Information portal on Hereditary Angioedema (HAE)

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This document was printed on 22.Nov.2008.

Glossary

Index

A

Abdomen

Abdomen is the medical (Latin) name for the cavity between the chest and pelvis and its internal organs.

ACE inhibitor

ACE inhibitors (short for Angiotensin Converting Enzyme inhibitors) are a class of medicinal substances used to treat high blood pressure or congestive heart failure. Among other things, ACE inhibitors inhibit degradation of bradykinin, leading to an increase in bradykinin levels, which can trigger angioedema. This can happen the first time an ACE inhibitor is taken or at any time later during the time these drugs are taken. Important examples of ACE inhibitors are captopril, enalapril, lisinopril and ramipril.

Adrenaline

Adrenaline is a hormone that is formed in the adrenal medulla and released into the blood in stressful situations. Among other things, adrenaline increases blood pressure, speeds up the heartbeat and dilates the bronchi. It is administered (in combination with other drugs) in an emergency involving anaphylactic shock. In this situation, it causes the blood vessels to constrict, increases cardiac output and makes it easier for the patient to breathe.

Agonist

An agonist is a naturally occurring or synthetic substance (e.g. a drug) that binds to a cell receptor and activates it, thereby triggering certain responses in the cell. An example of an agonist is the tissue hormone bradykinin, which increases the permeability of the blood vessels by binding to its receptor. The opposite of an agonist is an antagonist.

Allergy

An allergy is an overreaction of the immune system to substances in the environment that are usually harmless, such as pollen or food components, or to insect venom and drugs. The substances that trigger the allergy are called allergens. The body responds to allergens with signs of inflammation and production of antibodies. The tissue hormone histamine is the main cause of reactions such as swelling, redness and itching. In extreme cases, an allergic reaction can escalate to anaphylactic shock, which can result in cardiovascular failure. An allergic reaction can manifest itself on the skin in the form of wheals (urticaria).

Anaphylactic shock

Anaphylactic shock is the most severe form of an allergic reaction and can be triggered by allergens such as drugs, insect venom or food components. Within a few minutes of contact with the allergen, there is a rapid drop in blood pressure with reduced perfusion of important organs.
In extreme cases, fatal cardiovascular failure occurs.

Androgen

Androgen is the generic term for any natural or synthetic compound, usually a steroid hormone, which stimulates or controls the development and maintenance of masculine characteristics in vertebrates by binding to androgen receptors. This includes the activity of the accessory male sex organs and development of male secondary sex characteristics. Androgens, which were first discovered in 1936, are also called androgenic hormones or testoids. Androgens are also the original anabolic steroids. They are also the precursor of all estrogens, the female sex hormones. The primary and most well-known androgen is testosterone.

Angioedema

Angioedema is the name for an acute swelling that occurs in subcutaneous tissue or mucous membranes and can last from several hours to days. The swelling can affect both external areas (face, extremities and genitalia) and internal organs (digestive tract).
Laryngeal edema involves swelling in the larynx, which can be associated with life-threatening breathing difficulties.

Antagonist

A drug that attenuates or even completely eliminates the effect of an agonist by blocking the site at which it binds to its receptor is called an antagonist. In doing so, the antagonist has no physiological effect of its own. The active substance Icatibant is an antagonist that binds to the bradykinin B2 receptor, thereby inhibiting the effect of bradykinin.

Antifibrinolytic drug

An antifibrinolytic agent is a substance, such as a drug, that prevents the degradation of blood clots by inhibiting degradation of fibrin, an important component of the blood clot.

Antihistamines

Antihistamines are drugs used, among other things, to treat allergies or an anaphylactic shock. They bind to the receptor of the tissue hormone histamine, which is responsible for the symptoms of an allergic reaction, and attenuate or completely eliminate its effect.
Antihistamines have no effect on hereditary angioedema, as its symptoms are caused mainly by the peptide hormone bradykinin.

Ascites

Ascites is an accumulation of free fluid in the abdominal cavity. The causes of this can be diverse, e.g. severe liver disease (cirrhosis, tumour), inflammation of the peritoneum and protein deficiency.
Ascites can also occur in cases of hereditary angioedema.

ATII antagonist

ATII antagonists (also called angiotensin II antagonists) are drugs that lower blood pressure by blocking the binding site of the hormone angiotensin II.
In very rare cases, drug-induced angioedema can occur as a side effect.

Autosomal inheritance

Autosomal inheritance is the inheritance of a characteristic (of a gene) via what are known as autosomes, of which there are 22 pairs, rather than the sex chromosomes.
Inheritance can be either dominant or recessive.

