The Importance of Pharmacological Understanding

Knowledge of the pharmacology of any medicine is important when this is related to its formulation, strength, dosage, frequency of dosage and appropriate administration. This has been a significant element of my professional activities and gives me the experience necessary to act as an expert witness in relevant situations. 

Considering Existing Medication Records

This article is designed to explain why it is essential for those responsible for the administration of additional medicines to both animal and human patients consider existing records for medicines currently being prescribed: thereby ensuring that there are no damaging interactions and also ensuring appropriate frequency of dosage and administration and no medicinal duplications are initiated.

It is essential that prescribers have knowledge and an understanding of any records of adverse symptoms or reactions due to prescribed medicines within the patient’s record history, the relevant pharmacology involved, and the principles of toxicology - areas routinely addressed by toxicology / pharmacology expert witnesses or by endocrinology expert witnesses in cases involving diabetes and hormone-related therapies. This will ensure the minimisation of prescribing errors and consequential legal cases.  

The Scale and Severity of Medication Harm

It was recorded by the World Health Organisation in September 2023 that medication-related harm affects 1 in 30 patients in health care. More than a quarter of this harm is regarded as severe or life-threatening. 

This report also states that initial data for the Government’s NHS Resolution project related to medication errors indicates that anticoagulants, opioids, and anticonvulsants are the most common medications involved. The NHS Resolution project also states that high risk situations are more often associated with significant harm due to unsafe medication practices.  This report also outlines three major factors contributing to high risk situations: 

1. Medications, particularly high risk (high alert) medications 
2. Provider/patient factors and 
3. Systems factors (work or environment). 

Transitions of Care: A High-Risk Period

The total, annual number of undetected drug errors was estimated to affect around 1.8 million prescription items at transitions of care in hospitals in England. Of these, over half (52%) happened when patients were admitted to hospital and 44% when they were discharged. 3% occurred during transfers from one hospital to another and 1% occurred during transfers within the same hospital. These errors were estimated to affect around 380,000 episodes of patient care resulting in avoidable harm to 31,500 patients and 36,500 additional bed days at a cost of around £17.8 per day to the NHS and more than 40 deaths. The BMJ, Quality & Safety, March 2024.   

It was also reported that during 2023 34,000 medication errors were made with 21 incidents leading to patient death and a further 27 leading to serious harm. 5,500 patients were damaged in some way by a mistake with their prescription e.g. being given the wrong medication, wrong dosage or not being supplied with the medication at all. Digital Health, April 2024 

Contributing Factors and System Failures

High risk medicines are those which risk significant patient harm or death when used in error and when errors occur in prescribing high risk medications for older patients with multiple medical problems there is a significant risk of serious harm.  Healthcare Safety Investigation Branch

Medication errors occur when weak medication systems and/or human factors such as fatigue, poor environmental conditions or staff shortages affect prescribing, transcribing, dispensing, administration and monitoring practices which can result in severe harm, disability and even death for the patient concerned. Multiple interventions to address the frequency and impact of medication errors have already been developed, yet their implementation is varied. World Health Organisation 2023. 

The following examples illustrate some of the consequences of lack of due diligence if prescribers do not ensure that they have considered all relevant, available information before administering new medication or changing the dosage or frequency of dosage of existing medicines being taken by the patient. These examples are related to human patients. 

Case Example 1 

This case concerns a patient who suffered from several underlying, complex medical conditions which, according to her medical records, necessitated many hospital admissions between 2012 and 2020. 

The patient tripped and fell face forward in a supermarket car park whilst walking back to her car. She fractured her skull and suffered deviation of the septum.  These injuries were diagnosed in hospital on the same day, after she had been taken there by ambulance. 

She remained an inpatient for two weeks after which she was discharged. She experienced ongoing back pain whilst standing, sitting and walking and been prescribed several different analgesic medicines to control this pain since the above incident.  Some of these medicines contained opioids, including buprenorphine (BuTrans), tapentadol (Pyrexia), oxycodone and Targin whose formulation contains naloxone, a medication used to reverse the effects of opioids. Her medical records also state that Oramorph solution which contains 10mg morphine sulphate/5ml was also prescribed but gave her no significant pain relief.   

Relevant pharmacy records indicate that Oramorph 10mg/5ml was dispensed for her on three separate times over a six month period. These records also include two prescriptions dispensed ten days apart for 4 buprenorphine patches (BuTrans) 10 mcg/h and 4 buprenorphine 5 mcg/h patches.  One patch is normally applied weekly but this dosage information was not recorded for the patient. 

The patient later attended the hospital clinic for a routine check up. It was recorded that the prescribed Targin had been stopped the day before.  She was still applying buprenorphine 5 mcg/h transdermal patches at that time.  The locum who undertook the review as the consultant was on holiday recorded that she stated that she had experienced some hallucinations but considered these to be a result of her acute hospitalisation. Hallucinations are cited as being a common opioid side effect and he proposed that she reduce her intake and application of opioid medicines as she was over sedated. Her pain level should still be under control. 

The locum undertaking her review also indicated that he considered that her future prescriptions for buprenorphine should be 10 mcg/h transdermal patches. There is no statement within the medical records to confirm that the application of 5 mcg/h buprenorphine patches was discontinued after 10 mcg/h buprenorphine patches were dispensed for her. A further entry in her pharmacy records cites that another prescription for buprenorphine 5 mcg/h patches was dispensed for her only a week later and there is no record of confirmation being requested from the prescriber by the pharmacist as to whether this prescription had been issued in error. This lack of communication by the pharmacist to clarify what was happening was a professional breach of duty and contributed significantly to unfortunate events subsequently experienced by the patient due to opiod overdosage. 

