Prescribing should be based on a rational approach to a series of chal- lenges (see Box 2.1).
Making a diagnosis
Ideally, this should be a confirmed diagnosis but in reality many prescrip- tions are based on the most likely of several possible diagnoses.
Establishing the therapeutic goal
This is clear when relieving symptoms (e.g. pain, nausea, constipation), but other goals are less obvious to patients, such as in the case of preventive treatments (e.g. ACE inhibitors to prevent hospitalisation and extend life in patients with chronic heart failure). Prescribers should agree on goals and measures of success with patients (concordance).
Choosing the therapeutic approach
Drug therapy is often only one of several available approaches. Prescrib- ers should consider if it is better than no treatment or than an alternative treatment (e.g. physiotherapy, psychotherapy, surgery). Factors that should be considered when assessing the balance of benefit and harm are sum- marised in Box 2.11.
Choosing a drug
For most indications, more than one drug or class of drugs is available. Prescrib- ers need to consider the optimal choice for the individual patient, considering:
Absorption: Patients may find some oral formulations intolerable or may be vomiting and require parenteral administration.
Distribution: Distribution to a particular tissue sometimes dictates choice (e.g. lincomycin and clindamycin concentrate in bones).
Metabolism: Drugs that are extensively metabolised should be avoided in patients with severe liver disease.
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Excretion: Drugs that depend on renal excretion should be avoided in patients with impaired renal function.
Efficacy: Drugs with the greatest efficacy are preferred unless alterna- tives are more convenient, safer or less expensive.
Avoiding adverse effects: Prescribers should avoid drugs that are likely to cause adverse effects or worsen coexisting conditions (e.g. β- blockers for angina in patients with asthma).
Features of the disease: Antibiotic therapy should be based on the known or suspected sensitivity of the organism.
Severity of disease: The choice of drug (e.g. analgesic) should be appropriate to disease severity.
Coexisting disease: This may either be improved by a planned treatment or may rule that treatment out.
Avoiding adverse drug interactions: Prescribers should avoid giving combinations of drugs that might interact (Box 2.8).
Patient adherence: Prescribers should choose drugs with a simple dosing schedule or easy administration.
Cost: Prescribers should choose the cheaper drug (e.g. a generic or biosimilar) if two drugs are of equal efficacy and safety.
Genetic factors: Rarely, genotype may influence the choice of drug (pharmacogenomics).
Choosing a dosage regimen
Prescribers have to choose a dose, route and frequency of administration to achieve an effective steady- state drug concentration in the target tissue without toxicity. Manufacturers’ dosage recommendations are based on average patients, but the optimal regimen for an individual patient is never certain. Rational prescribing involves some general principles:
Dose titration: It is usual to start with a low dose and titrate slowly upwards as necessary. This is particularly important if the patient is prone to adverse pharmacodynamic effects or altered pharmacokinetic handling (e.g. renal or hepatic impairment), and when using drugs with a low thera- peutic index. In contrast, when early effect is important but the drug has a long half- life (e.g. digoxin, warfarin, amiodarone), an initial loading dose is given before the appropriate maintenance dose (Fig. 2.4).
If adverse effects occur, the dose should be reduced, or an alterna- tive drug prescribed. A lower dose may suffice if combined with another
2.11 Factors to consider when balancing benefits and harms of drug therapy
• Seriousness of the disease or symptom • Efficacy of the drug
• Seriousness of potential adverse effects • Likelihood of adverse effects
• Efficacy of alternative drugs or nondrug therapies • Safety of alternative drugs or nondrug therapies
synergistic drug (e.g. azathioprine reduces glucocorticoid requirements in inflammatory disease). The shape of the dose–response curve means that higher doses may not increase therapeutic effect but may increase toxicity.
Route: Factors influencing route of administration are shown in Box 2.12.
Frequency: Less frequent doses are more convenient but result in greater fluctuation between peaks and troughs in drug concentration (Fig 2.4).
Peaks can cause adverse effects (e.g. dizziness with antihypertensives), and troughs may be associated with loss of effect (e.g. antiparkinsonian drugs).
Modified- release formulations or split dosing are possible solutions.
Timing: For many drugs the time of administration is unimportant; how- ever, for others the timing of effect makes a difference (e.g. morning diuret- ics to avoid nocturnal diuresis).
Formulation: For some drugs there is a choice of formulation, which may influence palatability, absorption and bioavailability. Where these effects are important, drugs should occasionally be prescribed by brand name rather than ‘generic’ international name.
Duration: This ranges from a single dose (e.g. thrombolysis for myocar- dial infarction) to a course of treatment (e.g. antibiotics) to long- term treat- ment (e.g. insulin, antihypertensives, levothyroxine).
Involving the patient
Patients should, whenever possible, be involved in choices about drug therapy. It is important for them to be provided with sufficient information to understand the choice, know what to expect from the treatment and be aware of any monitoring required.
2.12 Factors influencing the route of drug administration
Reason Example
Only one route possible Gliclazide (oral)
Patient adherence Phenothiazines (two weekly IM depot injec- tions, not daily tablets, in schizophrenia) Poor absorption Furosemide (IV, not oral, in severe heart
failure)
Rapid action Haloperidol (IM, not oral, in acute behav- ioural disturbance)
Vomiting Phenothiazines (PR or buccal, not oral, in
nausea)
Avoidance of first- pass metabolism Glyceryl trinitrate (SL, in angina) Topical, avoiding systemic exposure Inhaled steroids in asthma
Ease of access Diazepam (PR, if IV access is difficult in status epilepticus)
Comfort Morphine (SC, not IV, in terminal care)
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Evidence shows that up to half of drug doses for chronic preventative therapy are not taken. This is termed ‘nonadherence’ and may or may not be intentional. Nonadherence reduces the likelihood of benefits to the patient and is costly in terms of wasted medicines and unnecessary health care episodes. An important reason may be lack of concordance with the prescriber about the goals of treatment. A more open and shared decision- making process might resolve any misunderstandings at the out- set and foster improved adherence, as well as improved satisfaction with health care services and confidence in prescribers. Fully engaging patients in shared decision making is sometimes constrained by various factors, such as limited consultation time and challenges in communicating com- plex numerical data.
Stopping drug therapy
It is important to review long- term treatment regularly to assess whether continuation is required. Elderly patients are keen to reduce their medica- tion burden and are often prepared to compromise on long- term preventa- tive therapy to achieve this.