-
Cureus Sep 2023The current guidelines state that propafenone can be used in combination with a beta-blocker or a calcium channel blocker for pharmacologic cardioversion of recent-onset...
The current guidelines state that propafenone can be used in combination with a beta-blocker or a calcium channel blocker for pharmacologic cardioversion of recent-onset atrial fibrillation in patients without structural heart disease. To prevent the conversion from atrial fibrillation to atrial flutter with a rapid ventricular rate, it is recommended to administer propafenone following the administration of a beta-blocker or a calcium channel blocker. However, this combination carries the potential risk of cardiogenic shock. There are several scenarios where this combination can lead to shock, attributed to the variable pharmacokinetics of propafenone among individuals and its significant drug interactions with commonly used AV nodal blockers, such as metoprolol and diltiazem. Additionally, a significant proportion of the population has genetic polymorphisms that affect the metabolism of these medications. While pill-in-the-pocket propafenone is also employed in outpatient settings, unexpected severe and life-threatening reactions have been reported. In this context, we present a case report of severe propafenone toxicity in a closely monitored inpatient setting aimed at converting atrial fibrillation.
PubMed: 37908936
DOI: 10.7759/cureus.46282 -
Cureus Dec 2023Taxanes, in combination with platinum-based drugs, are considered the initial treatment option for certain types of cancer, including ovarian cancer. Here, we report the...
Taxanes, in combination with platinum-based drugs, are considered the initial treatment option for certain types of cancer, including ovarian cancer. Here, we report the case of a 59-year-old woman who developed a malar rash on her face, a maculopapular rash on her forearms, and bluish discoloration on her fingers immediately following the end of the third cycle of chemotherapy. After discontinuing paclitaxel and using oral and topical steroids for rash and diltiazem and topical minoxidil for the treatment of Raynaud's phenomenon, the symptoms completely resolved. While taxanes are known to cause drug-induced lupus, there has never been any information on taxanes causing isolated Raynaud's phenomenon. This is the first case report that suggests paclitaxel-induced Raynaud's phenomenon along with paclitaxel-induced lupus.
PubMed: 38259408
DOI: 10.7759/cureus.50974 -
CPT: Pharmacometrics & Systems... Apr 2024Brigatinib is an oral anaplastic lymphoma kinase (ALK) inhibitor approved for the treatment of ALK-positive metastatic non-small cell lung cancer. In vitro studies...
Brigatinib is an oral anaplastic lymphoma kinase (ALK) inhibitor approved for the treatment of ALK-positive metastatic non-small cell lung cancer. In vitro studies indicated that brigatinib is primarily metabolized by CYP2C8 and CYP3A4 and inhibits P-gp, BCRP, OCT1, MATE1, and MATE2K. Clinical drug-drug interaction (DDI) studies with the strong CYP3A inhibitor itraconazole or the strong CYP3A inducer rifampin demonstrated that CYP3A-mediated metabolism was the primary contributor to overall brigatinib clearance in humans. A physiologically-based pharmacokinetic (PBPK) model for brigatinib was developed to predict potential DDIs, including the effect of moderate CYP3A inhibitors or inducers on brigatinib pharmacokinetics (PK) and the effect of brigatinib on the PK of transporter substrates. The developed model was able to predict clinical DDIs with itraconazole (area under the plasma concentration-time curve from time 0 to infinity [AUC] ratio [with/without itraconazole]: predicted 1.86; observed 2.01) and rifampin (AUC ratio [with/without rifampin]: predicted 0.16; observed 0.20). Simulations using the developed model predicted that moderate CYP3A inhibitors (e.g., verapamil and diltiazem) may increase brigatinib AUC by ~40%, whereas moderate CYP3A inducers (e.g., efavirenz) may decrease brigatinib AUC by ~50%. Simulations of potential transporter-mediated DDIs predicted that brigatinib may increase systemic exposures (AUC) of P-gp substrates (e.g., digoxin and dabigatran) by 15%-43% and MATE1 substrates (e.g., metformin) by up to 29%; however, negligible effects were predicted on BCRP-mediated efflux and OCT1-mediated uptake. The PBPK analysis results informed dosing recommendations for patients receiving moderate CYP3A inhibitors (40% brigatinib dose reduction) or inducers (up to 100% increase in brigatinib dose) during treatment, as reflected in the brigatinib prescribing information.
