Impact of maternal topiramate ingestion on ossification of skull and appendicular bones in rat fetuses.

The skull and appendicular bones are derived from different embryological sources during their development. The impact of prenatal exposure of topiramate on ossification of these bones is not adequately studied. The goal of this study was to assess the ossification patterns of the craniofacial bones and bones of the forelimbs and hindlimbs in 20-day-old rat fetuses after maternal exposure to topiramate at doses equivalent to human therapeutic doses. Three groups of Sprague-Dawley pregnant rats were used: control, topiramate 50mg/kg/day (T50) and topiramate 100mg/kg/day (T100). Topiramate was given by oral gavage from day 6 to day19 of gestation. Ossification was evaluated in the bones of 20 days fetuses after staining with Alizarin red. Results showed a significant reduction in complete ossified centers of the metacarpal, metatarsal and craniofacial bones in topiramate-exposed fetuses at both doses when compared to the control group. Also, a significant decrease in the length of ossified part of the long bones of the forelimbs and hindlimbs in topiramate-exposed fetuses at both doses was noted when compared to the control group. Crown-rump length and fetal weight were significantly decreased in topiramate treated groups compared to the control group. In all examined groups, there was a positive correlation between the crown-rump length and the lengths of humerus and femur. No abnormalities in the ossified bones and no significant changes in their ossification pattern were observed between the treated groups. In conclusion, prenatal administration of topiramate in doses equivalent to human therapeutic doses delayed ossification and development of craniofacial and appendicular bones in rat fetuses and their effects are not dose dependent at doses investigated. The implications of these findings in women who require topiramate therapy in pregnancy merit further evaluation.

Effect of prenatal administration of therapeutic doses of topiramate on ossification of ribs and vertebrae in rat fetuses.

There are few studies that have addressed the effects of prenatal exposure of topiramate on ossification of the bones derived from the paraxial mesoderm. This study aimed to evaluate skeletal ossification of ribs and vertebrae in 20-day-old rat fetuses after maternal exposure to two therapeutic doses of topiramate. Three groups of Sprague-Dawley pregnant rats were used: control, topiramate 50 mg/kg/day and topiramate 100 mg/kg/day treated groups. Topiramate was administered by gavage from day 6-19 of gestation. Fetuses were collected on day 20 by caesarean section. Fetal bones were stained with alizarin red and ossification was assessed. Results showed significant delayed ossification of ribs and vertebrae in topiramate-exposed fetuses at both doses and the effects were not dose dependent. In all examined groups, there was a direct correlation between the fetal weight and the number of complete ossified vertebral centers. Also, there were significant increases in skeletal abnormalities, particularly in ribs in both treated groups when compared to the control group. In conclusion, therapeutic doses of topiramate should be taken cautiously during pregnancy as they lead to fetal growth restriction and increases abnormalities of axial skeleton in rat fetuses.

Pediatric iron preparations for infants in Bahrain: some therapeutic concerns.

BACKGROUND: Infants and children are at a high risk for medication errors. OBJECTIVES: This retrospective study was conducted to determine the type and prevalence of prescribing errors related to pediatric iron preparations prescribed in primary care in Bahrain. METHODS: Prescriptions issued for infants and collected at 20 health center pharmacies for 2 weeks were audited, specifically for errors. RESULTS: Of 2,282 prescriptions dispensed for infants (mean age 9.14 +/- 0.91 months), 159 (7.0%) included an iron preparation. Iron preparations were mostly prescribed (90.6%) with brand names, several of which were neither listed in the primary care drug list nor were available as pediatric dosage forms. 42 (26.4%) prescriptions were issued without specifying the dosage forms, 14 (8.8%) without the duration of therapy and 4 (2.5%) without dosage. Iron dosage was stated as metric volume (ml) and metric weight (mg elemental iron) units in 78.6% and 9.4% of the prescriptions, respectively. The mean elemental iron (+/- SD) prescribed for treating anemia was 4.5 +/- 1.7 mg/kg body weight. A significant difference was observed between physicians and nurses regarding the amount of elemental iron prescribed for treating anemia. CONCLUSIONS: Prescribing of multiple brands of pediatric iron preparations unavailable in the primary care drug list and in pediatric dosage forms, prescribing iron as inconvenient decimal fractions (metric volume units), and omission errors in prescriptions, were common. This may be related to poor communications between the prescribers and the pharmacy services and a lack of information dissemination on newly introduced iron formulations. Moreover, frequent changes in brand availability in primary care may have created confusion for prescribers. The communication between pharmacy services and prescribers should be strengthened, and the procurement of multiple brands should be discouraged. A better management of drug supply and effective policies to minimize prescribing errors are needed in Bahrain.

