Cough mixture dependence and stroke: implications for pseudoephedrine regulation

At presentation in an emergency department, he was hypertensive (blood pressure, 220/140 mmHg) and hyperglycaemic. An upper motor neurone pattern of persistent dysarthria and left hemiparesis was evident. An electrocardiograph and transthoracic echocardiogram confirmed sinus rhythm and left ventricular hypertrophy. Magnetic resonance angiography of the brain showed subacute basal ganglia haemorrhage (Box) and an anterior communicating artery aneurysm. Renin levels were elevated at 124.7 mU/L (reference range, 4.5–46.0 mU/L) but renal artery stenosis was absent on ultrasound. Evaluation of an elevated initial normetadrenaline level of 1610 pmol/L (reference range, < 900 pmol/L) with a diagnostic algorithm1 suggested that phaeochromocytoma was unlikely. Hypertension, proteinuria, suboptimal renal function, inactive urine sediment and normal fasting blood glucose suggested hypertensive nephropathy. Antihypertensives were initiated to mitigate the risk of further stroke, nephropathy and cardiomyopathy. Results of an electroencephalogram were normal.

Further history revealed that the patient had nicotine dependence with occasional amphetamine and cannabis exposure. Before admission, he had an estimated intake of 1–2.5 bottles of cough mixture episodically (600–1500 mg of pseudoephedrine). A pattern of ingesting excessive amounts of various brands of over-the-counter combination pseudoephedrine and codeine cough mixture developed over 20 years, and he suffered cravings when abstaining. He visited various pharmacies, provided identification, was repeatedly cautioned, but rarely consulted doctors. A Naranjo score2 of 7 indicated a probable adverse drug reaction to pseudoephedrine, resulting in a disabling hypertensive haemorrhagic stroke.

During 2.5 months of inpatient rehabilitation, he regained full independence in self-care and mobility. His unstable employment was interdependent with pseudoephedrine misuse. He accepted counselling regarding constructive, non-pharmacological coping strategies for social stressors. Financial, legal and housing difficulties complicated his discharge plan. He planned to return to work as a driver.

Pseudoephedrine is associated with a modest elevation in blood pressure3 and hypertensive crises.4 Intracerebral haemorrhage associated with pseudoephedrine usage is anecdotally reported.5 Dependence and chronic psychoses have been reported6,7 but their prevalence is unknown. Night-shift workers, students, recreational or self-medicating users, and athletes are potentially vulnerable to misuse.

Project STOP is an initiative of the Pharmacy Guild of Australia (http://www.projectstop.com.au/index.html) to curb diversion of pseudoephedrine-containing medications from retail pharmacies into illegal amphetamines. However, it is not mandatory and the National Drugs and Poisons Schedule Committee has rejected the Pharmacy Guild’s proposal to enhance Project STOP’s capabilities using an electronic messaging tool for pharmacists (NotifyRx, RelayHealth, Atlanta, Ga, USA) to regulate codeine sales (excluding cough mixtures). In contrast, New Zealand authorities now restrict the supply of pseudoephedrine to prescription only. A concerted effort from all relevant parties, including tighter regulation or legislation, is essential for harm minimisation. We urge regulatory bodies to review the effectiveness of current practice.

Magnetic resonance angiogram of the patient’s brain showing likely hypertensive right basal ganglia haemorrhage