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Pharmacotherapy Flashcards

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1
Q

BMI indications for rx & surg

A

Rx:
27 w complications
30

Surg:
35 w compl
40

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2
Q

Benefits of modest wt loss @ 5-10% and >10%

A

5-10%:
-improved lipds
-↓ CVD risk
-↓ BP
-↑ insulin sens & glycemic control in T2DM
-↓ progression from pre-DM to T2DM

> 10%:
-more improvement in above
-↓ NAFLD/NASH and fibrosis
-improved OSA
-joint paint/arthritic conditions
-PCOS & fertility

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3
Q

FDA-approved for LONG-term use

A

Phentermine/Topiramate ER
Naltrexone/Bupropion
Orlistat

Semaglutide
Liraglutide
Setmelanotide

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4
Q

FDA-approved for SHORT-term use

A

Phentermine & similars:
Diethylpropion
Phendimetrazine
Benphetamine

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5
Q

OFF-LABEL use AOM’s for LONG-term (7)

A

Topiramate
Zonisamide
Bupropion
Other GLP1-RA
Metformin
Amyling agonist
SGLT2 inhibitors

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6
Q

Age cutoffs

A
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7
Q

Trade names:

Orlistat

A

Xenical

Alli

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8
Q

Trade names:

Phentermine/Topiramate ER

A

Qsymia

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9
Q

Trade names:

Naltrexone/Bupropion

A

Contrave

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10
Q

Trade names:

Liraglutide

A

Saxenda

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11
Q

Trade names:

Semaglutide

A

Wegovy

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12
Q

Trade names:

Setmelanotide

A

Imcivree

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13
Q

Trade names:

Phentermine

A

Lomaira
Adipex

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14
Q

Trade names:

Diethylpropion
Phendimetrazine
Benzphetamine

A

Diethylpropion:
…Tenuate (Tenuate Dospan)

Phendimetrazine:
…Bontril

Benzphetamine
…Regimex

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15
Q

Phentermine:

Dosage
Mech
Contraind
Adverse rxns
Pharmacokinetics

A

Dosage:
-most commonly 15-37.5 mg daily
-8, 15, 30, and 37.5 mg scored capsules

Mech:
-sympathomim amine –> hypoth NE release, other CNS effects

Contraind:
-Preg
-acute CHD
-closed angle glaucoma

Adverse rxns:
**dry mouth
**MAOI, EtOH, adren nerve block
-insomnia
-brux
-palpitations
-constip
-diff urinating
-HA
-irrit
-dysphoria
-change in libido
* NO e/o addiction or withdrawal

Pharmacokinetics:
-urinary excretion (careful w renal impairment!)
-t 1/2 is 7-20 hrs

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16
Q

Randos:

Diethylpropion
Phendimetrazine
Benzphetamine

-Dosages
-Usage notes
-DEA sched
-Excretion

A

Dosages:
-D: 25 (75 ER) TID
-P: 35 (105 ER) TID
-B: 25-50 once a day, up to TID

Usage notes:
-D: TID, short acting 4-6 hrs, weaker than phen

-P: TID 1 hr before meals, sometimes AM phenT w PM phenD, weaker than phen

DEA sched:
-B: IV
-P: III

*D&P excreted by urin ?B

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17
Q

Sympathomim contrainds

A

Preg (or planning)- X
Breastfeeding- X
Current ADR
Advanced/Sx CAD
Uncontrolled HTN
Hyperthyroid
Close angle glaucoma
Severe anxiety
Uncontrolled mental health

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18
Q

Sympathomim interactions

A

MAOI <14 days
Anesthesia
Caffeine
EtOH

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19
Q

Sympathomim SE

A

Dry mouth (muc erosions 1/1000)
Dia/Const
Diff sleeping
Dz
Dysgeu
↓ libido
CNS stim –> restless
Glaucoma, IOP
HA
↑ BP
↑ HR
Palps

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20
Q

EKG alerts while on sympathomim

A

-E/o ischemia/infarct
-LBBB, esp new
-multifocal PVCs
-QTc prolongation (tx w K, Mg)
…>460 kids, 450 M, 470 F

*LAD(?) common in obesity, reversed w wt loss

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21
Q

Phentermine/Topiramate ER

Dosage
Mech
Contraind
Adverse rxns
Pharmacokinetics

A

Dosage:
-AM 3.75/23 mg x 14 d
-then ↑ to 7.5/46 mg x 12 wks
…if <3%,
↑ again to 11.25/69 mg x 14 d
-then 15/92 mg (full strength) x 12 wks
…D/C if <5% @ 12 wks, but TITRATE QOD at least 7 days bc sz risk

Mech:
-Phen is sympathomim amine
–> catechol (NE) in hypothalamus ↓ app & food intake
-Top mech unknown, possibly GABA effects on appetite and satiety or by –| CANH

