.

I am going to discuss polypharmacy in older people, although with changes in society and healthcare over the past decade, this is likely an issue affecting people of all ages.

Polypharmacy, etc.

Specifically, there are two terms which help narrow-down the definition – they are appropriate polypharmacy – this is when a person is prescribed multiple medicines (anything more than five different types is often a starting point*), all of which are necessary and essential to maintain their health and wellbeing – I will provide some examples later-on, then, there is problematic polypharmacy, where an individual is prescribed medicines which either are unnecessary, ineffective or harmful individually – for example beta-blockers for someone who has asthma, or in combination, e.g. anti-inflammatory drugs and ace-inhibitors (for blood pressure) in someone who is dehydrated.

*This could be as many as 40 tablets a day

Beyond these two definitions, we have oligopharmacy – this is less common, and only something that has become a theme in recent years, where a person receives fewer drugs than they require – either because the benefits are not considered – for example, the use of Bisphosphonates (bone building drugs) in people with osteoporosis or, when there is some other limitation or constraint – perhaps through individual choice – many people dislike taking tablets every day, or through economic pressures – in the UK we are protected by means of subsidised prescriptions; this is not the case in many countries where medicines, specifically those which are proprietary – (often new on the market) can be very expensive.

We also have hyperpolypharmacy which is another term that has only been around a few years and refers to the sometimes extreme numbers of medicines people are prescribed for multiple conditions, which, particularly for older people are becoming the norm – the longer you live, the more time you have to acquire diseases or long-term conditions – asthma, diabetes, arthritis, depression, and the more medicines are available (or often recommended as best practice), resulting in frequent prescriptions of medicines that have never been tested in combination and no one really knows or understands the consequences – even for some drugs that have been available for decades – statins and anti-acid treatments, for example, we really don’t know what the effect of taking them for years in combination with a host of other, potentially newer medicines might be.

Finally, we have deprescribing – this is my favourite activity and probably a major part of my day job as a hospital doctor caring for older people – looking at what people are prescribed and balancing the harms and benefits with a person’s individual preferences and determining what is no longer required – essentially, this means usually stopping lots of medicines people have sometimes been taking for many years, which mostly provides a great sense of satisfaction to me and is appreciated by patients.

The irony associated with deprescribing is that in some ways it is contrary to what it is to be a doctor – up until quite recently, we, alongside opticians, dentists and vets were amongst the only people legally allowed to prescribe medicines; with the modernisation of healthcare in the past ten years, more and more non-medical prescribers – mostly nurses and pharmacists have joined with doctors in becoming accredited with the authority to prescribe. Doctors still however are by far the dominant force (in human society that is) who can prescribe pills, potions and treatments, many of which can do fantastic harm as well as benefit those treated.

I remember my first prescription soon after graduating from university in 1997 – I was working in Raigmore Hospital in Inverness at the time; I remember checking the dose of Morphine in the BNF – the British National Formulary, and watching as a nurse administered this powerful controlled medicine to a patient.

Here is a link to the very recent experiences of a junior doctor in 2016.

Nowadays I get more of a buzz from deprescribing however.

An aspect of this relates to our inability to always get people better.

If you think of the old model of care and treatment – a person might become ill, they would go to a doctor and they would be offered a treatment – whether a leech, poultice or selection of herbs, the act of the doctor using their knowledge and experience to help another was fundamental to the relationship, and often, likely, most certainly in the case of leeches, the patient’s recovery would have been in spite of the blood-sucking; the cured person would however ascribe their recovery to the leech, thank the doctor and get on with their life – reinforcing the good that is medicine.

Nowadays, particularly in the realms of minimally invasive surgery as well as a large variety of disciplines within medicine, studies have demonstrated the objective benefits of tablets, injections, creams and patches; evidence-based medicine has contended with the null hypothesis and supported the use or abandonment of treatments through clinical trials.

It is only in the past few years however that clinical trials have specifically looked to test their products on older people – previously, the standard would have been healthy young adults without any significant health problems – and these, for drugs that would often be then used in much older people with multiple health conditions.