B

Bioavailability

The bioavailability of a drug indicates how quickly and to what extent its active substance is absorbed by the body and becomes available at the site of action. Relative bioavailability compares the bioavailability of a certain pharmaceutical form of a drug, e.g. a tablet, to that of another pharmaceutical form. The different pharmaceutical forms are usually compared to intravenous administration of the drug, which has a bioavailability of 100%.

Bradykinin

Bradykinin is a naturally occurring peptide hormone that consists of nine amino acids and is formed locally in tissue. It is involved in the mediation of pain in the event of injury or inflammation. It increases the permeability of the vessels, dilates the blood vessels and causes smooth muscle to contract.
In hereditary angioedema, bradykinin is responsible for the development of swelling.

Bradykinin B2 receptor

The bradykinin B2 receptor is a molecule located in the membrane of cells in the vessel wall that binds the peptide hormone bradykinin. In doing so, it increases the permeability of the vessels. The active substance Icatibant can displace bradykinin from its receptor, thereby inhibiting its effect.

C

C1-esterase inhibitor

C1 esterase inhibitor is a protein that inhibits the activity of the enzyme C1 esterase. In types I and II HAE, there is either a C1 esterase inhibitor deficiency, or this enzyme does not function properly. These abnormalities are either congenital or acquired by spontaneous mutation of a gene on chromosome 11. If there is insufficient C1 esterase inhibitor activity, an increase in bradykinin concentrations can cause the typical symptoms of angioedema: swelling of the skin, larynx and gastrointestinal tract.

Clinical trial

A meticulously controlled test of a drug candidate or a new invasive medical device in patients or healthy volunteers.

Colic

Patients with colic suffer from extremely painful cramps affecting various organs, e.g. the intestine, kidneys or gall bladder. The cramps are like contractions because periods of pain alternate with symptom-free periods.

Complement

The complement system is an important part of the immune system. It consists of more than 30 proteins, which occur in soluble or cell-bound form in blood plasma. The complement system is involved in blocking pathogens like bacteria or fungi. However, it can also damage tissues if it gets out of control in certain (autoimmune) disorders.

Contraceptive

A contraceptive is a method of preventing pregnancy, e.g. the pill, which contains female sex hormones (oestrogens and progestogens). The pill is also thought to be a trigger for hereditary angioedema attacks.

D

Dominant inheritance

With dominant inheritance, a genetic trait prevails, even if it is found in only one parent. The trait is expressed in all offspring. With recessive inheritance, both parents must be carriers for the trait to show in their offspring.
An example of dominant inheritance is the inheritance of hereditary angioedema.

E

Edema

Edema [= Oedema] is an accumulation of fluid in the tissues or body cavities. In hereditary angioedema, fluid is released from the vascular system due to increased permeability of cell layers in the vessel wall.

Edema of the glottis

Edema of the glottis is a mostly acute and life-threatening swelling of the mucous membrane in the larynx.

ELISA - Enzyme-Linked ImmunoSorbent Assay

The Enzyme-Linked ImmunoSorbent Assay, or ELISA, is a biochemical technique used mainly in immunology to detect the presence of an antibody or an antigen in a sample. The ELISA has been used as a diagnostic tool in medicine and plant pathology, as well as a quality control check in various industries. Performing an ELISA involves at least one antibody with specificity for a particular antigen. The sample with an unknown amount of antigen is immobilized on a solid support (usually a polystyrene microtiter plate) either non-specifically (via adsorption to the surface) or specifically (via capture by another antibody specific to the same antigen, in a "sandwich" ELISA). After the antigen is immobilized the detection antibody is added, forming a complex with the antigen. The detection antibody can be covalently linked to an enzyme, or can itself be detected by a secondary antibody which is linked to an enzyme through bioconjugation. Between each step the plate is typically washed with a mild detergent solution to remove any proteins or antibodies that are not specifically bound. After the final wash step the plate is developed by adding an enzymatic substrate to produce a visible signal, which indicates the quantity of antigen in the sample. Older ELISAs utilize chromogenic substrates, though newer assays employ fluorogenic substrates with much higher sensitivity. In simple terms, an unknown amount of antigen in a sample is immobilized on a surface. One then washes a particular antibody over the surface. This antibody is linked to an enzyme that visibly reacts when activated, say by light hitting it in the case of a fluorescent enzyme; the brightness of the fluorescence would then tell you how much antigen is in your sample.

Enzyme

An enzyme is a protein that speeds up and controls biochemical reactions in the body.

Epsilon-aminocaproic acid

Epsilon-aminocaproic acid is a synthetically produced amino acid that inhibits the conversion of plasminogen to plasmin. Plasmin is a naturally occurring enzyme that plays a role in the degradation of blood clots. Epsilon-aminocaproic acid is chemically related to tranexamic acid and is also used to treat hereditary angioedema, although it has only a weak effect.