Gender-based treatment outcomes in diabetic hypertension.

BACKGROUND: In developing countries, gender-based treatment disparities in cardiovascular preventive therapy have received little attention. AIMS: To evaluate the gender-based differences in cardiovascular disease risk profile, drug prescribing pattern, and blood pressure (BP) and glycemic control rates in diabetic hypertensives treated at primary care setting in Bahrain. SETTINGS AND DESIGN: A retrospective study at primary care setting. MATERIALS AND METHODS: An audit of the medical records of 392 diabetic hypertensives (127 men, 265 women). RESULTS: BP and glycemic targets were achieved in < 10% and < 13% of diabetic hypertensives, respectively. Angiotensin converting enzyme inhibitors monotherapy was more often prescribed in males. Apart from this, no significant differences in prescribing pattern were observed between male and female diabetic hypertensives treated with either antihypertensive mono or multidrug therapies. With the exception of insulin which was more often prescribed to females, a similar prescribing pattern and rank order of antidiabetics, either as monotherapy or combinations, was observed in both genders. The majority of diabetic hypertensives were at high cardiovascular risk. The body mass index and total cholesterol level were greater in females. Prescribing lipid-lowering drugs and aspirin were suboptimal; aspirin was more often prescribed to males. There was no gender-based difference with regard to the use of lipid-lowering drugs. CONCLUSIONS: BP and glycemic controls were suboptimal in both male and female diabetic hypertensives treated by primary care physicians. Cardiovascular disease preventive strategies have received little attention regardless of gender or other risk factors. Gender-based treatment inequities also need to be addressed.

Prescription writing skills of residents in a family practice residency programme in Bahrain.

PURPOSE OF THE STUDY: To evaluate the prescription writing skill of final year residents in a family practice residency programme (FPRP) in Bahrain, and to compare skill of residents who have graduated from medical schools with problem based learning (PBL) versus traditional (non-PBL) curricula. STUDY DESIGN: Prescriptions issued by the residents were prospectively collected for two consecutive cohorts in May 2004 and May 2005. Prescription errors were classified as errors of omission (minor and major), commission (incorrect information) and integration (drug-drug interactions). RESULTS: In 69.6% of medications with major omission errors, dosage form (39.4%) and length of treatment (18.5%) were not specified. In 24.7% of medications with commission errors, dosing frequency (19.9%) and incorrect strength/dose (2.2%) were the most common errors. Integration errors comprised 5.7% of all prescribing errors. No significant differences were observed between PBL and non-PBL graduates with regard to the total number of prescriptions with errors, drugs per prescription, polypharmacy, and the total number of drugs with errors. The proportion of prescriptions with a potential for drug-drug interactions was comparable between PBL and non-PBL graduates. PBL graduates prescribed medications using brand names at a rate greater than non-PBL, whereas non-PBL graduates prescribed medications on inappropriate "as required" basis, and injections at a rate greater than PBL residents. CONCLUSIONS: Prescription writing skill of the final year residents in an FPRP programme was suboptimal for both PBL and non-PBL graduates. Integration of prescription writing skill and a rational pharmacotherapeutic programme into the FPRP curriculum is recommended.

Influence of medical training on self-medication by students.

