Protamine zinc

This crystalline salmiridine-insulin can be removed if desired, as by filtration but it is not necessary to do that, as the suspension of crystalline salmiridine-insulin may be preserved as thus prepared, and dispensed and used (in the same manner as known preparations of protamine insulin and protamine-zinc-insulin are used) in the original suspending medium in which it is formed. 

Insulin is ordered by die generic name (insulin zinc suspension, extended) or the trade (brand) name (Humulin U) (see the Summary Drug Table Insulin Preparations). The nurse must never substitute one brand of insulin for anodier unless the substitution is approved by the health care provider because some patients may be sensitive to changes in brands of insulin. In addition, it is important never to substitute one type of insulin for anodier. For example, do not use insulin zinc suspension instead of die prescribed protamine zinc insulin. 

Previous protamine exposure (e.g., during coronary artery bypass graft, or NPH insulin products containing protamine zinc)... 

A patient is required to take 10 units of U-40 isophane insulin suspension and 18 units of U-100 protamine zinc insulin. What volume, in milliliters, of each type will provide the desired dosage ... 

Insulin suspensions. When the hormone is injected as a suspension of insulin-containing particles, its dissolution and release in subcutaneous tissue are retarded (rapid, intermediate, and slow insulins). Suitable particles can be obtained by precipitation of apolar, poorly water-soluble complexes consisting of anionic insulin and cationic partners, e.g the polycationic protein protamine or the compound aminoqui-nuride (Surfen). In the presence of zinc and acetate ions, insulin crystallizes crystal size determines the rate of dissolution. Intermediate insulin preparations (NPH or isophane, lente or zinc insulin) act for 18 to 26 h, slow preparations (protamine zinc insulin, ultralente or extended zinc insulin) for up to 36 h. 

Protamine zinc insulin insulin complexed to excess protamine in order to prolong its duration of action... 

Protamine zinc and extended insulin zinc suspension (Ultralente) are often referred to as long-acting insulin preparations. These insulins have more protamine and zinc in the mixture than is found in isophane insuhn suspension. Insuhn zinc suspension, extended Ultralente Insulin), is quite similar to the protamine zinc insulin suspension except that it does not contain protamine. Both of these long-acting insuhns have an approximate duration of action of 36 hours. 

Semilente insulin is a suspension of amorphous insulin zinc. The onset is 1-3 hours after subcutaneous administration, reaches maximum effect in 5-10 hours and the effect lasts 10-16 hours. Isophane insulin (NPH Neutral solution. Protamine, Hagedorn s laboratoiy insulin) is an intermediate-acting preparation prepared with protamine. The maximum effect is reached in 4-12 hours and lasts 8-26 hours. Patients using these preparations who present for cardiac surgery are at increased risk for anaphylactic reactions to protamine. Ultralente insulin is a long-acting preparation formed with zinc rather than protamine. Zinc retards the release of insulin and these preparations have a duration of up to 36 hours. Protamine zinc insulin, which contains both protamine and zinc, has a duration of 28-36 hours. 

Long-acting Protamine zinc insulin injection 4-6 16-24 24-36... 

In a double-blind, crossover study of insulin aspart or soluble human insulin before meals and protamine zinc insulin before bedtime, 90 of 104 patients with type 1 diabetes completed the trial (5). Insulin aspart improved postprandial control by reducing hyperglycemic and hypoglycemic variations, but night-time control was inferior. There were 547 hypoglycemic episodes in the aspart... 

Insulin detemir has been compared with protamine zinc insulin in 59 patients with type 1 diabetes (3). All used insulin detemir for 6 weeks and protamine zinc insulin for 6 weeks in a randomized order. About 2.35 times higher doses of detemir were necessary than protamine zinc insulin. Fasting blood glucose concentrations were lower at the end of the detemir period and there were fewer attacks of hypoglycemia. 

In a 6-month, multinational, open, parallel-group comparison of insulin detemir and protamine zinc insulin in 448 patients with type 1 diabetes, the two treatments produced comparable HbAlc concentrations and fasting plasma glucose concentrations with less within-subject variation in fasting blood glucose with insulin detemir (4). The risk of hypoglycemia was 22% lower with insulin detemir and 34% lower for nocturnal hypoglycemia. 

The absorption of insulin glargine was delayed compared with protamine zinc insulin in a study using radioactive tracers (11). 

