Ecallantide is a drug used for the treatment of hereditary angioedema

Hereditary angioedema

Hereditary angioedema presents in the second to fourth decade, and is characterized by local swelling in subcutaneous tissues....

 (HAE) and in the prevention of blood loss in cardiothoracic surgery

Cardiothoracic Surgery

Cardiothoracic surgery is the field of medicine involved in surgical treatment of diseases affecting organs inside the thorax —generally treatment of conditions of the heart and lungs .-Cardiac / Thoracic:...

. It is an inhibitor of the protein kallikrein

Kallikrein

Kallikreins are a subgroup of serine proteases, enzymes capable of cleaving peptide bonds in proteins. In humans, plasma kallikrein has no known homologue, while tissue kallikrein-related peptidases encode a family of fifteen closely related serine proteases...

 and a 60-amino acid

Amino acid

Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...

 polypeptide which was developed from a Kunitz domain

Kunitz domain

Kunitz domains are the active domains of proteins that inhibit the function of protein degrading enzymes or, more specifically, domains of Kunitz-type protease inhibitors. They are relatively small with a length of about 50 to 60 amino acids and a molecular weight of 6 kDa...

 through phage display

Phage display

Phage display is a method for the study of protein–protein, protein–peptide, and protein–DNA interactions that uses bacteriophages to connect proteins with the genetic information that encodes them. Phage Display was originally invented by George P...

 to mimic antibodies

Antibody mimetic

Antibody mimetics are organic compounds that, like antibodies, can specifically bind antigens, but that are not structurally related to antibodies. They are usually artificial peptides or proteins with a molar mass of about 3 to 20 kDa...

 inhibiting kallikrein. On November 27, 2009, ecallantide was approved by the U.S. Food and Drug Administration for the treatment of acute attacks of hereditary angioedema for persons over 16 years of age.

If approved for cardiothoracic surgery, it could become a replacement for aprotinin

Aprotinin

The drug aprotinin , is the bovine version of the small protein basic pancreatic trypsin inhibitor, or BPTI, which inhibits trypsin and related proteolytic enzymes. Under the trade name Trasylol, aprotinin was used as a medication administered by injection to reduce bleeding during complex surgery,...

, which was withdrawn in 2007 after being shown to cause complications.

Adverse effects

The most common adverse effects are headache, nausea

Nausea

Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...

, fatigue

Fatigue

Fatigue may refer to:*Fatigue , structural damage from repeated loading*Fatigue , a state of physical and/or mental weakness*Fatigue , safety implications of tiredness...

 and diarrhea

Diarrhea

Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...

. Less common, but observed in more than 5% of patients in clinical trials, are respiratory tract infection

Respiratory tract infection

Respiratory tract infection refers to any of a number of infectious diseases involving the respiratory tract. An infection of this type is normally further classified as an upper respiratory tract infection or a lower respiratory tract infection...

s, fever, vomiting, itching and upper abdominal pain

Abdominal pain

Abdominal pain can be one of the symptoms associated with transient disorders or serious disease. Making a definitive diagnosis of the cause of abdominal pain can be difficult, because many diseases can result in this symptom. Abdominal pain is a common problem...

. Up to 4% of patients showed anaphylaxis

Anaphylaxis

Anaphylaxis is defined as "a serious allergic reaction that is rapid in onset and may cause death". It typically results in a number of symptoms including throat swelling, an itchy rash, and low blood pressure...

, which lead to a black box warning

Black box warning

In the United States, a black box warning is a type of warning that appears on the package insert for prescription drugs that may cause serious adverse effects...

 in the US.

Mechanism of action

HAE is caused by a mutation

Mutation

In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...

 of the C1-inhibitor

C1-inhibitor

C1-inhibitor is a protease inhibitor belonging to the serpin superfamily. Its main function is the inhibition of the complement system to prevent spontaneous activation. C1-inhibitor is an acute-phase protein that circulates in blood at levels of around 0.25 g/L. The levels rise ~2-fold during...

 gene. Defective or missing C1-inhibitor permits activation of kallikrein, a protease

Protease

A protease is any enzyme that conducts proteolysis, that is, begins protein catabolism by hydrolysis of the peptide bonds that link amino acids together in the polypeptide chain forming the protein....

 that is responsible for liberating bradykinin

Bradykinin

Bradykinin is a peptide that causes blood vessels to dilate , and therefore causes blood pressure to lower. A class of drugs called ACE inhibitors, which are used to lower blood pressure, increase bradykinin further lowering blood pressure...

 from its precursor kininogen. An excess of bradykinin leads to fluid leakage from blood vessels, causing swelling of tissues typical of HAE.

Ecallantide suppresses this pathogenetic mechanism by selectively and reversibly inhibiting the activity of plasma kallikrein.