Insulins to treat diabetes Flashcards by Brooke Thornburg

Insulin sources

-recombinant human insulin
-human insulin cDNA in plasmid (E.Coli or yeast)

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Humulin

-insulin cDNA in plasmid in E. Coli

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Novolin

-transformed yeast insulin cDNA

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Units of insulin

-100 units/mL
-28 units/mg insulin
-humulin also available in 500units/mL

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Insulins with rapid onset and short duration

-Lispro
-Aspart
-Glulisine

-mimic first phase

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Rapid Onset/ Shortish Action

Regular (R)

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intermediate onset and action

NPH (N)

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slow onset/ long action

-Glargine
-Detemir
-Degludec

-mimic second phase

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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

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Insoluble Insulin Complexes

-Lente insulins (no longer used)
-NPH insulin

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Semilente

-small amorphous particles

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Lente

-small amorphous and large crystalline complexes
-slow absorption, long acting

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Ultralente

-only large crystalline complexes
-very slow absorption, very long acting

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Insulin hexamer

-nucleated by zinc
-trimer of dimers
-slide 35??

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lente insulins

-zinc/insulin precipitates
-large complex size = prolong absorption from SC site
-monomer is absorbed
-slide 34

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NPH insulin

-Neutral Protamine Hagedorn
-bound insulin to protamine
-tissue proteases free insulin from protamine
-slow absorption, long action

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Mutated Human Insulins

-Lispro (humalog)
-Insulin Aspart (Novolog)
-Insulin Glulisine (Apidira)
-Insulin Glargine (Lantus)
-Insulin Detemir (Levemir)
-Insulin Degludec (Tresiba)

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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

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Lispro insulin (humalog) counseling

-5-15 min onset
-inj immediately before meals

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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

1. diet+exercise 2. "" + antidiabetic drugs 3. 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