insulin MOA
○ Regulation of carbs (CHO), fat, aa
○ Glucose: facilitate uptake of glucose in muscle and adipose tissue
§ Inhibit hepatic glucose output (glycogenolysis, gluconeogenesis)
○ Fat: enhance fat storage (lipogenesis)
§ Inhibit mobilisation of fat for energy in adipose tissue (lipolysis, FFA oxidation)
○ Protein: incr protein synthesis
§ Inhibit proteolysis in muscle tissue
○ Acts on liver, pancreas muscle, adipocytes
benefits of insulin
MOST EFFECTIVE HbA1c: 2.5% lowering
* Indication
○ All types of DM
* Choice of therapy: PREG with DM
PD of insulin
○ Response to insulin is highly variable between individuals and within indiv
○ ROA rapid and shorter for: IV> IM > SC
PK of insulin
○ A: activity after SC admin from inj site rate limiting step
§ SC depot formed
○ D: enter bloodstream after SC depot directly
○ M/E:
§ Exogenous: by kidney
§ Endogenous: by liver
injection factors
needle length
gauge size
syringe size
site
insulin vial size
stability of insulin
Needle length
Pen: 4mm ~ 12.7 mm
Syringes: 6mm ~ 12.7 mm (account for vial stopper)
○ Average skin thickness of 2.4mm (not based on BMI, race, age)
○ No need long needle (may enter IM instead, affect absorption)
○No need > 8mm
Gauge size
Syringe size:
site of injection
insulin vial size, amt
Stability of insulin (shelf life vs expiration date)
Injection technique
1) Pinch area to be injected
2) Insert needle 90* angle at center of pinched area
1. 45* if small children/ cachexic adults/ frail elderly
3) Release pinch/ continue to pinch
4) Press plunger to inject insulin
5) Hold syringe/ device at area for 5-10s
1. Insulin depot, not leak out
6) Remove syringe/ device
special considerations when inejcting
Angle of injection
* 45* if small children/ cachexic adults/ frail elderly
Pinching
* If use 6,8,12.7 mm
○ Don’t need pinch skinfold for meds to reach intended site
* 4-5mm needle
○ Don’t need pinch skinfold
○ Unless less SC fat (use arm, thighs for inj)
Factors affecting insulin absorption
lipoatrophy vs lipohypertrophy
Ultra-short acting
Rapid acting
Aspart
Lispro
Glulisine
——PPG
onset: 5-10min
1-2hr
duration of action: 3-5hr
One inj per meal (15min before)
Short acting
regular — PPG
30-60ming
2-4 hr
6-8hr
One inj per meal (30min before)
intermediate
NPH –FPG
onset: 1-2hr //6-12hr
duration of action: 10-16hr
2 inj for 24hcoverage
Long acting
Detemir —- FPG
Onset: 0.8-2hr
DOA:
12hrs for 0.2units/kg
20-24hrs for 0.4units/kg
2inj for 24hr coverage
Glargine U-100
1.5h
Peakless
24hr
1 inj for 24hr
Ultra long acting
Degludec —— FPG
Peakless
Duration of 42hr
Anytime of the day OD, sc inj
Glargine (U-300) ——FPG
36hr
OD, same time daily
stable mixed
unstable mixes to avoid
EG OF MIXED (cover FPG + PPG)
benefits of pre-mixed products