Topics: Humans; Rifampin; Cytochrome P-450 CYP3A Inhibitors; Itraconazole; Cytochrome P-450 CYP3A; Carcinoma, Non-Small-Cell Lung; ATP Binding Cassette Transporter, Subfamily G, Member 2; Lung Neoplasms; Neoplasm Proteins; Cytochrome P-450 CYP3A Inducers; Drug Interactions; Membrane Transport Proteins; Receptor Protein-Tyrosine Kinases; Models, Biological; Organophosphorus Compounds; Pyrimidines
PubMed: 38288787
DOI: 10.1002/psp4.13106 -
Cureus Mar 2024This study aims to assess the association between intravenous diltiazem and metoprolol in rate control for atrial fibrillation (AF) patients with rapid ventricular rate,... (Review)
Review
This study aims to assess the association between intravenous diltiazem and metoprolol in rate control for atrial fibrillation (AF) patients with rapid ventricular rate, focusing on rate control efficacy and hemodynamic adverse events. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, electronic searches were conducted in Embase, PubMed, and Cochrane Central Register of Controlled Trials (CENTRAL) until February 20, 2024. The primary outcome was achieving ventricular rate control < 110/min. Secondary outcomes included new hypotension (systolic blood pressure < 90 mm Hg) and bradycardia (heart rate < 60/min). Nineteen studies (three randomized controlled trials and 16 observational studies) were included in this meta-analysis. Pooled analysis showed intravenous metoprolol resulted in a 39% lower rate control attainment compared to diltiazem (OR: 0.61; 95% CI: 0.44 to 0.84; p = 0.002). There were no significant differences in bradycardia (OR: 0.51; 95% CI: 0.22 to 1.22; p = 0.13) or hypotension risk (OR: 1.08; 95% CI: 0.72 to 1.61; p = 0.72) between the two groups. Intravenous diltiazem demonstrated superior rate control efficacy compared to metoprolol in AF patients with rapid ventricular rate. However, no significant differences were observed in safety outcomes, namely, bradycardia and hypotension.
PubMed: 38646329
DOI: 10.7759/cureus.56560 -
Scientific Reports Feb 2024In the past, quadratus lumborum block (QLB) was mostly used for postoperative analgesia in patients, and few anesthesiologists applied it during surgery with opioid-free... (Randomized Controlled Trial)
Randomized Controlled Trial
In the past, quadratus lumborum block (QLB) was mostly used for postoperative analgesia in patients, and few anesthesiologists applied it during surgery with opioid-free anesthesia (OFA). Consequently, it is still unclear whether QLB in the supine position can provide perfect analgesia and inhibit anesthetic stress during surgery under the OFA strategy. To observe the clinical efficacy of ultrasound-guided quadratus lumborum block (US-QLB) in the supine position with OFA for lower abdominal and pelvic surgery. A total of 122 patients who underwent lower abdominal or pelvic surgery in People's Hospital of Wanning between March 2021 and July 2022 were selected and divided into a quadratus lumborum block group (Q) (n = 62) and control group (C) (n = 60) according to the random number table method. Both groups underwent general anesthesia combined with QLB in the supine position. After sedation, unilateral or bilateral QLB was performed via the ultrasound guided anterior approach based on images resembling a "human eye" and "baby in a cradle" under local anesthesia according to the needs of the operative field. In group Q, 20 ml of 0.50% lidocaine and 0.20% ropivacaine diluted in normal saline (NS) were injected into each side. In group C, 20 ml of NS was injected into each side. The values of BP, HR, SO, SE, RE, SPI, NRS, Steward score, dosage of propofol, dexmedetomidine, and rocuronium, the number of patients who needed remifentanil, propofol, or diltiazem, puncture point, block plane, duration of anesthesia, catheter extraction, and