Drugs
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)
HOW TO … Improve concordance
Simplify prescription regimens
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®)
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 (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
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 (eg digoxin, phenytoin, lithium)
Some medications will produce changes detectable at physical examination (eg bradycardia with β-blockade, black stool with iron therapy).
Table 6.1 Example of a patient drug summary sheet | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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
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 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 improvementRelated posts:
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