- StatPearls [BOOK]
- BOOKStatPearls Publishing: Treasure Island (FL)
- FDA recognized the combination of acetylsalicylic acid (250 mg), acetaminophen (250 mg) and caffeine (65 mg) as safe and effective in treating acute headache, especially migraine, and was considered ...
FDA recognized the combination of acetylsalicylic acid (250 mg), acetaminophen (250 mg) and caffeine (65 mg) as safe and effective in treating acute headache, especially migraine, and was considered effective also by the American Headache Society (Level A). This combination is well-tolerated in episodic tension-type headache, and considered superior to acetaminophen, and all components of this combination are considered safe during breastfeeding and can be taken orally for acute migraine attacks.
- Cluster-status migrainosus with a weekly periodicity responsive to high-flow oxygen: A case report. [Journal Article]
- CCephalalgia 2018 Jan 01; :333102418787263
- Background There are cases in the headache literature described as "cluster-migraine," but none of stereotyped cases of cluster headache evolving into status migrainosus. We believe this is the first...
Background There are cases in the headache literature described as "cluster-migraine," but none of stereotyped cases of cluster headache evolving into status migrainosus. We believe this is the first documented case of "cluster-status migrainosus". Case A 54 year-old female hospital administrator presented with headaches with a unique periodicity and semiology that were acutely responsive to high-flow oxygen. She experienced cluster headache attacks every Thursday morning at 3-4 am, which would evolve into status migrainosus lasting through Sunday evening. These attacks were preceded by prodromal depressed mood changes and fluid retention, and later followed by postdromal euphoria and auto-diuresis. These attacks initially occurred every other week and progressed to weekly attacks for 1.5 years. These headaches did not respond to trials of propanolol, sodium valproate, topiramate, amitriptyline, gabapentin, and carbamazepine for preventive treatment or to oral sumatriptan and butalbital-acetaminophen-caffeine for acute treatment. We started her on high-flow 100% oxygen for cluster headache, which successfully aborted greater than 80% of her weekly cluster headache attacks and prevented them from evolving into status migrainosus. Conclusion We believe this is the first case of "cluster-status migranosus" described in the medical literature. High-flow oxygen both aborted the cluster headaches and prevented the ensuing status migrainosus.
- Novel Multi-Modal Analgesia Protocol Significantly Decreases Opioid Requirements in Inflatable Penile Prosthesis Patients. [Journal Article]
- JSJ Sex Med 2018 Jul 12
- CONCLUSIONS: Multimodal pain management allows for effective pain control with minimal side effects, enhancing recovery.In our rigorous assessment of IPP patients, implementation of a novel MMA protocol achieved equivalent and effective pain control, while resulting in substantially fewer narcotics throughout the entire post-operative period following IPP implantation. Tong CMC, Lucas J, Shah A, et al. Novel Multi-Modal Analgesia Protocol Significantly Decreases Opioid Requirements in Inflatable Penile Prosthesis Patients. J Sex Med 2018;XX:XXX-XXX.
- Transaminase and Creatine Kinase Ratios for Differentiating Delayed Acetaminophen Overdose from Rhabdomyolysis. [Journal Article]
- WJWest J Emerg Med 2018; 19(4):731-736
- CONCLUSIONS: AST/ALT, CK/AST and CK/ALT ratios are significantly larger in rhabdomyolysis when compared to patients with acetaminophen toxicity. This result suggests that the ratios could be used to identify patients with rhabdomyolysis who otherwise might have been diagnosed as delayed acetaminophen toxicity. Such patients may not require treatment with N-acetylcysteine, resulting in cost savings and improved resource utilization.
- Interaction between 3,4‑dichlorophenyl‑propenoyl‑sec.‑butylamine (3,4‑DCPB), an antiepileptic drug, and cytochrome P450 in rat liver microsomes and recombinant human enzymes in vitro. [Journal Article]
- EJEur J Pharm Sci 2018 Jul 12
- The compound 3,4‑dichlorophenyl‑propenoyl‑sec.‑butylamine (3,4‑DCPB) is an antiepileptic drug. The purpose of the present research was to identify cytochrome P450 (CYP450) responsible for the metabol...
