Adverse Drug Reactions: The ABCs of ADRs

As part of Med Safety Week, the focus for this year is on promoting patient safety and a topic highlighted in this year’s theme is adverse drug reactions (ADRs), including raising awareness of potential ADRs and the importance of reporting these events.

What is the scale of the ADR problem?

According to data published this year, between 6-7% of hospital admissions in the United Kingdom (UK) are due to ADRs (NICE 2022). This confirmed the results of an earlier UK observational study, which showed 6.5% of admissions to one hospital in Nottingham were due to ADRs and of these, the authors believed 67% were preventable. (Howard, 2003).

This is consistent with data from a cohort study carried out in Nigeria on 1280 patients, which showed that “5.2% of patients had ADRs, 3.9% of these ADRs caused hospitalisation while 1.3% occurred during hospitalisation, and 62.7% of total ADRs were preventable” (Adedapo et al 2021).

In a US meta-analysis of 42 studies, it was found that ADRs counted for about 9% of hospital admissions in older adults and the authors of this study concluded that 33% of ADRs could have been prevented. (Hanlon and Gray 2022). In Singapore, it was found that ADRs due to hospital admissions was at 8.1% and patients reported with ADRs have a longer admission stay in the hospital than those who do not. (Chan et al 2016).

In summary, this is a global problem and a substantial proportion of these healthcare resources could have been saved if the ADRs had been prevented.

Can we prevent adverse drug reactions?

The preventability of ADRs was compared in developing and developed countries in an extensive literature review carried out by Angamo from data published over a 15-year period. He noted that the proportion of preventable ADRs in developed and developing countries were 71.7% to 59.6% respectively (Angamo et al 2016).

One of the key issues impacting our ability to accurately measure preventability is under-reporting, as many ADRs are never reported to any healthcare professional or regulatory agency. Several authors have highlighted that there could be a massive pool of unreported ADRs, as under reporting is a key issue that the healthcare system faces (Coleman, 2016; Raymond et al, 2022).

To support this an Australian retrospective review of hospital admissions due to ADRs from October to December 2019 is recorded at 9% and under-reporting of these ADRs was reported as over 99% (Raymond et al 2022).

What can I do?

According to the regulatory definition an ADR is “A response to a medicinal product which is noxious and unintended. Response in this context means that a causal relationship between a medicinal product and an adverse event is at least a reasonable possibility”. If people have not suspected this causal relationship, they may believe they do not need to report it.

Reporting all adverse events (AEs) that occur following administration of a medicine will improve the overall amount of data for the manufacturers and regulatory agencies to analyse. However, there are lots of different types of ADRs and not all of them are linked to medicines in an obvious way. This blog discusses the different types of ADRs and highlights the importance of reporting any AE that occurs with a medicinal product because it just might be the first time this ADR has been reported.

Classification of adverse drug reactions:

Type A

This is the most common type of reaction, sometimes called “Dose Related” or “Augmented” reaction and these ADRs tend to be the easiest to spot a link with the medication. Dose related ADRs are usually exaggerated effects of a drug’s pharmacological actions when given at the usual dose (NICE, 2022). These are dose dependent, therefore varying the dose of the drug will influence the impact of the adverse drug reaction. Increasing the dose means increasing the chances of these reactions occurring, and the management for this class of ADRs tends to be to reduce the dose (NHS Scotland, 2013).

Examples of type A reactions include feeling lightheaded or dizzy from blood pressure medication due to hypotension, dehydration with diuretics such as furosemide, hypoglycemia with insulin, bleeding with warfarin and excessive daytime drowsiness with sleeping tablets.

Type B

This class of ADRs are less common and they are also known as “Non-Dose Related” or “Bizarre” reactions. These reactions are different from the known pharmacological actions of the drug and they are not dose dependent. Management for bizarre adverse drug actions is usually to discontinue treatment. (NHS Scotland, 2013). Other factors could contribute to the occurrence of type B reactions, for example immune factors or genetic factors. Some examples of type B ADRs include rashes, jaundice or anemia.

Type C

Type C ADRs can carry on for a long period of time. They are also known as “Dose related and Time related” or “Chronic” reactions. Examples include osteonecrosis of the jaw with bisphosphonates, avascular necrosis of the hip or growth inhibition with corticosteroid therapy (NHS Scotland, 2013). It can be difficult to determine the cause as the medication may already have discontinued by the time the event is identified.

Type D

These ADRs are also known as “Time related” or “Delayed” reactions and they are usually not obvious because they do not occur immediately after use of drug. They only become apparent a while after the medicine was used. Examples of these ADRs include lymphomas in patients previously treated with chemotherapy.

Type E

Also known as “Withdrawal” or “End of use” reactions are reactions caused by withdrawal of a drug. These ADRs have been well-described to occur after withdrawal of many different classes of drugs for example opiates, corticosteroids, antipsychotic drugs, anti-depressants. (Routledge and Bialas, 1997). However, there may be subtle withdrawal effects that may not be so well known, so it is always good to monitor how you feel after stopping a medication.

Type F

This type of ADR is also known as “Unexpected failure of therapy”. Reactions are classified as Type F when the efficacy of the drug decreases. Examples of these include decreased clearance of a drug due to dialysis, or antibiotic resistance.

