Hydrochlorothiazide doses of 50 mg daily or less are acceptable during lactation. Intense diuresis with large doses may decrease breastmilk production.

With increasing availability of valve surgery, a pool of patients requiring chronic anticoagulation is emerging in our environment. The lower blood coagulability with low temperatures, though rare, can occur, putting patients at risk of bleeding. Recently, the author lost two patients with prosthetic valves on anticoagulation at the peak of the cold harmattan season. Before their death, despite dose reduction, the International Normalised Ratio (INR) kept increasing and they were reported to have died suddenly at home. This triggered the need to draw attention of clinicians especially in the tropics to this difficulty, so as to anticipate and confront it when necessary. Case 1 was a 42-year-old male hypertensive on life-style measures with Moduretic once daily and weekly 20 mg Propranolol to control his blood pressure. He had surgery in India for aortic aneurysm with placement of prosthetic valve in 2013, and was placed on an oral anticoagulant - Acitrom. In 2015 while on 3 mg daily dose, he had an INR of 2.8. By October, INR rose to 3.95 prompting a dose reduction to 2 mg daily. Early in January 2016 (peak of cold harmattan season), the INR went higher to 4.19. He was asked to skip doses on Saturday and Sunday. After a forthnight he was reported to have died suddenly at home and no autopsy was done. Case 2 was a 40-year-old female with mitral stenosis. She had mitral valve surgery with prosthetic valve placement in India in 2010 where she was put on warfarin. In 2015, she had episode of ecchymosis and INR returned 2.07. With dose reduction, the INR dipped to 1.21 prompting a dose increase to 6 mg. The INR increased to 2.73. By October of 2015, her INR rose to 3.72, prompting de-escalation to 5 mg daily. While on this, she presented in a peripheral centre with haemoptysis where her Warfarin was further de-escalated and Co-trimoxazole prescribed. Again, within a fortnight she was reported to have died suddenly; and no autopsy was done The curious similarity here is the increasing INR despite anticoagulant de-escalation in the cold harmattan season. This experience has not been reported locally to the knowledge of the author. Some workers have reported that clotting times are longer with cold; clotting times being 3 times longer at 27 degrees Centigrade than 37 degrees.1 The phenomenon of decreasing temperature progressively delaying thrombus initiation began at 30 degrees Centigrade, progressing rapidly below that; and reaching statistical significance at 24 degrees.2 However, significant inter-individual variability in this response has been observed and explains conflicting result of studies on this subject.3 One could understand, therefore, why such observation may be made in Jos where harmattan temperatures can drop to single digits.

The kinetics and photodegradation mechanism of the pharmaceutical mixture of hydrochlorothiazide (HCT) and amiloride (AML) has been studied in depth using a chemometric approach. Water solutions of HCT and AML, separately or in binary mixtures, were irradiated with forced light at different pH values (3, 7, 9 and 12). Multivariate Curve Resolution - Alternating Least Squares (MCR-ALS) modelling has been applied to the experimental data recorded by UV spectrophotometry and HPLC-UV/MS. 78 data sets were collected and their chemometric processing has allowed the simultaneous determination of the behaviour of the two drugs in the mixture when exposed to light and the dependence of their photodegradation kinetics on pH. MCR-ALS has been applied using three different implementations. Soft-MCR-ALS and hybrid Hard/Soft-MCR-ALS have been used to resolve the experimental data and to get the equilibrium and kinetic parameters of the investigated chemical processes. A third implementation of the MCR-ALS method has been used in the analysis of the incomplete data sets obtained when UV spectrophotometric and HPLC-UV/MS data were simultaneously analysed, using a row- and column-wise incomplete augmented data matrix arrangement. In these matrices, information from HPLC-UV detector was used as a bridge between the data recorded by UV spectrophotometry (acid-base and kinetic reactions monitoring) and the data obtained by HPLC-MS.

Green and sensitive spectrofluorometric methods have been developed and validated for the determination of timolol maleate (TML)/hydrochlorothiazide (HCT) and amiloride hydrochloride (AMH)/hydrochlorothiazide in tablets. The proposed spectrofluorometric procedures were found to be linear in the range of 4-12, 5-35 and 0.025-0.2 mg L-1 for HCT, TML and AMH, resp. The excitation and emission wavelengths for HCT, TML and AMH at room temperature were 270 and 375, 295 and 435, 330 and 415 nm, resp. The methods were validated with respect to ICH guidelines. The AMH showed higher sensitivity with lower values of LOD and LOQ values compared to HCT and TML. The proposed methods were applied to two pharmaceutical formulations; the method for HCT and AMH has proven as reliable assaying method, whereas the method for TML, when combined with HCT, is applicable to screening semi-quantitative analyses.

There is a dearth of reports on possible additive blood pressure (BP)-reducing effect of aerobic exercise on antihypertensive drug in humans. This study investigated the additive BP-reducing effect of aerobic exercise on BP in individuals with uncontrolled hypertension. In this 12-week double-blind study, 120 new-diagnosed individuals with mild-to-moderate hypertension were randomized to receive coamilozide + 5/10 mg of amlodipine + aerobic dance or coamilozide + 5/10 mg of amlodipine alone. Forty-five and 43 participants in exercise and control groups, respectively, completed the 12-week intervention. Addition of aerobic exercise to antihypertensive drug therapy significantly reduced systolic BP (7.1 mm Hg [95% confidence interval: 5.0, 9.3]; P < .001) and diastolic BP (1.7 mm Hg [95% confidence interval: 0.4, 3.0]; P = .009) at 12 weeks. BP control rate differed significantly between exercise (53.9%) and control (35.3%) groups, P < .001. Postintervention, proportion of participants in exercise group who had their number of antihypertensive drug reduced to one (20.3%) differed from that in control group (11.1%); (χ(2) = 11.0; P = .001). Combination of aerobic dance and antihypertensive drugs reduces number of antihypertensive drugs needed to achieve BP control and enhances BP control in individuals with hypertension on two antihypertensive drugs.