COMPARAISON DU SPECTRE D'ACTIVITÉ DE CERTAINS GESTAGÈNES DE SYNTHÈSE

1962 ◽  
Vol 40 (2) ◽  
pp. 217-231 ◽  
Author(s):  
P. A. Desaulles ◽  
Ch. Krähenbühl
Keyword(s):  
Side Effects ◽  
Inhibiting Activity ◽  
Highly Active ◽  
Steroid Group ◽  
Oral Activity ◽  
Good For ◽  
Low Incidence ◽  
Orally Active ◽  
Very High

ABSTRACT The progestational, androgenic, myotrophic, and gonadotrophin-inhibiting activities of C21, C19, and C18 steroids have been correlated: In the C21 steroid group, progestativomimetic action varies from 0.1 × progesterone (P) in the case of 17α-hydroxyprogesterone (HP) to 3 × P in the case of 17α-acetoxyprogesterone (AP); it is particularly high (15 × P) with 6α-methyl-17α-acetoxyprogesterone (MAP). These two acetoxyprogesterones are orally active, their activity being respectively 3 and 50 × that of 17α-ethinyltestosterone (ET). MAP is highly active in maintaining gestation, i. e. 42× P in the rat, and 25 × P in the rabbit. The androgenic effects of these steroids are confined to certain structures only. Only MAP displays marked myotrophic activity. Gonadotrophin-inhibiting activity which is low for P, increases for HP and AP and is greatest in the case of MAP, which in this respect is about 5 × more active than testosterone (T). In the C19 steroid group, progestativomimetic action, which is weak with T (0.01 × P), is somewhat higher with 17α-methyltestosterone (MT) and even higher with ET (0.3 × P). This progression also holds good for oral activity as well as for maintenance of gestation. The low incidence of side effects with ET is worth noting. Common to the C18 steroids is their very high oral progestativomimetic activity: 17α-methyl-19-nortestosterone (MNT) = 4 × ET; 17α-ethinyl-19-nortestosterone (ENT) = 3 × ET; 17α-methyl-△5–10-19-nortestosterone = 1.5 × ET; and 17α-allylestren-3-17β-ol (allylestrenol) = no less than 16 × ET. Their gestation-maintaining properties are weak with the exception of MNT (1 × P). All substances of this group, apart from allylestrenol, are more potent inhibitors of gonadotrophic function than testosterone.

EFFICACY OF CARVEDILOL COMBINED WITH ENDOSCOPIC VARICEAL LIGATION IN THE PREVENTION OF RECURRENT VARICEAL BLEEDING IN PATIENTS OF CIRRHOSIS

2016 ◽  
pp. 23-30
Author(s):  
Van Huy Tran ◽  
Thi Ngoc Diep Bui
Keyword(s):  
Side Effects ◽  
Beta Blocker ◽  
Variceal Bleeding ◽  
Poor Prognosis ◽  
Oesophageal Varices ◽  
Endoscopic Variceal Ligation ◽  
Efficacy And Safety ◽  
Orthostatic Hypertension ◽  
Key Words Carvedilol ◽  
Very High

Background: The recurrent variceal bleeding is still very high with a very poor prognosis. The combination of a non-selective beta-blocker and endoscopic variceal ligation (EVL) is still a standard therapy for the prevention, but many patients showed no response to propranolol. Carvedilol is a new, non-selective beta-blocker having intrinsic alpha-blocker activity, but the data about the efficacy and safety of carvedilol is still very limited. This study is aimed at assessing the efficacy and safety of carvedilol combined with EVL in the prevention of recurrent variceal bleeding. Patients and methods: 33 patients having variceal bleeding were enrolled. All patients received carvedilol and were performed the EVL until variceal eradication. All the patients were followed after 9 months. Results: rate of variceal eradication of oesophageal varices was 87.88%; the recurrence rate of variceal bleeding was 12.12% after 9 months. The side effects of carvedilol were rare and not severe, including vertiges, headache, and orthostatic hypertension. Conclusion: Carvedilol combined with EVL appeared as a relatively safe and effective in the prevention of recurrent variceal bleeding in patients of cirrhosis. Key words: carvedilol, variceal bleeding, EVL

scholarly journals Study on Highly Active Anti- Retroviral Therapy: prescription pattern and side effects

