Introduction to the "BRAINS & AIMS" series of pharmacological/prescribing principles of commonly prescribed (top 100) drugs: Education and discussion

Over the last 20 years, there has been a major drive to develop clinical pharmacology and prescribing teaching and assessment, most notably resulting in the creation of the prescribing safety assessment (PSA).1 The PSA has itself been a source of research around training and preparation for prescribing2 and the challenges it poses to candidates with dyslexia and other disabilities.3 In 2003, the British Journal of Clinical Pharmacology published a Core Curriculum, proposed by the British Pharmacological Society Clinical Section Committee,4 highlighting prescribing principles. While reviewing this with colleagues, the idea for developing a mnemonic to create a logical sequence and an aide-memoir of key prescribing principles emerged, leading to “BRAINS & AIMS” in 2005. * “BRAINS” encapsulates the higher-level principles to think about relating to the proposed drug, the patient and their condition (use your BRAINS: Benefits, Risks, Adverse Effects, Interactions, Necessary prophylaxis, Susceptibilities) before prescribing and “AIMS”, the action principles around prescribing/giving the drug (AIMS: Administering, Informing, Monitoring and Stopping). Further mnemonics emanated from this central “spine” to create an extended logical framework of principles, previously described in detail5 and introduced briefly in this Editorial and summarized in Table 1 with the overall structure in Figure 1. Mnemonics have a long history, with a system discovered back in 447 BC by the Greek poet Simonides, collectively known as the Ancient Art of Memory, which was revived in 1323 by Saint Thomas Aquinas, to recall Catholic doctrine and versions of biblical history.6 The Ancient Memory Arts have modern applications in pilot training, gambling and telepathy demonstrations, and rehabilitation of brain-damaged patients with episodic memory disorders.7 Mnemonics are also popular with and widely used by medical students and doctors. While acknowledging their limitations and not suiting all learning styles, mnemonics are supported by several studies demonstrating better retention.8-11 Returning to the BRAINS & AIMS mnemonic, here I provide a brief overview of its generally applicable concepts. We consider the whats, the whys, the hows and the wherefores. Regarding “what” is it used for, we base this on the British National Formulary (BNF) licenced indications and guideline recommendations, for example those of the Department of Health's body, the National Institute of Health and Care Excellence (NICE). “Why” considers the drug's effects and “how” the underlying mechanisms of action. “Wherefore” considers some of the supporting evidence (does it help as well as work?). Clearly, one should only prescribe a drug if the patient is likely to benefit from it. However, as Bertrand Russell cautioned, “The extent to which beliefs are based on evidence is very much less than believers suppose.”12 A straightforward approach may be taken, simply using licenced indications in the BNF. However, the decision is often complex, requiring assimilation of evidence from trials and recommendations from local NHS trusts, national/international societies and government body guidelines. The further challenge is to tailor this information to the individual patient and consider the other prescribing principles of BRAINS & AIMS. The patient may well have been excluded from the trial, due to their age, comorbidities or other potentially interacting medication, from where the evidence base is derived. Risks relate to opportunities, for example the use of a cheap and effective drug, besides the risks of harms: “Primum non nocere” (First do no harm), Hippocrates (Ἱπποκράτης, ca. 460 BC to ca. 370 BC) wrote about prescribing, writing, “I will prescribe regimens for the good of my patients according to my ability and my judgment and never do harm to anyone”. Risks of harms relate to adverse reactions, interactions and susceptible patients, medication errors (prescribing or drug administration), close contacts of the patient (radioactive or chemotherapeutic agents) and the wider population through the spread of antibiotic resistance from antibiotic overuse. Also, drug costs impact local and national drugs budgets, limiting the money available for other patients or treatments. Hence, the need for rational, balanced prescribing that carefully weighs up the benefit:risk ratio. These are defined as “An appreciably harmful or unpleasant reaction resulting from an intervention related to the use of a medicinal product; adverse effects usually predict hazard from future administration and warrant prevention, or specific treatment, or alteration of the dosage regimen, or withdrawal of the product”.13 I have arranged key related principles as: Prevent, Classify, Diagnose, Treat and Report (PC DeTeR).