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PDAT2 > 12 - Oral Diabetes Medication 1 > Flashcards

12 - Oral Diabetes Medication 1 Flashcards

1
Q

Pregnancy? / ADR / Disadvantages

Meglitinides

A

Not Recommended in Pregnancy / Unknown if excreted in breast milk

caution w/ Clopidogrel or cyclosporine

Elderly / Adrenal-Pituitary Insufficiency

Severe Renal/hepatic impairment

not recommended to take with another secretagogue

Headache / Upper Respiratory Infection / Diarrhea / Weight gain

Hypoglycemia (Repaglinide) / Dizziness (Nateglinide)

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2
Q

Pregnancy? / ADR / Disadvantages

PiaglitaZone

TZD

A

Not Recommended in Pregnancy

Unknown if excreted in breast milk

Increased risk/exacerbation of CHF

Edema / Weight Gain

Upper Resiperatory INFECTION

incresed risk in women for bone fractures / ovulation

COST

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3
Q

Dose

DAPAgliflozin

SGL2-Inhibitor

A

FARXIGA

5mg qd AM

in morning with or w/o food

no dose adj for hepatic impairment

NOT RECOMMENDED for <45ml/min eGFR

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4
Q

ALOgliptin DOSE

Nesina

A

Nesina but generic

25mg QD

with or without food

Renal adjustments, CrCl of:

30-60ml/min = HALF 12.5mg qd

<30ml/min = half again 6.25mg qd

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5
Q

PK’s

SGLT2 Inhibitors​

C-D-E-E GLIFLOZIN​

A

All 4 Drugs have

>80% Glucuronidation metabolism

Peaks around 1-2 hours

Excreted split in urine & feces

  • no dose adjustment for HEPATIC impairment*
  • except for CANAgliflozin* (invokana)
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6
Q

SITAgliptin

A

Januvia

NO GI ADVERSE EFFECTS!

headache / upper respiratory infection / nasopharyngitis

  • Avg A1c reduction: 0.5-0.8%
  • FPG reduction: 20-40mg/dl
  • 2hrPPG reduction: 40-50mg/dl
  • DI:
    • ​increase digoxin
    • increase risk of hypoglycemia w/ sulfonylurea or insulin​
  • ​Peak/Elim = 1-4 hours / 12 hours
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7
Q

Disadvantages of

Metformin

A

GI adverse effects

Risk of lactic acidosis

Caution with alcohol

Not appropriate with

moderate-severe renal impairment

Acute/unstable CHF

Liver impairment

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8
Q

Products

Sulfonylureas

Insulin Secretagogues

A

Second Gen:

GLIPizide

5mg QD-BID

Glimepiride

0.5-1.0mg QD

Glyburide / Glyburide Micro

  • not seen much in practice, due to CKD / CVD risk*
    2. 5 / 1.5 QD or BID
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9
Q

Specific details of: SAXAgliptin

DPP4

LASS GLIPTIN

A

Onglyza

Active Metabolite - 2+4hour Peak

Peripheral Edema / UTI / symptoms of URI

headache / symptoms of upper respiratory infection

  • Reduce A1C by 0.5% monotherapy
  • Combo with sulfonylurea / metformin / TZD - 0.5-0.9%
    • increase risk of hypoglycemia w/ sulfonylurea or insulin​​
  • Along with ALOgliptin may increase risk of*
  • HEART FAILURE*
  • monitor SOB / fatigue / weight gain*
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10
Q

Which drugs are OKAY TO USE for pregnancy?

A

Alpha Glucosidase Inhibitors
Acarbose / Miglitol

DPP-4 Inhibitors
LASS-gliptin

Metformin

  • Bromocriptine mesylate = CYCLOSET*
  • Bile Acid Sequestrant = Colesevelam*
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11
Q

MoA / Advantages

DPP4 Inhibitors

SITAgliptin / SAXAgliptin / LINAgliptin / ALOgliptin

A

Enhances the INCRETIN SYSTEM

particularly GLP-1

oral agent –> incretin system

QD DOSE / WEIGHT NEUTRAL

well tolerated in most patients

Can be used in Renal Insufficiency

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12
Q

Not Recommended / Precautions

PiaglitaZone

TZD

A

Black Box Warning - CHF

Contraindicated in NYHA C3/4 CHF

Liver Disease

Monitor LFTs at start of therapy

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13
Q

Advantages / Benefits

Alpha-Glucosidase Inhibitors

Acarbose (precose) / Miglitol (glyset)

