Hello Bloggers & Friends!
I am Back!!
After a small break here i start again with my blog posts.. When i was trying to decide on the topic to blog about there were various options. But, i wanted this blog post to be special as its coming after a break..
Finally decided on two special topics
1- Obesity drugs
2- Artificial pancreas.
Guess who won??
Go on reading!
Hope you find it useful!
India, once known for its indigenous food went
through some major changes in the past decade. The entry of processed foods,
ready to eat varieties, snacks dominated the Indian kitchen. Current situation
is such that mostly in the next 10 years homes will be built without
kitchens! Add on to this was the
improvements in technology like mobile phones and internet. Our people who were
once active slowly started getting more and more tied up in front of computers.
As a result the level of physical activity came down. Not to blame anybody but
these are some of the “side effects” of
modernization finally ending up in OBESITY!
So
what happens when we gain weight?
The chances of development of health related
problems increase.
To name a few.....
•
Coronary heart disease
•
Type 2 diabetes
•
Cancers (endometrial, breast, and colon)
•
Hypertension (high blood pressure)
•
Dyslipidemia (for example, high total cholesterol or high levels of
triglycerides)
•
Stroke
•
Liver and Gallbladder disease
•
Sleep apnea and breathing problems
•
Osteoarthritis (a breakdown of cartilage and bone within a joint)
•
Gynecological problems (abnormal periods, infertility)
•
Depression
The problem of obesity in India starts from very
young ages. A very popular Myth in India is that babies must be chubby.. We
tend to over feed , elders say that “its baby fat and will go away once the baby
grows” but that never happens!
What to do about this obesity??
The options to management of obesity are
1. Developing
healthy eating habits
2. Increasing
physical activity
3. Pharmocological
therapy (Drugs)
The first two options are safe options but effects
are only available long term. As humans we all need immediate results so the
third option also becomes important. When everything fails we have only one
option left - "GO UNDER THE KNIFE" But bariatric surgery has its own
side effects and should be avoided whenever possible.
In this review post lets discuss more about the
Third option - Drugs for obesity!
The decision to prescribe a weight-loss drug
involves a careful assessment of the risks and benefits. As a general rule, an
effective regimen should help patients lose at least 2kgs in the first 4 weeks,
or 5% of baseline weight in the first 3 months on therapy.
Two classes of weight-loss agents are currently
available
Noradrenergic
agents for short-term weight loss
Lipase
inhibitor for long-term weight loss.
Drugs
for short term weight loss :
Phentermine
is for short-term (up to 12 weeks) treatment of obesity and is the most widely
prescribed weight-loss drug in the United States. Phentermine stimulates the
sympathetic nervous system to release norepinephrine, one of the
neurotransmitters involved in modulating food intake. Phentermine suppresses
appetite and induces satiety because its effects last about 12 hours,
phentermine should be taken in the morning. When used in combination with diet
and exercise, phentermine has produced an average 3.6 kg greater weight loss
than placebo.
Adverse effects include irritability, nervousness,
restlessness, dry mouth, insomnia, constipation, and headache, but it has also
been associated with hypertension, tachycardia, and palpitations, so it should
not be taken by patients with cardiovascular disease or significant
hypertension. Blood pressure should be monitored during therapy.
Diethylpropion
is similar to phentermine.
Diethylpropion is available in 25-mg standard or 75-mg extended-release
formulations, and is approved for short-term treatment of obesity.
Benzphetamine
and Phendimetrazine: These drugs also act centrally,
releasing dopamine and norepinephrine, resulting in appetite suppression,
increased blood pressure, and increased heart rate. As schedule III drugs,
however, benzphetamine and phendimetrazine have more potential for addiction,
therefore are prescribed less often.
The above mentioned drugs stimulate the central
nervous system, and can increase blood pressure and heart rate, while releasing
glycerol and free fatty acids.
Drugs
for long term weight loss :
Orlistat
: It is a gastrointestinal and pancreatic lipase inhibitor. In the gastrointestinal tract, orlistat binds
to gastric and pancreatic lipases, preventing these enzymes from hydrolyzing
dietary fat into absorbable free fatty acids. When not absorbed, triglycerides
are excreted in the feces, along with cholesterol and fat-soluble vitamins.
Taken with meals, orlistat can block the absorption of 30% of ingested fat. In
this manner, orlistat reduces caloric intake and may have additional benefits.
Adverse effects of orlistat are fairly common which
include steatorrhea, bloating, fecal urgency, fecal incontinence, and oily
stools. Orlistat interferes with the absorption of fat-soluble vitamins A, D,
E, and K. This class of drug should probably be avoided in patients with
gastrointestinal disease or malabsorption syndromes.
There were some unlucky
drugs which were withdrawn from the market.
Sibutramine
:
Reason
for withdrawal - Increased risk for heart attack and stroke.