In single-dose, double-bhnd, euglycemic clamp studies, insulin glargine had a smoother metabolic effect with a peakless profile of action starting at 2-4 hours and continuing over 24 hours than protamine zinc insulin, whose peak occurred at 4 hours and whose activity subsequently fell (12). 

In a randomized, parallel-group study, there were fewer episodes of nocturnal and serious hypoglycemia when insulin glargine was compared with once- or twice-daily protamine zinc insulin (13,14). Other adverse reactions and reactions at the injection sites were identical. 

Insulin glargine did not cause a peak in blood insulin concentration, compared with protamine zinc insulin and crystalline insulin zinc suspension (ultralente) the effect lasted 24 hours, almost comparable to continuous subcutaneous infusion of a short-acting insulin (15). 

In general, one daily injection of insulin glargine gives more constant insulin concentrations and fewer nightly attacks of hypoglycemia than protamine zinc insulin. Treatment satisfaction was constantly better with insulin glargine in 517 patients (16). There was a consistent mean reduction in the perceived frequency of attacks of hypoglycemia. Other adverse effects were not mentioned. 

In 619 patients with type 1 diabetes treated with protamine zinc insulin and insulin lispro, randomized to once-daily insulin glargine or to once-daily or twice-daily protamine zinc insulin for 16 weeks in an open study, there was no difference in the frequency of hypoglycemic episodes, severe hypoglycemia, or HbAic (25). Fasting plasma glucose concentrations were lower with insulin glargine. 

In 518 patients with type 2 diabetes using protamine zinc insulin, with or without short-acting insulin, randomized to insulin glargine or protamine zinc insulin, there was less nocturnal hypoglycemia with insulin glargine (26). HbAic and mild symptomatic hypoglycemia was the same in both groups. 

In 426 patients with type 2 diabetes poorly controlled with oral therapy, randomized to protamine zinc insulin or insulin glargine, glucose concentrations after dinner were lower with insulin glargine and there were significantly fewer attacks of hypoglycemia (27). HbAic was 8.2 and 8.1% with insulin glargine and protamine zinc insulin respectively. 

There were no differences between human protamine zinc insulin and human ultralente insulin when either was added once or twice daily to insulin lispro (10). 

Premeal hyperglycemia is common. The short action of insulin lispro can then be extended by the addition of protamine zinc insulin. In a 3-month study in addition to a once-daily injection of protamine zinc insulin, at each meal insulin lispro or insulin lispro + protamine zinc insulin was injected the postprandial blood glucose concentration was lower, but the post-absorptive glucose concentration was higher in the insulin lispro-only group there was no difference in HbAic. The addition of protamine zinc insulin (30% at breakfast, 40% at lunch, and 10% at dinner) improved post-absorptive glucose and HbAic (12). 

Insulin Mix 25 (25% insulin lispro and 75% neutral protamine zinc insulin) reduced the glucose response to a standardized breakfast meal better than premixed 30% regular + 70% protamine zinc insulin when 22 patients with type 2 diabetes were studied three times in a double-blind fashion (13). Protamine zinc insulin mixed with insulin lispro has the same action profile of insulin lispro,... 

A crossover comparison of regular insulin + protamine zinc insulin at bedtime with insulin lispro + multiple protamine zinc insulin showed no effect on overall hypoglycemia but there was less frequent severe hypoglycemia with the second treatment (20). The reduction in HbAlc was small and not significant. Insulin doses were the same. Patients preferred the second treatment. 

Insulin probably exists in the pancreas as a zinc compound, but administration of insulin, per se, is effective in controlling diabetes. The main reason for using a zinc-containing preparation such as neutral protamine zinc insulin is that it is stable, dissolves more slowly and lasts longer than insulin, itself, when given by hypodermic injection. 

An important consideration to the pharmacologist is the useful lifetime of a drug in the body. Protein hormones have been modified chemically to lower their rate of removal from the bloodstream, prolong the effect of the injected hormone, and thus reduce the required frequency of administration. The modification of animal insulin by coupling to protamine-zinc is probably the best-known example. Others are the studies by Marshall on the possibility of lengthening the lifetime in the bloodstream of injected proteins by supplying them as dextran conjugates... 

Isophane insulin suspension Protamine zinc insuiin... 

Mixing drugs formulated for injection in a syringe may cause interaction, e.g. protamine zinc insulin contains excess of protamine which binds with added soluble insulin and reduces the immediate effect of the dose. 

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