A. 14- oral antidiabetics

Question 1

Classify the non-insulin antidiabetic agents

Answer 1

1. insulin secretagogues
2. biguanides
3. thiazolidinediones
4. agents affecting the endogenous incretin system
5. SGLT-2 inhibitors
6. 𝝰- glucosidase inhibitors
7. amylin mimetics
8. bile acid sequestrants
9. dopamine agonists

Question 2

mechanism of insulin secretagogues

Answer 2

1. closure of K channels in pancreatic B cells–> membrane depolarization–> Ca² influx triggers insulin release, glucagon release from 𝝰-cells ↓
2. continuous use of sulfonylureas enhances tissue response to insulin (especially muscle and liver) via changes in receptor function

Question 3

how are insulin secretagogues given?

Answer 3

oral

Question 4

give examples for insulin secretagogues

Answer 4

sulfonylurea 1st generation: tolbutamide
sulfonylurea 2nd generation: glimepiride, glipizide
meglitinide analogs: repaglinide

Question 5

difference between 1st and 2nd sulfonylureas?

Answer 5

1st is more toxic, 2nd is more potent

Question 6

indication for Sulfonylureas and meglitinide analogs

Answer 6

type 2 DM

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Question 7

SE of sulfonylurea

Answer 7

weight gain, hypoglycemia, rash, sulfonamide hypersensitivity reaction, ↑ cardiovascular risk

Question 8

SE of meglitinide

Answer 8

hypoglycemia

no sulfonamide hypersensitivity reaction!

Question 9

drug interactions with 1st generation sulfonylureas

Answer 9

cimetidine, insulin, and sulfonamides can induce hypoglycemia

Question 10

mechanism of biguanides (metformin)

Answer 10

1. activates AMP kinase–> reduces hepatic and renal gluconeogenesis–> post-prandial and fasting glucose levels ↓
2. intestinal glucose absorption ↓
3. insulin sensitivity ↑

Question 11

indications for metformin

Answer 11

type 2 DM
PCOS with insulin resistance- restore fertility
weight reduction in non-diabetic patients with obesity
hyperinsulinemia (obese patients)

Question 12

SE of metformin

Answer 12

GI symptoms
lactic acidosis (in patients with impaired renal/hepatic function)
AKI in patients receiving IV iodine contrast agents (stop 1 day before examination)
does not cause hypoglycemia!!

Question 13

mechanism of thiazolidinediones (e.g Rosiglitazone)

Answer 13

activate PPAR- ɣ:

1. ↑ GLUT 4 expression in muscle and AT–> ↑ glucose uptake
2. hepatic gluconeogenesis ↓
3. positive effect on lipid metabolism
4. adiponectin ↑ –> ↑ insulin sensitivity and fatty acid oxidation

Question 14

indication for Rosiglitazone

Answer 14

type 2 DM

Question 15

SE of rosiglitazone

Answer 15

weight gain, edema, anemia, hepatotoxicity

Question 16

contraindication for rosiglitazone

Answer 16

CHF and liver disease

Question 17

agents affecting the endogenous incretin system?

Answer 17

GLP-1 ( liraglutide, exenatide)

DPP-4 (vildagliptin)

Question 18

what is the effect of GLP-1 analogs and DPP-4 inhibitors?

Answer 18

insulin release ↑
glucagon release ↓
delayed gastric emptying 
satiety 
*DPP-4 inhibits incretin hormones released from endocrine cells in the small intestine in response to food. DPP-4 inhibitors release incretins

Question 19

how is Liraglutide given?

Answer 19

parenteral (daily)

Question 20

how is exenatide given?

Answer 20

parenteral (weekly)

Question 21

Indications for liraglutide

Answer 21

type 2 DM (Monotherapy or in combination)

weight loss

Question 22

SE of liraglutide

Answer 22

GI symptoms
nausea
acute pancreatitis

Question 23

indication for vildagliptin?

Answer 23

type 2 DM (monotherapy or in combination)

Question 24

SE of vildagliptin

Answer 24

headache, nasopharyngitis, upper respiratory tract infections

Question 25

mechanism of SGLT2 inhibitors (Dapagliflozin)

Answer 25

inhibit Na-glucose transporter in the PCT–> glucosuria–> blood glucose level ↓

Question 26

indications for dapagliflozin and canagliflozin

Answer 26

type 2 DM
CHF
type 1 DM–> combine with insulin in obese patients

Question 27

MOST IMPORTANT SE in dapagliflozin

Answer 27

genitourinary infections!!

Question 28

mechanism 𝝰- glucosidase inhibitors (acarbose)

Answer 28

inhibit the 𝝰- glucosidases in the intestinal brush border–> ↓ disaccharides degradation–> ↓ glucose absorption

Question 29

SE of acarbose

Answer 29

hypoglycemia

diarrhea and abdominal pain

Question 30

mechanism of amylin mimetics (pramlintide)

Answer 30

functions as a synergistic partner to insulin:

1. glucagon release ↓
2. delayed gastric emptying
3. suppress appetite

Question 31

pramlintide indication

Answer 31

type 1 DM

type 2 DM

Question 32

why is colesevelam given in type 2 DM ?

Answer 32

lowers glucose through unknown mechanisms

Question 33

why is bromocriptine given in type 2 DM?

Answer 33

lowers glucose through unknown mechanisms

Question 34

hypoglycemia value

Answer 34

<3.9 mmol/l

Question 35

agents controlling hypoglycemia

Answer 35

glucose IV (15-20g) 
glucgon parenteral 
diazoxide (oral or parenteral) 
octreotide (paranteral) 
streptozocin

Question 36

indication for giving glucose

Answer 36

hypoglycemia not associated with water loss or electrolyte imbalances

Question 37

indication for glucagon

Answer 37

acute hypoglycemia
management of severe β-blocker
*problem: can only act if there is glucagon in the liver or muscle

Question 38

indications for diazoxide

Answer 38

hypoglycemia caused by insulinoma

hypertensive emergency

Question 39

indication of octreotide

Answer 39

hypoglycemia caused by insulinoma

Question 40

indication for streptozocin

Answer 40

malignant pancreatic insulinoma