F

FAQ

FAQ stands for frequently asked questions, a list of questions that are often asked and the answers.

Fast-track (FDA)

Fast-track programmes from the FDA (FDA: Food and Drug Administration is an agency of the United States Department of Health and Human Services and is responsible for the safety regulation of drugs) promote development and accelerate testing of new drugs and biological products that are intended for treatment of severe or life-threatening diseases and show the potential to meet medical needs that have not been met previously.

Fibrin

Fibrin is a protein that plays an important role in the coagulation of blood. It is formed from its precursor fibrinogen under the influence of the enzyme thrombin.
Fibrin strands merge to form larger units, producing a kind of mesh that plugs the wound as a blood clot.

Fibrosis

Fibrosis is the conversion of organ tissue that has been damaged by chronic inflammation, circulatory disorders or degenerative processes into connective tissue that can no longer perform the original functions of the affected organ.

G

Glucocorticoids

Glucocorticoids are steroid hormones that are formed in the adrenal cortex. The most important examples are cortisone and cortisol. They influence metabolism, e.g. sugar metabolism, and have anti-inflammatory properties. They also suppress the activity of the immune system.
Synthetic glucocorticoids are used to treat allergies, for example.

H

Hereditary

Hereditary means inherited and signifies the transfer of characteristics and traits to the offspring. Certain disorders like hereditary angioedema can also be inherited.

Histamine

Histamine is a tissue hormone that is derived from the amino acid histidine and, among other things, plays an important role in allergic reactions.
In cases of allergy, it is the main cause of symptoms like swelling, redness and itching.

Hormone

A hormone is a messenger that is formed in glands and released into the blood stream for transfer to an organ or tissue, where it triggers certain effects by binding to its receptor.
Known examples of hormones are insulin and cortisone.

I

i.v.

i .v. stands for intravenous. An i.v. injection is, for example, the administration of a drug solution into a vein. An intravenous injection is usually administered by people who have been specially trained in this procedure (doctors, nursing staff).

Icatibant

Icatibant, a peptidomimetic molecule consisting of 10 amino acids, is a selective and effective antagonist of bradykinin B2 receptors.
By binding to these receptors, it inhibits the effect of the physiological tissue hormone bradykinin, e.g. in HAE.
Icatibant is in the last phase of clinical development for treatment of hereditary angioedema.

Idiopathic

Idiopathic means occurring with no identifiable cause.
Idiopathic disorders are disorders of unknown cause.

Incidence

The incidence is the number of new cases of a certain disease in the population within a defined period of time (see also prevalence).

Inhibitor

In medicine and pharmacology, an inhibitor is a drug that delays or inhibits biochemical processes.

Integrins

A large family of important proteins that enable cells to bind and respond to extracellular compounds. They are involved in various cell functions including wound healing, cell differentiation, growth of tumor cells, and natural cell death.

Intubation

Intubation is the insertion of a tube into the windpipe through the mouth or nose in order to secure the airways.

L

Laryngeal edema

Laryngeal edema is edema of the voice box (see also edema of the glottis).

Larynx

Larynx is the anatomical name for the voice box.

M

Manifestation

In medicine, the appearance signs or symptoms of a disorder is known as manifestation.

O

Oestrogens

Oestrogens are the most important female sex hormones. They are formed primarily in the ovaries and, to a lesser extent, in the adrenal cortex. There is a noticeable decline in oestrogen production during and after the menopause. Oestrogens can trigger hereditary angioedema attacks.

Open label study

If a drug is clinically tested in an open label study, the people involved in the study (doctor, patients, study assistants) know which drug or active substance the patient is taking, whereas in a double-blind study, in which an active substance is compared to a dummy drug (placebo) for example, neither the doctor nor the patient knows which product the latter is taking.

Orphan Drug Status

Orphan drug status provides special licensing conditions for drugs that are developed for treatment of rare diseases. For instance, a manufacturer that develops an orphan drug is granted a monopoly in the EU for the requested indication for a period of ten years. Orphan drug status is intended to provide an incentive for pharmaceutical companies to develop drugs for rare diseases.

P

Pathogenesis

In medicine, the development of diseases is known as pathogenesis.

Peptide

A peptide is a molecule in which at least two and up to about 100 amino acids are linked by what are known as amide or peptide bonds. Peptides can have various effects on the human body. For example, bradykinin is a peptide that acts locally as a hormone.