The compound 3,4‑dichlorophenyl‑propenoyl‑sec.‑butylamine (3,4‑DCPB) is an antiepileptic drug. The purpose of the present research was to identify cytochrome P450 (CYP450) responsible for the metabolism of 3,4‑DCPB and evaluate the effects of 3,4‑DCPB on the activities of CYP450 enzymes. 3,4‑DCPB was incubated with rat liver microsomes (RLMs) plus six CYP450 enzyme-specific inhibitors, or six recombinant human CYP450 enzymes (rhCYP450s). The concentrations of 3,4‑DCPB and six CYP450 enzyme-activities probe drugs were detected by high-performance liquid chromatographic (HPLC). The results showed that the prototype of 3,4‑DCPB was metabolized by multiple CYP450 enzymes into three metabolites, and the predominant isoforms were CYP2D6 (metabolite M1), CYP1A2 (M2), CYP2C19 and CYP3A4 (M3), respectively., in the presence of β-NADPH (1 mM) in RLMs or rhCYP450s. Compared with the control (PB-), phenobarbital pre-treatment (PB+) significantly enhanced levels (all of p < 0.01) of hydroxylmethytobutamide (CYP2C9), 4‑hydroxy‑mephenytoin (CYP2C19), acetaminophen (CYP1A2), 6‑hydroxychlorzoxazone (CYP2E1) and oxidized nifedipine (CYP3A4), respectively, in spite of dextrophan (CYP2D6) was not markedly enhanced in RLMs. Conversely, the inhibitory ratios of 3,4‑DCPB (16 μg/mL, 59 μM) on the activities of CYP2C9, CYP2C19, CYP1A2 and CYP2D6 were 97.6%, 59.0%, 53.5% and 36.5%, respectively. However, CYP2E1 (both of PB- and PB+) and CYP3A4 (PB+) were not inhibited by 3,4‑DCPB in RLMs. In conclusion, the present study showed that 3,4‑DCPB was metabolized by multiple CYP450 enzymes. 3,4‑DCPB inhibited the activities of CYP2C9, CYP2C19, CYP1A2 and CYP2D6, rather than that CYP2E1 and CYP3A4 enzymes, suggesting that the different effects of 3,4‑DCPB on the CYP450 enzymes might influence metabolic drug-drug interaction in antiepileptics therapy.
- Late oral acetaminophen versus immediate surgical ligation in preterm infants with persistent large patent ductus arteriosus. [Journal Article]
- JTJ Thorac Cardiovasc Surg 2018 Jul 11
- CONCLUSIONS: Late oral acetaminophen therapy for infants with persistent patent ductus arteriosus is associated with reduced surgical ligation but increased chronic lung disease. In light of a lack of improvement in clinical outcomes, the individual contributory effects of acetaminophen, surgical ligation, and prolonged exposure to patent ductus arteriosus require further study to define the optimal approach.
- TRPV1 mediates the anticonvulsant effects of acetaminophen in mice. [Journal Article]
- EREpilepsy Res 2018 Jul 03; 145:153-159
- CONCLUSIONS: These findings suggest that acetaminophen has an anticonvulsant effect in pentylenetetrazol-kindled mouse models and TRPV1 mediates the anticonvulsant action.
- Reactive Metabolite-induced Protein Glutathionylation: a Potentially Novel Mechanism Underlying Acetaminophen Hepatotoxicity. [Journal Article]
- MCMol Cell Proteomics 2018 Jul 13
- Although covalent protein binding is established as the pivotal event underpinning acetaminophen (APAP) toxicity, its mechanistic details remain unclear. In this study, we demonstrated that APAP indu...