Case Example 2 

This case concerns a male, diabetic patient who was was prescribed the SGLT2 inhibitor dapagliflozin 10mg at a dose of one tablet daily by his GP after a routine diabetes check up with the practice nurse.  SGLT2 inhibitors are diabetic medicines which delay and inhibit the absorption of glucose from a patient’s small intestine.  

The patient went to his local pharmacy to collect his dapagliflozin prescription and arranged to have a medication review a couple of days later as this was a new medicine for him. He had a second medication review a week after that but no mention relating to the potential side effect of a SGLT2 inhibitor being Fournier’s gangrene was made by the pharmacist during either of these medication reviews. 

Around that time he developed an infection and was diagnosed by a nurse practitioner as suffering from a perianal abscess for which he was initially prescribed flucloxacillin 500mg capsules at a dose of one capsule four times daily to treat the infection. A second prescription for penicillin 250mg tablets at a dose of one tablet daily was also issued for him as an alternative to be taken should the flucloxacillin not be effective. Both these substances are penicillins with the same same antibiotic spectra and therefore the taking of penicillin should the flucloxacillin not be effective was not therapeutically sensible. The organism should, ideally, have been identified before appropriate, alternative, antibiotics were prescribed to replace the flucloxacillin if required. 

He attended a local Urgent Care Centre two days later where an out of hours GP prescribed metronidazole 500mg, a nitroimidazole class antibiotic, together with naproxen to control his pain.  

Within a short time he was admitted to the Emergency Department of his local hospital where a diagnosis of Fournier’s gangrene was confirmed. He was prescribed antibiotics gentamycin, clindamycin and meropenem to be administered intravenously three times daily for 11 days. He required surgery to remove a perianal abscess and debridement of surrounding necrotic tissue.  

Fournier’s gangrene is a rare type of necrotising fasciitis or gangrene which affects the external genitalia or perineum. It commonly occurs in older men, but sometimes occurs in women and children. It is most likely to be diagnosed in patients with diabetes, alcoholics, or those who are immunocompromised. Necrotising fasciitis can occur anywhere in the body but when it develops in the male genitalia, it is called Fournier’s Gangrene (named after Jean Alfred Fournier who identified the condition in 1883). 

Even though Fournier’s Gangrene is a rare bacterial infection medical practitioners should be able to recognise the symptoms and make an accurate diagnosis promptly.  Professional bodies and the MHRA (Medicines and Healthcare Products Regulatory Agency) circulated relevant documentation for the diagnosis and treatment of Fournier’s gangrene to their registrants in 2019 when research study results indicated that it could be a rare side effect of SGLT2 inhibitors. 

SGLT2 inhibitors, also called gliflozins, are a class of prescription medicines that are licensed for use with diet and exercise to lower blood sugar in adults with type 2 diabetes.  Medicines in the SGLT2 inhibitor class include canagliflozin, dapagliflozin, empagliflozin or ertugliflozin. 

There was negligence by the pharmacist on duty at the community pharmacy by not advising Mr Vallance thoroughly about the side effects possible when taking a SGLT2 inhibitor.  He was told about possible kidney problems but no mention was made of Fournier’s gangrene which meant he was unaware of the existence of this rare side effect and therefore unable to ask about the possibility of this being the cause of his perianal infection when the first boil appeared between his buttocks. There was also negligence by the staff of his GP Practice as they took too long to consider that the cause of Mr Vallance’s infection might be Fournier’s gangrene. 

Conclusion 

The above case examples illustrate just some of the problems that patients experience when those responsible for recommending and prescribing changes in their current medication do not ensure they have considered existing records for medicines currently being prescribed for them thereby increasing the risk of possible, damaging medication interactions, inappropriate frequency of dosage and administration and medicinal duplications being initiated.

About the Author

Dr Sarah Cockbill qualified as a pharmacist in 1970 and practised as a registered pharmacist until 2019, when she left the Register of the General Pharmaceutical Council to focus on consultancy.

She has extensive experience across academic, community, hospital, veterinary, and regulatory pharmacy, as well as research in wound management at a cellular level and the chemistry and mode of action of many pharmaceutical formulations.

Dr Cockbill was the founder Secretary of the Veterinary Pharmacy Association and has served in numerous professional roles, including membership of the Royal Pharmaceutical Society’s (RPS) Membership Committee, the British Pharmacopoeia Commission’s Expert Panel for Veterinary Medicines, the RPS Education Expert Advisory Panel and Education Reference Group, and the RPS Veterinary Pharmacy Forum.

Between 2012 and 2014, she was a member of the RPS Welsh Pharmacy Board, and from 2002 to 2015, she was Course Tutor for the RPS MSc in Veterinary Pharmacy.

Her governance experience includes serving on the Royal Pharmaceutical Society of Great Britain’s Professional Disciplinary Committee (2006-2010) and the General Pharmaceutical Council’s Fitness to Practise Committee (2010–2012). She was also a pharmacy member of Monmouthshire Local Health Board, contributing to the Clinical Governance Committee, Primary Care Management Group, and Continuing Care Panel from 2000 to 2009.

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