FAFP2 Pharmaceutical care II
Lecture:
Obesity and its drug management
29. 4. 2020
PharmDr. Bc. Dana Mazánková, Ph.D.
mazankovad@vfu.cz
- based on the pathophysiology of insulin resistance
Abdominal obesity men > 102 cm
(waist circumference) women > 88 cm
Triglycerides > 2 mmol / l
HDL cholesterol Men < 1 mmol/l
Women < 1.3 mmol/l
Blood pressure 130/85 mmHg
Fasting blood glucose > 6 mmol / l
Metabolic syndrome
- postprandial concentrations of Glc and TG correlated with CV risk better
than their concentration in the fasting state
- excessive glc ↑ and ↑ TG leads to:
• free radicals --- oxidative stress
• endothelial dysfunction
• vasoconstriction
• atherosclerosis
• hypercoagulation
• sympathetic hyperactivity
Postprandial metabolic disorders
 Mechanical load
 joints
 Hypoventilation syndrome
 sleep apnea
 Disruption own self-regulation physiological functions
 CV disease
 reproduction
 cancer
 gastrointestinal
 hiatal hernia, reflux disease, hepatic steatosis
 venous and lymphatic system
 trophic skin
Risks of obesity
- mechanism of action: insulin resistance and chronic hyperinsulinemia
 Endometrial cancer
 risk factors - obesity, nuliparity
 endogenous estrogens
 aromatase of adipose tissue converts androgens to estrogens →
endometrium is exposed to increased estrogen exposure
 Gallbladder cancer - biliary stones
 Esophageal adenocarcinoma – reflux
 problem of frequent underdosing of chemotherapy
Risk of cancer
• Sibutramine
• Orlistat (Xenical®, Alli®)
• Phentermine (Adipex retard®)
• Rimonabant (Acomplia®)
Pharmacotheraphy in obesity
- mechanism of action:
- reuptake inhibitor of 5-HT and NA in the CNS, to a lesser extent of D
- it does not affect the 5-HT and D receptors
- it does not affect cholinergic, H1 and BDZ receptors
- evoking a sense of satiety
Sibutramine
- clinical experience:
• reduction energetic income (fats)
• reduction in body weight ( by 6.9 kg for placebo – by 12.9 kg for
sibutramine)
• decrease in blood glucose, insulinaemia, TAG, VLDL
• increase in HDL-cholesterol
- drug interactions: MAO inhibitor
- recommendations for patients:
Do not use sibutramine if you have taken an MAO inhibitor in the last
14 days.
Serious, life threatening side effects can occur if you use sibutramine
before the MAO inhibitor has cleared from your body.
- contraindications for sibutramine:
▫ severe or uncontrolled hypertension (high blood pressure)
▫ an eating disorder (anorexia or bulimia)
▫ a history of coronary artery disease (atherosclerosis)
▫ a history of heart disease (congestive heart failure, heart rhythm disorder)
▫ a history of heart attack or stroke
▫ taking stimulant diet pills – e. g. caffeine + ephedrine ("Elsinorské pills")
Sibutramine was withdrawn from many european markets in previous years
from safety reasons !
- mechanism of action:
- blocking the enzyme lipase - prevents fat absorption
- reduces cholesterol absorption
Orlistat
- indication:
- obese patients with an initial body mass index (BMI) of 30 kg/m2 or greater
- or 27 kg/m2 in the presence of other risk factors (hypertension diabetes, or
dyslipidemia)
- must be used together with a reduced-calorie diet and increased physical
activity !!
- orlistat is only part of a complete program of treatment that also includes
diet, exercise, and weight control
- avoid a diet that is high in fat
- high-fat meals taken in combination with orlistat can increase risk of
unpleasant side effects stomach or intestines
- for use only in adults that are overweight or obese
- usually taken 3 times per day with each main meal that contains some
fat (no more than 30 % of the calories for that meal)
- the fat content of daily diet should not be greater than 30 % of total
daily caloric intake
- for example, if you eat 1200 calories per day, no more than 360 of
those calories should be in the form of fat
- take the medicine either with meal or up to 1 hour after eating
- if meal is skipped, or meal that does not contain any fat, skip the dose
of the medicine
Information how to take orlistat
- decreased absorption of fat-soluble vitamins
- vitamin and mineral supplement may be needed
- take the supplement at bedtime, or at least 2 hours before or after taking
orlistat
High-risk co-medication:
cyclosporine: take 3 hours before or after this drug,
measure cyclosporine levels
levothyroxine: take at least 4 hours before or after this drug,
monitor thyroid function
▫ you are not overweight
▫ chronic malabsorption syndrome
▫ gallbladder problems
▫ pregnancy
 weight loss is not recommended during pregnancy, even if patient is
overweight!
▫ status after organ transplant
▫ taking cyclosporine
Contraindications for orlistat
Substantial weigh loss can increase the risk of cholelithiasis
Hepatotoxicity:
- immediately report signs and symptoms of hepatic dysfunction:
- itching, yellow eyes or skin, dark urine, or loss of appetite
- severe, continuous abdominal pain
Side effects:
- flatulence
- diarrhea
- oily stools
Information for brestfeeding women:
Taking orlistat can make it harder for your body to absorb fat-soluble
vitamins.
Vitamins are important if you are nursing a baby - vitamin and mineral
supplement may be needed.
- mechanism of action:
- canabinoid-receptor antagonist
- selectively blocking CB1 receptors in the brain and in peripheral organs
important in glucose and lipid (or fat) metabolism, including adipose
tissue, the liver, gastrointestinal tract and muscle
- switches off the same brain circuits that make people hungry when
they smoke cannabis
Rimonabant
- effect of action:
- reduces weight
- reduction of the weight and a very large range of regulation of plasma
lipids
- reduces lipid concentrations
- very significantly increases HDL-cholesterol and decreases C-reactive
protein
- aid to smoking cessation
Ribonamant was withdrawn from US and many european markets in previous years
(EMEA - 2009) from safety reasons !
- due to the risks of dangerous psychological side effects (depression), including
suicidality
1. CNS and neurotransmitters
- substances related to today's anorectics and antidepressants
2. Central ring of action of leptin and insulin
- leptin analogs
- ciliary neurotrophic factor (Axokine)
- neuropeptide Y
3. GIT - cholecystokinn analogues, drugs affecting GLP-1, ghrelin analogues
4. Energy expenditure
- β3-agonists
- thyroid receptor agonists
- drugs affecting uncoupling proteins
5. Inducing apoptosis of fat cells
Future treatment options in obesity
Bariatric procedures
Weight-loss surgery
- very effective is so-called gastric banding
- surgical method
- even after the surgery the slimming diet is needed!
Chirurgical options in obesity