Chapter 6
Drugs
Pharmacology in older patients
HOW TO . . . Improve concordance/adherence
HOW TO . . . Start ACE inhibitors
HOW TO . . . Manage pain in older patients
HOW TO . . . Initiate warfarin
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 (e.g. co-amoxiclav) or have an unpleasant taste (e.g. 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 (e.g. bisphosphonates) require even larger volumes
• Multiple tablets, with different instructions (e.g. before/after food) are easily muddled up or taken in a suboptimal way
• Some routes (e.g. topical to back) may be impossible without assistance
Absorption
• Many factors are different in older patients (↑ 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 (e.g. digoxin), the dose should be adjusted
• There is often an ↑ proportion of fat, compared with water. This reduces the volume of distribution for water-soluble drugs, giving a higher initial concentration (e.g. digoxin). It also leads to accumulation of fat-soluble drugs, prolonging elimination and effect (e.g. diazepam)
• There is reduced plasma protein binding of drugs with age, which ↑ the free fraction of protein-bound drugs such as warfarin and furosemide
Hepatic metabolism
• Specific hepatic metabolic pathways (e.g. conjugation) are unaffected by age
• Reducing hepatic mass and blood flow can impact on overall function which slows metabolism of drugs (e.g. theophylline, paracetamol, diazepam, nifedipine)
• Drugs that undergo extensive first-pass metabolism (e.g. propranolol, nitrates) are the most affected by the reduced hepatic function
• Many factors interact with liver metabolism (e.g. nutritional state, acute illness, smoking, other medications, etc.)
Renal excretion
• Renal function declines with age (see 
‘The ageing kidney’, pp. 382–383), 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 (e.g. digoxin, aminoglycosides), then dose adjustment for renal impairment is required (see Appendix 3 in UK British National Formulary (BNF))
• 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 (e.g. constipation—laxatives; dizziness—prochlorperazine). Before starting a medication, consider:
• What is the diagnosis? (e.g. dizziness due to postural drop)
• Can something be stopped? (e.g. opioid analgesia causing constipation)
• Are there any non-drug measures? (e.g. ↑ 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
• 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 (e.g. low BP 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
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 the patient, document risk, and review impact (e.g. ACE inhibitors when there is renal impairment)
3. Are there any likely interactions?
• Computer prescribing assists with drug–drug interactions, automatically flagging up potential problems
4. What is the best drug?
Choose the broad category of drug (e.g. which antihypertensive) by considering which will work best in this patient according to local and national guidelines, which is least likely to cause side effects (e.g. calcium channel blockers may worsen cardiac failure), and if there is any potential for dual action (e.g. a patient with angina could have a β-blocker for both angina and BP control).
Within each category of medication, there are many choices:
• Develop a personal portfolio of drugs with which you are very familiar
• Guidelines and formularies will often dictate choices within hospital
• Cost should be a consideration
• 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?
• In most cases, benefit is seen with drug initiation, further increments of benefit occurring with dose optimization (e.g. ACE inhibitors for cardiac failure where 1.25mg ramipril is better than 10mg with a postural drop)
• However, do not undertreat—use enough to achieve the therapeutic goal (e.g. 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 (e.g. has bradykinesia improved with a dopamine agonist?). Medication for less objective conditions (e.g. pain, cognition) requires careful questioning of the patient and family/carers
• Any adverse events—reported by the patient spontaneously, elicited by direct questioning (e.g. headache with dipyridamole) or by checking blood tests where necessary (e.g. thyroid function on amiodarone)
• Any capacity to ↑ the dose to improve the effect (e.g. 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 (e.g. 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 (e.g. prochlorperazine, night sedation)
• Medication should be regularly reviewed and discontinued if ineffective or no longer indicated, e.g. some psychotropic medications (e.g. 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
• An evidence-based comprehensive approach to medication review (e.g. STOPP START v2 criteria) can be useful1
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 ↑ age.
