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Transformin Growth Factor-β
Published in Jason Kelley, Cytokines of the Lung, 2022
The administration of exogenous TGF-β induces the production and secretion of TGF-β by cultured cells. Autoinduction is a term used to describe this ability of certain cytokines to induce their own expression by certain cells. Such a process represents a specialized variant of the autocrine hypothesis and a form of positive feedback. Although originally validated in transformed cell lines, the autocrine hypothesis may function in cell growth regulation under normal conditions (Kim et al., 1989a,b; van Obberghen-Schilling et al., 1988).
Carbamazepine
Published in Stanley R. Resor, Henn Kutt, The Medical Treatment of Epilepsy, 2020
Due to the time-dependent kinetics of CBZ it is useful to monitor CBZ serum concentrations 3 to 4 weeks after beginning therapy when complete “autoinduction” has developed. Autoinduction can be compensated for with a dose increase. If the patient takes another AED with enzyme-inducing properties such as phenobarbital (PB), primidone (PRM), or phenytoin (PHT), it may be very difficult to achieve sufficiently high serum concentrations despite very high doses.
Overview of the Biotransformation of Antiepileptic Drugs
Published in Carl L. Faingold, Gerhard H. Fromm, Drugs for Control of Epilepsy:, 2019
The enzymes responsible for epoxide formation, for epoxide hydrolysis, and for ring hydroxylations can all be induced, although not to the same extent and by the same drugs.36 It is not clear that the sulfur-containing conjugate metabolic route is induced. No evidence that direct N-glucuronidation could be enhanced by inducing agents was located during this review. The enzymes responsible for 10,11-epoxide formation have been shown to be saturated by high doses of carbamazepine given twice daily for 4 days. This saturation occurred despite significant autoinduction by the parent drug.37 Oxidation of carbamazepine to the epoxide does not seem to be correlated with oxidation of debrisoquin, sparteine, antipyrine, amitriptyline, or total metabolism of theophylline.36 Several drugs which inhibit cytochrome P-450 enzymes can decrease the clearance of carbamazepine. (See Fraigle and Feldman33 for details.)
An evaluation of mitapivat for the treatment of hemolytic anemia in adults with pyruvate kinase deficiency
Published in Expert Review of Hematology, 2022
Andrew B. Song, Hanny Al‐Samkari
In the phase 1 studies, mitapivat was readily absorbed in both the fasting and fed state. With doses of mitapivat of 700 mg or more, dose-normalized Cmax decreased with increasing doses. In the MAD study, dose-normalized Cmax and AUC0-τ on day 14 increased proportionally for the 15- and 60-mg dose cohorts but decreased with increasing dose from 120- to 700-mg dose cohorts. Pharmacokinetic parameters suggested autoinduction of mitapivat metabolism at doses of 120 mg every 12 hours or greater with plasma trough levels decreasing with subsequent doses and dose normalized Cmax decreasing with increasing doses of 120 mg or greater. Steady state mean plasma trough level was achieved on day 2 in the 15-mg dose cohorts and on day 7 in the 60-mg dose cohort. The terminal half-life was estimated to be 3–6 hours. 98% of mitapivat is protein bound in plasma. The volume of distribution is 42.5 L. Additional pharmacokinetic parameters are summarized in Table 1.
Impact of chronic medications in the perioperative period: mechanisms of action and adverse drug effects (Part I)
Published in Postgraduate Medicine, 2021
Ofelia Loani Elvir-Lazo, Paul F White, Hillenn Cruz Eng, Firuz Yumul, Raissa Chua, Roya Yumul
Carbamazepine is primarily used as an anticonvulsant, but it is considered as a second-line agent for treating bipolar affective disorders. Aside from its anticonvulsant properties, carbamazepine has also been shown to exhibit anticholinergic, antineuralgic, antidiuretic, muscle relaxant, antimanic, antidepressant, and antiarrhythmic properties. Carbamazepine depresses activity in the nucleus ventralis of the thalamus decreasing synaptic transmission (or summation of temporal stimulation) and leading to neuronal discharge by limiting the influx of sodium ions across cell membranes [96]. Carbamazepine has also been shown to stimulate the release of ADH and potentiate reabsorption of water by the renal tubules. Due to its similar chemical structure, it has been shown to have similar effects to tricyclic antidepressants. Carbamazepine is often used as monotherapy for the acute treatment of hypomania and mild-to-moderate mania or mixed episodes associated with bipolar disorder. It can also be used as monotherapy or adjunct treatment for focal onset seizures and generalized onset seizures. Lastly, a unique clinical indication that carbamazepine has been shown to be helpful in is the treatment of trigeminal or glossopharyngeal neuralgia [91]. Carbamazepine elimination depends on hepatic biotransformation and can undergo autoinduction and increase clearance by up to 300% over time.
Current research toward optimizing dosing of first-line antituberculosis treatment
Published in Expert Review of Anti-infective Therapy, 2019
Helen McIlleron, Maxwell T Chirehwa
The extent to which genetic variation governs the large differences in rifampin exposures observed between patients and between studies, is not well understood [30]. Organic-anion-transporting polypeptide1B1 (encoded by SLCO1B1) mediates transfer of rifampin into the hepatocyte, from where it is excreted via the bile. Studies describe associations between SLCO1B1 variants and rifampin as well as rifabutin. However, as the findings have been inconsistent across the studies in different populations, further studies are needed to confirm the associations and identify particular single nucleotide polymorphisms related to rifampin pharmacokinetics [82–87]. Functional polymorphisms of the gene encoding arylacetamide deacetylase, which efficiently converts rifamycins to 25-desacetylrifamycin metabolites, have been identified, however their clinical relevance has not been confirmed [86,88]. Although rifampin is also a substrate of p-glycoprotein and it causes autoinduction regulated by the pregnane X receptor, pharmacokinetic associations with variants in the genes encoding these proteins have not been described [86]. Similarly, isolated findings which should be confirmed ascribe changes in moxifloxacin pharmacokinetics to SNPs in SLCO1B1, UGT1A, and ABCB1 [89–91].