Diabetes mellitus 2

Question 1

Biguanide antidiabetic drugs

Answer 1

Metformin

Phenformin

Question 2

Metformin - MoA

Answer 2

Decreases hepatic glucose output and glucose absorption from the gut. Reduces expression of genes for gluconeogenesis enzymes. Increases insulin sensitivity. Increases glucose uptake and usage in skeletal muscle & adipose tissue. Does NOT stimulate insulin secretion

Question 3

Metformin - Clinical use

Answer 3

DM2 (1st line) esp obese pt with insulin resistance, or with hyperlipideamia
Prediabetics

Question 4

Metformin - Special consideration and contraindications

Answer 4

May enable loss of weight
Duration of action: 18h
Used alone or in comb with a sulfonylurea, meglitinide, alpha gucosidase inh or incretin mimetic.
Contraind: renal/hepatic disease, alcoholism, predisposition for lactic acidosis

Question 5

Metformin - Adverse effects

Answer 5

GI disturbances: diarrhea (30%)
Lactic acidosis (rare)
Weight loss

Question 6

Metformin - Interactions

Answer 6

Cimetidine can inhibit metabolism of metformin

Question 7

Phenformin - MoA

Answer 7

Binds to mitochondria and interfere with glucose oxidation –>lactic acidosis

Question 8

Phenformin - Special consideration and adverse effects

Answer 8

NOT used: fatal lactic acidosis as risk!

Adverse: lactic acidosis

Question 9

Thiazolidinediones

Answer 9

Pioglitazone

Rosiglitazone

Question 10

Thiazolidinediones - MoA

Answer 10

Agonists of peroxisome proliferator-activated receptor-γ (PPAR- γ). Increases transcription of insulin responsive genes that control glucose metabolism (GLUT-4 transporters). Results in increased insulin sensitivity and decreased insulin resistance. Suppress hepatic glucose output

Question 11

Thiazolidinediones - Clinical use

Answer 11

Adjunct to diet & exercise for DM2. Pt unwilling to use injectable agents.

Question 12

Thiazolidinediones - Special considerations and Contraindications

Answer 12

Oral adm.
Greater effect on skeletal muscle and adipose tissue, lesser on liver.

Contraind: heart failure risk

Question 13

Thiazolidinediones - Adverse effects

Answer 13

Edema, increased risk of heart failure
Increased body weight
Decrease bone mineral density, increases risk of osteoporosis and fractures in older women

Question 14

Pioglitazone - MoA

Answer 14

Partial PPAR-receptor agonist

Question 15

Pioglitazone - Clinical use

Answer 15

DM2 who cannot control disease with other oral drugs/unwilling to use insulin

Question 16

Pioglitazone - Special considerations

Answer 16

Increased HDL and decreased triglycerides in serum more than rosiglitazone

Question 17

Pioglitazone - Adverse effects

Answer 17

18 % risk of MI, stroke or death

Study: increased risk of bladder cancer

Question 18

Rosiglitazone - MoA

Answer 18

Full PPAR-receptor agonist

Question 19

Rosiglitazone - Special considerations

Answer 19

Increased LDL in serum more than pioglitazone

Question 20

Rosiglitazone - Adverse effects

Answer 20

Increased risk for MI 43%.

Increased Cardiovascular death risk 64%.

Question 21

α-Glucosidase inhibitors

Answer 21

Acarbose

Miglitol

Question 22

α-Glucosidase inhibitors - MoA

Answer 22

Competitive inhibition of α-Glucosidase, delaying starch and disaccharide digestion. Also decreases glucose absorption. Decreases postprandial hyperglycemia

Question 23

α-Glucosidase inhibitors - Clinical use

Answer 23

DM2 (usually in combo with other oral antidiabetic)

Question 24

α-Glucosidase inhibitors - Special consideration

Answer 24

Adm at first bite of meal.