wakefulness during the operation were monitored. There were no significant differences in the general data, number of cases requiring additional remifentanil, propofol, or diltiazem treatment, as well as puncture point and puncture plane between the two groups (P > 0.05). HR, SBP, and DBP values were higher in group Q than in group C at T1; HR, SPI, and SE, while RE values were lower in group Q than in group C at T3, SE, and RE; the Steward score was higher in group Q than in group C at T4 and T5, and the difference was statistically significant (P < 0.05). The extubation and awake times were lower in group Q than in group C, and the difference was statistically significant (P < 0.05). The SE, RE, and SPI values were lower at T1, T2, T3, and T4 than at T0. The Steward scores at T4 and T5 were higher in group Q than in group C, and were lower than at T0, with a statistically significant difference (P < 0.05). There were significant differences in the effectiveness of postoperative analgesia between the two groups at t1, t3 and t4 (P < 0.05). US-QLB in the supine position with OFA is effective in patients undergoing lower abdominal or pelvic surgery with stable intraoperative vital signs, complete recovery and better postoperative analgesia.
Topics: Humans; Analgesics, Opioid; Anesthetics, Local; Remifentanil; Propofol; Diltiazem; Supine Position; Pain, Postoperative; Nerve Block; Ultrasonography, Interventional
PubMed: 38409359
DOI: 10.1038/s41598-024-55370-5 -
The Korean Journal of Internal Medicine Jan 2024There may be many predictors of anticoagulation-related gastrointestinal bleeding (GIB), but until now, systematic reviews and assessments of the certainty of the... (Meta-Analysis)
Meta-Analysis
BACKGROUND/AIMS
There may be many predictors of anticoagulation-related gastrointestinal bleeding (GIB), but until now, systematic reviews and assessments of the certainty of the evidence have not been published. We conducted a systematic review to identify all risk factors for anticoagulant-associated GIB to inform risk prediction in the management of anticoagulation- related GIB.
METHODS
A systematic review and meta-analysis were conducted to search PubMed, EMBASE, Web of Science, and Cochrane Library databases (from inception through January 21, 2022) using the following search terms: anticoagulants, heparin, warfarin, dabigatran, rivaroxaban, apixaban, DOACs, gastrointestinal hemorrhage, risk factors. According to inclusion and exclusion criteria, studies of risk factors for anticoagulation-related GIB were identified. Risk factors for anticoagulant-associated GIB were used as the outcome index of this review.
RESULTS
We included 34 studies in our analysis. For anticoagulant-associated GIB, moderate-certainty evidence showed a probable association with older age, kidney disease, concomitant use of aspirin, concomitant use of the antiplatelet agent, heart failure, myocardial infarction, hematochezia, renal failure, coronary artery disease, helicobacter pylori infection, social risk factors, alcohol use, smoking, anemia, history of sleep apnea, chronic obstructive pulmonary disease, international normalized ratio (INR), obesity et al. Some of these factors are not included in current GIB risk prediction models. such as anemia, co-administration of gemfibrozil, co-administration of verapamil or diltiazem, INR, heart failure, myocardial infarction, etc.
CONCLUSION
The study found that anemia, co-administration of gemfibrozil, co-administration of verapamil or diltiazem, INR, heart failure, myocardial infarction et al. were associated with anticoagulation-related GIB, and these factors were not in the existing prediction models. This study informs risk prediction for anticoagulant-associated GIB, it also informs guidelines for GIB prevention and future research.