Even once we have adjusted the drug trials for older people, testing the medicines in the ‘field’ reality of complex 21^st century lives is more difficult – few studies are conducted with people who forget to take their medicines or who take too many or too few or who sometimes take some of their medicines and at other times forget to collect their prescriptions.

Deprescribing continued…

Sometimes I become frustrated with medicine – as I often see people prescribed medicines that are so obviously inappropriate, I forget that I am not normal – I (that is a doctor specialising in the care of older people), sees the world a little differently to others, fixating on the connections between disease, health, wellbeing, prognosis, outcome and patient preference, rather than say the broken bone or blocked artery.

For example, I cannot see a prescription for a blood pressure tablet in an older person without immediately considering whether it is putting them at risk of falling. I know another doctor, say a cardiologist or renal physician will see these drugs and think about the tremendous good that they are probably doing – allowing the heart to pump more effectively, preventing strokes or kidney failure.

It is true that some drugs have a miraculous effect on disease – to the extent that diseases are changing; for example, thanks to the safety and effectiveness of new drugs to treat rheumatoid arthritis, the numbers of people with cruelly deformed hands and joints are diminishing, to the extent that what was once common is now rare; people dying of heart failure – this condition has changed from being a routine presentation in the accident and emergency department to a chronic disease.

Numbers needed to treat and so on

For every medicine that is prescribed, there will be some people who will benefit, others who will not and some who will experience harm. Within medicine we measure this using statistical calculations called ‘numbers needed to treat’ and ‘numbers needed to harm’, or, NNT and NNH.

The smaller the NNT and the larger NNH, the better; sometimes people taking medicines for decades have no notion that they are not gaining any benefit. For example, for many years, the use of aspirin as ‘primary prevention’ that is, taking an aspirin a day in otherwise healthy people, was felt to offer protection from heart attacks and strokes. We now know that the potential harms of taking aspirin, specifically in relation to an increased risk of bleeding exceeds any benefit gained from taking the tablet in otherwise healthy people.

Here are some NNT: (this is leaving out some statistics specifically relating to confidence intervals)

18 older people need to be treated with blood pressure lowering drugs to prevent one person experiencing a heart attack or stroke in the subsequent five years, whereas you need to treat 570 50-year-old women with raised blood pressure for five years to prevent a heart attack.
70 to 150 people have to receive statins to lower their cholesterol to prevent a heart attack or stroke in those with no other health problems.
23 people have to receive the flu vaccine to prevent one person catching the illness (this excludes the herd immunity effect).

The numbers are occasionally random and not very personalised – for example, we need to consider all the other factors such as whether prescriptions are filled, whether drugs are taken as prescribed – e.g. on an empty stomach, whether other medicines are interacting – some medicines can either increase or reduce the effectiveness of others.

Essentially, it gets complicated and difficult.

I suspect, this is part of the reason that many doctors do not deprescribe – because of the very inexact and unscientific dimensions related to cause and effect.

Nevertheless, within the dark underbelly of medicine, where geriatricians live, there are some quite stunning effects often, from stopping and sometimes starting medicines.

Stopp and Start Guideline

For example, the Stopp Start Guideline (STOPP: Screening Tool of Older People’s potentially inappropriate Prescriptions. START: Screening Tool to Alert doctors to Right i.e. appropriate, indicated Treatments), published in 2008 in the Internal Journal of Clinical Pharmacology, has become a mainstay for guiding doctors and pharmacists in ways to rationalize medicines.

This guide, a good example of which can be obtained here provides examples of medicines that both potentially harm as well as benefit older people. A more recent review is here.

Much is very straightforward – for example, my favorite, probably within all of medicine is stopping blood pressure tablets in older people. To understand this, you have to know a little about the effect of blood pressure – it follows a curve in association with life expectancy – the lower your blood pressure – to a point, the better, with those with the highest levels having relatively shorter lives, usually, because of cardiovascular disease – that is, strokes, heart attacks, renal failure and so on.

Consequently, those people who survive to be very old – in their 90’s, tend to either have naturally low (but not too low) blood pressure or if they have raised blood pressure, it has been well controlled with medicines for many years.

