Low-dose and high-dose colchicine have comparable efficacy in the treatment of acute gout, but high dose carries significantly greater risk of adverse effects

2010 ◽  
Vol 15 (6) ◽  
pp. 170-171
Author(s):  
B. F. Mandell
Keyword(s):  
Adverse Effects ◽  
Low Dose ◽  
Comparable Efficacy ◽  
High Dose ◽  
Acute Gout

Captopril: Evaluation of Low Doses, Twice-Daily Doses and the Addition of Diuretic for the Treatment of Mild to Moderate Hypertension

1982 ◽  
Vol 63 (s8) ◽  
pp. 443s-445s ◽  
Author(s):  
◽  
Barry J. Materson
Keyword(s):  
Blood Pressure ◽  
Adverse Effects ◽  
Diastolic Blood Pressure ◽  
Low Dose ◽  
Moderate Hypertension ◽  
Treated Group ◽  
Daily Treatment ◽  
High Dose ◽  
Low Doses

1. We randomized 475 men whose diastolic blood pressure was 92–109 mmHg to either placebo- or captopril-treated (37.5, 75 and 150 mg/day) groups for 7 weeks. 2. After 7 weeks, the placebo-treated patients were given hydrochlorothiazide (25 mg twice daily), as were two-thirds of each captopril-treated group, and they were observed for 7 additional weeks. 3. Captopril reduced blood pressure by 12.2 ± 0.8/9.4 ± 0.4 mmHg at 7 weeks (n = 323) and captopril plus placebo by 10.3 ± 1.9/10.2 ± 0.9 at 14 weeks (n = 83); placebo by 20 ± 1.7/3.4 ± 0.8 (n = 76); captopril plus hydrochlorothiazide by 24.4 ± 1.1/16.2 ± 0.6 (n = 173). The effect of low-dose captopril was similar to that of a high dose. The effect of twice-daily captopril appeared to be equal to that of thrice-daily treatment but monitoring studies are needed to confirm this. 4. Only 15 out of 384 (3.9%) of patients were dropped from the study because of adverse effects. 5. Low-dose captopril may be useful in patients with mild to moderate hypertension.

scholarly journals Cushing’s disease: Does low-dose pasireotide offer a comparable efficacy and safety to high-dose?

2021 ◽  
Vol 2021 ◽  
Author(s):  
Mimi Wong ◽  
Usman H Malabu ◽  
Ipeson Korah ◽  
YongMong Tan
Keyword(s):  
Cushing’S Disease ◽  
Low Dose ◽  
Cushing's Disease ◽  
Comparable Efficacy ◽  
High Dose ◽  
List Type ◽  
Residual Tumour ◽  
Biochemical Effect ◽  
Free Cortisol

Summary Whilst literature is expanding on pasireotide use in the management of Cushing’s disease (CD), there is still currently much unknown about long-term and low-dose pasireotide use in CD. We present a 60-year-old female with residual CD after transphenoidal surgery (TSS), being successfully managed with S.C. pasireotide for over 10 years. For 6 years, her S.C. pasireotide was inadvertently administered at 360 µg twice daily (BID), almost half the recommended dose of 600 µg BID. Despite the low-dose, her urinary free cortisol (UFC) normalised within 6 months and Cushingoid features resolved. She remained in biochemical and clinical remission on the same low-dose for 6 years, before a medication audit discovered her mistaken dose and directed her to take 600 µg BID. With the higher dose 600 µg BID for the next 5 years, her glycaemia worsened without any changes in her UFC and residual tumour volume. Our case showed the continuing effectiveness and safety of treatment with S.C. pasireotide for more than 10 years, and that a low-dose regimen may be considered an option for responders by its safety profile. Learning points A lower dose of pasireotide may be effective in the initial treatment of CD than the recommended 600 µg BID dosage, though more studies are required to explore this. Low-dose pasireotide use has the benefit of minimising adverse effects. In the long-term, pasireotide has a sustained clinical and biochemical effect and is well tolerated.

scholarly journals Biological Effects of Short-Term or Prolonged Administration of 9-[2-(Phosphonomethoxy)Propyl]Adenine (Tenofovir) to Newborn and Infant Rhesus Macaques