A

PROVIDES PPG CONTROL

does not cause hypoglycemia on its OWN

A1C reduction: 0.5-1%

FPG reduction: 20-40 mg/dl

PPG reduction: 40-70 mg/dl

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14
Q

Dose

EMPAgliflozin

SGL2-Inhibitor

A

JARDIANCE

First anti-DM agent –> REDUCE RISK OF CV DEATH​

10mg qd AM

same as DAPA, except for dose

in morning with or w/o food

no dose adj for hepatic impairment

NOT RECOMMENDED for <45ml/min eGFR

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15
Q

ALOgliptin

DPP4 Inhibitor

A

Nesina, but GENERIC NOW! (cheaper)

Peak = 1-2hrs / Elim = 21 hours

100% bioavailable

Along with SAXAgliptin may increase risk of

HEART FAILURE

monitor SOB / fatigue / weight gain

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16
Q

Products

Thiazolidinediones (TZDs)

Insulin sensitizers

A

Pioglitazone

(Actos)

Rosiglitazone

  • Avandia*
  • not used due to elevated CV risk, but ban was lifted*
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17
Q

Pregnancy? / ADR / Disadvantages

Sulfonylureas

A

Glipizide / Glimepiride / Glyburide

Not Recommended in Pregnancy

Hypoglycemia / Weight Gain

Caution in Elderly / Allergic Skin Reaction

No black box warning

GI disturbances : NVD (less than metformin)

Primary and Secondary Failure

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18
Q

Dose / Indication

GLYburide MICRONIZED

Sulfonylurea

A

GLYburide Micronized

1T (1.5mg) qd/bid

micronized = 1.5mg / MaxClinical=6mg / MaxDose=12mg

half life of 4 hours = can dose BID

Initial Response= 30 minutes, peak = 2-4 hours

CYP2C9

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19
Q

Dose

CANAgliflozin

SGLT1 Inhibitor

A

Invokana

100mg QD

BEFORE first meal

ONLY SGLT2-I that is

  • NOT recommended for severe hepatic impariment / K+ DI’s*
  • no titration needed for <60ml/min EGFR*

NOT recommended for <45ml/min eGFR

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20
Q

Advantages / Benefits

SGLT2 Inhibitors​

A

Treat hyperglycemia in a NEW PATHWAY

Once daily Dosing + Weight Loss

EMPAgliflozin = indicated for reducing death in CV DISEASE!

FPG reduction of: 25-40mg/dl

0.5-0.9% A1C reduction

(but with baseline of 8%)

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21
Q

Examples of Fast Acting Carbs

A

All have ~15g of Carbs

3-4 glucose tablets

5-6 hard candies (chewed)

4 ounces (1/2 glass) of juice/ soda

1 Cup milk

Glucose Gel

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22
Q

Indication / MoA

SGLT2 Inhibitors

A

Treatment for T2DM as adjunct to diet + exercise

SGLT2 Inhibitors

Block the REABSORPTION of

filtered glucose

leading to glucosuria (urinating glucose)

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23
Q

Disadvantages / ADR

SGLT2 Inhibitor

A

CI = END STAGE RENAL DISEASE

Cost / Need for LAB monitoring

NOT REC pregnancy / breast feeding

  • NUMEROUS Side effects
    • UTI - glucose in urine
    • Kidney injury / decrease in eGFR
    • BONE FRACTURES
    • KETOACIDOSIS
    • CANAgliflozin
      • –> lower limb amputation
        • also hyperkalemia
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24
Q

What ORAL drugs are insulin

SENSITIZERS?