Peptidomimetic

A peptidomimetic is a peptide in which naturally and non-naturally occurring amino acids are linked by amide bonds. Among other things, peptidomimetics are used as drugs. For example, the bradykinin B2 receptor antagonist Icatibant is a peptidomimetic.

Pharmacokinetics

Pharmacokinetics is concerned with how quickly and to what extent the active substance of an administered drug is absorbed by the body, reaches the blood stream, is distributed throughout the body and is excreted again.

Phase I-IV

Drugs are developed in clinical trials, which are divided into different phases.

In phase I, the drug to be tested is used in humans for the first time. It is preceded by preclinical studies in which the toxicological properties of the drug have been tested. The purpose of this phase of development is to test primarily the safety and tolerability of the drug in a small number (up to about 50) of healthy volunteers. Data relating to the dosage, absorption/elimination (pharmacokinetics) and effect (pharmacodynamics) of the drug should also be obtained.

In phase II, the treatment concept is reviewed (proof of concept) using a select group of patients (50-200). The correct dose of the treatment should be established in this phase of the study. Further safety data are also recorded.

In phase III, proof that a predefined dose of the drug has a statistically significant effect should be obtained. To this end, the drug is tested on a larger patient group (200 to 10,000) and compared to either a dummy drug, a drug that has already been approved or an approved treatment method.

Once the drug has been approved, phase IV involves further testing of the safety profile of the drug. For example, this phase should identify very rare side effects, which may not necessarily have been possible to detect in the small number of patients used in previous studies.

Placebo

A placebo is a pharmacologically inactive preparation (e.g. tablet, gel, solution) used as a control for comparison with an active substance in double-blind studies. As neither the doctor nor the patient knows whether a placebo or the active substance is being used in such studies, the possibility that they may be influenced by knowledge of the preparation being taken is avoided.

Preclinical development

In the preclinical development phase, fundamental pharmacological and toxicological effects and properties of a drug are tested.
Clinical studies on humans may only be conducted if these preclinical studies have shown that the drug can be regarded as safe.

Prevalence

Prevalence indicates how many people in the population or in a certain section of the population suffer from a disease (see also incidence).

Proliferation

In medicine, proliferation means the propagation and growth of tissue through cell division.

Proof of concept study

In a proof of concept study (phase II), a drug that is in development is tested in humans in order to ascertain whether it actually has the presumed effect.

Prophylaxis

Measures that are taken in order to prevent diseases or their symptoms are known as prophylaxis.

Protein

Proteins are large biological molecules consisting of 100 to more than 1,000 amino acids. The amino acids are linked by what are known as amide bonds.
There are 20 amino acids present in humans and these can be linked to proteins in any order. Smaller protein compounds (< 100 amino acids) are called peptides.

R

Recessive inheritance

With recessive inheritance, both parents must be carriers for a certain trait to show in their offspring.
If only one parent has the recessive trait, it can be concealed by a trait from the other parent in their offspring. Even if a recessive trait does not show, it can still be passed on (see dominant inheritance).

Recurrence

A recurrence is the reappearance of a disease or its symptoms after regression of a previous episode.

Refractory

Unresponsive to medical treatment.

Rheumatoid Arthritis

A chronic disease of the joints that causes stiffness, swelling, weakness, loss of mobility, and eventual destruction and deformity of the joints. Considered to be an autoimmune disorder in which immune complexes are formed in joints and cause an inflammatory response.

S

Small molecule

A term for drugs or natural biological molecules below a certain size and specifically excluding large biological molecules such as proteins, antibodies, and genes of derivatives thereof.

Subcutaneous injection

A drug that is administered subcutaneously is injected under the skin. This is easier to perform than an intravenous injection. A subcutaneous injection can be administered by the patient. For example, the active substance Icatibant is administered subcutaneously.

Substitution

In medicine, substitution means replacement of a deficient naturally occurring substance through external administration of this substance. For example, diabetics undergo insulin replacement if their pancreas stops producing insulin or fails to produce enough insulin.

T

Tissue hormone

A tissue hormone is a messenger that is produced in specialised individual cells and has a primarily local effect.
Derivatives of amino acids such as histamine or small protein molecules (peptides) such as bradykinin are examples of tissue hormones.

Tranexamic acid

Tranexamic acid is a drug (antifibrinolytic agent) that prevents the breakdown of blood clots by inhibiting the fibrinolytic enzyme plasmin.

Trauma

In medicine, an injury or physical damage caused by an external force is known as trauma.

U

Urticaria

Urticaria is another name for hives. In this disorder, an allergen (foods, drugs) causes red, itchy wheals to form on the outer layer of skin. Urticaria can also be caused by emotional stress or physical influences (cold, heat, pressure).

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