2004 ◽  
Vol 48 (5) ◽  
pp. 1469-1487 ◽  
Author(s):  
Koen K. A. Van Rompay ◽  
Laurie L. Brignolo ◽  
Dennis J. Meyer ◽  
Christopher Jerome ◽  
Ross Tarara ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Low Dose ◽  
Biological Effects ◽  
Daily Administration ◽  
Time Range ◽  
High Dose ◽  
Short Term ◽  
Therapeutic Benefits ◽  
Short Period ◽  
Renal Tubular Disorder

ABSTRACT The reverse transcriptase inhibitor 9-[2-(phosphonomethoxy)propyl]adenine (PMPA; tenofovir) was previously found to offer strong prophylactic and therapeutic benefits in an infant macaque model of pediatric human immunodeficiency virus (HIV) infection. We now summarize the toxicity and safety of PMPA in these studies. When a range of PMPA doses (4 to 30 mg/kg of body weight administered subcutaneously once daily) was administered to 39 infant macaques for a short period of time (range, 1 day to 12 weeks), no adverse effects on their health or growth were observed; this included a subset of 12 animals which were monitored for more than 2 years. In contrast, daily administration of a high dose of PMPA (30 mg/kg subcutaneously) for prolonged periods of time (>8 to 21 months) to 13 animals resulted in a Fanconi-like syndrome (proximal renal tubular disorder) with glucosuria, aminoaciduria, hypophosphatemia, growth restriction, bone pathology (osteomalacia), and reduced clearance of PMPA. The adverse effects were reversible or were alleviated following either complete withdrawal of PMPA treatment or reduction of the daily regimen from 30 mg/kg to 2.5 to 10 mg/kg subcutaneously. Finally, to evaluate the safety of a prolonged low-dose treatment regimen, two newborn macaques were started on a 10-mg/kg/day subcutaneous regimen; these animals are healthy and have normal bone density and growth after 5 years of daily treatment. In conclusion, our findings suggest that chronic daily administration of a high dose of PMPA results in adverse effects on kidney and bone, while short-term administration of relatively high doses and prolonged low-dose administration are safe.

scholarly journals Varying Dose of Atropine in Slowing Myopia Progression in Children Over Different Follow-Up Periods by Meta-Analysis

2022 ◽  
Vol 8 ◽  
Author(s):  
Jiahe Gan ◽  
Shi-Ming Li ◽  
Shanshan Wu ◽  
Kai Cao ◽  
Dandan Ma ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Cohort Studies ◽  
Low Dose ◽  
First Year ◽  
High Dose ◽  
Moderate Dose ◽  
Myopia Progression ◽  
Axial Elongation ◽  
Dose Dependent

Purpose: To evaluate the efficacy and safety of atropine for slowing myopia progression and to investigate whether the treatment effect remains constant with continuing treatment.Method: Studies were retrieved from MEDLINE, EMBASE, and the Cochrane Library from their inception to May 2021, and the language was limited to English. Randomized controlled trials (RCTs) and cohort studies involving atropine in at least one intervention and placebo/non-atropine treatment in another as the control were included and subgroup analysis based on low dose (0.01%), moderate dose (0.01%–<0.5%), and high dose (0.5–1.0%) were conducted. The Cochrane Collaboration and Newcastle-Ottawa Scale were used to evaluate the quality of RCTs and cohort studies, respectively.Results: Twelve RCTs and fifteen cohort studies involving 5,069 children aged 5 to 15 years were included. The weighted mean differences in myopia progression between the atropine and control groups were 0.73 diopters (D), 0.67 D, and 0.35 D per year for high-dose, moderate-dose, and low-dose atropine, respectively (χ2 = 13.76; P = 0.001, I2 = 85.5%). After removing studies that provided extreme findings, atropine demonstrated a significant dose-dependent effect on both refractive change and axial elongation, with higher dosages of atropine resulting in less myopia progression (r = 0.85; P = 0.004) and less axial elongation (r = −0.94; P = 0.005). Low-dose atropine showed less myopia progression (−0.23 D; P = 0.005) and less axial elongation (0.09 mm, P < 0.001) in the second year than in the first year, whereas in high-dose atropine more axial elongation (−0.15 mm, P = 0.003) was observed. The higher dose of atropine was associated with a higher incidence of adverse effects, such as photophobia with an odds ratio (OR) of 163.57, compared with an OR of 6.04 for low-dose atropine and 8.63 for moderate-dose atropine (P = 0.03).Conclusion: Both the efficacy and adverse effects of atropine are dose-dependent in slowing myopia progression in children. The efficacy of high-dose atropine was reduced after the first year of treatment, whereas low-dose atropine had better efficacy in a longer follow-up period.

