Diabetic agents Flashcards
What is the first line action given to t2 prediabetic patients
Lifestyle modification
What is the first line drugs offered to patients with t2dm?
Metformin or DDP4 if contraindicated
What blood glucose level is considered high and requiring treatment?
> 48 mmol
T1DM require insulin, how is this produced?
Plasmid vector in bacteria carrying the human insulin gene (recombinant DNA) or enzyme modification of porcine insulin.
There is no C chain produced in artificial insulin.
What features are needed to diagnose T1DM?
Random plasma glucose >11mmol/L
- polydipsia
- polyuria
- lethargy
- weight loss
A raised glucose without symptoms is insufficient
How does metformin work?
It decreases gluconeogenesis and glycogenolysis in the liver, decreasing the circulating glucose.
It increases the use of glycogen stored within the muscles.
What is meant by a basal bolus regime?
Using two formulations of insulin which have different lengths of half life, typically use a long acting insulin once a day and a short acting insulin after meals
How do sulfonylureas work? Why can’t they be prescribed in T1DM?
They work by inhibiting the K ATP channel, causing the release of insulin.
Patients must have a pancreas which is still functionally able to produce and secrete insulin
If metformin is contraindicated, what is the first line drug of choice?
What is the HB1AC to initiate ?
DPP4 inhibitors or sulfonylureas
48mmol/mol
How do SGLT2 blockers act?
They prevent reabsorption of glucose in the PCT, as a competitive reversible inhibitor, resulting in loss within the urine.
What are the likely issues with taking a SGLT2 inhibitor?
Increased likelihood of UTI
Thirst and polyurea
Insulin is a hormone of which class and what is it secreted in response to?
It is a protein hormone
Secreted in response to:
- glucose concentration increase
- incretins concentration increase (GLP-1 & GIP)
- glucagon
- parasympathetic activity (M2)
What inhibits insulin?
- decreased plasma glucose
- cortisol
- sympathetic activity (alpha2)
What is the role of insulin?
Promote fat uptake
Inhibit glycogenolysis and gluconeogenesis
Why must insulin be given parentally?
To avoid digestion
What are the signs of diabetic ketoacidosis?
Hyperglycaemia, acidosis and ketonaemia
Can present with low blood ketones and hyperglycaemia may not always be present
What is the main treatment of diabetic ketoacidosis?
Fluids and then insulin, with glucose and potassium.
What are the contraindications of biguanides?
GI upset- Nausea, vomiting, diarrhoea, lactic acidosis
Not used if eGFR <30ml/min (unchanged)
What drugs interact with biguanides?
ACEi
Diuretics
NSAIDs
- any drugs which may impair renal function
Thiazide like diuretics increase glucose so can reduce action.
What are the contraindications of sulfonylureas?
Mild GI upset - vomiting, diarrhoea, hypoglycaemia
What drugs interact with sulfonylureas?
Hypoglycaemic agents
Thiazide like diuretics
Hepatic or renal impairment.
Name a sulfonylurea
Gliclazide
How do Thiazolidinediones work?
Increased insulin sensitivity in muscle and adipose, decreasing hepatic glucose production.
Activate PPAR-gamma; takes 6-8 weeks to have an effect and causes increased storage of fatty acids in adipocytes.
What are the side effects of glitazones?
GI upset Fluid retention Weight gain Fracture risk CVD concerns Bladder cancer
Name a Thiazolidinedione (glitazone)
Pioglitazone or rosiglitazone
what drug interactions should be considered when prescribing a SGLT2 inhibitor?
Antihypertensive and hypoglycaemic drugs already being taken
Name a SGLT-2 inhibitor
Dapaglifozin
Canagliflozin
What are the physiological effects of GLP-1?
Increase insulin secretion and decrease glucagon secretion Increase satiety Decrease liver glucose production Decrease gastric emptying Increase muscle glucose uptake
Name a DPP-4 inhibitor
Sitagliptin
Saxagliptin
How do DDP-4 inhibitors work?
Prevent incretin degradation and therefore increase plasma level. This inhibits glucagon release.
Causes insulin secretion and delay gastric emptying, reducing blood glucose.
Why do DDP-4 inhibitors have a lower risk of hypoglycaemia?
They do not stimulate insulin secretion at a normal blood glucose
What are the contraindications for DPP-4 inhibitors?
GI upset
Pancreatitis
Avoid in pregnancy
What drug interactions should you be aware of with use of DPP-4 inhibitors?
Hypoglycaemic agents
Thiazide like and loop diuretics - drugs increasing glucose can oppose action
How do GLP-1 receptors agonists work?
Increased glucose dependant synthesis of insulin, activation of GLP-1 receptors.
Name a GLP-1 receptor agonist
Exenatide
Liraglutide
How is GLP-1 administered?
Subcutaneous injection
What are GLP-1 contraindications?
GI upset
GORD
Stop below <30ml/min
What is the half life of insulin and it’s metabolism?
5 mins in plasma
Renal and hepatic metabolism
When is plasma glucose highest after meals?
2-3 hours
What two things modify absorption of insulin ?
Protamine and zinc
Name a rapid insulin and it’s features
Insulin aspart
10-20mins onset
Peak @ 40-50 mins
3-5 hr duration
Name a short acting insulin and it’s features
Soluble insulin ; humulin S or actrapid
30-60 min onset
Peak at 2-5hrs
5-8hr duration
Name a intermediate acting insulin and it’s features
Isophane insulin
Onset at 60-120 mins
Peak @ 4-12 hrs
18-24hr duration
Name a long acting insulin and it’s features
Insulin glargine
Onset 60-90 mins
Peak between 2-20hrs (plateau)
20-24 hr duration
What are the warnings for insulin’s?
Hypoglycaemia
Lipohypertrophy
Lipoatrophy
Renal impairment increasing hypo risk
What are the interaction problems with insulin?
Increase dose with steroids
Caution with other agents
What would make you suspect DKA?
BM > 11mmol/l and ... Infection Trauma\ stress Poor adherence ADR Ketosis
For first intensification what is considered treatment and optimal HB1AC?
Dual therapy
Rise to 58 mmol/mol
Aim for 53 mmol/mol
If second intensification, what is the management and HB1AC aim?
Triple therapy or insulin (if metformin contraindicated)
Aim for 53 mmol/mol
