Lecture 7: Diabetes

Front 1

quick pathophys of Type I DM

Back 1

selective B cell destruction
absolute insulin deficiency
insulin dependent
usually diagnosed at an early age

Front 2

quick pathophys of Type 2 DM

Back 2

tissue resistance to insulin
relative deficiency in insulin secretion
controlled by either oral/ injectable anti-diabetic meds or insulin
usually diagnosed later in life

Front 3

Gestational diabetes

Back 3

women without previous diagnosis of DM who experience hyperglycemia during pregnancy

Front 4

general approach to therapy of T1DM

Back 4

basal-bolus approach
-basal insulin is generally 50% of TDD, remaining provided with mealtime bolus doses
-common starting dosage is 0.6u/kg/day
-continuously reassess
-possible adjunct inj amylin mimetic

Front 5

general approach to treatment of T2DM

Back 5

includes orals, insulin, inj amylin mimetic, inj GLP-1 (incretin mimetic)
-combo therapy recommended if goals not reached
-continually reassess

Front 6

functions of insulin

Back 6

incr glucose uptake into cells
inhibits lipolysis and proteinolysis
inhibits hepatic glucose production
increases glycogen formation

Front 7

rapid acting insulin

Back 7

insulin lispro (humalog)
insulin aspart (novolog)
insulin glulisidine (Apidra)

Front 8

short acting insulin

Back 8

regular insulin (humulin R, Novolin R)

Front 9

Intermediate Acting insulin

Back 9

Neutral Protamine Hagedorn (NPH) Insulin

Front 10

long acting insulin

Back 10

insulin detemir (levemir)
insulin glargine (Lantus)

Front 11

lispro/aspart/glulisine
-onset of action
-peak
-duration of action

Back 11

-10-20 min
-1-3 hr
-3-6 hr

Front 12

regular insulin
-onset of action
-peak
-duration of action

Back 12

-30-60 min
2-4 hr
6-10 hr

Front 13

NPH insulin
-onset of action
-peak
-duration of action

Back 13

-1-2 hr
4-14 hr
-10-20 hr

Front 14

insulin detemir
-onset of action
-peak
-duration of action

Back 14

-1hr, 6-8 hr, 12-24 hr

Front 15

insulin glargine
-onset of action
-peak
-duration of action

Back 15

70 min, flat, 24 hr

Front 16

Insulin AEs

Back 16

allergic reactions
reactions at injection site
weight gain
hypokalcemia
hypoglycemia

Front 17

Insulin DIs

Back 17

hypoglycemic agents
hyperglycemic agents
beta-adrenergic blocking agents

Front 18

sulfonylureas approx dec in A1c

Back 18

1-2%

Front 19

meglitinides approx dec in A1c

Back 19

1-1.5%

Front 20

biguanides approx dec in A1c

Back 20

1-2%

Front 21

alpha-glucosidase inhibitors approx dec in A1c

Back 21

0.5%

Front 22

thiazolidinediones approx dec in A1c

Back 22

1-1.5%

Front 23

DPP-4 inhibitors approx dec in A1c

Back 23

0.5-1%

Front 24

sulfonylureas MOA

Back 24

stimulates pancreatic islet beta cell insulin release

Front 25

sulfonylureas first generation

Back 25

tolbutamide
tolazamide
chlorpropamide

Front 26

sulfonylureas second generation

Back 26

glyburide
micronized glyburide
glipizide
glimepiride

Front 27

sulfonylureas special considerations

Back 27

give with first main meal
hepatic metabolism: 2C9 substrates
renal/fecal elimination
caution in pts with sulfa ally

Front 28

sulfonylureas AEs

Back 28

hypoglycemia
weight gain
GI
hematologic rxns (thrombocytopenia, leukopenia, agranulocytosis, hemolytic anemia)
skin rxns (rash, photosensitivity)

Front 29

sulfonylureas DIs

Back 29

etoh
agents that induce/inhibit metabolism
drugs that intensify hypoglycemia
beta-adrenergic blocking agents

Front 30

meglitinides MOA

Back 30

stimulates release of insulin from functioning beta cells, stimulation of insulin release is glucose dependent (effect diminished at low glucose concentrations)

Front 31

meglitinides PK

Back 31

rapid onset, short duration
skip a meal, skip a dose; add a meal, add a dose
hepatic metabolism and renal and biliary elimination

