Guancydine (1-cyano-3-tert-amylguanidine), a new vasodilator and antihyperetnsive agent, lowers the blood pressure by reducing total vascular resistance without impairing sympathetic reflexes.
The authors have assessed the antihypertensive activity and safety of guancydine (125 mg) combined with quinethazone (50 mg) and reserpine (0.08 mg) in comparison with a fixed combination of quinethazone (50 mg) and reserpine (0.08 g) in patients with arterial hypertension.
Three drug regimen containing guancydine was administered to 25 patients (19 males, 6 females) with essential and renal hypertension in a capsule form, and quinethazone plus reserpine was given to 25 patients (16 males, 9 females) with essential hypertension for 12-weeks peiods respectively. The average daily dose of guancydine was 315.2 mg (range 163 mg to 375 mg).
The results obtained were as follows:
1) Seversity index was lowered on the guancydine-containing combination, averaging 54.9%(from 10.64 to 4.80), while average value of 48.3% (from 9.52 to 4.92) on the 2 drug regimen was obtained.
2) Blood pressure fell on both regimens. However, the decrease of average blood pressure was greater on the combination of drugs containing guancydine, with average reduction of 43/31 mmHg in supine and 43/33 mmHg in standing position. Average mean blood pressure reduction was 36 mmHg in sitting position.
During quinethazone-reserpine treatment without guancydine, the decrease of average blood pressure was 39/26 mmHg in supine and 36/24 mmHg in standing position. Average mean blood pressure reduction was 31 mmHg in sitting position.
Five patients who were refractory to other current antihypertensive drugs as well as two patients with renal hypertension showed a significant response to the 3 drug regimen containing guancydine.
Orthostatic hypotension was not observed in any cases of author´s series.
3). Pulse rate increased by an average of 2 beats per minute in supine and 5 beats per minute in standing position among the patients with the 3 drug regimen containing guancydine, while with the 2 drug regimen without guancydine, pulse rate decreased by an average of 4 beats per minute in supine and 3 beats per minute in standing position.
4) Body weight before and after treatment remained essentially unaltered on the 3 drug regimen containing guancydine, with the mean change of +0.06 kg. On the 2 drug regimen without guancydine there was a decrease in body weight, averaging 0.65 kg. 5) Side effects observed in 7 patients with the 3 drug regimen consisted of headache in 3, dizziness in 1, palpitation in 1, anorexia in 1 and nausea in 1, while 6 patients with quinethazone and reserpine complained of headache in 2, dizziness in 1, dry mouth in 1, constipation in 1 and nasal congestion in 1.
The above symptoms were transient and improved either by reducing the dosage or by not omitting the medication. There were no significant changes in chest X-ray, EKG, optic-fundi, serum creatinine or 24-hour urinary protein before and after treatment.
It is concluded that guancydine combined with quinethazone and reserpine can effectively reduce blood pressure without inducing fluid retention or tachycardia in this series, regardless of the level of blood pressure or refractoriness to previous therapy.
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