Sibutramine
hydrochloride is a centrally acting drug originally
used to treat depression, patients taking sibutramine experienced weight loss
as an unexpected effect. Although diminished hunger and increased satiety are
the most likely mechanisms of weight loss, sibutramine may also increase
thermogenesis, thus increasing energy expenditure by increasing metabolism
Lorcaserin
Reason
for concern : lorcaserin-induced valvular heart disease (as well as brain and
breast tumors)
Lorcaserin is an anti-obesity drug. The stimulation
of specific central serotonin receptors suppresses appetite and induces a
feeling of satiety. Users also noticed reduced BMI and waist circumference,
lower fasting glucose, lower A1c levels, lower total cholesterol, LDL
cholesterol, and triglycerides.
Phentermine/Topiramate:
Reason
for concern : cognitive disorders, metabolic acidosis, increased heart rate,
and birth defects, suggesting possible teratogenicity.
Qnexa combines low-dose phentermine with a
controlled-release form of topiramate, an antiepileptic drug often used for the
prevention of migraine headache. Topiramate reduces hunger and promotes weight
loss in a dose-dependent fashion, but the peripheral and central nervous system
effects (parasthesias, memory impairment, taste disturbance) are significant
and intolerable in some patients. Topiramate has the added advantage of having
mood-stabilizing properties.
Awaiting
!
Naltrexone/Bupropion
:
Contrave, another new dual anti-obesity agent, is
the combination of the antidepressant bupropion and sustained-release (SR) naltrexone,
a drug used to treat alcoholism and other addictions. Bupropion, approved for
both depression and smoking cessation, also increases dopamine levels at
specific receptors in the brain, which is believed to be responsible for its
appetite-reducing effects. These 2 drugs work on the brain reward system and
the hunger centers in the hypothalamus, and are believed to be synergistic in
reducing food intake.
If approved, this combination therapy could be
useful for patients who have issues with food craving. When used with a mild
hypocaloric diet and with exercise instruction in overweight or obese patients,
it is associated with greater weight loss and greater improvement in several
cardiometabolic risk factors compared with placebo. Combination treatment was generally well
tolerated; adverse effects included insomnia, nausea, headache, dry mouth, and
a small and transient increase in systolic and diastolic blood pressure.
Still
in research:
In
the Pipeline
Zonisamide/Bupropion
Antiepileptic zonisamide, an unanticipated effect
was weight loss. Zonisamide has sodium and calcium channel blocking activity,
as well as dose-dependent biphasic dopaminergic and serotonergic activity.
Empatic (made by Orexigen) is a fixed-dose combination of a proprietary formulation
of zonisamide SR and bupropion SR.
Fatigue,
drowsiness, sedation, nausea, and cognitive impairments (difficulty
concentrating, memory problems, speech and language difficulties) have all been
reported with zonisamide use.
Tesofensine
Tesofensine (made by NeuroSearch) is a triple
monoamine reuptake inhibitor that blocks the presynaptic uptake of
norepinephrine, dopamine, and serotonin. Originally being studied for
neurodegenerative conditions such as Parkinson and Alzheimer diseases,
unintended weight loss was observed in individuals treated with the drug.
The mechanisms through which tesofensine leads to
weight loss are a pronounced effect on appetite suppression and increased
energy expenditure. Minor adverse events included elevations in heart rate and
significant increases in blood pressure only at the highest tested dose.
Cetilistat
Cetilistat is a new lipase-inhibitor with a similar
mode of action to orlistat, inhibiting pancreatic lipase and blocking digestion
and absorption of dietary fat. Unpleasant adverse effects, including flatus
with discharge and oily spotting, were reported to be less compared to
orlistat. It is probable that, like
orlistat, cetilistat will also block the absorption of fat-soluble vitamins.
Pramlintide/Metreleptin
Pramlintide is an analogue of amylin, a hormone
secreted by pancreatic beta cells along with insulin. Amylin can increase the
absorption of glucose, slow gastric emptying, and by binding to hypothalamic
receptors, promote satiety, reduce food intake and elicit weight loss.
Metreleptin is recombinant methionine human leptin. Leptin is a neurohormone
secreted by adipocytes that also binds to receptors in the hypothalamus to
promote satiety. When someone reduces dietary intake to lose weight, leptin
levels drop, and this triggers a host of counter-regulatory responses aimed at
maintaining body weight. Administration of metreleptin restores leptin
concentrations and attenuates the effects of counter-regulation.
Pramlintide/metreleptin combination is an injectable therapy, which may limit
its application in the general obese population.
Finally!!!
An ideal weight loss medicine is yet to be found. As we all know Metformin for the treatment of type 2
diabetes, causes weight loss by reducing hepatic glucose production and
intestinal absorption from the gastrointestinal tract, and enhancing insulin
sensitivity. Liraglutide (Victoza®), another drug that is already approved for
the treatment of type 2 diabetes, induces moderate weight loss of approximately
2-3 kg. The glucagon-like peptide-1 (GLP-1) receptor agonists exenatide and
liraglutide are newer medications for diabetes that have favorable effects not
only on glycemic control but also on weight loss. These drugs do not qualify as
weight loss medicines but are useful in patients with combined problem of
weight gain and diabetes
LOSE WEIGHT
P.S - Not many drugs are available in India, Content of this blog post has been collected from authenticated sources.(www.medscape.com)
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