scholarly journals THE EFFECT OF LOW VERSUS HIGH DOSE OF ANTI-SNAKE VENOM ON OUTCOMES AND ADVERSE EFFECTS IN SNAKE BITE CASES AT M.G.M. MEDICAL COLLEGE AND HOSPITAL, JAMSHEDPUR, JHARKHAND: A CROSS-SECTIONAL OBSERVATIONAL STUDY

2020 ◽  
pp. 55-58
Author(s):  
Sanjay Kumar Pandey ◽  
Vikram Murmu ◽  
P. Sarkar ◽  
Debarshi Jana
Keyword(s):  
Adverse Effects ◽  
Snake Venom ◽  
Dose Group ◽  
Low Dose ◽  
Financial Burden ◽  
Snake Bite ◽  
High Dose Group ◽  
High Dose ◽  
Cross Sectional ◽  
Medical College

Background: Snakebite is a significant problem in rural India. It is an occupational hazard and causes considerable morbidity and mortality. It is a significant financial burden on victims and hospitals. Fortunately, these bites are eminently treatable and curable. A lack of universal consensus for the dose of Anti Snake Venom(A.S.V.) exists. Low vs. high dose is the most debated topic. Dose-related adverse effects are enduring issues in the snake bite management protocols. Objective: To observe the effects of the low and high dose of A.S.V. on results and side effects in snake bite cases in MGMM COLLEGE and hospital in Jharkhand, India. Materials and Methods: We did a cross-sectional in the medical emergency and intensive care unit of M.G.M. Medical College, Jamshedpur. We analyze the prescriptions of 58 snakebite patients admitted to the I.C.U/emergency. We analyzed data during the study period of 3 months. We used descriptive statistics and Microsoft Excel 2007. Fisher's Exact Test is used to analyze statistically Result: A.K.I. was found in 5 (21%) low dose group and 9 (26%) high dose group, patients with neuroparalysis required ventilator/Ambu bag support in 3 (13%) low dose group and 6 (18%) patients high dose group. The hospital stay duration was 3.98 for the low dose group and 5.22 days for the high dose group. The mortality rate was 4% in the low dose group versus 6% in the high dose group. The manifestation of adverse effects of A.S.V. was also found to be significantly low in a low dose A.S.V. group Conclusion: we compared treatment outcomes and found low doses of A.S.V. may be utilized to optimize the effective dose and minimize its adverse effects. A beneficial trend for the low-dose group is seen.

The toxicological effects of bisphenol A and octylphenol on the reproductive system of prepubertal male rats

2016 ◽  
Vol 33 (2) ◽  
pp. 133-146 ◽  
Author(s):  
Müfide Aydoğan Ahbab ◽  
Nurhayat Barlas ◽  
Gözde Karabulut
Keyword(s):  
Treatment Group ◽  
Adverse Effects ◽  
Reproductive System ◽  
Low Dose ◽  
Hormone Level ◽  
Sperm Head ◽  
Male Rats ◽  
Control Group ◽  
High Dose ◽  
Treatment Groups

The aim of the present study was to assess and compare the individual adverse effects of bisphenol A (BPA) and octylphenol (OP) on the reproductive system of prepubertal male rats. Rats were exposed to BPA and OP at doses of 125 and 250 mg/kg/day, by gavage, for 90 days. At the end of the study, the testes, epididymis, prostate gland, and seminal vesicle were removed and examined histopathologically. Also, 3-β-hydroxysteroid dehydrogenase expressions were analyzed and serum testosterone and luteinizing hormone (LH) levels were measured. Sperm head count of caput epididymis was performed using a hemocytometer. Seminiferous and epididymal round tubules were evaluated for tubule diameter, lumen diameter, and height of tubule epithelium. There were significant increases in relative testes weights in BPA125, OP125, and OP250 groups compared with the control. Atrophic tubules, pyknotic tubules, combined tubules, congestion, vacuolization of Sertoli cell, cell debris in the lumen, tubules without sperm, and degeneration of tubules were noted in the tissue specimens obtained from the treatment groups compared with the control group. Sperm head counts were decreased in all treatment groups except for the low-dose BPA group. Testosterone (T) levels decreased in the BPA and high-dose OP treatment groups. LH levels increased in BPA treatment groups and the low-dose OP treatment group and decreased in the high-dose OP group. Epithelial height of high-dose BPA and OP treatment groups increased compared with the control group. Furthermore tubular height of low-dose BPA and high-dose OP groups increased with respect to control levels. In the OP250 treatment group, thyroxine hormone level was increased compared to other groups. Also, in the OP125 treatment group, triiodothyronine hormone level was increased compared with other groups. The results of this study showed that BPA and OP affect the steroidogenic enzyme expression and T production in Leydig cells. In conclusion, BPA and OP have adverse effects on the male reproductive system of prepubertal rats.

