Insulin used in diabetes Flashcards
insulin sources
recombinant human insulin could be produced in large quantities using cDNA found in E. Coli, humulin (Lilly), and in transformed yeast, novolin (Novo Nordisk)
standard unit of insulin
100 units/mL
how many units/mg of insulin?
28 units/mg
unitage of humulin R
500 units/mL
onset/duration of lispro (humalog)
15 minutes / 6-8 hours
onset/duration of aspart (novolog)
15 minutes / 3-5 hours
onset/duration of glulisine
15 minutes / 3 to 5 hours
onset/duration of regular insulin (R)
30 minutes to 1 hour / 8 to 12 hours
onset/duration of NPH insulin (N)
1 to 1.5 hours / 24 hours
onset/duration of glargine (lantus)
1 to 1.5 hours / over 24 hours
onset/duration of detemir (levemir)
1 to 2 hours / over 24 hours
onset/duration of degludac (tresiba)
1 hour / over 24 hours
mimicking natural insulin secretion pattern
modifies insulin to alter the availability and absorption from subcutaneous injection sites
delayed absorption - prolong onset and duration
increase absorption - decrease time to onset and duration
purpose of modified insulins
provide flexibility/convenience in dosing
be able to mimic basal levels (2nd phase) and preprandial dose levels (1st phase)
NPH (Neutral Protamine Hagedorn) insulin (N)
The insulin is complexed with protamine, tissue proteases have to break down protamine to be able to release the insulin, slows absorption time
lispro insulin
reverse positions of P28 and K29 on insulin B chain. Interferes with the ability to form a dimer. Monomers are absorbed much more readily from the site of injection, fast absorption time.
ultra fast onset/very short action insulin place in therapy
injected immediately before meals
insulin aspart
proline 28 in B chain is switched to aspart
interferes with ability to dimerize
monomer is absorbed much quicker from site of injection, rapid onset
insulin glulisine
Asn 3 and Lys 29 in B chain are switched to Lys and Glu
Interferes with ability to dimerize
Monomer is absorbed much quicker from site of injection, rapid onset
insulin glargine
Ask 21 of a chain is changed to Gly and 2 Arg residues are added to the end of the B chain (30 and 31)
insulin solubility can change at different pH (Clear solution at pH=4, when introduced to physiological pH it precipitates). Slowly and steadily released from injection site over 24 hours
basal insulins place in therapy
inject once daily
insulin detemir
discontinued
the 30 of B chain is deleted and Lys 29 is myristylated
binds to serum albumin extensively
insulin degludec
Thr 30 of B chain is replaced by y-Glu/C16 fatty acid. Binds to serum albumin extensively. insulin will hang out in blood stream for a long time, gradually little amounts will come off albumin and is absorbed very slowly
multi-dose insulin regimens
fast onset, short acting is taken before meals and long, or intermediate acting is taken at bedtime or at bedtime and after breakfast
Afrezza
regular human insulin in a dry powder that can be inhaled
Afrezza onset/duration
rapid onset/shorter duration of action than SC injection
Afrezza place in therapy
used as pre-prandial insulin
Afrezza contraindications
patients with asthma and COPD, may reduce lung function (decreased FEV)
Afrezza mechanism
molecules aggregate and for a large surface area for insulin to bind
IV insulin place in therapy
regular human insulin for severe hypoglycemia or ketoacidosis
mode of action of insulin
decreased liver glucose output
increase fat storage
increase glucose uptake
adverse reaction to insulin
hypoglycemia
lipodystrophy
lipohypertrophy
lipoatrophy
hypoglycemia
blood glucose <70 mg/dL; caused by too much insulin and/or not enough food (glucose)
symptoms of hypoglycemia
weakness, sweating, hunger, tachycardia, increase irritability, tremor, blurred vision, seizures, coma, increased sympathetic output
treatment of hypoglycemia
glucose if awake and alert
glucagon if unconscious or can’t swallow
agents that increased blood glucose
catecholamines
thyroid hormone
isoniazid
glucocorticoids
calcitonin
phenothiazines
oral contraceptives
somatropin
morphine
agents that may increase the risk of insulin hypoglycemia
ethanol
ACE inhibitors
Fluoxetine
somatostatin
anabolic steroids
MAO inhibitors
B-adrenergic blockers
Vigorous, unaccustomed exercise
ethanol’s role in increase risk of hypoglycemia
inhibits gluconeogenesis so glucose is not brought back into the blood
B blocker’s role in increase risk of hypoglycemia
counteract catecholamines and mask symptoms of hypoglycemia
exercise’s role in increase risk of hypoglycemia
skeletal muscle muscle contraction stimulates glucose uptake
lipodystrophy
changes in fat (i.e. on upper leg) at over used injection site
lipohypertrophy
accumulation of fat in subcutaneous tissue
lipoatrophy
loss of fat in subcutaneous tissue; less common with recombinant insulin
treatment of T1DM
insulin + diet + exercise
