Протамин сульфат: свойства, применение и побочные эффекты

Pharmaceutical drug
Common side effects include low blood pressure, slow heart rate, allergic reactions, and vomiting. While there is no evidence of harm from using during pregnancy it has not been well studied in this group. Protamine works by binding with heparin. It was originally made from the sperm of salmon (salmine, salmon protamine). It is now mainly made using recombinant biotechnology.

Protamine sulfate is usually administered to reverse the large dose of heparin administered during certain surgeries, especially heart surgery where anti coagulation is necessary to prevent clot formation within the cardiopulmonary bypass pump apparatus. A dose of protamine is given, by drip administered over several minutes, once the patient is off pump, when extracorporeal circulation and anticoagulation are no longer needed. It is also used in gene transfer, protein purification and in tissue cultures as a crosslinker for viral transduction. In gene therapy, protamine sulfate has been studied as a means to increase transduction rates by both viral and nonviral mediated delivery mechanisms (e. g. utilizing cationic liposomes). Protamine is used in insulin aspart protamine and NPH insulin.

Dosage for heparin reversal is 0.5mg to 1.0 mg  mg protamine sulfate IV for every 100 IU of active heparin. Partial thromboplastin time (PTT) should be monitored at 5 to 15 minutes after dose then in 2–8 hours afterward.

Protamine has been reported to cause allergic reactions in patients who are allergic to fish, diabetics using insulin preparations containing protamine, and vasectomized or infertile men. These occur at rates ranging from 0.28% to 6%. Avoiding rapid infusion of protamine sulfate and pre treating at risk patients with histamine receptor antagonists (H1 and H2) and steroids may minimize these reactions. A 5 to 10 mg test dose is recommended following pretreatment before administering the full dose. Albrecht Kossel (1853 1927) a German biochemist showed that the substance, called "nuclein", consisted of a protein component and a non protein component. Kossel further isolated and described the non protein component. This substance has become known as nucleic acid, which contains the genetic information found in all living cells. Although the first protamine was isolated by Friedrich Miescher in 1869 from salmon sperm, Protamine published article was in 1874. Later, Kossel was awarded the Nobel Prize in Physiology or Medicine in 1910 for his research in cell biology, the chemical composition of the cell nucleus, and for his work in isolating and describing nucleic acids. All protamine precipitated as the double salt of platinum and was free of sulfur and phosphorus. Protamine sulfate was originally made from the sperm of salmon. The protamine of salmon, later named “salmine”, which can be extracted with hydrochloric acid and precipitated with platinum chloride, corresponds to about 26.8 % of the dried sperm. Protamine sulfate was approved for medical use in 1969 and now it is mainly made using recombinant biotechnology. Protamine sulfate replaced hexadimethrine bromide (Polybrene), another cationic agent that was the original heparin reversal agent in the early days of heart surgery, until studies in the 1960s suggested that hexadimethrine bromide might cause kidney failure when used in doses in excess of its therapeutic range.