Drugs For Type 2 DM Flashcards
What are the 2 insulin secretagogues drugs
Sulphonylureas ( Glyburide)
Meglitinide ( Repaglinide)
What is the MOA of Glyburide and Repaglinidine
Bind to ATP sensitive K+ channel → prevent K+ efflux → K+ accumulates → activates depolarization → stimulate insulin containing vesicles → release of insulin
PK for Glyburide and Repaglinidine
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
AE & CI for Glyburide and Repaglinidine
Glyburide
1. Hypoglycemia
2. Weight gain
3. Secondary resistance
Repaglinide
CI: pregnant, hepatic or renal insufficiency
What are the 2 Insulin Sensitizers
Biguanides ( Metformin)
Thiazolidinediones (Rosiglitazone)
MOA of Metformin
Impairs mitochondrial respiration → reduced ATP generation → AMP accumulates → activation of AMP kinase → gene expression
Clinical Use of Metformin
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
AE & CI Of Metformin
Diarrhoea, dyspepsia, lactic acidosis
CI: heart failure,
hypoxia, renal failure, lung disease, liver disease
MOA of Rosiglitazone
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
PK of Rosiglitazone
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
Clinical use of Rosiglitazone
Improve insulin sensitivity
● Increase expression of GLUT4 → increase glucose uptake
● Change in fat metabolism
● Redistribution of fat
AE & CI of Rosiglitazone
Fluid retention, hepatotoxicity, weight gain
CI: heart failure, hepatic failure, pregnancy
What drug Reduces intestinal carb absorption
Alphaglucosi dase inhibitor (Acarbose)
MOA of Acarbose
Competitively inhibits intestinal membrane bound alpha-glucosidases → inhibits glucose absorption → starch blocker
PK of Acarbose
Relatively weak antidiabetic effect
*Taken at the start of main meals to have maximal inhibition of glucose absorption
Clinical Use of Acarbose
Decrease postprandial glucose
AE of Acarbose
Flatulence, diarrhoea, abdominal pain
Drugs that increase glucose excretion
SGLT inhibitor (Dapagliflozin)
Drugs acting via GLP-1 ( Sitagliptin, Exenatide)
Amylin analogue (Pramlintide)
MOA of SGLT inhibitor (Dapagliflozin)
Blocks SGLT-2 → prevents reabsorption of filtered glucose
(Sodium glucose transporter inhibitors)
Clinical Use of SGLT Inhibitor (Dapagliflozin)
● Elimination of glucose through the urine
● Eliminates water by osmotic diuresis → lowers BP
AE of SGLT Inhibitor (Dapagliflozin)
Higher risk of UTI
MOA of Drugs acting via GLP-1 (Sitagliptin, Exenatide)
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
PK of Sitagliptin
Well absorbed in GIT, excreted unchanged in the urine
(DPP-4 inhibitor)
Clinical Use of Sitagliptin
Enhances the availability of endogenous GLP-1 incretin hormones
AE of Sitagliptin
Headache, diarrhoea, increased risk of pancreatitis
Clinical use of Exenatide
Act as agonist at GLP-1 receptors
Incretin mimetic
AE of Exenatide
Increased risk of pancreatitis
PK of Pramlintide ( Amylin Analogue)
S.c injection immediately before major meals
Clinical Use of Pramlintide ( Amylin Analogue)
Used for T1D and T2D
● Prolongs gastric emptying time
● Reduces postprandial glucagon secretion
● Reduces food intake (through appetite
suppression)
AE of Pramlintide ( Amylin Analogue)
Nausea, anorexia, vomiting
What does GLP 1 do
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.
