Term
| In what population of obese patients is pharmacotherapy indicated as an adjunct to lifestyle modificaiton? |
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Definition
Phentermine, Sibutramine and Orlistat
1) BMI>30 kg/m2
2) BMI > 27kg/m2 with major obesity-related comorbidity (HTN, diabetes, OSA) |
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Term
| What is the central problem of effective pharmacotherapy for obesity? |
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Definition
Compensatory orexigenic responses evoked by efforts to reduce weight (decrease resting energy expenditure and causes hunger)
- Leptin (adipose), Insulin (pancreas) and Ghrelin (stomach and upper intestine) serve as adiposity signals |
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Term
| What are the molecular adiposity signals and how do they regulate energy homeostasis? |
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Definition
1) Leptin (adipose)
2) Insulin (pancreas)
1 and 2 bind two different types of neurons in the Arcuate Nucleus of the hypothalamus: anorexigenic neurons that produce proopiomelanocortin (POMC) and orexigenic neurons that produce NPY and agouti-related protein (Agrp)
3) Ghrelin (stomach and upper intestine) |
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Term
| What are the 3 arms neuroendocrine regulation of energy homeostasis and food intake? |
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Definition
1) Adiposity (Long-term)
- Major site of action is Arcuate nucleus of hypothalamus
- Leptin (adipose)
- Insulin (pancreas)
- Ghrelin (stomach and upper intestine)
2) Satiety (short term)
- Vagal and spinal nerves that target nucleus tractus solitarius (NTS)
- Long-term adiposity signals "set gain" on satiety signals.
3) Adrenergic
- Major target sites in CNS: paraventricular nucleus (PVN) in hypothalamus and brainstem
- Major target sites in peripheral organs: heart, adrenals, adipose tissue, muscle, liver
- Increases adrenergic input coupled to lowered food intake raises resting metabolic rate and thermogenesis. |
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Term
| What are the major central and peripheral Orexigenic and Anorexigenic factors? |
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Definition
1) Orexigenic (eat more)
- Central: NPY, Agrp, MCH, Cannabinoid, Ghrelin, GHRH
- Peripheral: Ghrelin, Cannabinoid
2) Anorexigenic
- Central: NE, Leptin, Insulin, alpha-MSH, CNTF, 5-HT, TRH, CRH
- Peripheral: NE, CCK, GLP=1, PYY, Amylin |
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Term
| What are the 5 classes of anti-obesity drugs and which are FDA approved to treat obesity? |
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Definition
**Sympathomimemtic drugs are used short-term
**Orlistat, Belviq and Qsymia are used for long-term
1) Reduce food intake
- sympathomimetic (Phentermine, Diethylpropion, Benzphetamine, Phendimetrazine)
- Serotonergic (Belviq)
2) Alter metabolism/absorption
- Orlistat
3) Increase energy expenditure
- none approved
4) Combinatorial
- None approved
5) Combination therapy
- Qsymia |
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Term
How do each of the following drugs treat obesity (mechanism and long/short-term use
1) Belviq
2) Phentermine/Diethylpropion
3) Orlistat
4) Qsymia |
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Definition
1) Selective serotonergic drug that acts on 5-HT2C receptors in brain that suppresses appetite (in theory, long-term management)
- Given when BMI> 30 or >27 with co-morbidity
2) Sympathomimetic amine that causes NE release from synaptic granules (short-term)
1-2 are appetite suppressants
3) Gastric and pancreatic lipase inhibitor that causes 30% loss of ingested fat (only one currently approved for long-term)
- Give for patients at risk for DM type II, with high LDL or pre-existing CVD
4) Phentermine (appetite suppressant- 5HT) and Topiramate (anti-convulsant)
- Give for BMI>30 or >27 with co-morbidity |
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Term
| What side effect is a major concern when using Belviq? |
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Definition
Selective serotonergic drug that acts on 5-HT2C- appetite suppressant.
Drug:Drug interactions with other serotonergic drugs (serotonin syndrome!) |
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Term
| How is treatment of anorexia nervosa generally approached? |
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Definition
1) Initial weight restoration (effective in 85%, but does not address dysfunctional attitudes)
2) Maintenance and psychotherapy |
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Term
True or False
Current obesity drugs only result in modest weight loss, though significantly improved metabolic parameters. |
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Definition
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Term
| What are the major drug therapy strategies for Anorexia? |
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Definition
Combination therapy is key and maintenance of weight gain is issue
Olanzapine has good, sustained weight gain and psychological improvement
1) Antipsychotic drugs: Pimozide, Sulpiride
2) Atypical antipsychotic drugs: Olanzapine
3) Antidepressants: amitriptyline and lithium
4) Serotonin-specific medications: fluoxetine, cyproheptadine
5) Prokinetic agents: cisapride
6) Appetite stimulants: Dronabinol, clonidine
7) Opiate antagonists: naloxone and naltrexone |
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Term
| What are the therapeutic options for treating cachexia? |
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Definition
1) Treat underlying diseases
Anti-cancer therapy (if appropriate)
ART for HIV
2) Increase nutritional intake
3) Dietary advice
4) Nutritional supplementation
5) Pharmacotherapy |
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Term
| What are the 5 major pharmacological strategies for treating Cachexia in cancer and AIDS patients? |
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Definition
1) Appetite stimulants: antiserotonergic drugs, cannobinoids, glucocorticoids, progestational drugs
2) Mood disorders: glucocorticoids, progestational drugs, cannabinoids
3) GI motility: prokinetic drugs
4) Muscle growth stimulation: anabolic hormones, growth hormone, eicosapentaenoic acid, branched-chain amino acids
5) Cytokine production: melatonin, progestational drugs, thalidomide |
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Term
| How do Mc4r antagonists work to treat cachexia? |
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Definition
| Inhibits melanocortin signaling onto POMC neurons in the hypothalamus, stimulating food intake |
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