6.1) Diabetes

Question 1

What is prescribed to Type 1 diabetics?

Answer 1

Insulin

Question 2

Outline the properties of insulin

Answer 2

Is a protein, so must be given paraenterally to avoid digestion in the gut
T1/2= ~5 minutes in plasma
Usual biphasic pattern of release, cyclical corresponding with food intake

Question 3

What are some of the pharmacokinetics of insulin?

Answer 3

Routinely delivered via subcutaneous injection.
Soluble insulin forms hexamers which delays absorption from the site of injection— dosing should be 15-30 mins prior to meals for optimal response.
Site of administration should be rotated to avoid lipodystrophy.

Question 4

Insulin profiles

Answer 4

Different classes of preparations exist based on pharmacokinetics and responses:
Rapid
Short
Intermediate
Long

Question 5

Why are combinations of insulin classes often used?

Answer 5

To allow a mixture of both short and long acting insulins for optimal coverage.
Known as ‘basal-bolus’ dosing

Question 6

What are the side effects, adverse reactions ad interactions to consider with insulin?

Answer 6

hypoglycaemia, lipodystrophy- lipohypertrophy or lipoatrophy

X renal impairment- hypoglycaemia risk
Dose needs increasing with systemic steroids caution with other hypoglycaemic agents

Question 7

What is the primary management for type 2 diabetes?

Answer 7

Lifestyle modification— weight loss and diet management

Question 8

After lifestyle modifications, which treatments are considered for T2DM management?

Answer 8

Non-insulin therapies
Insulin therapies reserved for severe disease when beta cells no longer producing any endogenous insulin.

Question 9

Give an example of a biguanide

Answer 9

Metformin

Question 10

What is the mechanism of action of biguanides?

Answer 10

Decreases hepatic gluconeogenesis

Question 11

Why is weight loss associated with biguanides like metformin?

Answer 11

These drugs suppress appetite, and thus cause weight loss.

Question 12

What are some of the side effects and contraindications to biguanides?

Answer 12

GI upset— nausea and vomiting, diarrhoea

X excreted unchanged by the kidneys— inappropriate for patients with eGFR <30mL/min

Question 13

What are some of the drugs that interact with metformin?

Answer 13

ACEi, diuretics (potential to increase plasma [glucose]), NSAIDs— drugs that impair renal function

Question 14

Which class of drugs function by stimulating beta cell pancreatic insulin secretion? How?

Answer 14

Sulfonylureas

Block ATP-dependant K+ channels

Question 15

Give an example of a sulfonylurea

Answer 15

Gliclazide

Question 16

What is one of the essential requirements in order to prescribe sulfonylureas?

Answer 16

Need residual pancreatic function in order to have an effect.

Question 17

Why are sulfonylureas associated with weight gain?

Answer 17

These drugs enhance the anabolic effects of insulin and promote storage of plasma glucose as adipose tissue.

Question 18

What are some of the side effects and contraindications of using sulfonylureas?

Answer 18

mild GI upset- N+V, diarrhoea and hypoglycaemia

X hepatic and renal disease— use with caution, as well as individuals at risk of hypoglycaemia

Question 19

Which drugs may interact with sulfonylureas?

Answer 19

Other hypoglycaemic agents, loop and thiazide diuretics (increase plasma glucose so can reduce SU action)

Question 20

What is the mechanism of action of glitazones?

Answer 20

Decrease hepatic glucose output via activation of PPAR-gamma, which regulates gene transcription

Question 21

Why are agents such as pioglitazone and rosiglitazone not used as readily as other agents?

Answer 21

Associated with idiopathic abnormalities such as an increased risk of fractures and bladder cancer

Question 22

What are the side effects and contraindications associated with glitazones?

Answer 22

GI upset, fluid retention increased fracture risk and increased risk of bladder cancer

X heart failure- due to fluid retention risk

Question 23

Give examples of sodium- glucose co-transporter inhibitors (SGLT-2 inhibitors)

Answer 23

Dapagliflozin
Canagliflozin

Question 24

What is the mechanism of action of gliflozins?

Answer 24

Decrease glucose absorption from tubular filtrate, increase urinary excretion of glucose via competitive (reversible) inhibition of SGLT-2 in PCT

Question 25

What are some of the side effects and contraindications associated with the gliflozins?

Answer 25

UTI and genital infections (due to increase urinary [glucose]), thirst and polyuria, increased risk of pancreatitis

X hypovolaemia- possible hypotension

Question 26

What are the possible interactions with gliflozins?

Answer 26

Antihypertensives (agents that cause hypovolaemia) and other hypoglycaemic agents

Question 27

Give examples of dipeptidyl peptidase-4 inhibitors (gliptins)

Answer 27

Sitagliptin
Saxagliptin