Ambrose O. Isah

Chloroquine-induced pruritus

Chloroquine-induced pruritus remains one of the most common side-effects in the use of chloroquine in the prophylaxis and treatment of uncomplicated malaria before the advent of artemisinin-based combination therapies. It has been reported to vary from a tolerable to intolerable intensity among susceptible individuals resulting in disruption of treatment and development of resistance to the drug thus leading to therapeutic failures as reported. This scourge is quite challenging due to the complex physiologic mechanism that has not been fully elucidated. Factors observed to be responsible in the induction of pruritus such as age, race, heredity, density of parasitaemia; impurities in formulations, plasmodial specie, dosage form and metabolites have been discussed in this review. Efforts to ameliorate this burden have necessitated the use of drugs of diverse pharmacological classes such as antihistamines, corticosteroids and multivitamins either alone or as a combination. This review is to look into the use of chloroquine retrospectively, and consider its re-introduction due to its safety. Efficacy can be attained if the pruritic effect is resolved.

Medication errors among health professionals in Nigeria: A national survey

BACKGROUND Medication errors are preventable causes of patient harm with significant contributions to adverse drug events but they remain understudied in Nigeria. OBJECTIVES To estimate the prevalence of self-reported medication errors among health professionals and examine their knowledge of medication errors with the hope of identifying appropriate measures to promote medication safety. METHODS A cross sectional survey among doctors, pharmacists and nurses in 10 tertiary hospitals. Information was obtained using a self-administered structured questionnaire. Correct responses evaluating the knowledge of prescription, dispensing and administration errors were scored one mark each and the composite scores computed. Appropriate statistics were applied to summarize and establish the relationship between variables at 5% level of significance using SPSS 17.0. RESULTS A total of 2,386 professionals participated in the study (46.3% nurses, 44.9% doctors, 8.8% pharmacists).The prevalence of self-reported medication errors was 47%.The professional groups differ in their knowledge of all the aspects of medication errors with professional cadres influencing knowledge.Overwork was the most reason for being error prone (59.2%) and only 35.5% had ever reported medication error. 33.4% did not think reporting was necessary. CONCLUSIONS The prevalence of medication errors is high among health care professionals in Nigeria. Knowledge gaps and practice deficiencies were identified requiring interventions.

Efficacy of Initiating Therapy with Amlodipine and Hydrochlorothiazide or Their Combination in Hypertensive Nigerians

In order to evaluate whether amlodipine or hydrochlorothiazide would be preferable to initiate therapy, 90 untreated hypertensive Nigerians of both genders aged 31–86 years with blood pressure >160/90 and ≤180/120 mm Hg were recruited into a randomized 48-week study. Patients, 30 each in amlodipine, hydrochlorothiazide, and amlodipine–hydrochlorothiazide groups, were treated, respectively, with amlodipine 5 mg for 6 weeks and the dose increased to 10 mg till week 12, after which hydrochlorothiazide 25 mg was added; hydrochlorothiazide 25 mg till week 6, after which amlodipine 5–10 mg was added; and amlodipine 5–10 mg + hydrochlorothiazide 25 mg. Body mass index, blood pressure, heart rate, and 24-hour urine volume were evaluated at baseline and at the end of weeks 1, 3, 6, 12, 24, 36, and 48. The primary efficacy variables were decreased in mean trough sitting diastolic and systolic blood pressure such that blood pressure < 140/90 mm Hg was regarded as normalized. At week 48 in the amlodipine group, 27 patients versus 25 patients in the hydrochlorothiazide group had diastolic blood pressure <90 mm Hg (90% vs. 83.3%; P <.03). In the amlodipine group, 23 patients versus 20 patients in the hydrochlorothiazide group had blood pressure < 140/90 mm Hg (76.7% vs. 66.7%; P <.01). In the amlodipine–hydrochlorothiazide group, 27 patients (90%) and 15 patients (50%) had diastolic blood pressure <90 mm Hg and blood pressure < 140/90 mm Hg, respectively. This study has demonstrated that a regimen of amlodipine to which hydrochlorothiazide is subsequently added provides superior efficacy on blood pressure control when compared with a regimen of hydrochlorothiazide to which amlodipine is subsequently added or with ab initio amlodipine–hydrochlorothiazide combination therapy.

