Oral Hypoglycaemic and Insulin

Question 1

Oral hypoglycaemic indications

Answer 1

Hyperglycaemia in diabetes mellitus type II

Question 2

Treatment for type II diabetes

Answer 2

Trial diet and exercise and then start metformin, titrate up dose, add sulfonylurea (dual therapy), then try acarbose, glitazone, DDP4 (dual with either previous) or incretin mimetic (dual or triple). Finally parenteral insulin may be required, combo with above drugs.

Question 3

Cellular pharmacodynamics metformin

Answer 3

Metformin suppresses hepatic gluconeogenesis and GI glucose absorption, and increases insulin sensitivity and peripheral glucose uptake (at least partially though upregulating AMPK).

Question 4

Sulfonyreas cellular pharmacodynamics

Answer 4

block pancreatic β-cells hyperpolarising via ATP-dependent K+ channels, depolarising and allowing calcium entry, and thus potentiating normal glucose-stimulated proinsulin release.

Question 5

Meglitinides (glinides) cellular pharmacodynamics

Answer 5

Are functionally similar to sulfonyreus (different binding site) but act quicker and last shorter

Question 6

Acarbose cellular pharmacodynamics

Answer 6

Acarbose inhibits a carbohydrate digesting brush border enzyme in the SI delaying glucose absorption.

Question 7

Glitazones cellular pharmacodynamics

Answer 7

Glitazones activate PPARγ, upregulating genes that reduce insulin resistance and inhibit hepatic gluconeogenesis.

Question 8

Incretin mimetics cellular pharmacodynamics

Answer 8

Incretin mimetics are long acting functional analogues of the ‘incretin’ GI hormones GLP-1 and GIP, which stimulate pancreatic β-cells and inhibit α-cells while blood glucose is high (response is reduced in diabetes). Also slow gastric emptying and cause satiety.

Question 9

DPP-4 inhibitors cellular pharmacodynamics

Answer 9

DPP-4 inhibitors (Incretin enhancers) prevent degradation of incretins.

Question 10

Oral hypoglycaemics systemic pharmacodynamics

Answer 10

Hypoglycaemic, improving symptoms of diabetes, and reducing amount of insulin required

Question 11

Oral hypoglycaemics dosing

Answer 11

Oral agents (take with food). Incretin mimetics by subcutaneous injection (oral version in trials)

Question 12

Contrainducations oral hypoglycaemics

Answer 12

Hypersensitivity, renal/hepatic failure, pregnancy (use insulin).

Question 13

Contraindications glitazones

Answer 13

heart failure, cardiac disease;

Question 14

Contraindications metformin

Answer 14

Prior to surgery (dehydration), acidosis

Question 15

Contraindications sulfonylureas

Answer 15

stress conditions (hypoglycaemic)

Question 16

Contraindications acarbose

Answer 16

GI disease

Question 17

Oral hypoglycaemics adverse drug reactions

Answer 17

• Hypoglycaemic (especially secretagogues)
• Weight gain (secretagogues and glitazones)
• Weight loss (incretins, metformin)
• GI symptoms (metformin, secretagogues, incretin mimetics)

Question 18

Metformin adverse drug reactions

Answer 18

Lactic acidosis

Question 19

Adverse drug reactions glitazones

Answer 19

• Fluid retention - worsening HF, CHD
• Fractures

Question 20

Adverse drug reactions acarbose

Answer 20

Flatulence, bloating

Question 21

Adverse drug reactions incretin mimetics

Answer 21

Pancreatitis

Question 22

Adverse drug reactions DPP-4 inhibitors

Answer 22

CNS symptoms

Question 23

Insulin indications

Answer 23

Diabetes mellitus, type I and II (after trialling oral hypoglycaemics)

Question 24

Insulin comparison

Answer 24

When moving type II diabetic on to insulin, maintain oral therapy but drop back to metformin + sulfonylurea and drop dose of these.

Question 25

Cellular pharmacodynamics of insulin

Answer 25

Various formulations of the hormone insulin physiologically produced by pancreatic β-cells. Bind to insulin receptors (tyrosine kinase) on muscle and adipose tissue cells causing phosphorylation of IRS-1 which acts as a secondary messenger. Causes translocation of GLUT4 to plasma membrane, allowing glucose entry to cell. Also, upregulates glycogenesis, amino acid uptake, lipid uptake, fatty acid esterification and potassium uptake; and inhibits proteolysis, gluconeogenesis and lipolysis.

Question 26

Systemic pharmacodynamics insulin

Answer 26

Reduces elevated blood glucose levels to normal (physiologically, postprandially)

Question 27

Dosing of insulin

Answer 27

Parenteral only. Pen injectors (easy to use, don’t require drawing up dose), syringes (cheap) and implantable pumps (expensive, infection) are available. Insulin regimens should be tailored to the individual to maintain a compromise between simplicity and tight glycaemic control. For example, the ‘basal-bolus’ regimen involves administering a very short acting immediately prior to meals and an intermediate/long before bed. Alternatively a premix may be used, eg. 70% of dose in morning to cover breakfast and day and the final dose to cover dinner and night.

Question 28

Contraindications insulin

Answer 28

Hypersensitivity used to be an issue, now recombinant human insulin used; hypoglycaemia

Question 29

Adverse drug reactions insulin

Answer 29

Hypoglycaemia (shaking, sweating, dizziness, headache -> acute brain damage) due to excessive dose or forgetting to eat, hyperglycaemia (thirst, polyuria, nausea, dry skin) due to insufficient dose or rebound (compensatory catecholamine, cortisol release, esp. at night), allergy