OBJECTIVE: To examine the influence of medical training on the knowledge, attitude and practice of self-medication by medical students. SUBJECTS AND METHODS: This was a cross-sectional, descriptive study. A self-developed, pre-validated questionnaire containing open-ended and close-ended items was used for data collection. Medical students in the 2nd and 4th year of the medical course at the Arabian Gulf University Bahrain filled in the questionnaire anonymously. Data were analyzed using SPSS and results expressed as counts and percentages. 2-tailed Chi2-test was applied and p < 0.05 was considered significant. RESULTS: The respondents (n = 141) had a mean age of 19.94 A+/- 1.21 years. Overall, they had a fair knowledge about appropriate self-medication but knowledge of the benefits and risks of self-medication was adequate. Self-medication was perceived to be time-saving, providing quick relief in common illnesses, a learning experience, economical, and convenient. Among the perceived disadvantages were adverse drug reactions, inappropriate drug use, and the risk of making a wrong diagnosis. Majority of the respondents had a positive attitude favoring self-medication and read the package insert. The practice of self-medication was common and often inappropriate. The commonest indications for self-medication were cough, cold and sore throat (63.2% in Year 2) and headache (78.3% in Year 4). Mild illness, previous experience, and lack of time were the most frequent reasons for resorting to self-medication. Analgesics were the commonest drugs used, and drugs were mostly obtained from private pharmacies. Students of Year 4 had better knowledge about appropriate self-medication (58.7% versus 35.8%, p = 0.02), had greater awareness of the risks of self-medication and would discourage others from practicing self-medication (58.7% versus 40.4%, p = 0.04). They had a more confident attitude (54.3% versus 35.1%, p = 0.03) and a smaller number of them would seek a prescription (34.8% versus 54.3%, p = 0.03). They practiced self-medication more often (73.3% versus 52.6%, p = 0.02) and more appropriately (58.7% versus 35.8%, p = 0.02). CONCLUSION: This cross-sectional study shows that senior medical students tend to have greater knowledge of appropriate self-medication, have a more confident as well as concerned attitude towards self-medication, and tend to practice self-medication more often and appropriately.

Health care providers' perceptions of the problems and causes of irrational use of drugs in two Middle East countries.

It is now evident that both developed and developing countries are experiencing many aspects of inappropriate use of drugs in their health care facilities. This is the first study in the region performed to examine the most common problems of irrational use of drugs and their causes in two Middle East countries--Jordan and Syria. Ninety senior participants from Jordan (50-15 physicians and 35 pharmacists) and Syria (40-12 physicians and 28 pharmacists) were enrolled in this study. The participants were asked to fill two questionnaires that deal with the problems and causes of irrational use of drugs in their country. Additionally, the participants were asked to perform a prescription analysis using WHO prescribing indicators on 40 prescriptions taken randomly from a comprehensive health centre in their country. The main drug use problems identified in the two countries were almost the same, but they vary in the percentage of occurrence and include excessive use of antibiotics and antidiarrhoeals, overprescribing of nonsteroidal anti-inflammatory drugs, prescribing by tradename, excessive use of antibiotics to treat minor upper respiratory infections and self-medication by the public. The main causes of irrational use of drugs were poor medical records, lack of patient education about illnesses and drugs, no family doctor system, lack of standard treatment guidelines and lack of continuing medical education for doctors and pharmacists. The results of this study are important for decision-makers to utilise when putting policies and strategies to improve the use of drugs in both countries.

Pharmacoepidemiology of antihypertensive drugs in primary care setting of Bahrain between 1998 and 2000.