Topics: Humans; Anemia; Anticoagulants; Diltiazem; Gastrointestinal Hemorrhage; Gemfibrozil; Heart Failure; Helicobacter Infections; Helicobacter pylori; Myocardial Infarction; Risk Factors; Verapamil
PubMed: 38062723
DOI: 10.3904/kjim.2023.098 -
Medicine Oct 2023Currently, there is no gold standard for monitoring noxious stimulation during surgery, and the surgical pleth index (SPI) is only one of many monitoring methods. It is... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Currently, there is no gold standard for monitoring noxious stimulation during surgery, and the surgical pleth index (SPI) is only one of many monitoring methods. It is commonly used in the monitoring of conventional opiate anesthesia, but its effectiveness in opioid-free anesthesia (OFA) has not been evaluated. Therefore, the aim of this study was to observe the guidance value of the surgical pleth index in opioid-free anesthesia for patients undergoing lower abdominal or pelvic surgery.
METHODS
A total of 122 patients who underwent lower abdominal or pelvic surgery in our hospital between March 2021 and July 2022 were selected and equally divided into OFA (F) and control (C) groups according to the random number table method. Both groups underwent ultrasound-guided unilateral/bilateral quadratus lumborum block in the supine position according to the surgical field. In group F, 0.50% lidocaine and 0.20% ropivacaine (in 20 mL of 0.9% normal saline) were injected on each side. In group C, 20 mL 0.9% normal saline was injected on each side. Group F received general anesthesia without opioids and group C received general anesthesia with opioids. BP, pulse oxygen saturation, PETCO2, reactionentropy, stateentropy, and SPI values; Steward score; dosage of propofol, dexmedetomidine, rocuronium, and diltiazem; extubation time; and awake time were monitored in both groups.
RESULTS
There were no significant differences in the general data between the 2 groups (P > .05). There were no significant differences in SPI values at T0, T1, T2, T3, T4, and T5 or the number of cases requiring additional remifentanil, propofol, and diltiazem between the 2 groups (P > .05). The stateentropy, reactionentropy, and Steward scores were higher in group F than in group C at T4 and T5, while the extubation and awake times were lower in group F than in group C (P < .05). The heart rate and SPI of group F were lower than that of group C at T3 (P < .05).
CONCLUSION
The guiding value of SPI in OFA was similar to its use in opiated anesthesia. Its clinical efficacy is exact, vital signs are stable, enabling rapid, and complete regaining of consciousness.
Topics: Humans; Analgesics, Opioid; Anesthesia, General; Diltiazem; Propofol; Saline Solution
PubMed: 37904423
DOI: 10.1097/MD.0000000000035172 -
Annals of Cardiac Anaesthesia 2023In this study the authors have tried to examine the role of magnesium alone or in combination with diltiazem and / or amiodarone in prevention of atrial fibrillation... (Clinical Trial)
Clinical Trial
OBJECTIVES
In this study the authors have tried to examine the role of magnesium alone or in combination with diltiazem and / or amiodarone in prevention of atrial fibrillation (AF) following off-pump coronary artery bypass grafting (CABG).
BACKGROUND
AF after CABG is common and contributes to morbidity and mortality. Various pharmacological preventive measures including magnesium, amiodarone, diltiazem, and combination therapy among others have been tried to lower the incidence of AF. Most of the studies have been performed in patients undergoing conventional on-pump CABG. In this uncontrolled trial, efficacy of magnesium alone or in combination with amiodarone and / or diltiazem has been studied in patients undergoing off-pump CABG.
METHODS
One hundred and fifty patients undergoing off-pump CABG were divided into 3 groups, Group M (n=21) received intraoperative magnesium infusion at 30mg/ kg over 1 hour after midline sternotomy; Group MD (n=78) received magnesium infusion in similar manner with diltiazem infusion at 0.05 μg/kg/hr throughout the intraoperative period; Group AMD (n=51) received preoperative oral amiodarone at a dose of 200 mg three times a day for 3 days followed by 200 mg twice daily for another 3 days followed by 200 mg once daily till the day of surgery along with magnesium and diltiazem infusion as in other groups. AF lasting more than 10 min or requiring medical intervention was considered as AF.
