Oxford Handbook of Geriatric Medicine (2 edn)
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Pharmacology in older patients
Perhaps the most common intervention performed by physicians is to write a prescription. Older patients will have more conditions requiring medication; polypharmacy is common.
In the developed world:
The over 65s typically make up around 14% of the population yet consume 40% of the drug budget
66% of the over 65s, and 87% of the over 75s are on regular medication
34% of the over 75s are on three or more drugs
Care home patients are on an average of eight medications
Good prescribing habits are essential for any medical practitioner, but especially for the geriatrician.
Administration challenges include:
Packaging may make tablets hard to access—childproof bottles and tablets in blister packets can be impossible to open with arthritic hands or poor vision
Labels may be too small to read with failing vision
Tablets may be large and difficult to swallow (eg co-amoxiclav) or have an unpleasant taste (eg potassium supplements)
Liquid formulations can be useful, but accurate dosage becomes harder (especially where manual dexterity is compromised)
Any tablet needs around 60ml of water to wash it down and prevent adherence to the oesophageal mucosa—a large volume for a frail older person. Some tablets (eg bisphosphonates) require even larger volumes
Multiple tablets, with different instructions (eg before/after food) are easily muddled up, or taken in a suboptimal way
Some routes (eg topical to back) may be impossible without assistance
Absorption
Many factors are different in older patients (increased gastric pH, delayed gastric emptying, reduced intestinal motility and blood flow etc.)
Despite this, absorption of drugs is largely unchanged with age—exceptions include iron and calcium, which are absorbed more slowly
Distribution
Some older people have a very low lean body mass, so if the therapeutic index for a drug is narrow (eg digoxin) the dose should be adjusted
There is often an increased proportion of fat compared with water. This reduces the volume of distribution for water-soluble drugs giving a higher initial concentration (eg digoxin). It also leads to accumulation of fat-soluble drugs, prolonging elimination and effect (eg diazepam)
There is reduced plasma protein binding of drugs with age, which increases the free fraction of protein-bound drugs such as warfarin and furosemide
Hepatic metabolism
Specific hepatic metabolic pathways (eg conjugation) are unaffected by age
Reducing hepatic mass and blood flow can impact on overall function which slows metabolism of drugs (eg theophylline, paracetamol, diazepam, nifedipine)
Drugs that undergo extensive first pass metabolism (eg propranolol, nitrates) are most affected by the reduced hepatic function
Many factors interact with liver metabolism (eg nutritional state, acute illness, smoking, other medications, etc.)
Renal excretion
Renal function declines with age (see 
‘The ageing kidney’, p.384), which has a profound impact on the handling of drugs that are predominantly handled renally
Drugs, or drugs with active metabolites, that are mainly excreted in the urine include digoxin, gentamicin, lithium, furosemide, and tetracyclines
Where there is a narrow therapeutic index (eg digoxin, aminoglycosides) then dose adjustment for renal impairment is required (see UK British National Formulary (BNF) Appendix 3)
Impaired renal function is exacerbated by dehydration and urinary sepsis—both common in older patients
Prescribing ‘rules’
1. Is it indicated?
Treatment of new symptom
Some symptoms trigger a reflex prescription (eg constipation—laxatives; dizziness—prochlorperazine). Before starting a medication, consider:
What is the diagnosis? (eg dizziness due to postural drop)
Can something be stopped? (eg opioid analgesia causing constipation)
Are there any non-drug measures? (eg increase fibre for constipation)
Optimizing disease management
For example: a diagnosis of cardiac failure should trigger consideration of loop diuretics, spironolactone, ACE inhibitors, and β-blockers.
Ensure the diagnosis is secure before committing the patient to multiple drugs (may be difficult where there is no clear diagnostic gold standard, eg with TIAs)
Do not deny older patients disease modifying treatments simply to avoid polypharmacy
Do not deny treatment because of potential side effects—while these may impact on functional ability, or cause significant morbidity (eg low blood pressure with β-blockade in cardiac failure) and need to be discontinued, this should usually be after a trial of treatment with careful monitoring
Conversely, do not start treatment to improve mortality from a disease if the patient has limited life span for other reasons (eg extreme frailty)
Preventative medication
For example: BP and cholesterol lowering.
Limited evidence base in older patients—be guided by biological fitness
Ensure the patient understands the rationale for treatment
2. Are there any contraindications?
Review past medical history (drug-disease interactions common)
Contraindications often relative, so a trial of treatment may be indicated, but warn patient, document risk and review impact (eg ACE inhibitors when there is renal impairment)
3. Are there any likely interactions?
Review the medication list
Computer prescribing assists with drug–drug interactions, automatically flagging up potential problems
4. What is the best drug?
Choose the broad category of drug (eg which antihypertensive) by considering which will work best in this patient (eg ACE inhibitors work less well in African Caribbeans), which is least likely to cause side effects (eg calcium channel blockers may worsen cardiac failure) and is there any potential for dual action? (eg a patient with angina could have a β-blocker for both angina and blood pressure control).
Within each category of medication, there are many choices:
Develop a personal portfolio of drugs with which you are very familiar
Hospital formularies will often dictate choices within hospital
Cost should be a consideration—eg simvastatin is ‘off patent’ and likely to be cheaper than a newer statin
Pharmaceutical companies will try to convince you of the benefits of a new brand. Unless this is a novel class of drug, it is likely that existing brands have a greater proven safety record with similar benefit. Older patients have greater potential to suffer harm from new drugs, and are unlikely to have been included in clinical trials. Time will tell if there are real advantages—in general stick to what you know
▶Never be the first (or last) of your peers to use a new drug.
