Diabetes pharmacology

Question 1

Diabetes

Answer 1

chronic metabolic condition

elevated blood glucose levels

Question 2

The 3 ps of diabetes

Answer 2

• Polydipsia- excessive thirst
• Polyuria - Excessive urination
• Polyphagia - Extreme hunger

Question 3

Diagnosis of diabetes mellitus

Answer 3

Hyperglycaemia

Blood gas:
FPG- 5.6-6.9mmol/L
2hr PG - 7.8-11.0mmol/L
HbA1c - > or equal to 48mmol/L

Question 4

Pancreas and blood glucose

Answer 4

Glucagon- Increases blood glucose levels

Insulin- Decreases blood glucose levels

Question 5

Insulin

Answer 5

Protein that consists of 2 polypeptide chains:
A chain 21 amino acids
B chain 30 amino acids

Porcine or bovine source of insulin - elicits immune response
Genetically engineered human insulin

Question 6

Insulin

Answer 6

Increased glucose levels signals the B cells in pancreas to secrete insulin.

Insulin promotes the exit of glucose from the blood stream

Question 7

Pharmacodynamic action of insulin

Answer 7

• Insulin binds to specific insulin receptors on the surface of target cells, primarily in muscle, fat, and liver tissue.
• This binding activates the insulin receptor tyrosine kinase
• GLUT4 is a glucose transporter that helps move glucose from the bloodstream into the cells.
• In response to insulin, GLUT4 is translocated (moved) from internal storage vesicles to the cell membrane. Once on the cell surface, GLUT4 allows glucose to enter the cell from the blood. This process is crucial for lowering blood glucose levels after meals.

Question 8

Once glucose is inside of the cell

Answer 8

Glycogenesis- Glucose –> glycogen

Fat storage-Insulin promotes the storage of fat by encouraging lipogenesis (the formation of fatty acids and triglycerides) and inhibiting lipolysis (the breakdown of fat).

ATP- used for the the production of ATP for energy release.

Question 9

Classification of diabetes
Type 1 DM:

Answer 9

Type 1 DM:

Gestational diabetes

Question 10

Classification of diabetes
Type 2 DM:

Answer 10

Other causes e.g.
pancreatic disease, cystic
fibrosis, drug/chemicalinduced (steroids),
monogenic diabetes

Question 11

What is type 1 DM

Answer 11

Lack of insulin secretion
Autoimmune destruction of B cells
Treatment: Exogenous insulin administration

Question 12

What is type 2 diabetes

Answer 12

Insulin resistance (low number of receptors)

Treatment:
Lifestle adjustment (healthy diet, smoking
cessation, regular physical activity) - try to reduce BMI as reduction leads to increase insulin receptors
Oral ant-diabetic drugs: Metformin (first line medication)

Question 13

Diabetes complications

Answer 13

Eyes- retinopathy, cataracts

Kidneys- Nephropathy

PNS- Neuropathy

Brain- Stroke

Heart- Coronary heart disease

Extremities- Peripheral vascular damage, reduced blood flow, reduced healing–> Gangrene, foot ulcers

Question 14

Insulin replacement therapy

Answer 14

Given once or twice a day
slow acting or fast acting or mixture
Available as pre filled pen dispensing systems or in vials that need to be drawn up using sub cut syringes

Frequent Blood glucose checks

Risk of hypoglcaemia

Administered subcutanoeusly

Question 15

Target sites for different oral drug classes used in Type 2
diabetes post-metformin

Answer 15

Sulphonylureas,Non-SU secretagogues,GLP-1 which target pancreatic Beta cells to increase insulin secretion

Biguanides, TZDs - Target the liver to decrease glucose production

Dipeptidyl peptidase 4 (DPP4) inhibitors (“Gliptins”) which targets the gut to enhance the level of active incretin hormones.
ALso Alpha-glucosidase inhibitors delay intestinal carbohydrate absorption.

SGLT2 inhibitors (“flozins”)- targets the kidney which allows for inhibition of glucose reabsorption in the kidney

TZDs which target muslce and adipose tissues which increase glucose uptake

Question 16

Diabetes type 2 meds oral hypoglycaemic agents

Answer 16

• Medication aims to increase insulin secretion
  Examples: Tolbutamide, Glibenclamide (sulphonulureas)

Question 17

Pharmacodynamics of Sulphonylureas

Answer 17

Promote insulin secretion from β-cells in the pancreas.
* Sensitise β-cells to glucose.
* Limits glucose production in the liver.
* Decreases liver insulin clearance.

Question 18

Pharmacokinetics of sulphonylureas

Answer 18

Glibenclamide
Liver metabolism
Half life: 10 hours
Excretion Renal/Biliary

Tolbutamide
Liver metabolism (CYP 2C19)
Half life: 4-6 hrs
Excretion Renal

Common adverse effect: Hypoglycaemia

Question 19

Pharmacology of Metformin

Answer 19

Mechanisms of action
* Increases glucose uptake
* Decreases intestinal absorption of glucose
* Reduces production of glucose by the liver

Pharmacokinetics
* Metabolism: None
* Excretion: Renal
* Half life: 6 hours

• Reduced risk of hypoglycaemia
• Does not increase insulin secretion
• Not used in people with kidney disease

Question 20

Symptoms of diabetes:
hypoglycaemia

Answer 20

• Patient feels dizziness, confusion, anger
• Ensure medication is taken just before food.
• Ensure patients on insulin or hypoglycaemic medication
  have a source of readily available glucose (sweets or chocolate) with them at all times.
• Unconscious patients will need i.v. glucose or i.m. glucagon

Question 21

Diabetes symptoms :
Hyperglacaemia

Answer 21

• Patient passes large volumes of urine
• Thirst or dehydration
• Breath smells like pear drops (diabetic ketoacidosis)
• Patient needs careful re-hydration and correction of their blood glucose levels.

Question 22

Blood glucose monitoring

Answer 22

• Ensure it is performed on time
• Follow trust protocols strictly
• Mistakes in protocol have led to fatalities
• When in doubt ask your consultant nurse