Drug Treatment Of Type 2 Diabetes

Question 1

Insulin on muscle cells effect?

Answer 1

Increase glucose uptake by translocation of glut 4 onto membrane, glycogen synthesis, amino acid uptake and protein synthesis

Question 2

Insulin effect on adipocytes?

Answer 2

Increase glucose uptake, increase triglyceride synthesis, decreases FFA and glycerol release

Question 3

Treatment for beta cell dysfunction?

Answer 3

Sulphonylureas, GLP-1 analogues and DDp-4 inhibitors

Question 4

treatment for insulin resistance?

Answer 4

Metformin and TZDs (thiazolidinediones)

Question 5

Treatment for renal glucose absorption?

Answer 5

SGLT-2 inhibitors

Question 6

Sulfonylureas?

Answer 6

Glicazide, glipizide and glimepiride, orally active- all bound to plasma protein

Question 7

Sulfonylureas action?

Answer 7

Cause insulin release,

Sulfonyureas bind to ATP K channels, closing it. Hence depolarisation, calcium ions influx, releasing insulin granules

Question 8

Sulfonylureas secondary action?

Answer 8

Decrease lipolysis, decrease clearance of insulin and sensitize beta cells to glucose

Question 9

Major side effect of sulfonylureas?

Answer 9

Hyppoglycaemia

Drug interaction: allopurinol, aspirin and alcohol

Question 10

Consider when prescribing sulfonylureas these drugs ….?

Answer 10

Oral contraceptives and corticosteroids because they decrease glucose tolerance

Question 11

Biguanides- metformin action?

Answer 11

Increase glucose uptake in muscle and decrease glucose production by liver

Question 12

Metformin mechanism of action?

Answer 12

Suppression of hepatic glucose production

1. Inhibits mitochondrial complex 1- decrease ATP synthesis, and gluconeogenesis needs energy.
   Increase in AMP which inhibits fructose 1,6 bisphosphate key enzyme in gluconeogenesis
2. Activating AMP activated protein kinase- nuclear transcription factors SHP, which inhibits expression of gluconeogenesis genes PEPCK and glucose 6 phosphatatse

Question 13

Biguanides secondary action?

Answer 13

1. Increase insulin sensitivity- by AMPK insulin binding to its receptors
2. Increased GLUT 4 translocation
3. Pushes heart muscle to use glucose by MAPCK and PKC
4. Increase fatty acid oxidation
5. Decrease glucose absorption from GI tract

Question 14

Properties of metformin?

Answer 14

Oraly active
Doesn’t bind to plasma proteins, excreted unchanged in urine.
Half life 1.3 and 4.5 hours
Also used for PCOS

Question 15

Adverse effect of metformin?

Answer 15

Lactic acidemia
Metallic taste, nausea, abdominal discomfort, diarrhoea, anorexia more common
Decreases absorption of vitamin B12 and folate

Question 16

Metformin contraindications?

Answer 16

Hepatic disease
Past history of lactic acidosis
Chronic hypoxia lung disease causes metabolic acidosis

Question 17

Pioglitazone?

Answer 17

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

Question 18

Pioglitazone?

Answer 18

Liver metabolism and excreted in faeces 2/3 and urine 1/3

Plasma half life Is 3 to 7 hours

Question 19

Glitazones adverse effects?

Answer 19

Weight gain, fluid retention, liver damage

Question 20

Glucagon like peptide 1 analogs?

Answer 20

Exenatide
Decreases hepatic glucose output, increases glucose-dependent insulin secretion, decreases gastric emptying (not absorbing nutrients)

Question 21

Glucagon like peptide 1 analogs exenatide?

Answer 21

Subcutaneous, adjuvant therapy, side effects are mild belching, sour stomach diarrhoea

Question 22

Semaglutide?

Answer 22

Oral, protected from proteolytic degradation

Question 23

Difference in exenatide to GLP 1?

Answer 23

Resistant to DDP 4 degradation

Question 24

Dipeptidyl peptidase 4?

Answer 24

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

Question 25

DPP 4 inhibitors examples?

Answer 25

Vildagliptin, sitagliptin and Saxagliptin

Question 26

Sodium glucose transporter protein inhibitors examples?

Answer 26

Dapagliflozin and canagliflozin

Question 27

Effects of SGLT2 inhibitors?

Answer 27

Reverse of glucotoxicity,
Insulin sensitivity better, increased glut4 translocation

Gluconeogenesis decreases
Improved beta cell function

Question 28

Side effects of sglt2 inhibitor?

Answer 28

Rapid weight loss, tiredness, dehydration, and worsen uti and thrush

Question 29

Treatment for loss of b cell mass?

Answer 29

Insulin replacement

Question 30

Treatment for b-cell dysfunction?

Answer 30

Sulphonylureas, GLP-1 analogues, DDP-4 inhibitors

Question 31

How does glucose cause insulin release?

Answer 31

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.

Question 32

Glucagon like peptide 1 increases?

Answer 32

Insulin release

Question 33

Incretins effect?

Answer 33

Oral glucose elicits higher insulin secretory response than iv

Question 34

How do GLP1 work?

Answer 34

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

Question 35

How do Glucose dependent insulinotropic polypeptides work?

Answer 35

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