12 - Oral Diabetes Medication 1 Flashcards
Pregnancy? / ADR / Disadvantages
Meglitinides
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)
Pregnancy? / ADR / Disadvantages
PiaglitaZone
TZD
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
Dose
DAPAgliflozin
SGL2-Inhibitor
FARXIGA
5mg qd AM
in morning with or w/o food
no dose adj for hepatic impairment
NOT RECOMMENDED for <45ml/min eGFR
ALOgliptin DOSE
Nesina
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
PK’s
SGLT2 Inhibitors
C-D-E-E GLIFLOZIN
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)
SITAgliptin
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
Disadvantages of
Metformin
GI adverse effects
Risk of lactic acidosis
Caution with alcohol
Not appropriate with
moderate-severe renal impairment
Acute/unstable CHF
Liver impairment
Products
Sulfonylureas
Insulin Secretagogues
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
Specific details of: SAXAgliptin
DPP4
LASS GLIPTIN
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*
Which drugs are OKAY TO USE for pregnancy?
Alpha Glucosidase Inhibitors
Acarbose / Miglitol
DPP-4 Inhibitors
LASS-gliptin
Metformin
- Bromocriptine mesylate = CYCLOSET*
- Bile Acid Sequestrant = Colesevelam*
MoA / Advantages
DPP4 Inhibitors
SITAgliptin / SAXAgliptin / LINAgliptin / ALOgliptin
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
Not Recommended / Precautions
PiaglitaZone
TZD
Black Box Warning - CHF
Contraindicated in NYHA C3/4 CHF
Liver Disease
Monitor LFTs at start of therapy
Advantages / Benefits
Alpha-Glucosidase Inhibitors
Acarbose (precose) / Miglitol (glyset)
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
Dose
EMPAgliflozin
SGL2-Inhibitor
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
ALOgliptin
DPP4 Inhibitor
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
Products
Thiazolidinediones (TZDs)
Insulin sensitizers
Pioglitazone
(Actos)
Rosiglitazone
- Avandia*
- not used due to elevated CV risk, but ban was lifted*
Pregnancy? / ADR / Disadvantages
Sulfonylureas
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
Dose / Indication
GLYburide MICRONIZED
Sulfonylurea
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
Dose
CANAgliflozin
SGLT1 Inhibitor
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
Advantages / Benefits
SGLT2 Inhibitors
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%)
Examples of Fast Acting Carbs
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
Indication / MoA
SGLT2 Inhibitors
Treatment for T2DM as adjunct to diet + exercise
SGLT2 Inhibitors
Block the REABSORPTION of
filtered glucose
leading to glucosuria (urinating glucose)
Disadvantages / ADR
SGLT2 Inhibitor
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
-
–> lower limb amputation
What ORAL drugs are insulin
SENSITIZERS?
TZDs
PioglitaZone / RosiglitaZone –> PPAR-Y
Metformin
Dose
Bile Acid Sequestrant
Colesevelam = Welchol
MoA = unknown, maybe incretins and hepatic glucose
3.75g QD WF
may divide into BID
650mg tablets = huge
15/15 Rule
for Hypoglycemia Treatment
- 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
- patient should eat a meal / snack
Products
Meglitinides
Insulin Secretagogues
Repaglinide
ADR of hypoglycemia (Prandin)
Nateglinide
ADR of Dizzinesss (Starlix)
Indicated for adult patients with:
T2DM as monotherapy or combo with a INSULIN SENSITIZER
MoA / Advantages
Sulfonylureas
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
Dose / Indication
PioglitaZone
TZD
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
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
SAXAgliptin
Onglyza
ALOgliptin
Nesina
Both are DPP4 - LASS Gliptin
PK’s
Alpha-Glucosidase Inhibitors
Acarbose (precose) / Miglitol (glyset)
Onset: <1 hour
Duration <6 hours
need to take TID
very low bioavailability <2% acarbose
miglitol bioavailability of 100%