Diabetes Drugs Flashcards
What is the goal of insulin therapy for pts with T1DM?
Achieve normal glycemic control
Use basal insulin to replace insulin made under fasting conditions, and posprandial insulin for more rapid action
Insulin MOA (3 primary organs and its effects)
Liver
Inhibit secretion of glucagon from alpha cells, thus decreasing gluconeogenesis and glycogenolysis
Muscle
Upregulate GLUT4 and increase glucose uptake. Increase protein synthesis and inhibit proteolysis
Adipose
Increase glucose uptake and decrease lipolysis
Name the different forms of rapid acting insulin
Insulin aspart
Insulin lispro
Insulin glulisine
What is the intermediate acting insulin?
NPH Insulin
Name the long acting insulins
Insulin glargine
Insulin detmir
Insulin
Administration
SubQ via syringe, pen, or pump
Note: You should change site of administration over time, as insulin promotes lipid storage in adipose cells
Compare Conventional Insulin Therapy with Intensive Insulin Therapy
Conventional: Two injections per day containing both NPH insulin and regular insulin
Risk of hyperglycemia at night
Intensive: Once/twice daily basal insulin to lower fasting glucose, with pre-meal bolus of rapid insulin to control postprandial glucose
Needs more patient commitment; higher cost
Major symptoms of Hypoglycemia
Mild: Tremor, palpitations, sweating, hunger
Moderate: Headache, mood change, decreased attention, patients may need assistance
Severe: Unresponsive, Unconscious, convulsions, death
What is the best treatment for T2DM?
Diet and exercise
What is the DOC for patients unable to control T2DM with diet and exercise along?
Metformin
Metformin
MOA
Blocks complex 1 in mitochondrial oxidative phosphorylation, leading to an antagonization of adenylate cyclase in the liver (preventing gluconeogenesis). Also causes increased AMP, leading to higher AMPK, causing increased insulin sensitivity, glucose uptake.
Lower plasma glucose and insulin resistance
Metformin
Adverse Effects
Mostly well tolerated (some GI effects, potential B12 def)
Major AE: Lactic Acidosis that may be fatal
-Paritcular risk in high risk pt (elderly, renal/hepatic insufficiency)
Metformin
Contraindications
Pregnent/lactating women
Renal or hepatic insufficiency
Elderly (risk renal insufficiency)
Anyone at risk for lactic acidosis
Anyone taking iodinated contrast agent for radiography (risk of agent-induced acute renal failure)
What are the two Thiazolidinediones?
Pioglitazone
Rosiglitazone
Pioglitazone and Rosiglitazone
MOA
Agonist for PPARy
Increases gene transcription of GLUT4 in muscle, increased adiponectin
Increases Insulin SENSITIVITY
Pioglitazone and Rosiglitazone
Indications
Used in monotherapy or in combo with metformin, sulfonylureas, or insulin for T2DM
Decreases FASTING blood glucose
Pioglitazone and Rosiglitazone
Adverse Effects
Weight gain
Fluid retention and peripheral edema
-Increased risk HEART FAILURE
Increased risk bone fracture
Hepatotoxic
Pioglitazone and Rosiglitazone
Contraindications
Liver disease
Heart failure
Pregnancy
What two classes of drugs are known as insulin secretagogues? What is each of their durations?
Sulfonylureas (longer acting, primarily affect fasting glucose)
Meglitinides (shorter duration, primarily affect postprandial glucose)
What sulfonylurea drugs are commonly used today?
