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Cloudy insulin

An example of what cloudy insulin should look like after it's been properly resuspended.

Suspension is a part of the liquid your insulin is mixed with to change its action profile.

The three major suspension types you'll see are Isophane, Protamine Zinc, and Zinc suspensions. Neutral insulins do not use an added suspension.

A suspension is either minerals, proteins, or both, added to the insulin's diluting liquid to slow their absorption in the body and make them work longer. [1][2]

Suspended insulins are cloudy or milky in appearance, even before they have been rolled; they must be rolled or resuspended before use or they will not be properly effective.

Analog mixed insulins are suspended by the use of protamine to create special insulin crystals. These mixes also begin with the basic insulins: Humalog or Novolog/NovoRapid.

The long-acting analog insulins Lantus and Levemir don't have the "traditional" types of suspension but they are prolonged by other means. Lantus doesn't form crystals until it's under the skin; the crystals are slow to absorb. Levemir uses a binding to albumin in the bloodstream to prolong its action.

R/Neutral insulins-no suspensionEdit

Novolin R

R/Neutral insulin has no suspension.

R or neutral insulin is basically zinc insulin crystals dissolved in clear fluid with nothing added to alter its action or speed. [3]--no suspension.   R/Neutral insulins also have no buffer. [4]

The zinc suspension of Lente-type insulin binds R/Neutral, causing the short-acting insulin to slow, losing its short-acting effect. [5][6], so combining them would be incompatible [7]

From 1921 to the 1930's when PZI was developed, R was the only kind of insulin available.



Isophane suspension insulinsEdit

Novolin N

NPH insulin is isophane suspended.

NPH or isophane insulins combine protamine, zinc and insulin. The difference between NPH and its older brother, PZI, is the amount of protamine in the formula; PZI insulin has more protamine in it. The salmon-derived protamine is less readily absorbed than insulin itself; basically the system must absorb all of the protamine present in the formulation before the absorption process of the insulin can begin. [4]

Mixed insulins contain a given ratio of R/Neutral and NPH/isophane insulin. These are all phosphate buffer insulins, just as NPH/isophane insulin without any addition of R/Neutral is. The phosphate buffer makes them incompatible with the Lente-type insulins for combining. [4][7] These mixed insulins are a combination of intermediate-acting NPH/isophane insulin with short-acting R/Neutral producing intermediate-acting insulins.



Protamine zinc suspension insulinsEdit

91 main

Protamine Zinc Insulin (PZI) is suspended by using more protamine in the formula than for NPH/Isophane insulin.

The difference between PZI and its younger brother, NPH, is the amount of protamine in the formula; PZI insulin has more protamine in it.[9] The salmon-derived protamine is less readily absorbed than insulin itself; basically the system must absorb all of the protamine present in the formulation before the absorption process of the insulin can begin. [4] Since there's more protamine present in Protamine Zinc insulin, it takes the body longer to absorb it before going on to the absorption of the insulin itself. The longer absorption period of the extra protamine is how PZI has more duration. Both NPH/isophane and PZI insulins use phosphate buffers which makes them incompatible with the Lente-type insulins for combining. [4][7]



Zinc suspension insulinsEdit

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Lente insulins are suspended by adding more zinc to the forumula and also by the size of their insulin crystals.

The Lente family of insulins consist of insulin crystals of basically two different sizes--the larger ultralente and the smaller semilente insulin crystals, with added zinc. Combining the short-acting semilente with the slow-acting ultralente in a ratio of 3 parts semilente to 7 parts ultralente produces the intermediate-acting Lente insulin.

It is the addition of zinc and the size of their respective crystals which controls the rate of their absorption, as the only protein present in the Lente family is the insulin itself; they all have acetate buffers. [4]

The phosphate buffer used for both NPH/isophane and PZI insulins is incompatible with Lente-type insulins. Phosphates alter the profile of Lente-type insulins, making them about as fast-acting as R/Neutral. [4][7]

The zinc suspension of Lente-type insulin binds R/Neutral, causing the short-acting insulin to slow, losing its short-acting effect. [5][6], so combining them would be incompatible as well [7]



ReferencesEdit

  1. Diabetes Forecast-page 5. American Diabetes Association (2006).
  2. Insulin-Pharmacology, Types of Regimens & Adjustments. Endotext.org.
  3. Humulin R. Eli Lilly.
  4. 4.0 4.1 4.2 4.3 4.4 4.5 4.6 DeRuiter, Jack. Insulin Preparations-Regular Insulin. Auburn University.
  5. 5.0 5.1 Deckert, T. (1980). Intermediate-Acting Insulin Preparations: NPH (Isophane) & Lente. Diabetes Care.
    Note--in 1980, there was only beef Lente-type insulin--no pork or r-DNA/GE/GMLente insulins
  6. 6.0 6.1 Resource Guide. American Diabetes Association (2005).
  7. 7.0 7.1 7.2 7.3 7.4 Insulin Therapy-Mixing Precautions. RxEd.org.
  8. 8.0 8.1 8.2 8.3 8.4 8.5 8.6 Insulin. InChem.
  9. Greco, Deborah (2010). Treating Diabetes Mellitus in Dogs and Cats. Western Veterinary Conference.

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