5. What dose should be started?
‘Start low and go slow’
Drugs are usually better tolerated at lower doses, and can be optimized if there are no adverse reactions
In most cases, benefit is seen with drug initiation, further increments of benefit occurring with dose optimization (eg ACE inhibitors for cardiac failure, where 1.25mg ramipril is better than 10mg with a postural drop)
However, do not under treat—use enough to achieve the therapeutic goal (eg for angina prophylaxis, a β-blocker dose should be adequate to induce a mild bradycardia)
6. How will the impact be assessed?
Schedule follow-up looking for:
Efficacy of the drug eg has the bradykinesia improved with a dopamine agonist? Medication for less objective conditions (eg pain, cognition) requires careful questioning of patient and family/carers
Any adverse events—reported by the patient spontaneously, elicited by direct questioning (eg headache with dipyridamole) or by checking blood tests where necessary (eg thyroid function on amiodarone)
Any capacity to increase the dose to improve the effect (eg ACE inhibitors in cardiac failure)
7. What is the time frame?
Many older patients remain on medication for a long time. 88% of all prescriptions in the over 65s are repeats. 60% of prescriptions are active for over 2 years, 30% over 5 years, and 6% over 10 years
This may be appropriate (eg with antihypertensives) and if so, the patient should be aware of this and seek an ongoing supply from the GP
Some drugs should never be prescribed long term (eg prochlorperazine, night sedation)
Medication should be regularly reviewed and discontinued if ineffective or no longer indicated, eg some psychotropic medications (eg lithium, depot antipsychotics) were intended for long-term use at initiation, but the patient may have had no psychiatric symptoms for years (or even decades). They can contribute to falls, and cautious withdrawal may be indicated
Taking a drug history
An accurate drug history includes the name, dose, timing, route, duration, and indication for all medication. Studies have suggested that patients will report their drug history accurately around half of the time, and this figure falls with increasing age.
Reasons for problems arising
Inadequate information to the patient at the time of prescribing
Multiple medications
Multiple changes if side effects develop
Use of both generic and brand names
Variable doses over time (eg dopa agonists, ACE inhibitors)
Cognitive and visual impairment
Over-the-counter drugs
Useful sources of information
The patient's actual drugs—they will often bring them along in a bag to outpatients or when admitted
Many seasoned patients will carry a list of their current medication—written either by them or a healthcare professional
Computer-generated print outs of current medication from the GP
Dosette® and Nomad® systems will incorporate information about the medication they contain
A telephone call to the GP surgery will yield a list of active prescriptions (but not over-the-counter medication)
Family members will often know about medication, especially if they help administer them
Medical notes will often contain a list of medication at the last hospital attendance
These can be extremely useful, but have limitations. A prescription issued does not mean that it was necessarily dispensed, or that the medication is being taken correctly and consistently. Previously prescribed medications may still be being taken and patients may occasionally use another patient's medication (eg a spouse).
Good habits
Every time a patient is seen (in clinic, day hospital, admission, etc.) take time to review the medication and make an up-to-date list
Begin correspondence with a list of current medication
If changes are made, or a new medication tried and not tolerated, document the reason for this, and communicate this to all people involved in care (especially the GP)
Always include allergies and intolerances in the drug history
Solutions
Take the drug history with meticulous care—ask directly about:
Inhalers
Topical medication (creams, eye drops, patches, etc.)
Occasional use medication
Intermittent use medication (eg 3-monthly B12 injections, depot antipsychotics, weekly bisphosphonates, etc.)
Over-the-counter (non-prescription) medication—a growing number of drugs are available (in the UK, including proton pump inhibitors (PPIs) and statins)
Herbal and traditional remedies
Clarify how often occasional use medication is taken—analgesia may be used very regularly, or not at all
Be non-judgemental. If you suspect poor concordance (eg BP failing to settle despite multiple prescriptions) then the following questions can be useful to elicit an accurate response:
‘Have you managed to take all those tablets I suggested?’
‘Which tablets do you find useful?’
‘Do any of the tablets disagree with you?’—if yes, then ‘How often do you manage to take it?’
‘What triggers you to remember?’ (eg take with each meal, leave by toothbrush, etc.)
Scrutinize computer-generated lists carefully. Remember to look at when the prescription was last issued and estimate when they would be due to run out (eg 28 tablets to be taken once a day, last issued 3 months ago means that the drug has either run out, or not been taken regularly)
The gold standard is to ask the patient to bring in all of the medication that they have at home—both old and new. Go through each medication and ask them to explain which they take, and how often. This allows:
Comparison with a list of medication that they are supposed to be taking
Old drugs to be discarded (if necessary retain them and return to pharmacy)
Concordance to be estimated (by looking at date of dispensing and number of tablets left)
Clarification of doses, timings, and rationale for treatment. In a less-pressured setting (eg DH) it is useful to generate a list for the patient to carry with them (see Table 6.1 for example)
Education of patient and family where needed (eg reason for taking)
| Medication | Brand name | Reason | Dose | Morning | Lunch | Evening | Duration |
|---|---|---|---|---|---|---|---|
Aspirin | Thin blood, prevent heart attack | 75mg | √ | Lifelong | |||
Simvastatin | Zocor | Lower cholesterol; prevent heart attack | 40mg | √ | Lifelong | ||
Ramipril | Tritace | Lower blood pressure Prevent heart attack | 5mg | √ | Lifelong | ||
Atenolol | Tenormin | Lower blood pressure, prevent angina attacks | 50mg | √ | Lifelong | ||
Isosorbide mononitrate | Ismo | Prevent angina attacks | 20mg | √ | √ | Lifelong | |
Glyceryl trinitrate (GTN) spray | Treat angina | 1 puff | As needed | ||||
Amoxicillin | Amoxil | Antibiotic for chest infection | 500mg | √ | √ | √ | 7 days |
| Medication | Brand name | Reason | Dose | Morning | Lunch | Evening | Duration |
|---|---|---|---|---|---|---|---|
Aspirin | Thin blood, prevent heart attack | 75mg | √ | Lifelong | |||
Simvastatin | Zocor | Lower cholesterol; prevent heart attack | 40mg | √ | Lifelong | ||
Ramipril | Tritace | Lower blood pressure Prevent heart attack | 5mg | √ | Lifelong | ||
Atenolol | Tenormin | Lower blood pressure, prevent angina attacks | 50mg | √ | Lifelong | ||
Isosorbide mononitrate | Ismo | Prevent angina attacks | 20mg | √ | √ | Lifelong | |
Glyceryl trinitrate (GTN) spray | Treat angina | 1 puff | As needed | ||||
Amoxicillin | Amoxil | Antibiotic for chest infection | 500mg | √ | √ | √ | 7 days |
Convert to once-a-day dosing where possible (eg change captopril tds to ramipril once daily (od))
Try to prescribe medications to be taken at the same time of day—this may challenge firmly held views (eg that warfarin must be taken at night)
Try to use medications that have dual indications for the patient (eg β-blockade for both hypertension and angina)
Consider a daily dose reminder system (eg dosette® box) or a monitored dosage system (eg Nomad®)
Do they understand the reason for taking the medication, and how to take it correctly? Are there any problems the patient is attributing to the medication (perhaps incorrectly)?