Acetaminophen: Neonatal hepatotoxicity due to late pregnancy exposure

1987 ◽  
Vol 45 ◽  
pp. 718-719
Author(s):  
G.A. Miranda ◽  
M.A. Arroyo ◽  
C.A. Lucio ◽  
M. Mongeotti ◽  
S.S. Poolsawat
Keyword(s):  
Low Dose ◽  
Fetal Liver ◽  
Late Pregnancy ◽  
Toxic Chemicals ◽  
Control Group ◽  
High Dose ◽  
Over The Counter ◽  
Liver And Kidney ◽  
Neonatal Liver ◽  
Childbearing Women

Exposure to drugs and toxic chemicals, during late pregnancy, is a common occurrence in childbearing women. Some studies have reported that more than 90% of pregnant women use at least 1 prescription; of this, 60% used more than one. Another study indicated that 80% of the consumed drugs were not prescribed, and of this figure, 95% were “over-the-counter” drugs. Acetaminophen, the safest of all over-the-counter drugs, has been reported to induce fetal liver necrosis in man and animals and to have abortifacient and embryocidal action in mice. This study examines the degree to which acetaminophen affects the neonatal liver and kidney, when a fatty diet is simultaneously fed to the mother during late pregnancy.Timed Swiss Webster female mice were gavaged during late pregnancy (days 16-19) with fat suspended acetaminophen at a high dose, HD = 84.50 mg/kg, and a low dose, LD = 42.25 mg/kg; a control group received fat alone.

Evaluation of hippocampus in rhesus monkeys after chronic (1-year) inhalation exposure to marijuana: I. Electron microscopy

1990 ◽  
Vol 48 (3) ◽  
pp. 398-399
Author(s):  
A.M. Andrews ◽  
S.W. Wilson ◽  
A.C. Scallet ◽  
S.F. Ali ◽  
J. Bailey ◽  
...  
Keyword(s):  
Synaptic Vesicles ◽  
Rhesus Monkeys ◽  
Low Dose ◽  
Inhalation Exposure ◽  
Synaptic Cleft ◽  
High Dose ◽  
Withdrawal Time ◽  
Treatment Groups ◽  
Ultrastructural Evidence ◽  
Male Rhesus

Exposure of rhesus monkeys (Macaca mulatta) to marijuana via inhalation or to intravenous delta-9-tetrahydrocannabinol (THC), reportedly caused ultrastructural evidence of increased synaptic width. Chronic marijuana smoke in a single rhesus monkey examined after a six month withdrawal time caused ultrastructure changes in the septal, hippocampal and amygdala regions; the synaptic cleft was widened, electron opaque material was found in the cleft and in the pre- and postsynaptic regions, with some clumping of the synaptic vesicles. The objective of our study was to assess neuropathological alterations produced by chronic inhalation of marijuana smoke.Nineteen male rhesus monkeys, 3-5 years of age and weighing 3-8 kg, were divided into four treatment groups: a) sham control, b) placebo smoke (7 days/ week) c) low dose marijuana (2 times/week with 5 days/week sham) and d) high dose marijuana (7 times/week). A smoke exposure consisted of smoke from one cigarette (2.6% THC) burned down to 10 mm butt length. Smoke was administered via smoke generator (ADL II, Arthur D. Little, Inc. Cambridge, MA) and nose-mouth only masks (local production) equipped with one-way valves.

