Evaluation of the effect of various endodontic irrigants, medicaments and chemical quenching reversal agents on dentine fluorescence

There is an increased use of oral anticoagulants for the prevention of venous and arterial thrombosis. Vitamin-K antagonists have been used for decades as the main oral anticoagulants but they have the draback a complex therapeutic management, slow onset of action and by a different oral intake caused by dietary vitamin K intake. New non-vitamin K antagonist oral anticoagulants (NOACs) have been developed to overcome the limitations of warfarin. Their management is easier as it requires a fixed daily dose without coagulation monitoring. Although their therapeutic profile is safe, proper attention should be paid in case of unexpected need for the reversal of their coagulation effect and in case a patient needs to have a scheduled surgery. For non-acute cardiac surgery, discontinuation of NOACs should start at least 48 hours prior surgery. Intracranial bleedings associated with NOACs are less dangerous comparing to those warfarin-induced. NOACs need to be stopped ≥24 hours in case of elective surgery for low bleeding-risk procedures and ≥48 hours for high bleeding-risk surgery in patients with normal renal function and 72 hours in case of reduced CrCl < 80. The therapy with NOACs should be resumed from 48 to 72 hours after the procedure depending on the perceived bleeding, type of surgery and thrombotic risks. There are some available NOAC reversal agents acting within 5 to 20 minutes. In case of lack of reversal agent, adequate diuresis, renal replacement therapy and activated charcoal in case of recent ingestion should be considered.

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A Review on the Use of Reversal Agents of Direct Oral Anticogulant Drugs in Case of Gastrointestinal Bleeding

Reviews on Recent Clinical Trials ◽

10.2174/1574887115666200624193938 ◽

2020 ◽

Vol 15 ◽

Author(s):

Veronica Ojetti ◽

Angela Saviano ◽

Mattia Brigida ◽

Luisa Saviano ◽

Alessio Migneco ◽

...

Keyword(s):

Gastrointestinal Bleeding ◽

Major Bleeding ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Medical Emergency ◽

Management Approach ◽

Emergency Setting ◽

Reversal Agents ◽

Life Threatening ◽

Andexanet Alfa

Background : Major bleeding is a life-threatening condition and a medical emergency with high mortality risk. It is often the complication of anticoagulant’s intake. Anticoagulants are commonly used for the prevention and the treatment of thrombotic events. The standard therapy with vitamin K antagonist (warfarin) has been frequently replaced by direct oral anticoagulants (DOACs). The latter agents (rivaroxaban, apixaban, edoxaban, dabigatran, betrixaban) showed a better efficacy and safety compared to standard warfarin treatment and they are recommended for the reduction of ischemic stroke. Literature data reported a high risk of gastrointestinal bleeding with DOACs, in particular with dabigatran and rivaroxaban. In case of life-threatening gastrointestinal bleeding, these patients could benefit from the use of reversal agents. Methods: We performed an electronic search on PUBMED of the literature concerning reversal agents for DOACs and gastrointestinal bleeding in the Emergency Department from 2004 to 2020. AIM: This review summarizes the current evidences about three reversal agents idarucizumab, andexanet alfa and ciraparantag, and the use of the first two in the emergency setting in patients with an active major bleeding or who need urgent surgery to offer physicians indications for a better management approach in order to increase patient’s safety. Conclusion: Although these agents have been marketed for five years (idarucizumab) and two years (andexanet alfa) respectively, and despite guidelines considering antidotes as first-line agents in treating life-threatening hemorrhage when available, these antidotes seem to gain access very slowly in the clinical practice. Cost, logistical aspects and need for plasma level determination of DOAC for an accurate therapeutic use probably have an impact on this phenomenon.. An expert multidisciplinary bleeding team should be established so as to implement international guidelines based on local resources and organization.

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Preclinical and Clinical Data for Factor Xa and “Universal” Reversal Agents

The American Journal of Medicine ◽

10.1016/j.amjmed.2016.06.009 ◽

2016 ◽

Vol 129 (11) ◽

pp. S80-S88 ◽

Cited By ~ 15

Author(s):

Truman J. Milling ◽

Scott Kaatz

Keyword(s):

Clinical Data ◽

Factor Xa ◽

Reversal Agents

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Structure activity relationships and the binding mode of quinolinone-pyrimidine hybrids as reversal agents of multidrug resistance mediated by P-gp

Scientific Reports ◽

10.1038/s41598-021-96226-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Jerónimo Laiolo ◽

Priscila Ailin Lanza ◽

Oscar Parravicini ◽

Cecilia Barbieri ◽

Daniel Insuasty ◽

...

