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Therapeutics II > Noninsulin agents > Flashcards

Noninsulin agents Flashcards

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1
Q

Oral agents

A

-metformin
-SGLT-2
-GLP-1
-DPP-4
-Sulfonylureas
-TZDs

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2
Q

Injectable agents

A

-GLP-1
-GIP and GLP-1

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3
Q

Person centered approach

A

-glycemic goals
-weight goals
-hypoglycemic risk (older peep)
-history of CVD/KD
-med cost

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4
Q

Metformin (Glucophage) MOA

A

-dec hepatic glucose production
-inc intestinal glucose utilization
-can inc GLP-1 secretion
-modest effect on inc tissue uptake and use by muscle

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5
Q

Metformin clinical applications

A

-adjunct to diet in t2dm
-combo
-consider for use in all t2dm

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6
Q

Why metformin recommended in t2dm

A

-reduce CVD rrisk
-extensive experience
-efficacious w minimal hypoglycemia
-positive/weight neutral effects
-cost effective

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7
Q

Off label indications metformin

A

-t1dm who are overweight w low ketoacidosis risk
-PCOS to lower androgen/inc ovulation

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8
Q

Overall efficacy metformin

A

-A1c 1.5-2%
-FBG: 60-80mg dec

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9
Q

Metformin excretion

A

-urine
-kidney function

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10
Q

Metformin advantages

A

-low hypoglycemia risk
-low lipids (LDL, TG)
-inc fibrinolysis = CV protection
-dec macrovasc probs
-dec stroke risk
-dec diabetic deaths

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11
Q

metformin disadvantages

A

-risk factor for fatal lactic acidosis (rare)
-GI side effects
-Vit B13 deficiency
-dementia risk

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12
Q

Risk factors of lactic acidosis in metformin use

A

-renal dysfunction (use eGFR not SCr)
-HF
-alcoholics
-shock
-COPD
-hepatic failure
-surgery/contrast dye

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13
Q

metformin and surgery

A

-hold metformin 1-2 days before and then around 2 days after depending upon pt status

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14
Q

Metformin GI effects

A

-30-50% pt
-diarrhea/flatulence
-N/V
-take w largest meal of the day
-titrate dosage

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15
Q

Vit B12 deficiency + metformin

A

-can worsen neuropathy
-monitor/provide supplementation
-check annually esp in pt w anemias and/or neuropathy

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16
Q

Risk of dementia w metformin

A

-controversial
-some say it does some say it doesn’t

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17
Q

Metformin dosing

A

-initial 500mg BID or 850mg qd wf
-titrate weekly and inc dose by 250-500mg

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18
Q

max dose of metformin

A

-2g/day actual
-2.5g/day according to package inserts

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19
Q

Metformin dosage forms

A

-500mg, 850mg, 1000mg

-SustainedActing formulation back (less GI effects) (recalled in 2020 bc NDMA levels that inc cancer and liver damage)

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20
Q

metformin and eGFR > 60

A

-no contraindication
-monitor SCr annually

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21
Q

metformin and 45 < eGFR < 60

A

-dafe
-continue use
-monitor SCr 3-6 month

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22
Q

metfromin and 30 < eGFR < 45

A

-not recommended
-recude dose by 50% if already taking
-monitor SCr q3months

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23
Q

metformin and eGFR < 3o

A

-do NOT start
-STOP if taking

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24
Q

SGLT2

A

-major transporter of renal glucose
-inhibition allows renal glucose excretion
-pissing sugar

