By : Johnny Lau

Achieve weight loss
(Aim for 10% reduction from baseline weight)

 Maintain

weight loss  Improve and prevent complications of obesity  Conventional therapy includes reducing energy intake through dietary modification, and increasing energy output by increasing activity and reducing sedentary behaviour

 Lifestyle

changes are the cornerstone

 Reducing

sedentary behaviour  Increasing physical activity  Eating behaviour modification  Fat and calorie restriction
 Reduce
 to

fat intake

< 30% of total caloric intake

 Increase

exercise or daily activities

 Physically

capable adults should start with 15min daily of low-intensity activity e.g. walking (AMH)

 Consult
 E.g.

doctors in stopping or replacing drugs that may contribute to weight gain
corticosteroids, some antipsychotics

Patient has tried diet and exercise for 6 months and have:

     

BMI of 25-27 kg/m2 (Asian bodies) with at least 2 of :
T2 DM CHD Cerebrovascular disease HPT Hyperlipidaemia WC of >90cm for men & 80cm for women

 

BMI of more than 27.5kg/m2 (Asian bodies) Symptomatic obesity complications eg: severe osteoarthritis, reflux oesophagitis, obstructive apnoea.

Programs should include diet and exercise!!

MOA
 GI

lipases break down fat into long chain fatty acids. Orlistat inhibits GI lipases, preventing breakdown of fat and therefore absorption of approx 30% of dietary fat

 Criteria
 Patient

has a BMI of at least 27.5kg/m2 or at least 25kg/m2 with co-morbidities (Hypertension, diabetes, high cholesterol, CHD) *Applying to Asian bodies (CPG)

 Contraindications
 Pancreatic

enzyme deficiency states (low lipase

formation)  Major GI surgery  Malabsorption syndrome

Orlistat can cause further nutrient malabsorption Orlistat reduces intestinal long chain fatty acids, and reduce cholecystokinin which induces gallbladder emptying. Decreased gallbladder emptying can cause gallbladder formation.

 Cholestasis

 Specific

considerations

 Nephrolithiasis

Oxalate excretion may increase, increasing risk of kidney stone formation.

 Vitamin

deficiency & Breastfeeding

Absorption of fat-soluble vitamins may decrease Inappropriate to use during pregnancy; no data

 Pregnancy

 Adverse
 Fatty

effects

or oily stools  Oily spotting  Oily evacuation  Abdominal pain  Flatulence
 Dosage

: Usually 120mg tds with each main meal containing fat.

Practice points:
 Orlistat

reduces absorption of lipid soluble vitamins A, D, E & K  Taking a multivitamin containing A,D,E,K & B carotene is recommended (2 hours prior or after dose)  Dose above 360mg/day does not provide additional benefit and is not recommended.
 Drug

interaction:

 Cyclosporin

plasma levels are reduced by Orlistat. Take doses 2 hours apart.  Vitamin K changes can affect coagulation. Take with caution if on warfarin (monitoring).

 Costly  Treatment
 E.g.

maybe adequate in reducing surrogate markers of morbidity
BP, total cholesterol and ratio of total cholesterol to HDL

 Positive

effects on mortality have not been demonstrated  Treatment longer than 4 years not studied. Consequently, is also the only medication that can be taken long term up to 4 years.
(CPG)

 Amphetamine  MOA

derivative that suppresses appetite

 Sympathomimetic

increasing norepinephrine and dopamine release from the CNS, increasing energy expenditure. Neurotransmitters also signal a fight-orflight response in the body  This puts a halt to the hunger signal, causing loss in appetite.

 Contraindications
 Severe

cardiac disease, hyperthyroidism, glaucoma, sibutramine and MAO inhibitor treatment (hypertensive crisis)  Existing heart valve abnormalities (cases of valvular heart disease have been reported) (CPG)
 Adverse

effects

 Palpitations,

tachycardia, elevated BP, restlessness, insomnia, euphoria, tremor, headache

 Specific
 Drugs

considerations

that increase BP  Concurrent treatment with drugs that increase serotonin toxicity eg: antidepressants, opioids  Epilepsy ( may increase seizure activity)
 Dosage
 Usually

15mg once daily up to maximum of 40mg once daily before breakfast (at least 10 hours before bed) to prevent insomnia. (AMH)

Practice points
 For

short term use, usually for not more than 3 months. Interval of 4-12 weeks before resuming (AMH + CPG). Withdrawal symptoms and dependence can occur with longer treatment.  Abuse is possible as phentermine is related to amphetamines. Can be habit forming.  Non Pharmacological Counseling (see below)

MOA
 specifically

inhibits serotonin and noradrenaline reuptake without affecting their release. It enhances postingestive satiety and increases resting metabolic rate.