As people age, there are various changes within the body – the external ones are easy to see – wrinkles and thin skin; inside the body, the process of deterioration is also happening – our lungs and heart become less effective, our kidneys struggle to filter, our eyes to see and our brains to process.

Consequently the effects of drugs become increased – a drug that was ok for a 35-year-old might not be good for someone who is 80, yet, because of practice and traditional approaches to care, people often remain on high doses even when they are either not doing any good or even potentially causing harm.

The biggest harm experienced by older people in relation to blood pressure treatment is falling and the consequent associated injuries – physical, psychological and emotional, or, fractures, anxiety and social isolation.

Determining whether a person no longer requires a blood pressure medicine is quite easy – we can measure their blood pressure; as to whether a blood pressure medicine is outright harmful is also quite straightforward – essentially, we measure a person’s blood pressure when they are lying down then repeat the test with them standing-up; if their blood pressure drops more than 20 systolic or 10 diastolic points and they feel dizzy, wobbly or light-headed, they may have postural hypotension which is caused by their blood pressure medicines; stopping the treatment usually works, although sometimes other treatments are required.

As to why this test is so difficult to undertake either in primary or secondary care I am not clear – on my ward, we have managed to crack the challenge and this is now part of our routine screen for patients who have fallen, for many other areas, probably thousands of people across the UK, this test isn’t done, the people continue taking the potentially harmful medicine and continue falling.

There are a host of other similar medicines which I will list at the end of this document.

I should say, it is important for anyone who is prescribed medicines not to suddenly stop taking them – some drugs need to be withdrawn slowly and others are not the cause of the symptoms – always consult your doctor!

A few specialist areas…

I have already mentioned blood pressure drugs and falls, here are a few other very commonly prescribed medicines that are potentially harmful:

Drugs that work on the central nervous system (CNS) – there are a multitude of medicines which affect our levels of alertness and consciousness; whether pain killers such as Morphine and Tramadol, through to antidepressants, anti-psychotics, anticonvulsants or anti-anxiety drugs like Diazepam and Lorazepam; all contribute to a slowing of response time, increased drowsiness, falls, and, potentially dehydration and malnutrition.

This is not to say that people should stop taking their epilepsy medicines, but for those older people who are prescribed regular pain killers for a fracture or sprain they had 10 years before or who have been inappropriately prescribed antipsychotic medicines (ten years ago, these were the mainstay of treatment for people with behavioural symptoms associated with dementia – in recent years we have learned than unless used by specialists in controlled situations, they can cause people to fall and shorten their lives because of heart attacks and strokes) review might be appropriate.

Another class of drug that potentially affects the CNS are anticholinergics or antimuscarinics – they stop the chemical Acetylcholine from working in the body, the side effects of which can be beneficial – supporting breathing in people with asthma or COPD, incontinence in those with sensitive bladders or settling symptoms of nausea and sickness.

Unfortunately these medicines all carry with them potential side effects, which in older people can result in confusion.

An anticholinergic scale has been created to determine which medicines have the strongest anticholinergic potential; most people who are prescribed these medicines will not experience any ill effects, some, particularly those who are older and those with dementia or a history of delirium (acute confusion) are at increased risk and should be assessed.

Anticholinergic Burden Scale

A total score of three or more is considered clinically relevant.

Antibiotics

Antibiotics are an entire class of medicine which I have not yet mentioned – discovered by Alexander Fleming in the 1920s and now one of the most commonly prescribed and important medicines in society. Antibiotics have saved the lives of countless people who would otherwise have died and they have transformed modern medicine.

The use of antibiotics in the UK remains controlled and all require a prescription, in other countries there is a much looser attachment to regulation and compliance resulting in major limitations in their use – predominantly because of bacterial resistance.

There is a campaign running globally to limit the use of antibiotics in order to control the development of resistance.

Here is a link to a very recent blog by Sally Davies, the Chief Medical Officer on the subject.

Behind these issues, is the heavy reliance within health and social care on ‘bacteria’ as a cause of health problems; in older people in particular, infections are blamed for a whole range of upsets – from falls to confusion, pain and reduced mobility. This is to the extent that there is an inside joke that an older person going to A&E without a cough, who has fallen will be given antibiotics for a urine infection.

