Diabetes Pharmacology Type I and Type II Flashcards
Earliest signs of diabetes?
Increased: Postprandial chylomicrons VLDL cholesterol Gluconeogenesis, ketogenesis Plasma triglycerides
Three microvascular injuries that occur with diabetes?
Cataracts and retinopathy
Nephropathy
Neuropathy
How to prevent cataracts and retinopathy?
Keep A1c below 9%
How to prevent nephropathy?
Keep A1c below 8%
How to prevent neuropathy?
Keep A1c below 7%
What are the four goals of therapy?
- ) Prevent hyperosmolar coma/ketoacidosis
- ) Reduce microvascular injury
- ) Reduce hypertension
- ) Prevention of atherosclerotic disease
Two general types of drugs that increase plasma insulin?
Insulin
Secretagogues
Three general types of insulins?
Rapid acting and short acting
Moderate acting
Long acting
What are the rapid acting insulin?
Lispro insulin (Humalog) Insulin aspart (Novolog)
What are the short acting insulin?
Regular insulin
What are the moderate acting insulins?
Isophane/NPH
What are the long acting insulins?
Glargine
Detemir
Degludec
What are two types of secretagogues?
Sulfonylureas
Short-acting secretagogues
What are the sulfonylureas?
Glyburid
Glipizide
Glimepiride
What are the short acting secretagogues?
Repaglinide
Nateglinide
What are intermediate-mixed insulins preparations?
Isophane + regular insulin or Lispro
What may be used in a patient that has a high insulin dosage requirement?
Pramlintide
What are two general categories of direct acting agents for increased glucose uptake?
Biguanides
Thiazolidinediones
What are the Biguanides?
Metformin
What are the thiazolidinediones?
Pioglitazone
Rosiglitazone
What are the two general categories of GLP-1 mechanism for increased tissue glucose uptake?
GLP-1 Analogs
Dipeptidyl peptidase inhibitors
What are the GLP-1 analogs?
Liraglutide
Exenitide
What are the Dipeptidyl peptidase inhibitors?
Sitagliptin
Linagliptin
Saxigliptin
What does metformin cause?
Increased insulin sensitivity
Decreased gluconeogenesis
How does metformin mediate its affects?
Not well understood but increase AMP:ATP ratio activating AMP kinase
What are contraindications of metformin?
Hepatic and renal insufficiency
MI
Uncompensated CHF
What can metformin cause?
Lactic acidosis
How do thiazolidinediones work?
Ligands for cytosolic and nuclear PPAR receptors
What are the two PPAR receptors?
Gamma
Alpha
What affect to thiazolidinediones have?
Increased fatty acid uptake
Increased fatty acid oxidation
Increased insulin sensitivity and glucose uptake
Anti-inflammatory affects
What are the two thiazolidinediones?
Pioglitazone
Rosiglitazone
What receptors does pioglitazone work on?
PPAR-alpha
PPAR-gamma
What receptors does rosiglitazone work on?
PPAR-gamma
Which thiazolidinedione has better lipid metabolism effects?
Pioglitazone (PPAR-alpha)
What do incretins/GLP-1 do?
Increase GLUT-2 expression in beta-cells of the pancreas
When is GLP-1 released and where?
From small intestine and colon in response to carbohydrate, protein and fat intake
What enzyme breaks down GLP-1 and GIP?
DPP4
What do dipeptidylpeptidase inhibitors do?
Inhibit DPP4 increasing the life span of GLP-1 and GIP
What releases GLP-1?
Distal small intestines and colon
What releases GIP?
Duodenum
Jejunum
What are the effects of GLP-1 (7-36) amide (active form)?
Increased: Insulin secretion Satiety Beta-cell survival Decreased: Glucagon secretion Gastric emptying Food intake
What is are the effects of GLP-1 (9-36) amide (inactive form)?
Increased independent glucose clearance
Cardioprotective
Vasoactive
What are the effects of GIP (1-42) active form?
Increased: Insulin secretion Lipogenesis Beta-cell survival Decreased: Lipolysis
What are the effects of GIP (3-42) inactive form?
None
What are the GLP-1 analogs?
Exenatide
Liraglutide
Which GLP-1 analog has reduced DPP4 sensitivity?
Liraglutide
What are examples of DPP4 inhibitors?
Sitagliptin
Linagliptin
What are amylin analogs?
Pramlintide
What are alpha-glucosidase inhibitors?
Acarbose
Miglitol
What are inhibitors of sodium-glucose transport?
Dapagliflozin
Empagliflozin
Canagliflozin
What is amylin?
Small peptide hormone that is released into the bloodstream by the beta cells of the pancreas along with insulin after a meal
What is the only drug approved to lower blood sugar in Type I diabetics since insulin?
Pramlintide
Mechanism of action of Pramlintide?
Inhibit release of glucagon
What do alpha-glucosidase inhibitors do?
Inhibit intestinal alpha-glucosidase slowing post-prandial increase in plasma glucose
What does alpha-glucosidase enzyme do?
Digests carbohydrates
What is more commonly used among “skinny” Type II diabetics?
Alpha-glucosidase inhibitors
Where do SGLT-2 transporters work and what do they do?
Co-transport sodium and glucose in the proximal convoluted tubule
What are the SGLT-2 inhibitors?
Canagliflozin
Empagliflozin
Dapagliflozin
What do the SLGT-2 inhibitors cause?
Decrease in reabsorption of glucose and sodium from the PCT allowing it to be released in the urine
What are side effects of glucose in the urine?
Polyuria/dehydration
Urinary tract infections (fungal)
Urine loss of 200-500 Kcals/day
Ketoacidosis
What drug is acid-soluble and precipitates at body pH?
Glargine insulin
What drug heavily binds to albumin?
Detemir insulin
What is the standard insulin therapy for Type I diabetics?
Glargine insulin (once daily) + rapid acting insulin with meals or insulin pump with rapid-acting insulin