Contraind:
(see individ)

Adverse rxns:
(see individ)

Pharmacokinetics:
-Phen met liver and excreted by kids
-Top excreted by kids

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22
Q

Phentermine/Topiramate ER

Contrainds

A

Sx CAD
Active mania
Uncontr HTN
Closed angle glaucoma
Preg
Ca ox kid stones
MAOI in past 14 days

** monitor for preg w monthly UPT and document 2 FORMS of contraception

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23
Q

EKG alerts while on sympathomim

A

-E/o ischemia/infarct
-LBBB, esp new
-multifocal PVCs
-QTc prolongation (tx w K, Mg)
…>460 kids, 450 M, 470 F

*LAD(?) common in obesity, reversed w wt loss

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24
Q

Phentermine/Topiramate ER

Adverse rxns

A

Common:
Paresthesias
Dysgeusia
Dz
Insom
Constipation
Dry mouth
Attn disturbance

Serious:
*nephrolithiasis
metbolic acidosis
acute angle closure glaucoma
Depression & SI

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25
Orlistat: Dosage Mech Contraind Adverse rxns Pharmacokinetics
Dosage: -60-120 TID w meals Mech: -Lipase inh --| 30% fat abs Contraind: -Preg -Chronic malabs -Cholestasis Adverse rxns: -diarrhea, oily stools -fecal incont -RARE hepatotox -fat sol vit def -↑ urinary oxalate Pharmacokinetics: -likely mainly within GI wall -minimal systemic absorption
26
Naltrexone/Bupropion HCL ER Dosage Mech Contraind Adverse rxns Pharmacokinetics
Dosage: -8/90 mg, Titrate up over 4 wks 1. 1 AM 2. 1 AM + 1 PM 3. 2 AM + 1 PM 4. 2 + 2 -D/C if <5% wt loss @ 12 wks Mech: -Natrexone is opioid antag -Bup: weak --| reuptake of NE & DA -both may work in hypoth & mesolimp/DA circuit to ↓ app & reward Contraind: -Uncontrolled HTN -Sz d/o -AN / bulimia -abrupt d/c of EtOH, benz/barbs, anti-eps -chronic opiod use -MAOI within 14 d Adverse rxns: -Bup & metabs --| CYP2D6 -N/V -constip -HA -dz -insomnia -dry mouth -diarrhea SERIOUS: -worsening depression & SI -hepatotoxicity -sz Pharmacokinetics: -Bup: ext metabolized into active metabolites, 87% metabs excreted by kids -Nal: excreted by kids
27
Liraglutide & Semaglutide: Dosage Mech Contraind Adverse rxns Pharmacokinetics
Dosage (for obesity): Lira: 3 mg daily Sema: 2.4 mg WEEKLY Mech: -hypothalamus ↓ intake, ↑ satiety -improves glucose metab -?↓ gastric emptying Contraind: -med thyr CA (black box lira) -MEN2 -preg Adverse rxns: ** acute pancreatitis ** acute gb dz (?2/2 wt loss) ** hypoglycemia esp. w insulin/secretagogues ** suicidal ** N/V --> AKI ** hydrate -C/D -HA -dz -fatigue -↑ HR -dyspepsia / abd pain -↑ lipase -high fat foods --> nausea Pharmacokinetics: Lira: -SC lira only 55% bioavailable -endog metab, no specific organ -intact lira not excreted Sema: -SC sema 89% bioavail -metab following proteolytic cleavage, beta ox of FA sidechain -98% bound to alb -excr via urine and feces
28
Lira dosing
Over 5 wks: ... 0.6 mg x 7 d ... +0.6 mg per wk ... 3 mg maintenance dose Consider D/C if <4% wt loss @ 16 wks
29
Sema dosing
Over 5 MONTHS: ...0.25 mg x 4 wks ...then 0.5, 1.0, 1.7, 2.4 maint If 2.4 not tol, decrese to 1.7 for up to 4 wks. If 2.4 still not tolerated then D/C
30
Setmelanotide: Dosage Mech Contraind Adverse rxns Pharmacokinetics
Dosage: (DAILY SC) 6-11 yo: 1 mg x 2 wks ...titrate to 2 mg 12-adult: 2 mg x 2 wks ...titrate to 3 mg Mech: --> MC4R pathway in pts w def in POMC, PCSK-1, LEPR ... ↓ hunger, ↑ EE Contraind: none d/c in preg unless ben>risk? Adverse rxns: -spont erection -Depr & SI -** skin pigmentation & darkening of nevi -most commonly: inj site pain & pig, GI (n/v/d/pain), HA, back pain, fatigue Pharmacokinetics: -T 1/2 11 hrs -broken down into smaller peptides, 39% excr unchnaged in urine