Reasons for problems arising
• Inadequate information to the patient at the time of prescribing
• Multiple changes if side effects develop
• Use of both generic and brand names
• Variable doses over time (e.g. dopa agonists, ACE inhibitors)
• Cognitive and visual impairment
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 printouts of current medications from the GP. Increasingly available via shared electronic networks
• 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 taken and patients may occasionally use another patient’s medication (e.g. 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 medications
• 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:
• Topical medication (creams, eye drops, patches, etc.)
• Intermittent-use medication (e.g. 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 (e.g. 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?’ (e.g. 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 (e.g. 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)
• Pharmacists play an invaluable and ↑ role in ‘medicines reconciliation’, especially at transitions of care
• The gold standard is to ask the patient to bring in all of the medications 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 medications 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 the date of dispensing and the number of tablets left)
• Clarification of doses, timings, and rationale for treatment. In a less-pressured setting (e.g. DH), it is useful to generate a list for the patient to carry with them (see Table 6.1, for example)
• Education of the patient and family where needed (e.g. reason for taking)
HOW TO . . . Improve concordance/adherence
Simplify prescription regimens
• Convert to once-a-day dosing where possible
• Try to prescribe medications to be taken at the same time of the day—this may challenge firmly held views (e.g. that warfarin must be taken at night)
• Try to use medications that have dual indications for the patient (e.g. β-blockade for both hypertension and angina)
• Consider a daily-dose reminder system (e.g. Dosette® box) or a monitored dosage system (e.g. Nomad®)
Educate the patient and family
• 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 (e.g. nausea with citalopram, headache with dipyridamole)
• Promote personal responsibility for medication—this should not be something that the patient feels has been imposed
• Enlist the support of family and carers in monitoring
Monitor
• 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 (e.g. phenytoin, lithium)
Some medications will produce changes detectable at physical examination (e.g. bradycardia with β-blockade, black stool with iron therapy).
Table 6.1 Example of a patient drug summary sheet
| Medication | Brand name | Reason | Dose | Morning | Lunch | Evening | Duration |
| Aspirin | Thins blood, prevents heart attack | 75mg | √ | Lifelong | |||
| Simvastatin | Zocor® | Lowers cholesterol; prevents heart attack | 40mg | √ | Lifelong | ||
| Ramipril | Tritace® | 5mg | √ | Lifelong | |||
| Atenolol | Tenormin® | 50mg | √ | Lifelong | |||
| Isosorbide mononitrate | ISMO® | Prevents angina attacks | 20mg | √ | √ | Lifelong | |
| Glyceryl trinitrate (GTN) spray | Treats angina | 1 puff | As needed | ||||
| Amoxicillin | Amoxil® | Antibiotic for chest infection | 500mg | √ | √ | √ | 7 days |
Drug sensitivity
Altered sensitivity
Many older patients will have altered sensitivity to some drugs, e.g.:
• Receptor responses may vary with age. Alterations in the function of the cellular sodium/potassium pumps may account for the ↑ sensitivity to digoxin seen in older people. ↓ β-adrenoceptor sensitivity means that older patients mount less of a tachycardia when given agonists (e.g. salbutamol) and may become less bradycardic with β-blockers
• Altered coagulation factor synthesis with age leads to an ↑ sensitivity to the effects of warfarin
• The ageing CNS shows ↑ susceptibility to the effects of many centrally acting drugs (e.g. 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
Drugs that may require dose adjustment in older patients
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 ↑ sensitivity may require dose alteration:
• Aminoglycosides (dose determined by weight, and reduced if impaired renal function)
• Diazepam (start with 2mg dose)
• Digoxin (low-body-weight older patients rarely require >62.5 micrograms maintenance dose)
• Opiates (start with 1.25–2.5mg morphine to assess impact on CNS)
• Oral hypoglycaemics (↑ sensitivity to hypoglycaemia with ↓ awareness—avoid long-acting preparations such as glibenclamide, and start with lower doses of shorter-acting drugs, e.g. gliclazide 40mg)
Adverse drug reactions
More common and complex with ↑ age—up to three times more frequent in the over 80s. Drug reactions account for considerable morbidity, mortality, and hospital admissions (1 in 25 hospital admissions may result from avoidable drug adverse reactions).