Although covalent protein binding is established as the pivotal event underpinning acetaminophen (APAP) toxicity, its mechanistic details remain unclear. In this study, we demonstrated that APAP induces widespread protein glutathionylation in a time-, dose- and bioactivation-dependent manner in HepaRG cells. Proteo-metabonomic mapping provided evidence that APAP-induced glutathionylation resulted in functional deficits in energy metabolism, elevations in oxidative stress and cytosolic calcium, as well as mitochondrial dysfunction that correlate strongly with the well-established toxicity features of APAP. We also provide novel evidence that APAP-induced glutathionylation of carnitine O-palmitoyltransferase 1 (CPT1) and voltage-dependent anion-selective channel protein 1 are respectively involved in inhibition of fatty acid β-oxidation and opening of the mitochondrial permeability transition pore. Importantly, we show that the inhibitory effect of CPT1 glutathionylation can be mitigated by PPARα induction, which provides a mechanistic explanation for the prophylactic effect of fibrates, which are PPARα ligands, against APAP toxicity. Finally, we propose that APAP-induced protein glutathionylation likely occurs secondary to covalent binding, which is a previously unknown mechanism of glutathionylation, suggesting that this post-translational modification could be functionally implicated in drug-induced toxicity.
- Cryopreserved human intestinal mucosal epithelium: a novel in vitro experimental system for the evaluation of enteric drug metabolism, P450 induction, and enterotoxicity. [Journal Article]
- DMDrug Metab Dispos 2018 Jul 13
- We report here a novel in vitro enteric experimental system, cryopreserved human intestinal mucosa (CHIM), for the evaluation of enteric drug metabolism, drug-drug interaction, drug toxicity, and pha...
We report here a novel in vitro enteric experimental system, cryopreserved human intestinal mucosa (CHIM), for the evaluation of enteric drug metabolism, drug-drug interaction, drug toxicity, and pharmacology. CHIM were isolated from the small intestines of four human donors. The small intestines were first dissected into duodenum, jejunum and ileum, followed by collagenase digestion of the intestinal lumens. The isolated mucosa were gently homogenized to yield multiple cellular fragments followed by cryopreservation in a programmable liquid cell freezer and stored in liquid nitrogen. After thawing and recovery, CHIM were found to retain robust P450 and non-P450 drug metabolizing enzyme activities, to demonstrate dose-dependent induction of gene expression of CYP24A1 (approx. 300-fold) and CYP3A4 (approx. 3-fold) by vitamin D3, and induction of CYP3A4 (approx. 3-fold) by rifampin after treatment for 24 hours. Dose-dependent decreases in cell viability quantified by cellular ATP content was observed for naproxen and acetaminophen, with a higher enterotoxicity observed for naproxen, consistent with what is observed in humans in vivo. The results suggest that CHIM may be a useful in vitro experimental model for the evaluation of enteric drug properties including drug metabolism, drug-drug interactions, and drug toxicity.
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- Assay system development to measure the concentration of sargramostim with high specificity in patients with autoimmune pulmonary alveolar proteinosis after single-dose inhalation. [Journal Article]
- JIJ Immunol Methods 2018 Jul 09
- During a clinical trial of a Saccharomyces cerviciae-derived recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF), sargramostim, in patients with autoimmune pulmonary alveola...
During a clinical trial of a Saccharomyces cerviciae-derived recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF), sargramostim, in patients with autoimmune pulmonary alveolar proteinosis (aPAP), we conducted a pharmacokinetic study of single-dose sargramostim inhalation. Several problems were encountered whereby sargramostim formed an immune-complex with GM-CSF autoantibodies (GMAbs) immediately after entering the body; thus, we could not measure the concentration of sargramostim using a commercial high sensitivity enzyme-linked immunosorbent assay (ELISA). Moreover, the ELISA could not discriminate inhaled sargramostim from intrinsic GM-CSF. To solve these problems, we developed a novel ELISA system with a capture antibody that is specific for sargramostim and a detection antibody capable of binding with GM-CSF. This system quantified the serum sargramostim concentration, but not E. coli-, CHO-, or HEK293T-derived human recombinant GM-CSF. Using this system, serum pharmacokinetics were estimated in five patients after inhalation of 250 μg sargramostim, with a mean Cmax of 9.7 ± 2.85 pg/ml at a Tmax of 2 ± 1.22 h.