Syncope following oral chloroquine administration in a hypertensive patient controlled on amlodipine.

Amlodipine has achieved global use and acceptability in the monotherapy of moderate to severe essential hypertension. Chloroquine is still the choice antimalarial drug in areas where there is little antimalarial resistance and for the treatment of rheumatological disorders (systemic lupus and rheumatoid arthritis) which may be associated with hypertension. Thus, there exists a high probability of the concurrent use of chloroquine with amlodipine. We provide the first report to our knowledge of a possible severe adverse drug interaction between amlodipine and chloroquine in a hypertensive patient. A 48 year old male physician, who is a known hypertensive (initial blood pressure 172/110 mmHg) had achieved optimal blood pressure control of 136/86 mmHg after oral amlodipine 5 mg daily for 3 months, according to his medical records. He developed a slight frontal headache and fever, and self administered four tablets of chloroquine sulphate (total 600 mg base) at about 09.00 h, based on the presumptive self diagnosis of malaria fever. Two hours later, whilst he conducted a medical clinic, he became nauseated, dizzy and collapsed from the upright posture. The nurse on duty immediately called the medical team on the emergency roster. Upon arrival, the patient was conscious, alert, but disoriented. His extremities were cool and he was placed in a head-down position on a couch. The body temperature was 38.8° C, the radial pulse was regular, of poor volume, and there was a bradycardia of 52 beats min−1. The initial blood pressure was systolic 80 mmHg and the diastolic was unrecordable by mercury sphygmomanometer or Omron-automatic sphygmomanometer. An intravenous access was obtained for the infusion of 5% dextrose-saline (0.9%) solution. Blood samples were obtained for blood sugar, chemistry and malaria parasites. After 1 h of infusion of the dextrose-saline (about 800 ml), the blood pressure rose to 110/75 mmHg, and the pulse to 84 beats min−1, regular and good volume. 12 lead -ECG was unremarkable, there were no malaria parasites detected and the patient was ambulant 2 h after the onset of his syncope. His long-term recovery was also unremarkable and sustained. Chloroquine alone causes a hypotensive response [1, 2] and increases forearm blood flow, by decreasing forearm vascular resistance [2]. Recent evidence indicates that chloroquine causes venodilation via the release of nitric oxide in human forearm veins [3]. Thus, chloroquine may reduce both preload and afterload, but this is rarely symptomatic in healthy adults after oral dosing. The oral administration of chloroquine in the presence of amlodipine in this hypertensive patient, appears to have triggered a vasovagal syncope, which was correctable by dextrose-saline infusion. Amlodipine releases nitric oxide from canine coronary microvessels [4] and lacidipine increases endothelial nitric oxide formation in human endothelium in hypertensive patients [5]. Stimulation of endothelial nitric oxide synthase may thus be a property common to long acting calcium antagonists. Chloroquine also blocks the fast inward K+ channels in feline myocytes [6]. The patient had no malaria parasitaemia, and hence mechanistically the syncope may be as a result of acute synergistic hypotensive, venodilator and cardiac effects of the amlodipine and chloroquine, possibly acting via augmented nitric oxide production and calcium channel blockade. Since malaria fever per se is associated with orthostatic intolerance, this possible adverse interaction may be unrecognized and unreported. We urge caution in patients receiving combined treatment with 1,4 dihydropyridine calcium antagonists and aminoquinoline antimalarial drugs.