L28- Antidiabetic Drugs I Flashcards
_____ is the generally the main treatment for DM type I
exogenous insulin injection (SQ) to control blood glucose and avoid ketoacidosis
why is DKA less apparent in DM type II
insulin secretion is sufficient enough to restrain ketogenesis but not enough to overcome hyperglycemia
generally describe DM type II treatment
-noninsulin hypoglycemic agents
- 20% require exogenous insulin for optimum health
- insulin is NOT for survival
Insulin:
- (1) MW
- (2) AAs
- (3) arrangement
- MW = 5808
- 51 AAs arranged on 2 polypeptides connected via 2 disulfide bonds
β-cells are stimulated to release insulin by….
Glucose*, most important
AAs
GI hormones- Incretins (responds to ingestion of food)
describe the effect of Incretins
- respond to ingestion of food / glucose
- enhances secretion of insulin
Note- compared to IV glucose administration, about 4x more insulin is released upon ingestion / oral administration due to Integrins
describe the mechanism of Insulin secretion
1) β-cell: glucose influx via GLUT2
2) inc glycolysis + citric acid cycle
3) inc ATP
4) closes K(ATP) channel
5) dec K+ efflux
6) cell depolarization
7) Ca++ channels open
8) Ca++ triggers exocytosis and insulin is secreted
describe the structure and function of Insulin receptor
2 covalently linked heterodimers: α and β subunits bind their counterpart
α- extracellular, insulin recognition
β- transmembrane, contains TK
Insulin binds α-subunit –> β subunit activated –> Tyr residue phosphorylation (β subunit) –> cytoplasmic protein phosphorylation
list the general cellular effects of Insulin
- upregulates GLUT4 to membrane
- metabolic actions (anabolism)
- cell growth / differentiation
- gene expression
describe the production of exogenous Insulin
recombinant human DNA: proinsulin gene placed w/in a plasma –> insulin is generated by E. coli or yeast
Ex:
mammilian proinsulin mRNA –> proinsulin cDNA –> plasmid –> infect`s E. coil
list the insulin preparation types
Rapid Acting
*Short Acting (normal human insulin)
Intermediate Acting
Long Acting
list the rapid-acting insulin analogs
Insulin Lispro
Insulin Aspart
Insulin Glulisine
how is rapid-acting insulin different from normal insulin (short-acting)
Native insulin (short-acting) is usually in hexamer form –> slows down absorption
Rapid-acting insulin only provides monomers for absorption for a much faster onset of action— as a result from changing AAs in insulin B chain
Rapid Acting insulin:
- given via (1) route, at (2) time of day
- given to mimic (3)
- usually associated with (4) administration
1- SQ (can be given IV)
2- 15 mins before meals
3- prandial release of insulin
4- long acting insulin (for basal insulin levels)
Short Acting insulin, aka (1):
- (2) formulation
- given via (3) route, at (4) time of day
1- regular insulin
2- soluble crystalline zinc insulin
3- SQ (IV in emergencies)
4- 30 mins before meals
Intermediate Acting insulin, aka (1):
- (2) formulation
- given via (3) route
- (4) uses
1- NPH (neutral protamine Hagedorn), Isophane insulin
2- suspension of cystralline zinc insulin + protamine
3- SQ
4- basal insulin control (usually combined with rapid/short acting insulin for mealtime control)
list the long-acting insulin analogs
- Insulin Glargine
- Insulin Detemir
- Insulin Degludec* (longest duration of action)
how is long-acting insulin different from normal insulin (short-acting)
Normal- monomers form hexamers
Long-Acting- precipitation of multiple hexamers –> slow dissociation into insulin monomers (once a day SQ injections)
describe the appearance of all the insulins
all are clear
ONLY NPH is cloudy due to protamine addition
what is the main insulin formulation combination prescribed
Rapid Acting Insulin (mealtime) + Long Acting Insulin (basal)
much more effective than regular (short-acting) insulin + NPH
IV insulin:
- predominately in (1) form
- (2) are indications for use
1- IV infusion
2- ketoacidosis, preoperative period, labor / delivery, ICU situations
always IV insulin in hospitals
Inhaled Insulin:
- (1) formulation
- levels peak at (2)
1- regular human insulin in dry powder formulation
2- 12-15 mins (returns to baseline at 3hrs)
Inhaled Insulin:
- (1) AEs
- (2) must be monitored
- (3) contraindications
1- cough, throat pain, hypoglycemia
2- pulmonary function
3- asthma, COPD, smokers
list the types of insulin regimens
Basal-Bolus Insulin Regimens:
- long acting at night or in morning
- mealtime insulin (before)
-Insulin Pump Therapy: releases rapid acting (glulisine, lispro) or insulin (short-acting)
describe the main AE of insulin
Hypoglycemia- most serious and common AE
- rapid acting is LOWER risk than short acting insulin
- long acting is LOWER risk than NPH
how is Hypoglycemic episodes managed (insulin OD)
Mild Hypoglycemia: give OJ, glucose, sugary beverage/food
Severe Hypoglycemia = unconciousness / stupor: IV glucose infusion
*if IV is not available –> give glucagon SC or IM
list some drugs that cause hypoglycemia
- ethanol (inhibits gluconeogenesis)
- β-blockers (inhibits SNS => glucose mobilization)
- Salicylates (inhibits sensitivity to blood glucose)
list some drugs that cause hyperglycemia
- epinephrine
- glucocorticoids
- atypical antipsychotics
- HIV protease inhibitors
- phenytoin
- clonidine
- Ca++ channel blockers
- diuretics
describe DM management of hospitalized patients
Illness => inc insulin resistance
-oral antidiabetics replaced with insulin –> restarted on discharge