Open evaluation of amlodipine in the monotherapeutic treatment of mild to moderate hypertension in nigerian patients

Abstract The efficacy and tolerability of amlodipine, a new second-generation dihydropyridine calcium channel blocker, as antihypertensive monotherapy was evaluated in an open 12-week study in 24 hypertensive patients. Treatment with amlodipine was started at 5 mg daily after a 2-week washout period and adjusted to 10 mg daily if the patients diastolic blood pressure was >90 mmHg after 2 weeks of therapy. The response rate was 91%, and blood pressure was normalized in 72.7% of patients after 12 weeks of therapy. The blood pressure profiles were similar in the supine, sitting, and standing positions, with a decrease in mean supine blood pressure from 180.7 ± 3.7 mmHg/113.1 ± 1.3 mmHg at baseline to 146.3 ± 2.7 mmHg/88.0 ± 1.2 mmHg at 12 weeks. A slight but significant initial increase in heart rate was observed in all positions during the first week of therapy, but no further increase was seen beyond the first week, even though doses were subsequently increased. Adverse experiences were mild and transient and included frequent micturition, pedal edema, headache, and poor erection. The results suggest that once-daily amlodipine is an effective and well-tolerated monotherapy for the treatment of hypertension.

Amlodipine versus nifedipine in the treatment of mild-to-moderate hypertension in black Africans

Abstract This single-blind, parallel-group, randomized trial compared the efficacy and tolerability of amlodipine with sustained-release nifedipine in 45 black African patients between the ages of 29 and 65 years. Amlodipine and nifedipine were administered after a 2-week washout period at a dose of 5 mg once daily and 20 mg twice daily, respectively. Dose was increased to 10 mg once daily for amlodipine and 40 mg twice daily for nifedipine in patients with diastolic blood pressure >90 mm Hg after 2 weeks. Treatment lasted for 12 weeks. Blood pressure was significantly reduced in both groups by week 12, with normalization rates of 75.0% for amlodipine and 72.2% for nifedipine. There was also a significant increase in heart rate in both groups by week 1 (heart rate in the erect position, +6.2 beats/min and +14.3 beats/min for amlodipine and nifedipine, respectively). No changes were observed in body weight or laboratory variables. Three patients in the nifedipine group withdrew from the study because of adverse effects (headache, two patients; severe palpitations/tachycardia, one patient). Other adverse effects, including pedal edema, frequent micturition, and dizziness, were mild and transient in most cases. Amlodipine and nifedipine have similar antihypertensive effects; amlodipine appeared to be better tolerated.

A profile of adverse effects of antihypertensive medicines in a tertiary care clinic in Nigeria

Background: There has been a dearth of comprehensive data on the profile of adverse reactions to antihypertensive medicines in the Nigerian setting despite increased use. Objective: This study was aimed to characterize the adverse reactions experienced in the homogenously black African population. Methods: The study was carried out at the University of Benin Teaching Hospital, Benin City, Nigeria, in consenting eligible hypertensive patients ≥18 years. Adverse reactions were sought using patients self-report and a medicine-induced symptom checklist. Results: A total of 514 patients (340 females) aged 22–97 years were studied. Thirteen percent, 27.6%, 26.7%, 22.0%, and 10.7% were on 1, 2, 3, 4, and ≥5 medicines, respectively, for control of their blood pressure with the frequency of adverse effects increasing proportionately up to four medicines. Adverse reactions to antihypertensive medicines were reported by a total of 93 (18.1%) patients. Diuretics – 27.9%, calcium channel blockers (CCBs) – 26.8%, and angiotensin-converting enzyme inhibitors (ACEIs) – 26.8% accounted for most of the adverse reactions seen, notably frequent micturition and headaches (CCB); excessive micturition and dizziness (diuretics); dry irritating cough (ACEI). Notable complaints for all patients using the checklist were increased frequency of micturition, reduction in libido, and headaches. The reactions resulted in the discontinuation and substitution of therapy in 49.5% of the patients. Conclusions: The characterization of these reactions in Nigerians requires further studies as frequent micturition reported is still a neglected complaint in antihypertensive therapy.

