Pharmacotherapies for Obesity: Past, Current, and Future Therapies

Past therapies for the treatment of obesity have typically involved pharmacological agents usually in combination with a calorie-controlled diet. This paper reviews the efficacy and safety of pharmacotherapies for obesity focusing on drugs approved for long-term therapy (orlistat), drugs approved for short-term use (amfepramone [diethylpropion], phentermine), recently withdrawn therapies (rimonabant, sibutamine) and drugs evaluated in Phase III studies (taranabant, pramlintide, lorcaserin and tesofensine and combination therapies of topiramate plus phentermine, bupropion plus naltrexone, and bupropion plus zonisamide). No current pharmacotherapy possesses the efficacy needed to produce substantial weight loss in morbidly obese patients. Meta-analyses support a significant though modest loss in bodyweight with a mean weight difference of 4.7 kg (95% CI 4.1 to 5.3 kg) for rimonabant, 4.2 kg (95% CI 3.6 to 4.8 kg) for sibutramine and 2.9 kg (95% CI 2.5 to 3.2 kg) for orlistat compared to placebo at ≥12 months. Of the Phase III pharmacotherapies, lorcaserin, taranabant, topiramate and bupropion with naltrexone have demonstrated significant weight loss compared to placebo at ≥12 months. Some pharmacotherapies have also demonstrated clinical benefits. Further studies are required in some populations such as younger and older people whilst the long term safety continues to be a major consideration and has led to the withdrawal of several drugs

Fenitrothion: toxicokinetics and toxicologic evaluation in human volunteers.

An unblinded crossover study of fenitrothion 0.18 mg/kg/day [36 times the acceptable daily intake (ADI)] and 0.36 mg/kg/day (72 X ADI) administered as two daily divided doses for 4 days in 12 human volunteers was designed and undertaken after results from a pilot study. On days 1 and 4, blood and urine samples were collected for analysis of fenitrothion and its major metabolites, as well as plasma and red blood cell cholinesterase activities, and biochemistry and hematology examination. Pharmacokinetic parameters could only be determined at the higher dosage, as there were insufficient measurable fenitrothion blood levels at the lower dosage and the fenitrooxone metabolite could not be measured. There was a wide range of interindividual variability in blood levels, with peak levels achieved between 1 and 4 hr and a half-life for fenitrothion of 0.8-4.5 hr. Although based on the half-life, steady-state levels should have been achieved; the area under the curve (AUC)(0-12 hr) to AUC(0-(infinity) )ratio of 1:3 suggested accumulation of fenitrothion. There was no significant change in plasma or red blood cell cholinesterase activity with repeated dosing at either dosage level of fenitrothion, and there were no significant abnormalities detected on biochemical or hematologic monitoring

Challenges for Australia's Bio/Nanopharma Policies: trade deals, public goods and reference pricing in sustainable industrial renewal

Industrial renewal in the bio/nanopharma sector is important for the long term strength of the Australian economy and for the health of its citizens. A variety of factors, however, may have caused inadequate attention to focus on systematically promoting domestic generic and small biotechnology manufacturers in Australian health policy

Adherence to disease management interventions for chronic obstructive pulmonary disease patients: Patients' perspectives

BACKGROUND: The management of chronic obstructive pulmonary disease (COPD) requires a disease management approach - a combination of pharmacotherapy, pulmonary rehabilitation and behavioural changes. Patient adherence to therapy has been found to be poor, with a negative influence on outcomes.AIM: To explore facots associated with adherence t disease management interventions from COPD patients' perspectives.METHOD: A subset of 28 patients with moderate to severe COPD participating in a community-based randomised controlled trial were interviewed in-depth about their health beliefs, and attitudes to and experiences with their disease, its management and their relationships with health professionals. The interviews were transcribed verbatim and analysed thematically.RESULTS: Patients with a range of sociodemographic backgrounds and varying disease severity were interviewed. Adherence to disease management programs in COPD was found to be a complex process driven by health beliefs and experiences related to patient, treatment, disease and health professionals. 18 major themes related to adherent behaviour were identified, The balance between reservations in following treatment recomendations and motivating factors for following those recommendations was likely to determine decisions to adhere to disease management programs.CONCLUSION: The study highlighted the importance of consulation with the patient in the management of COPD. Treatment recommendations that fitted into patients' existing routines were more likely to be successful. Health professionals could enhance adherence by being empathic, improve patients' knowledge about the disease and faith in the treatment, and reduce their concerns about the treatment

Smoking cessation: COPD patients' perspective

Background: Smoking cessation is the most useful and cost effective way to reduce the risk of developing chronic obstructive pulmonary disease (COPD) and stop its progression. Long-term success rates with smoking cessation programs are known to be poor. Aim: To identify the factors influencing the outcomes of smoking cessation programs in COPD patients from their perspective. Method: In-depth interviews were conducted with 27 patients with a history of smoking, chosen from a cohort of 173 patients with moderate to severe COPD participating in a community-based randomised trial. Results: The study sample consisted of 6 females and 21 males with a mean age of 69.6 years and a mean smoking history of 58.5 = 34.1 pack years. Six patients continued to smoke at the time of the interview. Patients had attempted both pharmacological and non-pharmacological methods for quitting. Smoking cessation in COPD patients was influenced by various barriers and facilitators pertaining to patient, health, treatment and healthcare providers. Conclusion: Health professionals may be able to improve the outcomes of smoking cessation programs in COPD patients by being more proactive in offering combination smoking cessation interventions with adequate follow-up

Reference-Based Pricing Schemes: Effect on Pharmaceutical Expenditure, Resource Utilisation and Health Outcomes

Pharmaceutical expenditure is rising more rapidly than the general inflation rate in most advanced countries. One strategy that has been introduced to control pharmaceutical costs is reference-based pricing (RBP). Its potential is restricted to those specific segments of the drug market where several drugs (and/or their generic forms) exist without substantial evidence that any particular agent is superior. Three broad approaches have been adopted. These involve the aggregation of drugs into generic groups, related drug groups (e.g. ACE inhibitors) or drugs grouped by therapeutic indication (e.g. antihypertensives). For each drug group, a single reimbursement level or reference price is set. Drugs above the reference price require part or total payment by the patient. The experience with RBP ranges from over 10 years in Germany (involving all levels of RBP) to the more recent implementation of RBP for related drug groups in Australia. This review summarises the current state of knowledge on RBP from the published experiences in the countries where RBP has been adopted. The published systematic reviews of RBP from the countries that have implemented it suggest that RBP has been successful at temporarily capping drug prices for the RBP drug groups and achieving short term cost savings. However, other factors influencing total pharmaceutical expenditure have often occurred simultaneously and make it difficult to isolate specific effects of RBP. Further investigation is required before any valid conclusions can be drawn about the net effect of RBP on healthcare costs. RBP has withstood the initial legal challenges of pharmaceutical companies and the criticisms of some clinicians. Where the reference price is based on the lowest priced drug(s) in the group, RBP appears to be one of the few strategies likely to be effective at encouraging doctors to use the least expensive agents as first-line therapy and utilise more expensive agents in those who experience side effects or poor efficacy.Cost containment, Healthcare expenditure, Pharmacoeconomics