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Obesity Canada > 12. Pharmacotherapy in obesity management > Flashcards

12. Pharmacotherapy in obesity management Flashcards

1
Q

Healthy behaviour changes alone generally
achieve only a how many % weight loss, which is most often not sustained over the long term?

A

3-5%

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2
Q

what are the criteria that Health Canada has established for a pharmacotherapeutic agent to receive regulatory approval for long-term weight managemen?

A
  1. The agent must be studied in clinical trials of at least one year in duration.
  2. The agent must produce a placebo-adjusted mean weight loss of ≥ 5% or demonstrate a ≥ 5% weight loss in at least 35% of patients, with this proportion being more than double that in
    placebo.
  3. The agent should demonstrate an improvement in obesity-related comorbidities.
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3
Q

who is indicated for obesity drug treatment?

A

Pharmacotherapy is indicated for long-term weight management in Canada for individuals with a BMI ≥ 30 kg/m2 or ≥ 27 kg/m2
with comorbidities associated with excess body fat (e.g., T2DM, hypertension, dyslipidemia, obstructive sleep apnea).

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4
Q

what are 4 meds approved for obesity managment in Canada?

A

Orlistat 120mg tid
liraglutide 3mg SC daily
naltrexone/bupropion 16/180mg BID
semaglutide 2.4mg sc weekly

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5
Q

what is recommended to prevent obesity for anti-psychotic medication use weight gain?

A

metformin

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6
Q

what should be identified before initiating obesity pharmacotherapy?

A

goals of therapy;
targets of treatments

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7
Q

Obesity medications are intended as part of a long-term treatment strategy because..?

A

Clinical trials of pharmacotherapy for obesity management consistently demonstrate regain of weight when treatment is stopped.

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8
Q

The use of pharmacotherapy for obesity management is not recommended in ..?

A

pregnant or breastfeeding women, nor in women who are trying to conceive

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9
Q

how does orlistat work?

A

semisynthetic derivative of lipstatin - a potent and selective inhibitor of pancreatic lipase, thereby inhibiting the breakdown of dietary triglycerides into absorbable
free fatty acids - 30% ingested TGs are excreted, primarily in the feces;
orlistat does not target appetite or satiety mechanisms

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10
Q

what is the dose of orlistat?

A

120mg tid (during or up to 1 hour after meals)

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11
Q

what is the indication of orlistat?

A

weight reduction or reducing the risk of weight regain after prior weight loss in patients with a BMI >30 or 27 in the presence of comorbidities (e.g. hypertension, T2DM, dyslipidemia, excess visceral fat)

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12
Q

what is the effectiveness of orlistat?

A

2.9% weight loss at one year;
54% and 26% of patients achieved >5% and >10% weight loss;

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13
Q

what is the side effect of orslistat?

A

GI side effects - oily spotting and loose stools, flatus with discharge, fecal urgency and increased defecation;

interefere with the absorption of fat-soluble vitamins (ADEK) - need to take multivitamin at least 2 hours before or after taking orlistat

rare casese of severe liver injury or acute liver failure

some may develop increased levels of urinary oxalate on orlistat - oxalate nephropathy with renal failure have been reported;

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14
Q

long-term orlistat effect? at 6 months, 1 year, 2 year

A

18%, 6%, 2% persistence rates

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15
Q

contraindication of orlistat?

A

chronic malabsorption syndrome or cholestasis;
some may develop increased levels of urinary oxalate on orlistat - oxalate nephropathy with renal failure have been reported;

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16
Q

drug interaction with orlistat?

A

anti-coagulants - INR monitor - due to vit K absorption reduced;

levothyroxine or iodine salts - affect absorption - monitor thyroid function

reduction in plasma cyclosporine levels - monitor;

change in anti-convulsant medications - monitor seizures

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17
Q

what does GLP1 do?

A

act centrally on the pro-opiomelanocortin neurons to improve satiation and satiey and reduce hunger, with a transiet effect to decrease gastric emptying

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18
Q

what does liraglutide do?

A

increase insulin release and suppresses glucagon during times of glucose elevation

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19
Q

what is the dose of liraglutide?

A

start 0.6mg daily, titrate each week, upto 3.0mg daily for obesity
(1.2 or 1.8mg for diabetes)

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20
Q

what was the result of liraglutide?

