Chapter 3 MPPT Controllers
3.1 Perturb & Observe Algorithm
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fitness, and (4) may help with maintenance of weight loss. Physical activity should be an integral part of weight loss therapy and weight maintenance. Initially, moderate levels of physical activity for 30 to 45 minutes, 3 to 5 days per week should be encouraged. All adults should set a long-term goal to accumulate at least 30 minutes or more of moderate intensity physical activity on most, and preferably all, days of the week. The combination of a reduced calorie diet and increased physical activity is recommended since it produces weight loss, decreases abdominal fat, and increases cardiorespiratory fitness.69
Behavioural and Psychological Therapy: This is a useful adjunct when incorporated into treatment for weight loss and weight maintenance. Practitioners need to assess the patient’s motivation to enter weight loss therapy; assess the readiness of the patient to implement the plan and then take appropriate steps to motivate the patient for treatment. Behavioural therapy strategies to promote diet and physical activity should be used routinely, as they are helpful in achieving weight loss and weight maintenance.69
Pharmacotherapy: Weight loss drugs approved by the FDA may be used as part of a comprehensive weight loss program including diet and physical activity for patients with a BMI of ≥ 30 with no concomitant obesity- related risk factors or diseases, and for patients with a BMI of ≥ 27 with concomitant obesity-related risk factors or diseases. Drugs should never be used without concomitant lifestyle modification. Continual assessment of drug therapy for efficacy and safety is necessary. If the drug is efficacious in helping the patient lose and/or maintain weight loss and there are no serious adverse effects, it can be continued. If not, it should be discontinued.69 Prescription medications currently evaluated as antiobesity agents include:
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bupropion SR, metformin, rimonabant, sibutramine, topiramate, orlistat, and low-dose orlistat.29. A recent review article on pharmaceutical interventions for obesity by Caveney et al.80 Showed the following current and future antiobesity drugs as discussed below.
Current Anti-obesity Drugs
Amphetamine: This is a central adrenergic agonist which causes central noradrenaline release.
Its weight loss properties were first shown in 1938.It has a high abuse and addiction potential can also cause elevation of cardiac output and blood pressure. Therefore, it is very rarely used for obesity management.
Amphetamine derivatives: These include Benzphetamine, Phendimetrazine, Diethylpropion, and Phentermine. Mechanism of action is similar to that of amphetamine through central norepinephrine and dopamine release. They are approved only for short treatment periods of up to 12 weeks
Rimonabant: This is a selective cannabinoid receptor (CB1) antagonist. It was withdrawn from the market in 2009 because its use was found to be associated with severe psychiatric side effects, such as depression, anxiety and suicidal ideation.
Sibutramine: This is a serotonin and norepinephrine reuptake inhibitor which was approved as an antiobesity drug in 1997 US-FDA and recently withdrawn from market in 2010 due to its cardiovascular side effects.
Mazindol: This ia sympathomimetic amine initially approved as an anti-obesity drug in1973 by US-FDA and later withdrawn from US market in 2001because of allegations of increased risk of cardiac valvulopathy with its use.
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Fenfluramine: This is a serotonin reuptake inhibitor that can also cause serotonin release from vesicular storage. It was approved in1973 by US-FDA and withdrawn from the United States 1997and later from other countries after reports of valvular heart damage (caused by selective stimulation of 5-HT2B receptors on human cardiac valves) and primary pulmonary hypertension.
Phenylpropanolamine: This drug acts by causing central norepinephrine and epinephrine release. It was approved in1979 by US-FDA and withdrawn in 2000 because of increased risk of haemorrhagic stroke.
Dinitrophenol: This drug acts through the uncoupling of oxidative phosphorylation from the production of ATP, leading to calorie loss as heat. It was introduced in the United States in 1933 and withdrawn in 1938 because of cases of fatal hyperthermia, rashes and cataract.
Ephedra: This is also a sympathomimetic drug approved in 1947 and banned in 2004 by US-FDA because of the associated increased risk of cardiovascular and neuropsychiatric adverse events with its use.
Orlistat (Xenical): This is a gastrointestinal lipase inhibitor that acts by inhibiting the absorption of dietary fat.
Lorcaserin (Arena): This is a selective 5-HT2C receptor agonist.
Qnexa (Vivus): This is a combination of phentermine and topiramate.
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Future Anti-obesity Drugs
Drugs that are presently undergoing different phases of drug trial for future management of obesity include the following:
Contrave (Orexigen): This is a combination of naltrexone and bupropion.
Cetilistat (Norgina BV/Takeda): This is a pancreatic lipase inhibitor.
Empatic (Orexigen): It is a drug combination of bupropion and zonisamide.
Tesofensine (NeuroSearch): A triple reuptake inhibitor (serotonin, norepinephrine and dopamine).
Liraglutide (NovoNordisk): This is GLP-1 analogue already approved for type 2 diabetes mellitus and presently is is undergoing phase 3 studies for obesity.
Peptide YY (PYY), Pancreatic polypeptide (PP): These drugs include Obinepitide (Nastech), TM30339 (Nastech) and PP1420 (Wellcome Trust). Obinepitide is a synthetic analogue of PYY and PP. TM30339 targets the PP Y4 receptor while PP1420 is a PP analogue.
Neuropeptide Y (NPY) modulator: Example include Velneperit which is a NPY Y5 receptor antagonist.
Melanin-concentrating hormone-1 receptors antagonists: An example is BMS-830216 (Bristol Myers Squibb).
Pramlintide plus Metreleptin: Pramlintide is a synthetic analogue of amylin while metreleptin is an analogue of human leptin.
Agouti related peptide (AgRP) antagonists: An example is TTP435 (TransTech).
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Methionine aminopeptidase 2 (MetAP2) inhibitor: ZGN-433 (Zafgen).
Sodium glucose transporter 2 (SGLT2) inhibitor: PF04971729 (Pfizer).
Diglyceride Acyltransferase1(DGAT1) inhibitor: PF-04620110 (Pfizer).
Dopamine (D3) receptor antagonists: GSK598809 (GSK).
Mu-opioid receptor antagonists: GSK1521498 (GSK).
Vabicaserin (Wyeth): This is an antipsychotic drug.
Other anti-obesity drugs in development are Melanocortin-4 receptor (MC4R) agonists and 5-HT6 receptor ligands
Bariatric Surgery (Weight Loss Surgery) : Weight loss surgery is an option in carefully selected patients with clinically severe obesity (BMI ≥ 40 or ≥35 with comorbid conditions) when less invasive methods of weight loss have failed and the patient is at high risk for obesity-associated morbidity or mortality.69There are several types of weight loss procedures (bariatric surgery) that are categorized by their mechanism of action: Restrictive (e.g., Adjustable gastric banding), Malabsorptive (e.g., Bileopancreatic diversion), or a combination of Restrictive and Malabsorptive peocedures (e.g., Roux-en-Y gastric bypass).29
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CHAPTER THREE