Benefit/Risk Profile of Combined Antiplatelet Therapy with Ticlopidine and Aspirin

1991 ◽  
Vol 65 (05) ◽  
pp. 504-510 ◽  
Author(s):  
Raffaele De Caterina ◽  
Rosa Sicari ◽  
Walter Bernini ◽  
Guido Lazzerini ◽  
Giuliana Buti Strata ◽  
...  
Keyword(s):  
Platelet Function ◽  
Low Dose ◽  
Bleeding Time ◽  
Ex Vivo ◽  
Stable Coronary Artery Disease ◽  
High Dose ◽  
Single Drug ◽  
Before And After ◽  
Serum Thromboxane ◽  
Artery Disease

SummaryTiclopidine (T) and aspirin (ASA) are two antiplatelet drugs both capable of prolonging bleeding time (BT), with a different mechanism of action. A synergism in BT prolongation has been reported and is currently considered an argument for not recommending their combination. However, a profound suppression of platelet function might be a desirable counterpart of a marked prolongation of BT, with a possible use in selected clinical situations. We therefore studied ex vivo platelet function (aggregation by ADP 0.5-1-2.5 μM; adrenaline 0.75-2.5 μM; collagen 1.5-150 μg/ml; arachidonic acid 1 mM; PAF 1 μM; adrenaline 0.17 μM + ADP 0.62 μM; serum thromboxane ([TX]B2 generation) and BT (Mielke) in 6 patients with stable coronary artery disease receiving such combination. Patients underwent sequential laboratory evaluations at baseline, after 7 days of T 250 mg b.i.d., before and after the intravenous administration of ASA 500 mg, respectively, and, finally, after a minimum of 7 days of sole ASA oral administration (50 mg/day). The experimental design, therefore, allowed a comparison of T and ASA effects (2nd and 4th evaluation), and an assessment of the combination effect (3rd evaluation). Platelet aggregation in response to all doses of ADP was depressed more by T than by ASA. Conversely, responses to adrenaline, and arachidonate were affected more by ASA than by T. For all other agents, differences were not significant. T + ASA combination was more effective (p <0.05) than either treatment alone in depressing responses to high-dose collagen (% over control, mean ± SEM: T: 95 ± 3; ASA: 96 ± 5; T + ASA: 89 ± 4). Serum TXB2 (basal, ng/ml: 380 ± 54) did not change with T (372 ± 36), dropped to <1 ng/ml on ASA injection and slightly re-increased to 9.1 ± 3.1 ng/ml on oral low-dose ASA. BT (basal 7.4 ± 0.6 min) was affected similarly by T (9.2 ± 0.8) or ASA (9.7 ± 0.9) alone, but increased to 15.0 ± 0.7 min on combination treatment (106% increase over control). Thus, the strong synergism in BT prolongation by ASA-T combination has a counterpart in the inhibition of platelet function in response to strong stimuli such as high-dose collagen, not otherwise affected significantly by single-drug treatment. This effect is a possible rationale for the clinical evaluation of T + ASA combination.

Intensive Initial Oral Anticoagulation and Shorter Heparin Treatment in Deep Vein Thrombosis

1984 ◽  
Vol 52 (03) ◽  
pp. 276-280 ◽  
Author(s):  
Sam Schulman ◽  
Dieter Lockner ◽  
Kurt Bergström ◽  
Margareta Blombäck
Keyword(s):  
Deep Vein Thrombosis ◽  
Oral Anticoagulation ◽  
Dose Group ◽  
Low Dose ◽  
Clinical Signs ◽  
Coagulation Factor ◽  
High Dose ◽  
Vein Thrombosis ◽  
Heparin Treatment ◽  
Deep Vein

SummaryIn order to investigate whether a more intensive initial oral anticoagulation still would be safe and effective, we performed a prospective randomized study in patients with deep vein thrombosis. They received either the conventional regimen of oral anticoagulation (“low-dose”) and heparin or a more intense oral anticoagulation (“high-dose”) with a shorter period of heparin treatment.In the first part of the study 129 patients were randomized. The “low-dose” group reached a stable therapeutic prothrombin complex (PT)-level after 4.3 and the “high-dose” group after 3.3 days. Heparin was discontinued after 6.0 and 5.0 days respectively. There was no difference in significant hemorrhage between the groups, and no clinical signs of progression of the thrombosis.In the second part of the study another 40 patients were randomized, followed with coagulation factor II, VII, IX and X and with repeated venograms. A stable therapeutic PT-level was achieved after 4.4 (“low-dose”) and 3.7 (“high-dose”) days, and heparin was discontinued after 5.4 and 4.4 days respectively. There were no clinical hemorrhages, the activity of the coagulation factors had dropped to the same level in both groups at the time when heparin was discontinued and no thromboembolic complications occurred.Our oral anticoagulation regimen with heparin treatment for an average of 4.4-5 days seems safe and reduces in-patient costs.

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