Anti Diabetic

Question 1

Insulin - genetically engineered recombinant human insulin to limit allergic reactions
Parenterally administered (IM, IV for acute emergencies such DKA)

Answer 1

Rapid acting:
LISPRO, ASPART - prevent dimer formation as monomers are more active

Intermediate acting:
NPH (neutral protamine hagedorn); ISOPHANE - insulin is precipitated in micro crystals to decrease its solubility

Long acting (basal insulin, no peak): 
GLARGINE; zinc formulations to produce aggregrates to decrease solubility

Question 2

Biguanide

Answer 2

Metformin - 1st line for type2

MOA:
actions on mitochondria of hepatocytes to increase AMP:ATP ratio to active AMPK (AMP dependant protein kinase)
(1) inhibit Adenylate Cyclase activity to inhibit glucagon pathway
(2) improved insulin receptor function/sensitivity hence potentiate residual insulin activity
(3)delays carbohydrate absorption, suppress apetite to encourage weight loss
(4)promote gene transcription for glucose uptake in skeletal muscle, adipose and liver;
(5) fatty acid oxidation and reduced synthesis of LDL and VLDL - reduced risk of atherosclerosis;

Question 3

Sulphonureas

Answer 3

Glipzide, Tolbutymide, Chromopromide

MOA:

Block ATP dependate k channel to cause depolarisation
influx of Calcium cause CICR to promote exocytosis of insulin containing vesicles

Used in early type2 DM

Side effects:
severe hypoglycaemia
appetite stimulating - weight gain

Question 4

Glitazones

Answer 4

PIOGLITAZONE

MOA:
PPAR - gamma agonist
promote transcription of genes involved in insulin signalling (e.g GLUT4 to increase glucose uptake in muscles, fatty acids transporters to reduce FFA concentrations, lipoprotein lipase)

Used as additive to Metformin or Exogenous insulin to reduce dosage

Side effects: Weight gain, fluid retention, linked with bladder cancer, heart failure and osteoporosis

Question 5

Acarbose

Answer 5

MOA:
alpha glucosidase inhibitor
delays carbohydrates absorption in small intestine
reduce glucose spike post prandial

Used as additive to Metformin or Exogenous insulin to reduce dosage

Side effects: diarrhoea and flatulence

Question 6

Incretins memetics

Answer 6

Incretins include GIP (glucose dependant insulinotrophic peptides - K cells) and GLP1 (glucagon peptide 1 - L cells). Incretins promote insulin release and inhibit glucagon pathway

Exenatide: amino acids changes from incretins to prevent DDP4 cleavage. Give twice daily. Nauzea as side effect

Exenatide LAR: Long acting of duration by binding to polymer microspheres. Given Weekly, less nauzea

Liraglutide: Additional fattly side chain to prevent albumin binding and renal clearance to increase duration of action

Question 7

DDP4 inhibitors - GLIPTINS

Answer 7

Sitagliptin-well tolerated, weight neutral
vildagliptin -associated with RTIs and headaches

MOA
Enhance endogenous incretin levels
increasing 1st phase insulin response (absent in Type 2 DM)