Exam 2: Diabetes Medications Flashcards
What makes the various insulin preparations
have differnt pharmacokinetic profiles?
They are modified with different amino acids.
This is reflected in their names:
Long Acting: Gly + Arg = glargine
Short acting: Lys + Pro = lispro,
Asp = aspart, Glu + Lys = glulisine
What is a rapid acting insulin?
Standard
Name in intermediate acting insulin
NPH = “isophane”
What are the two long-acting insulins
we need to know, and which one has no peak ?
Detemir
Glargine: no peak
What is the “Dawn Effect”
and how does that affect insulin dosing?
Corisol causes endogenous glucose production in the morning
so you need an overnight dose of insulin
What is the key side effect of insulin
and how do you treat it?
What will exacerbate this side effect?
Hyperglycemia (<70) due to excessive dose or mistimed dose
Tx: glucose or glucagon
Exacerbated by EtOH, beta blockers, salicylates
Your patient was just diagnosed with DM type 1.
She is a bright high school student who eats three good meals a day.
What medication would you provide?
Long acting insulin like Glargine or Detemir at bedtime
Short acting like Lispro or Aspart before each meal.
Your see your patient again in two weeks and look at her blood sugar diary.
Her blood sugar is low when she wakes up but tends to be high after meals. How do you adjust her dose?
Decrease her long acting bedtime dose.
Increase her mealtime doses.
What are the two key problems in DM Type 2?
Which one tends to happen first?
1st: decreased insulin sensitivity
2nd: decreased insulin secretion
You just diagnosed a new patient with DM type 2.
What is your first treatment of choice?
Lifestyle modification: increased exercise and weight loss
What is the MOA for Metformin?
Insulin sensitiation
Activation of AMP-dependent protine kinase AMPK
Leading to:
Decreased liver gluconeogenesis and lipogenesis
Increased liver fatty acid oxidation
Increased GLU uptake in muscles/fat cells
What is the first line medication for diabetes type 2?
Metformin
(Also for pre-diabetes)
What are the pros and cons of Metformin?
Pros: euglycemic, slight weight loss, decreased microvascular complications, ok during pregnancy,
somewhat additive effect with drugs with a different MOA.
Cons: N/V/D and metalic taste (which may lead to wt loss)
C/I re renal dysfunction and
severe liver dz (can lead to lactic acidosis)
NOTE: D/C before using contrast dyes
What is the MOA and effect of thiazolidenediones (TZDs)
Name one.
increase insulin sensitivity in target tissues
MOA: altering the expression of insulin responsive genes
via PPAR alpha receptor
Result: decreased FFA and increased GLU utilization in adipose tissue, decreased GLU output from liver
Pioglitazone
What are the pros and cons of TZDs
(Thiazolidenediones like Pioglitazone)
Pros: anti-inflammatory, improved lipids, no hypoglycemia, no lactic acidosis
Cons: fluid retention/edema, weight gain, decreased bone density and increased fractures
What is the MOA of insulin secretagogues?
They mimic glucose by getting beta cells to release insulin.
MOA: block K+ channel to increase depolarization and Ca+ influx leading to insulin release.
What do secretatgogues need in order to work?
Beta cells!
Secretagogues do not work in patients with severe DM type 2 who have little or no remaining functional beta cells.
How do secretagogues effect insulin sensitivity?
They don’t.
What are the pros and cons of Sulfonureas?
Name one.
Pros: increase insulin secretion
Cons: severe hypoglycemia, weight gain, drug-drug interactions can either increase or decrease effectiveness
C/I: hepatic and renal disease
Glipizide
What are the pros and cons of Non-sulfonurea Secretagogues?
(AKA Meglitinides)
Name one
Pros: increase insulin release from Beta cells
Cons: hypoglycemia (less than sulfonureas), drug-drug interactions can increase risk of hypoglycemia
NOTE: rapid absorption: good after a meal
Repaglinide
What do GLP-1 Receptor Agonists do
and what is their MOA?
