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The Prescription Cascade: Why Less Is Often More in Medicine
Recent guidance from the Royal Australasian College of Physicians (RACP) has brought renewed attention to a critical issue in modern medicine: the growing concern around overprescription and what experts call the “prescribing cascade.” This development aligns perfectly with what we…
Correct Dosing Newsletter July 2023
Thank you for your interest and finding your way to this, our first, newsletter. If you’re seeing this on our website, please make sure you add your email to our mailing list (at the bottom of the page) so you…
Aspirin And Evidence-based Prescribing: Professor Simon Dimmitt On This Medical Life Podcast
Website contributor, Professor Simon Dimmitt, has returned as a guest on the podcast, This Medical Life, this time contributing to episode 32, Aspirin: From Poultices To Pills. He was asked back because Aspirin is one of the drugs that features prominently…
Symptoms and disease control may be sufficient (and outcomes including survival superior) on lower drug doses than marketed, because of greater safety
The clinical dose response for desired outcomes is often not well established at drug launch. With time, lower doses of many drugs have been found sufficient, with important benefits of greater safety, tolerability and complaince, e.g. pain medicines, antihypertensives, antithrombotics,…
Drug combinations? Polypill
Drug combinations - ? Polypill
The young physician starts life with 20 drugs for each disease, and the old physician ends life with one drug for 20 diseases -William Osler
Drugs must often be prescribed together for the same, related or different indications. Such will always risk interactions, in particular re competition for uptake/actions in the target organ/tissues and for elimination from the body.
Dose Response
Along with the desired clinical benefit, prescribed drugs necessarily cause a variety of unintended effects, some of which may impair quality of life, cause harms, or prove fatal. The risk of all of these effects naturally increases with dose. Higher doses are inevitably less safe and should be specifically warranted, e.g. with (all) steroids.
Reduction of significant symptoms, like shortness of breath, angina or pain are obviously important goals. However, symptoms relief is rarely complete before significant toxicities emerge.
In prevention, much is made of the ‘control’ of surrogate measures like cholesterol and glucose concentrations or blood pressure levels. However, increasing data from large clinical trials clarifies which drugs and doses are necessary with respect to the major clinical outcomes, in particular mortality.
Bibliography
Bibliography
Our affiliations include:
University of Western Australia
University of Newcastle
Flinders University
Birmingham University
Oxford University
Psychotropic Dosing
Effective dose 50% (ED50) = the mean population dose necessary to achieve half the maximum (Emax) possible drug effect. ED50 was estimated from comparative dosing based on reductions in anxiety & related measures and published PET-serotonin transporter EC50 data.
Psychotropics are antagonists and so the mid-part of the dose-response curve plateaus, in contrast to adverse events which continue to increase.
Opioid Dosing
Effective dose 50% (ED50) = the mean population dose necessary to achieve half the maximum (Emax) possible opioid effect, was estimated from published dose response data and based on estimates of analgesic efficacy.
Being u-receptor agonists, the mid-part of the dose-response curve is exponential, doses should be increased with care.
COX-I Dosing
Effective dose 50% (ED50) = the mean population dose necessary to achieve half the maximum (Emax) possible drug effect. ED50 was estimated from published analgesic dose response data (aspirin & paracetamol based on human dose-response data, others on comparative animal work).
Being prostaglandin synthetase antagonists, the mid-part of their dose-benefit curve plateaus, and in contrast a wide range of adverse events continue to increase.