Basic essence of Pharmacovigilance is prevention of ADRs and its precise diagnosis is crucially a primary step, which still remains a challenge among clinicians. 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. 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. 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. 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.

COVID-19 is a pandemic viral pneumonia caused by β-coronavirus SARS-CoV-2. It is associated with many complications including extreme systemic inflammatory response which eventually causes acute respiratory distress syndrome (ARDS), hypercoagulability, cytokine storm, failure of vital organs, and a high incidence of death. Bacterial secondary infec

Valproic acid (VPA) has toxic metabolites that can elevate oxidative stress markers, and the hepatotoxicity of VPA has been reported. Coenzyme Q10 (CoQ10) is one of the most widely used antioxidants. The effect of CoQ10 on epileptogenesis and VPA hepatotoxicity were examined. Rats were randomly divided into five groups: the control group received 0.5% methylcellulose by oral gavages daily and saline by intraperitoneal injection three times weekly. The PTZ group received 1% methylcellulose by gavages daily and 30 mg/kg PTZ by intraperitoneal injection three times weekly. The valproic acid group received 500 mg/kg valproic acid by gavage and 30 mg/kg PTZ, as above. The CoQ10 group received 200 mg/kg CoQ10 by gavages daily and 30 mg/kg PTZ, as above. The Valproic acid + CoQ10 group received valproic acid and CoQ10, as above. Results: CoQ10 exhibited anticonvulsant activity and potentiated the anticonvulsant effect of VPA. CoQ10 combined with VPA induced a more significant reduction in oxidative stress and improved the histopathological changes in the brain and liver compared to VPA treatment. In addition, CoQ10 reduced the level of toxic VPA metabolites. These findings suggest that the co-administration of CoQ10 with VPA in epilepsy might have therapeutic potential by increasing antiepileptic activity and reducing the hepatotoxicity of VPA.

Background: The kidneys are considered one of the most susceptible organs for adverse drug effects, particularly in post-transplant conditions. Tacrolimus (FK506), a calcineurin inhibitor immunosuppressant, is an essential component in the transplantation regimen. Despite that, nephrotoxicity is a severe drawback for its chronic utilization, where oxidative stress might be implicated. Kaempferol (KMF) is a natural flavonoid that has many adaptable biological activities, including antioxidant action. Objective: Exploring the KMF protective effect on FK506-induced nephrotoxicity and the underlying role of calcineurin B1. Methods: Twenty-four male albino-Wistar rats were randomly divided into three equal groups. The control group received solvents: propylene glycol, i.p. and 0.5% carboxymethyl cellulose, PO; FK506 group was injected with FK506 (0.6 mg/kg, i.p.), and FK506+KMF group was given FK506 (0.6 mg/kg, i.p.) and KMF (10 mg/kg, PO). The treatment regimen for all groups was once daily for 30 days. ELISA technique applied for measuring FK506 trough level and nephrotoxicity biomarkers in serum (cystatin C and urea) on days 15 and 30, and in kidney tissue homogenate (MDA and calcineurin B1) on day 30. Results: In FK506-treated rats, the FK506 trough level was 7.84 ± 1.31 ug/l on day 15 and 9.54 ± 1.45 ug/l on day 30. FK506 use has significantly (P< 0.01) increased biomarkers levels of cystatin C (325% and 477%), urea (177% and 245%), MDA (1253%), except calcineurin B1 that has decreased (97%). The KMF combination has resulted in a significant reduction in the FK506 trough level by day 30 (6.79 ± 1.35 ug/l, P< 0.01). KMF has significantly ameliorated the levels of cystatin C (46% and 73%, P< 0.001), urea (38% and 68%, P< 0.001), MDA (75%, P< 0.001), and calcineurin B1 (1833%, P< 0.05). Conclusion: Oxidative stress and calcineurin B1 are contributing factors in FK506-induced nephrotoxicity. Hence, inhibition of calcineurin enzyme is not limited to the immune cells. KMF could be a novel nephroprotective antioxidant.

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). 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 (1mg/Kg), the dopamine D2 antagonist haloperidol (1.5 mg/Kg), or the GABAA receptor antagonist, bicuculline (1mg/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. Keywords: Khat (Catha edulis), Hot plate, formalin, Tail flick, Opioidergic, dopaminergic, GABAergic .

A novel corona virus SARS-CoV-2 has led to an outbreak of the highly infectious pandemic COVID-19 complicated viral pneumonia. Patients with risk factors frequently develop secondary infections where the role of appropriate antibiotics is mandatory. However, the efforts of drug repurposing lead to recognizing the role of certain antibiotics beyond the management of infection. The current review provided the detailed antiviral, immunomodulatory effect, unique pharmacokinetic profile of two antibiotics namely azithromycin (AZ) and doxycycline (DOX). It summarizes current clinical trials and concerns regarding safety issues of these drugs. Azithromycin (AZ) has amazing lung tissue access, wide range antibacterial efficacy, conceivable antiviral action against COVID-19. It also showed efficacy when combined with other antiviral drugs in limited clinical trials, but many clinicians raise concerns regarding cardiovascular risk in susceptible patients. DOX has a considerable role in the management of pneumonia, it has some advantages including cardiac safety, very good access to lung tissue, potential antiviral, and immunomodulation impact by several mechanisms. The pharmacological profiles of both drugs are heightening considering these medications for further studies in the management of COVID-19.