A

8% weight loss at one year;
33% patients lost more than 10% of body weight

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21
Q

result of liraglutide at 3 years?
in addition to intensive behavioural therapy?

A

6% loss ;
7.5% loss

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22
Q

what is the side effect of liraglutide?

A

nausea - central and peripheral effect;
GI upset;
higher risk of gallstones;
small increased risk of pancreatitis;

23
Q

contraindication of liraglutide?

A

personal or family hx of medullary thyroid cancer or a personal history of multiple endocrine neoplasia type 2 – increased risk of medullary thyroid cancer in rodent studies

24
Q

what is naltrexone? how does it work for obesity?

A

opioid receptor antagonist;

Naltrexone disrupts the auto-inhibitory effect
of β-endorphin on the pro-opiomelanocortin cells by blocking the
μ-opioid receptors.

Naltrexone/bupropion also influences the mesolimbic reward system, resulting in a reduction in cravings

25
Q

what is bupropion? how does it work for obesity?

A

antidepressant that inhibits the uptake of dopaine and norepinephrine;

Bupropion induces satiety centrally by enhancing production and
release of α-melanocyte stimulating hormone (α-MSH) and β-endorphin from the pro-opiomelanocortin cells in the arcuate nucleus
of the hypothalamus;

Naltrexone/bupropion also influences the mesolimbic reward system, resulting in a reduction in cravings

26
Q

what is the dose of naltrexone/bupropion?

A

16/180MG BID;
one tablet (8/90mg) daily for the first week, increase by one tablet each week until the maintenance dose of two tablets twice daily (total daily dose 32 mg/360 m

27
Q

what is the result of natre/bupro treatment?

A

Among patients with overweight or obesity without diabetes,
naltrexone/bupropion 16 mg/180 mg BID with a hypocaloric diet
(500 kcal/day deficit) and exercise was associated with weight loss
of -6.1% versus -1.3% in placebo. Weight loss of ≥ 5% was seen
in 48% of patients, and ≥ 10% weight loss was seen in 25% of
patients with naltrexone/bupropion, compared with 16% and 7%
in the placebo group, respectively.5

28
Q

what is the predictive of greater weight loss by nalt/bup tx?

A

A combined analysis of three naltrexone/bupropion trials found that early
improvements in cravings were predictive of greater weight loss.45

29
Q

how to measure reduction in cravings?

A

the Control Of Eating Questionnaire (COEQ)

30
Q

The most common side effects of naltrexone/bupropion include?

A

nausea, constipation, headache, vomiting, insomnia, dry mouth,
dizziness and diarrhea.

Most nausea events occur during the
dose-escalation period and are transient.

31
Q

Naltrexone/bupropion is contraindicated in patients with?

A

uncontrolled hypertension;

Any opioid use - Opioid therapy should be
discontinued for seven to 10 days prior to initiation of naltrexone/
bupropion to prevent the precipitation of opioid withdrawal;

seizure disorders, anorexia
nervosa, bulimia and patients undergoing abrupt discontinuation
of alcohol, benzodiazepines, barbiturates or anti-epileptic medications

32
Q

Naltrexone/bupropion should be dosed with caution with which medication classes?

A

Naltrexone/bupropion should be dosed with caution with
any medications that lower seizure threshold

33
Q

Monoamine inhibitors can increase the risk of XXX reactions, and naltrexone/
bupropion should therefore not be used within 14 days of taking monoamine inhibitors.

A

Monoamine inhibitors can increase the risk of hypertensive reactions, and naltrexone/
bupropion should therefore not be used within 14 days of taking monoamine inhibitors.

34
Q

There are multiple potential medication interactions with naltrexone/bupropion, which stem from ?

A

There are multiple potential medication interactions with naltrexone/bupropion, which stem from the effect of bupropion and its
metabolites to inhibit the hepatic CYP2D6 enzyme system

35
Q

Among patients already receiving naltrexone/bupropion, medications metabolized by CYP2D6 should be started at the
lower end of their recommended dosage range with cautious titration.
examples of medications are?