Medication summaries (see Table 6.1) can assist with this
Warn of predictable side effects that are likely to pass (eg nausea with citalopram, headache with dipyridamole)
Promote personal responsibility for medication—this should not be something that the patient feels has been imposed
Enlist support of family and carers in monitoring
Check tablet boxes and see if they are gone
Look at how often a repeat prescription has been requested
Some medications can have serum levels checked (eg digoxin, phenytoin, lithium)
Some medications will produce changes detectable at physical examination (eg bradycardia with β-blockade, black stool with iron therapy).
Drug sensitivity
Altered sensitivity
Many older patients will have altered sensitivity to some drugs, for example:
Receptor responses may vary with age. Alterations in the function of the cellular sodium/potassium pumps may account for the increased sensitivity to digoxin seen in older people. Decreased β-adrenoceptor sensitivity means that older patients mount less of a tachycardia when given agonists (eg salbutamol) and may become less bradycardic with β-blockers
Altered coagulation factor synthesis with age leads to an increased sensitivity to the effects of warfarin
The ageing CNS shows increased susceptibility to the effects of many centrally acting drugs (eg hypnotics, sedatives, antidepressants, opioid analgesia, antiparkinsonian drugs, and antipsychotics)
Adverse reactions
Certain adverse reactions are more likely in older people, because of this altered sensitivity:
Baroreceptor responses are less sensitive, making symptomatic hypotension more likely with antihypertensives
Thirst responses are blunted, making hypovolaemia due to diuretics more common
Thermoregulation is blunted, making hypothermia more likely with prolonged sedation
Allergic responses to drugs are more common because of altered immune responses
Despite the variations in drug handling, most drugs have a wide therapeutic index, and there is no clinical impact.
Only drugs with a narrow therapeutic index or where older patients may show very marked increased sensitivity may require dose alteration:
ACE inhibitors
Aminoglycosides (dose determined by weight, and reduced if impaired renal function)
Diazepam (start with 2mg dose)
Digoxin (low body weight older patients rarely require more than 62.5micrograms maintenance dose)
Non-steroidal anti-inflammatory drugs
Opiates (start with 1.25–2.5mg morphine to assess impact on CNS)
Oral hypoglycaemics (increased sensitivity to hypoglycaemia with decreased awareness—avoid long-acting preparations such as glibenclamide, and start with lower doses of shorter-acting drugs, eg gliclazide 40mg)
Warfarin (load more cautiously)
Adverse drug reactions
More common and complex with increasing age—up to three times more frequent in the over 80s. Drug reactions account for considerable morbidity, mortality, and hospital admissions (one study estimated a quarter of US hospital admissions relate to medication complications).
Older people are not a homogeneous group, and many will tolerate medications as well as younger ones, but a number of factors contribute to the increased frequency:
Altered drug handling and sensitivity occur with age, made worse by poor appetite, nutrition and fluid intake
Frailty and multiple diseases make drug–disease interactions more common, for example:
Anticholinergics may precipitate urine retention in a patient with prostatic hypertrophy
Benzodiazepines may precipitate delirium in a patient with dementia
These relationships become even more complex when the large numbers of drugs that are prescribed for multiple conditions interact with the diseases as well as each other, eg an osteoporotic patient is prescribed a bisphosphonate, then sustains a vertebral crush fracture and is given a non-steroidal which exacerbates gastric irritation and causes a gastrointestinal bleed
Errors in drug taking make adverse reactions more likely. Mistakes increase with:
Increasing age
Increasing numbers of prescribed drugs (20% of patients taking three drugs will make errors, rising to 95% when 10 or more drugs are taken)
Cognitive impairment
Living alone
Strategies to minimize adverse drug reactions
Prescribe sensibly
Consider possible drug–drug and drug–disease interactions whenever a new drug is started
Some drugs are associated with high rates of drug–drug interaction, eg warfarin, amiodarone, SSRIs, antifungals, digoxin, phenytoin, and erythromycin
For every new problem, consider if an existing medication could be the cause. Try to avoid the so-called prescribing cascade, where side effects are treated with a new prescription, rather than discontinuing the offending drug. If multiple medications are possible culprits then stop one at a time and watch for improvement
Optimize concordance
Use extreme caution at times of care transfer as information is often lost
ACE inhibitors
Common indications include blood pressure control, vascular risk reduction, heart failure, and diabetic nephropathy.
