Author: John Carter

Anti-Obesity Drugs: Long-Term Efficacy and Safety: An Updated Review

SGLT-2 inhibitors, such as dapagliflozin, empagliflozin, and canagliflozin, block glucose reabsorption from the renal tubules and result in glycosuria. Interestingly, these drugs are effective, to some extent, in individuals without diabetes 74. Theoretically, the amount of glucose loss in urine is approximately 75 g/d (300 kcal energy deficit). Resultantly, 7–8 kg of weight loss owing to these medications can be expected in patients with diabetes over 6–12 months. However, in previous clinical studies with diabetic patients, only 2–3 kg weight loss was achieved with such agents; this was attributed to compensatory hyperphagia/increased appetite 75. Thus, combining an appetite suppressor, such as phentermine, with a SGLT-2 inhibitor can serve as a good option for weight management.

Drug Distribution to Tissues

AWithdrawn from the market for safety issue related to an increased cancer incidence in February 2020. Today, it remains the longest licensed antiobesity drug for long-term use and is available over the counter (Alli®). As a non-central nervous system agent, orlistat 120 mg is prescribed for adults and adolescents ≥12 years of age 19. Omega-3 PUFA (4g a day) were shown to decrease the TG levels by 30%, respective of the baseline levels, and can thus be used in the treatment of pancreatitis 31.

Blood-brain barrier

The identification of specific lipid biomarkers and mechanism-based knowledge of particular metabolic lipid processing pathways in connection to different pathologies is basis for developing innovative therapeutic approach for treating different pathologies. In addition, we mention the use of lipid carriers in drug delivery, particularly the use of lipidic prodrugs. Lipidic prodrugs contain the drug covalently attached to the lipid carrier (e.g., FA, glyceride, PL, or steroid). Drug-lipid conjugates can also join the physiological lipid trafficking pathways and accomplish drug targeting to specific sites 22.

The Challenges of Blood Pressure Control in Dialysis Patients

Active transport seems to be limited to drugs structurally similar to endogenous substances (eg, ions, vitamins, sugars, amino acids). They tend to come from animal and dairy products but can also be found in some fruits and vegetables. And they’re important for several functions in your body, including your vision, bone health, immunity and blood clotting. Some drugs leave the bloodstream very slowly because they bind tightly to proteins circulating in the blood. Others quickly leave the bloodstream and enter other tissues because they are less tightly bound to blood proteins. As unbound drug is distributed to tissues and its level in the bloodstream decreases, blood proteins gradually release the drug bound to them.

HOW ARE FAT-SOLUBLE VITAMINS USED?

Adipose TG lipase inhibition is responsible for TG buildup, while the inhibition of hormone-sensitive lipase. Surplus triacylglycerols, sterols, and sterol esters are enclosed by the PL monolayer and create lipid droplets. Naltrexone/bupropion (Contrave®) is a drug combination for the long-term management of weight loss. Each component of this medication has been used in other medical conditions since the 1980s 18. As there is no potential of abuse with this medication, it is not a controlled substance. Volume of distribution has nothing to do with the actual volume of the body or its fluid compartments but rather involves the distribution of the drug within the body.

  1. This approval followed that of a lower dose (1.8 mg daily Victoza®) in 2010 for T2DM management 52.
  2. The representation of various diseases caused by disruption in the physiological lipid metabolism.
  3. Omega-3 PUFA (4g a day) were shown to decrease the TG levels by 30%, respective of the baseline levels, and can thus be used in the treatment of pancreatitis 31.
  4. At high drug concentrations, the amount of bound drug approaches an upper limit determined by the number of available binding sites.
  5. Lipidic prodrugs contain the drug covalently attached to the lipid carrier (e.g., FA, glyceride, PL, or steroid).

Substantial research has been dedicated to the development of a newer generation of anti-obesity drugs. Compared to placebo, these drugs cause a significant weight reduction, including meaningful improvements in cardiometabolic profiles, while demonstrating good tolerability and safety in patients with obesity. Lipids have vast potential in disease therapy, from being disease markers that enable drug targeted therapy, to being natively used as a supplement, as well as being part of the lipid drug formulation and used as a carrier for a particular drug.

Because the CNS is so well perfused, the drug distribution rate is determined primarily by permeability. Drugs reach the central nervous system (CNS) via brain capillaries and cerebrospinal fluid (CSF). Although the brain receives about one sixth of cardiac output, drug penetration is restricted because of the brain’s permeability characteristics.

Both approaches have pharmacokinetic difficulties, as lipidization may bring in undesirable pharmacokinetic effects, such as increased uptake by the reticuloendothelial system and increasing non-specific plasma protein binding when administered intravenously 32. For example, several lipophilic variants of BCNU were clinically tried but have not shown improved clinical efficacy over BCNU 33. Formulation lipids, such as LCT, MCT, as well as DG, MG, FA, and PL, are used to improve drug absorption.

WHAT ARE SIDE EFFECTS OF FAT-SOLUBLE VITAMINS?

Decreased blood flow (eg, in shock) may lower the concentration gradient across the intestinal mucosa and reduce absorption by passive diffusion. In most clinical trials that evaluated pharmacologic interventions for more than 12 months, a weight loss of 4% to 8% was typical 56; however, this is rather disappointing considering the high prices of these drugs. Therefore, upon initiation of an anti-obesity medication, health providers must communicate several important messages to their patients. First, not every drug will produce effective results in patients and individual responses will vary widely. Second, when the maximal therapeutic effect of a drug is achieved, a plateau will be reached. The optimal dose of liraglutide for weight loss is 3 mg daily; however, to prevent the side effects of nausea and vomiting, treatment should be initiated with 0.6 mg QD and gradually escalated each week by 0.6 mg up to 3 mg 38.