31
Topiramate (off label) Dosage Mech Contraind Adverse rxns Pharmacokinetics
Dosage: 25-200 daily split BID (titrated up) Mech: -enhances GABA activity Contraind: -preg (CLEFT PALATE) -closed angle glaucoma Adverse rxns: -attn difficulty -mem loss -paresthesias -fatigue -somnol -acute angle closure glauc -KIDNEY STONES -dysgeusia -depr & SI -↓ bone min density -??typo MAOI, EtOH, adre nerve block Pharmacokinetics: -adjust dose for renal, liver impairment, or elferly
32
Zonisamide (off label) Dosage Mech Contraind Adverse rxns Pharmacokinetics
Dosage: 25-100 NIGHTLY (can incr wkly by 25) Mech: -stabilizes Na & Ca channels Adverse rxns: -similar to Top Pharmacokinetics: -avoid in renal impairment
33
Bupropion (off label) Dosage Mech Contraind Adverse rxns Pharmacokinetics
Dosage: (titrated up) 150-450 XR daily 100-200 SR QD-BID 100 IR QD-TID Mech: -Bup: weak --| reuptake of NE & DA -may work in hypoth & mesolimp/DA circuit to ↓ app & reward Contraind / Adverse rxns: -May lower sz threshold! --| CYP2D6, drug interactions Pharmacokinetics: -Bup: ext metabolized into active metabolites -87% metabs excreted by kids
34
Lower dose GLP1-R1
Lira @ 1.8 /d (max 2) Sema @ 1 /wk (max 2.4) ORAL Sema 14 mg /d Dula @ 4.5 sq/wk -high fat foods --> nausea
35
Metformin Dosage Mech Contraind Adverse rxns Pharmacokinetics
Dosage: -500-2000 daily -us. 1000 BID or 2000 XL daily Mech: --> AmpK ↓ gluconeo in liver ↑ mm glucose uptake ?alter gut ubiome Contraind: -GFR < 30 (caution 30-45) Adverse rxns: -Nausea -Cramping -other GI -B12 deficiency ...Ca supp, low fat foods may ↓ side effects Pharmacokinetics -adjust dose for renal/hep impairment, elderly
36
Amylin mimetic (Pramlinitide) Dosage Mech Contraind Adverse rxns Pharmacokinetics
Dosage: **SUBQ T1DM- 15 ug before meals ...+15 every 3 days ...50 ug TIDAX T2DM- 60 ug before meals x 3d ...then 120 ug TIDAC Mech: -delayed gastric empt -↓ post-prandial gluconeo -↓ app centrally Contraind Adverse rxns: -N/V -hypoglycemia... **reduce insulin before meals 50%! -HA -inj site rxn -pancreatitis Pharmacokinetics: -peaks @ 20 min -lasts 3 hrs
37
SGLT2 inhibitors Dosage Mech Contraind Adverse rxns Pharmacokinetics
Dosage: -Cana 100-300 -Dapa 5-10 -Empa 10-25 Mech: ↑ renal glucose excretion Contraind: -not rec for GFR <30-45 Adverse rxns: -gu fungal infxn -phimosis -nec fasc -limb amputations -↑ thirst -↑ UOP -DKA -hypoglycemia w other meds Pharmacokinetics: -
38
Weight loss: (avg %bw lost, >= 5%, >=10%) Phentermine Phentermine/Topiramate ER Naltrexone/Bupropion Orlistat Semaglutide Liraglutide Setmelanotide Gelesis
Phen: *most cost effective tx -7.4% but variable -49-82% (>5%) -16-76% (>10%) Phentermine/Topiramate ER: -10.9% on full dose 15/92 (~1/2 on 1/2 dose) -67% (>5%) -47% (>10%) Naltrexone/Bupropion: -5.4% - 8.1% -42-57% (>5%) -21-25% (>10%) Orlistat: -3.9% (2.3% @ 2 yrs) -21% (>5%) -12% (>10%) Semaglutide: -up to 14.9%! -84.8% (>5%) -73% (>10%) -53.4% (>15%) Liraglutide: -9.2% (6.1% in preDM trial) -62% (>5%) -34 (>10%) Setmelanotide: -12.5-25.6% (n = only 10-11 pts each!) -45-80% achieved >10% wt loss Gelesis: -3% wt loss -59% (>5%) -25% (>10%)
39
DEA schedules
IV: Phentermine/Topiramate ER
40
Max doses
Phentermine: -37.5 mg Phentermine/Topiramate ER: -15/92 mg Naltrexone/Bupropion: -4 tabs/d = 32/360 Orlistat: -120 TID Semaglutide -2.4 mg WEEKLY Liraglutide -3 mg daily Setmelanotide -2 kids, 3 adults
41
D/C criteria
42
Liver metabolizes...
43
Brain fog Depression Paresthesias Contraindications
Topiramax Zonisamide
44
CVD Uncontrolled HTN Hyperthyroid Contraindications
Phetermine Phen/top Diethylpropion
45
Gastroparesis Contraindications
GLP1-RA