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25
SGLT-2 uses
-adjuct to diet/exercise t2dm -recommended +/- metformin as initial therapy
26
SGLT-2 also good for pt w
-ASCVD or high risk -HF -CKD
27
SGLT efficacy
-A1c: 0.5-1% -FBG: 25-35mg -PPG: 40-60 -weight: 1-5kg -x: dec
28
SGLT adverse effects
-UTI -genital micotic infections -inc urination
29
UTI from SGLT
-53% inc risk of UTI in t2dm in general -not contraindicated in asx bacteruria -pt w lots of UTIs should be seen for risk factors -consider SLGT if pt UTI free for year
30
Genital mycotic infections (SGLT)
-already 81% inc risk in t2dm -counsel on s/s and hygiene -d/c in life threatening infections
31
FDA warning for serious genital infections
-necrotizinf faciitis of perimeum (Fournier's gangrene) -need abx and surgery -seek med attention (tenderness, swelling, fever)
32
SLGT2 and urination
-pt w bladder probs not gonna want it -AM dosing
33
other adverse effects SGLT2
-hypotension due to osmotic diuresis (worse on diuretics) -hyperkalemia (rare) -inc cholesterol -DKA FDA warning
34
DKA risk and SGLT
-t2dm w mild elevated BG -euglycemic -illness, dec food/water intake, dec insulin dose, alcohol -dont give to t1dm
35
DKA recommendations w SGLT
-hold 3 days before surgery (4 if ertugliflozin) -restart once oral intake back to baseline -wait until risk factors resolve -discuss sick day rules
36
SGLT FDA warning
-DKA -bone fracures + dec BMD -AKI -amputation risk
37
SGLT and bone fractures (canagliflozin)
-canagliflozin -loss of BMD at spine and hip -other flozins fine -caution hypotension as fall risk
38
SGLT and AKI (canagliflozin and dapagliflozin)
-50% cases start within one month of starting tx -pt improve after d/c -volume depletion and hypotension likely causes
39
SGLT cautions
-dehydration or hypotension risk (diuretics, NSAIDs, ACEI/ARBs)
40
SGLT and amputation
-canagliflozin -toes -weigh risk v benefits -monitor pain sores -risk factors: amputations, PVD, neuropathy, foot ulcers
41
SGLT drugs
-Canagliflozin -Dapagliflozin -Empagliflozin -Ertugliflozin
42
Canagliflozin dosing
-100mg qd -max 300mg -max 100mg if eGFR 30-60 and no signs of albuminuria -or <30 may use if albuminuria >300 but don't start
43
SGLT2 contraindication
-end stage renal failure on HD -not gonna d/c until they are on dialysis tho -use in pt w eGFR>20
44
Dapagliflozin dosing
-5mg -10 max
45
Empagliflozin dosing
-10mg -max25
46
Ertugliflozin dosing
-5mg qd -max 15
47
SGLT2 counseling
-stay hydrated -monitor renal function -suspend use during acute illlness or planned surgery (3days (4 on ertugliglozin))
48
SGLT2 CV benefits
-better on outcome, hospitilizations -good for renal protection -starting to be used outside of diabetes (HF and CKD)
49
GLP-1 drugs
-Liraglutide -Dulaglutide -Semaglutide -Exenatide -Lixisenatide
50
GLP1s
-stimulate B-cell growth -inhibit B-cell death -short acting -inhibit glucagon -delays emptying (slow absorption) -dec appetite -highly resistant to DPP-IV -inc first and second-phase insulin secretion -GLUCOSE DEPENDENT (insulin only released w BG) less risk of hypoglycemia
51
Clinical applications of GLP-1
-intial therapy +/- metformin -preferred to insulin in t2dm -if insulin used, combo w GLP1 for better efficacy
52
GLP1 efficacy
-A1c more effective than SGLT2 -short-acting = PPG control -long-acting = FBG control -weight loss UP
53
GLP1 excretion
-short acting GLP-1 eliminated by kidneyss
54
GLP-1 contraindication
-severe renal disease -pancreatitis (TG>300) -thyroid cancer
55
GLP1 adverse effects
-dose dependent nausea -V/D -dose titration dec sx and will improve over couple weeks -acute pancreatitis -inc risk of thyroid tumors -gall bladder disease -Gastroparesis (avoid) -Retinopathy
