Pentoxifylline

Authors:

Krishna M. Baradhi, Pavan Annamaraju, Preeti Patel

Findings:

Pentoxifylline, a xanthine derivative and PDE inhibitor, improves blood flow by reducing viscosity and enhancing red blood cell flexibility. It is FDA-approved for symptomatic treatment of claudication, although its efficacy relative to other treatments is debated. Off-label uses supported by varying levels of evidence include venous ulcers, severe alcoholic hepatitis (especially when corticosteroids are contraindicated), osteoradionecrosis, diabetic neuropathy, and Kawasaki disease. It exhibits anti-inflammatory (TNF-α inhibition) and immunomodulatory effects, potentially benefiting conditions like diabetic nephropathy, post-CABG recovery, and cerebrovascular disease, but requires careful monitoring due to adverse effects (mainly GI upset) and drug interactions (e.g., increased bleeding risk with antiplatelets/warfarin, interaction with theophylline).

Participants:

The text summarizes findings from various studies involving different participant groups, including patients with peripheral vascular disease (claudication), venous ulcers, severe alcoholic hepatitis, osteoradionecrosis, type-2 diabetic nephropathy, cerebrovascular disease, multi-infarct dementia, Kawasaki disease, Behcet syndrome, sickle cell disease, chronic kidney disease, patients undergoing cardiopulmonary bypass or coronary artery bypass graft (with EF <= 30%), and specific populations like those with hepatic/renal impairment or older adults. Animal models mentioned include Wistar rats, albino rats, and murine macrophage cell lines.

Dosage:

Available as a 400 mg extended-release oral tablet. Intermittent claudication: 400 mg orally 3 times daily with meals (reduce to twice daily for GI intolerance). Severe alcoholic hepatitis: 400 mg orally 3 times daily for 4 weeks. Venous leg ulcer: 400 mg orally 3 times daily. Diabetic neuropathy: 400 mg orally 3 times daily after meal. Kawasaki disease: 20 mg/kg/day. Renal impairment (CrCl < 30 mL/min): Reduce dose to 400 mg/day. Older patients: Start at lower dosage. Monitoring for bleeding risk needed, especially at daily doses > 800 mg in CKD patients.

Study Quality Assessment:

The text is a review article (StatPearls) citing multiple sources, including meta-analyses, a network meta-analysis, Cochrane reviews, systematic reviews, prospective randomized studies (some double-blind, placebo-controlled, multicenter), retrospective studies, animal studies, and case reports. Specific methodological details mentioned include double-blind placebo-controlled designs for some trials. Limitations noted include insufficient evidence for osteoradionecrosis prophylaxis (ref 10, 11) and the need for further research for certain off-label uses (e.g., osteoradionecrosis, Behcet's, sickle cell). Monitoring recommendations for bleeding risk, especially in specific patient groups (CKD, >800mg/day), are highlighted (ref 40).

All Effects:

Authors:

Zyta Beata Wojszel

Findings:

This literature review provides an overview of nootropics ('smart drugs'), categorizing them (classical, brain metabolism enhancers, cholinergics, plants/extracts) and discussing representatives like Piracetam, Meclofenoxate, Ginseng, and Ginkgo. It outlines mechanisms (e.g., improving brain metabolism/blood flow, cholinergic function, antioxidant effects), indications (primarily impaired cognition, memory, learning), dosages, side effects (generally mild but specific contraindications exist), and discusses use by students. While potentially effective for cognitive impairment, the review highlights insufficient evidence for efficacy and long-term safety in healthy individuals.

Participants:

Review covers studies involving humans (healthy, cognitively impaired, various ages including children, students, elderly, specific patient groups like Alzheimer's, stroke, dementia, schizophrenia, hyperkinetic disorder), animal models (rats, mice, chicks), and in vitro cell cultures.

Dosage:

Review details dosages for numerous substances: Deanol (500-2000mg/day), Meclofenoxate (500-2000mg/day), Nicergoline (30-60mg/day), Piracetam (2-8g/day depending on use), Pyritinol (300-600+mg/day), Vinpocetine (10-30mg/day), Naftidrofuryl (300-600mg/day), Dihydroergotoxine (up to 6mg/day), Lecithin (1.2g x3/day to 10-15g/day), Ginseng (200mg extract or 0.5-2g root/day), Ginkgo (120-300mg extract/day), Centella (60-120mg extract or 600mg leaves/day), Ashwagandha (750-1250mg extract or 6-10g root/day), Bacopa (200-400mg extract/day adults), Guarana (75mg extract tablet), Eleuthero (2-3g root or 20-40 drops extract/day), Rhodiola (100-600mg extract/day depending on standardization), Schisandra (2-6g fruit/day), Maca (1.5-3g powder/day).

