Diabetes PHARM Insulin Flashcards
Insulin
Synthesis
Insulin is synthesized by the beta cells of the pancreas
Cleavage of the C peptide (connecting peptide) converts pro insulin into insulin
Peptide hormone
Insulin therapy
Examples
- Rapid acting, short duration
- Short acting, short duration
- Slow acting, intermediate duration
- Slowest acting, Longest duration
Rapid acting, Short Duration
Insulin
Examples
Pharmakokinetics
Glulisine > aspart > lispro
Onset: 15 minutes
Peak: 1.5hours
Duration: 5 hours
*take 15 minutes before meal onset
*change in 2 a.a decreases ability to cluster
increases absorption
Short acting, Short Duration
Insulin
Examples, peak, onset, duration
Humulin R
Novolin R
Onset: 30-60 minutes
Peak: 3 hours
Duration: 6.5 hours
Insulin
MOA
Anabolic hormone
Increase uptake of a.a, FFA, nucleic acids, and glucose by liver, muscle, adipose tissue
Synthesis of proteins, glycogen, and adipose
Decrease catabolism
- gluconeogenesis
- glycogenolysis
- FFA oxidation
Insulin
SE
Hypoglycemia
- too much insulin
- not enough carbohydrates
Lipohypertrophy at injection site
- anabolic
- fat deposites with subcutaneous injections
- rotate sites
Insulin
Dose adjustments
Preprandial BG
Alcohol
- Delayed hypoglycemia 24 hours post alcohol consumption
- prevents liver counter-regulatory response
Excessive exercise
- exercise induced hypoglycemia
- reduce basal and/or bolus dosage, eat carbohdyrate
Illness, stress, trauma
- counter-regulatory hormones -> hyperglycemia
Bolus Insulin therapy
Examples and indications
Pre-prandial or meal time
- Rapid acting, short duration
- insulin aspart
- insulin glulisine
- insulin lispro - short acting, short duration
- humulin R
- novolin R
Basal insulin
Examples and Indication
- Slower acting, intermediate duration
- Humulin N
- Novolin N - slowest acting, longest duration
- Degludec > glargine > detemir
Indication:
basal control
prevent glucose fluctuations between meals and overnight
Slower acting, Intermediate duration insulin
Examples, onset, peak, duration
NPH insulin
- neutral protamine hagedorn insulin
- conjugation with protamine slow absorption
- higher risk allergic reaction
Humulin N
Novolin N
Onset: 1-2 hours
Peak: 5-8 hours
Duration: up to 18 hours
Slowest acting, longest duration insulins
Indications and examples
Indication: basal insulin control
- less hypoglycemia than intermediate insulins
- U refers to concentration
Examples
- Degludec > glargine > detemir
- longest acting
- less hypoglycemic risk
Slowest acting, longest duration insulins
Pharmakokinetics
onset: 1.5 hours
Peak: no peak
Duration: 24,30,42 hours
Dosing: once a day
Pre-mixed insulin
Examples
Pre-mixed insulin
Indication: BID injection schedule, morning meal, night time meal
Dosage: Reported as ratio N:R
Examples:
Humulin N: Humulin R
Novolin N: Novolin R
Pre-mixed insulin
Pharmakokinetics and disadvantage
Onset: 30-60 minutes (short acting insulin)
Peak: variable, dependent on ratio
Duration: up to 18 hours (intermediate insulin)
CON
- not tight control
- no insulin dosed with lunch time meal
Therapy Regimes
T1DM
- Twice daily pre-mixed regime
- Intensive Basal-bolus regime
Advantages Basal-bolus regime
- better A1C control
- better macrovascular and microvascular outcomes
- rapid acting insulin benefits > short acting insulin benefits (glulisine > aspart > lispro > humulin R)
- Self management: pre-prandial BG, match insulin with BG and meal
- Long acting insulin (degludec > glargine > detemir) used for basal control
- prevents hypoglycemia
Glycemic targets
- Adults < 7%
- Children / adolescents < 7.5%
- elderly, pailiative, frail, functional dependence < 7.1-8.5%
- pregnancy <6.5%
Suboptimal control
T1DM
Strategies
- Intensive basal-bolus insulin regime
- subcutaneous injections
- BG monitoring at minimum TID
- sliding scale based on carbohydrate intake - continuous glucose monitoring with continuous subcutaneous insulin infusion
- improves QOL, FOH, A1C control - Patient education
- diet, exercise, sick day/stress management
Initiation Therapy
T2DM
Pre-assessment
Assess A1C
macrovascular and microvascular complications (heart, kidney, eyes, feet)
Determine target
healthy behaviour counselling (diet, exercise, weight loss, smoking cessation)
Initiation Therapy
T2DM
Pathways
- Pre-diabetes A1C betwen 6.1%-6.4%
- diet , exercise
- re-assess 3 months - Diabetes A1C < 1.5% over
- metformin + exercise + diet
- diet + exercise
- re-assess 3 months - Diabetes A1C > 1.5% above (7.5%)
- Metformin + secondary medication
- Second line: sulfonylureas, meglitinides, thionazolidinediones, GLP1 agonists, DPP4i, SGLT2i - Symptomatic hyperglycemi, metabolic decompensation, elevated A1C > 6.5%
- Metformin + insulin therapy (basal first)
Re-assessment A1C in 3 months
T2DM
Treatment pathways
- Diabetic A1C not controlled, asymptomatic hyperglycemia
- Addition SGLT2i (MACE, HF, nephroprotective)
- Addition GLP1 agonist (MACE, CVE)
- Avoid thiazolidinediones (weight gain, cardiotoxic)
- Avoid sulfonylureas, meglitinides (weight gain, hypoglycemia with insulin)
- Symptomatic hyperglycemia, A1C still not controlled (on basal insulin therapy)
- addition of Secondary medication (SGLT2i, GLP1 agonist, DPP4i)
- addition of bolus insulin (intensive basal-bolus regime)
*advance therapy if no control in 3-6 months
Do not combine these diabetic drugs
GLP1 agonist with DPP4i
Thiazolidinediones with insulin
Sulfonylureas with meglitinides
*same mechanism of action
hypoglycemia
Somogyi Effect
Pathophysiology and management
BG high in the morning
Pathophysiology:
Hypoglycemia at night time
activation counter-regulatory hormones (cortisol)
increase glucose via glycogenolysis and gluconeogenesis (liver)
Treatment
- decrease basal insulin
- carbohydrate snack before bed
Diagnosis
- check insulin regular time points
- no hypoglycemia detected, likely dawn phenomenon
Dawn Phenomenon
Pathophysiology and management
BG is high in the morning
Pathophysiology
- counter-regulatory hormones (cortisol, GH) released at night time 4am which result glucagon release and breakdown of glycogen to glucose and liver gluconeogenesis
Treatment
- increase basal insulin at night
Diagnosis
- take insulin mutiple times overnight
- if no hypoglycemia detected then dawn phenomenon