Things are even more complicated as many older people have a condition called ‘asymptomatic bacteruria’ – for more details, see here. That is, they have bacteria in their urinary tract but they aren’t doing any harm or causing any disease or symptoms and consequently do not cause confusion or falls and do not require treatment.

That is not to say that urine infections cannot be serious – life-threatening even, just, that their centrality to older people falling is not necessarily as clear.

Whether an older person receives a course of Trimethoprim or Nitrofurantoin – the most commonly prescribed antibiotics for urine infections is not specifically my focus, more, as with the discussion above relating to falls and blood pressure – if a person falls at home because their blood pressure is too low (because of unnecessary medicines) and is brought to A&E and receive antibiotics for a urine infection they either don’t have or doesn’t require treating, they will be made no better, indeed they will be exposed to the risks of antibiotics – disrupting the healthy microbiome and potentially causing serious gut infections such as Clostridium difficile. Antibiotics can as also discussed interact with other drugs and increase their toxicity – a common agent being Warfain (which is used less nowadays but still a very common medicine) – most frustratingly however for the person who has fallen, their opportunity for intervention – for the blood pressure medicine to be stopped and their risk of falling reduced, will have been missed and the whole encounter ineffective – a dance macabre of systems, process, health and technology.

Supplements

Another growth area in our society relates to the prescription of dietary supplements – whilst these are not strictly considered medicines or pharmacy, they are ordered on prescriptions.

If you look in the fridge on any hospital ward in the UK you will see a variety of different coloured dietary supplements – most providing increased amounts of protein, carbohydrate or fat, depending on individual need.

I haven’t tried many dietary supplements although I gather some are more palatable than others, some people enjoy them, others dislike any type or consistency.

The usual route for receiving dietary supplements (called ONS, or Oral Nutritional Supplementation by those in the know) is when a person is eating inadequately, or found to be losing weight.

Weight loss can be intentional – through increased exercise or dieting, in older people it is much more often a sinister indication of deterioration, if rapid, potentially indicating severe infection or cancer or when slower and more insidious, the general decline associated with increasing age and frailty.

Ironically, in most of these situations, ONS does little to prevent loss of weight – it does not reverse the systematic process associated with people coming to the end of their natural lives and is really only of benefit to either support people who have an inability to consume adequate calories – for example, after a major operation or recovering from some other trauma or infection, pending a return to wellbeing and ability to participate in normal diet.

Essentially in many instances, we have medicalised the process and instead of doctors and nurses engaging in person-centered discussions about prognosis and the future, it is easier to prescribe the supplements and hope that they will do some good.

Even the Care Quality Commission and the National Audit for Dementia (currently running in 2016 in the UK) are interested in weight and its monitoring – with poor monitoring of the residents in care homes’ weight or those in hospital seen as an indicator of poor care – yet, the issue is much more complex than this.

A common theme to all of the areas so far discussed is effectiveness; writing a prescription and moving-on is not enough; we need to be able to determine whether the medicine has made any difference, whether it has helped or harmed, whether an individual’s quality of life is better now than before. Ironically, a fundamental for determining these changes on a human level relates to ‘continuity of care’ – being able to see the same doctor or nurse throughout the span of treatment or care, interacting with someone who can not only monitor weight, but can also detect subtle changes in behaviour, skin colour, tone of voice, brightness of the eye – these many ineffable characteristics which are still within the realm of people.

Potentially bad medicines…

There are some medicines that are never right, that always cause me consternation when prescribed for older people…

Here are a few of my favourites with explanatory notes:

Haloperidol – this atypical antipsychotic agent was once felt to be a panacea in terms of the treatment of people with dementia; if an older person with dementia was too loud, difficult, non-compliant, aggressive or agitated, a dose of this was felt to work. Over the past five to ten years we have discovered how potentially harmful this drug and other similar agents – such as Risperidone and Olanzapine are in terms of making confusion worse, causing falls, heart attacks, strokes, dehydration and death.

