Journal of In Silico & In Vitro Pharmacology

Introduction

Protamine is a polypeptide derived from the sperm of salmon fish. It is now made using recombinant DNA technology. Protamine, a strong base, binds to unfractionated heparin, a commonly used anticoagulant, and neutralises it. Because the activity of heparin is short-lived due to metabolism, protamine is rarely necessary to reverse it. However, it has been safely used as an antidote for years in cardiovascular procedures when heparin's activity must be ended quickly. However, protamine can cause deadly Adverse Drug Reactions (ADRs) such as hypotension and pulmonary arterial hypertension in a small Percentage of Cases (PAH).

Discussion

Hypotension, anaphylaxis, PAH, bradycardia, hepatic renal impairment, cardiovascular collapse, and mortality are some of the adverse effects of protamine that have been recorded. The rate of occurrence ranges from 0.06%-10.6%. The pathophysiology of ADRs is thought to involve immunologic and no immune (pharmacogenetic variants) processes. Protamine was supplied through the peripheral (cephalic) vein in this example because it causes the release of histamine and hypotension when given through the central vein. Protamine is given as a tiny bolus (test dose) to detect any hemodynamic instability early. In this case, there were two bouts of hypotension and PAH. After 60% fresh protamine infusion, the first incident occurred. The second episode was caused by protamine re-challenge and occurred after a 10% protamine infusion. Protamine-related ADR is prevalent in individuals with a history of fish allergy, past vasectomy, and those on Neutral Protamine Haledon (NPH) insulin. Although these are not absolute contraindications, even with recombinant protamine, caution should be exercised, and preoperative identification of these risk factors is required. Cross-reactivity occurs because protamine shares antigens with fish proteins. Vasectomy disrupts the blood-testis barrier, making the host more susceptible to sperm antigens. NPH insulin is a protamine, zinc, and insulin crystalline suspension. In this preparation, chronic protamine exposure resulted in the development of specific immunoglobulin E antibodies in 50% of patients and a 95- fold higher risk of severe protamine hypersensitivity events. None of the risk variables were present in this patient on recombinant protamine. Glimepiride was administered to the patient as an anti-diabetic medicine. Preoperative skin prick testing for hypersensitivity produces false negative results and is not 100% specific. As a result, skin testing is not done on a regular basis at our facility. The negative inotropic action of protamine and the release of nitric oxide cause hypotension. Vasopressors are used to treat this, and antihistamines and anti-inflammatory drugs are used to prevent it.

Conclusion

Advanced pharmacokinetic and pharmacogenetic tests may be developed and implemented to assist prevent protamineinduced ADRs. Newer compounds, such as oligoethylene glycol functionalized guanidinocalixarene, which selectively neutralises heparin intended as an antidote and is extremely biocompatible, may be a safer alternative.