Pharmacology of Type 2 Diabetes Flashcards
what does niddm
noninsulin-dependent diabetes mellitus type 2 basically
what are biguanides such as metformin
do not affect release of insulin glucagon growth hormone (GH) cortisol somatostatin.
Act through AMPK, increasing AMP levels, inhibiting glycerophosphate dehydrogenase
decrease hepatic gluconeogenesis
where is metformin absorbed
small intestine
how do biguanides reducs blood glu conc
decreased hepatic glucose production
potentiate insulin action on muscle and adipose tissue
stimulation of glycolysis in tissues, stimulates glucose
uptake
decrease carbohydrate absoption
stimulate lactate production
decreases LDL and VLDL
inhibit expression of genes involved in gluconeogenesis
what are side effects of biguanides
side effects:
diarrhoea, nausea and metallic taste
rare lactate acidosis
decreases intestinal absorption of folate and vitamin B12
what are advantages of biguanides
does NOT
cause hypoglycaemia
stimulate appetite
cause weight gain
what is the acute action of SULPHONYLUREAS on t2dm
Acutely
Increase insulin release
Increase plasma insulin concentration
Decrease hepatic clearance of insulin. lowering blood glucose conc
what hapens when SULPHONYLUREAS are taken chronically
No acute increase in insulin release BUT decreased
plasma glucose concentration still remains
Chronic hyperglycaemia per se decreases insulin
release
Down regulation of sulphonylurea receptor
what are the side effects of SULPHONYLUREAS
Main adverse effect is hypoglycaemia Neuroglycopenia lack of glucose supply to brain Confusion and coma Take oral glucose If severe give iv glucose glucagon adrenaline
which is more potent meglitinides or sulphonylureas
sulphonylureas are more potent
MEGLITINIDES
Repaglinide (Prandin; generic; 1998)
Nateglinide (Stalix; 2000),
describe the action of these drugs
Take just before meal Close K+ ATP channels on b-cells Share 2 binding sites with sulphonylureas but have their own distinct binding site More selective for b cell than cardiac/vascular K+ ATP channels
what receptors are thiazolidenediones selective agonists for
Selective agonists for
PPARg (nuclear Peroxisome Proliferator- Activated
Receptor g)
PPARg combines with RXR (retinoid X receptor)
where are the following,
PPARy (nuclear Peroxisome Proliferator- Activated
Receptor y)
PPARy combines with RXR (retinoid X receptor),
receptors found
found in adipose tissue, muscle and liver
what is adverse effect of Troglitazone
liver toxicity
what is adverse effect of rosiglitazone
cardiovascular problems
what is adverse effect of pioglitazone
risk of bladder cancer
describe mechanism of action of THIAZOLIDENEDIONES
Activates insulin responsive genes that control
carbohydrate and lipid metabolism
Needs insulin to be effective
Reduces insulin resistance in peripheral tissues
Reduces glucose production by liver
Increases glucose uptake in muscle and adipose tissue
potentiates actions of insulin
increase adipocyte number & lipogensis
THIAZOLIDENEDIONES why do can they cause some weight gain
weight gain (1-4kg) due to increased differentiation of
adipocytes, fluid retention by stimulating amiloride
sensitive Na+ absorption
what does incretin do
incretin stimulates insulin release
how is incretin produced
post translational processing of preproglucagon
describe mechanism of action of a-GLUCOSIDASE INHIBITORS
Inhibits intestinal brush border a-glucosidase
Inhibits carbohydrate breakdown and reduce
postprandial increase in blood glucose levels, effective for type 1 and 2 diabetes
what are the side effects of
a-GLUCOSIDASE INHIBITORS
flatulence and diarrhea
a patient reports that a glucosidase inhibitors caused him to have a hypogylcaemic event is this a consistent story
no because these drugs do not cause hypos
how do Sodium glucose transporter 2
(SGLT2)inhibitors work
SGLT2 inhibitors inhibit glucose re-uptake in
kidney - up to 10% excretion of calorie intake
how do AMYLIN ANALOGUES work
decrease gastric emptying, inhibit glucagon, promotes fullness so the [atient eats less
why is it important to tackle rising incidence of obesity
major risk factor for type 2 diabetes. there are some drug treatments such as orlistat