Pharmacovigilance and the Null Hypothesis

Over the past few years, the media has been replete with criticism of the failure of pharmacovigilance (PV) systems to prevent harm to people. In both the US and Europe this has resulted in calls for more effective PV. Indeed, on both sides of the Atlantic there is a flurry of funded activity to find better data sources, to use better analysis tools and to be more proactive in risk management. It was arguably rofecoxib (Vioxx ) that instigated the activity because of the increased incidence of myocardial infarction. Because heart attack is serious and common, and the drug was very widely used, the public health impact was great and the public outcry loud; the regulators had been much too slow in taking action. Much of the above is summarized beautifully in a review by Greener. Just after the Vioxx issue became public, Edwards wrote ‘‘The Vioxx situation was not a failure of regulation itself, neither was it an issue of data collection, nor of the quality of studies performed. It was and is a complex decision-making/communication challenge in which some improvements are possible. Making wise drug safety decisions is not easy y’’. There was an early signal about that problem, and about 6 months after the drug was launched there were warnings in the product literature. The increase in risk over background was small, even though the absolute numbers affected and the public health impact were large, and a fairly large study was needed to evaluate this. The key question was, and is, who makes the decision to do such a study, when, and who should fund and perform the study.

Impact of comorbidity on adverse drug reaction profile in a cohort of patients treated with Artemisinin combination therapies for uncomplicated malaria in Nigeria

Artemisinin‐based combination antimalarial therapy (ACTs), is still highly effective in uncomplicated falciparum malaria, however, there remain some concerns in relation to its safety and tolerability. Comorbid disease conditions may influence susceptibility to adverse drug reactions (ADRs) as the presence of multiple disease conditions may predisposes patients to ADRs due to the use of many medicines. There is therefore need to assess the impact of comorbidities on the ADR profile of malaria patients treated with ACTs. The study was carried out in health care facilities spread across Nigeria. From the database of over 10,000 patients recruited into an initial cohort, data for 1000 patients with comorbidities was extracted and matched with a control group of 1000 randomly selected patients with no comorbidity. There were 1105 adverse drug reactions in all, of which 66.2% were recorded in patients with comorbidity, and 34% are patients without comorbidity. The mean age of patients with comorbidities was 38.3 ± 17.5 years and 23.8 ± 17.2 for those without comorbidity. Out of the 979 patients with comorbidity, 36% were hypertensive, 2.2% hypertensive‐diabetes, 16.4% peptic ulcer disease, 10.4% HIV/AIDS, 4.4% diabetes and 4.3% were asthmatic. Patients with comorbidity were three times more likely to have adverse drug reaction than those without comorbidity (Odds ration = 2.96; 95% CI = 2.23–3.93). HIV/AIDS and osteoarthritis were significantly associated with development of adverse drug reactions. Probability was <0.0001. Age, weight, and height of patients were also found to be risk factor for development of adverse drug reactions.

Prescription pattern of antimalarial drugs in a Nigerian tertiary institution before and after the 2005 policy

Following a change in the policy for malaria treatment in Nigeria, artemisinin‐based combination therapies (ACTs) were adopted in 2005 as first‐line therapy instead of chloroquine due to reports of resistance. We assessed the pattern of prescription of antimalarial drugs in a tertiary institution before and after the policy change.

Pharmacovigilance Indicators: Desiderata for the Future of Medicine Safety

The thalidomide tragedy highlighted an unacceptable harm and potential risks of taking medicines [1]. This resulted in a global resolve that such a tragedy should never occur again, and all machinery to achieve this was put in place in the more developed countries in a rather systematic manner. This initial and prompt response ultimately resulted in the establishment of the WHO Programme for International Drug Monitoring (PIDM) schemes [2]. The initial focus was on suspected adverse drug reactions however over time the scope broadened to include other medicine-related problem. The occurrences regarding issues on medicinal safety after the thalidomide experience underscore the need for continuous watchfulness. The nomenclature has become more embracing and issues bordering on medicines safety coined “pharmacovigilance.”