A - 13 + 14. Pancreatic hormones and parenterally applied antidiabetic drugs. Pharmacotherapy of IDDM + Oral antidiabetics. Pharmacotherapy of non-insulin dependent diabetes mellitus Flashcards
This contains both A13 and A14.
Which pancreatic cells produce what hormone?
A-cells - glucagon
B-cells - insulin
D-cells - somatostatin
F-cells - pancreatic polypeptide
DM1 and DM2 main difference
DM1 - elevated glucagon, needs exogenous insulin
DM2 - spectrum of insulin problems, both production and resistance
- lowered B-cell sensitivity to glucose
- circulating insulin is usually enough to prevent ketoacidosis
B-cell stimulants
glucose mannose arginine leucine vagus
Insulin structure
A and B chain held together by c-peptide
Insulin action tissues
Liver
Muscle
Adipose
Insulin receptor
Tyr-kinase
Elimination of insulin
Breakage of disulfide bridges -> excretion through liver and kidneys
Insulin glucose transporter effects
GLUT4 translocation in muscle and adipose
Insulin muscle effect
Increased glucose uptake -> glycogen synthase -> increased glycogenolysis
Protein uptake increase
Insulin adipose effect
LPL increase (reduces circulating FA)
Glucose uptake increase
Lipolysis decrease
Insulin liver effect
Glycogenesis and triglyceride synthesis increase
Gluconeogenesis, glycogenolysis , ketogenesis decrease (indirect effect of decreased lipolysis in adipose)
Ultra short acting insulin preps
Lispro insulin
Given subcutanously to DM1 around 5 min before meals
Active for 3-4 hours regardless of dosage
Short acting insulin preps
Regular insulin
30 min after admin, works for 5-7 hours
Intermediate/long acting insulin preps
Isophane
Insulin + protamine (10:1) ratio
Given subcutanously
Onset 90 min, lasts 24 hours
Ultra long acting insulin preps
Glargine
Precipitates subcutanously, slow dissolving
Lasts >24 hours
Complications of insulin preps
Lipodystrophy at injection site
Hypoglycemia
Allergy
Development of insulin resistance
Oral antidiabetics: insulin secretagogues action
Closes K+ channels on B-cells -> depol -> insulin release
Oral antidiabetics: insulin secretagogues - sulfonyrureas
Glipizide
Glimpiride
Oral antidiabetics: insulin secretagogues - meglitinides
Repaglinide
Rapid onset, short duration - taken before meals
Oral antidiabetics: insulin secretagogues - SE
Hypoglycemia (less than insulin preps)
Rashes, allergies
Weight gain
Oral antidiabetics: Biguanides action
Inhibits gluconeogenesis in liver and kidneys
Stimulation of glucose uptake and glycolysis
Activates AMP-stimulated protein kinase
Oral antidiabetics: Biguanides names
Metformin
Modern drug choice for DM2;
- Reduces glucose levels after meals and fasting
- Reduces endogenous insulin in patients with insulin resistance (insulin sparing)
- No weight gain
Oral antidiabetics: Biguanides SE
- GI problems
- Lactic acidosis
Oral antidiabetics: Thiazolidinediones action
Increases tissue sensitivity to insulin by activating PPAR-gamma receptor
Oral antidiabetics: a-glucosidase inhibitors action
Inhibits a-glucosidase within intestines, inhibiting breakdown of polysaccharides, slowing absorption of glucose
Oral antidiabetics: a-glucosidase inhibitors name
Acarbose
Oral antidiabetics: DPP-4 inhibitor
Vildagliptin
GLP-1 degredation
Oral antidiabetics: SGLT-2 inhibitor
dapagliflozin
Inhibits SGLT-2, responsible for 90% of glucose reuptake in kidneys
SE: rapid weightloss from glucosuria, dehydration