Question 25

α-Glucosidase inhibitors - Adverse effects

Answer 25

Increased Flatulence, abd bloating

Question 26

Acarbose - Interactions

Answer 26

Increases bioavailability of metformin

Question 27

Miglitol - Interactions

Answer 27

Decreased Iron absorption | Decreased Absorption of ranitidine and propranolol

Question 28

GLP-1 mimetics

Answer 28

``` Exenatide Liraglutide Albiglutide Dulaglutide Lixisenatide ```

Question 29

Incretin mimetics - MoA

Answer 29

Enhances effect of glucagon-like peptide-1 (GLP-1) Stimulation of glucose-dependent insulin secretion, increased uptake of glucose by muscle and fat tissue, decreased glucagon secretion, slowed gastric emptying, increased satiety, and decreased food intake.

Question 30

Incretin mimetics - Clinical use

Answer 30

DIA2, comb with sulfonylurea or metformin --> improve A1C values and decreases body weight.

Question 31

Exenatide - Special consideration

Answer 31

Adm subcutn twice daily. Once weekly injection. Monitor for abd pain

Question 32

Exenatide - Adverse effects

Answer 32

Mild-moderate nausea, pancreatitis (pt with hypertriglycidemia/ gallstones). Abdominal pain

Question 33

Liraglutide and Albiglutide - Administration

Answer 33

Adm subc once daily

Question 34

Liraglutide - Adverse effects

Answer 34

Dose-dependent & treatment-duration-dependent thyroid C-cell tumor (study). Increased Risk for pancreatitis

Question 35

Once weekly injected drugs

Answer 35

Exenatide, Albiglutide, Dulaglutide

Question 36

DPP-4 inhibitors

Answer 36

Sitagliptin Linagliptin Saxagliptin

Question 37

DPP-4 inhibitors - MoA

Answer 37

Increases GLP-1 levels: Stimulation of glucose-dependent insulin secretion, increased uptake of glucose by muscle and fat tissue, decreased glucagon secretion, slowed gastric emptying, increased satiety, and decreased food intake.

Question 38

DPP-4 inhibitors- Clincal use

Answer 38

DM2: improve glycemic control

Question 39

DPP-4 inhibitors- Special consideration

Answer 39

Well suited for old, frail people | Once daily oral adm

Question 40

DPP-4 inhibitors - Adverse effects

Answer 40

Joint and skeletal muscle pain Nasopharyngitis Rhinitis

Question 41

Sodium-glucose cotransporter 1 inhibitors

Answer 41

Canagliflozin Dapagliflozin Empagliflozin

Question 42

SGLT inhibitors - MoA

Answer 42

Inhibit SGL2: Decreased renal glucose reabsorption, Increased urinary glucose excretion, and lower blood glucose.

Question 43

SGLT inhibitors - Special consideration and Cotraindication

Answer 43

Efficacy dependent of glomerular filtration. Contraindication: pt with GFR <50mL/min

Question 44

SGLT inhibitors - Adverse effects

Answer 44

Weight loss, lower BP. Increased incidence of UTI and genital yeast infections (because increased urinary glucose and facilitate growth of bacteria). Volume depletion Diabetic ketoacidosis increased risk of osteoporosis and bone fractures (increased urinary calcium excretion)

Question 45

Canagliflozin and Dapagliflozin - Contraindication

Answer 45

Dehydration, heart failure, low BP, taking diuretics and ACE inhibitor.

Question 46

Canagliflozin and Dapagliflozin - Adverse effects

Answer 46

Acute renal injury (azotemia)

Question 47

Empagliflozin - Special consideration

Answer 47

Reduces progression to renal disease in DIA2 with high risk of cardiovascular event.

Question 48

Amylin analogue

Answer 48

Pramlintide acetate

Question 49

Amylin analogue - MoA

Answer 49

Antihyperglycemic effect Decreases Rate of rise of blood glucose by slowing gastric emptying (Slows the rate at which food is delivered from the stomach to the intestines ), suppressing glucagon secretion and glucose output by the liver, Decreases appetite --> weight loss

Question 50

Amylin analogue - Clinical use

Answer 50

Weight loss and glycemic control in DM. | DM1 and DM2 on insulin treatment.

Question 51

Pramlintide acetate - Adverse effect

Answer 51

Hypoglycemia (esp in coadministration with insulin) | Nausea, anorexia, headache

Question 52

Dopamine agonist

Answer 52

Bromocriptine

Question 53

Bromocriptine - MoA

Answer 53

Resets disturbed circadian rhythm and reduces hepatic glucose output and serum triglycerides and free fatty acids.

Question 54

Bromocriptine- Clincal use

Answer 54

Hyperprolactinemia, Parkinson disease. | Study: Decreases insulin resistance and A1C

Question 55

Bromocriptine - Special consideration

Answer 55

Decreased Dopamine cause disturbances in circadian rhythm and can lead to insulin resistance, obesity and diabetes. Should be taken with food

Question 56

Dopamine - Adverse effects

Answer 56

Nausea