scholarly journals Ultrarapid drug metabolism: PCR-based detection of CYP2D6 gene duplication

1998 ◽  
Vol 44 (5) ◽  
pp. 914-917 ◽  
Author(s):  
Linda S W Steijns ◽  
Jan Van Der Weide

Abstract The enzyme debrisoquine 4-hydroxylase (CYP2D6), which metabolizes many widely used drugs, is highly polymorphic. The activity of the enzyme ranges between subjects from ultrafast to a complete absence. Therefore, metabolic capacity varies, producing intersubject differences in therapeutic efficacy and side effects at standard recommended doses. Up to 7% of Caucasians may demonstrate ultrarapid drug metabolism (UM) because of inherited alleles with multiplicate functional CYP2D6 genes, causing an increased amount of enzyme to be expressed. Identification of UM subjects is of potential clinical importance for adjustment of doses in drug therapy, as well as to avoid misidentification of noncompliance. In our study, we tested recently designed PCR assays for the detection of the UM genotype. We found a 3.5% prevalence of UMs carrying duplicate active CYP2D6 genes in a population consisting of 202 psychiatric patients.

Medicines are an essential part of the treatment of children. They help to reduce morbidity and mortality. It is important to recognize, however, that all medicines have potential side effects and additionally medication errors can occur at any stage (prescription, dispensing, or administration). Due to physiological differences in relation to drug metabolism and the potential protein-displacing effect on bilirubin, neonates are at greater risk of drug toxicity. Drug therapy is an integral part of the management of both pain and sedation in children.


1968 ◽  
Vol 57 (4) ◽  
pp. 565-577 ◽  
Author(s):  
K. E. Røkke ◽  
J. H. Vogt

ABSTRACT A report is given on 95 thyrotoxic patients treated with a combination of 400 mg propylthiouracil and 400 mg of potassium perchlorate. Perchlorate was stopped when a marked remission of symptoms was obtained, on an average after less than 7 weeks. Euthyroidism was found on an average after 7.2 weeks. The basal metabolic rate, PBI, plasma total cholesterol and weight showed a fairly rapid normalization. Thirteen of the 95 patients were given radio-iodine therapy shortly before drug therapy was started. The remaining 82 cases were grouped together with the 23 cases previously reported. Of the total of 105 cases, 96 became euthyroid on combined therapy. For the frequency of side-effects, the thirteen cases mentioned above were included, giving a total of 118 cases. Eight cases showed an increase in goitre size and 15 cases had other side-effects, of which three were granulocytopenia due to propylthiouracil. The possibility of a higher frequency of mainly minor side-effects on combined therapy has to be balanced against the seemingly rapid and reliable therapeutic effect. Combined treatment, perhaps with even smaller doses than reported here, can be recommended in selected cases of thyrotoxicosis where a shortening of the thyrotoxic state seems of importance, or possibly where difficulties due to iodine exposure may be anticipated, provided adequate control measures are taken.


2020 ◽  
Vol 17 (4) ◽  
pp. 270-278
Author(s):  
Maha Nasr ◽  
Rawan Al-Karaki

Nanotechnology is currently a hot topic in dermatology and nutraceutical/cosmeceutical delivery, owing to the advantages it provides in terms of enhancing the skin permeation of drugs, as well as increasing their therapeutic efficacy in the treatment of different dermatological diseases. There is also a great interest in the topical delivery of nutraceuticals; which are natural compounds with both therapeutic and cosmetic benefits, in order to overcome the side effects of topically applied chemical drugs. Quercetin is a key nutraceutical with topical antioxidant and anti-inflammatory properties which was reported to be effective in the treatment of different dermatological diseases, however, its topical therapeutic activity is hindered by its poor skin penetration. This review highlights the topical applications of quercetin, and summarizes the nanocarrier-based solutions to its percutaneous delivery challenges.


2020 ◽  
Vol 20 (6) ◽  
pp. 700-708
Author(s):  
Mitra Korani ◽  
Sara Nikoofal-Sahlabadi ◽  
Amin R. Nikpoor ◽  
Solmaz Ghaffari ◽  
Hossein Attar ◽  
...  

