Antidiabetic Agents Flashcards
What are the functions of all the Key cell types of the endocrine pancreas? Alpha Beta Delta G F
Alpha: Glucagon Beta: Insulin Delta: Somatostatin G: Gastrin F: Pancretic Polypeptide
What positively regulates Insulin release?
GLucose (subs) Amino Acids (subs) Incretins (horm) Epi/B2- Adrenergic Stim (horm) Vagus Stim (neuro)
What negatively regulates Insulin release?
NE/alpha 2 Adrenergic stim (neuro)
Amylin (horm)
What are the receptors on the Beta Cell that stimulate Insulin release?
Glucose dn reg.
ATP Sensitive K+ Channel
leads to voltage dependant Ca++ Channel opening
How does insulin work on the adipose and skeletal muscle cells?
GLUT 4 translocation
What actions does insulin have on metabolic pathways?
(+)FA, glycogen, Protein synth
(-) Beta Ox, Glycogenolysis, Glycolysis, Protein catabolism
What is the main mediatior of T1DM onset?
Autoimmune destruction of Beta Cells
Genetic Predisposition
What are the precursors of Full blown T2DM?
Insulin resistance and insulin secretory defect Genetic Pre-disposition Obesity Nutrition Physical Activity
What are the Signs and Symptoms of T1DM?
Polyuria Thirst Blurred Vision Weight Loss/Polyphagia Weakness/Dizziness Paresthesia Dec. LOC can be rapid or gradual onset
How do we diagnose diabetes clinically?
Glucose Challenge
High Blood Glucose after a meal.
What is the most common type of administration of Insulin?
Sub Cutaneous Injection
What is the theraputic goal of Insulin therapy?
Maintain blood glucose concentrations between 90 and 120 mg/dL.
Waht are the kinetic considerations of Insulin administration?
Diffusion into peripheral tissues is greater than with intrinsically derived insulin.
How is insulin kinetics altered?
Changing the AA sequence to make it stick together for a longer or shorter amount of time.
What are key features of Rapid acting insulin?
AA alteration in C terminal of B peptide Prevents insulin complex formation Duration of 3-5 hrs
What are key features of Short acting insulin?
Identical to human insulin 4-12 hrs
What are key features of Intermediate acting insulin?
Protaimine Insulin complex
10-20 hrs
What are key features of Long acting insulin?
AA changes make it precipitate at a more neutral pH
12-20 hrs
Myristic acid added to inc duration to 22-24 hrs
What are examples of Rapid acting Insulin?
Lispro
Aspart
Glulisine
Inhaled insulin
When do you want to use short acting insulin?
In response to a meal.
What are examples of Intermediate acting Insulin?
NPH
What are examples of Long acting Insulin?
Glargine
Detemir
What is the most common adverse effect to insulin?
Hypoglycemia is most common. Hypersensitivity(rare) Resistance (rare) Lipohypertrophy Lipoatrophy
How is Lipohypertrophy avoided?
Inject insulin at a different place each time.
When is glucagon therapy used?
Use if pt can’t take in glucose by mouth(unconcious)
What are the key points of Metformin use?
1st line agent
Doesn’t prduce hypoglycemia
Not dependant on B cell function
What is the MOA of Metformin?
Dec. Hepatic Glucose output
Increase peripheral glucose utilization
Activation of hepatic enzyme AMP-activated protein kinase
What are the Adverse effects of Metformin?
GI disturbances
Vit B12 deficiency
What is the MOA of Sulfonylureas and Meglitinides?
Inhibition of ATP-sensitive potassium channel of B cell, insulin release
What are the Contraindications of the Glucosidase inhibitors?
Those with GI diseases bc: Inhibits brush border glucosidase enzyme and subsequent absorption of glucose
What is the MOA of Thiazolidinediones?
Dec peripheral resistance by activating peroxisome proliferator-activated receptor
Effect on glucagon metabolism/insulin signaling
What are the AA of Thiazolidinediones?
Peripheral edema, weight gain, hepato tox,
Bone Fractures
Hypoglycemia
What is the MOA of Amylinomimetics?
Inhibits glucagon release
Inhibits gastric emptying
Anoretic effect.
What is the MOA of Incretins?
Insulin secretion
otherwise the same as the amylinomimetics
What is the MOA of DPP inhibitors?
inhibit incretin degradation.
