Eur J Clin Pharmacol (1996) 51 : 45–48 © Springer-Verlag 1996 PHARMACODYNAMICS A. A. Ajayi · M. A. Afolabi · M. O. Balogun A. Q. Adigun · O. E. Ajayi · A. O. Akintomide Oral therapy with combined enalapril, prazosin and hydrochlorothiazide in the acute treatment of severe hypertension in Nigerians R eceived : 17 July 1995/Accepted in revised form: 16 January 1996 Abstract Objective: The efficacy, safety, tolerability and speed of onset of the hypotensive action of the combination of oral enalapril (10 mg) prazosin (1 mg) and hydrochlorothiazide (50 mg) has been assessed in 12 Nigerians with severe hypertension (Diastolic BP ≥115 mmHg). Patients: The ages of the patients ranged from 30–60 years, and the serum creatinine from 52–732 μmol·l 1 . The initial blood pressure was 200/130 mmHg. Results: The combination significantly reduced systolic and diastolic blood pressure respectively. The hypoten- sive action appeared within 0.5 h and led to a fall in BP to 175/120 mmHg, and the peak action occurred at 4 h, when the BP was 138/99 mmHg, and it per- sisted upto 24 h (160/101 mmHg). Despite the significant fall in blood pressure, no reflex tachycardia was observed. Transient dizziness was seen in 2 patients, but otherwise all claimed improvement in clinical sta- tus and a clearer sensorium. Conclusion: The combination may be a useful oral treat- ment for the rapid control of severe hypertension in Blacks. Key words Hypertension, Enalapril, Prazosin, Thiazide, Nigerians; drug combination Introduction Hypertension remains the commonest cardiovascular disease of black Africans [1], and constitutes a significant risk for strokes, renal impairment, conges- tive heart failure and death in these patients [2]. High blood pressure is more severe in blacks [3]. Severe hypertension is associated with an upward resetting of the cerebral blood flow-mean arterial blood pressure relationship [4]. This cerebral dysautoregula- tion increases the risk of cerebral infarction with hypotensive drugs, and so raises the necessity for a therapeutic regime that can safely, rapidly and effectively lower blood pressure by an adequate extent, especially in hypertensive heart failure or encephalopa- thy. Parenteral therapy has been used for the initial treatment of severe hypertension, but this modality is handicapped by expensive cost, increased cerebral infarction [5, 6] and the need for frequent and inten- sive monitoring. The use of orally active drugs, either as monotherapy or in combination, has been advocated [7]. There is no consensus about rational oral therapy, especially in black Africans. Earlier studies have demonstrated the efficacy of slow release Nifedipine [8, 9], atenolol [9] and labetalol [10] in black Africans. However, there are problems of reflex tachycardia [9] and frequent dosing, owing to the short duration of action [8, 9]. Angiotensin converting enzyme inhibitors have been shown to lower arterial blood pressure, whilst preserv- ing cerebral blood flow [11], and without causing reflex tachycardia [12]. Although these pharmacodynamic effects make ACE-inhibitors suitable for rapid and safe use in a hypertensive crisis, monotherapy with these agents have been shown to have poor efficacy in Nigerians [13] and other Africans [14] with essential hypertension. Activation of the renin-angiotensin system by diuretics, or in malignant hypertension, or the concurrent use of enalapril and α-adrenoceptor blocker, prazosin, results in a profound hypotensive response on treatment of healthy Nigerians [15] and Japanese subjects [16]. The aim of the present study was to evaluate the safety, efficacy, rapidity of onset and duration of action of an oral enalapril, prazosin and thiazide diuretic combination in Nigerians with severe hypertension. A. A. Ajayi (*) · M. A. Afolabi · M. O. Balogun A. Q. Adigun · O. E. Ajayi · A. O. Akintomide College of Health Sciences, Department of Medicine, Obafemi Awolowo University, Ile-Ife, Osun State, Nigeria