Other

It is important to note that not all adverse drug reactions fall into these categories. Not all ADRs are dose related or time related. Some reactions could be due to allergies or occur in other various circumstances. It is just important to report these reactions or what you suspect is an adverse drug reaction so that it can be reviewed for further action.

What happens after you report an adverse drug reactions?

When the manufacturer or regulatory agency receives a report it joins the other reports they have received, to provide a body of data on potential drug adverse reactions. If there is a suspected causal relationship between a medicine and an event there will be an evaluation of all available data on this, including the reports sent by people taking or prescribing the medication. The more detail you can provide the more accurate the outcome of this evaluation will be. For example if we see patterns such as a specific timing from taking the medication to onset of the reaction, or treatments that seem to work well, or investigations that pick up the events before they become serious, this can provide useful information to pass on to future patients taking this medication.

Please see our other blogs for information on how to report ADRs.

References

Adedapo, ADA, Adedeji, WA, Adedapo, IA, Adedapo, KS. Cohort study on adverse drug reactions in adults admitted to the medical wards of a tertiary hospital in Nigeria: Prevalence, incidence, risk factors and fatality. Br J Clin Pharmacol. 2021; 87: 1878– 1889. https://doi.org/10.1111/bcp.14577

Angamo, M.T., Chalmers, L., Curtain, C.M. et al. Adverse-Drug-Reaction-Related Hospitalisations in Developed and Developing Countries: A Review of Prevalence and Contributing Factors. Drug Saf 39, 847–857 (2016). https://doi.org/10.1007/s40264-016-0444-7

Briefing Note Safety of medicines -adverse drug reactions Key facts. (n.d.). [online] Available at: https://www.who.int/docs/default-source/medicines/safety-of-medicines–adverse-drug-reactions-jun18.pdf?sfvrsn=4fcaf40_2. [accessed on 17 November 2022]

www.sqadia.com. (n.d.). What are the types of ADRs? | Classification in Pharmacology. [online] Available at: https://www.sqadia.com/programs/what-are-the-types-of-adrs?cid=2586056&permalink=what-are-the-types-of-adrs-animation. 

Chan, S. L.,  Ang, X.,  Sani, L. L.,  Ng, H. Y.,  Winther, M. D.,  Liu, J. J.,  Brunham, L. R., and  Chan, A. (2016)  Prevalence and characteristics of adverse drug reactions at admission to hospital: a prospective observational study. Br J Clin Pharmacol,  82:  1636– 1646. doi: 10.1111/bcp.13081.

Coleman JJ, Pontefract SK. Adverse drug reactions. Clin Med (Lond). 2016 Oct;16(5):481-485. doi: 10.7861/clinmedicine.16-5-481. PMID: 27697815; PMCID: PMC6297296.

derangedphysiology.com. (n.d.). Classification of adverse drug reactions | Deranged Physiology. [online] Available at: https://derangedphysiology.com/main/cicm-primary-exam/required-reading/variability-drug-response/Chapter%20320/classification-adverse-drug-reactions. 

Adverse drug reaction information continued

Guidance on adverse drug reactions Guidance on adverse drug reactions Contents. (n.d.). [online] Available at:

https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/949130/Guidance_on_adverse_drug_reactions.pdf.

‌Hanlon, J.T. and Gray, S.L. (2022). Deprescribing trials: A focus on adverse drug withdrawal events. Journal of the American Geriatrics Society, 70(9), pp.2738–2741. doi:10.1111/jgs.17883.

Howard, R.L., Avery, A.J., Howard, P.D. and Partridge, M., (2003). Investigation into the reasons for preventable drug related admissions to a medical admissions unit: observational study. BMJ Quality & Safety, 12(4), pp.280-285.

Knowledge.scot.nhs.uk. (n.d.). Adverse Drug Reactions ABCDE Classification. [online] Available at: http://www.knowledge.scot.nhs.uk/ecomscormplayer/ADRmodule2/4-abcde.html. [Accessed 9 Nov. 2022].

MSD Manual Consumer Version. (n.d.). Types of Adverse Drug Reactions – Drugs. [online] Available at: https://www.msdmanuals.com/en-gb/home/drugs/adverse-drug-reactions/types-of-adverse-drug-reactions.

NICE. (n.d.). CKS is only available in the UK. [online] Available at:https://cks.nice.org.uk/topics/adverse-drug-reactions/.

Raymond Li, Kate Curtis, Syed Tabish Zaidi, Connie Van, Ronald Castelino. (2022) A new paradigm in adverse drug reaction reporting: consolidating the evidence for an intervention to improve reporting. Expert Opinion on Drug Safety 21:9, pages 1193-1204.

Riedl MA, Casillas AM. Adverse drug reactions: types and treatment options. Am Fam Physician. 2003 Nov 1;68(9):1781-90. PMID: 14620598.

Routledge, P.A. and Bialas, M.C. (1997). Adverse reactions to drug withdrawal. Adverse Drug Reaction Bulletin, [online] 187(1), pp.711–714. Available at: https://journals.lww.com/adversedrugreactbull/Abstract/1997/12000/Adverse_reactions_to_drug_withdrawal.1.aspx [Accessed 9 Nov. 2022].

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