Diabetes Druges Flashcards
Clear solution of insulin
Only insulin suitable for intravenous use
Human sequence
Regular insulin
Cloudy suspension of insulin aggregated with protamine and zinc
Longer time to break down aggregates –> delayed, longer time course vs regular insulin
NPH insulin
Mixture of NPH and regular insulin in fixed proportions (70%, 30%)
Pre-mixed insulins
Synthetic insulins where one or more amino acids of human insulin have been changed to yield either very short or long acting insulins
Insulin analogs
Insulin analogs that more readily form monomers in solution
Compressed time course of action relative to regular insulin
Shorter onset of action and quicker deactivation
Time course closer to that or normal meal-induced peak of pancreatic insulin
Lispro insulin
Insulin aspart
Lispro insulin amino acid changes
Normal pro-lys dipeptide at positions B28 and B29 are reversed
Insulin aspart amino acid changes
B28 proline is replaced by an aspartic acid residue
Long acting insulin analog
Amino acid asparagine normally found at position A21 is replaced by glycine and 2 arginines are added to the C-terminus of the B-chain
Soluble at pH4 but poorly soluble at pH7
Forms a fine ppt in interstitial fluids
Insulin glargine
Long acting due to self-associated at the subcutaneous injection sites and by binding albumin in the blood stream
Threonine at B30 omitted and a C14 fatty acid chain is attached to B29
Insulin Detemir
Short acting insulin
Regular
Lispro
Insulin aspart
Intermediate acting
NPH
Long acting
Insulin Glargine
Insulin Detemir
How are intermediate and long acting insulins given?
To mimic a 24 hour basal insulin secretion
How are short acting insulins given?
Pre-prandially to mimic nutrient-stimulated insulin secretion
What are the goal for glycemic control??
- fasting and pre-prandial glucoses 70-130mg%
- post-prandial glucoses 2 hours after a meal less than 180 mg%
- Hemoglobin a1C less than 7%
What are some examples of insulin regimens?
Split-mixed regimens
Dinner NPH moved to bedtime to move peak of action from 3am to 7am
Basal-bolus regimen ( short acting analog before each meal and once per day insulin glargine)
Continulous subcutaneous insulin (CSI) = insulin pump therapy
What are some side effects of insulin?
Hypoglycemia Insulin allergy Lipoatrophy Lipohypertorphy Insulin edema Weight gain ? Atherosclerosis (high doses) ? Increased cancer (high doses)
Simulate insulin secretion by the pancreas
Interact directly with B-cells potassium transporter causing depolarization and secondarily calcium influx
Sulfonylureas
Sulfonylurea drugs
Glipizide
Glyburide
Glimepiride
SE of sulfonylurea drugs
Hyponatremia (rare)
Disulfiram-like reaction (rare)
Rashes/GI upset
Hypoglycemia (common)
Insulin-sensitizing drugs
Reduce insulin resistance
Making a given amount of insulin more effective at reducing hepatic glucose production and or increases peripheral glucose utilization in the presence of medications
Reduce glucose levels approximately 50mg%
Metformin (biguanide)
Thiazolidinediones (rosiglitazone, pioglitazone)
Biguanide
Major effect is to make the liver more sensitive to insulin
CI in renal insufficiency
Metformin
SE of Metformin
GI side effects Lactic acidosis (serious)
Make peripheral tissues (fat and muscle) more sensitive to insulin by activating PPAR (peroxisome proliferator-activated receptor)
Thiazolidinediones (rosiglitazone, pioglitazone)
SE of Thiazolidinediones
Liver toxicity
Weight gain
Fluid retention
CI in heart failure
Rosiglitzaone may increase cardiac ischemic events
Pioglitazone has a FDA advisory for increased cancer risk
Glucosidase inhibitors
Inhibits enteric enzymes that break down complex carbohydrates, resulting in partial malabsorption of carbs
Reduces post-prandial hyperglycemia
Acarbose
Major side effects of Acarbose
Bloating, abdominal discomfort, diarrhea, flatulence
GLP-1 analog Augments insulin secretion Increases beta-cell mass Inhibits glucagon secretion Promotes a bit of weight loss
Exenatide
Liraglutide
Inhibitor of GLP-1 protease DPP-4
Prolongs the action of GLP-1 in portal circulation
Sitagliptin
Inhibits the sodium-glucose transport protein (SGTP-2) that reabsorbs glucose
Leads to loss of glucose in the urine
Decreases serum glucose by 20 mg% and decreases glycated hemoglobin by 0.75%
Canagliflozin
SE of Canagliflozin – SGTP-2 inhibitor
Genital yeast infections
Lower HgbA1C by 1.5%
Sulfonylureas
Metformin
Lower HgbA1C by 0.75%
Acarbose
Thiazolidinediones
DPP-4 inhibitors
SGPT-2 inhibitors
What is a common combination treatment for type 2 diabetes?
Insulin or an oral sulfonylurea with an insulin sensitizing drug
Sulfonylurea/DPP-4 OR Insulin
WITH
Metformin OR Thiazolidinedione
A rapid-acting insulin secretion-stimulating agent for the treatment of type 2 diabetes
Not recommended as mono therapy – >may be added to metformin therapy for those patients with continued postprandial hyperglycemia
Meglitinide