* For more detailed descriptions of these, see Webb and Archer.5 Understanding the mechanisms of drug-drug interactions helps one work out what the effect of the interaction is and to remember them. The main mechanisms are pharmacokinetic (PK; “What the body does to drugs”, absorption, distribution, metabolism and excretion, ADME) and pharmacodynamic (PD; “What drugs do to the body”). A given drug-drug interaction may be due to a combination of ADME-PK and PD mechanisms. Interactions are either synergistic or antagonistic, and some are used to beneficial effect, while others cause serious adverse effects. For a few drugs, it is recommended to coprescribe another drug to reduce the incidence of side effects, which vary depending on the patient's susceptibilities. Common examples include gastrointestinal prophylaxis with proton pump inhibitors, laxatives (and antiemetics) with opioids and bone prophylaxis (eg, bisphosphonates, alendronate) for corticosteroids. A risk is establishing a therapeutic cascade or contributing to polypharmacy, ie, adding more drugs to reduce the side effects of another, with their incumbent adverse effects. Some patients have a deficiency (“gap”) in the way they handle a drug (pharmacokinetics) and/or have an increased sensitivity to the pharmacodynamic effects of a drug. I have summarized general characteristics according to the mnemonic “A SAD GAP”* (Allergy, Sex, Age, Disease (comorbidities), Genetic, Altered physiology, Pregnancy (and breast feeding).* For examples of these, see Webb and Archer.5 A similar mnemonic for susceptibilities was recently published in the British Journal of Clinical Pharmacology: “I GASPED”: Immunological, Genetic, demographic (Age and Sex), Physiological and Exogenous factors (eg, drug-drug interactions) and Diseases and disorders such as renal failure.14 The key elements of prescription-writing and administering are encapsulated in “I-DRAFFT”*: ID drug/ID patient, Dose, Route, Allergy check, Formulation, Frequency, Timing. Several of these dosing criteria are informed by the pharmacokinetic processes or vice versa, such as bioavailability (Dose, Route), rate of absorption/Tmax (Formulation), volume of distribution (loading Dose) and clearance/half-life (maintenance Dose and dosing Frequency and Timing). As a guide, consider the key points of BRAINS & AIMS to discuss (and document) with the patient (identifying ideas, concerns and expectations, choices, check understanding and agreement) and with relatives/carers, nurses, pharmacists and doctors. Monitoring is needed for the beneficial and adverse effects of drugs. This may be simple subjective assessments such as pain relief or objective assessments for adverse effects such as hypertension, elevated blood glucose and osteoporosis (Dexa scanning) with corticosteroids, renal function with angiotensin converting enzyme (ACE) inhibitors, and creatine kinase (CK) and liver functions (LFTs) with statins. The frequency and importance of clinical measurements and investigations for making prescribing decisions have recently been presented in the British Journal of Clinical Pharmacology.15 Considerations here are to identify the appropriate duration of treatment (eg, antibiotic stewardship), reasons for stopping (monitoring results) or importance of not stopping as well as any precautions for stopping/slow withdrawal, for example with corticosteroids, opiates, benzodiazepines, beta-blockers, selective serotonin re-uptake inhibitors and analgesia-associated headache (which may represent a failure to stop appropriately). Applying STOPP/START (screening tool of older people's prescriptions/screening tool to alert to right treatment) criteria for potentially inappropriate prescribing in older people may improve clinical outcomes in multimorbid older people. Several new STOPP categories were created in version 2, namely, antiplatelet/anticoagulant drugs, drugs affecting or affected by renal function and drugs that increase anticholinergic burden.16 Thus, the BRAINS & AIMS principles provide a structured approach to “what you need to know about” drugs. The related question is “which drugs do you need to know about”. This was addressed by the development of the evidence-based lists of the most prescribed “top 100” drugs/classes, originally published in the British Journal of Clinical Pharmacology in 201117 and updated in 2018.18 The next thought was to try to put the two together: to apply BRAINS & AIMS principles to the top 100 drugs/classes and create a series of articles. The British Journal of Clinical Pharmacology has very recently published a Dutch list of 134 essential drugs.19 The aim of these papers is not to provide a definitive/authoritative prescribing resource; for that, refer to national or local resources, guidelines and drug monographs. Instead, it is to support education and spark discussion and debate. It is not possible to be fully comprehensive and include everything, and we will likely have missed something that you think is important or interesting, or incompletely explored or mischaracterised something. If you think we have, we invite you to write a letter to the Editor. Similarly, we are aware that we have written certain aspects from a British perspective, which may be less relevant or differ substantially from global use. If you find interesting differences compared with your own experience, please contact the journal to inform us. The manuscripts in the series are intended for a broad readership, including students and teachers of medicine, pharmacy and pharmacology, and the general readership of the British Journal of Clinical Pharmacology to encourage discussion and to establish an updatable source of reference. More advanced-level material is indicated in italics and highlighted in italics in the papers. We start the “BRAINS & AIMS" series of commonly prescribed (Top 100) drugs with metformin (this Editorial accompanies the first paper in the series—metformin20) at the centenary of its discovery (in 1922).21 While metformin was first used in 1957 in France, some of its key mechanisms of action were not elucidated until this century.22 There are no conflicts of interest to declare. Data sharing is not applicable to this article as no new data were created or analyzed in this study.