 Efficacy

-> 5-8% weight loss of 1-4% placebo.

 Beneficial

changes in lipids, uric acid levels and glycaemic control (in Type II DM) may associated with increased heart rate, systolic and diastolic BP

 Use

 Contraindications
 Concurrent

MAOi and SSRI treatment due to risk of serotonin toxicity. (CPG)  Bipolar disorder  Phentermine treatment  History of eating disorders (anorexia, bullimia) due to risk of abuse.  Any condition exacerbated by BP or heart rate increase.

 Specific

considerations

 Pregnancy

ADEC Category C. Inappropriate to lose weight during pregnancy.

 Adverse

effects

 Increased

heart rate, palpitations, raised BP, insomnia, dizziness, headache, anxiety.

 Dosage
 10mg

to 15mg OD.

 Practice

points

 Treatment

unlikely to be effective if <5% weight lost by 3 months.  In a clinical trial, alternating treatment after 12 weeks with 6 placebo weeks is equivalent to continuous treatment for 48 weeks.

Fluoxetine and other SSRIs
treatment

 May aid weight loss in depressed patients  But effect appears to last only 6 months despite

continued

Metformin  May be useful in managing obesity in those with type 2 diabetes, polycystic ovarian syndrome (PCOS), and impaired glucose tolerance, due to appetite suppressive effect.  Care should be taken with its use in subjects with cardiac, renal or hepatic decompensation as it may result in lactic acidosis.  Side effects include nausea, flatulence, bloating and diarrhoea.

1.

Bulking laxative agent
  

Assist in weight reduction by inducing satiety Generally are ineffective alone Efficacy over calorie restriction and exercise has not been proven

2.

Other laxatives
 

Misused by some patients attempting weight loss Severe fluid and electrolyte imbalance may result without loss of adipose tissue

3.

Thyroxine

Use to increase metabolic rate is contraindicated due to metabolic complications associated with excess thyroxine E.g. arrhythmias, hypertension and bone disease

3.

Diuretics
 

Lead to electrolyte imbalance Do not reduce weight by fluid loss e.g boxers, jockeys, and weight lifters

1.

Take a balanced meal with reasonable amounts of fat and carbohydrates at the right time in the right amount. A calorie deficit of 500 to 1000 kcal/day from maintenance requirement (Low Calorie Diet) is important for weight loss and prevention of weight regain (Evidence Level A). Goal of weight loss should be set with patient with a reasonable target. Aim for 10% reduction from baseline can significantly reduce obesity related risk factors. A reasonable goal is a 10% weight reduction from baseline over 6 months of therapy. (CPG)

2.

3.

4.

Ensure sufficient physical activity of at least 30 minutes of exercise at least 4 days a week. Rapid weight reduction may lead to increased risk of gallstones, electrolyte abnormalities and weight regain. A calorie deficit of 500 to 1000 kcal/day can result in weight loss at a rate of 0.5 to 1 kg/week.
(CPG Evidence B)

5.

6.  

Counseling
Diet should not be have more than 30% of calories in fat. If meal does not contain much fat or if meal is missed, Orlistat dose can be omitted.  Strongly recommended to be taken with a mildly reduced hypocaloric diet to be determined by a dietician.

7.

Focus of weight loss should be switched to improving health rather to physical appearance. In children, the aim should be to reduce body fat rather than to lose weight, as they tend to “grow into their weight”. (CPG) Behaviour Therapy:
  

8.

9.

Portion and stimulus control Stress management (certain groups) Family support or support groups.

Pharmacotherapy drugs should always be given in conjunction with diet and physical exercise to be effective. of pharmacotherapy drugs for weight loss should be decided by medical professionals for appropriate use

 Use

Pharmacotherapy Principles & Practice By Marie A. Chisholm-Burns, Marie A. Chisholm, Barbara G. Wells, Terry L. Schwinghammer, Patrick M. Malone, Jill M. Kolesar, John C. Rotschafer (2007)


http://www.drugscenter.org/xenical/index.php/category/side-ef

Manufacturer product leaflet.  Clinical Practice Guidelines (Management of Obesity 2004)  Diabetes Mellitus: A Guide To Patient Care. Addie et. Al. (2007)Lippincott Wilkins & Williams  http://www.drugs.com/pro/phentermine.html  AMH (Australia Medical Handbook) 2008  Pharmacotherapy Handbook 6th edition

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