Ahmed S. Ali

Dilemmas of the causality assessment tools in the diagnosis of adverse drug reactions

Importance: Basic essence of Pharmacovigilance is prevention of ADRs and its precise diagnosis is crucially a primary step, which still remains a challenge among clinicians. Objective: This study is undertaken with the objective to scrutinize and offer a notion of commonly used as well as recently developed methods of causality assessment tools for the diagnosis of adverse drug reactions and discuss their pros and cons. Evidence review: Overall 49 studies were recognized for all assessment methods with five major decisive factors of causality evaluation, all the information regarding reasons allocating causality, the advantages and limitations of the appraisal methods were extracted and scrutinized. Findings: From epidemiological information a past prospect is designed and subsequent possibility merged this background information with a clue in the individual case to crop up with an approximation of causation. Expert judgment is typically based on the decisive factor on which algorithms are based, nevertheless in imprecise manner. The probabilistic methods use the similar principle; however connect probabilities to each measure. Such approaches are quite skeptical and liable to generate cloudy causation results. Causation is quite intricate to ascertain than correlation in Pharmacovigilance due to numerous inherent shortcomings in causality assessment tools. Conclusions and relevance: We suggest that there is a need to develop a high quality assessment tool which can meticulously establish suitable diagnostic criteria for ADRs with universal acceptance to improvise the fundamental aspect of drug safety and evade the impending ADRs with the motive to convert Pharmacovigilance into a state of art.

Characterization of the Antinociceptive Mechanisms of Khat Extract (Catha edulis) in Mice

This study investigated the antinociceptive mechanisms of khat extract (100, 200, and 400 mg/kg, i.p.) in four pain models: two thermic (hot plate, tail-flick) and two chemical (acetic acid, formalin) models. Male mice were pretreated intraperitoneally (i.p.) with the opioid receptor blocker naloxone (5 mg/kg), the cholinergic antagonist atropine (2 mg/kg), the selective α1 blocker prazosin (1 mg/kg), the dopamine D2 antagonist haloperidol (1.5 mg/kg), or the GABAA receptor antagonist, bicuculline (1 mg/kg) 15 minutes prior to i.p. injection of khat extract (400 mg/kg). Khat extract reduced the nociceptive response of mice in the four pain tests. Naloxone significantly inhibited the antinociceptive effect of khat extract in the hot plate, tail-flick, and the first phase of formalin tests. Bicuculline significantly antagonized the antinociceptive effect of khat extract on the hot plate and tail-flick tests. Haloperidol significantly reversed the antinociceptive effect of khat extract on the tail-flick test and the first phase of formalin test. These results provide strong evidence that the antinociceptive activity of khat extract is mediated via opioidergic, GABAergic, and dopaminergic pathways. The mechanism of the antinociceptive action of khat may be linked to the different types of pain generated in animal models.

Detection of adverse drug reactions by medication antidote signals and comparison of their sensitivity with common methods of ADR detection.

Objective To determine the PPVs of selected ten medication antidote signals in recognizing potential ADRs and comparison of their sensitivity with manual chart analysis, and voluntary reporting recognizing the same ADRs. Method The inpatient EMR database of internal medicine department was utilized for a period of one year, adult patients prescribed at least one of the ten signals, were included in the study, recipient patients of antidote signals were assessed for the occurrence of an ADR by Naranjo’s tool of ADR evaluation. PPVs of each antidote signal were verified. Result PPV of Methylprednisolone and Phytonadione was 0.28, Metoclopramide and Potassium Chloride – 0.29, Dextrose 50%, Promethazine, Sodium Polystyrene and Loperamide – 0.30, Protamine and Acetylcysteine – 0.33. In comparison of confirmed ADRs of antidote signals with other methods, Dextrose 50%, Metoclopramide, Sodium Polystyrene, Potassium Chloride, Methylprednisolone and Promethazine seem to be extremely significant (P value > 0.0001), while ADRs of Phytonadione, Protamine, Acetylcysteine and Loperamide were insignificant. Conclusion Antidote medication signals have definitive discerning evaluation value of ADRs over routine methods of ADR detection with a high detection rate with a minimum cost; Their integration with hospital EMR database and routine patient safety surveillance enhances transparency, time-saving and facilitates ADR detection.

Effects of different routes of nicotine administration on gastric morphology and hormonal secretion in rats

What is the central question of this study? Does chronic administration of nicotine by different routes affect gastric hormonal secretions and morphology in rats? What is the main finding and its importance? Chronic nicotine administration increased levels of gastrin, ghrelin and histamine but decreased prostaglandin E2. Nicotine administered orally and by inhalation had a marked negative impact on the histological structure of the gastric mucosa compared with intraperitoneal administration. The negative impact of nicotine administration on gastric structure was associated with an increased concentration of gastrin and decreased prostaglandin E2, which might be the cause of gastric/peptic ulcers in heavy smokers. The increase in ghrelin concentration and its effect following chronic nicotine administration needs further investigation.

Therapeutic Drug Monitoring of Tacrolimus in Saudi Kidney Transplant Patients

Background: Tacrolimus is immunosuppressive agent used for the prevention of rejection in kidney transplant patients, has narrow therapeutic range, and variable pharmacokinetics. Objectives: To identify the optimum Tacrolimus blood trough level for Saudi kidney transplant patients (SKTP). Method: The research population consisted of 100 SKTP at the Armed Forces Hospital in the Southern Region (AFHSR) treated with Tacrolimus and followed-up for a period of 24 months (2012 till 2014). Results: A significant relationship between Tacrolimus trough level and incidence of kidney rejection was remarkably found only after 180 days post-transplantation. During this period, Tacrolimus mean trough level (ng/ml) was 7.4 ± 0.2 in SKTP with no rejection, 5.3 ± 0.7 for those with acute rejection, and 3.8 ± 0.4 for those with chronic rejection. Furthermore, the coefficient of variation (CV%) which reflects fluctuation in Tacrolimus trough level, was obviously high in SKTP with acute rejection in all post-kidney-transplant periods. Conclusion: After 6 month post- kidney transplantation in SKTP, Tacrolimus trough level (

Impact of thymoquinone on cyclosporine A pharmacokinetics and toxicity in rodents

Cyclosporine A (CsA) is an immunosupprsant drug used to prevent graft rejection and in the treatment of several autoimmune diseases. Thyomquinone (TQ), a bioactive component of Nigella sativa, has strong antioxidant properties and has been used in prevention of many toxicities, hence its protective effect and pharmacokinetic interactions with CsA was investigated in this study.

Basic Principles of Therapeutic Drug Monitoring

Therapeutic drug monitoring (TDM) is a tool that can guide the clinician to provide effective and safe drug therapy in the individual patient. It is a team work service; the clinical pharmacist plays an important role to guide the team. TDM involves not only measuring drug concentrations, but also the clinical interpretation of the result. This requires knowledge of the pharmacokinetics, sampling time, drug history; the patients clinical condition and specific laboratory results. The following review summarize the criteria to insure optimal TDM service.