Cautions
Renal disease
Use ACE inhibitors with extreme caution if there is a known history of renal artery stenosis, as renal failure can be precipitated. If the clinical suspicion of this is high (renal bruit, uncontrolled hypertension that is unexplained) then consider investigating for renal asymmetry with an ultrasound before starting treatment
Renal impairment per se is not a reason to withhold ACE inhibitors (indeed they are effective treatment for some types) although the dose may need to be reduced
Monitor renal function before and after treatment. Sudden deterioration may indicate renal artery stenosis, and the ACE should be stopped pending investigation
If a patient becomes unwell (dehydrated, septic, etc.) they may need temporary withdrawal of the ACE inhibitor
Hypotension
Early ACE inhibitors (eg captopril) were associated with a risk of first dose hypotension, and so many patients were given an in-hospital test dose
This is rare with newer ACE inhibitors, and cautious outpatient initiation is acceptable
Older patients are more prone to postural hypotension. Check blood pressure lying and standing, and ask about postural symptoms (eg light-headedness)
The risk of hypotension is greater with volume-depleted patients—eg those on high dose diuretics, on renal dialysis, dehydrated from intercurrent illness or in severe cardiac failure. Correct dehydration before initiation where possible
ACE inhibitor induced hypotension is common in patients with severe aortic stenosis, and they should probably be avoided (unless under cardiological supervision)
‘Start low, and go slow’. Monitor carefully. This may take multiple clinic visits, but avoids complications
Cough
Many ACE inhibitors cause a persistent dry cough. Always warn the patient about this, as it can cause considerable distress. Forewarned is forearmed, and many patients will be prepared to accept this side effect if the ACE inhibitor is the best choice for them
Changing to an angiotensin receptor blocker (ARB) removes the cough in most cases, but ARBs are not quite as effective in terms of risk reduction
Hyperkalaemia
There is a risk of hyperkalaemia when ACE inhibitors are used with potassium-sparing diuretics, eg spironolactone (in heart failure) or with non-steroidals
Be aware, and monitor electrolytes. Most tolerate a potassium of up to 5.5mmol/L
The tendency to hyperkalaemia can be useful in patients who are also on potassium-losing diuretics (eg furosemide) as the two may balance each other out—overall hypokalaemia is more common in patients with heart failure
Screen for contraindications
Check baseline renal function and electrolytes
Warn patient about possible cough and postural symptoms
An example of initiation/titration is as follows
Week 1
Start ramipril 1.25mg at night.
Week 2
Check renal function, blood pressure (lying and standing) and check for postural symptoms.
Week 4
Increase ramipril to 2.5mg at night.
Week 6
Check renal function, blood pressure (lying and standing) and check for postural symptoms.
Week 8
Increase ramipril to 5mg at night.
Continue titrating the dose upwards as tolerated, but most older patients will develop postural symptoms at higher doses, increasing the risk of falls. The goal should be for safe optimization.
Once established on an ACE inhibitor, periodic renal monitoring is sensible (perhaps annually).
If a patient becomes acutely unwell
Dehydration increases susceptibility to ACE inhibitor induced renal failure and hypotension
Correct the dehydration first—treat cause, give fluid supplementation, and stop diuretics
Temporary cessation of ACE inhibitor may be needed if dehydration prolonged (>24hr)
Monitor renal function daily
Remember to restart the ACE inhibitor after recovery
Amiodarone
Indications include rate control and prevention of supraventricular cardiac arrhythmias (commonly AF) and prevention of paroxysmal ventricular arrhythmias.
Intravenous amiodarone is now included on the advanced life support protocols for cardiac arrest (
www.resus.org.uk).
Cautions
Interacts with many drugs, including warfarin (often co-prescribed for AF stroke prophylaxis; amiodarone increases warfarin effect) and statins (increased incidence of myopathy with higher statin doses)
Can cause deranged TFTs in either direction. Baseline thyroid function should be taken before initiation and then at 6-monthly intervals. Measure TSH, free T4 and free T3—see ‘HOW TO . . . Manage amiodarone-induced thyroid dysfunction’, p.139
Nausea and anorexia are common (~30%), and may respond to dose reduction. Less frequently, liver function becomes deranged—check at baseline and every 6 months; hepatitis may reverse with dose reduction
Photosensitivity can occur, so amiodarone is unlikely to be suitable for avid gardeners or outdoor workers
Corneal microdeposits often occur (90%), that can cause a glare with night driving (if this is likely to be a problem then avoid amiodarone); microdeposits are reversible, and do not threaten vision
Pulmonary problems may occur (fibrosis, alveolitis, pneumonitis). They are the most serious amiodarone-related side effects, and often occur early (months). Any new respiratory symptoms should trigger clinical assessment, CXR, and pulmonary function tests
Peripheral neuropathy may occur—be alert for early signs of this and stop the drug promptly to avoid progression
Starting oral amiodarone
Check TFTs and LFTs
Load with:
Week one—200mg tds
Week two—200mg twice daily (bd)
From week 3 onwards use the maintenance dose of 200mg od
See the patient at 6–8 weeks intervals to check for adverse effects and efficacy
Check TFTs and LFTs at 6-month intervals
In the longer term, the dose may be reduced further in frail older patients to 100mg od (or even alternate days) without losing efficacy, as the half-life is extremely long
Overview
Despite this long list of side effects and cautions, amiodarone is often well-tolerated and effective in older patients. It is less negatively inotropic than many alternative antiarrhythmics, and is excreted primarily by the liver; it therefore has a useful part to play.
Amiodarone contains 37% iodide, which impacts on thyroid homeostasis, causing alterations in TFTs in up to 50% of patients.
