Diabetes Drugs Flashcards
What type of substance is Insulin?
Hormone
Where in the body is Insulin made?
pancreatic beta cells
How does insulin effect blood glucose levels?
facilitates uptake of glucose into skeletal muscle and adipose tissue by increasing nbr of glucose transporters (GLUT 1 & GLUT 4)
What is the molecular structure of insulin?
2 amino acid chains (A&B) - 51 amino acids, 3 disulfide bonds
Disease: not enough insulin
Type I / IDDM / Juvenile Onset Diabetes
Disease: response to insulin not adequate
Type II / NIDDM / Adult Onset Diabetes
what condition does insulin treat other than diabetes?
hyperkalemia
(IV-Insulin –> dose-dependent decline in serum potassium
Treatment for Hyperkalemia
10 units IV insulin + 25g dextrose lowers serum potassium by 1 meq/L (mmol/L) w/in 10-20 min lasts 4-6 hours
ECG changes from hyperkalemia
peaked T-waves (think peaked, potassium, Paris - Eiffel Tower)
Insulin production - basal rate
1 U/hr … up to 40 U/day
Insulin (endogenous) duration of action
30-60 min
Insulin - mechanisms of action
increase number of glucose transporters (GLUT 4) so facilitates uptake of glucose into skeletal muscle and adipose tissue
(GLUT 1 transporters respond to blood glucose levels)
Insulin - metabolism
kidney and liver - 50% 1st pass
IV Insulin - elimination half-time
5-10 min
but sustained effect b/c tightly bound to tissue receptors
What is the relationship between plasma insulin concentration and number of insulin receptors?
inverse
(e.g., high glucose levels -> high insulin levels -> down regulation of insulin receptors -> insulin resistance -> need even more insulin to overcome)
What is insulin made from?
Now: manufactured by recombinant DNA technology
Before: extracted from beef & pork (good not any more –> reduces chance of allergy)
Categories of insulin (by duration of action)
Rapid-acting (Lispro)
Short-acting (regular - CZI - crystalline zinc insulin)
Intermediate-acting (Isophane: NPH)
Long-acting (Ultralente)
What type of insulin do we use in the OR?
Short-acting (regular)
(e.g., Humulin or Novolin)
Only IV insulin (can also be given subQ)
From pork, beef, human, or genetically engineered w/ E. coli
Short-acting Insulin onset/duration
Onset 30-60 min
Duration 6-8 hours
Names for Intermediate-acting Insulin
Isophane Insulin Suspension =
Neutral Protamine Hagedorn (Humulin-N and Novolin-N)
Where does the protamine in NPH come from?
Salmon sperm
Intermediate-Acting Insulin onset/duration
Onset 1-2 hours
Duration 10-16 hours
Name(s) for long-acting insulin
Ultralente
Why is Ultralente Insulin long-acting?
Large particle size and crystalline form
Basic approach to taking insulin daily
maintain basal level, plus rapid-acting at meal times if necessary
1 U Insulin - effect on blood glucose
1 U insulin lowers blood glucose 25-30 mg/dL
Formula for insulin dosage in OR
Units/hr = (glucose/150)
After giving insulin in the OR, how long to wait before testing blood glucose?
30 min
Most common basal insulins patients take
Lantus (glargine ~24 hrs)
Levemir (detemir ~18 hrs)
Side effects of insulin
Hypoglycemia Allergic reactions Lipodystrophy Resistance Drug Interactions
Most serious side effect of hypoglycemia
Irreversible brain damage
Initial symptoms of hypoglycemia
Other symptoms
Initial: diaphoresis, tachycardia, hypertension
Other:
Rebound hyperglycemia
CNS symptoms
Treatment options
Insulin - drug interactions
Epinephrine (inhib. secretion of insulin)
MAO Inhibitors (potentiate hypoglycemic effects)
Antibiotics (Tetracycline) (increase duration and can cause hypoglycemia)
Salicylates
Categories of oral drugs for treatment of NIDDM
Sulfonylureas
Meglitinides
Biguanides
Aloha-Glucosidaise Inhibitors
Sulfonylureas (oral hypoglycemic) - mechanism
stimulate release of endogenous insulin
so only for Type II - Type I can’t be stimulated
Sulfonylureas - risk
hypoglycemia
Sulfonylureas - example
Glyburide
Meglitinides - mechanism
stimulate insulin secretion
Meglitinides - risk
hypoglycemia
Meglitinides - example
Repaglinide
Biguanides - mechanism
inhibit glucose production by liver
Biguanides - example
Metformin
Metformin - what type of rug
Biguanide
Glyburide - what type of drug
Sulfonylurea
Alpha-Glucosidase Inhibitors - mechanism
slow digestion and absorption of carbohydrates
Alpha-Glucosidase Inhibitors - example
Arcabose
Glyburide - don’t give to patient allergic to:
sulfa drugs
it’s a Sulfonylurea, derivative of sulfonamide.
Sulfonylureas - Pharmacokinets
GI absorption
Protein binding (90-95%)
Metabolism: Liver (renal excretion)
Side effects of sulfonylureas
hypoglycemia, esp. w/long acting
Fetal effects of sulfonylureas
cross placenta - can cause fetal hypoglycemia
Glyburide (Micronase)
- which generation sulfonylurea
- duration
2nd generation
stimulates insulin over 24 hours
Glipizide (Glucotrol)
- which generation sulfonylurea
- duration
2nd generation
stimulates insulin over 12 hours
When to use Metformin
When sulfonylurea treatment has failed
Advantage of biguanides in treatment of NIDDM
- decrease in blood glucose with very low risk of hypoglycemia
- positive effect on blood lipids - may lead to some weight loss
Risk w/biguanides in treatment of NIDDM
severe lactic acidosis
Metformin (Glucophage) - metabolism
100% renal clearance (unchanged - no hepatic metabolism)
Use cautiously (or not at all) with renal failure)
Metformin (Glucophage) - mechanism of action
lowers blood glucose
(inhibits hepatic gluconeogenesis, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization)
Arcabose - type of drug
Intestinal glycosidase inhibitor
Arcabose - mechanism
decreases carbohydrate digestion and absorption
Arcabose - benefits
- NO hypoglycemia
- can be used with insulin
Blood glucose level for surgery
180 (closer to 120 if possible)
How much insulin should patient take morning of surgery?
Half dose
Infusion level for Insulin
BG/150 = Units/hr
Add what when administering insulin?
10 - 20 meq KCL to each liter of IV fluid (to avoid hypokalemia)
Should patients take oral hypoglycemic agents morning of surgery?
No
When to discontinue oral hypoglycemics before surgery?
24-48 hours
Target blood glucose to maintain during surgery
150-180 mg/dL
Cardiac risk w/diabetic patients
occult cardiac disease (don’t get angina because of de-innervation around heart)
Test to determine long-term blood glucose control (and therefore cardiomyopathy and heart failure)
Hb A1C
Normal 5
7 or below = good
8-10 poor control