Journal scan for the Clinical Pharmacist: A review of 10 recent papers of immediate clinical significance, harvested from the January 2024 edition of the MEDICINE, Elsevier
From the desk of the Editor-in-Chief
CLINICAL PHARMACOLOGY| VOLUME 52, ISSUE 1, P1-64, JANUARY 2024
(1). Simon RJ Maxwell. Pharmacodynamics and pharmacokinetics for the prescriber. Elsevier. 2024;52(1):1-10.
Abstract
Pharmacodynamics is the study of how drugs have effects on the body. This is typically by interacting with receptors located in cell membranes or in the intracellular fluid, although there are many other types of drug target. The relationship between the drug dose and its effect is described mathematically by the doseresponse curve. Drugs acting at the same receptor (or tissue) differ in the size of the response they can achieve (efficacy) and the amount of drug required to achieve it (potency). Drug receptors can be classified on the basis of their selective response to different drugs. Constant exposure of tissues to drugs sometimes leads to a reduced response (desensitization). Pharmacokinetics is the study of the ways drugs are handled in the body. It is usually divided into four phases: absorption of a drug from the site of administration, distribution throughout the body, metabolism and excretion from the body. Differences in these four processes, arising from patient-specific factors (e.g. age, disease, interacting drugs, genetic background), explain much of the interindividual variation in drug response. This article describes the basic principles of pharmacodynamics and pharmacokinetics, and how they support rational prescribing decisions.
(2) Munir Pirmohamed. Pharmacogenetics for the prescriber. Elsevier. 2024;52(1):11-14.
Abstract
Pharmacogenetics is the study of how genetic factors affect the response to drugs (efficacy, adverse effects). Variation in genes can affect either a drug’s pharmacokinetics (how the drug is handled in the body) or its pharmacodynamics (how it interacts with proteins in the body to produce its effects). Such variation needs to be evaluated in combination with clinical and environmental factors to personalize either drug choice or drug dose in individual patients. There are some well-characterized examples of pharmacogenetic variation in clinical practice. As our knowledge of the human genome increases, the challenge will be to translate these findings on genetic variation into clinical practice by integrating the use of genetic tests into clinical pathways in primary and secondary care.
(3). Gurpreet S Jutley et al. Adverse drug reactions and interactions. Elsevier. 2024;52(1):15-22.
Abstract
Adverse drug reactions (ADRs) remain a challenge in modern healthcare, particularly given the increasing complexity of therapeutics, an ageing population and rising multimorbidity. These factors also influence the number of drugs taken on average by patients. Prescribers should be aware of the potential for the drugdrug interactions (DDIs) that commonly arise in clinical practice. This article summarizes some of the key facts about ADRs and DDIs and explores aspects relating to their prevention, diagnosis and management in clinical practice.
(4) Andrew W. Hitchings. Monitoring drug therapy. Elsevier. 2024;52(1):23-30.
Abstract
The effects of drugs vary significantly between individuals, and monitoring is essential to ensure the desired effect is achieved. Wherever possible, therapeutic effects should be monitored directly, using a measure that captures how the patient feels, functions or survives (a ‘clinical endpoint’). In practice, it is often not feasible to use a clinical endpoint to guide therapy, particularly for preventive treatments. The next best option is to use a surrogate endpoint: a measure that predicts whether the clinical endpoint will be achieved. For a few drugs, neither a clinical nor a surrogate endpoint is available. In these instances, if the drug has a narrow therapeutic index and there is a predictable relationship between its concentration and its effects, it may be appropriate to measure its concentration in the blood. This article discusses approaches to monitoring the efficacy of drug therapy using clinical and surrogate endpoints and plasma concentration monitoring. Specific guidance is provided for plasma concentration monitoring of digoxin, gentamicin, vancomycin, phenytoin, lamotrigine, lithium and theophylline.
(5). Iain M MacIntyre. Prescribing medicines for patients with renal impairment. Elsevier. 2024;52(1):31-35
Abstract
Renal impairment is common worldwide and poses a significant challenge to safe drug prescribing. As renal function falls, drug clearance decreases and exposure to free drug often increases, leading to increased risks of toxicity and adverse drug reactions. There is also a risk of therapeutic failure as some drugs become less effective when renal function declines or dose reductions are excessive. Polypharmacy is common in this patient group, increasing the risk of drug interactions. It is therefore important that prescribers have a good understanding of the altered pharmacokinetics seen in renal disease and understand the need for dose alterations of some drugs, as well as enhanced monitoring for early signs of drug toxicity.
