T1 L14:Drug treatement of Type 2 Diabetes Flashcards
what tissues does insulin target
liver
adipose
skeletal muscle
advantages of metformin
cheap
effective
safe-least side effects
what does insulin do to the hepatic cells (processes)
2m
Decreases:
gluconeogenesis, glycogenolysis, ketogenesis,
(increases glycogen synthesis)
what & how do muscle cells do to respond to insulin
3m
decreases- glycogenolysis & amino acid release
increases GLUT-4 translocation to the membrane and hence increase glucose uptake, glucose oxidation, glycogen synthesis, amino acid uptake, protein synthesis
what do adipocytes do in response to insulin
increase glucose uptake, increase triglyceride synthesis; decrease FFA and glycerol release
what is the net effect of insulin
is to cause hypoglycemia
and increase fuel storage in muscle, fat tissue and liver
what happens to the insulin sensitivity and insulin conc from a normal to a t2 diabetic
usually, insulin sensitivity is high and insulin conc is low.
Both decrease in t2 but reverse as well- high resistance and low insulin conc
what causes hyperglycaemia
Renal glucose absorption
Loss of beta-cell mass
Insulin resistance
what is an example of a sulfonylureas
when are they active, and what are they bound to and %
Gliclazide
glipizide
orally active
90-99% bound to plasma protein
What is the primary mechanism of how sulfonylureas act
- stimulates endogenous insulin release
- binds to ATP-sensitive-K-channel, inhibiting cell opening to ATP
- causing beta cells to depolarise and ca influx and insulin release
-
what are the secondary mechanisms of how sulfonylureas work
Sensitize ß-cells to glucose
Decrease lipolysis
Decrease clearance of insulin by the liver
who is sulfonylureas best used on and what is it’s side effects
The best patient-
- over 40 years
- DM duration less than 10 years
Side effect-hypoglycaemia
give an example of a biguanide
Metformin
what do biguanides do and secondary effects (3m)
increase glucose uptake in muscle and decrease glucose production by liver (Increasing insulin sensitivity via):
- Enhances peripheral glucose uptake
- –Increased GLUT 4 translocation through AMPK
-Increases fatty acid oxidation via decreasing insulin-induced suppression of fatty acid oxidation
what is the mechanism of action of biguanides
It reduces hepatic glucose production:
via AMP-activated protein kinase (AMPK) dependent and independent pathways
AMPK increases expression of the nuclear transcription factor SHP which in turn inhibits the expression of hepatic gluconeogenic genes. ie G-6-P glucose-6-phosphatase
what other properties of metformin is peculiar (3)
- orally active
- does not bind plasma proteins
- often combined in a single pill with other anti-diabetic medications
what other syndrome can metformin treat
also used for polycystic ovary syndrome
when can you not use metformin
hepatic disease
past history of lactic acidosis (any cause)
cardiac failure
Give an example of a Glitazones (thiazolidinediones
Pioglitazone-
how does Pioglitazone function
3m
Activate peroxisome proliferator-activated receptor-g (PPARg)
(involved in involved in transcription of insulin-responsive genes and in regulation of adipocyte lipid metabolism)
what does pioglitazone cause
and what does it need to work
It needs the presence of endogenous or exogenous insulin to:
- decrease gluconeogenesis, glucose output, and triglyceride production in liver
- increase glucose uptake and utilization in skeletal muscle
- Cause differentiation of adipocytes
what are the adverse effects of pioglitazone
interactions due to liver metabolism.
weight gain
fluid retention
what is a major advantage of Glucagon-like peptide-1 analogs GLP-1
It increases satiety and reduces food intake
give an example of a GLP-1
Exenatide
