Drugs for Diabetes Mellitus - Ch. 60 Flashcards
What can untreated diabetes lead to?
Heart disease
kidney disease
eye disease
Erectile dysfunction (impotence)
Nerve damage
Immunosuppression
Poor wound healing
What are symptoms of diabetes mellitus?
Unusual thirst
Frequent urination
Weight change (gain or loss)
Extreme fatigue
Blurred vision
Frequent infections
Slow healing cuts/bruises
Numbness/tingling in hands and feet
Trouble getting an erection
What percent of people have each type of diabetes mellitus?
Type 1 = ~10%
Type 2 = ~90%
What is Type 1 diabetes?
Lack of insulin production
Production of defective insulin
-Need exogenous insulin
What complications can arise due to type 1 DM?
Retinopathy
Nephropathy
Neuropathy
Diabetic ketoacidosis (DKA)
What drug therapies are available for Type 1 DM?
Insulin (required treatment)
Certain oral antihyperglycemic agents can be used as adjuctive agents
What is Type 2 DM?
Cause by insulin deficiency and/or insulin resistance
What is insulin resistance?
Reduced number insulin receptors
Receptors less responsive
What is Gestational diabetes?
Hyperglycemia onset during pregnancy that resolves at the end of pregnancy
What medications are used for Gestational diabetes?
Insulin is normally medication of choice
Metformin may be used
What testing is available for diabetes mellitus?
Blood glucose measurement
Glucose tolerance test
% HbA1c (glycated hemoglobin)
Average blood glucose over the past 3 months
What is glycated Hb?
Glucose + hemoglobin
Compare the proportion life-time of RBCs 3 months in non-diabetic and diabetics? (HbA1c)
Non-diabetic = 4-5.9%
Diabetic = >6.5%
What are insulins?
Function as a substitute for endogenous hormone
Effects are the same as normal endogenous insulin
What do insulins improve a diabetic’s ability to do?
Take up glucose into cells
Make proteins and TGs
Make glycogen from glucose in liver
Convert glucose to fatty acids in adipose tissue
What are the types of insulins?
- Rapid-acting
- Short-acting
- Intermediate-acting
- Long-acting
What is the onset of Rapid-acting?
10-15 minutes
What is the peak of rapid-acting?
60-90 minutes
What is the duration of rapid-acting?
3-5 hours
Examples of rapid-acting insulins?
Insulin lisper (Humalog)
Insulin aspart (NovoRapid)
When is rapid-acting insulin taken?
With each meal
What is the onset of short (fast) acting?
30-60 minutes
What is the peak of short acting?
2-3 hours
What is the duration of short-acting?
6-7 hours
Example of short-acting insulin?
Regular insulin (Humulin R or Novalin R)
How is regular insulin administered?
SC
IV infusion pump
IM (rarely)
What is the onset of intermediate-acting?
1-3 hours
What is the peak of intermediate-acting?
5-8 hours
What is the duration of intermediate-acting?
10-18 hours
Example of intermediate-acting insulin?
NPH (neutral protamine Hagedorn)
What is NPH?
Intermediate-acting insulin:
Isophane insulin suspension
Cloudy appearance
What insulins are basal therapy insulins?
Intermediate and long-acting
What is the onset of long-acting?
90 minutes
What is the peak of long-acting?
No pronounced peak
What is the duration of long-acting insulin?
24 hours
Example of long-acting insulins?
Insulin glargine (Lantus)
What is insulin glargine?
Long-acting insulin
Clear, colourless solution
What does diabetes Canada recommend the use of to achieve good glycemic control?
Base insulins + rapid acting insulins
What are the 3 components of BBIT?
- Basal insulin (long-acting)
- Bolus (short-acting or meal-time) insulin
- Correction insulin
What is the target glucose range for BBIT?
5-10 mmol/L
What is the purpose of BBIT?
Prevents blood sugar highs and lows
What can occur if too much insulin is taken?
Hypoglycemia
What is the alert value for Hypoglycaemia?
<3.9 mmol/L
What are the levels for Hypoglycemia?
Level 1 - 3.0 & 3.9 mmol/L
Level 2 - <3.0 mmol/L
Level 3 - Needs assistance to treat
What are warning signs of hypoglycemia?
CNS effects
SNS activation (gives early symptoms)
What can hypoglycaemia possibly cause?
Coma and death
What does insulin interact with?
B-Blockers
Alcohol
Glucocorticoids
Epinephrine
Furosemide and thiazide diuretics
What happens when Beta blockers interact with insulins?
Increase hypoglycaemic effect
-Blood glucose lowers
What do Beta-blockers do to lower blood glucose levels?
Reduce glycogenolysis (glycogen to glucose)
-Exacerbates insulin-induced hypoglycemias
Also can mask signs of SNS activation
(tachycardia, palpations)
What happens when Alcohol interact with insulins?
Increase hypoglycaemic effect
-Blood glucose lowers
What does alcohol do to lower blood glucose levels?
Reduces liver glycogenolysis
What happens when Glucocorticoids interact with insulins?
Reduce effect of insulin
-Blood glucose levels increase
What happens when Epinephrine interacts with insulins?
Reduce effect of insulin
-Blood glucose levels increase
What happens when furosemide and thiazide diuretics interact with insulins?
Reduce effect of insulin
-Blood glucose levels increase
What should you ensure when insulin is ordered?
