6.1) Diabetes Flashcards
What is prescribed to Type 1 diabetics?
Insulin
Outline the properties of insulin
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
What are some of the pharmacokinetics of insulin?
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.
Insulin profiles
Different classes of preparations exist based on pharmacokinetics and responses:
Rapid
Short
Intermediate
Long
Why are combinations of insulin classes often used?
To allow a mixture of both short and long acting insulins for optimal coverage.
Known as ‘basal-bolus’ dosing
What are the side effects, adverse reactions ad interactions to consider with insulin?
hypoglycaemia, lipodystrophy- lipohypertrophy or lipoatrophy
X renal impairment- hypoglycaemia risk
Dose needs increasing with systemic steroids caution with other hypoglycaemic agents
What is the primary management for type 2 diabetes?
Lifestyle modification— weight loss and diet management
After lifestyle modifications, which treatments are considered for T2DM management?
Non-insulin therapies
Insulin therapies reserved for severe disease when beta cells no longer producing any endogenous insulin.
Give an example of a biguanide
Metformin
What is the mechanism of action of biguanides?
Decreases hepatic gluconeogenesis
Why is weight loss associated with biguanides like metformin?
These drugs suppress appetite, and thus cause weight loss.
What are some of the side effects and contraindications to biguanides?
GI upset— nausea and vomiting, diarrhoea
X excreted unchanged by the kidneys— inappropriate for patients with eGFR <30mL/min
What are some of the drugs that interact with metformin?
ACEi, diuretics (potential to increase plasma [glucose]), NSAIDs— drugs that impair renal function
Which class of drugs function by stimulating beta cell pancreatic insulin secretion? How?
Sulfonylureas
Block ATP-dependant K+ channels
Give an example of a sulfonylurea
Gliclazide
What is one of the essential requirements in order to prescribe sulfonylureas?
Need residual pancreatic function in order to have an effect.
Why are sulfonylureas associated with weight gain?
These drugs enhance the anabolic effects of insulin and promote storage of plasma glucose as adipose tissue.
What are some of the side effects and contraindications of using sulfonylureas?
mild GI upset- N+V, diarrhoea and hypoglycaemia
X hepatic and renal disease— use with caution, as well as individuals at risk of hypoglycaemia
Which drugs may interact with sulfonylureas?
Other hypoglycaemic agents, loop and thiazide diuretics (increase plasma glucose so can reduce SU action)
What is the mechanism of action of glitazones?
Decrease hepatic glucose output via activation of PPAR-gamma, which regulates gene transcription
Why are agents such as pioglitazone and rosiglitazone not used as readily as other agents?
Associated with idiopathic abnormalities such as an increased risk of fractures and bladder cancer
What are the side effects and contraindications associated with glitazones?
GI upset, fluid retention increased fracture risk and increased risk of bladder cancer
X heart failure- due to fluid retention risk
Give examples of sodium- glucose co-transporter inhibitors (SGLT-2 inhibitors)
Dapagliflozin
Canagliflozin
What is the mechanism of action of gliflozins?
Decrease glucose absorption from tubular filtrate, increase urinary excretion of glucose via competitive (reversible) inhibition of SGLT-2 in PCT
What are some of the side effects and contraindications associated with the gliflozins?
UTI and genital infections (due to increase urinary [glucose]), thirst and polyuria, increased risk of pancreatitis
X hypovolaemia- possible hypotension
What are the possible interactions with gliflozins?
Antihypertensives (agents that cause hypovolaemia) and other hypoglycaemic agents
Give examples of dipeptidyl peptidase-4 inhibitors (gliptins)
Sitagliptin
Saxagliptin
