Drug Treatment Of Type 2 Diabetes Flashcards
Insulin on muscle cells effect?
Increase glucose uptake by translocation of glut 4 onto membrane, glycogen synthesis, amino acid uptake and protein synthesis
Insulin effect on adipocytes?
Increase glucose uptake, increase triglyceride synthesis, decreases FFA and glycerol release
Treatment for beta cell dysfunction?
Sulphonylureas, GLP-1 analogues and DDp-4 inhibitors
treatment for insulin resistance?
Metformin and TZDs (thiazolidinediones)
Treatment for renal glucose absorption?
SGLT-2 inhibitors
Sulfonylureas?
Glicazide, glipizide and glimepiride, orally active- all bound to plasma protein
Sulfonylureas action?
Cause insulin release,
Sulfonyureas bind to ATP K channels, closing it. Hence depolarisation, calcium ions influx, releasing insulin granules
Sulfonylureas secondary action?
Decrease lipolysis, decrease clearance of insulin and sensitize beta cells to glucose
Major side effect of sulfonylureas?
Hyppoglycaemia
Drug interaction: allopurinol, aspirin and alcohol
Consider when prescribing sulfonylureas these drugs ….?
Oral contraceptives and corticosteroids because they decrease glucose tolerance
Biguanides- metformin action?
Increase glucose uptake in muscle and decrease glucose production by liver
Metformin mechanism of action?
Suppression of hepatic glucose production
- Inhibits mitochondrial complex 1- decrease ATP synthesis, and gluconeogenesis needs energy.
Increase in AMP which inhibits fructose 1,6 bisphosphate key enzyme in gluconeogenesis - Activating AMP activated protein kinase- nuclear transcription factors SHP, which inhibits expression of gluconeogenesis genes PEPCK and glucose 6 phosphatatse
Biguanides secondary action?
- Increase insulin sensitivity- by AMPK insulin binding to its receptors
- Increased GLUT 4 translocation
- Pushes heart muscle to use glucose by MAPCK and PKC
- Increase fatty acid oxidation
- Decrease glucose absorption from GI tract
Properties of metformin?
Oraly active
Doesn’t bind to plasma proteins, excreted unchanged in urine.
Half life 1.3 and 4.5 hours
Also used for PCOS
Adverse effect of metformin?
Lactic acidemia
Metallic taste, nausea, abdominal discomfort, diarrhoea, anorexia more common
Decreases absorption of vitamin B12 and folate
Metformin contraindications?
Hepatic disease
Past history of lactic acidosis
Chronic hypoxia lung disease causes metabolic acidosis
Pioglitazone?
Activate peroxisome proliferator activated receptor gamma, involved in transcription of insulin responsive genes and in regulation of adipocyte lipid metabolism, has to be in presence of insulin
Pioglitazone?
Liver metabolism and excreted in faeces 2/3 and urine 1/3
Plasma half life Is 3 to 7 hours
Glitazones adverse effects?
Weight gain, fluid retention, liver damage
Glucagon like peptide 1 analogs?
Exenatide
Decreases hepatic glucose output, increases glucose-dependent insulin secretion, decreases gastric emptying (not absorbing nutrients)
Glucagon like peptide 1 analogs exenatide?
Subcutaneous, adjuvant therapy, side effects are mild belching, sour stomach diarrhoea
Semaglutide?
Oral, protected from proteolytic degradation
Difference in exenatide to GLP 1?
Resistant to DDP 4 degradation
Dipeptidyl peptidase 4?
Breaks down incretins cuts of 1-2 amino acids, GLP1 and GIP, so they can’t activate receptor but bind to it.
Increased levels of incretins
DPP 4 inhibitors examples?
Vildagliptin, sitagliptin and Saxagliptin
Sodium glucose transporter protein inhibitors examples?
Dapagliflozin and canagliflozin
Effects of SGLT2 inhibitors?
Reverse of glucotoxicity,
Insulin sensitivity better, increased glut4 translocation
Gluconeogenesis decreases
Improved beta cell function
Side effects of sglt2 inhibitor?
Rapid weight loss, tiredness, dehydration, and worsen uti and thrush
Treatment for loss of b cell mass?
Insulin replacement
Treatment for b-cell dysfunction?
Sulphonylureas, GLP-1 analogues, DDP-4 inhibitors
How does glucose cause insulin release?
Glucose taken up by glut 2 recpetor and is metabolised. ATP is created and binds to ATP sensitise K channel closing it. Build up changing voltage, open voltage dependent ca channels, come in. Release of insulin, by movement of insulin granules.
Glucagon like peptide 1 increases?
Insulin release
Incretins effect?
Oral glucose elicits higher insulin secretory response than iv
How do GLP1 work?
Produced by L cells mainly located in the distal gut (ilium and colon) but secreted also from proximal gut
Stimulates glucose-dependent insulin release
Suppresses hepatic glucose output by inhibiting glucagon secretion in a glucose dependent manner
Inhibition of gastric emptying; reduction of food intake and body weight
Enhances ß-cell proliferation and survival in animal models and isolated human islets
How do Glucose dependent insulinotropic polypeptides work?
Produced by K cells in the proximal gut
Stimulates glucose-dependent insulin release
Minimal effects on gastric emptying; no significant effects on satiety or body weight
Potentially enhances ß-cell proliferation and survival in islet cell lines
Stimulates glucagon secretion