56
gall bladder disease from GLP-1
-esp high dose and long term use -inc risk of gallstones, inflammation, biliary sludge -use caution/avoid in preexisting gallbladder disease -consider d/c if gallbladder probs -prevent w low fat diet, hydration, activity
57
Gallstones (cholelithiasis)
-cholestero or bilirubin stones -can block flow of bile = pain, infection, inflammation -may alter bile composition -rapid weight loss = rapid mobilization of cholesterol from adipose tissue during weight loss into bile
58
gallbladder disease
-ab pain (right upper quadrant) -N/V -fever -use GLP w ca
59
Retinopathy in GLP-1
-caused by rapid drop in A1c -CAUTION pt w nonproliferative retinopathy -AVOID in proliferative diabetic retinopathy
60
Dulaglutide (trulicity) dosing
-0.75-4.5mg -qweek -do NOT use in ESRD -needles included
61
Semaglutide (Ozempic) dosing
-0.25 x 4 weeks then 0.5mg-2mg -qweek -needles included
62
Liraglutide (victoza) dosing
-0.6mg x 7 days the 1.2-1.8mg -qd
63
Exenatide (Byetta) dosing
-5mcg x month then 10 mcg -BID -avoid if CrCl<30
64
Lixisenatide (Adylyxin) dosing
-10mcg x 14 fays then 20mcg -avoid eGFR< 15 -qd
65
Dulaglutide (trulicity) counseling
-admin in thigh, ab, arm -single dose pens -remove cap, press pen aginst skin and press button -good for needlephobes
66
Semaglutide (ozempic) counseling
-admin thigh, ab, arm -store pens in fridge -can store 56 days at room temp -check flow every pen
67
Liraglutide (victoza) counseling
-give any time of day independent of meals -admin in thigh, ab, arm -pre-filled pens
68
Oral semaglutide (rybelsus)
-3mg PO x 30 days then inc 7mg qd -inc 14mg if needed -can change to 7mg if on 0.5mg SQ -take 30 min before first food or other oral meds with no more than 4 oz water (vomiting)
69
GLP1 benefits
-CVD and renal
70
dual GIP/GLP1
-Tirzepatide (Mounjaro)
71
Tirzapatide (mounjaro)
-enhance both phase insulin secretion -reduce glucagon levels in glucose-dependent manner -delay gastric emptying -inc satiety
72
Tirzepatide (Mounjaro) efficacy
-A1c: 1.5-2.3 close to metformin -FBG: 40-60 -weight loss 6-11kg
73
tirzepatide adverse effects
-similar to GLPs -N/V/D -pancreatitis, thyroid tumors, gallbladder disease -tachycardia
74
Tirzepatide dosing
-2.5mg SQ weekly -adjust qmonth by 2.5mg/week -up to 15mg weekly
75
DPP-4 inhibitors
-Sitagliptin (Januvia) -Saxagliptin (Onglyza) -Linagliptin (Tradjenta) -Alogliptin (Nesina) -not as strong efficacy -weight neutral -renal dosing
76
DPP-4 adverse effects
-nasopharygitis -upper RTI -headaches -pancreatitis -joint pain -HF risk (sitagliptin fine tho)
77
which DPP-4 for HF
-sitagliptin
78
Whidh DPP-4 not renally eliminated
-linagliptin -no dose adjustment required
79
Sitagliptin dosing
-100mg CrCl >50 -50 mg CrCl 30-50 -25mg for CrCl <30 or HD
80
Saxagliptin dosing
-2.5-5mg qd -2.5mg for CrCl <50
81
Linagliptin
-5 mg qd -no renal dose adjustment
82
Alogliptin
-25mg qd CrCl > 50 -12.5mg CrCl 30-50 -6.25mg CrCl < 30 or HD
83
Sulfonylureas moa
-stimulate insulin release from B cells -may inc binding between insulin and receptors or inc amt of receptors -glucose independent tho (hypoglycemia)
84
Sulfonylurea clinical application
-adjuct diet/exercise t2dm -combo w insulin and non insulin -CHEAP
85
Sulfonylurea efficacy
-A1c: dec 1-2% -FBG dec 60-70
86
2nd gen sulfonylureas
-Glipizide* -Glyburide -Glimepiride -we dont use 1st gen
87
Sulfoynlurea kinetics
-glyburide and glipizide more effective when taken 30 min BEFORE meal -metabolized by liver -excreted in urine -glipizide metabolized w/o formation of active metabolites = better in renal disease
88
sulfonylurea preferred in renal disease
-glipizide -no formation of active metabolites -good for elderly too
