Drugs Used To Treat Obesity And Hyperlipidemia

Front 1

Obesity

Back 1

can lead to organ complications

adipose haslimited ability to store fat

theexcess fat that does NOT go to adipose causes the health problems

adipose expansion: becomes insulin resistant

Front 2

Process

Back 2

-caloric excess and inactivity --> adipose espansion

-dysregulated lipolysis --> flux of fatty acids to liver

Front 3

Metabolic syndrom

Back 3

Obesity(Abdominal) plus at least 2 of the following

-high serum triacyglycerides

-low HDL

-hypertension

-hyperglycemia

Front 4

Medical management of obesity

Back 4

if BMI above 25 or waist circum. is above cutoff -->conduct laboratory investigation to assess comorbidities: BP, HR, fasting glucose, triacyglycerides, lipid profile,

--> asses and screen for depression and mood disorders

--> treat comorbidities and other health risks if present

-->assess readiness to change behaviours and barriers to weight loss

Front 5

Medical management of obesity

Back 5

Pharmacotherapy if BMI is above 27 plus risk factors or if its straight above 30

Front 6

Pharmacological treatment of obesity

Back 6

Not much available

Only 2 classes of drugs are currently available

1. appetite suppressants

2. lipase inhibitors

safety concerns over long term use of appetite suppressants (3 month use limit)

Lipase inhibitors have significant GI advers effects

Front 7

Appetite supressants

Back 7

-not available in Canada

-alter the release and reuptake of neurotransmitters involved in controlling appetite

-Sibutramine: limits reuptake of norepinephrine and serotonin by nerve terminals -- prolongs sympathetic activation, supresses appetite

-increased risk of CVD in high risk cardiac patients

Phentermine: sympathomimetic amine

-only currently available member of this group --> promotes the release of norepinephrine and dopamine - prolongs sympathetic activation, supresses appetite

elevationsin heart rate and blood pressure with phentermine limit its duration of use to3 months

Front 8

Lipase inhibitors

Back 8

thisgroup of drugs inhibits the digestive enzymes, lipases ... decreases breakdownof dietary fat, thus limiting fat absorption from the intestine

orlistat is the only currently availablemember of this group, and is the only anti-obesity medication with worldwideapproval

orlistat inhibits both gastric andpancreatic lipases

adversegastrointestinal side effects limit the tolerability in many patients(especially if dietary fat intake is greater than 30% of total calories)

Front 9

Potential future pharmacological treatment of obesity

Back 9

1. thyroid hormone receptor agonist

2. GLP-1 analogs, such as liraglutide

3. direct specific AMPK activators

Front 10

Thyroid hormone receptor agonists

Back 10

•in adults, thyroid hormones regulate basalmetabolic rate through the following actions:

1) stimulation of Na+/K+ATPaseactivity

2) stimulation of carbohydrate absorption fromthe intestine and release of fatty acidsfrom adipocytes

3) upregulation of b-adrenergic receptors in many tissues, including the heart and nervoussystem

Front 11

Thyroid hormone rece

Back 11

TRa = heart and brain --> HR and anxiety increase

TRB = in adipose and liver --> increased metabolism (increasing lipolysis and FA oxidation)

TRB activation also seems to lower circulating LDL

THyroid hormones act at the liver to increase LDL receptor expression

thyroidhormones normally increase the expression of low density lipoprotein (LDL)receptors in the liver to increase the uptake of cholesterol from blood

inhypothyroid patients less cholesterol is removed from the blood by the liver,resulting in less cholesterol excretion in bile

Front 12

GLP-1 Analogs

Back 12

liraglutide (degradation-resistant GLP-1analog) is approved (in Canada, 2010) for the treatment of T2DM, and is underclinical investigation for the treatment of obesity

incretins(GLP-1, GIP) bind incretinreceptors on bcells to stimulate insulin secretion

Front 13

Direct, specific AMPK activators

Back 13

metformin acts predominantly onliver, indirect activation of AMPK

opportunity for development ofdirect , specific AMPK activators that target adipose (and other metabolictissues)

The net effect of AMPK activation is stimulation of hepatic fatty acid oxidation and ketogenesis, inhibition of cholesterol synthesis, lipogenesis, and triglyceride synthesis, inhibition of adipocyte lipolysis and lipogenesis, stimulation of skeletal muscle fatty acid oxidation and muscle glucose uptake, and modulation of insulin secretion by pancreatic beta-cells.[1]