Increase glucose dependent insulin secretion
Decrease gastric emptying and increased satiety, decreased hepatic fat, possible decreased beta cell apoptosis
MOA: GLP-1 mimetics: enter the beta cell via the same receptor
Name a GLP-1 receptor agonist.
How is it formulated?
Exenatide and Exendatide LAR extended release
Formulation: injectable
What are the pros and cons of GLP-1 Receptor Agonists?
Pros: increase insulin secretion (they require glucose!), weight loss, decreased hepatic fat, increased beta cell mass
Cons: N/V/D (44%) which can decrease with use or can lead to acute renal failure
Increase hypoglycemia if used with secretagogues.
C/I: gastroparesis
What is the MOA and effect of DPP-4 Inhibitors?
(Dipeptidyl Peptidase 4 Inhibitors)
MOA: stop metabolism of GLP-1 by DPP-4
leading to prolonged GLP-1 action
Effect: increased incretin > insulin secretion
leading to increased glucose mediated insulin secretion
What are the pros and cons of DPP-4 Inhibitors?
Name one.
Pros: increased insulin secretion, weight neutral
Cons: increased hypoglycemia with secretagogoes
potentially fatal hepatic failure
hypersensitivity reactions (urticaria, etc)
possible severe disabling joint pain (Tx: D/C)
Sitagliptin
the “gliptins”
What is the MOA and effect of Alpha-glucosidase Inhibitors?
Name one.
MOA: inhibit alpha-glucosidase, which metabolizes small sugars.
Effect: decreased digestion of carbs leading to
decreased GLU absorption in GI (take at mealtime)
Acarbose (carbs not absorbed)
What are the pros and cons of alpha-glucosidase inhibitors?
Pros: decreased blood sugar
Cons: abdominal pain, diarrea, gas
(decrease with use or dose titration)
increased hypoglycemia with sulfonureas or insulin
NOTE: Tx hypoglycemia with oral glucose, NOT dissacharides because cannot digest them!
C/I: chronic bowel disease due re abdominal pain
What is the MOA and effect of Renal SGLT-2 Inhibitors?
Name one.
MOA: inhibit Sodium-dependent GLucose Transporter in proximal tubule of kidney
Effect: decreased glucose reabsorption leading to decreased blood sugar.
Canagliflozin (CAN affect GLucose FLO)
What are the pros and cons of SGLT-2 Inhibitors?
Pros: possible weight loss and possible improved cardiovascular disease (re Na+ loss)?
Cons: increased glucose in urine can lead to UTIs and genital mycotic infections (3-15%)
Electrolyte changes (increased K+, Mg++, Phos)
C/I: DM type I (not tested yet)
What is the MOA and the effect of Amylin Agonists?
MOA: mimics beta cell amylin,
which causes decreased glucagon release
Effect: decreased gastric emptying and increased satiety
What are the pros and cons of Amylin Agonists?
What is its formulation?
Pros: decreased blood glucose, increased satiety
Cons: hypoglycemia, N, HA, anorexia
Formulation: injectible, taken like insulin before meals
for type 1 and type 2 DM
Your patient is on metformin but needs another medication to better control his type 2 DM.
Your patient also has high LDL and arthritis.
What do you prescribe?
What would you warn the patient about?
Pioglitazone (thiazolidenedione)
Because: anti-inflammatory and improves lipid profile
Warn patient about edema (peripheral, pulmonary, macular) and risk of fracture
Which two types of medications
have the greatest risk of hypoglycema?
Insulin
Sulfonylureas
Which medications do NOT lead to weight gain?
Weight loss: Biguanides (Metformin)
GLP-1 receptor agonists (Exenatide)
Weight Neutral: DPP-4 Inhibitors (Sitagliptin)
Your patient has been a type 2 diabetic for 20 years and now has virtually no beta cells left.
What can you prescribe?
Insulin
Metformin and Thiazolidenediones (insulin sensitizers)
Alpha-glucosidase Inhibitors (decreased digestions of carbs)
Renal SGLT-2 inhibitors (decreased renal GLU reabsorption)