PURPOSE: To compare pattern of antihypertensive drug utilization in 1998 with 2000 following the: (a) publication of 1999 World Health Organization/International Society of Hypertension (WHO/ISH) guidelines for drug management of hypertension; and (b) introducing new antihypertensives to the essential drug list, in primary care, Bahrain. METHODS: Retrospective prescription-based survey carried out in seven out of 20 primary care health centers in Bahrain. A total of 9272 patients comprising 6543 with uncomplicated hypertension and 2729 with diabetic hypertension were studied. RESULTS: Between 1998 and 2000, the prescription rate of beta-blockers and methyldopa significantly declined (p < 0.0001) while the rate of angiotensin converting enzyme (ACE) inhibitors and calcium channel blockers (CCBs) increased (p < 0.0001) in uncomplicated hypertension. However, in diabetic hypertension there was a non-significant decline in utilization of beta-blockers, CCBs, methyldopa, and diuretics whereas a significant increase in prescribing of ACE inhibitors (p < 0.0001). Inclusion of Perindopril into the essential drug list resulted in an overall increase in utilization of ACE inhibitors: use of captopril and enalapril declined while lisinopril and perindopril increased. Substitution of immediate-release (IR) indapamide by sustained-release (SR) formulation did not change the overall utilization of diuretics; however, intra-class changes were evident with a significant decline in use of thiazide diuretics and concomitant increase in use of SR indapamide by 2000. CONCLUSIONS: The antihypertensive prescribing pattern is influenced by WHO/ISH guidelines as well as by introduction of new antihypertensives to primary care essential drug list in primary care. The choice of a drug is also influenced by presence of co-morbidity with diabetes mellitus.

Assessing prescription writing skills of pre-clerkship medical students in a problem-based learning curriculum.

OBJECTIVE: To audit the acquisition of prescribing skills of pre-clerkship medical students in a problem-based learning (PBL) curriculum that incorporates a prescribing program. MATERIAL AND METHODS: Student performance in pharmacotherapy stations included in six out of eight end-of-unit-objective structured practical examinations (OSPE) was evaluated using a rating checklist. RESULTS: Prescription writing skills of 539 students (66.2% female and 33.8% male) were appraised. With the exception of refill element, the other physician-related components including prescriber's identity, date of prescription order, patient's identity, the symbol Rx "Take Thou", and prescriber's signature were written by 96.1% of the students (95% confidence interval (CI) 94.1 - 97.5). However, the drug-related components such as the appropriateness of drug(s) selected, strength, dosage form, quantity to be dispensed and directions for use were written satisfactorily by 50.2% of the students (95% CI 46.0 - 54.4). With respect to prescribing skills, the mean total score of Year 4 students did not significantly differ from that of Year 2 (69.4 (CI 65.7 - 73.1) vs. 66.3 (CI 62.7 to 69.9); p = 0.237). However, the mean scores of individual drug-related components such as appropriateness of drug(s) selected, dosage form, and direction for use were significantly higher in Year 4 than that of Year 2 students (p < 0.05). Of 381 rationally prescribed drugs, 81.1% were written with generic names. CONCLUSION: This study revealed that the students acquire prescribing skills to a limited extent during the pre-clerkship phase in a PBL program. Prescribing errors and deficits were found to be mainly associated with drug-related components. Further training and assessment of prescribing skills during the clerkship and internship period are needed to achieve mastery of this skill as a terminal competency of graduating physicians.

An evaluation of prescribing errors in primary care in Bahrain.

OBJECTIVES: Prescribing errors are preventable and are considered an important target for improving healthcare. The aim of this study was to identify prescribing errors and their determinants in a primary care setting. METHODS: Prescriptions with errors were collected on a daily basis by the pharmacy staff during the first two weeks of September 2003 in 18 out of 20 primary care health centers in Bahrain. Prescribing errors were classified as omission (minor and major), commission and integration errors. RESULTS: Out of 77,511 prescriptions dispensed, 5,959 (7.7%) were identified to contain errors. The frequency of prescribed medication items in 5,959 prescriptions was 16,091. Of these medications, 13,630 (84.7%) were with errors and only 13.2% were written using generic names. Minor errors of omission such as absence of physician's stamp (34.4%), date (9.8%), and information about patients' address (3.8%), age (3.5%) and sex (0.5%) were not specified. Major errors of omission accounted for 93.6% and were as follows: strength/dose (31.0%), length of therapy/ quantity (29.5%), dosage form (19.7%), and frequency of dosing (13.4%). In 6.3% errors of commission (incorrect information) the most common was strength/dose (3.3%), followed by frequency of dosing (2.6%), dosage form (0.3%), and length of therapy/quantity (0.1%). Major errors of omission associated with topical preparations were significantly higher than those with systemic preparations. However, prescriptions with systemic preparations had a higher rate of commission errors. Significant differences in errors were found in prescriptions ordered by family physicians and general practitioners. In 9.2% of prescriptions with errors, potential drug-drug interactions were expected. CONCLUSIONS: This nationwide survey revealed that in primary care, a considerable proportion of prescriptions contained errors. Strategies to minimize medication errors by improving the prescribing skills, adherence to essential drugs list, and use of National Formulary are needed.