A

selective serotonin reuptake inhibitors, beta blockers, anti-psychotic agents, type 1C anti-arrhythmic agents and many tricyclic anti-depressants, such as citalopram, metoprolol, risperidone, propafenone and desipramine

36
Q

Bupropion may result in reduced efficacy of xxx
and should therefore not be used in
combination with it.

A

tamoxifen

37
Q

Bupropion is primarily metabolized by the CYP2B6 enzyme system. Therefore, naltrexone/bupropion dosing should not exceed
one tablet twice daily when used with CYP2B6 inhibitors. examples are?

A

ticlopidine, clopidogre

38
Q

Naltrexone/bupropion should be avoided
in patients taking CYP2B6 inducers as these may …

A

reduce efficacy
of naltrexone/bupropion by reducing bupropion exposure (e.g.,
ritonavir, lopinavir, efavirenz, carbamazepine, phenobarbital,
phenytoin)

39
Q

what can occur when
naltrexone/bupropion is used concomitantly with dopaminergic medicaitons? (levodopa, amantadine)

A

central nervous system toxicity

40
Q

what is semaglutide? how does it work?

A

Semaglutide is a once-weekly, subcutaneously administered, human
GLP-1 analog that acts centrally on the POMC/CART neurons to improve satiation and satiety, reduce hunger and reduce cravings.43

41
Q

what dose is near maximal therapeutic efficacy for A1C lowering for semaglutide?

A

1mg weekly

42
Q

what is the dose of longterm obesity treatment of semaglutide?

A

2.4mg qweekly

43
Q

what is the titrating dose of semaglutide?

A

start with 0.25mg weekly for 4 weeks, 0.5mg, 1mg, 1.7mg, 2.4mg

44
Q

what was the result of semaglutide?

A

2.4 mg with health-behaviour modification resulted in -14.9% weight loss at 68 weeks.

86.4% of patients lost ≥ 5% body weight;
69.1% of patients lost ≥ 10% body weight;
50.5% of patients lost ≥ 15% body weight

45
Q

In a study of semaglutide 2.4 mg weekly vs. liraglutide 3 mg daily amongst 338 people with overweight or obesity without diabetes, what was the mean weight loss at 68 weeks?

A

-15.8% with semaglutide
vs. -6.4% with liraglutide.

46
Q

does liraglutide have effect in blood pressure and lipid profile?

A

yes - Among patients with obesity and prediabetes, liraglutide reduced systolic blood pressure by -2.8 mmHg compared with placebo over three years, with modest improvements in lipid parameters. A heart rate increase of two beats per minute (BPM) was observed,
in keeping with what is seen in the GLP-1 class.3

47
Q

does semaglutide have effect in blood pressure and lipid profile?

A

Semaglutide reduced systolic blood pressure by -6.1 mmHg vs.
-1.1 mmHg with placebo at 68 weeks, with modest improvement
in lipid parameters, in a study of people with obesity without type
2 diabetes (see Table 2). A heart rate increase of +3.5 BPM was
noted vs. -0.7 BPM with placebo, in keeping with what is seen in
the GLP-1 class.1

48
Q

The only obesity pharmacotherapy available in Canada which has been specifically studied amongst patients with obstructive sleep
apnea is ?

A

. Among patients with moderate or severe obstructive sleep apnea who were unable or unwilling to use a continuous positive airway pressure machine, liraglutide 3.0 mg combined with health-behaviour modification significantly reduced
the number of apnea-hypopnea index events by -12.2 events per
hour, compared with a reduction of -6.1 events per hour with
health-behaviour modification alone.13

49
Q

which med is approved in US as dual GIP/GLP-1 agonist for treatment of diabetes?

A

tirzepatide

50
Q

Weight loss with
tirzepatide 15 mg weekly ranged from..?

A

9.5 - 12.9%; superior to semaglutide

51
Q

The proportion of patients achieving at least 5% weight loss were for tirzepatide 5 mg, 10 mg and 15 mg, respectively?

A

85%, 89% and 91%

52
Q

The most
common adverse events of tirzepatide?

A

gastrointestinal side effects of mild
to moderate severity and transient, occurring primarily during dose
escalation.

53
Q

Significant improvements were seen with systolic and diastolic blood pressure from tirzepatide. t/f?

A

t

Obesity Canada (13 decks)

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