Pharm of Obesity Flashcards
Appetite and satiety are controlled by?
The hypothalamus (arcuate nucleus) which communicates with peripheral organ systems.
What hormone stimulate appetite?
Ghrelin released by the stomach when empty.
What hormone inhibits appetite and is produced by adipocytes?
Leptin.
Intestine produces which hormone that inhibits appetite?
PYY 3-36
Insulin _____ appetite.
Insulin inhibits appetite.
Phentermine MOA (3 main actions)
Sympathomimetic (stimulate both alpha and beta adrenergic receptors peripherally and centrally)
Enhance lipolysis, decrease weight secondary to stimulating peripheral beta 3 adrenergic receptors on adipose tissues.
Act on the arcuate nucleus of the hypothalamus to suppress appetite and prolong satiety.
What are some ways Phentermine can be used?
Can be used as monotherapy or in combination with topiramate for short-term management of overweight (obesity).
To maximize benefits and ensure success of therapy, these agents must be used in combination with regular exercise, proper dieting and overall healthy lifestyle changes.
Phentermine resembles what?
Resembles hyper-activity of the sympathetic nervous system (insomnia, hypertension, increase risk of stroke, myocardial infarction etc.)
What drug is addiction a concern in and why?
Phentermine.
Addiction is a concern since this agent like the closely related amphetamines and cocaine stimulated dopamine release into the nucleus accumbens (reward center). This action is mediated via the meso-limbic pathway
What drugs can’t patients taken when taking Phentermine? Why?
Beta adrenergic blockers
Alpha blockers
Dopamine antagonists
Phentermine has an agonistic effect on all these receptors.
Is phentermine a permanent cure for obesity?
No. Not a permanent cure for obesity. Many patients may regain the weight shortly after the drug therapy is terminated.
Topiramate is commonly given with what drug as an extended release capsule?
Topiramate and Phentermine.
Used in combination with phentermine for short-term management of overweight.
Topiramate MOA
Blocks neuronal Na+ channels, enhance GABAA transmission and antagonize the AMPA receptor
These actions lead to decrease appetite and prolongs satiety.
Formulated as an extended release capsule to ensure a smooth steady state concentration during therapy.
What drug is commonly used as an adjunct anti seizure agent for treatment of focal and tonic –clonic seizures.
Topiramate.
Topiramate ADEs
Topiramate may cause sedation, psychomotor slowing, fatigue, speech or language problems and renal stones
Hypersensitivity have also occurred in some patients.
Lorcaserin MOA
Lorcaserin is a 5HT2C receptor agonist, these receptors are found almost exclusively in the brain including the hypothalamus where specific nuclei are stimulated to release proopiomelanocortin (POMC).
Believed to decrease food consumption and enhance / promote satiety.
Lorcaserin was approved by the FDA to treat what?
Chronic overweight in patients with a body mass index (BMI) > 27.
Lorcaserin ADEs
Relatively new to the market with limited history on its adverse effect profile. However, as a serotonin agonist, there is risk of serotonin syndrome – a potentially fatal constellation of symptoms related to serotonin excess.
Serotonin syndrome: high body temp., agitation, increased reflexes, tremor, sweating, dilated pupils, diarrhea.
Memory impairment, somnolence, confusion and disturbances with attention has been reported in patients taking lorcaserin.
Lorcaserin should not be used with what other drugs?
Antidepressants such as SSRIs, SNRIs, tricyclic anti depressants.
Bupropion
Triptans
Bupropion MOA
Resembles amphetamine in its pharmacology, increases both serotonin and dopamine levels in the brain.
Believed to suppress appetite and prolong satiety secondary to its dopamine and serotonin actions..
Also increase energy expenditure secondary to stimulating proopioidmelanoncortin (POMC) neurons in the brain.
What drug can also be used to treat atypical depression?
Bupropion
Bupropion is often used in conjunction with what drug to treat the overweight?
Used in combination with naltrexone for the treatment of overweight.
Bupropion is contraindicated in what kinds of patients?
Bupropion lowers the threshold for seizures and is therefore contraindicated in patients a history of epilepsy or seizures.
Also contraindicated in patients with eating disorders, or electrolyte abnormality since it produces electrolyte imbalance.
May cause sexual dysfunction albeit less frequently than other anti depressants.
Naltrexone MOA
Blocks mu-opioid receptors on the POMC neurons preventing feedback inhibition of these neurons and further POMC activity.
Reduce appetite, help control food cravings, increase metabolism and improve control over eating behavior.
What drug can also be used in an outpatient setting to detoxify patients addicted to opioids?
Naltrexone
What drug is naltrexone combined with to treat the overweight?
Naltrexone is also used in combination with bupropion (the combination is called contrave).
Naltrexone ADEs
Constipation, headaches, nausea, dizziness, insomnia, and xerostomia have all been reported in patients taking naltrexone.
Orlistat MOA
Inhibits gastric and pancreatic lipases within the intestine thereby decreasing the absorption of ingested fats (triglycerides), subsequently reducing weight.
What drug has the FDA withheld approval and why?
Show significant activity in treating overweight but the FDA has withheld approval due to concerns of inadequate data on safety.
Orlistat ADEs
May interfere with absorption of fat soluble vitamins ( ADEK) possibly leading to bleeding, night blindness etc.
Weight loss drugs currently in clinical use are classified as either _______ or inhibitors ________.
Weight loss drugs currently in clinical use are classified as either appetite suppressants or inhibitors of fat absorption.
Appetite suppressants targets the _________ to control food intake and the duration of satiety.
Appetite suppressants targets the arcuate nucleus of the hypothalamus to control food intake and the duration of satiety.
Suppressors of fat absorption targets ____________ in the GI tract.
Suppressors of fat absorption targets gastric and pancreatic lipases in the GI tract.
