Pharmacotherapy Flashcards
BMI indications for rx & surg
Rx:
27 w complications
30
Surg:
35 w compl
40
Benefits of modest wt loss @ 5-10% and >10%
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
FDA-approved for LONG-term use
Phentermine/Topiramate ER
Naltrexone/Bupropion
Orlistat
Semaglutide
Liraglutide
Setmelanotide
FDA-approved for SHORT-term use
Phentermine & similars:
Diethylpropion
Phendimetrazine
Benphetamine
OFF-LABEL use AOM’s for LONG-term (7)
Topiramate
Zonisamide
Bupropion
Other GLP1-RA
Metformin
Amyling agonist
SGLT2 inhibitors
Age cutoffs
Trade names:
Orlistat
Xenical
Alli
Trade names:
Phentermine/Topiramate ER
Qsymia
Trade names:
Naltrexone/Bupropion
Contrave
Trade names:
Liraglutide
Saxenda
Trade names:
Semaglutide
Wegovy
Trade names:
Setmelanotide
Imcivree
Trade names:
Phentermine
Lomaira
Adipex
Trade names:
Diethylpropion
Phendimetrazine
Benzphetamine
Diethylpropion:
…Tenuate (Tenuate Dospan)
Phendimetrazine:
…Bontril
Benzphetamine
…Regimex
Phentermine:
Dosage
Mech
Contraind
Adverse rxns
Pharmacokinetics
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
Randos:
Diethylpropion
Phendimetrazine
Benzphetamine
-Dosages
-Usage notes
-DEA sched
-Excretion
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
Sympathomim contrainds
Preg (or planning)- X
Breastfeeding- X
Current ADR
Advanced/Sx CAD
Uncontrolled HTN
Hyperthyroid
Close angle glaucoma
Severe anxiety
Uncontrolled mental health
Sympathomim interactions
MAOI <14 days
Anesthesia
Caffeine
EtOH
Sympathomim SE
Dry mouth (muc erosions 1/1000)
Dia/Const
Diff sleeping
Dz
Dysgeu
↓ libido
CNS stim –> restless
Glaucoma, IOP
HA
↑ BP
↑ HR
Palps
EKG alerts while on sympathomim
-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
Phentermine/Topiramate ER
Dosage
Mech
Contraind
Adverse rxns
Pharmacokinetics
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
Phentermine/Topiramate ER
Contrainds
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
EKG alerts while on sympathomim
-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
Phentermine/Topiramate ER
Adverse rxns
Common:
Paresthesias
Dysgeusia
Dz
Insom
Constipation
Dry mouth
Attn disturbance
Serious:
*nephrolithiasis
metbolic acidosis
acute angle closure glaucoma
Depression & SI
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
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
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
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
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
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
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
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
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
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
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
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
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
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%)
DEA schedules
IV:
Phentermine/Topiramate ER
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
D/C criteria
Liver metabolizes…
Brain fog
Depression
Paresthesias
Contraindications
Topiramax
Zonisamide
CVD
Uncontrolled HTN
Hyperthyroid
Contraindications
Phetermine
Phen/top
Diethylpropion
Gastroparesis
Contraindications
GLP1-RA
Glaucoma
Contraindications
Phen
Phen/Top
Diethylpropion
Zonisamide
Nephrolithiasis
Contraindications
Topiramate
Phen/Top
Orlistat
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
Vit D def
Contraindications
Orlistat
SI risks
-phen/top
-top
-nal/bup (box warning)
-bup
-GLP-1 agonists
-setmelanotide
Contraind w MAOI
-phen(?)
-phen/top
-nal/bup
Common weight promoting medicines (classes)
Antipsychotics
Antidepressants
Sleep agents
Neuropathic agents
B-blockers
Steroids
DM meds
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
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
Anti-seizure meds that promote wt gain
-Wt neg
Carbemaz
Gabapentin
Valproate
Pregabalin
Wt neg:
-Lamotri
-Top
-Zonis
Mood stab that promote wt gain
Li
Gabapentin
Divalproex
Valproate
Vigabatrin
Cariprizane
Carbemaz
Wt neg:
Lamotri
Migraine meds that promote wt gain
Amitriptyline
Gabapentin
Paroxetine
Valproic acid
Some BB
Neg:
Top
Sleep agents that promote wt gain
Mirtazepine
Gyn med that promotes wt gain
Depo provera
Hormones that promote wt gain
-Glucocorts
-Estrogen
Neutral:
-prog
-test (wt neg)
Neuropathic agents that promote wt gain
gabapentin
pregabalin
CV meds that promote wt gain
BB:
-propranolol
-atenolol
-metoprolol
Older/less lipophil CCB (edema):
-nifed
-amlo
-felo
DM meds that promote wt gain
Insulin
Sulfonylureas
TZDs
Meglitinides
Neg:
-Metformin
-GLP1 ag
-SGLT2 inh
-a-glucosidase inh
-Pramlinitide
HIV meds that promote wt gain
some HAART protease inh
Chemotx that promote wt gain
Tamox
Cyclophos
MTX
5-FU
Aromatase inh
Corticosteroids
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
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
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
Other AOM uses in kids
ON LABEL:
Metformin & Lira:
>= 10 yo for T2DM
OFF-label:
Metformin:
-Obesity
>= 10 yo for PCOS
AOM in pregnancy?
FDA-approved meds are contraindicated!
Cat X- phen, phen/top, bup/nal, phenD
Special populations:
Depression
Bupropion (?1st choice)
Special populations:
BED
Lisdexa (FDA approved)
Also (off-label):
Top
Dulox
Fluox
Bupropion
Special populations:
NES
Sertraline
Citalo
Escitalo
Special populations:
DM
Metformin
GLP1 ag
SGLT2 inh
Glucosidase inh
Weight neutral:
DPP4
Acarbose
Special populations:
Premenstrual carbs
Spironolactone in latter half of cycle-2nd day menses (scant evidence)
HIV meds that promote wt gain
some HAART protease inh