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 ↑ 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, e.g.:
• 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 with each other, e.g. 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 ↑ with:
• ↑ numbers of prescribed drugs (20% of patients taking three drugs will make errors, rising to 95% when ten or more drugs are taken)
Strategies to minimize adverse drug reactions
• Consider possible drug–drug and drug–disease interactions whenever a new drug is started
• Some drugs are associated with high rates of drug–drug interactions, e.g. 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/adherence
• Use extreme caution at times of care transfer—medicines reconciliation is important
ACE inhibitors
Common indications include BP 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 inhibitor should be stopped pending investigation
• If a patient becomes unwell (dehydrated, septic, etc.), they may need temporary withdrawal of the ACE inhibitor—provide your patient with ‘sick day rules’
Hypotension
• Older patients are more prone to postural hypotension. Check BP lying and standing, and ask about postural symptoms (e.g. light-headedness)
• The risk of hypotension is greater with volume-depleted patients, e.g. 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, although beneficial in this condition, should be started slowly
• ‘Start low and go slow.’ Monitor carefully
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
Hyperkalaemia
• There is a risk of hyperkalaemia when ACE inhibitors are used with potassium-sparing diuretics, e.g. spironolactone
• Be aware, and monitor electrolytes. Most tolerate a potassium level of up to 5.5mmol/L
• The tendency to hyperkalaemia can be useful in patients who are also on potassium-losing diuretics (e.g. furosemide), as the two may balance each other out—overall hypokalaemia is more common in patients with heart failure
HOW TO . . . Start ACE inhibitors
• Screen for contraindications
• Check baseline renal function and electrolytes
• Warn the patient about possible cough and postural symptoms
An example of initiation/titration is as follows
Week 1
Start ramipril 1.25mg daily.
Week 2
Check renal function and BP (lying and standing), and check for postural symptoms. ↑ ramipril to 2.5mg.
Week 4
Check renal function and BP (lying and standing) and check for postural symptoms. ↑ ramipril to 5mg at night.
Continue titrating the dose upwards, as tolerated, but most older patients will develop postural symptoms at higher doses, ↑ 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 ↑ susceptibility to ACE inhibitor-induced renal failure and hypotension
• Correct the dehydration first—treat the cause, give fluid supplementation, and stop diuretics
• Temporary cessation of the ACE inhibitor may be needed if dehydration prolonged (>24h)—‘sick day rules’
Analgesia
Older patients are more likely to suffer chronic pain than younger ones, owing to the ↑ frequency of conditions such as osteoarthritis, osteoporosis, etc.
Pain management is more challenging, and a standard ‘pain ladder’ approach is 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 (ATN), exacerbated by intercurrent infection or dehydration
• Peptic ulceration and gastrointestinal bleeding—there is an ↑ risk with ↑ 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 ↑ 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 (e.g. ibuprofen 0.6g/day)
• Avoid using two NSAIDs together (this includes low-dose aspirin)
• Consider co-prescription of a gastric-protective agent (e.g. 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-dependent, 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
HOW TO . . . Manage pain in older patients
Diagnose the cause
Chronic abdominal pain may be due to constipation that will respond to bowel care, rather than analgesia.
