Diabetes Drugs Flashcards
What is the ultimate result of T1 and T2 DM?
Hyperglycemia
Polyuria, polydipsia, glucosuria, unexplained weight loss despite polyphagia, fatigue & blurred vision and in some cases ketoacidosis
T1DM
Obesity, fatigue, polyuria and polydipsia can be present, although patients are often asymptomatic. IFG and IGT can be detected and precede the onset of diabetes.
T2DM
What are the treatment goals for diabetes?
Try to achieve and maintain glycemic control as close to the normal range as possible to prevent the chronic complications of sustained hyperglycemia
What is the main SE of intensive insulin therapy for diabetes?
Increased risk of hypoglycemia
What is the only treatment for T1DM?
Insulin
What transporter does insulin upregulate in liver, muscle and adipose?
GLUT4
What are the 4 classes of insulin?
- Rapid acting
- Regular
- Intermediate acting
- Long acting
What insulin type are detmir and glargine?
Long acting
What can happen if the same sites are continuously used for insulin?
Lipodystrophy - inappropriate lipid storage
Insulin SE
Hypoglycemia
- Tremor
- Palpitations
- Intense Hunger
- Headaches
- Altered Mental Status
What is non-medical treatment for T2DM?
Change in diet and exercise - this can increase insulin sensitivity and decrease BP
What type of surgery can benefit T2DM patients?
Bariatric Surgery
What is the DOC for treating all T2DM patients?
Metformin
Is metformin associated with weight gain?
NO - actually can cause weight loss
What is the main advantage of metformin?
No hypoglycemia
Metformin Effects
- Lowers fasting plasma glucose
- Decreased hepatic gluconeogenesis
- Increased insulin sensitivity
Metformin MOA
Inhibits the first unit of the electron transport chain which leads to decreased ATP and increased AMP which inhibits adenylate cyclase blocking glucagon’s pathway.
***Overall decreases gluconeogenesis and increases insulin sensitivity
Metformin SE
- Inhibits absorption of Vitamin B12
- Lactic acidosis - rare but can be FATAL (high risk patients)
What is the mechanism of lactic acidosis in use of metformin?
Inhibition of gluconeogenesis decreases lactate being used up as a substrate which increases its concentration. When combined with another condition like decreased renal clearance of lactate, it can lead to toxic build-up.
Metformin Contraindications
- Pregnancy and lactation
- Impaired liver or renal function
- Elderly
- Use of contrast agent
What are the thiazolidinediones and what is their effect?
- Pioglitazone
- Rosiglitazone
“Insulin sensitizers” that increase the sensitivity of adipose tissue, skeletal muscle and liver to the effects of endogenous insulin.
Pioglitazone/Rosiglitazone MOA
Thiazolidinediones are agonists for the peroxisome proliferator-activated
receptor-transcription factor (PPAR). Activation of the PPAR transcription factor by thiazolidinediones influences the expression of multiple genes involved in promoting 1) increased insulin sensitivity and 2) decreased plasma glucose levels
Pioglitazone/Rosiglitazone Indications
- Mono or combo therapy for T2DM
* ** Takes time to see efficacy
Pioglitazone/Rosiglitazone SE
- Weight gain
- Fluid retention
- Increased bone fracture risk in women
Pioglitazone/Rosiglitazone Contraindications
- Liver disease
- Heart failure
- Pregnancy
What are the insulin secretagogues?
- Sulfonylureas
- Meglitinides
What are the sulfonylureas?
- Glimepiride
- Glyburide
- Glipizide
What are the meglitinides?
- Repaglinide
- Nateglinide
Sulfonylurea MOA
Bind Sur1 and block the channel leading to increased intracellular K+ leading to depolarization and activation of Ca2+ channels to release pre-formed insulin
Sulfonylurea Indication
Reduce fasting plasma glucose - long duration of action
What is the action of sulfonylureas dependent upon?
Functional beta cells
Sulfonylurea SE
- Hypoglycemia
- Weight gain
Sulfonylurea Contraindications
- Elderly (renal impairment)
- Renal or liver disease
- T1DM
- Pregnancy
- Sulfa allergy
Sulfonylurea DDIs
Highly protein bound so can interact with:
- Aspirin
- Warfarin
Meglitinide MOA
Bind different region of Sur1 leading to secretion of pre-formed insulin but has a RAPID and SHORTER duration that sulfonylureas
What is melitinide dependent on?
Glucose - less risk of hypoglycemia
Nateglinide affects primarily only _________
Postprandial glucose
Repaglinide affects both ____________ and _____________.
Postprandial and fasting glucose
Melitinide SE
- Hypoglycemia
- Weight gain
Meglitinide Contraindication
- Liver disease
- Pregnancy
What is the incretin effect?
Plasma insulin levels to oral glucose are significantly greater than to IV glucose
GLP-1
Made by L cells of small intestine and mediates the incretin effect
What degrades GLP-1?
DPP-IV
Exenatide/Liraglutide Indications
- Alternative to insulin in T2DM
Exenatide/Liraglutide Effects
- Reduce fasting and postpradial glucose
- Promotes weight loss
Exenatide/Liraglutide SE
Minor GI effects
Exenatide/Liraglutide MOA
GLP-1 homologs
Sitagliptin/Saxagliptin MOA
DPP-IV inhibitors - increase half life of GLP-1
Sitagliptin/Saxagliptin Indications
- Decrease fasting and prostprandial glucose
- Mono or combo therapy for T2DM
Acarbose/Miglitol MOA
Inhibit alpha-glucosidase which hydrolyzes dietary carbohydrates and delays the absorption of glucose
Acarbose/Miglitol Indications
- Postprandial hyperglycemia control
- Less potent than sulfonylureas and metformin
NOT 1st line
Acarbose/Miglitol SE
- GI effects from unabsorbed carbohydrates
Do NOT cause hypoglycemia
Acarbose/Miglitol Contraindications
GI diseases
Canagliflozin/Dapagliflozin MOA
Inhibit SGLT2 in proximal renal tubule which prevents the normal process of glucose reabsorption
Canagliflozin/Dapagliflozin Indications
- Mono and combo therapy for T2DM
What are the effects of Canagliflozin/Dapagliflozin?
- Weight loss
- Decreased BP
Canagliflozin/Dapagliflozin SE
- UTIs
- Thirst/dehydration
- Increase LDL cholesterol
Canagliflozin/Dapagliflozin Contraindications
Renal Impairment
Bromocriptine MOA
DOPA D2 agonist - exact MOA for diabetes is unknown but thought to normalize morning DOPA levels
Colesevalam MOA
Increases bile acid synthesis by increasing excretion of bile by binding to bile and preventing reabsorption -which leads to lowering of LDL
Colesevalam Indications
Add on therapy to 1st line treatments for T2DM
What is the most effective medication to lower hyperglycemia?
Insulin
Pramlintide MOA
Amylin homolog - amylin is endogenous hormone that is co-secreted with insulin and contributes to post-prandial glucose control
Pramlintide Effects
- Inhibits hepatic gluconeogeneis
- Slow gastric emptying
- Inhibits glucagon
- Increases satiety
Pramlintide Indications
Adjunct therapy in T1 or T2 patients using insulin but are not at adequate control
Pramlintide SE
- Weight loss
- GI effects
- Risk for severe hypoglycemia