Early amiodarone changes
Alterations in TFTs in a euthyroid patient most common
Usually high TSH or decreased thyroxine (T4) concentrations
This is typically transient, resolves after about 3 months and does not indicate that hypothyroidism has occurred
Monitor at 3-monthly intervals
Changes with longer-term amiodarone therapy include
Euthyroid changes
Minor increase in T4
Suppression of triiodothyronine (T3)
Suppression of TSH
Manage by monitoring thyroid function every 6 months
Hyperthyroidism
More common when there is occult underlying thyroid disease and in areas with low oral iodine intake (up to 12% incidence)
Diagnose with increased free T3 and free T4 with suppressed TSH concentrations
Withdraw amiodarone where possible
No immediate improvement as amiodarone has a long half-life
Where amiodarone needs to be continued, this can be treated with carbimazole as for standard hyperthyroidism. May be resistant. Adding steroids may help
Amiodarone can also cause a destructive thyroiditis, releasing thyroid hormone into the circulation and causing hyperthyroidism. Treatment is with high-dose steroids
Hypothyroidism
More common in areas with low iodine intake (up to 13% incidence)
Diagnose with decreased free T3 and free T4 concentrations with elevated TSH concentrations
An elevated TSH alone is not diagnostic—may be transient, especially in the first three months of treatment. If the patient is well, recheck in 3 months
Amiodarone withdrawal is rarely necessary. Adding levothyroxine sodium will correct the problem
Analgesia
Older patients are more likely to suffer chronic pain than younger ones, owing to the increased frequency of conditions such as osteoarthritis, osteoporosis, etc.
Pain management is more challenging and a standard ‘pain ladder’ approach not always useful because of the altered sensitivity of the older patient to certain classes of analgesic medication.
Non-steroidal anti-inflammatory drugs
Includes aspirin (especially at analgesic doses).
Potential problems
Fluid retention causing worsening hypertension, cardiac failure, and ankle swelling
Renal toxicity—risk of acute tubular necrosis, exacerbated by intercurrent infection, or dehydration
Peptic ulceration and gastrointestinal bleeding—there is an increased risk with increased age, and the bleeds tend to be more significant
▶The number of older patients requiring hospitalization because of NSAID-induced deterioration in renal or cardiac function actually exceeds the number with gastrointestinal bleeds.
Age itself is probably not an independent risk factor for most complications of NSAID treatment, but factors such as comorbidities, co-medications, hydration, nutritional status and frailty are linked to an increased risk, all of which are more common with advancing age
Guidance for use in older patients
NSAIDs should be used with extreme caution in older patients, and avoided altogether in the very frail
Should be given for a short period only
Use low-dose moderate potency NSAIDs (eg ibuprofen 0.6g/day)
Avoid using two NSAIDs together (this includes low-dose aspirin)
Consider co-prescription of a gastric-protective agent (eg omeprazole) for the duration of the therapy
Avoid using ACE inhibitors and NSAIDs together—they have opposing effects on fluid handling, and are likely to cause renal toxicity in combination
Opioid analgesia
Wide range of drugs sharing many common features, but with qualitative and quantitative differences.
Potential problems include constipation, nausea and vomiting, anorexia, confusion, drowsiness, and respiratory depression.
Guidance for use in older patients
Most of these are dose dependant, and careful up-titration will obtain the right balance of analgesic effect and adverse effects
Constipation is common (worse in older people) but can be managed with good bowel care
Most adverse effects are reversible once the medication is reduced or discontinued
Chronic abdominal pain may be due to constipation that will respond to bowel care rather than analgesia.
Weight loss and physical activity helps with many pains (eg arthritis)
Temperature treatments (eg hot/cold packs applied to painful joint)
TENS machines
Alternative therapies (eg acupuncture, aromatherapy) can help
Avoidance of (non-essential) activity that provokes pain if possible
For example: topical capsaicin for post-herpetic neuralgia, local nerve blocks for regional pain, massage for musculoskeletal pain, joint replacement for arthritic pain, or radiotherapy for pain from bony metastases
Well-tolerated and with few side effects
Before moving from this, ensure that the maximum dose is being taken regularly (ie 1g taken four times a day) for optimal analgesic effect. Many patients will find taking an occasional paracetamol ineffective—explain that regular dosing increases analgesic effect
Second line therapy in most older patients
Options to deal with mild (eg codeine, dihydrocodeine), moderate (eg tramadol) and severe pain (eg morphine, diamorphine, fentanyl)
Compound preparations are useful when adding an opioid to regular paracetamol, as it limits the number of tablets taken. Co-codamol (codeine and paracetamol) has variable doses of codeine (8mg, 15mg, or 30mg per tablet) allowing up titration of the opioid component
All affect same receptors, so use as a continuum—if regular maximum dose codeine is not working, then step up to the next level of opioid strength (eg if 60mg codeine four times daily (qds) is not sufficient then change to tramadol 50mg qds or morphine sulphate M/R 5mg bd)
Various formulations for the delivery of strong opiates. Liquids are useful if there are swallowing problems (eg morphine sulphate solution). Slow-release tablets (eg morphine sulphate M/R) and transdermal patches (eg fentanyl) provide constant analgesic effect for continuous pain. Parenteral opiates are used in terminal care (subcutaneous injections of morphine and diamorphine for intermittent pain; 24hr infusion pumps for constant pain)
Monitor for side effects—active bowel care with initiation
Very fit older patients can be given short courses of NSAIDs
Cyclo-oxygenase-2 (COX-2) inhibitors have a limited role
Depression is often coexistent (consequent or causal). Treatment can help with overall pain management
Informal (‘positive mental attitude’) and formal psychotherapeutic approaches may be preferable to side effects of analgesic medication
Steroids
Oral steroids (usually prednisolone) are given for many conditions in older patients, commonly COPD exacerbation, polymyalgia rheumatica, rheumatoid arthritis, and colitis. Treatment may be long term. Although the benefits of treatment usually outweigh the risks, awareness of these can minimize harm. Discuss likely side effects with patients and carers.