Comparison of the quality of diabetes care in primary care diabetic clinics and general practice clinics.

OBJECTIVES: To compare the quality of care provided to diabetic hypertensive patients by diabetic clinics versus general practice clinics (GP-clinics) in a primary care setting. MATERIALS AND METHODS: A retrospective analysis of medical records of patients from six primary care centres in Bahrain. RESULTS: The recommended target blood pressure <130/85 mmHg was achieved in 6.8 and 10%, and glycated haemoglobin <7% was attained in 14.8 and 11% of patients attending diabetic clinics (n=177) and GP-clinics (n=180), respectively. Although complementary antihypertensive combinations were prescribed at a rate less than that recommended in guidelines, combinations were significantly more often prescribed for patients attending the GP-clinics (46.7% [95% CI 39.4-53.9] versus 33.4% [CI 26.8-40.6]; p=0.01). The prescribing pattern and rank-order of antihypertensive and oral hypoglycaemic agents prescribed, either as monotherapy or in combinations, were similar in both clinics. The majority of diabetic hypertensive patients attending diabetic clinics or GP-clinics were at high cardiovascular risk. Anthropometric characteristics were recorded consistently in patients attending diabetic clinics. Laboratory investigations were extensively utilized for monitoring patients attending diabetic clinics. CONCLUSIONS: In primary care, in both diabetic clinics and GP-clinics, hypertension and diabetes were inadequately controlled, with no difference between the two settings. An integrated approach involving diabetic clinics managed by primary care physicians and nurses trained in diabetes management, and supported by national guidelines, is needed.

Antihypertensive drug-associated sexual dysfunction: a prescription analysis-based study.

PURPOSE: To determine whether primary care physicians take into consideration age, gender and diabetes mellitus as risk factors for sexual dysfunction (SD) when prescribing antihypertensives. METHODS: A prescribing survey on hyperternsive patients with or without diabetes mellitus in primary care setting of Bahrain was carried out. RESULTS: In 5301 hypertensive patients, we found that a beta-blocker (atenolol) was the most commonly prescribed drug and was significantly more often prescribed for young male hypertensives (< 45 years). A relatively high dose of atenolol (100 mg/d) was extensively used as both mono- and combination-therapies. With the exception of middle-aged hypertensives (45-64 years) and elderly diabetic-hypertensives (> or = 65 years), no significant age- and gender-related differences were observed regarding the prescription of thiazide diuretics. A significant trend of prescribing methyldopa in females as monotherapy was evident. Angiotensin converting enzyme (ACE) inhibitors, the second most commonly prescribed drugs, were significantly more often prescribed for young, middle-aged hypertensive males and for middle-aged diabetic-hypertensive males. beta-blocker/diuretic combination was prescribed least for the young and elderly hypertensive males. However, prescription of an ACE inhibitor with either a diuretic or a calcium channel blocker (CCBs) was less frequent and lacked gender-related differences. CONCLUSIONS: We infer that antihypertensive-induced SD received little attention as was evident from: (a) over-prescription of relatively high dose of beta-blockers to young hypertensive males; (b) lack of gender- and age-related difference regarding the type and dose of diuretics prescribed; (c) underutilization of effective and complementary combinations expected to cause least impact on sexual function, such as ACE inhibitors with either a diuretic or with a CCB; and (d) a relative lack of discrimination while selecting antihypertensive drugs, particularly as monotherapy between hypertensive versus diabetic-hypertensive patients. With the exception of ACE inhibitors alone and combination of diuretic/beta-blocker, the choice of antihypertensives did not conform to international guidelines. In view of drug-induced SD adversely influencing the quality of life and thereby drug-compliance, interventions aimed at improving physicians' awareness should be attempted.