RESULTS
The overall incidence of postoperative AF was 12.6% with 11.7% in group AMD, 19% in group M, and 11.5% in group MD, which was not statistically significant.
CONCLUSIONS
It is concluded that the use of amiodarone and/or diltiazem in addition to magnesium did not result in additional benefit of lowering the incidence of AF.
Topics: Humans; Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Coronary Artery Bypass; Diltiazem; Magnesium; Postoperative Complications; Treatment Outcome
PubMed: 37861573
DOI: 10.4103/aca.aca_35_23 -
Heart (British Cardiac Society) Aug 2023Atrial fibrillation (AF) is associated with adverse events including conduction disturbances, ventricular arrhythmias and sudden death. The aim of this study was to... (Observational Study)
Observational Study
OBJECTIVE
Atrial fibrillation (AF) is associated with adverse events including conduction disturbances, ventricular arrhythmias and sudden death. The aim of this study was to examine brady- and tachyarrhythmias using continuous rhythm monitoring in patients with paroxysmal self-terminating AF (PAF).
METHODS
In this multicentre observational substudy to the Reappraisal of Atrial Fibrillation: interaction between hyperCoagulability, Electrical remodelling and Vascular destabilisation in the progression of AF (RACE V), we included 392 patients with PAF and at least 2 years of continuous rhythm monitoring. All patients received an implantable loop recorder, and all detected episodes of tachycardia ≥182 beats per minute (BPM), bradycardia ≤30 BPM or pauses ≥5 s were adjudicated by three physicians.
RESULTS
Over 1272 patient-years of continuous rhythm monitoring, we adjudicated 1940 episodes in 175 patients (45%): 106 (27%) patients experienced rapid AF or atrial flutter (AFL), pauses ≥5 s or bradycardias ≤30 BPM occurred in 47 (12%) patients and in 22 (6%) patients, we observed both episode types. No sustained ventricular tachycardias occurred. In the multivariable analysis, age >70 years (HR 2.3, 95% CI 1.4 to 3.9), longer PR interval (HR 1.9, 1.1-3.1), CHADS-VASc score ≥2 (HR 2.2, 1.1-4.5) and treatment with verapamil or diltiazem (HR 0.4, 0.2-1.0) were significantly associated with bradyarrhythmia episodes. Age >70 years was associated with lower rates of tachyarrhythmias.
CONCLUSIONS
In a cohort exclusive to patients with PAF, almost half experienced severe bradyarrhythmias or AF/AFL with rapid ventricular rates. Our data highlight a higher than anticipated bradyarrhythmia risk in PAF.
TRIAL REGISTRATION NUMBER
NCT02726698.
Topics: Aged; Humans; Atrial Fibrillation; Atrial Flutter; Bradycardia; Heart Ventricles; Tachycardia, Ventricular
PubMed: 36948572
DOI: 10.1136/heartjnl-2022-322253 -
Cureus Jul 2023Angioedema is a documented but uncommon adverse effect of dihydropyridine calcium channel blockers such as amlodipine. We present the case of a 38-year-old man who...
Angioedema is a documented but uncommon adverse effect of dihydropyridine calcium channel blockers such as amlodipine. We present the case of a 38-year-old man who presented to the emergency department (ED) with severe swelling of his upper lip that had begun earlier in the day. His medical history was notable for hypertension treated with amlodipine; his only other medication was a multivitamin. The patient denied any known drug allergies, new foods, insect bites, recent travel, or sick contacts. Physical examination showed hypertension and massive edema isolated to the upper lip; it was otherwise unremarkable. Laboratory results showed no abnormalities aside from a slight normocytic anemia. The patient was diagnosed with angioedema, with amlodipine suspected as the cause. Amlodipine was discontinued and treatment was initiated with IV glucocorticoids and diphenhydramine. The swelling improved steadily over the next 36 hours and the patient was discharged on hospital day 3.
PubMed: 37484793
DOI: 10.7759/cureus.42202