Insulin Flashcards
What si teh role of insulin
- Stimulates uptake of glucose into liver, muscle and adipose tissue
- Decreases hepatic glucose output via inhibition of gluconeogenesis
- Inhibits glycogenolysis
- Promotes uptake of fats
- Ideal insulin treatment would be to reinstate the normal daily insulin profile to prevent both hyperglycaemia and hypoglycaemia
What are types of insulin available
Animal Porcine and Bovine Recombinant DNA technology • Human short acting insulins • Human rapid acting insulin analogues • Isophane intermediate acting insulin • Long acting basal analogue insulins • Very long acting basal analogue insulins
What affectstheduraton of action ofisulins
Once absorbed, duration o action 4-5 minutes. Only difference - rate at which absorbed. Some take time to break down. Fast acti ones are more momnomeric. Some ar more bound together so slow breakdown.
Describe recombinant dna technology
- Has allowed for the development and production of analogues – the insulin molecule structure is modified to alter the pharmacokinetic properties, primarily affecting the absorption of the drug from subcutaneous tissue
- B26-30 region altered
How many types of insulin are there
Over 20 different types are insulin in use in various strengths and forms (vials, cartridges, disposable pens)
U100. 100 units per ml. Obesity a problem need to use u200, u300 etc
Liable to prescribing error s- could accidnetllay give too much
What are the 6 mai insulin categories and how are they absorbed
• Ultrafast acting • Rapid acting • Short acting • Intermediate acting • Long acting • Very long acting • Absorption into blood stream via subcutaneous injection • Formulation of insulin influences rate of absorption
Describe ultra fast acting insulin apart
Ss
Describe rapid acting insulin
- Rapid onset of action 5 to 15 minutes • Inject just before eating
- Peaks ~ 60 minutes
- Duration 4 to 6 hours
Humalog, Novorapid, Apidra)
Describe short acting insulin
Actrapid, Humulin S, Hypurin Bovine and Porcine Neutral)
• Starts to work 30 to 60 minutes
• Need to inject at least 15 to 30 minutes before
eating several times daily to cover meals • Peaks at 2 to 3 hours
• Duration 8 to 10hours
Describe intermediate acting insulin
Intermediate acting insulin (Insulatard, Humulin I and Insuman Basal, Hypurin Bovine and Porcine Isophane)
• Slower onset 2 to 4 hours
• Peaks 4 to 8 hours
• Duration up to 12 to 20 hours
Describe long and very on acting insuin
Long and very acting insulin (Glargine, Detemir, Degludec)
• Slow onset 2 to 6 hours
• Duration up to 24 hours
• Very long up to 50+ hours (DEGLUDEC insulin)
What are fixed. combination
- Novomix 30
- Humulin M3
- Humalog Mix 25 and 50
- Hypurin Porcine 30/70
- Insuman Comb 15 and 25 and 50
- And modes of delivery using syringes, insulin Pens, insulin pumps
Describe insulin pump therapy
Sensor augmented pump therapy with threshold suspend
What are the adverse effects of insulin
- Hypoglycaemia
- Hyperglycaemia
- Lipodystrophy – lipohypertrophy or lipoatrophy
- Painful injections - hypertrophy of adipose, and scarring if you keep injecting into same space
- Insulin allergies
Describe the safer administration of insulin
- In UK 4 to 5% population has diabetes
- 30 to 40% treated with insulin
- Insulin errors are very common in UK with approximately prescribing errors in ~20% cases
- Why? Too much will lead to hypoglycaemia and too little to hyperglycaemia
- Look online for Safer Insulin Prescribing module
Why does blood glucose rise
- Inability to produce insulin due to beta cell failure and / or
- Insulin production adequate but insulin resistance prevents insulin working effectively
How do we treat type 2 diabetes
Type2
– Lifestyle plus non-insulin therapies
• Biguanides, sulphonylureas, thiazolidinediones, DPP4 inhibitors, α- Glucosidase inhibitors, SGLT2s, GLP1 analogues and Insulin
• Plus non pharmacologic methods via bariatric surgery and very low calorie diets
• Above require patient education and ability to monitor results of therapy