(6) Rupert A. Payne. Polypharmacy and deprescribing. Elsevier. 2024;52(1):36-39.
Abstract
Polypharmacy is a common issue in clinical practice, with 20% of adults given ≥5 regular medications. It particularly impacts elderly individuals and those with multiple morbidities, and is worsened by single-disease, guideline-driven prescribing and service pressures. Although sometimes appropriate, it can also be problematic, associated with a range of adverse outcomes including hazardous prescribing, excess treatment burden, poor quality of life, higher health service use, and increased morbidity and mortality. Polypharmacy management is complex because of the presence of multiple problems, competing priorities and clinical uncertainty. The mainstay of management is currently medication review, which should be holistic and patient-centred, and employ shared decision-making. Key elements include addressing unnecessary prescribing, ineffective prescribing, drug safety and cost-effectiveness. Deprescribing is a core means of reducing polypharmacy, although there are several important barriers to its delivery, including a weak evidence base. In the longer term, preventing inappropriate polypharmacy requires a significant shift in prescribing culture, deployment of decision-support tools, and is likely to take considerable time to achieve.
(7). Simon R.J. Maxwell. Writing prescriptions: how to avoid common errors. Elsevier. 2024;52(1):40-44.
Abstract
Prescribing medicines is the primary tool used by most healthcare systems to cure illness, relieve symptoms and prevent future disease. Prescribing is probably the most complex intellectual task that doctors undertake, requiring the formulation of an appropriate treatment regimen from the many thousands available, taking into account the infinite variation in the patients they encounter. Not surprisingly, suboptimal prescribing is common and represents an obvious target for quality improvement in healthcare. Common prescribing errors include omission of medicines that are indicated, selecting inappropriate drugs, choosing an incorrect dosage or frequency of administration, and failures in the prescription-writing process. Factors involved in poor prescribing include the performance of prescribers themselves, the complexity of the tasks required of them and the systems in which they work. Prescribing can be improved by better education and training of prescribers, focusing on a rational approach. Other improvements should include better supervision and team-working, input from clinical pharmacists, electronic prescribing systems supported by decision support software, standardization of prescribing documentation and governance arrangements that recognize the importance of prescribing as part of good healthcare.
(8). Y.K. Loke et al. How to appraise clinical trials. 2024;52(1):45-50
Abstract
Treatment decisions should be based on high-quality data, ideally obtained from randomized controlled trials. However, randomized trials are not immune from bias and other important limitations. Critical appraisal of such studies must consider both the methodological rigour of the study and the applicability of the results to routine clinical practice. Readers should work systematically through trial reports to establish the aims of the study and consider whether the methods used are able to provide an unbiased answer. Particular attention should be directed towards randomized patient allocation, ensuring that the treatment and control groups are equally balanced at the start. There should be adequate follow-up and sufficient blinding of the investigator and participants so that important outcomes are reliably recorded without any interference from preconceived notions. The trial’s Results section should be reviewed to confirm that the researchers have transparently reported all data (positive or negative) relevant to the study question. Critical appraisers should also consider how closely the conduct of the trial (e.g. selection of patients, follow-up arrangements) reflects real-world medicine, and the applicability of the trial results to everyday clinical practice.
(9). Mostafa Meshaal Ahmad. Clinical pharmacology of biological medicines. Elsevier. 2024;52(1):51-55
Abstract
Biological treatments have evolved from an initial focus on vaccines to include various other therapeutic approaches. This article focuses on monoclonal antibodies, which are large, complex molecules, produced using living organisms, that target specific antigens. They differ from the traditional chemical drugs in having distinct pharmacokinetic and pharmacodynamic characteristics. This article discusses the different clinical applications and challenges of their use, providing an overview of the recent advances in this field.
(10). Chris Humphries. The emergency treatment of poisoning. Elsevier. 2024;52(1):56-61
Abstract
Poisoning is a common presentation in emergency care and can occur in many situations. It is important to understand the priorities in the care of poisoned patients, the key principles in toxicology and the value of clinical signs and symptoms. Clinicians face challenges when dealing with uncertainty in undifferentiated patients, which can be minimized through appropriate self-directed learning. There is also value in departmental planning to avoid significant logistical issues. The future direction of emergency treatment of poisoning is likely to see improvements in primary prevention, reductions in protocol variation and new targets for treatment.