2012 ◽  
Vol 26 (1) ◽  
pp. 12-18
Author(s):  
Sujata Sapkota ◽  
Rajani Shakya ◽  
Basudev Pandey
Keyword(s):  
Side Effects ◽  
Drug Regimen ◽  
World Health ◽  
Management Tools ◽  
Prescription Pattern ◽  
Highly Active ◽  
Regimen Change ◽  
Initial Regimen ◽  
Health Organization ◽  
Multiple Drugs

Since the introduction of Highly Active Anti Retroviral therapy (HAART) by World Health Organization in 1996, it has been the employed method of drug use in HIV management. Involvement of multiple drugs in the regimen, has also invited multiple complications and side effects is one of them. High chances of occurrence of side effects has called for the need of proper identification and therapy management tools for each HAART user and has highlighted the importance of individualized drug therapy. The aim of the study the prescription pattern of the HAART regimen; frequency of regimen change and its major causes; and the side- effects from HAART. The study was conducted in the ART Clinic of SukraRaj Tropical & Infectious Disease Hospital, Teku. 109 patients, who came to the clinic to refill their prescription, were interviewed by the researcher. After interview, medication file of each patient was reviewed to study the prescribed drug regimen, drug changes and identified reasons for the drug change (as identified by the physicians and recorded in patient medication file); reported side effect experience and laboratory reports were analyzed to study the effect of the HAART regimen on hemoglobin and Alanine Aminotransferase enzyme. The study revealed that the most prescribed HAART regimen constituted a combination of Zidovudine, Lamivudine and Nevirapine. 52% of the patients reported having experienced side effects from HAART. 23.85% patients had to have their initial regimen changed because of drug toxicity. Nausea (15.6%), vertigo (14.7%), decreased hemoglobin (11.9%), skin rash/ allergy (9.2%) were the major side effects experience reported by the patients. In addition to some side effects like nausea, vertigo etc; decrease in the level of hemoglobin after the initiation of HAART was evident. Decrease in Zidovudine containing regimen, during the regimen change was apparent and was mostly related to its hemoglobin lowering activity. DOI: http://dx.doi.org/10.3126/jnpa.v26i1.6630 JNPA. XXVI(1) 2012 12-18

scholarly journals Efavirenz induced gynecomastia, hidden reality: a case series

2020 ◽  
Vol 7 (11) ◽  
pp. 1747
Author(s):  
Dnyanesh N. Morkar ◽  
Ankita Aneja ◽  
Rishabh Agarwal
Keyword(s):  
Side Effects ◽  
Hiv Infection ◽  
Side Effect ◽  
Case Series ◽  
Drug Adherence ◽  
Resource Limited Settings ◽  
Hiv Patients ◽  
Highly Active ◽  
Resource Limited ◽  
Haart Therapy

The prognosis of HIV infection has considerably improved following the introduction of highly active anti-retroviral therapy by reducing AIDS related morbidity and mortality. At the same time, ART drugs are well known for their side effects. Gynaecomastia is a lesser known side effect of a commonly used anti-retroviral drug efavirenz. There are very few reports of HAART-induced gynaecomastia in resource-limited settings. The current study presents a series of three cases that developed ultrasound confirmed gynaecomastia following efavirenz containing HAART. Initial reports of gynaecomastia related to HAART were in HIV patients with lipodystrophy, they were termed as pseudogynaecomastia. Gradually, few reports of efavirenz related gynaecomastia were published wherein other causes of gynaecomastia were ruled out. Several hypothesis have been suggested for the pathophysiology of development of gynaecomastia related to efavirenz consumption. All other causes were ruled out in our patients too. The incidence of gynaecomastia is increasing in men with HIV on HAART therapy, proper identification and management will promote better drug adherence.

Perspectives on HAART: switch maintenance therapy

2003 ◽  
Vol 14 (9) ◽  
pp. 577-582 ◽  
Author(s):  
C L S Leen
Keyword(s):  
Side Effects ◽  
Highly Active Antiretroviral Therapy ◽  
Nucleoside Reverse Transcriptase Inhibitor ◽  
Transcriptase Inhibitor ◽  
Clear Trend ◽  
Highly Active ◽  
Hypersensitivity Skin ◽  
Reverse Transcriptase Inhibitor ◽  
Switch Maintenance Therapy