What are the key challenges for patient with type 2 diabetes
Ss
What are the nice targets in typ 2 diabetes
- In general target for all is HbA1c 6.5 to 7.5%
- HbA1c 6.5%:Diet and first 2 treatment steps
- HbA1c 7.5%:Beyond this or if at risk of severe hypoglycaemia
- Common sense: Limited life expectancy and Co morbid conditions
Describe metformin
• decrease Insulin resistance leading to increased glucose by tissues
• decrease hepatic glucose production (reduces hepatic
gluconeogenesis)
• Limits weight gain
• decrease CVS events (UKPDS)
• Can be combined with all other diabetes medications
• Side effects include GI symptoms
• Lacticacidosisrare
• Vitamin B12 deficiency uncommon
• Stop if CKD < 30ml/min or significant comorbidities
• Dose range typically 500mg to 2.5g (also Modified Release available) and Cost low
Describe sulphonylureas
Stimulate beta cell to release insulin • Extensive experiencedecrease Microvascular risk (UKPDS) • Side effects • Weight gain • Hypoglycaemia • Cost low • Commonly used include Gliclazide (Modified Release too) (hepatic metabolism so can be used in renal impairment), Glimepiride
Wha is acarbose
Acarbose: α glucosidase inhibitor
• Only 1 available in the class
• Inhibits breakdown of carbohydrates to glucose by blocking action of the enzyme α Glucosidase
• Side effects are predictable! Flatulence, loose stools and diarrhoea
• Modest reduction in HbA1c ~ 0.5%
• Rarely if ever used nowadays
What are glitazones
Glitazones [Pioglitazone]
• increase insulin sensitivity in muscle and adipose tissue and decrease hepatic glucose output
• They bind to and activate one or more peroxisome proliferator-activated receptors (PPARs)
• Can be used in combination with other oral agents
• Cardiovascular concerns with Rosiglitazone - Weight gain, fluid retention, cvs events such as angina - increase cholesterol.
• Pioglitazone still available but concerns regarding weight gain, fluid retention and heart failure, effects on bone metabolism and bladder cancer
• Rarely used nowadays
Describe glucagon like peptide 1 therapies
• Alternative hormone system influencing glucose metabolism
• High glucose in Type 2 diabetes due to insufficient release of insulin and over production of glucagon
• GLP1therapy(Exenatide,Liraglutide, Lixisenatide)
• Increase insulin secretion from the beta cells
• Decreases production of Glucagon from alpha cells
Switches off desire to eat - safety centre in hypothalamus - promote weight loss and improve control. A to fo former medicines promote weight gain
Descrive the physiological effects of gulp-1
Ss
Describe gliptis or dpp4 inhibitors
Sitagliptin, Vildagliptin, Saxagliptin, Linagliptin
• Inhibits DPP-4 activity increasing postprandial active GLP-1 concentrations
• Side effects include GI symptoms, ?pancreatitis
• Low risk of hypoglycaemia
• Weight neutral
• Modest HbA1c reduction
• Cost high
What are the adverse effects o glp1 agonists
- Gastrointestinal symptoms, nausea, loose stools or diarrhoea
- Gastro oesophageal reflux
- Low risk of hypoglycaemia
- Occasional painful to inject
- ? Pancreatitis and pancreatic carcinoma
- NICE and FDA found no evidence of pancreatitis in the reported studies
- Generally perceived to be safe and well tolerated agents
- Widely used
- Avoid if eGFR < 30ml/min
Descrive dapagliflozin
A novel insulin-independent approach to remove excess glucose
Dapagliflozin selectively inhibits SGLT2 in the renal proximal tubule
*Increases urinary volume by only ~1 additional void/day (~375 mL/day) in a 12-week study of healthy subjects and patients with Type 2 diabetes.4
Sodium-Glucose Co -Transp
What are the adverse effects f glifozins
Glifozins: adverse side effects
• Can be used for patients with Type1 and Type 2 diabetes as add on therapy
• Dapagliflozin, Canagliflozin and Empagliflozin available
• Side effects can be predicted
• Increase risk of lower urinary tract symptoms including genital and urinary infections especially in women (5%)
• Polyuria
• Hypoglycaemia risk low