Aims: Here, three liposomal formulations of DPPC/DPPG/Chol/DSPE-mPEG2000 (F1), DPPC/DPPG/Chol (F2) and HSPC/DPPG/Chol/DSPE-mPEG2000 (F3) encapsulating BTZ were prepared and characterized in terms of their size, surface charge, drug loading, and release profile. Mannitol was used as a trapping agent to entrap the BTZ inside the liposomal core. The cytotoxicity and anti-tumor activity of formulations were investigated in vitro and in vivo in mice bearing tumor. Background: Bortezomib (BTZ) is an FDA approved proteasome inhibitor for the treatment of mantle cell lymphoma and multiple myeloma. The low solubility of BTZ has been responsible for the several side effects and low therapeutic efficacy of the drug. Encapsulating BTZ in a nano drug delivery system; helps overcome such issues. Among NDDSs, liposomes are promising diagnostic and therapeutic delivery vehicles in cancer treatment. Objective: Evaluating anti-tumor activity of bortezomib liposomal formulations. Methods: Data prompted us to design and develop three different liposomal formulations of BTZ based on Tm parameter, which determines liposomal stiffness. DPPC (Tm 41°C) and HSPC (Tm 55°C) lipids were chosen as variables associated with liposome rigidity. In vitro cytotoxicity assay was then carried out for the three designed liposomal formulations on C26 and B16F0, which are the colon and melanoma cancer mouse-cell lines, respectively. NIH 3T3 mouse embryonic fibroblast cell line was also used as a normal cell line. The therapeutic efficacy of these formulations was further assessed in mice tumor models. Result: MBTZ were successfully encapsulated into all the three liposomal formulations with a high entrapment efficacy of 60, 64, and 84% for F1, F2, and F3, respectively. The findings showed that liposomes mean particle diameter ranged from 103.4 to 146.8nm. In vitro cytotoxicity studies showed that liposomal-BTZ formulations had higher IC50 value in comparison to free BTZ. F2-liposomes with DPPC, having lower Tm of 41°C, showed much higher anti-tumor efficacy in mice models of C26 and B16F0 tumors compared to F3-HSPC liposomes with a Tm of 55°C. F2 formulation also enhanced mice survival compared with untreated groups, either in BALB/c or in C57BL/6 mice. Conclusion: Our findings indicated that F2-DPPC-liposomal formulations prepared with Tm close to body temperature seem to be effective in reducing the side effects and increasing the therapeutic efficacy of BTZ and merits further investigation.


1991 ◽  
Vol 29 (2) ◽  
pp. 7-8

Bromocriptine, lysuride (formerly lisuride, Revanil – Roche) and pergolide (not yet marketed in the UK) are dopamine agonists developed for use in the treatment of patients with Parkinson’s disease. Combination of a dopamine agonist with levodopa plus a dopa-decarboxylase inhibitor (‘co-dieldopa’)* may have advantages at all stages of the disease. The aim of combined co-dieldopa + agonist treatment is to limit some of the problems with prolonged co-dieldopa use alone; especially fluctuations in motor disability.1 It is still not clear how the three agonists compare with each other for therapeutic efficacy, duration of action, and side effects, nor how they are best combined with co-dieldopa.


Author(s):  
Parminderpal Singh ◽  
Kiranjit Kiranjit

Objective: The present study was aimed to analyze the side effects of olmesartan medoxomil and enalapril in hypertensive subjects.Methods: The study consisted of newly diagnosed hypertension categorized according to 7th report of Joint National Commission on prevention, detection, evaluation, and treatment of high blood pressure. The subjects were divided into two groups. The Group A subjects received olmesartan, and Group B subjects received enalapril. Pressure was recorded both in supine and sitting positions. The appearance of side effects was observed in the follow-up, i.e., dry cough, headache, postural hypotension, angioedema, dizziness, skin rashes, taste alterations, and urticaria. A statistical data were prepared on the basis of information obtained and analyzed thoroughly for antihypertensive effects and side effects of olmesartan and enalapril. SPSS software was used for analysis.Results: There was observed an increase in the incidence of taste alteration with drug therapy in Group B (Enalapril). There was observed an increase in the incidence of postural hypotension with drug therapy in both groups. In Group A (Olmesartan), the incidence of postural hypotension at the beginning of trial, 4 weeks, and 8 weeks was 0%, 2%, and 2%, respectively. In Group A (Olmesartan), there was no incidence of a headache at the beginning of trial, at 4 weeks and 8 weeks.Conclusion: From the study, it can be concluded that both olmesartan and enalapril are effective in Stage I and Stage II hypertension, but olmesartan is tolerated well with lesser side effects.


Ozone Therapy ◽  
2017 ◽  
Vol 1 (3) ◽  
pp. 53
Author(s):  
Marianno Franzini ◽  
Giulia Ionita

In the context of multidisciplinary care of elderly patients, this work will want to consider the presence of osteo-articular and muscular pain, mostly chronic, of these subjects. The treatment has made use of oxygen-ozone therapy, given the absence of side effects of this minimally invasive technique, and the possibility of its use simultaneously with an already established poly-drug therapy, as typically found in the geriatric patient.


Sign in / Sign up

Export Citation Format

Share Document