Consider non-drug measures
• Weight loss and physical activity help with many pains (e.g. arthritis)
• Temperature treatments (e.g. hot/cold packs applied to painful joints)
• Alternative therapies (e.g. acupuncture, aromatherapy) can help
• Avoidance of (non-essential) activity that provokes pain, if possible
Consider targeted therapy
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
Regular paracetamol
• Well tolerated and with few side effects
• Before moving from this, ensure that the maximum dose is being taken regularly (i.e. 1g taken four times a day (qds)) for optimal analgesic effect. Many patients will find taking an occasional paracetamol ineffective—explain that regular dosing ↑ the analgesic effect
Opioid analgesia
• Second-line therapy in most older patients
• Options to deal with mild (e.g. codeine), moderate (e.g. tramadol), and severe pain (e.g. morphine)
• 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 the same receptors, so use as a continuum—if the regular maximum dose of codeine is not working, then step up to the next level of opioid strength
• Various formulations for the delivery of strong opiates. Liquids are useful if there are swallowing problems. Slow-release tablets and transdermal patches provide constant analgesic effect for continuous pain. Be mindful of slow onset of action/accumulation with patch formulation
• Parenteral opiates are used in terminal care (subcutaneous (s/c) injections of morphine and diamorphine for intermittent pain; 24h infusion pumps for constant pain)
• Monitor for side effects—active bowel care with initiation
Other drug options
• Very fit older patients can be given short courses of NSAIDs
• Neuromodulators have role in neuropathic pain
Psychological factors
• 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, PMR, 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 all steroid-treated older patients should be offered bone protection at the outset, unless the course is certain to be very short (e.g. <2 weeks). This should consist of daily calcium and vitamin D, along with a bisphosphonate (weekly preparations, e.g. alendronate 70mg, improve concordance)
• Steroids can precipitate impaired glucose tolerance or frank diabetes. Monitor sugar levels periodically (e.g. 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 ↑ fragility are common
• Muscle weakness occurs with prolonged use, predominantly 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’, pp. 480–481)
• There is an ↑ 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 the treatment of giant cell arteritis (GCA)) 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 an association between steroid use and peptic ulceration, particularly in hospitalized patients
• Adrenocortical suppression means that the stress response will be diminished in chronic steroid users. If such a patient becomes acutely unwell (e.g. septic), the exogenous steroid dose will need to be temporarily ↑ (e.g. double the usual oral dose, replace with intramuscular (im) hydrocortisone if unable to take by mouth). Counsel the patient with ‘sick day rules’. 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:
• Could a steroid-sparing agent (e.g. azathioprine) be used instead?
• Is the patient taking adequate bone protection?
• What is the BP and blood glucose?
Warfarin
Common indications range from absolute (PE, DVT, artificial heart valve replacement) to relative (stroke prophylaxis in AF). Increasingly direct oral anticoagulants (DOACs) are being used instead, but warfarin remains in common use.
Cautions
• Risk is ↑ if the patient is unable to take medications reliably, so it 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, e.g. 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 ↑ sensitivity to warfarin (e.g. 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 ↑ 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 the risk with further testing—FBC and iron studies might indicate occult blood loss. If warfarin is not essential, then a full gastrointestinal work-up may be appropriate before starting in fitter patients
• 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
Reassessment of risk/benefit balance
• Patients often take warfarin for many years
• During that time, there is usually a 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 ↑ and cannot be reduced, e.g. a patient falls frequently despite intervention or has a major bleed that could recur (e.g. diverticular)
• Any drug must be stopped, unless there is a net benefit to the individual patient. In conjunction with the patient (and carer), the indication for warfarin should be reviewed periodically, perhaps annually in frail older people and after any significant event, e.g. hip fracture
Usual target international normalized ratio
(See Table 6.2.)
Table 6.2 Target international normalized ratios (INRs)
| Indication | Target INR | Duration |
| AF | 2.5 | Lifelong |
| Venous thromboembolism (VTE) | 2.5 | Varies. Usually 6 months. Lifelong if recurrent or with ongoing precipitant (e.g. malignancy). Shorter duration if identifiable precipitant and high bleeding risk |
| Recurrent VTE 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 warfarin needs reversing with vitamin K and fresh frozen plasma
• For life-threatening bleeds (e.g. intracerebral haemorrhage), prothrombin complex concentrate can be used for rapid reversal
► If a patient bleeds at target INR, always consider the possibility of an underlying serious disease, e.g. bladder or gastrointestinal malignancy.
HOW TO . . . Initiate warfarin
Discuss the 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 (e.g. 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
• Prescribe warfarin to be taken at 6 p.m.
• Medical notes should state the 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 has 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 ↑ the dose of warfarin than to deal with bleeding from an overdose.
• The INR will then need checking daily, then on 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
Further reading
British National Formulary. Oral anticoagulants section. 
http://ww.bnf.org.
Direct oral anticoagulants
This class of drugs (DOACs) is also known as novel/new oral anticoagulants (NOACs) and is increasingly being used in place of warfarin as evidence of non-inferiority emerges.
