Hypoglycemic drugs

Question 1

Insulin sensitisers: 2 names, general MOA

Answer 1

Metformin, pioglitazone

Increase insulin sensitivity by increasing expression of receptors, without increasing insulin amount directly

Question 2

Metformin: Class, indications, moa, adr, contraindications

Answer 2

Insulin sensitizer (Biguanide)
FIRST LINE FOP T2D!
Increase density of insulin receptors in tissues, decrease intestinal glucose absorption but increase muscular glucose absorption
Metallic taste
Lowers basal and prandial plasma glucose
Take with or after meals to avoid GIT effects
B12 malabsorption and deficiency
Lactic acidosis

Question 3

Pioglitazone: Class, indications, moa, adr, contraindications

Answer 3

Insulin sensitizer (thiazolidinediones)
Activate PPAR-y, increase GLUT1 and GLUT4 production to enhance tissue sensitivity
Fluid retention -weight gain, edema, HF
Bone fractures *osteoporotic patients
CYP450 INDUCER, be careful with oral contraceptives

Question 4

Insulin secretagogues: 2 classes, general MOA

Answer 4

Sulfonylureas, meglitinides

Target ATP-sensitive potassium channel in b cells, to enhance insulin-release pathway

Question 5

2nd gen sulfonylureas: Class, names, moa, adr, contraindications

Answer 5

Insulin secretagogues
Glipizide, gliclazide
Targets ATP-sensitive potassium channels in B cells, inhibits K+ efflux to trigger the Ca2+ influx-dependent exocytosis
Weight gain
Though lower hypoglycemic risk than 1st gen, clibenclamide still has risk
Sulfa allergy, hepatic, renal impairment

Question 6

Meglitinides: Class, names, indications, moa, advantage, contraindications

Answer 6

Insulin secretagogues
Repaglinide, nateglinide
Targets AT-sensitive potassium channels in B cells in a glucose-dependent manner
*Similar moa to sulfonylureas, just more rapid onset and shorter DOA hence better for prandial use
Lower risk of hypoglycemia because insulin release is glucose-dependent
Hepatic impairment

Question 7

Acarbose: Class, indication, moa, adr, contraindications

Answer 7

a-glucosidase inhibitor
Not a preferred choice bc of side effects
a-glucosidase enzymes include amylase, maltase, sucrase, isomaltase found on small intestine villi, all hydrolyse oligosaccharides to simple sugars
Reversible inhibitor: for prandial use
Administered with food (hence not absorbed)
Remaining undigested carbohydrates digested by gut bacteria, may cause gaseous distension
IBD, renal, hepatic disease

Question 8

Incretin-based therapy: 2 classes, general MOA, advantage

Answer 8

Dipeptidyl peptidase 4 inhibitors, GLP-1 receptor agonist
Target hormonal side (incretins) which lower insulin secretion in a glucose-dependent manner. Both are rapidly inactivated by dipeptidyl peptidase 4.
Advantage is that they work in a glucose-dependent manner, low risk of hyperglycemia

Question 9

2 naturally-occuring incretins

Answer 9

Glucagon-like peptide 1 (GLP-1)

Glucose-dependent insulinotropic polypeptide (GIP)

Question 10

Dipeptidyl peptidase 4 inhibitors: Class, suffix, moa, adr, advantage and disadvantage

Answer 10

Incretin-based therapy
“-liptin”
Dipeptidyl peptidase 4 inactivates incretins. Inhibitors prolong action of incretins, increase insulin secretion and decrease glucagon secretion
GIT effects, flu-like symptoms, skin reactions (pt with pancreatitis)
Expensive, but no dose adjustment needed for those w chronic kidney disease

Question 11

GLP1 receptor agonist: Class, names, indications, administration, moa, adr, contraindications, disadvantage

Answer 11

Incretin-based therapy
Exenatide, liraglutide
Act on receptors of B cells in the presence of glucose
SUBQ INJECTION
Can help with weight loss, heart failure *OBESE PATIENTS
Initial rapid release of insulin and glucagon suppression. Delay gastric emptying, reduce appetite
GIT effects (pt w pancreatitis)
Expensive

Question 12

Which classes of drugs act in a glucose-dependent manner? What is the advantage?

Answer 12

Meglitinides, DP4 inhibitors, GLP1 Agonists

Lowest risk of hypoglycemia

Question 13

SGLT2 Mechanism of action

Answer 13

Expressed in PCT, low affinity, high capacity glucose transporter
Responsible for 90% of reabsorption of filtered glucose

Question 14

SGLT2 inhibitors: Suffix, moa, adr, advantages, contraindications

Answer 14

“-agliflozin”
Reduce reabsorption of filtered glucose, lower renal threshold for glucose, increase glucose excretion
Benefits for HF from atherosclerosis and renal disease
UTI!!!!, polyuria
Canagliflozin- increased risk of lower limb amputation

Question 15

Which is the only class of drug administered via subq?

Answer 15

GLP1R agonists

Question 16

Which classes of drugs are suitable for patients with CVS disease?

Answer 16

SGLT2 inhibitors, GLP1 agonists