Switch studies have been carried out to explore changes in side effects in adherence. Discontinuing the protease inhibitor (PI) component of highly active antiretroviral therapy (HAART) regimen is often associated with improved adherence and improved quality of life. Following switching from a PI to a non-nucleoside reverse transcriptase inhibitor or abacavir, there is however a clear trend toward an improved metabolic profile particularly in insulin resistance and triglyceride levels when patients discontinue their PI. Peripheral wasting is likely to be associated with nucleoside analogues and for individuals with isolated fat accumulation, modification of HAART is not recommended. Virological suppression can be maintained following switch if adequate suppression of the virus has been achieved for at least six months prior to switch and the patient has not been previously exposed to suboptimal HAART. Discontinuing the PI preserves this class of agents for future use. Switching however may be associated with other side effects; hypersensitivity, skin rashes, hepatic or neuropsychiatric events.

scholarly journals Evaluation of Chemical Strategies for Improving the Stability and Oral Toxicity of Insecticidal Peptides

Biomedicines ◽  
2018 ◽  
Vol 6 (3) ◽  
pp. 90 ◽  
Author(s):  
Volker Herzig ◽  
Aline de Araujo ◽  
Kathryn Greenwood ◽  
Yanni Chin ◽  
Monique Windley ◽  
...  
Keyword(s):  
Oral Toxicity ◽  
Peptide Backbone ◽  
Insect Midgut ◽  
Peptide Toxins ◽  
Oral Activity ◽  
The Stability ◽  
Reduced Rate ◽  
Chemical Strategies ◽  
Orally Active ◽  
Insecticidal Peptides

Spider venoms are a rich source of insecticidal peptide toxins. Their development as bioinsecticides has, however, been hampered due to concerns about potential lack of stability and oral bioactivity. We therefore systematically evaluated several synthetic strategies to increase the stability and oral potency of the potent insecticidal spider-venom peptide ω-HXTX-Hv1a (Hv1a). Selective chemical replacement of disulfide bridges with diselenide bonds and N- to C-terminal cyclization were anticipated to improve Hv1a resistance to proteolytic digestion, and thereby its activity when delivered orally. We found that native Hv1a is orally active in blowflies, but 91-fold less potent than when administered by injection. Introduction of a single diselenide bond had no effect on the susceptibility to scrambling or the oral activity of Hv1a. N- to C-terminal cyclization of the peptide backbone did not significantly improve the potency of Hv1a when injected into blowflies and it led to a significant decrease in oral activity. We show that this is likely due to a dramatically reduced rate of translocation of cyclic Hv1a across the insect midgut, highlighting the importance of testing bioavailability in addition to toxin stability.

Sotalol hydrochloride (Betapace): a new antiarrhythmic drug

1993 ◽  
Vol 2 (5) ◽  
pp. 397-406
Author(s):  
CS Dunnington
Keyword(s):  
Side Effects ◽  
Antiarrhythmic Drug ◽  
Action Potential Duration ◽  
Antihypertensive Agent ◽  
Left Ventricular ◽  
Monophasic Action Potential ◽  
Class Iii ◽  
Cardiac Tissues ◽  
Supraventricular Tachyarrhythmias ◽  
Low Incidence

Sotalol hydrochloride (Betapace), recently released by the Food and Drug Administration for general use, is used to treat a variety of ventricular and supraventricular tachyarrhythmias. The drug's dominant action is the result of combined nonselective beta-adrenergic antagonism (Class II effect) and monophasic action potential duration prolongation in all cardiac tissues (Class III effect). It causes less left ventricular depression than propranolol and has a low incidence of toxicity. It is a useful addition to the antiarrhythmic drug armamentarium. This article reviews the drug's pharmacokinetic, pharmacodynamic and electrophysiologic properties, clinical uses and potential side effects. Reports on the drug's use as an antianginal and antihypertensive agent are also discussed.

scholarly journals Importance of genomic studies for drug withdrawal with mental toxicities

2011 ◽  
Vol 1 (1) ◽  
pp. 11 ◽  
Author(s):  
Da Yong Lu ◽  
Ting-Ren Lu
Keyword(s):  
Side Effects ◽  
Clinical Evidence ◽  
Drug Withdrawal ◽  
Antidepressant Treatment ◽  
Genetic Characteristics ◽  
Genetic Status ◽  
Genomic Studies ◽  
New Drug Development ◽  
Low Incidence ◽  
Incident Rate

Undesired side-effects and toxicities of drugs, especially in the area of new-drug development, are negligibleless, unpredicable and often disastrous once being encountered. The suicidal behavior caused by antidepressant treatment is a typical of clinical evidence recently being discovered. We previously hypothesized that patients’ genetic status would decide the suicidal incident rate of antidepressants - it is pharmacogenetics of antidepressants may contribute of this toxicity in patients. In this review, we discuss this problem by comparing many strings of pharmacogenomics evidence of antidepressants recently being published with many other strings of evidence such as drug withdrawal with hepatotoxicity. We argue herein that pharmacogenetics may be very useful in drug withdrawal for mental toxicity. Because this is low-incidence toxicities, which are more reliable on human’s genetic characteristics. We stress the importance of genomics studies for drug withdrawal in future.