Extent of use of immediate-release formulations of calcium channel blockers as antihypertensive monotherapy by primary care physicians: multicentric study from Bahrain.

BACKGROUND: The issue of cardiovascular safety of calcium channel blockers (CCBs) has been widely debated in view of reflex increase in sympathetic activity induced by immediate release (IR) / short acting formulations. It is generally agreed that such CCBs should not be used alone in the management of hypertension. AIMS: We have determined the extent to which primary care physicians prescribe CCBs as monotherapy, especially the immediate release formulations, in the management of uncomplicated hypertension and diabetic hypertension - with an emphasis upon the age of the patients. SETTING, DESIGN AND METHODS: A retrospective prescription-based study was carried out in seven out of 18 Health Centres in Bahrain. The study involved a registered population of 229,300 representing 46% of registered individuals, and 35 physicians representing 43% of all primary care physicians. The data was collected between November 1998 and January 1999 using chronic dispensing cards. RESULTS: In all categories CCBs were the third commonly prescribed antihypertensive as monotherapy, with a prescription rate of 11.1% in uncomplicated hypertension, 18% in diabetic hypertension and 20.1% in elderly patients above 65 years of age. Nifedipine formulations were the most extensively prescribed CCBs. Almost half of the CCB-treated patients were on IR-nifedipine, whereas IR-diltiazem and IR-verapamil, and amlodipine were infrequently prescribed. CONCLUSION: Prescription of IR-formulations of CCBs as monotherapy by primary care physicians does not conform with recommended guidelines. In view of concerns about the safety of such practice, measures to change the prescribing pattern are required.

Prescribing patterns and therapeutic implications for diabetic hypertension in Bahrain.

OBJECTIVE: To determine drug prescription patterns and the extent of conformity with World Health Organization/international Society of Hypertension (WHO/ISH) guidelines in diabetic hypertension. DESIGN: Retrospective prescription-based survey. SETTING: Seven primary-care health centers, comprising approximately one-third of primary-care health centers in Bahrain. PATIENTS: Patients with type 2 diabetes and hypertension. MAIN OUTCOME MEASURE: The prescribing pattern of antihypertensive and antidiabetic drugs. RESULTS: Among a study sample of 1,463 patients with type 2 diabetes and hypertension, antidiabetic agents were prescribed as monotherapy in the following descending order: glyburide, gliclazide, insulin, and metformin. As combinations, sulfonylureas plus metformin was most popular, followed by metformin plus insulin, and sulfonylureas plus insulin. Sulfonylurea and metformin with insulin was rarely used. There was no significant difference in prescribing of glyburide and metformin between the elderly and young middle-aged diabetic patients; many patients older than 65 years were treated with a beta-blocker along with a long-acting sulfonylurea. Both as monotherapy and in overall use, beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, and calcium-channel blockers were most often prescribed. Among 35.5% patients treated with antihypertensive combinations, various two- and three-drug combinations of beta-blockers, ACE inhibitors, calcium-channel blockers, and diuretics were often used. The proportion of patients taking atenolol 100 mg/d was higher with combination regimens. Hydrochlorothiazide 25 mg or equivalent thiazide diuretics were extensively used. CONCLUSIONS: The prescribing pattern of antihypertensives in diabetic hypertension differs in many instances from WHO/ISH guidelines, especially regarding the choice of antihypertensive drugs and their combinations. The appropriateness of antidiabetic drug choice is questionable in relation to the antihypertensive used.

Neurobiological correlates of panic disorder and agoraphobia.

Panic Disorder and agoraphobia offer considerable diagnostic and management challenges, particularly in general practice. We describe a typical case of panic disorder in a young adult. The recent advances in our understanding of brain functions can be used to explain to a certain extent the biologic basis of panic disorder. A hypothetical model integrating current views on panic disorder and agoraphobia has been proposed. The management principles including the role of cognitive therapy and pharmacotherapy have been discussed.

Antihypertensive drug prescription trends at the primary health care centres in Bahrain.