Study Quality Assessment:

Review based on original research articles, meta-analyses, systematic reviews, and relevant animal studies. Mentions specific methods used in cited studies (e.g., EEG/ERP mapping, psychometric tests, behavioral tests like Morris water maze, T-maze, radial arm maze, passive avoidance). Notes use of double-blind, placebo-controlled designs in some cited human trials. Acknowledges limitations such as lack of clinical evidence for efficacy/safety in healthy individuals (especially long-term), questionable benefit in severe dementia for some nootropics, inconsistent findings in some areas (e.g., lecithin, Ginkgo in healthy young adults), and potential lack of dose-dependency for some effects. Funding source for publication acknowledged.

All Effects:

Findings:

Pentoxifylline (PTX) administration in rats subjected to transient global brain ischemia significantly improved hippocampal-dependent spatial memory and cognitive abilities in the Morris Water Maze test compared to sham-operated and vehicle-treated animals. Ischemia caused marked CA1 pyramidal cell loss; however, there was no statistically significant difference in the number of viable pyramidal cells between the control and PTX-treated groups after 4 days. The study concludes PTX had a protective effect against cognitive impairment induced by transient global ischemia in rats.

Participants:

Animal model: Adult male Wistar rats (n=32), 12-13 weeks old, weighing 250-300 g.

Dosage:

200 mg/kg PTX injected intraperitoneally (IP) at the beginning of the reperfusion phase following 20 min ischemia.

Study Quality Assessment:

Animal study (rats, n=32) comparing control, sham-operated, vehicle, and PTX-treated groups. Methods included bilateral common carotid artery occlusion (ischemia model), Morris Water Maze testing for spatial memory, Nissl staining for histopathology (CA1 pyramidal cell count). Statistical analysis used one-way ANOVA and Tukey's test. Ethics committee approval mentioned. Funding source acknowledged (Cellular and Molecular Research Centre, Tehran University of Medical Sciences; Amin Pharmaceutical Company).

All Effects:

Findings:

Pentoxifylline is an orally active haemorheological agent improving red blood cell deformability, reducing blood viscosity, and decreasing platelet aggregation/thrombus formation. Studies show it improves walking distance, rest pain, paraesthesia, muscle blood flow, cramps, and leg ulcers in peripheral vascular disease (60-100% of patients). In cerebrovascular disorders (approx. 85% improved), it improves psychometric tests, neuromotor/speech deficits, and increases cerebral blood flow, particularly to ischaemic areas. It is generally well-tolerated, with gastrointestinal symptoms being most common (approx. 3%).

Participants:

Patients with peripheral vascular disease, patients with cerebrovascular disorders.

Dosage:

600 to 1200 mg/day for peripheral vascular disease; Usually 600 to 1200 mg/day (300 to 600 mg/day in Japan) for cerebrovascular disorders.

Study Quality Assessment:

Review article summarizing findings from 'Extensive open and placebo-controlled studies'. Mentions comparisons with placebo and other drugs (nylidrin, adenosine, naftidrofuryl, co-dergocrine mesylate, pyrithioxine). Mentions study duration ('at least 6 weeks'). Mentions formulation ('conventional controlled release formulation'). Notes side effects were not significantly greater than placebo.

All Effects:

Findings:

Pentoxifylline treatment significantly reduced positive symptoms (PANSS), errors in the incongruent Stroop test, and reaction time in the congruent Stroop test compared to placebo. The number of categories achieved in the WCST was significantly higher in the pentoxifylline group. The study concludes that Pentoxifylline can help alleviate cognitive deficits and reduce psychotic symptoms in schizophrenia.

Participants:

N=52 patients diagnosed with chronic schizophrenia

Dosage:

400 mg dose of Pentoxifylline, twice a day for 8 weeks

Study Quality Assessment:

Randomized double-blind placebo-controlled clinical trial; N=52; Duration: 8 weeks; Assessments: Positive and Negative Syndrome Scale (PANSS), Wisconsin Card Sorting Test (WCST), digit span, Stroop test, Rey Auditory and Verbal Learning Test; Statistical methods mentioned (Kolmogorov-Smirnov test, t-test, Mann-Whitney test, chi-square test, generalized estimating equation model); Conflict of interest statement: Authors declared no potential conflicts.

All Effects: