diabetic drugs Flashcards
The Pancreas
• Can be found just “tucked in”
the angle formed by the gastric pylorus and the proximal duodenum
The Pancreas
• You’ve already learned it has two functions:
1) Exocrine (various digestive enzymes)
2) Endocrine
The Endocrine Pancreas
Produces insulin (signalling a “fed” state), glucagon (signalling a “hungry” state), gastrin, somatostatin, and many others. releases into blood stream
Beta cells
secrete insulin which causes BG to decrease (after all, you’re in the fed state and need to stash that
energy)
alpha cells
secrete glucagon which causes BG to
delta cells
secrete somatostatin which regulates a LOT of things (and gets
very, very complicated!)
The Exocrine Pancreas
Releases bicarb (why?) reverses bicarb so digestive zymogens can work and digestive zymogens to break down fats and proteins • All goes awry with pancreatitis
) Diabetes insipidus
Critter doesn’t produce or kidneys don’t respond toVasopressin (Antidiuretic Hormone/ADH)
diabetes mellitus type 1
Insulin-Dependent DM (IDDM)”
DM type 2
Non-Insulin-Dependent DM (NIDDM) Broadly, Type 1 DM is an absolute insulin deficiency and Type 2 DM is a relative deficiency of insulin
DM type 3
Other
• Due to side effects of drugs, toxins, viral infections, genetic predispositions, etc. Variable in course & treatment
DM type 4
Gestational
• Women may develop extreme insulin resistance during their third trimesters of pregnancy (same time they might be prone to blowing out mitral valves, eh?) as a result of hormonal changes
Type 1 DM
• These critters must receive insulin or suffer from the four “classic” symptoms of hyperglycemia:
Polyphagia -Polydipsia -Polyuria -Polyweightloss(?)
Type II DM
• These critters produce variable
amounts of insulin and exhibit insulin resistance.
»These critters typically require increasing doses of insulin and combination therapy with other antihyperglycemics
uncontrolled Type 4 DM can lead to
xtremely large babies, dystocia, and neonatal hypoglycemia
why are plasma insulin levels are not an accurate measure of insulin production
nsulin is removed from circulation so rapidly (3-5 minute half-life). c protein measurement better guide
C-Protein
NOT to be confused with Protein C or C- reactive protein!
• A 31 amino acid peptide used to differentiate Type 1 DM from Type 2 DM
Half-life of C-Protein is
~30 minutes
– Therefore ~5X as much in the blood stream as insulin
insulin is produced by
β-cells in the pancreas in response (generally) to glucose (the archetypical “fed state”)
Insulin’s main effect target tissues are
liver, fat, and muscle
• Insulin exhibits anabolic effects on these target tissues
Insulin is increasingly being used by perfusionists for
hyperkalemia therapy (what’s this? what’s “normalkalemia?), often in conjunction with glucose to “drive” potassium intracellularly
hat else can you do to lower potassium levels?
?
…perfusionists have started to seek much “finer” control of glucose levels on bypass, so
insulin drip and anti-hyperglycemic protocols have become much more common.
Rapid onset/short-acting insulin
Regular insulin (Humulin R, Novolin R) -Insulin aspart (Novolog) -Insulin glulisine (Apidra) -Insulin lispro (Humalog). Given IV or subcutaneously (SQ)
regular insulin
(Humulin R, Novolin R) Rapid onset/short-acting insulin
insulin aspart
(novolog) Rapid onset/short-acting insulin
insulin glulisine
(apidra) Rapid onset/short-acting insulin
insulin lispro
(humalog) Rapid onset/short-acting insulin
-Neutral Protamine Hagedorn (NPH) insulin
(Humulin N, Novolin N) *Only given SQ. its only intermediate lasting insulin
Long acting insulins
Insulin glargine (Lantus) -Insulin detemir (Levemir)
- Both have fatty-acid side-chain attachments that cause them to bind albumin for longer action.
- Give only SQ
- Do NOT mix with other types of insulin!
Insulin glargine
(Lantus) Long acting insulins
Insulin detemir
(Levemir) Long acting insulins
Various mixtures of
compatible insulin also exist.
• The goal is to minimize hyper- and hypoglycemia
Why “Fine” Glucose Control is Important
decreases retinopathy and nephropathy
Fine” Glucose Control Measurement
TheADArecommendsdiabetics’blood glucose (BG) maintain a mean of 154 mg/ml.
Long-term BG measurement is via
Glycated (glycosylated) Hb (HbA1c)
*Normal HbA1C is
<7.0%
Pramlintide
(Symlin) ia an amylin analog. B cells make it
Amylin is a
polypeptide released by the pancreas in conjunction with insulin
amylin works with insulin by
to moderate physiologic glucose levels by slowing gastric emptying and digestion (why would this be a good thing…remember, insulin is the hormone signalling a “fed” state)
By slowing digestion Pramlintide
spreads out” glucose absorption over a longer period.
• Given SQ at meals. • Also causes post-
prandial satiety
Incretin Mimetics
-
- Exenatide (Byetta): SHORT ACTING -Liraglutide (Victoza): LONG ACTING. Both are proteins that are given SQ prior to eating
- Side effects are mainly GI
Exenatide
(Byetta): SHORT ACTING Incretin Mimetics
Liraglutide
(Victoza): LONG ACTING Incretin Mimetics
*Incretins are hormones
released by the GI tract post-prandially that stimulate the pancreas to release insulin, slow gastric emptying, decrease glucagon release, and encourage β-cell growth
Oral Insulin “Adjuncts”
• Often used as part of
progressive combination
therapy” for Type 2 DM.
Insulin Secretagogues
Increase β-cells production of insulin (so critter must still have functioning pancreas), lower hepatic glucose production, and increase peripheral insulin sensitivity.
-Glyburide
(Diabeta, Micronase) Insulin Secretagogues Sulfonylureas
glimepiride
(Amaryl) Insulin SecretagoguesSulfonylureas
glipizide
(Glucotrol) Insulin Secretagogues Sulfonylureas
-Nateglinide
(Starlix) Insulin Secretagogues glinide
Repaglinide
(Prandin) Insulin Secretagogues glinide
Insulin Sensitizers
Increase peripheral cellular sensitivity to insulin without increasing insulin secretion (why might this be a good thing?)
metformin
(Glucophage) insulin sensitizer Biguanides
Pioglitazone
(Actos) insulin sensitizer Thiazolidinediones
-Rosiglitazone
(Avandia) insulin sensitizer Thiazolidinediones
Biguanides
Prevents hepatic gluconeogenesis (huh?)
***This is very important because hepatic glucose production is the main source of excessive glucose in Type-2 DM! Often used in combination with insulin or other oral antiglycemics
• Diarrhea is a very common side-effect
Thiazolidinediones
Increase intracellular receptors in skeletal muscle, liver, and adipose tissue to become more sensitive to endogenous insulin.
• Side effects include weight gain, liver damage, and increased CV risks (a bad thing) & others
α-Glucosidase Inhibitors
- Acarbose (Precose) -Miglitol (Glyset)
- Work by reversibly inhibiting an enzyme in the small intestines that helps digest polysaccharides into simple sugars.
- This delays complex sugar digestion which “spreads out” the post-prandial blood glucose spike. *Don’t cause hypoglycemia by themselves, but will contribute significantly in combination RX.
Acarbose
(precose) α-Glucosidase Inhibitors
miglitol
(glyset) α-Glucosidase Inhibitors
Dipeptidyl Peptidase-IV Inhibitors
Saxagliptin onglyza -Sitagliptin (Januvia)*Work at the cellular level to increase post- prandial insulin release while inhibiting glucagon (insulin’s physiologic antagonist) release.
Saxagliptin
Onglyza). Dipeptidyl Peptidase-IV Inhibitors
-Sitagliptin
Januvia) Dipeptidyl Peptidase-IV Inhibitors
SGLT2 is a
low affinity, high capacity transport mechanism in the proximal tubule. It’s designed to “capture” glucose lost in renal filtration
Sodium Glucose Co-Transporter Inhibitors (SGLT Inhibitors)
• Glucose is therefore
freely “lost” into the urine.
Canagliflozin
(Inkovana) Sodium Glucose Co-Transporter Inhibitors (SGLT Inhibitors)
Dapagliflozin
(Farxiga) was almost approved for use in the U.S. (and is still used extensively in Europe) but it was found to have one small side- effect (besides nasty intractable urinary tract yeast infections. bladder cancer but got approved A 6-fold increase in bladder cancer.