PURPOSE: To determine the antihypertensive drug prescribing pattern by primary care physicians in patients with uncomplicated essential hypertension; to identify whether such pattern of prescription is appropriate and in accordance with international guidelines for pharmacotherapy of hypertension; and to estimate the impact of such prescriptions on cost of treatment. METHODS: A prescription-based survey among patients with uncomplicated essential hypertension was conducted in seven out of a total of 18 health centres in Bahrain. The relevant data for our study was collected using cards, designed for chronically-ill patients. RESULTS: A total of 1019 male and 1395 female (62.9%) out of 3838 of the study population were on monotherapy, whereas 596 male and 828 female (37.1%) were on antihypertensive combination therapy. Among the monotherapy category, the various antihypertensive drugs used were as follows: beta-blockers (58.8%), angiotensin converting enzyme (ACE) inhibitors (14.2%), calcium channel blockers (11.1%), diuretics (8.1%) and alpha-methyldopa (7.0%). With respect to overall utilization pattern, beta-blockers were the most frequently prescribed (65.5%), diuretics ranked second (27.4%), followed by ACE inhibitors (20.6%), calcium channel blockers (19.9%) and alpha-methyldopa (8.5%). Within each class of antihypertensives used, the most frequently used individual agents were as follows: (a) among beta-blockers 97.7% used atenolol; (b) among the diuretics, indapamide (35.4%), hydrochlorothiazide (HCTZ) (32.7%), HCTZ in combination with triamterene (25.7%), and chlorthalidone (4.6%); (c) among the ACE inhibitors, captopril (44.9%), enalapril (29.7%), and lisinopril (19.0%); (d) among the calcium channel blockers, nifedipine (98.2%). Significant age- and gender-related differences in prescribing patterns were seen. Short-acting nifedipine monotherapy was inappropriately prescribed in a significant number of patients above the age of 50 years. ACE inhibitors accounted for approximately two-thirds of the total antihypertensive drug expenditure, although these drugs represent only one-fifth of overall antihypertensives used. There is a trend towards excessive use of expensive thiazide-like diuretics such as indapamide which seems to be unjustifiable practice, particularly in a study population free from diabetic hypertensive patients. CONCLUSIONS: The general pattern of antihypertensive utilization appears to be in accordance with the guidelines of WHO and the Joint National Committee issued in the 1990s. The trends of prescribing of antihypertensives were in favour of conventional ones such as the beta blockers and diuretics, and the introduction of newer classes of antihypertensives had a generally minimal impact on the prescribing profile. Almost two-thirds of the patients were treated with monotherapy. A disproportionately large percentage of antihypertensive drug cost was due to overt use of ACE inhibitors, and indapamide, instead of thiazide diuretics. The use of short-acting calcium channel blockers especially in the elderly is unjustifiable.

Rational pharmacotherapy of hypertension in the elderly: analysis of the choice and dosage of drugs.

OBJECTIVES: To determine in older people with uncomplicated hypertension: (a) the pattern of prescribing of antihypertensives; (b) the extent of physicians' adherence to recommendations on dosage for antihypertensive combinations; (c) whether prescribing practice conforms with recommended therapeutic guidelines; and (d) the frequency of prescribing of other drugs which have the potential to alter the efficacy of antihypertensive agents. METHODS: A survey of prescribing in older patients with uncomplicated hypertension in primary care setting of Bahrain was conducted. RESULTS: Of the 432 (56.5%) patients on monotherapy, 192 (44.4%) were treated with beta-blockers, 87 (20.1%) with calcium channel blockers (CCBs), 53 (12.3%) with alpha-methyldopa, 47 (10.9%) with diuretics, 46 (10.6%) with angiotensin converting enzyme (ACE) inhibitors, and 7 (1.6%) with hydralazine. Of the 1146 patients on mono- or combination therapies, 434 (56.8%) were treated with beta-blockers, 244 (31.9%) with diuretics, 211 (27.6%) with CCBs, 139 (18.2%) with ACE inhibitors, 103 (13.5%) with alpha-methyldopa 8 (1.0%) with brinerdine and 7 (0.9%) with hydralazine. In the 332 (43.5%) patients on combination therapy, 15 different two- and three-antihypertensive drug combinations were prescribed: a diuretic with a beta-blocker (37.2%) and a beta-blocker with either a CCB (20.9%) or an ACE inhibitor (12.4%) were the most popular two-drug regimens. The most commonly prescribed triple drug regimens were a diuretic and a beta-blocker plus either a CCB (26.1%) or an ACE inhibitor (17.4%) and diuretic plus an ACE inhibitor and a CCB (15.2%). Daily dosage of beta-blockers, ACE inhibitors and alpha-methyldopa were somewhat high in a considerable proportion of patients on both mono- and combined therapies. A substantial proportion (9.7%) of patients on monotherapy were treated with immediate release nifedipine. CONCLUSION: The pharmacotherapy of hypertension in elderly patients was found in some instances not to conform to recommended guidelines. For certain classes of antihypertensive agent such as beta-blockers, ACE inhibitors and alpha-methyldopa, neither the principles of geriatric pharmacology nor of antihypertensive combination therapy, and in particular, the need to reduce daily dosage, were followed. The use of immediate release nifedipine in the elderly is irrational, and instead, the use of long-acting dihydropyridine CCBs should be considered. The results of long-term randomized clinical trials published during the last decade have had a minimal impact on clinical practice of primary care physicians in Bahrain.