Keyword(s):

Multidrug Resistance ◽

Molecular Complexes ◽

Binding Mode ◽

Reversal Agents ◽

Structure Activity Relationships ◽

Structure Activity ◽

Doxorubicin Toxicity ◽

Key Residues ◽

Nanomolar Range ◽

Experimental Structure

AbstractP-gp-associated multidrug resistance is a major impediment to the success of chemotherapy. With the aim of finding non-toxic and effective P-gp inhibitors, we investigated a panel of quinolin-2-one-pyrimidine hybrids. Among the active compounds, two of them significantly increased intracellular doxorubicin and rhodamine 123 accumulation by inhibiting the efflux mediated by P-gp and restored doxorubicin toxicity at nanomolar range. Structure–activity relationships showed that the number of methoxy groups, an optimal length of the molecule in its extended conformation, and at least one flexible methylene group bridging the quinolinone to the moiety bearing the pyrimidine favored the inhibitory potency of P-gp. The best compounds showed a similar binding pattern and interactions to those of doxorubicin and tariquidar, as revealed by MD and hybrid QM/MM simulations performed with the recent experimental structure of P-gp co-crystallized with paclitaxel. Analysis of the molecular interactions stabilizing the different molecular complexes determined by MD and QTAIM showed that binding to key residues from TMH 4–7 and 12 is required for inhibition.

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Comparison of the effect of isopropyl alcohol and chlorhexidine solution rinses on body temperature of female cats undergoing sterilization surgery

Journal of Feline Medicine and Surgery ◽

10.1177/1098612x20979565 ◽

2021 ◽

pp. 1098612X2097956

Author(s):

Rachael E Kreisler ◽

Michelle L Douglas ◽

Karissa N Harder

Keyword(s):

Body Temperature ◽

Heat Loss ◽

Isopropyl Alcohol ◽

Body Condition Score ◽

High Volume ◽

Veterinary Students ◽

Reversal Agents ◽

Duration Of Surgery ◽

Chlorhexidine Solution ◽

Recovery Temperature

Objectives Isopropyl alcohol 70% as a rinse agent for chlorhexidine scrub has been shown to decrease body temperature more quickly than chlorhexidine solution in mice prepared aseptically prior to surgery. For this reason, some high-quality, high-volume (HQHV) surgical sterilization clinics use chlorhexidine solution rather than alcohol. We sought to determine if temperature upon entry to recovery, heat loss per kg and rate of temperature decline during surgery were different between cats rinsed with chlorhexidine solution vs 70% isopropyl alcohol following surgical scrub, and if there were significant predictors of recovery temperature. Methods Female cats admitted for surgery to trap–neuter–return (TNR) clinics at a veterinary college were assigned chlorhexidine solution or alcohol rinse agents via block randomization. Veterinary students and veterinarians performed spay surgeries using HQHV techniques. In recovery, heat support and reversal agents were available for cats with a low body temperature or that were slow to recover. Baseline values, outcome variables and duration of each stage (preparation, surgery, recovery) were assessed using Wilcoxon rank-sum and t-tests. Recovery temperature was evaluated using random effects multiple linear regression. Results The recovery temperature, heat loss per kg, heat loss per min, need for reversal and need for heat support in recovery were not significantly different between rinse groups. Weight <2.3 kg, body condition score <4, duration of surgery and postinduction temperature were predictors of recovery temperature. The rate of heat loss in the first 30 mins of surgery was slightly lower for cats in the alcohol rinse group and the recovery duration was shorter for cats weighing less <2.3 kg in the alcohol rinse group. Conclusions and relevance There were no clinically meaningful differences in body temperature between chlorhexidine and alcohol rinses. Both chlorhexidine solution and isopropyl alcohol 70% are appropriate rinse agents for aseptic preparation of feline spay surgeries.

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