Cautions
Osteoporosis—this is most marked in the early stages of treatment. Older people will have diminishing bone reserves anyhow, and there is a strong argument for putting all steroid-treated older patients on bone protection at outset, unless the course is certain to be very short (eg less than 2 weeks). This should consist of daily calcium and vitamin D, along with a bisphosphonate (weekly preparations eg alendronate 70mg, improve concordance)
Steroids can precipitate impaired glucose tolerance or frank diabetes. Monitor sugar levels periodically (eg weekly capillary blood sugar, or urinalysis) in all steroid users. Steroids worsen control in known diabetics, necessitating more frequent monitoring
Hypertension may develop because of the mineralocorticoid effect of prednisolone, and this should be checked for regularly
Skin changes occur, and are particularly noticeable in older patients with less resilient skin. Purpura, bruising, thinning, and increased fragility are common
Muscle weakness occurs with prolonged use, dominantly proximal in distribution. This leads to problems rising from chairs, climbing stairs etc. and may be the final straw for a frail older person with limited physical reserve. (See ‘Muscle symptoms’, p.478)
There is an increased susceptibility to infections on steroids, and the presentation may be less acute, making diagnosis more difficult. Candidiasis (oral and genital) is particularly common and should be treated promptly
High doses (as used in treatment of giant cell arteritis) can cause acute confusion and sleep disturbance, and older people are particularly prone. Give steroids in the morning if possible
Cataracts may develop with long-term steroid use. If vision declines, look for cataracts with an ophthalmoscope and consider specialist referral
Peritonitis may be masked by steroid use—the signs being less evident clinically. Have a higher index of suspicion of occult perforation in a steroid-treated older patient with abdominal pain. There is also a weak association between steroid use and peptic ulceration
Adrenocortical suppression means that the stress response will be diminished in chronic steroid users. If such a patient becomes acutely unwell (eg septic), the exogenous steroid dose will need to be temporarily increased (eg double the usual oral dose, replace with intramuscular hydrocortisone if unable to take by mouth). Suppression can continue for months after stopping chronic steroids; have a low threshold for ‘covering’ acute illness
Stopping treatment
Many patients are on fairly low doses of steroids for a long period. It can be difficult to completely tail the dose, as steroid withdrawal effects (fevers, myalgia, etc.) can often be mistaken for disease recurrence, and this often needs to be done very slowly (perhaps reducing by as little as 1mg a month). There is no such thing as a ‘safe’ dose of steroid so, for every patient you see on steroids, ask the following:
Can the dose be reduced?
Could a steroid sparing agent (eg azathioprine) be used instead?
Is the patient taking adequate bone protection?
What is the blood pressure and blood glucose?
Warfarin
Common indications range from absolute (PE, DVT, artificial heart valve replacement) to relative (stroke prophylaxis in AF).
Cautions
Risk is increased if the patient is unable to take medication reliably, so is not suitable without supervision for cognitively impaired patients, or those who self-neglect. If there is an absolute indication, then consider supervised therapy (by spouse, family, or carers via a dispensing system) or (rarely) a course of low molecular weight heparin instead
Risk is higher if there is a high probability of trauma, eg recurrent falls
Excess alcohol consumption is associated with poor concordance and falls. Liver enzymes are induced, making control of anticoagulation more difficult. Highly variable intake is especially problematic
Comorbidity may increase sensitivity to warfarin (eg abnormal liver function, congestive cardiac failure) and should be screened for
GPs will often be good judges of risk—consider discussing borderline cases
Side effects
Bleeding is the major adverse event, ranging from an increased tendency to bruise to major life-threatening bleeds. The most significant include intracerebral haemorrhage and gastrointestinal blood loss.
Warfarin does not cause gastric irritation, but may accelerate blood loss from pre-existing bleeding sources. Ask carefully about history of non-steroidal use (including aspirin) and gastrointestinal symptoms (upper and lower). If any are present then quantify risk with further testing—full blood count and iron studies might indicate occult blood loss. If the warfarin is not essential, then a full gastrointestinal work-up may be appropriate before starting in the fitter patients. In frailer patients, consider warfarin with empirical PPI
Nosebleeds are common in older patients, and may become more significant on warfarin. Often due to friable nasal vessels that are amenable to treatment by ENT surgeons, so reducing the risk of epistaxis on warfarin
Patients often take warfarin for many years
During that time, there is usually change in both the risk (serious bleeding) and the benefit (reduced thromboembolism) of anticoagulation. The most common scenario is that the antithrombotic benefit of anticoagulation remains, but that the bleeding risk increases and cannot be reduced—eg a patient falls frequently despite intervention, or has a major bleed that could recur (eg diverticular)
Any drug must be stopped unless there is a net benefit to the individual patient. In conjunction with patient (and carer), the indication for warfarin should be reviewed periodically; perhaps annually in frail older people, and after any significant event, eg hip fracture
Usual target international normalized ratio (INR)
(See Table 6.2.)