A

TZDs
PioglitaZone / RosiglitaZone –> PPAR-Y

Metformin

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25
Q

Dose

Bile Acid Sequestrant

A

Colesevelam = Welchol

MoA = unknown, maybe incretins and hepatic glucose

3.75g QD WF

may divide into BID

650mg tablets = huge

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26
Q

15/15 Rule

for Hypoglycemia Treatment

A
  • 1st check BG, if <70mg/dl
    • Tak_e 15g of SIMPLE carb_ (FAST acting sugar)
    • monitor the BG in 15 Minutes
  • REPEAT if <70mg/dl STILL
    • but if its <50mg/dl –> GIVE 30g of simple carb
  • Prefer >80mg/dl
  • After initial treatment:
    • patient should eat a meal / snack
      • to maintain BG level
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27
Q

Products

Meglitinides

Insulin Secretagogues

A

Repaglinide

ADR of hypoglycemia (Prandin)

Nateglinide

ADR of Dizzinesss (Starlix)

Indicated for adult patients with:

T2DM as monotherapy or combo with a INSULIN SENSITIZER

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28
Q

MoA / Advantages

Sulfonylureas​

A

INSULIN SECRETAGOGUE

Stimulates insulin secretion from pancreatic beta cells

Improve insulin sensitivity + Reduce glucose output from liver

Relatiely INEXPENSIVE

For recent onset T2dm and FBG >200mg/dl

Decreases A1C 1-2%, reduces FBG 50-70 mg/dl

similar effects of Metformin(biguanide) on Hba1c & FPG

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29
Q

Dose / Indication

PioglitaZone

TZD

A

1T QD

start w/ 15 mg, can titrate to MAX 45mg/day

Titration >4 weeks, may take up to 12 weeks.

Mono/Combo therapy for T2DM

<8% A1c + Need for Combo therapy

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30
Q

Which 2 drugs had a FDA alert saying that they:

  • *INCREASE risk of**
  • *HEART FAILURE**

(esp those with preexistant heart / kidney disease)
monitor SOB / fatigue / weight gain

A

SAXAgliptin
Onglyza

ALOgliptin
Nesina

Both are DPP4 - LASS Gliptin

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31
Q

PK’s

Alpha-Glucosidase Inhibitors

Acarbose (precose) / Miglitol (glyset)

A

Onset: <1 hour

Duration <6 hours

need to take TID

very low bioavailability <2% acarbose

miglitol bioavailability of 100%

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32
Q

Products

DPP-4 Inhibitors

(LASS)

A

Sitagliptin

Januvia - 100mg qd

Saxagliptin

Onglyza - 2.5-5mg qd

Linagliptin

Tradjenta - 5mg qd, no dose adjustment

Alogliptin

Nesina - 25mg qd

33
Q

Products

Alpha-Glucosidase Inhibitors

A

Acarbose (precose)

Miglitol (glyset)

BOTH SAME DOSE

SLOW TITRATION

TAKE IN MORNING WITH FOOD TID

34
Q

Doses for JANUVIA

Sitagliptin = DPP4-I

A

100mg QD

with or without food

mono or combo therapy w/ metformin or PPARy agonist

Pts with renal insufficiency:

Moderate, CrCl 30-50 ml/min - 50mg qd

Severe & ESRD, CrCl <30 ml/min** - **25mg qd

35
Q

Why choose a Sulfonylurea?

Glipizide or Glimepiride

A

insulin S__ecretagogue

Preferred for patients with:

Chronic Kidney Disease

Cardiovascular Disease

36
Q

Dose

Alpha-Glucosidase Inhibitors

Acarbose (precose) / Miglitol (glyset)

A

TAKE WITH FIRST BITE OF MEAL

very slow titration,

same dose both drugs

25 mg daily for 2-4 weeks

25 mg BID for 2-4 weeks

25 mg TID for 2-4 weeks

50 mg TID, if needed

37
Q

Dose / Indication

Repaglinide, if A1C <8%

Meglitinide

A

Repaglinide

HbA1c <8% or renal impairment CrCl 20-40mL

0.5mg TID

Administer within 30 min prior to meal

<4 doses/day, titrate according to BG​

MAX = 16mg/day (depending on meal pattern)

38
Q

What ORAL medications are dosed TID?

