ORAL HYPOGLYCEMIC agents

Question 1

groups included in oral drugs for DM:

Answer 1

1. biguanides
2. sulfonylurease
3. glinides/meglitinides
4. thiazolidinediones (insulin sensitizers)
5. alpha-glucosidase inhibitors
6. gliptins (incretin mimetics / DPP-4 inhibitors = dipeptidyl peptidase-4 inhibitors)
7. SGLT-2 inhibitors (sodium-glucose cotransporter 2)

Question 2

biguanides → drugs included:

Answer 2

1. metformin

2. phenformin

Question 3

biguanides → mechanism of action:

Answer 3

1. insulin SENSITIZER
2. activates AMP-kinase
3. decrease hepatic gluconeogenesis
4. increase glycolysis
5. increase peripheral glucose uptake & reduce glucose absorption from the GI-tract

Question 4

biguanides → pharmacokinetics:

Answer 4

1. NO hypoglycemia
2. NO weight gain
3. reduce microvascular risk
4. well absorbed from GI-tract
5. duration of action → 4 (phenformin)-12h (metformin)

Question 5

biguanides → indications:

Answer 5

1. initial drug of choice in DM2

2. experimental uses in other diseases with insulin resistance → PCOS, NAFLD, premature puberty

Question 6

biguanides → CONTRAindications:

Answer 6

1. kidney disease
2. heart disease
3. liver failure
4. resp. tract dysfunctions
5. should be discontinued in → acute MI, exacerbation of HF, sepsis, other that can cause acute renal failure
6. use with CAUTION → pat. >80y, HF & alcohol abuse

Question 7

biguanides → side effects:

Answer 7

1. GI-disturbances → diarrhea, cramps
2. lactic acidosis
3. decreased B12 & folate absorption (long-time usage)

Question 8

sulfonylurease → drugs included:

Answer 8

1st generation:

 1. tolbutamide
 2. chlorpropamide

2nd generation:

 1. glyburide
 2. glipizide
 3. gliclazide
 4. gliquidone

3rd generation:
1. glimepiride

Question 9

sulfonylurease → mechanism of action:

Answer 9

1. K-channel blockers on pancreatic beta-cells → stimulation of insulin release
2. may reduce hepatic glucose & increase peripheral insulin sensitivity

Question 10

sulfonylurease → pharmacokinetics:

Answer 10

1. well-absorbed from GI-tract
2. strong binding to plasma albumin
3. most excreted in urine
4. reduce microvascular risk
5. t1/2 = 4-12h

Question 11

sulfonylurease → indications:

Answer 11

1. DM2

2. glyburide → minimal transfer across placenta → alternative to insulin for diabetes in PREGNANCY

Question 12

sulfonylurease → CONTRAindications:

Answer 12

1. PREGNANCY (cross the placenta)
2. hepatic & renal insufficiency → acc. can cause hypoglycemia
3. renal impairment particular problem for glyburide → safer options = glipizide or glimepiride

Question 13

sulfonylurease → side effects:

Answer 13

1. increased appetite → weight gain
2. hyperinsulinemia
3. postprandial hypoglycemia
4. allergic skin reactions
5. bone marrow suppression

Question 14

glinides/meglitinides → drugs included:

Answer 14

1. meglitinide
2. repaglinide
3. nateglinide

Question 15

glinides/meglitinides → mechanism of action:

Answer 15

(same as for sulfonylurease but different binding sites)’

1. 1. K-channel blockers on pancreatic beta-cells → ONLY to SUR1 subunit
2. stimulation of insulin release

Question 16

glinides/meglitinides → pharmacokinetics:

Answer 16

1. very good absorption from GIT
2. fast elimination
3. excretion with bile (90%)
4. rapid onset (30 min → faster than sulfonylureases) & short duration of action
5. LOW risk of postprandial hypoglycemia

Question 17

glinides/meglitinides → indication:

Answer 17

postprandial hypoglycemia

Question 18

glinides/meglitinides → CONTRAindications:

Answer 18

1. concurrent use with sulfonylureas & gemfibrozil (lipid lowering drug)
2. caution → hepatic impairment

Question 19

glinides/meglitinides → side effects:

Answer 19

1. weight gain (lower than sulfonylureases)
2. postprandial hypoglycemia (lower than sulfonylureases)
3. frequent dosing schedule

Question 20

thiazolidinediones → drugs included:

Answer 20

1. pioglitazone
2. rosiglitazone
3. troglitazone

Question 21

thiazolidinediones → mechanism of action:

Answer 21

1. stimulation of nuclear receptors → peroxisome proliferative activated receptors (PPAR-gamma)
2. increased of insulin action
3. increased glucose utilization in peripheral tissues
4. decreased gluconeogenesis in the liver

Question 22

thiazolidinediones → pharmacokinetics:

Answer 22

1. effect after 1-4 weeks → max. effect after 6-8 weeks
2. NO hypoglycemia
3. lower BP
4. antioxidant properties
5. decrease of FFA & TG plasma levels, increases HDL
6. rosiglitazone → ↑ LDL, ↑ TG, ↑ HDL
7. pioglitazone → ↓ TG , ↑ HDL

Question 23

thiazolidinediones → indication:

Answer 23

1. 2nd or 3rd line treatment in DM2

2. PCOS (polycystic ovarian syndrome) → can cause ovulation to resume

Question 24

thiazolidinediones → CONTRAindications:

Answer 24

1. nursing mothers

2. severe HF

Question 25

thiazolidinediones → side effects:

Answer 25

1. troglitazone → hepatoxicity
2. rosiglitazone → cardiovascular risks, increase in LDL
3. pioglitazone → increased risk of bladder cancer
4. weight gain (water retention)
5. edema, HF (water retention)
6. osteopenia → increased risk of fractures

Question 26

alpha-glucosidase inhibitors → drugs included:

Answer 26

1. acarbose
2. miglitol
3. voglibose

Question 27

alpha-glucosidase inhibitors → mechanism of action:

Answer 27

1. inhibit α-glucosidase enzymes → delay digestion of carbohydrates → ↓ postprandial glucose level
2. postprandial rise in plasma glucose decrease in both normal & diabetic subjects

Question 28

alpha-glucosidase inhibitors → pharmacokinetics:

Answer 28

1. acarbose → poorly absorbed
2. miglitol → well absorbed
3. effects → may depend on intestinal microflora changes
4. when given ALONE → no risk of hypoglycemia
5. overall effect = small!!

Question 29

alpha-glucosidase inhibitors → CONTRAindications:

Answer 29

1. IBD = inflammatory bowel disease

2. colonic ulcerations Intestinal obstruction

Question 30

alpha-glucosidase inhibitors → side effects:

Answer 30

1. GI-tract disturbances → flatulence, loose stools & diarrhea, bloating, cramps
2. limits the use of these agents in clinical practice

Question 31

gliptins → drugs included:

Answer 31

1. alogliptin
2. sitagliptin
3. linagliptin
4. saxagliptin

Question 32

gliptins → mechanism of action:

Answer 32

1. inhibitor of DPP-4 (resp. for inactivation of incretin) → potentiates GLP-1
2. prolonged activity of incretin → ↑ insulin release (meal) & ↓ inappropriate secretion of glucagon

Question 33

gliptins → pharmacokinetics:

Answer 33

1. ORALLY

2. recommendations are monotherapy or combined with metformin/thiazolidinediones

Question 34

gliptins → indication:

Answer 34

DM2

Question 35

gliptins → CONTRAindications:

Answer 35

1. hepatic/renal impairment
2. pregnancy/lactation
3. angioedema/urticaria
4. hypersensitivity
5. ketoacidosis
6. DM1

Question 36

gliptins → side effects:

Answer 36

1. UTI’s
2. resp. tract infections → headache, sinusitis
3. diarrhea
4. pancreatitis
5. NO hypoglycemia

Question 37

SGLT-2 inhibitors → drugs included:

Answer 37

1. canagliflozin

2. dapaglifozin

Question 38

SGLT-2 inhibitors → mechanism of action:

Answer 38

1. inhibition of the sodium-glucose cotransporter 2 (SGLT-2) → ↓ reabsorption of glucose, ↑ urinary glucose excretion, ↓blood glucose
2. causes proximal diuresis (decrease the reabsorption of glucose in the proximal convoluted tubule) + calorie leakage → into urine

NO hypoglycemia

weight reduction

BP reduction (due to decreased reabsorption of sodium → leads to osmotic diuresis → decreased BP)

Question 39

SGLT-2 inhibitors → indication:

Answer 39

DM2

Question 40

SGLT-2 inhibitors → CONTRAindication:

Answer 40

renal dysfunction

Question 41

SGLT-2 inhibitors → side effects:

Answer 41

1. increased risk of genitourinary infections (UTI’s)
2. polyuria
3. hypotension (volume depletion), dizziness
4. increased LDL
5. increased creatinine (transient)