Amlodipine alters hemorheological parameters: Increased efficacy at the cost of edema?

Background Despite several decades of use of calcium channel blockers, the side effect of edema persists as a class effect, and its mechanism is unresolved. Amlodipine has effects on hemorheology (HR), and its hemodilutory property may partly contribute to its antihypertensive action. This aspect is not well studied, and the literature is sparse in this regard. Objective This experiment was planned to determine effect of a single-dose administration of amlodipine on HR parameters in normal human volunteers. Methods and results Amlodipine (5 mg) or S (-) amlodipine (2.5 mg) was administered to 27 normal human volunteers. Whole-blood viscosity (WBV) at different shear rates, plasma viscosity (PV), red cell rigidity (RCR), red cell aggregation (RCA), hematocrit (Hct), plasma hemoglobin, along with plasma drug concentration were determined at time intervals, t = 0, 4, 8, 12, and 24 h. Statistically significant reductions were observed at tmax = 4 h in WBV at shear rates of 0.512 s–1 (p < 0.005), WBV at shear rates of 5.26 s–1 (p < 0.01), PV (p < 0.05), and Hct (p < 0.01). At t = 8 h, as drug concentration reduced, some of the changes persisted and later slowly decreased with the decreasing drug concentration till t = 24 h. Red blood cell–related parameters such as RCA and RCR remained unaltered. WBV values at all shear rates, when corrected for Hct = 0.45, did not show deviation from their original values at any time. Conclusions Amlodipine causes a reduction in Hct and blood viscosity, along with hemodilution. These effects persist as long as the drug remains in plasma. Edema resulting from chronic dosing may be explained by the aforementioned effects. It is possible that antihypertensive action of the drug may be due to a combination of vasodilatation and an improvement in the HR properties.

Haemorheology in diabetic foot.

A prospective study was undertaken to study the haemorheology in patients with diabetic foot lesions. Haemorheology of 30 patients with foot lesions and 30 age and sex matched controls was studied. The haemorheological parameters evaluated were whole blood and plasma viscosity and RBC filter ability. Plasma viscosity was significantly increased (p < 0.05). It substantiates the need for using rheomodulators in management of diabetic foot lesions.

Hematocrit and whole blood viscosity in newborns: analysis of 100 cases.

Hematocrit (Hct) and whole blood viscosity was studied at a mean age of ten hours in 100 neonates. Group A (n = 25), were term normal newborns, Group B (n = 25) were preterms, Group C (n = 20) were term small for gestation (SGA) and Group D (n = 30) had perinatal hypoxia. Blood viscosity was estimated in all cases at shear rates 94.5, 51.2, 20.4 and 8.1 and intergroup variability in viscosity compared at shear rate 51.2. The mean hematocrit (Hct) (59.4%) and viscosity (8.2 cps) was higher in Group A as compared to other groups, but the difference was not significant (p greater than 0.05). The upper limit of viscosity in Group C (11.9 cps) was higher than in all other groups but this difference was also not significant (p greater than 0.05). With decrease in shear rates a reciprocal increase in viscosity was noted in all four groups. Seventeen neonates (17%) had polycythemia of which eight (47.5%) were SGA. Twelve per cent preterms were polycythemic. Only 3% of neonates had hyperviscosity. The mean Hct and viscosity of the 17 cases with polycythemia was 70.9 and 9.21 cps, respectively, which was significantly higher than mean Hct and viscosity of Group A (p less than 0.05). Partial exchange transfusions were done in five neonates with Hct greater than 75%, of which only one had hyperviscosity. Post-exchange viscosity was not estimated. Whereas, three neonates with polycythemia were symptomatic, none of these had hyperviscosity. A linear correlation between Hct and viscosity was observed (r = 0.67).

Efficacy and safety of 1-2, dimethyl-3-hydroxypyrid-4-one (L1) as an oral iron chelator in patients of beta thalassaemia major with iron overload.

Twenty-four patients with beta thalassaemia major, aged 8-22 years (mean 15.3 +/- 8.1) were given 1-2, dimethyl-3-hydroxypyrid-4-one (L1) orally for a period of three months. The drug was given in the dose of 25 mg/Kg/day for the first week and gradually increased to 100 mg/Kg/day which was continued until 3 months. The mean urinary iron excretion was 5.73 +/- 3.648 mg/day on 25 mg/Kg/day of L1; 15.2 +/- 11.225 mg/day on 50 mg/Kg/day; 24.2 +/- 12.69 mg/day on 75 mg/Kg/day and 36.3 +/- 19.4 mg/day on 100 mg/Kg/day of L1. Serum ferritin estimated by ELISA before and 3 months after L1 therapy in 21 patients showed significant drop in levels, the mean drop being 964.3 +/- 844.4 (P less than 0.001). The only side-effects noted were transient gastrointestinal symptoms in 5 patients and skeletomuscular pain in 3 patients. Both these groups of symptoms were of transient nature. The efficacy of L1 appears to be excellent and equivalent to the standard iron chelation therapy available at present i.e. desferrioxamine. It appears to be free of major toxicity. L1 is also a specific chelator for iron as it does not deplete trace metals. L1 appears to be a cheap and effective oral alternative to desferrioxamine for treating iron overloading.