10 Diabetes- Insulins and Oral Hypoglycaemic agent Flashcards
What is insulin secreted in response to? What is insulin inhibited by? What is the role of insulin?
Why does insulin need to be given parenterally? What are the injection sites used for it (need to be rotated)?
Insulin= a protein
–> to avoid digestion in the gut
Injection sites:
- Upper arms
- Thighs
- Buttocks
- Abdomen
How is human insulin produced? In what unit is it formulated
Recombinant DNA (bacteria/yeast) or Enzymatic modicfication of porcine
What is the half life of insulin like in plasma?
What is the concentration of insulin in plasma greatest?
What can be added to insulin to modify its absorption?
- t1/2 - ~ 5 minutes in plasma – renal and hepatic metabolism and elimination
- [plasma] greatets after 2-3 hr – dose 15-30 min prior to meals
- Protamine and zinc used to modify absorption
Identify 4 different types of insulin. (insulin analogues)
What are the warnings/contraindications for insulin and what are the important interactions to consider?
Warnings/contraindications:
- Hypglycaemia
- Lipohypertrophy/lipoatrophy
- Renal impairment- hypeglycaemia risk
Important interactions:
- Steroids?
- Other hypoglycaemic agents
Sometimes a long acting insulin is given to a patient with short acting insulins given in between. What is this called and why is it done?
To mimic normal release of insulin- have baseline insulin
What factors should lead you to suspect diabetic ketoacidosis?
- blood glucose > 11mmol/L
- infection
- stress/trauma
- poor insulin adherence
- ADRs
- ketosis
How should diabetic ketoacidosis be treated?
FIRST- fluids
NEXT- insulin (stat dose), glucose, K+ (as insulin may cause hypokalaemia)
Biguanides are typically the first drug offered in the treatment of type 2 diabetes. How do biguanides work? (3)
- Decrease hepatic glucose output (gluconeogenesis, glycogenolysis)
- Increase glucose utilisation in skeletal muscle
- Supress appetite- limit weight gain
What are the main side effects of biguanides and what important drug interactions should we be aware of?
Side effects:
- GI upset- nausea, vomiting, diarrhoea
- (Stop if eGFR <30mL/min- excreted unchanged by kidneys)
Interactions:
- Anything impairing renal function- can increase glucose so reduce action of metformin
- ACEi
- Diuretics
- NSAIDs
Name a Biguanide.
metformin
How do sulfonylureas work to treat type 2 diabetes? What does it require in order to work? (1)
Typically used in combination or first line if metformin contraindicated
- Block ATP-dependant K+ channels–> stimulate β̞-cell pancreatic insulin secretion
Need residual pancreatic function
What are the side effects, important interactions and contraindications to be aware of with sulfonylureas?
Side effects:
- Mild GI upset
- Weight gain
- Hypoglycaemia
- Hypersensiitivity reactions
Interactions:
- Other hypoglycaemic agents
- Thiazide like diuretics (increase glucose so impair function)
Contraindications:
- Hepatic impairment
- Renal impairment
Name an examples of a sulfonylureas.
Gliclazide
How do thiazolidinediones (glitazones) work to treat types 2 diabetes? (2) What are their durations of action like?
- Insulin sensitisation in muscle and adipose
- Decrease hepatic glucose output
Activate PPAR-y gene transcription- duration of action= 6-8 weeks
What are the major side effects and interactions for glitazones?
Side effects:
- GI upset
- Fluid retention (weight gain)
- Fracture risk
- CVD concerns
- Bladder cancer
Important interactions:
- Other hypoglycaemic agents
Name 2 glitazones (Thiazolidinediones).
Pioglitazone
Rosiglitazone
How do sodium glucose co-transporter inhibitors (SGLT-2 inhibitors or gliflozins) work to treat types 2 diabetes?
- Decrease glucose absorption from tubular filtrate –> increase urinary glucose excretion
(used in type 1 and type 2)
What are the side effects and interactions to be aware of for SGLT-2 inhibitors (using them to treat diabetes)?
Side effects:
- UTIs
- Thirst
- Polyuria
Interactions:
- Other hypoglycaemic agents
- Other antihypertensives
Give 2 examples of SGLT-2 inhibitors.
Dapagliflozin
Canagliflozin
How do gliptins (dipeptidyl peptidase-4 inhibitors) (DPP-4 inhibitors) work to treat type 2 diabetes?
- Dipeptidyl peptidase-4 destroys hormone incretin
- Incretins: help the body produce more insulin only when it is needed and reduce the amount of glucose being produced by the liver when it is not needed
- There with gliptins- more incretin in body
- Also supress appetite
Low risk of hypoglycaemia when administered alone- incretins are glucose dependent
What are the side effects and important interactions to remember when prescribing gliptins (DPP-4 inhibitors)?
Side effects:
- GI upset
- Pancreatitis risk
Interactions:
- Other hypoglycaemic agents
- Drugs increasing glucose eg certain diuretics
AVOID IN PREGNANCY
Give 2 examples of Dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins).
Sitagliptin
Saxagliptin
How do Glucagon-like peptide-1 receptor agonists work to treat type 2 diabetes? How are they administered? When are they indicated?
Administered: Subcutaneous injection
Indicated: add-on if triple therapy ineffective
What are the side effects and interactions to be aware of with GLP-1 receptor agonists?
Side effects:
- GI upset
- GORD
Interactions:
- Other hypoglycaemic agents
STOP if eGFR <30mL/min
What is diabulimia?
Condition- patient with type 1 diabetes deliberately stops taking their insulin for the purpose of weight loss
Name two GLP-1 agonists to treat type 2 diabetes (Glucagon- like peptide-1).
Exenatide
Liraglutide
Useful summary of drugs used to treat type 2 diabetes:
