Insulins to treat diabetes Flashcards
Insulin sources
-recombinant human insulin
-human insulin cDNA in plasmid (E.Coli or yeast)
Humulin
-insulin cDNA in plasmid in E. Coli
Novolin
-transformed yeast insulin cDNA
Units of insulin
-100 units/mL
-28 units/mg insulin
-humulin also available in 500units/mL
Insulins with rapid onset and short duration
-Lispro
-Aspart
-Glulisine
-mimic first phase
Rapid Onset/ Shortish Action
Regular (R)
intermediate onset and action
NPH (N)
slow onset/ long action
-Glargine
-Detemir
-Degludec
-mimic second phase
Modified insulin effect on dosing
-delay absorption to prolong onset and duration
-increase absorption to dec onset and duration
-provides flexible dosing
-basal levels vs preprandial dose
-2 phases
-slide 33
Insoluble Insulin Complexes
-Lente insulins (no longer used)
-NPH insulin
Semilente
-small amorphous particles
Lente
-small amorphous and large crystalline complexes
-slow absorption, long acting
Ultralente
-only large crystalline complexes
-very slow absorption, very long acting
Insulin hexamer
-nucleated by zinc
-trimer of dimers
-slide 35??
lente insulins
-zinc/insulin precipitates
-large complex size = prolong absorption from SC site
-monomer is absorbed
-slide 34
NPH insulin
-Neutral Protamine Hagedorn
-bound insulin to protamine
-tissue proteases free insulin from protamine
-slow absorption, long action
Mutated Human Insulins
-Lispro (humalog)
-Insulin Aspart (Novolog)
-Insulin Glulisine (Apidira)
-Insulin Glargine (Lantus)
-Insulin Detemir (Levemir)
-Insulin Degludec (Tresiba)
Lispro insulin
-HUMALOG
-reverse P28 (proline) and K29 (lysine) positions on insulin B chain = dec self-association
-insulin dimer and hexamer formation in reg insulin (not this one tho?)
-monomer absorbed faster
-5-15 min onset (quick)
-inj immediately before meals
Lispro insulin (humalog) counseling
-5-15 min onset
-inj immediately before meals
Insulin dimer
-slide 38
Human insulin primary structure
Insulin Aspart
-Novolog
-human, except P28 in B chain switched to aspartate
-5-15 min onset, short duration
-inj immediately before meals
Insulin Glulisine
-Apidra
-Asn 3 and Lys 29 in B chain switch to Lys and Glu
-rapid onset, short duration
-inj immediately before meals
Insulin Glargine
-Lantus
-Asn21 of chain switch to Gly
-2 Arg residues added to end of B chain (30 and 31)
-clear solution (pH 4)
-precipitates post injection
-slowly released from injection site (precipitation form) over 24 hours
-once daily
-no pronounced peak compared to NPH which is good and steady
Insulin Detemir (Levemir)
-discontinued
-Thr 30 of B chain replaced by fatty acid
=makes insulin bind to serum albumin and itll ride around the body for awhile
-Lys 29 mysristylated
-bind serum albumin extensively
-clear solution
-inj once or twice daily
Insulin Degludec
-Tresiba
-Thr 30 of B chain replaced by fatty acid
-binds albumin extensively
-clear solution
-inj once daily
PK chart of insulins
-rapid insulins: spike that mimics first phase
-NPH spikes then falls
-basals: long flat curve
Common Multi-dose insulin regimens
-fast onset, short action: take before meals
-long/intermediate acting: take at bedtime and AFTER breakfast
Insulin mixtures
-NPH + regular
-NPL + Lispro
-Degludec + Aspart
-give preprandial bolus and prolonged basal level
-single injection
Inhaled insulin
-Afrezza
-human insulin as dry powder
-rapid onset, SHORT duration
-use as pre-prandial insulin
-do NOT use in pt with asthma/COPD
-may reduce lung function (dec FEV)
-slide 50 structure
Routes of admin
-all are SubQ
-insulin infusion pump: Buffered regular and rapid acting (lispro, aspart, glulisine)
-IV: regular (for severe hyperglycemia or ketoacidosis)
-inhalation: afrezza
Types of pt using insulin
-Type I diabetics
-Pt with ketosis and hyperosmolar coma
-some type II
Mode of action of insulin in diabetic
-dec liver glucose output
-inc fat storage
-inc glucose uptake
Adverse reactions to insulin
-hypoglycemia
-lipodystrophy**
-Lipohypertrophy
-lipoatrophy
-insulin resistance
Hypoglycemia
-too much insulin, not enough food
-weakness, sweating, hunger, tremor, seizures, coma
-neural cells need glucose
Hypoglycemia tx
-glucose
-glucagon inj if cant swallow
Agents that can inc BG in insulin users
-catecholamines*
-thyroid hormone
-isoniazid
-GCs*
-calcitonin
-phenothiazines
-oral contraceptices
-somatropin
-morphine*
-*inc glucose output from liver
Agents that inc risk of insulin hypoglycemia
-ETHANOL**
-ACE-I
-somatostatin
-B-blockers*
-fluoxetine
-steroids
-MAO inhibitors
-vigorous exercise
Lipodystophy
changes in fat at over used inj site
Lipohypertrophy
-accumulation of fat in SC tissue
-more common
Lipoatrophy
-loss of fat in SC tissue
-less common
Insulin resistance
-immune response to insulin
-rarer
Tx overview for type I DM
-insulin + diet + exercise
-always insulin bc they cant make any
Overview of type II DM tx
- diet+exercise
- ”” + antidiabetic drugs
- diet/exercise + insulin
Which insulin preparation has longest duration of
Glargine
Which insulin prep is NOT genetically modified?
-Lispro
-Aspart
-Glulisine
-NPH
-NPH
-NPL is bc it with lispro?
Lente insulins
-not using these
-large complex sixe = prolonged absorption
-Zn helps complex insulin = prolonged activity
Ways to prolong action
-Zn (lente)
-protamine
-precipitation
-add fatty acid