89
Sulfonylureas adverse effects
-hypoglycemia -weight gain -hematologic -allergy (steven johnsons)(sulfa)
90
hypoglycemia + sulfonylurea risk
-renal/hepatic probs -elderly or malnourished -other hypoglycemic drugs
91
sulfonylurea hematologic adverse effects
-leukopenia -thrombocytopenia -aplastic anemia -sulfa component
92
sulfonylurea dosing
-start low and slow esp in old ppl -inc dose every 1-2 weeks until max -max dose inc side effects w no benefit
93
sulfonylurea max dosing
-about 60-75% of current max dose listed -glipizide might actually be 20mg
94
Glipizide dose
-start 2.5-5mg qd -max 40mg (20mg for XL)
95
Glyburide dose
-start 1.25-5mg qd -max 20mg
96
Glyburide micronized dose
-start 1.5-3mg qd -max 12mg
97
Sulfonylurea population cautions
-elderly -renal/hepatic disease -irregular dietary intake -alcoholics -with hypoglycemic agents -all inc risk of hypoglycemia
98
Sulfonylurea best candidates
-type 2 only -short duration of diabetes (newly diagnosed) -FBS < 250mg/dL -high fasting C-peptide levels
99
Sulfonylurea treatment failure
-25% primary failure -after 5 years, 50-75% secondary failure -common failure after 612 months
100
Thiazolidinediones (TZDs) MOA
-bind to peroxisome proliferator activator receptor y on fat cells and vascular cells (PPAR-y) -improve cell response to insulin w/o inc secretion -dec insulin resistance -dec hepatic glucose production
101
other benefits of TZDs
-Pioglitazone can dec TG by 10-20% -LDL unchanged w Pioglitazone but maybe inc w rosiglitazone (converts LDL to large fluffy ones?) -inc HDL 3-9 mg/dL -inc endothelial function -slight dec in BP
102
TZD efficacy
-dec A1c 0.5-1.5% -FBG dec 60-70 -dependent on insulinemia
103
TZD adverse effects
-Hepatotoxicity -resume ovulation (good in PCOS tho) -exacerbations of HF -macular edema -inc fracture risk 25%
104
TZD hepatotxicity
-check baseline LFTs -do NOT start is LFTs > 2.5x nl -check LFTs periodically -d/c if LFTs > 3x normal -monitor N/v, ab pain, fatigue, anorexia, urine
105
TZD monitoring
-LFTs > 3x = d/c -N/V -ab pain -fatigue -anorexia -dark urine
106
TZD and HF
-caution in pt w NYHA class 3-4 HF -inc edema -inc weight
107
which TZD we using
-pioglitazone
108
Pioglitazone (TZD) dosing
-start 15-30mg qd -max 30-45mg -inc dose every 12 WEEKS
109
Tx principles for T2DM
-treat aggressively to achieve goals -start diet/exercise -consider metformin and combo therapy -consider weight
110
considerations for T2DM tx
-disease states -BG and A1c -HYPOglycemia risk -SE -impact on weight -cost and other pt factors
111
T2DM tx in ASCVD, HF, CKD
-SGLT2is and GLP1s
112
When to start dual therapy T2DM
-A1c > 1.5-2% above goal -or A1c > 7.5-9% -at least 8.5% get them on 2
113
Insulin tx for T2DM
-prefer GLP1 when possible -use insulin if: -weight loss -hyperglycemia signs -A1c > 10% -BG> 300mg/dL -recommend BASAL insulin combo therapy w GLP1 -go to basal-bolus insulin for tighter control if no GLP1 -be aware of overbasalization -additional therapy if goals not reached after 3 months
114
Overbasalization
-if basal dose is 0.5units/kg/day or high variability in BG readings -evaluate basal level and consider basal-bolus
115
1st line for T2DM w ASCVD
-GLP1 or SGLT2
116
1st line in pt w HF
-SGLT2
117
1st line in pt w CKD
-SGLT2 -GLP1 if not
118
Efficacy considerations
-Metformin -consider combo -avoid risk of HYPOglycemia when necessary
119
Tx for pt that need to minimize weight gain
-GLP1 or SGLT2
120
Rx to avoid in pt that need to minimize weight gain
-sulfonylureas -meglitinides -TZDs
121
Cost considerations
-cheaper: sulfonylureas and TZDs
122
drug chart
drug chart

Therapeutics II (55 decks)

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