As an antipsychotic this drug can be effective and it is also used very effectively in palliative care, outside of these areas it is best avoided (note – on the Anticholinergic Burden Score it is a ‘3’)

Tramadol – this is a synthetic opiate which is commonly used as a strong pain-killer when simpler treatments such as Paracetamol or Co-Codamol are ineffective; for some people it is effective, for many, particularly for older people and specifically those with any degree of confusion it is likely to cause a significant worsening in symptoms and is best avoided.

Cetirizine – this is a supposedly non-sedative antihistamine – commonly prescribed for allergic conditions as well as sometimes vertigo. In short-term use it is sometime although not always effective; taken longer term its sedative effects can be significant in older people and can also contribute to increased confusion, both of which can result in falls.

Oxybutinin – this drug is sometimes prescribed for irritable bladder – sometimes associated with incontinence in older people. If you ever find a person who is prescribed this drug, ask them if their mouth is dry – this is the most common side effect; more significantly however, for older people, side-effects relating to constipation and confusion and urinary retention (inability to pass urine) can cause significant harm.

Example of appropriate polypharmacy

This is an example of an imaginary 85 year old man who is living independently in a town in the UK. In the past he has experienced a heart attack and a stroke, he also has diabetes, high blood pressure, an enlarged prostate, chronic obstructive pulmonary disease (COPD), arthritis and constipation. Here is what he might be prescribed:

Clopidogrel 75mg once in the morning	To prevent blood clots
Atorvastatin 40mg at night	To lower cholesterol
Bisoprolol 5mg twice a day	To protect heart
Ramipril 5mg twice a day	To lower blood pressure
Bendromefluthiazide 2.5mg once a day	To lower blood pressure
Spironolactone 25mg once a day	To protect heart
Amlodipine 5mg once a day	To lower blood pressure
Gliclazide 80mg twice a day	To control blood sugar
Metformin 500mg two tablets three times a day	To control blood sugar
Tamsulosin 400mcg once a day	To help with prostate
Paracetamol 500mg two tablets four times a day	Pain relief
Lactulose 15mls twice a day	Treat constipation
Movicol Sachets one twice a day	Treat constipation
Spiriva inhaler once a day	COPD
Symbicort inhaler two puffs twice a day	COPD
Salbutamol inhaler as required	COPD
Ibugel cream three times a day	Pain relief

I think this would qualify as polypharmacy – this would add up to approximately 30 medicines a day, excluding his inhalers – and think, what might happen if he falls and hurts his back and requires more pain relief or needs to take antibiotics…

Example of deprescribing

Imagine another patient – she is a 91-year-old woman living in a nursing home. She has limited mobility, only able to walk with assistance of two people, she is doubly incontinent. She needs help with dressing, eating and drinking; she has a past medical history of Alzheimer’s type dementia, Diabetes, falls, asthma, depression, stroke and she broke her left hip three years ago.

Initial medicine chart:

Donepezil 10mg at night	For Alzheimer’s
Zopiclone 3.75mg at night	To help sleep
Gliclazide 80mg on the morning	For diabetes
Metformin 500mg twice a day	For diabetes
Cinnarizine 5mg once a day	For ?dizziness
Co-Codamol 30/500 two tablets four times a day	For pain
Movicol 2 sachets a day	For constipation
Salbutamol inhaler as required	For asthma
Seretide inhaler two puffs a day	For asthma
Atrovent inhaler two puffs four times a day	For asthma
AdcalD3 two tablets a day	For bones
Alendronate 70mg once a week	For bones
Lansoprasole 30mg once a day	For indigestion
Amitriptyline 25mg at night	For depression
Citalopram 40mg once a day	For depression
Amlodipine 5mg once a day	For blood pressure
Aspirin 75mg once day	For stroke
Dipyridamole 200mg twice a day	For stroke

A narrative rationalisation of these medicines is:

Is she gaining any benefit from Donepezil in terms of her Alzheimer’s which is likely to be advanced; this could be causing her side effects – agitation or insomnia – discuss with relatives or carers or Older People’s Mental Health Team about stopping

She might not need the Zopiclone if the Donepezil is not required and preventing her from sleeping. In general sleeping tablets are ineffective with long-term use and significantly increase the risk of falls in older people. Consider stopping.