Compared to warfarin, the main advantages are
• Reduced rates of bleeding (especially intracerebral)
• No food or alcohol interactions
The main disadvantages include
• Harder to reverse—although short duration of action means that the drug clears from the system quickly, and reversal agents are in development
• Dose needs adjustment for renal impairment
• Some agents require twice-daily dosing
• Short duration of action means that any missed doses render the patient unanticoagulated
• Less familiar medications, and prescribers should note numerous drug interactions with commonly used drugs (e.g. tramadol, clarithromycin)
• Limited long-term outcome data, particularly in the older patient
• Not licensed for metallic heart valve thromboprophylaxis
When to use?
• Patients who have been stable on warfarin should not be changed
• Patients in whom it is unacceptable/very difficult to monitor INR, or who have an unstable INR, would be good candidates for a DOAC
• When initiating anticoagulation, discuss options with patients and be guided by local policy
► If a patient is not a candidate for warfarin, it is unlikely they will be ‘safe’ on a DOAC, and careful risk/benefit analysis is always needed (e.g. a frequent faller will be no safer on a DOAC than on warfarin).
Proton pump inhibitors
PPIs (e.g. 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 but are not without problems. 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, and microscopic colitis
• Hyponatraemia and hypomagnesaemia can occur—consider checking in non-specific presentations
• 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 ↑ likelihood of recurrence
• Enteric bacterial infections (e.g. 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 ↑ 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 (e.g. H2 antagonists such as ranitidine)
• Transient dyspepsia or occasional heartburn are inadequate indications for long-term PPI treatment
• In 1° care, review the need for the drug periodically
• In 2° care, be careful not to extend an initial appropriate PPI prescription for prophylaxis against gastrointestinal bleeding
• When antibiotics are prescribed in hospital, suspend the PPI prescription to reduce the risk of CDAD
• In (confirmed or possible) CDAD, stop PPIs
HOW TO . . . Manage drug-induced skin rashes
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 or urticarial, or resemble erythema multiforme
• Certain drugs may produce predictable eruptions:
• 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, sulfonamides, 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 the 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, e.g. 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 (e.g. calamine), and weak topical steroids may help
• Oral antihistamines are often given, with variable success. Sedating antihistamines (e.g. hydroxyzine) may help sleep
Treat the complications
• More likely if extensive and prolonged
► Consider dermatology referral if not improving after 2 weeks off the suspected drug.
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 ingredients, and may contain impurities. Herbal medicines have adverse effects and drug interactions (see Table 6.3).
Table 6.3 Overview of herbal medicines
| Name | Use | Adverse effects | Drug interactions |
| Garlic | |||
| Ginkgo | Memory problems | ||
| Ginseng | Performance enhancer | ||
| Glucosamine/chondroitin | Osteoarthritis | Hypoglycaemic agents (reduced efficacy) | |
| St John’s Wort | |||
| Echinacea | Immune stimulant | Immunosuppressants | |
| Valerian | Sedation | CNS depressants | |
| Saw palmetto | Prostatic symptoms | Finasteride |
Breaking the rules
A great deal of prescribing in geriatric practice relies on individually tailored assessment and pragmatic decision-making, as inter-individual variation ↑ with age. In addition, trials often exclude older subjects, making the evidence base an extrapolation. 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 medications 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, e.g.:
• Steroids and bisphosphonates
• Furosemide and a potassium-sparing diuretic (or an ACE inhibitor)
• Non-steroidals and a gastric protection agent
While certain disease–drug interactions are very likely and should be avoided, others may be an acceptable risk. For example:
• Are to be used with caution with asthma, yet they have such a good impact on cardiovascular risk reduction that these cautions are not absolute. Often ‘asthma’ is, in fact, COPD with little β-receptor reactivity, so cautious β-blockade initiated in hospital while monitoring the lung function may be appropriate
• In patients with peripheral vascular disease, they 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 the 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
1 O’Mahony D, O’Sullivan D, Byrne S, et al. STOPP/START criteria for potentially inappropriate prescribing in older people: version 2. Age Ageing 2015; 44: 213–18.