Front 32

meglitinides drug names

Back 32

Repaglinide (Prandin)
Nateglinide (Starlix)

Front 33

meglitinides special considerations

Back 33

not useful in combo with sulfonylureas
can be used in pts with sulfa allergies
to be taken just prior to eating

Front 34

meglitinides AEs

Back 34

hypoglycemia
weight gain

Front 35

meglitinides DIs

Back 35

etoh
genfibrozil- can inhibit metabolism of meglitinides and therefor cause their levels to rise
Contraindicated with repaglinide
agents that induce/inhibit metabolism
drugs that can intensify hypoglycemia
beta-adrenergic blocking agents

Front 36

biguanides MOA

Back 36

reduces hepatic gluc production and improves insulin sensitivity (by inc peripheral glucose uptake and utilization)

Front 37

biguanides PK

Back 37

administered PO and absorbed slowly
excreted unchanged by kidneys
regular and ER formulations

Front 38

biguanides drug names

Back 38

metformin (IR and ER)

Front 39

biguanides special considerations

Back 39

slowly titrate dose- inc 500 mg qweek
give with meals
hold dose for 2 days before and 2 days after iodinated contrast study
no drink etoh
CI in renal impairment and in pts with high risk for lactic acidosis (dehydration, surgery)
avoid in hepatic impairment

Front 40

biguanides BBW

Back 40

lactic acidosis
-rare but fatal in 50% of cases
-highest risk in pts with renal/hepatic impairment, conditions that may cause hypoxemia or reduce organ perfusion, dehydration, or excessive etoh intake

Front 41

biguanides AEs

Back 41

GI
dec absorption of vit B12 and folic acid
metallic taste
lactic acidosis

Front 42

biguanides DIs

Back 42

cimetidine- 60% inc in peak metformin conc.
cationic drugs excreted by renal tubular secretion may also inc metformin conc
nephrotoxic drugs
etoh

Front 43

alpha-glucosidase inhibitors MOA

Back 43

inhibits alpha-glucosidase and pancreatic alpha-amylase, thereby delaying glucose absorption
lowers post-prandial blood glucose surges

Front 44

alpha-glucosidase inhibitors clinical consideration

Back 44

no hypoglycemia with monotherapy
if seen with combo therapy, treat with gluc tablets or gel, fructose, or lactose. cannot use sucrose

Front 45

alpha-glucosidase inhibitors drug names

Back 45

acarbose (Precose)
migiltol (Glyset)

Front 46

alpha-glucosidase inhibitors PK

Back 46

administered PO
only 2% absorbed
eliminated via urine and feces

Front 47

alpha-glucosidase inhibitors AEs

Back 47

mostly GI- can be minimized by dose titration and time on drug
liver dysfunction with acarbose

Front 48

alpha-glucosidase inhibitors DIs

Back 48

digestive enzymes
metformin
pramlintide

Front 49

alpha-glucosidase inhibitors CIs

Back 49

IBD
cirrhosis
colonic ulceration
partial intestinal obstruction
disorder of digestion or absorption
SCr >2 or CrCl <25

Front 50

alpha-glucosidase inhibitors monitoring

Back 50

Cr at baseline
AST/ALT q3mo x 1 y then periodically for acarbose

Front 51

thiazolidinediones (TZDs) MOA

Back 51

dec insulin resistance and enhance physiologic response to insulins
inc uptake of gluc by muscle and adipose tissue and dec gluc production by liver
selective agonists of peroxisome proliferator-activated receptor-gamma (PPAR-gamma)
PPAR family controls glucose, cholesterol, and fatty acid regulation

Front 52

TZDs drug names

Back 52

Avandia, Actos

Front 53

TZDs AEs and BBWs

Back 53

CHF (BBW)
Myocardial ischemia (BBW for Avandia)
bladder cancer (Actos)
fluid retention
weight gain
elevation of liver enzymes
elevation of plasma lipids
inc fracture risk

Front 54

TZDs drug interactions

Back 54

potent inhibitors or inducers
Gemfibrozil may inc levels

Front 55

DPP-4 Inhibitors MOA

Back 55

slow the metabolism and subsequent inactivation of incretins GLP-1 and GIP by competitively inhibiting a protein/enzyme, DPP-4. By preventing GLP-1 and GIP inactivation, they are able to potentiate the secretion of insulin and suppress the release of glucagon