Correct route
Correct type
Timing of the dose
Correct dose
-Second check, co-sign
What are diabetes drugs used for?
Lower blood glucose levels in patients with type 2 diabetes in addition to diet and lifestyle changes
What diabetes drugs target the pancreas?
Insulin secretagogues
What are Insulin secretagogues?
Increase insulin production in Type 2 DM
Act on Beta cells of pancreas
What are the classes of Insulin secretagogues?
- Suphonylureas
- Non-suphonylureas
What are examples of Suphonylureas?
Glyburide
chlorpropamide, tolbutamide
glimepiride,
glipizide (Glucotrol)
What does glyburide do?
Stimulate insulin secretion from beta cells
Improve sensitivity to insulin in muscles, liver and fat (easier to take up)
Decreasing rate of insulin metabolism and breakdown via liver
What is the most common adverse effect of sulphonylureas?
Hypoglycemia
-usually mild but can be severe
When are sulphonylureas taken?
Taken with breakfast
usually one per day (orally)
What are Non-suphonylureas?
meal-time drugs
Short-half life
Examples of Non-suphonylureas?
Repaglinide, nateglinide
What is the difference between the classes of Insulin secretagogues?
Same drug target but different duration of action
Examples of Thiazolidinediones (TZDs)?
Rosiglitazone
pioglitazone
How are Thiazolidinediones (TZDs) administered?
PO
What are incretins?
Released by intestinal contents to stimulate insulin release
-GLP-1 ((glucagon-like peptide-1) and GIP
(glucose-dependent insulinotropic peptide)
What breakdown incretins?
Enzyme DPP-4
dipeptidyl-peptidase 4
What diabetes drugs act on the incretin pathway?
Gliptins (DPP-4 inhibitors)
incretin mimetics
SGLT-2 inhibitors
Examples of Gliptins (DPP-4 inhibitors)?
Sitagliptin (Januvia)
saxagliptin
linagliptin
Examples of incretin mimetics?
Excenatide (byetta)
liraglutide, semaglutide, dulaglutide (daily/weekly)
New drug: Tirzepatide (GIP and GLP-1 agonist)
What is Exenatide?
Synthetic form of a saliva protein of the Gila monster
-Synthetic GLP-1 mimetic
What adverse effects are associated with incretin mimetics?
Decrease appetite (weight loss drug)
Major AE = GI upset
What do DPP-4 enzyme inhibitors (Gliptins) do?
Reduce incretin metabolism
-High plasma incretin levels
How are Gliptins administered?
Oral once daily with or without food
-type 2 only
How is Exenatide administered?
SC
What diabetic oral drug site of action is the liver?
Biguanides
Example of biguanide?
Metformin (oral)
What does metformin do?
Decrease hepatic production of glucose
Increase tissue sensitivity to insulin, increases uptake of glucose
Metformin does NOT cause what?
Hypoglycemia
-Doesn’t increase insulin secretion from the pancreas
What can metformin use lead to?
Net weight loss
What adverse effects are associated with Metformin?
GI disturbances: nausea, diarrhea, decreased appetite
Lactic acidosis -rare, 50% mortality
When is lactic acidosis caused by metformin a concern?
People who have renal insufficiency
When is metformin taken?
2-3/day with meals to reduce GI adverse effects
What is the newest group of type 2 DM drugs?
Na-Glucose transporter inhibitors
What do Na-Glucose transporter inhibitors do?
Inhibit glucose transporter in the nephron (PT)
sodium-glucose transporter subtype 2 (SGLT2)
loss of glucose in urine (plus water)
Examples of Na-Glucose transporter inhibitors?
Canagliflozin
Dapagliflozin
empagliflozin
What adverse effects are associated with Na-Glucose transporter (SGLT-2) inhibitors?
Increased urination
-hypotension, dizziness possible
UTIs
What do Thiazolidinediones (TZDs) do?
Decrease insulin resistance
“insulin sensitising agents”
Increase glucose uptake and use in skeletal muscle
Inhibit glucose and TG production in the liver
What warnings are there for rosiglitazone (advandia) use?
Increased risk of angina, MI and heart failure
What are other injectable diabetes drugs are there?
Amylin mimetics
What is amylin?
Co-released with insulin
=delays gastric emptying and inhibits glucagon secretion
-reduce postprandial glucose
Example of amylin mimetic?
Pramlitide
What is Pramlintide?
Acts as amylin
Supplement to insulins (Type 1 and 2)
SC INJECTION
What do alpha-glucosidase inhibitors do?
Reversibly inhibit the enzyme alpha-glucosidase in the brush border of the small intestine
Inhibits digestion of oligo and disaccharides
Delayed absorption of glucose
Examples of alpha-glucosidase inhibitors?
Acarbose
Miglitol
How must alpha-glucosidase inhibitors be taken?
With meals to prevent excessive postprandial blood glucose elevations
What do oral/non-insulin agents interact with?
Glucocorticoids
What does glucorticoids do to oral/non-insulin agents?
Decrease the effect of hypoglycaemic medication
-increase blood glucose
If hypoglycemias occurs what should you do?
Give glucagon if required
Eat 120-200 mL clear fruit juice, glucose tablets/gel, tsp of corn syrup/honey or drink a non-diet soda
After liquid snack eat a meal soon like crackers or half a sandwich
monitor blood glucose