Glipizide
Glimepride
Glyburide
Sulfonylurea
MOA
Inhibit Sur1 subunit of the Kir6.2 channel on beta cells. Causes an increase in intracellular K+, stimulatign Ca2+ influx and causing release of insulin-containign granules
Sulfonylureas
Indications and Uses
Long duration of glucose lowering effect, primarily affecting fasting plasma glucose
Activity is dependent on function of beta cells, which will likely lose function over time
Sulfonylureas
Adverse Effects
Hypoglycemia– seen more in pts with renal or hepatic insufficiency
Weight gain
Describe the metabolism of Glipizide, Glyburide, and Glimepride and how that affects their potential uses and toxicites
Glyburide and Glimepride are metabolized in liver to active metabolites, so they may cause increased drug conc and toxicity in renal or hepatic insufficiency
Glipizide is metabolized in liver to an inactive metabolite, so it is safer to use in patients with renal insufficiency
Sulfonylureas
Contraindications
Elderly people with renal or liver insufficiency
T1DM
Pregnant/lactating women
Sulfa allergy
Sulfonylureas
Drug Interactions
Sulfonylureas are highly protein bound drugs, so it is easy to knock them off with other drugs (salicylates, B blockers, warfarin, fibrates) and cause toxicity
Meglitinides
MOA
Bind a different part of Sur1 subunit of the Kir6.2 channel on Beta cells, inhibiting it and causing increase in intracellular K+, then ca2+, then release of insulin granules
What is the major difference between meglitinides and Sulfonylureas?
Meglitinides are much more rapid acting and used to affect postprandial blood glucose
They are glucose-dependent, whereas sulfonylureas are not
Name the two Meglitinides
Repaglinide
Nateglinide
Meglitinides
Adverse Effects
Hypoglycemia
Weight gain
Meglitinides
Contraindications
Liver disease
Pregnancy
What is the major difference between Nateglinide and Repaglinide?
Nateglinide does not require dose adjustment in renal insufficiency
List the GLP-1 homologs
Exenatide
Liraglutide
Describe the Incretin Effect
Oral glucose induces a much better plasma insulin response than IV glucose does because of release of incretins form intestines, which potentiate insulin release at beta cells
Exenatide
MOA
Binds GLP-1 receptor on beta cells and potentiates glucose-induced insulin release
Suppresses glucagon production
Makes periphery more sensitive to insulin
What is the advantage of giving exenatide over recombinant GLP-1?
GLP-1 has a very short half life (2 min) because it is rapidly broken down by DPP-IV
Exenatide acts longer than GLP1 itself, and exenatide reduces both fasting and postprandial glucose
List the DPP-IV Inhibitors
Sitagliptin
Saxagliptin
DPP-IV Inhibitors
MOA
Inhibit breakdown of GLP1 by DPP-IV, thus allowing more activity of GLP1
Alpha-glucosidase inhibitors
MOA
Reduce postprandial blood glucose by inhibiting the digestion of polysaccharides in the small intestine (inhibit alpha-glucosidase enzyme)
Alpha-glucosidase inhibitors
Adverse Effects
May cause GI side effects – do not use when pt has any GI disorder
Do NOT treat any hypoglycemia with complex carbs because the patient won’t be able to break them down
SGLT2 Inhibitors
MOA
Work to inhibit SGLT2 Na+/Glucose linked transporter protein in the kidney
Promotes glucose excretion from kidney by preventing its reabsorption in the PCT
SGLT2 Inhibitors
Adverse Effects
Increased risk UTIs
Thirst/dehydration
Hypotension
Hyperkalemia
Bromocriptine
MOA
Direct D2 agonist
Given in quick release in early morning
Decreases gluconeogenesis, lipolysis, and lipogenesis
Colesevelam
MOA
Bile acid binding resin that is also used to treat dyslipidemia
Prevent bile acid from being reabsorbed in the small intestine. Bile acids can then bind receptors in the colon to stimulate GLP1 secretion and thus potentiate insulin release
Pramlintide
MOA
Amylin homolog that inhibits hepatic gluconeogenesis, slows gastric emptying, and lowers glycogenolysis
Reduces POSTPRANDIAL glucose excursion
Pramlintide
Indications
Used as an adjunct to insulin therapy
Increases risk of severe hypoglycemia, so insulin dosage should be lowered before adding pramlintide
