Question 16

College Answer

This question was best answered using a systematic approach. Many candidates did not address the impact of adverse reactions on management, in particular how to prevent or minimise their occurrence. Reasonable list should include effects of drug alone and drug on drug.

Expected reactions (ie extensions of known pharmacologic effects) are many and should include pharmaceutic (eg. compatibility issues), pharmacokinetic (eg. absorption, enzyme induction), pharmacodynamic (eg. innocent bystander organs, competition). Unexpected reactions include idiosyncratic (haematological, hepatic, dermatological), and allergic (mild through to anaphylaxis and anaphylactoid). Management requires detailed drug history: drugs administered (over the counter as well as prescription drugs), alcohol intake, previous drug reactions, conditions that make adverse effects more likely (eg. respiratory depression and sleep apnoea, or severe airways disease). Examination: to look for conditions that may make reactions more likely. Careful prescribing (ie only using drugs when indicated) with attention to potential interactions (including physical incompatibilities etc), and appropriate monitoring (eg. drug levels, organ function).

Twenty-three out of forty-one candidates passed this question.

Discussion

This is a question which would benefit from a systematic approach. An alternative to the college system is the one offered in Table 1 from the  Lancet article by Edwards et al (2000). Apparently, that is the official classification used in "the industry".

Classical pharmacological classification of adverse drug reactions

Dose-related reactions

• This can include adverse effects at either normal dose or overdose.
• These may include expected extesions of the therapeutic effect of the drug, eg. bleeding in heparin.
• Toxic effects eg. serotonin syndrome
• Side effects are included, eg. anticholinergic effects of tricyclics 

Non-dose-related reactions

• This refers to drug effects which are totally unrelated to the dose (i.e. any exposure is enough to trigger such a reaction).
• Allergic reactions
• Anaphylaxis
• Idiosyncratic reactions, eg. purpura or drug-induced SLE

Dose and time related reactions

• This refers to drug effects which occur due to dose accumulation, or with prolonged use
• Adrenal suppression with corticosteroids is one example.

Time related reactions

• This refers to drug effects which occur due to prolonged use in a drug which doesnt tend to accumulate.
• An example might be tardive dyskinesia afte decades of using typical antipsychotics

Withdrawal reactions

• This refers to the undesired effects of ceasing the drug
• Classical examples might include opiate withdrawal and rebound hypertension after stopping clonidine.

Unexpected failure of therapy

• This category has been added to describe an undesirable reduction in the drug's efficacy (or, the undesirable increase thereof)
• Examples may include increased clearance by dialysis and plasmapheresis, drug interactions alterinc metabolism, and the effects of critical illness on protein bindind and elemination.

Management of adverse drug reactions

Immediate management:

• ABCs
• Identification and withdrawal of the offending agent
• Immediate IM adrenaline (500mcg) for anaphylaxis
• Hydrocortisone and antihistamines for allergic reactions

Investigation

• need for thorough drug history
• search for evidence of previous drug reactions
• thorough history of allergies
• search for predisposition to adverse effects
• Assessment of drug interactions
• Investigations (such as plasma concentration measurements, biopsies, and allergy tests)
• Organ system function assessment (EUC, LFTs, TFTs, FBC for neutropenia, etc)
• Rechallenge with the drug should be considered

Prevention

• awareness of impaired clearance mechanisms due to organ pathology
• careful prescribing
• attention to drug interactions
• rational management of polypharmacy
• monitoring of drug levels
• staff education regarding safe prescribing and administration
• pharmacist participation in ICU rounds

Leape, Lucian L., et al. "Pharmacist participation on physician rounds and adverse drug events in the intensive care unit." Jama 282.3 (1999): 267-270.

Edwards, I. Ralph, and Jeffrey K. Aronson. "Adverse drug reactions: definitions, diagnosis, and management." The Lancet 356.9237 (2000): 1255-1259.

Cullen, David J., et al. "Preventable adverse drug events in hospitalized patients: a comparative study of intensive care and general care units." Critical care medicine25.8 (1997): 1289-1297.

 

Bates, David W., et al. "Incidence of adverse drug events and potential adverse drug events: implications for prevention." Jama 274.1 (1995): 29-34.