46
Glaucoma Contraindications
Phen Phen/Top Diethylpropion Zonisamide
47
Nephrolithiasis Contraindications
Topiramate Phen/Top Orlistat
48
Sz Contraindications
-no nal/bup if any h/o sz -bup off label may lower sz threshold -diethylpropion(?) -Need to D/C phen/top slowly from max dose, QOD, to ↓ sz risk
49
Vit D def Contraindications
Orlistat
50
SI risks
-phen/top -top -nal/bup (box warning) -bup -GLP-1 agonists -setmelanotide
51
Contraind w MAOI
-phen(?) -phen/top -nal/bup
52
Common weight promoting medicines (classes)
Antipsychotics Antidepressants Sleep agents Neuropathic agents B-blockers Steroids DM meds
53
Antipsychotics that promote wt gain
** Risperdone (14% had >7%) Li Quetia Olanza Cloza Valproic acid Iloperidone Paliperidone Divalproex Oxycarbazepine ...Others in appendix **Ziprasidone (7% had >7%, least in category) ... consider adding metformin or topiramate
54
Antidepressants that promote wt gain -Wt neg
SSRI: *Parox *Cital -Escitalo -Sertraline -Dulox *TCA's: -Amitriptyline -Doxepin -Imipramine MAOI -Isocarboxazid -Phenelzine -Mirtazapine -Brexipraxole SNRI: ?*Venlafax Wt neg: Bup
55
Anti-seizure meds that promote wt gain -Wt neg
Carbemaz Gabapentin Valproate Pregabalin Wt neg: -Lamotri -Top -Zonis
56
Mood stab that promote wt gain
Li Gabapentin Divalproex Valproate Vigabatrin Cariprizane Carbemaz Wt neg: Lamotri
57
Migraine meds that promote wt gain
Amitriptyline Gabapentin Paroxetine Valproic acid Some BB Neg: Top
58
Sleep agents that promote wt gain
Mirtazepine
59
Gyn med that promotes wt gain
Depo provera
60
Hormones that promote wt gain
-Glucocorts -Estrogen Neutral: -prog -test (wt neg)
61
Neuropathic agents that promote wt gain
gabapentin pregabalin
62
CV meds that promote wt gain
BB: -propranolol -atenolol -metoprolol Older/less lipophil CCB (edema): -nifed -amlo -felo
63
DM meds that promote wt gain
Insulin Sulfonylureas TZDs Meglitinides Neg: -Metformin -GLP1 ag -SGLT2 inh -a-glucosidase inh -Pramlinitide
64
HIV meds that promote wt gain
some HAART protease inh
65
Chemotx that promote wt gain
Tamox Cyclophos MTX 5-FU Aromatase inh Corticosteroids
66
Gelesis 100 (Plenity) -wt loss -indications -dosing -contraind -precautions -adv rxns
-cellulose + citric acid -3% wt loss -59% (>5%) -25% (>10%) Ind: -BMI 25-40 Dosing: -3 capsules TID w 16 oz water 20-30 mins before meals Contra: -preg Precautions: -absorption of other meds -esoph anat abnL -strictures (Crohn's) -GERD -ulcers -altered GI motility (surgeries) Adv rxn: -abd pain / distension -constip -flatulence -diarrhea -nausea
67
Newer AOM & CVD outcomes
Phen/Top Nal/Bup Sema/Lira All ↓ LDL, TG, A1C, and SBP All ↑ HDL *EXCEPT Nal/Bup ↑ SBP!!! And no change to LDL
68
FDA-approved AOMs in kids for OBESITY (4)
"SLOP" >= 6 yo: Setmel >= 12 yo: Lira, LONG-term ...wt over 60 kg, BMI equ over 30 for age using Cole criteria >= 12 yo: Orlistat, LONG-term >= 16 yo: Phen, SHORT-term
69
Other AOM uses in kids
ON LABEL: Metformin & Lira: >= 10 yo for T2DM OFF-label: Metformin: -Obesity >= 10 yo for PCOS
70
AOM in pregnancy?
FDA-approved meds are contraindicated! Cat X- phen, phen/top, bup/nal, phenD
71
Special populations: Depression
Bupropion (?1st choice)
72
Special populations: BED
Lisdexa (FDA approved) Also (off-label): Top Dulox Fluox Bupropion
73
Special populations: NES
Sertraline Citalo Escitalo
74
Special populations: DM
Metformin GLP1 ag SGLT2 inh Glucosidase inh Weight neutral: DPP4 Acarbose
75
Special populations: Premenstrual carbs
Spironolactone in latter half of cycle-2nd day menses (scant evidence)
76
HIV meds that promote wt gain
some HAART protease inh

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