A

Meglitinides
Repaglinide / Nateglinide

Alpha Glucosidase Inhibitors
Acarbose / Miglitol
after TITRATION, QD -> BID -> TID -> TID

Dopamine Receptor Agonist = _Bromocriptine_
​taken with ALL meals

39
Q

Dopamine Receptor Agonist

DOSE

A

Bromocriptine = Cycloset

0.8mg qd

within 2 hours after AWAKENING

Titrated weekly by 1 tablet to therapeutic dose of

1.6-4.8mg qd

40
Q

Dose

ERTUgliflozin

SGLT2-Inhibitor

A

STEGLATRO

5mg qd

  • doesnt have to be AM,* with or without food
  • No dose adj for HEPATIC impairment, but not studied in severe*

not rec for <60ml/min / condraindicated <30ml/min

41
Q

Products

SGLT2 Inhibitors

A

C-D-E-E GLIFLOZIN

CANAgliflozin

Invokana - 100mg

DAPAgliflozin

Farxiga - 5mg

EMPAgliflozin

Jardiance - 10mg

ERTUgliflozin

Steglatro - 5mg

42
Q

What ORAL medications are dosed

BID?

A

Alpha Glucosidase Inhibitors
Acarbose / Miglitol
titration = QD -> BID -> tid -> tid

TZD: Just Rosiglitazone

Sulfonylurea: Just MicronizedGlyburide

Dopamine Receptor Agonist = Bromocriptine
taken with ALL meals

May divide BID - Bile Acid Sequestrant = Colesevelam

43
Q

Adv / Disadvantages

Dopamine Receptor Agonist

Bromocriptine = Cycloset

A

Appropriately timed daily admin of drug

decreases BOTH FPG & PPG, but ONLY with other t2dm drugs

need to be taken w/ food & weekly titration

NOT TYPICALLY USED TO TO ADR & DIFFICULTY OF USE

nausea / fatigue / dizziness / constipation / headache

44
Q

Dose / Indication

Glipizide

Sulfonylurea

A

Glipizide

Drug of choice in Moderate Renal Insufficiency (IR)

1T (5mg) QD - BID

Take 30min BEFORE food

5mg / MaxClinical=20mg / MaxDose=40mg

Initial Response (IR) = 30 minutes, peak = 1-3 hours

XR = 2-3 hours, peak = 6-12 hours

45
Q

Indication / MoA

Alpha-Glucosidase Inhibitors

Acarbose (precose) / Miglitol (glyset)

A

monotherapy or
in COMBINATION WITH SULFONYLUREA

not recommended for intestinal or liver disease

Competitive inhibitor of :
pancreatic alpha amylase & brush border alpha
glucosidases
delay carb hydrolysis & absorption of glucose

PPG REDUCTION!

46
Q

Why Combination Products?

A

Useful when BG is STABLE

can REDUCE Pill BURDEN

usually not recommended for INITIAL Therapy

47
Q

Dose / Indication

Glimepiride

Sulfonylurea

A

reduced dose in RENAL INSUFFICIENCY (1mg)

1T QD

0.5-1.0mg / MC = 4mg / MAX = 8mg

48
Q

Onset / PK

Meglitinides

A

FAST onset: <30 minutes

Mainly liver metabolism:

Rapaglinide = CYP3A4 / CYP2C8

Nateglinide: CYP3A4 / CYP2C9

Duration = 4-6 hours

need to take MULTIPLE DOSES

within 30min of each meal

49
Q

Signs & SYmptoms of

hypoglycemia

A

Shakey / Sweaty

Blurred Vision / Headache

Hunger / Weakness / Fatigue

CONFUSION

IRRITABILITY

FAST HEART BEAT

50
Q

MoA / Advantages

Meglitinides

Repaglinide / Nateglinide

A

INSULIN SECRETAGOGUE

MOA: Stimulate insulin release from pancreas

_low risk of severe hypoglycemia_ vs sulfonylureas

  • Flexibility in lifestyle - dose coupled w/ meals
    • high initial response rate
  • Can be used in:
    • mild-moderate RENAL INSUFFICIENCY
    • Hepatic DYSFUNCTION
      • Repaglinide with slow dose titration
51
Q

Not Recommended / Precautions

DDP4 Inhibitors

SITAgliptin / SAXAgliptin / LINAgliptin / ALOgliptin

A

Caution with _ANTIRETROVIRALS_

(SAXA/LINAgliptin)