Patterns of utilization of antihypertensive drug combinations in Bahrain: do they conform with international guidelines?

OBJECTIVES: To explore the prescribing pattern and rationale of antihypertensive combination drug therapy at the level of primary health care centers; and to analyze the extent of physicians' adherence to dosage range of antihypertensives in combination regimens as recommended by Guidelines Subcommittee of WHO/ISH 1999. SUBJECTS, MATERIAL AND METHODS: A prescribing survey of antihypertensive combination regimens among patients with uncomplicated essential hypertension was conducted in 7 out of a total of 18 health centers in Bahrain. The relevant data for our study was collected using cards designed for chronically ill patients. RESULTS: A total of 2414 hypertensive patients (62.9%), of a 3838 study population, were on monotherapy, whereas 1414 (37.1%) were on antihypertensive combination therapy. Among those who were treated with drug combinations, 85.1% (n = 1212) received two-drug, 14.2% (n = 202) received three-drug and four- and five-drug regimens were used by 0.6% and 0.07%, respectively. Prescription analysis revealed that 17 different two- and three-antihypertensive drug combinations were prescribed for each category. The four major two-drug regimens were ranked in the following order: a beta-blocker with a diuretic (40.4%) used more frequently in females than in males (p < 0.0001), a beta-blocker with a calcium channel blocker (19.7%), a beta-blocker with an ACE inhibitor (12.8%) and a diuretic with an ACE inhibitor (7.3%) - used more frequently in males than in females (p = 0.001, 0.01, and 0.028, respectively). The most frequently prescribed three-drug regimens were diuretic and a beta-blocker plus either an ACE inhibitor (30.7%) or a calcium channel blocker (22.3%), beta-blocker plus an ACE inhibitor and a calcium channel blocker (16.3%), and a diuretic plus an ACE inhibitor and a calcium channel blocker (11.4%). There was no gender-related difference among triple-drug regimens. There was a trend towards using high doses of the beta-blocker atenolol, ACE inhibitors and methyldopa. CONCLUSION: The prescribing patterns of some practising physicians were analyzed in terms of conformity with guidelines of combination of drugs and dosages. The use of antihypertensive combination therapy and the doses of individual drugs in combination regimens seem to be partly non-compliant with guidelines issued by WHO recommendations; this is illustrated by excessive prescription of some irrational combinations, as well as limited prescription of some rational combinations. In addition, a tendency to use high doses of certain classes of antihypertensive combinations was observed.

A preliminary observation on in vitro inhibitory effect of cyclosporin-A upon growth of Leishmania tropica promastigotes.

Cyclosporin-A, an immunomodulatory drug was assessed for its leishmanicidal activity in vitro. A Sudanese strain of L. tropica has been used in this study. The results obtained suggested a weak leishmanicidal action of this drug on L. tropica promastigotes.