Front 56

DPP-4 Inhibitors drug names

Back 56

silagliptin (Januvia)
Saxagliptin (Onglyza)
Linagliptin (Tradjenta)

Front 57

DPP-4 Inhibitors PK

Back 57

metabolized via liver, substrate of P-glycoprotein
excreted primarily in urine

Front 58

DPP-4 Inhibitors AEs

Back 58

hypoglycemia
nasopharyngitis, URI, HA
pancreatitis
hypersensitivity/ allergic reaction, rash, SJS

Front 59

DPP-4 Inhibitors DIs

Back 59

digoxin
inhibitors of hepatic metabolism- P450, PGP
drugs that intensify hypoglycemia
beta-adrenergic blocking agents

Front 60

Colesevelam (WelChol)

Back 60

bile acid sequestrant
improves glycemic control in adults with Type 2 DM
unknown MOA

Front 61

bromocriptine mesylate (Cycloset)

Back 61

dopamine receptor agonist
MOA by which cycloset improves glycemic control is unknown
take within 2 hours after waking in the morning with food

Front 62

bromocriptine mesylate (Cycloset) AEs

Back 62

N/V. OH, syncope, exacerbate psychosis, HA, hallucinations, Raynaud-like phenomenon

Front 63

bromocriptine mesylate (Cycloset) DIs

Back 63

3A4 inhibitors/inducers
ergot alkaloids
antipsychotics
triptans/Linezolid/antidepressants

Front 64

injectible antidiabetic drugs and approx dec in A1c

Back 64

amylin agonist - 0.4-0.6%
GLP-1 agonist (Incretin Mimetic)- 1%

Front 65

Amylin mimetic drug name

Back 65

Pramlinitide (Symlin)

Front 66

Amylin mimetic MOA

Back 66

synthetic analog of human amylin that acts by dec postprandial plasma gluc rise, suppressing glucagon secretion, slowing gastric emptying, which promotes satiety

Front 67

Amylin mimetic
take when as indicated for __.

Back 67

At mealtimes
Type 1: adjunct treatment in pts who use mealtime insulin therapy and who have failed to achieve desired gluc control despite optimal insulin therapy
-type 2: adjunct treatment in pts who use meatime insulin therapy and have failed to achieve desired gluc control despite optimal insulin therapy, with or without a concurrent sulfonylurea agent and/or metformin

Front 68

Amylin mimetic AEs

Back 68

hyperglycemia
GI
injection site rxn

Front 69

Amylin mimetic DIs

Back 69

drugs that intensify hypoglycemia- BBW with insulin use
beta-adgrenergic blocking agents
drugs that slow intestinal motility
oral drugs should be taken 1 hour before or two hours after injection pramlintide

Front 70

Amylin mimetic CIs

Back 70

for use with K+ salts d/t slowing through GI tract leading to potential local ADR (ulceration) and inc K+ reaction

Front 71

Amylin mimetic special considerations

Back 71

admin in addition to insulin, not in same syringe
must dec rapid acting insulin dose by 50% when initiating pramlintide
inject immediately prior to meals
subq
caution if using concurrent oral drugs that require rapid onset of NTI drugs

Front 72

GLP-1 agonist (Incretin Mimetic) MOA

Back 72

activates GLP-1 receptor, inc insulin secretion, dec glucagon sec, delaying gastric emptying and suppressing appetite
for use as adjunctive rx for T2DM

Front 73

GLP-1 agonist (Incretin Mimetic) Special considerations

Back 73

given 60 min prior to a meal -Byetta
Bydureon and Victoza to be given without regard for meals

Front 74

GLP-1 agonist (Incretin Mimetic) drug names

Back 74

Exenatide (Byetta)
Exenatide ER (Bydureon)
Liraglutide (Victoza)

Front 75

GLP-1 agonist (Incretin Mimetic) AEs

Back 75

hypoglycemia
GI
acute pancreatitis
BBW- thyroid C-cell tumor risk

Front 76

GLP-1 agonist (Incretin Mimetic) BBW

Back 76

thyroid C-cell tumor risk

Front 77

GLP-1 agonist (Incretin Mimetic) DIs

Back 77

delays gastric emptying and therefore can affect absorption of oral drugs
drugs that intensify hypoglycemia
beta-adrenergic blocking agents