Patients with Arthralgia

Risk for Pancreatitis

52
Q

DPP4 Inhibition

MoA

A

DPP4 normally BREAKS DOWN incretin hormone quickly

inhibiting it –>

MORE INCRETIN AVAILABLE

lower Fasting BG & Postprandial BG

  • Incretin Hormones:
    • GLP-1
      • less GLUCAGON
        • ​decreases HEPATIC GLUCOSE production
    • GIP + GLP-1
      • MORE INSULIN
        • increases GLUCOSE UPTAKE by peripheral tissue
53
Q

Primary Failure

of Sulfonylurea

A

Patient NEVER responds to the drug

Glipizide / GLYburide / Glimepiride

54
Q

Onset / PK

PioglitaZone

TZD

A

Delayed onset: 4 weeks, up to 12 weeks

Mainly liver metabolism: CYP3A4 / CYP2C8

both active & inactive metabolites

Peak @ 2-4 hours

vs 1 hour for Rosiglitazone

55
Q

Pregnancy? / ADR / Disadvantages

DPP4 Inhibitors

SITAgliptin / SAXAgliptin / LINAgliptin / ALOgliptin

A

Okay for pregnancy (only other is metformin)

COST

A1c reduction may be lower

Increased risk of hypoglycemia w/ insulin or secretagogues

FDA Warning / Post-Market Cases:

Severe Joint Pain (within 1 month of initiation)

Pancreatitis / Hypersensistivity RXN

56
Q

Secondary Failure of

Sulfonylurea

A

Glipizide / GLYburide / Glimepiride

Drug USED TO WORK

initially controlled on the drug,but control is LOST OVER TIME

  • Signs: FPG>140mg/dl - HbA1c > 8%
    • ​Addition or switch to another medication
      • after 6 months of therapy
  • _​​_Causes:
    • Decreasing Beta cell fxn or NON ADHERENCE
57
Q

SAXAgliptin Dose

Onglyza

A

2.5-5mg QD

normally 5mg

For Renal insufficiency

(CrCl <50ml/min)

half dose to _2.5mg QD_

58
Q

SEVERE

hypoglycemia treatment

A

GLUCAGON EMERGENCY KIT

0.5-1mg

IM, SC or IV into Buttocks / upper arm / thigh

may be repeated in 15 min if needed

  • if no response in 15 minutes
    • CALL AMBULENCE 911
  • may cause N/V, turn patient on side
    • give CARB SNACK

​DEXTROSE IV 25G okay in inpatient or clinic setting

59
Q

Not Recommended / Precautions

PiaglitaZone

TZD

A

Black Box Warning - CHF

Contraindicated in NYHA C3/4 CHF

Liver Disease

Monitor LFTs at start of therapy

60
Q

Dose / Indication

Repaglinide, if A1C >8%

GREATER THAN 8%

Meglitinide

A

Repaglinide

HbA1c greater than >8%

1-2mg TID

Administer within 30 min prior to meal

<4 doses/day, titrate according to BG

MAX = 16mg/day (depending on meal pattern)

61
Q

SGL2

Sodium Glucose Co-transporter 2

A

180g of glucose is filtered daily in glomeruli

almost ALL (99%) is REABSORBED

through SGLT2

low-affinity transporter expressed mainly in the KDNEY

inhibition –> glucose in URINE

62
Q

LINAgliptin Dose

A

Tradjenta

5mg QD

NO DOSAGE ADJUSTMENT!

63
Q

Why choose Meglitinide over Sulfonylurea?

A

Repaglinide/Nateglinide > Glyburide/Glimepiride/Glyburide

Lower risk of SEVERE hypoGLYCEMIA

compared to sulfonylureas

64
Q

Advantages of

Metformin

A

Insulin Sensitizer

No Direct action on PANCREAS

MoA not likely to cause hypoglycemia

Weight loss

Inexpensive

used in combination w/ other orals or Injectables

65
Q

Onset / PK

DPP4 Inhibitor

SITAgliptin / SAXAgliptin / LINAgliptin / ALOgliptin

A

Varies between the drugs

Typically 1-4 hours

SAXAgliptin has an active metabolite

its bioavailability is still unknown due to this

66
Q

hypoglycemia

Definition

A

Since some meds can cause hypoglycemia

BG of <70mg/dl

S/S may appear in normal ranges

esp if they had CHRONIC HYPERglycemia

67
Q

What drug class has a….

