Drugs For Type 2 DM

Question 1

What are the 2 insulin secretagogues drugs

Answer 1

Sulphonylureas ( Glyburide)
Meglitinide ( Repaglinide)

Question 2

What is the MOA of Glyburide and Repaglinidine

Answer 2

Bind to ATP sensitive K+ channel → prevent K+ efflux → K+ accumulates → activates depolarization → stimulate insulin containing vesicles → release of insulin

Question 3

PK for Glyburide and Repaglinidine

Answer 3

Glyburide
1. Binds tightly to plasma protein,
2. metabolised by cytochrome P450,
3. excreted by liver and kidney
4. Hypoglycemic action may increase if taken with Salicylates and Warfarin

Repaglinide
1. Rapid Absorption
2. Very fast onset of action
3. Short duration of action
4. Taken for Pt. with sulfonylurea allergy
5. Not effective in decreasing random glucose
6. Given just before meal

Question 4

AE & CI for Glyburide and Repaglinidine

Answer 4

Glyburide
1. Hypoglycemia
2. Weight gain
3. Secondary resistance

Repaglinide
CI: pregnant, hepatic or renal insufficiency

Question 5

What are the 2 Insulin Sensitizers

Answer 5

Biguanides ( Metformin)
Thiazolidinediones (Rosiglitazone)

Question 6

MOA of Metformin

Answer 6

Impairs mitochondrial respiration → reduced ATP generation → AMP accumulates → activation of AMP kinase → gene expression

Question 7

Clinical Use of Metformin

Answer 7

Drug of choice
Does not cause hypoglycemia in large doses.
Promotes weight loss
● Increase insulin sensitivity
● Increase uptake of glucose
● Increase fatty acid uptake and oxidation
● Decrease intestinal absorption of glucose
● Decrease hepatic output of glucose

Question 8

AE & CI Of Metformin

Answer 8

Diarrhoea, dyspepsia, lactic acidosis

CI: heart failure,
hypoxia, renal failure, lung disease, liver disease

Question 9

MOA of Rosiglitazone

Answer 9

Bind to receptor PPAR-gamma → activate receptor → migration of drug receptor complex to the DNA → activation of transcription of genes in glucose and f.a. metabolism

Question 10

PK of Rosiglitazone

Answer 10

Rapidly absorbed, highly protein bound, metabolised in the liver, slow onset and offset of action (weeks - months)
*Slow because expression of genes, proteins and cell function takes time

Question 11

Clinical use of Rosiglitazone

Answer 11

Improve insulin sensitivity
● Increase expression of GLUT4 → increase glucose uptake
● Change in fat metabolism
● Redistribution of fat

Question 12

AE & CI of Rosiglitazone

Answer 12

Fluid retention, hepatotoxicity, weight gain
CI: heart failure, hepatic failure, pregnancy

Question 13

What drug Reduces intestinal carb absorption

Answer 13

Alphaglucosi dase inhibitor (Acarbose)

Question 14

MOA of Acarbose

Answer 14

Competitively inhibits intestinal membrane bound alpha-glucosidases → inhibits glucose absorption → starch blocker

Question 15

PK of Acarbose

Answer 15

Relatively weak antidiabetic effect
*Taken at the start of main meals to have maximal inhibition of glucose absorption

Question 16

Clinical Use of Acarbose

Answer 16

Decrease postprandial glucose

Question 17

AE of Acarbose

Answer 17

Flatulence, diarrhoea, abdominal pain

Question 18

Drugs that increase glucose excretion

Answer 18

SGLT inhibitor (Dapagliflozin)
Drugs acting via GLP-1 ( Sitagliptin, Exenatide)
Amylin analogue (Pramlintide)

Question 19

MOA of SGLT inhibitor (Dapagliflozin)

Answer 19

Blocks SGLT-2 → prevents reabsorption of filtered glucose
(Sodium glucose transporter inhibitors)

Question 20

Clinical Use of SGLT Inhibitor (Dapagliflozin)

Answer 20

● Elimination of glucose through the urine
● Eliminates water by osmotic diuresis → lowers BP

Question 21

AE of SGLT Inhibitor (Dapagliflozin)

Answer 21

Higher risk of UTI

Question 22

MOA of Drugs acting via GLP-1 (Sitagliptin, Exenatide)

Answer 22

Increase insulin secretion and reduce appetite
GLP-1 binds to the receptor and activates adenylate cyclase → increases cAMP conc. → antidiabetic effect kicks in only when glucose levels are high

Question 23

PK of Sitagliptin

Answer 23

Well absorbed in GIT, excreted unchanged in the urine

(DPP-4 inhibitor)

Question 24

Clinical Use of Sitagliptin

Answer 24

Enhances the availability of endogenous GLP-1 incretin hormones

Question 25

AE of Sitagliptin

Answer 25

Headache, diarrhoea, increased risk of pancreatitis

Question 26

Clinical use of Exenatide

Answer 26

Act as agonist at GLP-1 receptors

Incretin mimetic

Question 27

AE of Exenatide

Answer 27

Increased risk of pancreatitis

Question 28

PK of Pramlintide ( Amylin Analogue)

Answer 28

S.c injection immediately before major meals

Question 29

Clinical Use of Pramlintide ( Amylin Analogue)

Answer 29

Used for T1D and T2D
● Prolongs gastric emptying time
● Reduces postprandial glucagon secretion
● Reduces food intake (through appetite
suppression)

Question 30

AE of Pramlintide ( Amylin Analogue)

Answer 30

Nausea, anorexia, vomiting

Question 31

What does GLP 1 do

Answer 31

GLP-1 is secreted from the L-cells in the jejunum and ileum. It slows gastric emptying, reduces food intake, suppresses glucagon secretion and stimulates insulin secretion. It may also increase beta-cell cell mass and maintain beta-cell efficiency.