Gliclazide and Metformin – there is little evidence that tight control of blood sugars in older people, particularly those with dementia in nursing homes benefit, check HbA1C and consider reducing and stopping; aim for random blood sugars below 11 mmol, move away from a stringent diabetic diet which may encourage her to eat more. You might want support from the diabetic team in the community. Too low blood sugars can cause confusion, falls and brain injury.

Cinnarizine – often left on repeat prescriptions, most people taking this don’t know what it is for and it isn’t doing them any good – it can also worsen confusion and contribute to falls. Stop!

Co-codamol 30/500 – this is very strong codeine with paracetamol, she may require pain relief – this needs to be regularly reviewed, it is likely that this dose contributes to worsening confusion and constipation, also the high regular dose of paracetamol might be too large for her body weight, risking liver injury. If she does need pain relief, would paracetamol alone be adequate? Would a topical preparation be better? What is causing the pain? Could her laxatives be reduced if she is no longer taking codeine?

Inhalers – clarify the severity of her chest symptoms – it could be that she no longer requires inhalers given that her exercise tolerance is now so poor, even so, check that she can use them – if she is unable to coordinate her breathing, it is likely that the medicine is not working on her lungs, instead contributing to a dry, sore throat. Alternative inhalers are available for people who struggle with the technique, or, they might not be needed at all.

Adcal D3 – it is likely that she does not experience any exposure to daylight and her dietary intake of calcium and vitamin D is poor – these could contribute to falls and there is mixed evidence as to their benefit. For some patients they are difficult to swallow and a daily chore – is this something the patient wants?

Alendronate – given the patient’s previous fall and broken hip, it is likely that she has osteoporosis which this drug can successfully treat in combination with calcium and vitamin D – in order to benefit from this drug and not experience significant side effects, it needs to be taken when standing or sitting very upright, for thirty minutes, on an empty stomach with ‘plenty of water’ (plenty is the scientific measurement used by the British National Formulary) – can she achieve this? Is the medicine likely to cause her stomach upset? Is her life expectancy (which is somewhere in the region of one to two years) adequate for the medicine to have any effect? Could she stop taking the antacid medicine Lansoprasole if she doesn’t take this?

Amitriptyline – this is a tricyclic antidepressant with powerful anticholinergic properties, sometimes used to help with chronic pain or insomnia. This dose is likely too high and it probably shouldn’t be prescribed to her. This needs to be withdrawn slowly. Note, she is also prescribed a too high dose of Citalopram, another antidepressant – you might want to consider speaking with her mental health team before reducing this to the recommended dose, if it is needed at all. The combination of the two drugs increases confusion and can increase risk of falling.

Amlodipine – check her blood pressure; is this required at all? Is it doing any good? Is it doing any harm? Suggest to stop.

Aspirin and Dipyridamole – this is the old treatment for stroke prevention; we nowadays use one tablet instead of three, which are difficult to swallow and have side effects of stomach upset and headache; did she actually have a stroke in the past? What is the evidence for this? What will be the benefit in terms of her quality of life and life expectancy if she is not prescribed the alternative (Clopidogrel) at all?

I know people might think I am exaggerating – below is an example of the actual prescription of a different patient who has dementia and lives in a nursing home – see if you can spot the ‘dodgy drugs’

By the end of the day, the patient’s medicines can be potentially reduced dramatically – she might feel better, be less confused and eat more. All of this is difficult and potentially time-consuming, but very worthwhile for the patient; in patients who are older it is important to explain why you are stopping the medicines that another doctor has told them are critical to their wellbeing – the vast majority of people are aware that they are a poison and doing them harm and delighted to stop; for those frailer patients who perhaps lack insight or mental capacity, a discussion with their next of kin is very important – it is also important to explain your rationale which is solely to improve the quality of an individual’s life rather than save money.

Drugs, side effects and hospital admission

A 2004 study at two hospitals in the UK over a six-month period showed the frequency of admissions associated with adverse drug reactions – these totalled over six per cent of all admissions (there are over five million emergency hospitals admissions each year in England).

Many of the associated side effects are potentially avoidable.