Black Box Warning - CHF

Contraindicated in NYHA C3/4 CHF

Liver Disease / Hepatotoxicity

Monitor LFTs at start of therapy

A

TZDS

Pioglitazone

Rosiglitazone

68
Q

Which ORAL medications can be used with patients with

RENAL INSUFFICIENCY?

A

DPP-4 Inhibitors
Renal Dose adjustments, except LINAgliptin = Tradjenta

Meglitinides
can be used in mild to moderate renal insufficiency
no adjustment in NATEglinide

Not ideal but GLIPIZIDE is the sulfonylurea that is preferred in moderate renal insufficiency.

69
Q

LINAgliptin

DPP4 Inhibitor

5mg QD, no dose adjusting

A

Tradjenta

NO DOSAGE ADJUSTMENT!

Low BV of 30%

Peak @ 1.5 hours / Elim 12 hours

Hypoglycemia

70
Q

Adv / Disadv

Bile Acid Sequestrant

Colesevelam

A

Effects not seen until 4-18 weeks

Reduction of A1C is ONLY 0.3-.54%

TAKES TOO LONG & NOT AS EFFECTIVE

  • also need to SPACE OUT FROM OTHER DRUGS*
  • GI obstruction / Constipation / Headace / Dypepsia*
71
Q

Dose / Indication

Nateglinide

Meglitinide

A

Nateglinide

no RENAL or HEPATIC dose adjustment

120mg TID

Administer within 30 min prior to meal

if closer to A1C goal (<8%), can start at 60mg TID

72
Q

MoA / Advantages

Pioglitazone

TZD

A

INSULIN SENSITIZER - Selective agonist for PPAR-Gamma

Improve insulin sensitivity + Enhance glucose uptake

  • Lower BP / Lipid profile*
  • Reduced C-Reactive protein + PAI-1 levels*
  • Decreases A1C 0.5-1.5%*, reduces FBG 30-60 mg/dl
73
Q

What ORAL drugs are insulin

SECRETAGOGUES?

A

Sulfonylurea
Glipizide / Glyburide / Glimepiride

Meglitinides
repaGLINIDE / nateGLINIDE

74
Q

Dose / Indication

GLYburide nonmicronized

Sulfonylurea

A

GLYburide

NOT recommended for CrCl <60ml/min

1T (2.5mg) QD

normal = 2.5mg/ MaxClinical=10mg / MaxDose=20mg

Initial Response= 30 minutes, peak = 2-4 hours

CYP2C9, half life = 10hrs

75
Q

Disadvantages / ADR

Alpha-Glucosidase Inhibitors

Acarbose (precose) / Miglitol (glyset)

A

GI EFFECTS!

TID Dosing + slow titration (2-4 weeks)

need glucose treatment if taken with hypoglycemic drug

(liver labs) ​LFT testing EVERY 3 MONTHS

  • Contraindications
    • various GI related diseases
      • IBS / Ulcers / Cirrhosis / Intestinal obstruction
    • Liver Disease
  • ​Flatulence / Ab Pain / Diarrhea
76
Q

C D E E -gliflozin

A

SGLT2 Inhibitors

Cana / Dapa / Empa / Ertu

100 / 5 / 10 / 5

Invok(c)ana / Farxiga / Jardiance / Steglatro

b4 first meal / AM / AM / no need for AM or food

77
Q

L A S S -gliptin

A

DPP4-Inhibitors

Lina / Alo / Saxa / Sita

5 / 25 / 5 (2.5) / 100

  • Tradjenta* / NesinA / Onglyza / Januvia
  • no dose adj* / risk of Heart failure + active metabolite /
78
Q

Which medication was the FIRST ANTI-DM AGENT with the additional indication to

reduce risk of CV DEATH???

A

EMPAgliflozin = Jardiance

25mg QD AM

CDEE-gliflozin = SGLT2 Inhibitor

PDAT2 (22 decks)

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