| Indication | Target INR | Duration |
|---|---|---|
Atrial fibrillation | 2.5 | Lifelong |
Venous thromboembolism | 2.5 | Varies. Usually 6 months. Lifelong if recurrent or with ongoing precipitant (eg malignancy). Shorter duration if identifiable precipitant and high bleeding risk |
Recurrent venous thrombo-embolism while on warfarin | 3.5 | Lifelong |
Mechanical prosthetic heart valves | 3.5 | Lifelong |
| Indication | Target INR | Duration |
|---|---|---|
Atrial fibrillation | 2.5 | Lifelong |
Venous thromboembolism | 2.5 | Varies. Usually 6 months. Lifelong if recurrent or with ongoing precipitant (eg malignancy). Shorter duration if identifiable precipitant and high bleeding risk |
Recurrent venous thrombo-embolism while on warfarin | 3.5 | Lifelong |
Mechanical prosthetic heart valves | 3.5 | Lifelong |
What to do when the INR is too high
Always look for the reason why the INR became elevated and correct this factor
If there is no sign of bleeding, then stop warfarin and monitor the INR as it falls
If the INR >8 but there is no bleeding, a small dose of vitamin K (0.5–2.5mg) can be given to partially reverse the INR
Do not give vitamin K routinely as control of anticoagulation will be made more difficult for weeks afterwards
If there is bleeding, then the warfarin needs reversing with vitamin K and fresh frozen plasma
For life-threatening bleeds (eg intracerebral haemorrhage) prothrombin complex concentrate can be used for rapid reversal
▶If a patient bleeds at target INR, always consider the possibility of underlying serious disease, eg bladder or gastrointestinal malignancy.
Further reading
Discuss risks and benefits of treatment with the patient—the indication is rarely absolute.
Ensure the patient is told
There will be frequent blood tests and monitoring
Many medications interact with warfarin, so before taking any new medication (including over the counter), always check compatibility with the doctor, dentist, or pharmacist
Use paracetamol or codeine-based analgesia (never NSAIDs)
Alcohol interacts with warfarin metabolism, and should be taken in moderation and on a regular basis (avoid binge drinking)
Vitamin K-containing foods (eg spinach) should not have variable intake
If trauma occurs, bleeding may last longer. Apply pressure to wounds and seek medical help if it does not stop
Give the patient an anticoagulant treatment book that will hold details of their treatment schedule and reinforce the information that you give them
Induction
Check baseline clotting
Prescribe warfarin to be taken at 6pm
Medical notes should state indication, target INR, and duration of therapy
The normal adult induction dose (10mg day 1, 10mg day 2, then an INR) is rarely appropriate in older patients who are more sensitive to its effects
Reduce the dose if the patient is frail, has a low body weight, has multiple comorbidities, or a deranged baseline clotting
For most older patients 5mg /5mg /INR is a safer approach
If there are multiple factors causing concern, then 5mg /INR is better
▶There is no rush. If the indication is absolute, then the patient should also be on therapeutic heparin until the INR is in range. It is much easier to increase the dose of warfarin, than to deal with bleeding from an overdose.
The INR will then need checking daily, then alternate days until a pattern becomes clear
Many haematology departments will offer automatic dosing with a schedule for retesting
The INR testing can gradually be done less frequently, stretching to 12-weekly in long-term users
Induction in hospital is now often done by anticoagulation teams
Common side effect in older patients—thought to be due to altered immune function. Rarely life-threatening, but cause considerable distress.
Make the diagnosis
Variable in appearance, but most commonly toxic erythema—symmetrical, erythematous, itchy rash, trunk > extremities, lesions may be measles-like, urticarial, or resemble erythema multiforme
Certain drugs may produce predictable eruptions:
Acneiform rash with lithium
Bullous lesions with furosemide
Target lesions with penicillins and phenytoin
Psoriasis-like rash with β-blockers
Urticaria with penicillin, opiates and aspirin
Fixed drug eruption (round purple plaques recurring in the same spot) with paracetamol, laxatives, sulphonamides, and tetracyclines
Toxic epidermal necrolysis is a rare, serious reaction to drugs such as non-steroidals, allopurinol, and phenytoin. The skin appears scalded, and large areas of epidermis may shear off causing problems with fluid and electrolyte balance, thermoregulation, and infection
Take a careful drug history to elicit a temporal relationship to medication administration—eg within 3 days of starting a new drug (may be as long as 3 weeks), or becoming worse every morning after a regular drug is given
Stop the drug
Stop multiple medications one at a time (stop drugs started closest to the onset of the rash first), and watch for clinical improvement
May get slightly worse before improving
Usually clears within 2 weeks
Advise the patient to avoid the drug in the future
Soothe the skin
Emollients, cooling agents (eg calamine) and weak topical steroids may help
Oral antihistamines are often given with variable success. Sedating antihistamines (eg hydroxyzine) may help sleep
Treat the complications
More likely if extensive and prolonged.
Risks include:
Hypothermia
Hypovolaemia
Secondary infection
▶Consider dermatology referral if not improving after 2 weeks off the suspected drug.
Proton pump inhibitors
PPIs (eg omeprazole, lansoprazole) are very effective in reducing gastric acid secretion and therefore in treating peptic ulcers and gastro-oesophageal reflux disease (GORD). They are perceived as very safe drugs. The combination of effectiveness and safety has led to them being one of the most commonly prescribed drug classes.
However, PPIs are often prescribed without an appropriate indication, or are initiated appropriately but not discontinued after a treatment course. Overall, over 50% of PPI use is unnecessary.
