Drugs For Obesity

Front 1

Ghrelin

Back 1

Increased eating
Arcuate nuclesus of hypothalamus

Front 2

Leptin
Glucagon like peptide-1 (GLP-1)
Peptide Y (PYY)

Back 2

Decreased eating
Arcuate Nucleus of hypothalamsu

Front 3

Neuropeptide Y (NPY)
Agouti Related Protein
Opioids (mu)
Galanin

Back 3

Incr eating--
Paraventricular nucleus of hypothalamus

Front 4

Melanocyte stimulating hormone
Corticotropin releasing hormone
Cholecystokinin

Back 4

Decreased eating
Paraventricular nucleus of hypothalamus

Front 5

Orexin
Melanocyte concentration hormone

Back 5

Increased eating
Lateral Hypothlamus (only one)

Front 6

α2
5-HT1A

Back 6

Incr eating
Hypothalamus

Front 7

α1 and β2
5-HT1B and 2C
Histamine H1 and H3

Back 7

Decr eating
Hypothalamus

Front 8

Dopamine

Back 8

Incr eating
Nucleus Accumbens (only one)

Front 9

Opioids

Back 9

Incr eating
Amygdala (only one)

Front 10

Neuropeptide Y (NPY)
Agouti Related Protein
Opioids (mu)

Back 10

Incr eating
Brainstem

Front 11

Leptin
Melanocyte stimulating hormone
Cholecystokinin

Back 11

Decr eating
Brainstem

Front 12

Ghrellin

Back 12

Incr eating
Vagus nerve

Front 13

Leptin
CCK
GLP-1
PYY

Back 13

decr eating
Vagus Nerve

Front 14

Cannabinoid CB1

Back 14

Incr eating
various/undetermined

Front 15

Dopamine D1 and D2

Back 15

Decr eating
various/undetermined

Front 16

Guidelines for therapy based on BMI

Back 16

Front 17

Sympathomimetics (Diethylpropion and Phentermine)
a. Mechanism of action

Back 17

Appetite suppressants
(1) The norepinephrine transporter (NET) normally removes norepinephrine from the synaptic cleft so terminating its actions.
(2) Norepinephrine is sequestered into vesicles via the vesicular monoamine transporter (VMAT).
(3) Amphetamine and similar drugs enhance release of norepinephrine
(a) Norepinephrine is released into the cytoplasm from vesicular stores
(b) The direction of the monoamine transporters (including NET and VMAT) is reversed
(4) The released norepinephrine acts on hypothalamic receptors (α1 and β2) to decrease eating
(5) Weight regain occurs upon cessation of therapy

Front 18

Sympathomimetics (Diethylpropion and Phentermine)--Adverse Effects

Back 18

(1) Insomnia (if taken in late in the day)
(2) Cardiovascular effects (hypertension, palpitations, arrhythmias, valvular heart disease)
(3) Potential for abuse

Front 19

Sympathomimetics (Diethylpropion and Phentermine)--Contraindications

Back 19

(1) Patient with hypertension or cardiovascular disease
(2) Diabetics may experience decreased insulin or oral hypoglycemic dosage requirements soon after starting therapy and prior to any weight loss
(3) History of drug abuse

Front 20

Sympathomimetics (Diethylpropion and Phentermine)--Drug interaxns

Back 20

MAO inhibitors

Front 21

Sympathomimetics (Diethylpropion and Phentermine)--Clinical use

Back 21

(1) Short-term (up to 12 weeks) use in weight management
(2) Mean weight loss of about 3 kg more than with placebo
(3) As tolerance develops, they become ineffective, and the risk of dependence and abuse increases.

Front 22

Lorcaserin
a. Mechanism of action

Back 22

(1) Lorcaserin is an agonist of the the 5-HT2C receptor designed to promote weight loss.
(2) Activation of the 5-HT2C receptor decreases food intake through the proopiomelanocortin system of neurons.

Front 23

Lorcaserin--Adverse Effects

Back 23

Headache, nausea and dizziness

Front 24

Lorcaserin--contraindications & precautions

Back 24

Potential for serotonin syndrome when taken with other drugs which modulate serotonin

Front 25

Lorcaserin--drug interactions

Back 25

(1) Inhibits CYP2D6 which would increase the serum concentrations of drugs metabolized by this P450 isoenzyme
(2) Potential for serotonin syndrome

Front 26

Lorcaserin--Clinical Use

Back 26

(1) Approved for use in obese patients (body mass index [BMI] of >30
kg/m2) and for patients who are overweight (BMI >27 kg/m2) and
have one weight-related risk factor such as hypertension, dyslipidemia or type 2 diabetes.
(2) Moderate effect on weight loss (3%-4% reduction of individual’s body weight)

Front 27

Phentermine and topiramate combination
a. Mechanism of action

Back 27

1) Phentermine - see above
(2) Topiramate is an antiepileptic drug. Some patients experience weight loss with topiramate and it is hypothesized that this may be due tobappetite suppression resulting from both antagonism of AMPA receptors and metabolic acidosis.

Front 28

Phentermine and topiramate combination--Adverse Effects

Back 28

(1) Insomnia and cardiovascular effects related to the phentermine
(2) Cognitive impairment, and metabolic acidosis and kidney stones with topiramate
(3) Those associated with the combination include dry mouth, paresthesia, constipation, and dysgeusia

Front 29

Phentermine and topiramate combination-Contraindications & precautions

Back 29

Contraindicated for use in pregnancy - Topiramate is associated with increased risk of oral clefts when taken in the first trimester of pregnancy

Front 30

Phentermine and topiramate combination--Drug Interactions

Back 30

(1) Phentermine - MAO inhibitors
(2) Inhibitors and inducers of P450 enzymes have corresponding effects on blood levels of topiramate

Front 31

Phentermine and topiramate combination--Clinical Use

Back 31

(1) Approved for use in obese patients (body mass index [BMI] of >30 kg/m2) and for patients who are overweight (BMI >27 kg/m2) and have one weight-related risk factor such as hypertension, dyslipidemia or type 2 diabetes.
(2) 7%-9% reduction of individual’s body weight

Front 32

Impairment of food absorption (orlistat)
1. Mechanism of action

Back 32

a. Lipase hydrolyzes dietary fat (triglycerides) into absorbable free fatty acids and monoacylglycerols.
b. Micelle formation allows absorption of approximately 90% of dietary triglyceride as monoacylglycerol and fatty acids; cholesterol and fat-soluble vitamins absorbed with lipids
c. Orlistat is a synthetic derivative of the naturally-occuring lipase inhibitor, lipostatin (produced by the mold Streptomyces toxytricini). Orlistat forms a covalent bond with active sites in the lipase.
d. By inhibiting GI lipase, approximately 1/3 of dietary triglyceride is excreted unchanged in stool; absorption of cholesterol and fat-soluble vitamins are also decreased

Front 33

Impairment of food absorption (orlistat)--Adverse Effects

Back 33

a. Flatulence with discharge
b. Oily spotting
c. Fecal urgency
More likely to occur after high-fat dietary indiscretions and are associated with a high incidence of drug discontinuation.

Front 34

Impairment of food absorption (orlistat)--Drug interactions

Back 34

Absorption of fat-soluble vitamins is decreased. Supplements are required. They should be taken 2 hours before or 1 hour after taking orlistat.

Front 35

Impairment of food absorption (orlistat)--Clinical Use

Back 35

a. Approved for long term use in patients >12 years old.
b. After one year, orlistat produces a weight loss of about 9–10%.

Front 36

Drugs which affect weight (for information only)

Back 36

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