Critical evaluation of the claims made by pharmaceutical companies in drug promotional material in Pakistan

Background: In Pakistan, there is no mechanism to monitor the drug promotional campaign by pharmaceutical industry despite the fact that there is enough evidence that irrational pharmacotherapy is increasingly encountered even in the developed countries due to unethical practices of pharmaceutical promotion. Objectives. To audit the drug promotional claims made by the pharmaceutical companies in Pakistan.Methods: Drug promotional pamphlets and brochures containing claims for the drugs, which were circulated by the pharmaceuticalrepresentatives were collected from 122 general practitioners (GPs) from Karachi and Larkana cities of the Sindh Province. The claims were critically analyzed and audited with the help of currently available evidence in the medical literature.Results: 345 distinct advertisements covering 182 drugs from different manufacturers were critically analyzed for information content. Sixty two out of 345 (18%) of the reviewed advertisements were adjudged to be misleading / unjustifiable, which were again classified as, exaggerated (32%), ambiguous (21%), false (26%), and controversial (21%). The primary source of information (approximately 78%) about the newly launched drugs for the GPs was found to be the pharmaceutical representatives followed by hospital doctors (5%) and colleagues (5%). Furthermore, 110 (90%) GPs were of the view that the drug promotion has definitely an influence on their prescribing pattern.Conclusions: Since GPs in Pakistan rate pharmaceutical companies as their primary source of information regarding drugs, it can be anticipated that inappropriate advertisement claims would lead to irrational prescribing if physicians had no any other information to follow

Effects of changes in pH on the contractility of vascular smooth muscle

Hydrogen ion concentration (H+) is an important regulator of many cellular functions including contractility of the vascular smooth muscle cells. In many physiological and pathological states, changes in pH may have profound effects on the contractility of blood vessels and thus on the peripheral vascular resistance and blood pressure. Therefore, it is necessary to understand the likely outcome of the situations in the conditions, where pH changes are frequent. In this review, the mechanisms involved in the contractile responses of vascular tissues to pH changes are discussed

Reliability of rodent animal models in biomedical research

Despite the discrepancies observed between the data generated from humans and animals, it is a usual practice that the results obtained from animal models are extrapolated on humans. This review stresses that while animal models are essential for the research and development, a critical caution needs to be practiced in interpreting the results. Uncritical reliance on the results of animal experimentation can be dangerously misleading and has resulted in damages to human health in several cases. This review also discusses the role of certain confounding factors in using animal models due to which appropriate precautions need to be taken while deciding to conduct a study using animal models and caution is warranted in extrapolating the data obtained from pre-clinical studies on humans

Acidosis-induced relaxation of human internal mammary artery is due to activation of ATP-sensitive potassium channels

Metabolic acidosis is associated with various clinical situations including diabetes mellitus and renal diseases. The aim of this study was to investigate the effects of acidosis on the resting as well as precontracted human left internal mammary artery. The vessels were obtained from the patients undergoing coronary artery bypass grafting surgery at The Aga Khan University Hospital, Karachi. Left internal mammary artery was cut into rings and isometric tension recording experiments were performed. Decrease in pH of the bathing solution from 7.4 to 6.8 had no effect on the resting tension of left internal mammary artery, whereas, acidic pH markedly relaxed the contractions to 24.8 mM KCl and 300 nM phenylephrine. Interestingly, when the KCl- or phenylephrine-contracted rings were treated with 3 microM glibenclamide; an inhibitor of ATP-sensitive potassium (K(ATP)) channels, the relaxant effect of acidosis was abolished. Similarly, acidosis failed to cause relaxation of 100 nM endothelin-1-induced contraction in Ca2+-free bathing solution or in the presence of a voltage-dependent Ca2+ channel inhibitor, verapamil (10 microM), whereas, endothelin-1-induced contraction was attenuated by acidosis in Ca2+-containing normal solution. From all these data, it is concluded that under the acidic pH conditions, opening of K(ATP) channels occurs; resulting in the hyperpolarization, decrease in Ca2+ influx via voltage-dependent Ca2+ channels and subsequent relaxation of human left internal mammary artery

Reasons of refusal and drop out in a follow up study involving primigravidae in Pakistan

Objective: To determine the reasons underlying the refusals to participate and drop outs from a follow up study involving primigravidae. Design: A descriptive study. Methods: Aga Khan University and Aga Khan Hospital for Women, Karachi, jointly initiated a nested case-control study on primigravidae for determining the predictability of preeclampsia using various biochemical markers in blood. The protocol-eligible study subjects were counseled along with their accompanying family members to participate in the study. All women recruited in this study were followed up throughout their pregnancy till delivery. Results: One thousand six hundred and sixty-five primigravidae were identified as the potential study subjects. Out of which, 1,307 (78.5%) consented and 358 (21.5%) refused to participate in the study. The most common reason underlying the refusal was inability to get permission from the family members (n=84, 34.4%) followed by fear of prick (n=51, 20.9%). For 114 refusals, either the reason was not mentioned by the counseled women (n=60) or the data was missing (n=54). Out of 1,307 women recruited in the research, only 611 (46.7%) women completed the study according to the prescribed protocol. Among the rest, 102 (7.8%) subsequently withdrew from the research, 503 (38.5%) were dropped out, and 91 (7.0%) were lost to follow up. Conclusions: Refusal to participate and drop out from the research program are two significant factors hindering the smooth flow of a study. In Pakistan, the major reason for the refusal by the protocol-eligible pregnant women for participating in a research program is the unwillingness of the family members