Side effects
Common side effects are headache, nausea, diarrhoea, and constipation
Infrequent idiosyncratic reactions include acute interstitial nephritis, erythema multiforme, pancreatitis, microscopic colitis, hyponatraemia, ad hypomagnesaemia
Hydrochloric acid aids protein digestion and absorption of vitamin B12 and calcium, and is active against pathogens. PPI use is associated with:
Community and hospital incidence of CDAD and increased likelihood of recurrence
Enteric bacterial infections (eg Salmonella, Campylobacter)
Community- and hospital-acquired pneumonia
Long-term use is associated with higher rates of hip fracture, possibly caused by altered calcium absorption
Interactions
There are a few important interactions:
The effects of phenytoin and warfarin are enhanced
The effects of clopidogrel are reduced
Plasma concentrations of digoxin are increased slightly
Appropriate prescribing
Always specify the indication for treatment and its intended duration
In GORD, always first address non-drug factors (obesity, alcohol) and consider the use of less potent acid-suppression (eg H2 antagonists such as ranitidine)
Transient dyspepsia or occasional heartburn are inadequate indications for long-term PPI treatment
In primary care, review the need for the drug periodically
In secondary care, be careful not to extend an initial appropriate PPI prescription for prophylaxis against gastrointestinal bleeding
In (confirmed or possible) CDAD, consider stopping PPIs
Herbal medicines
Use of herbal supplements by older adults is common (some studies estimate 30–50%). Most patients do not discuss this with their doctors so remember to ask. Herbal medicines are not regulated like drugs, contain variable quantities of active ingredient and may contain impurities. Herbal medicines have adverse effects and drug interactions (Table 6.3).
| Name | Use | Adverse effects | Drug interactions |
|---|---|---|---|
Garlic | Hypertension High cholesterol Antiplatelet | Bleeding Gastrointestinal upset Hypoglycaemia | NSAIDs Antiplatelets Anticoagulants |
Gingko | Memory problems | Seizures Bleeding Headaches Dizziness Gastrointestinal upset | NSAIDs Antiplatelets Anticoagulants Monoamine oxidase inhibitors (MAOIs) Trazodone |
Ginseng | Performance enhancer | Hypertension Tachycardia | NSAIDs Antiplatelets Anticoagulants |
Glucosamine/ chondroitin | Osteoarthritis | Nausea Diarrhoea Heartburn | Hypoglycaemic agents (reduced efficacy) |
St John's wort | Antidepressant Anxiolytic | Nausea Allergy Dizziness Headache Photosensitivity | Cytochrome P450 drugs Anticoagulants Antivirals SSRIs Statins |
Echinacea | Immune stimulant | Allergy Hepatitis Asthma Vertigo | Immunosuppressants |
Valerian | Anxiety Insomnia | Sedation | CNS depressants |
Saw palmetto | Prostatic symptoms | Constipation Diarrhoea Decreased libido Hypertension Urinary retention | Finasteride |
| Name | Use | Adverse effects | Drug interactions |
|---|---|---|---|
Garlic | Hypertension High cholesterol Antiplatelet | Bleeding Gastrointestinal upset Hypoglycaemia | NSAIDs Antiplatelets Anticoagulants |
Gingko | Memory problems | Seizures Bleeding Headaches Dizziness Gastrointestinal upset | NSAIDs Antiplatelets Anticoagulants Monoamine oxidase inhibitors (MAOIs) Trazodone |
Ginseng | Performance enhancer | Hypertension Tachycardia | NSAIDs Antiplatelets Anticoagulants |
Glucosamine/ chondroitin | Osteoarthritis | Nausea Diarrhoea Heartburn | Hypoglycaemic agents (reduced efficacy) |
St John's wort | Antidepressant Anxiolytic | Nausea Allergy Dizziness Headache Photosensitivity | Cytochrome P450 drugs Anticoagulants Antivirals SSRIs Statins |
Echinacea | Immune stimulant | Allergy Hepatitis Asthma Vertigo | Immunosuppressants |
Valerian | Anxiety Insomnia | Sedation | CNS depressants |
Saw palmetto | Prostatic symptoms | Constipation Diarrhoea Decreased libido Hypertension Urinary retention | Finasteride |
Breaking the rules
A great deal of prescribing in geriatric practice relies on individually tailored assessment and pragmatic decision making. While what is described in the preceding pages is appropriate for many, there are times when ‘rules must be broken’ in the best interests of the individual patient. This requires careful consideration of risks and benefits; the patient should usually be reviewed to assess the impact of the decision.
Polypharmacy can cause problems, but is sometimes appropriate—depriving patients of beneficial treatments because they are old, or already on multiple other medications, can also be wrong. In a recent study of medication changes during a geriatric admission, the total number of drugs was the same at admission and discharge, but they had often been changed. In other words, there was active evaluation of medication going on—the goal being not just to limit the number of drugs, but also to optimize and individually tailor treatment.
Where side effects are very likely, but the drug is definitely indicated, then it may be appropriate to co-prescribe something to treat the expected adverse effect, for example:
Steroids and bisphosphonates
Opiates and laxatives
Furosemide and a potassium-sparing diuretic (or an ACE inhibitor)
Non-steroidals and a gastric protection agent
Whilst certain disease-drug interactions are very likely, and should be avoided, others may be an acceptable risk. For example:
β-blockers:
Are to be used with caution with asthma, yet they have such a good impact with on cardiovascular risk reduction that these cautions are not absolute. Often the ‘asthma’ is in fact COPD with little β-receptor reactivity, so cautious β-blockade initiated in hospital whilst monitoring the lung function may be appropriate
Can reduce the signs of hypoglycaemia in diabetics, but cardiovascular disease is common in people with diabetes, and the risks of treatment are usually outweighed by the benefits
In patients with peripheral vascular disease can cause a small reduction in walking distance, but this risk is usually outweighed by the reduction in the risk of cardiac death
Fludrocortisone (for postural hypotension) will worsen supine hypertension and cause ankle swelling. But if postural symptoms are severe then it may be appropriate to accept hypertension and associated risk
Amlodipine may worsen ankle swelling in a patient with chronic venous insufficiency, but if this is the best way of controlling hypertension, it may be appropriate to accept a cosmetic problem
