Redefining the ACE-inhibitor dose-response relationship: substantial blood pressure lowering after massive doses.
OBJECTIVE
The blood pressure-lowering dose-response relationship for angiotensin converting enzyme (ACE) inhibitors is assumed to flatten at doses higher than those conventionally used in clinical practice. However, existing clinical trial data do not adequately address the haemodynamic effects of high ACE inhibitor dosages. Therefore, we examined the blood pressure responses in patients presenting to hospital following a deliberate ACE inhibitor overdose.


METHODS
The study design was a retrospective case review, and included all patients who presented to our hospital in the past 5 years after an ACE inhibitor overdose. The data collected were heart rate and systemic blood pressure at various times after ingestion and maximum haemodynamic derangement; these were compared to baseline or recovered values.


RESULTS
Data from 33 patients (24 men) were evaluated. The median (inter-quartile range, IQR) age of the patients was 49 years (IQR: 42-56 years). The median stated dose ingested was 140 mg (IQR: 60-280 mg), which is 20x (IQR: 7-42) the defined daily dose. The maximum fall in systolic blood pressure was 50 mmHg (IQR: 40-64 mmHg), diastolic blood pressure was 35 mmHg (IQR: 26-43 mmHg) and mean blood pressure was 39 mmHg (IQR: 30-47 mmHg).


CONCLUSIONS
The observed reduction in blood pressure following an overdose of an ACE inhibitor was greater than anticipated based on data from therapeutic doses. We conclude that a blood pressure-lowering dose-response relationship extends to higher ACE inhibitor doses than those conventionally used in clinical practice.
Christie
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GA
Scottish Poisons Information Bureau, Royal Infirmary of Edinburgh, 51 Little France Crescent, Edinburgh EH16 4SA, UK.
Lucas
C
C
Bateman
D N
DN
Waring
W S
WS
D000319:Adrenergic beta-Antagonists / Q000009:adverse effects / Q000627:therapeutic use; D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000009:adverse effects / Q000627:therapeutic use; D003404:Creatinine / Q000097:blood; D004232:Diuretics / Q000009:adverse effects / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D062787:Drug Overdose; D017723:Drug Utilization Review / Q000706:statistics & numerical data; D004562:Electrocardiography / Q000379:methods; D004636:Emergency Service, Hospital / Q000706:statistics & numerical data*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy; D009638:Norepinephrine / Q000009:adverse effects / Q000627:therapeutic use; D017257:Ramipril / Q000009:adverse effects / Q000627:therapeutic use; D012189:Retrospective Studies
D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000894:Anti-Inflammatory Agents, Non-Steroidal; D002121:Calcium Channel Blockers; D004232:Diuretics; D003404:Creatinine; D017257:Ramipril; D009638:Norepinephrine