Combinations of Morphine with Ketamine for Patient-controlled Analgesia

2003 ◽  
Vol 98 (5) ◽  
pp. 1195-1205 ◽  
Author(s):  
Gorazd Sveticic ◽  
Andrea Gentilini ◽  
Urs Eichenberger ◽  
Martin Luginbühl ◽  
Michele Curatolo
Keyword(s):  
Lumbar Spine ◽  
Side Effects ◽  
Drug Concentration ◽  
Optimization Procedure ◽  
Hip Surgery ◽  
Patient Controlled Analgesia ◽  
Pain Scores ◽  
Lockout Interval ◽  
Novel Method ◽  
Low Incidence

Background According to previous studies, the addition of ketamine to morphine for intravenous patient-controlled analgesia (PCA) may be beneficial. The authors developed and applied a new model to optimize the combination of morphine, ketamine, and a lockout interval for PCA after lumbar spine and hip surgery. Methods One-hundred two patients undergoing lumbar spine or hip surgery participated in the study. The analgesic effect of PCA during 48 h after surgery was optimized under restrictions dictated by side effects. Initially, eight combinations of morphine, ketamine (expressed as drug concentration in the solution administered), and a lockout interval (i.e., minimal allowed time between two consecutive PCA boluses) were empirically chosen and investigated. To determine subsequent combinations, an optimization model was applied until three consecutive steps showed no decrease in pain score. Results The authors analyzed 12 combinations with an allowed morphine and ketamine range in a PCA solution of 0-2 mg/ml and a lockout interval range of 5-12 min. During the optimization procedure, a reduction in mean pain scores with a low incidence of side effects was observed. The procedure converged to a morphine-to-ketamine ratio of 1:1 and a lockout interval of 8 min. Conclusions Using a novel method to analyze drug combinations, the study supports combinations of morphine with ketamine in a ratio of 1:1 and a lockout interval of 8 min for postoperative PCA following spine and hip surgery.

Docetaxel in combination with carboplatin for chemo-naive patients with epithelial ovarian cancer

2002 ◽  
Vol 12 (6) ◽  
pp. 704-709
Author(s):  
Y. Aoki ◽  
T. Sato ◽  
I. Tsuneki ◽  
M. Watanabe ◽  
H. Kase ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
University Hospital ◽  
Time Curve ◽  
Randomized Controlled Clinical Trials ◽  
Highly Active ◽  
Gynecology And Obstetrics ◽  
Major Toxicity ◽  
Clinically Significant ◽  
Low Incidence ◽  
Grade 3

We conducted a study of docetaxel-carboplatin combination therapy to confirm the efficacy and toxicity in chemotherapy-naive patients with ovarian cancer. Docetaxel 70 mg/m2 and carboplatin (area under the concentration-vs.-time curve of 5) were administered consecutively on day 1 of a 21-day cycle for five planned cycles in chemo-naive patients with the International Federation of Gynecology and Obstetrics stage IC to IV ovarian cancer with or without successful cytoreductive surgery at staging laparotomy. Twenty-six patients (median age, 53 years; range, 34–76 years) were enrolled into this trial at Niigata University Hospital. The major toxicity with this regimen was neutropenia. The incidence of grade 3 and 4 neutropenia were 27% (7/26) and 69% (18/26), respectively. However, the neutropenia was brief and reversible with G-CSF support. Nausea/emesis, fatigue, arthralgia/myalgias, and alopecia were the most common nonhematologic toxicities, in which no grade 3 or 4 toxicity was observed. Neurotoxicity was infrequently observed. Nine of 11 assessable patients responded to the regimen. We conclude that the combination of carboplatin and docetaxel seems to be highly active in ovarian cancer with the major toxicity of neutropenia, and the extremely low incidence of clinically significant neurotoxicity. Randomized controlled clinical trials should be conducted to define a role for this regimen in ovarian cancer.

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