4- Thursday Pharmacotherapy News – 7th October

1 – Arginine vasopressin and pathophysiology of COVID-19: An innovative perspective

• In Covid-19, systemic disturbances may progress due to development of cytokine storm and dysregulation of and plasma osmolarility due to high release of pro-inflammatory cytokines and neuro-hormonal disorders.
• Arginine vasopressin (AVP) which is involve in the regulation of body osmotic system, body water content, blood pressure and plasma volume, that are highly disturbed in Covid-19 and linked with poor clinical outcomes.
• Release of AVP from hypothalamus is augmented in Covid-19 due to stress, high pro-inflammatory cytokines, high circulating AngII and inhibition of GABAergic neurons.
• In turn, high AVP level leads to induction of hyponatremia, inflammatory disorders, and development of complications in Covid-19 by activation of NF-κB and NLRP3 inflammasome with release of pro-inflammatory cytokines.
• Therefore, AVP antagonists might be novel potential therapeutic modality in treating Covid-19 through mitigation of AVP-mediated inflammatory disorders and hyponatremia.

Source: ScienceDirect

2 – Factors regulating dynamics of angiotensin-converting enzyme-2 (ACE2), the gateway of SARS-CoV-2: Epigenetic modifications and therapeutic interventions by epidrugs

• Angiotensin-converting enzyme-2 (ACE2) is one of the major components of the renin-angiotensin system (RAS) and participates in the physiological functions of the cardiovascular system and lungs.
• Recent studies identified ACE2 as the receptor for the S-protein of the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and thus acts as the gateway for viral entry into the human body.
• This review is mainly focused on the impact of environmental toxicants, drugs, endocrine disruptors, and hypoxia as controlling parameters for ACE2 expression and its possible modulation by epigenetic changes which are marked by DNA methylation, histone modifications, and micro-RNAs (miRNAs) profile.

Source: ScienceDirect

3 – A Systematic Review of Blinatumomab in the Treatment of Acute Lymphoblastic Leukemia: Engaging an Old Problem With New Solutions

• This study aims to assess the current literature for blinatumomab in the treatment of adult and pediatric B-cell acute lymphoblastic leukemia (ALL).
• Blinatumomab, a first-in-class bispecific T-cell engager monoclonal antibody, facilitates cytotoxic T-cell activation and subsequent eradication of CD19-positive B cells.
• Blinatumomab provides a paradigm-shifting treatment option; however, many questions surrounding optimal patient selection, sequencing, and cost-effectiveness remain.

Source: Sage Journals

4- Evaluation of a Fixed-Dose Regimen of 4-Factor Prothrombin Complex Concentrate for Warfarin Reversal

• ThiFixed-dose (FD) regimens of 4-factor prothrombin complex concentrate (4F-PCC) may be effective for the emergent reversal of warfarin; however, the optimal dosing is unknown.
• The purpose of this study is to report our experience with FD 4F-PCC compared with a historical weight-based dosing cohort for warfarin reversal.
• An FD strategy of 2000 units for warfarin reversal for CNS bleeds or INR ≥6.1 was comparable to weight-based dosing.
• The FD strategy of 1000 units for INR ≤6 achieved target INR less often than weight-based dosing.
• Application of findings suggest that higher doses may be needed to achieve target INR.

Source: SAGE Journals

5 – INR Response to Low-Dose Vitamin K in Warfarin Patients

• Literature suggests that 2 mg of vitamin K intravenously (IV) provides a similar effect as 10 mg to reverse warfarin.
• Doses <5 mg haven’t been studied in depth.
• The objective was to determine the international normalized ratio (INR) reduction effect of ultra low-dose (ULD) IV vitamin K.
• ULD IV vitamin K reversed INR similarly to doses of 1-2 mg without rebound.
• A ULD strategy may be considered in patients requiring more cautious reversal.

Source: SAGE Journals

6 – High- Versus Low-Molecular-Weight Hyaluronic Acid for the Treatment of Rotator Cuff Tendinopathy: A Triple-Blind Randomized Comparative Trial

• Shoulder pain most commonly originates from the tendon structures of the rotator cuff.
• In this study they compared the clinical effects of high- versus low-molecular-weight (LMW) hyaluronic acid for the management of rotator cuff tendinopathy.
• Both medications are effective for the treatment of tendinopathy.
• The benefits last at least for 3 months, and pain alleviation lasts partially for 6 months.
• The shoulder injection of LMW hyaluronate is more tolerable to the patient.
• Therefore, we recommend LMW hyaluronate as the first choice for the management of rotator cuff tendinopathy.

Source: SAGE Journals

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