Etilefrine, sold under the brand name Effortil among others, is a sympathomimetic

medication Medication (also called medicament, medicine, pharmaceutical drug, medicinal product, medicinal drug or simply drug) is a drug used to medical diagnosis, diagnose, cure, treat, or preventive medicine, prevent disease. Drug therapy (pharmaco ...

used as an

antihypotensive agent An antihypotensive, also known as a vasopressor, is an agent that raises blood pressure by constricting blood vessels, thereby increasing systemic vascular resistance. This is different from inotropes which increase the force of cardiac contra ...

to treat

orthostatic hypotension Orthostatic hypotension, also known as postural hypotension, is a medical condition wherein a person's blood pressure drops when they are standing up ( orthostasis) or sitting down. Primary orthostatic hypotension is also often referred to as ne ...

. It is usually used

by mouth Oral administration is a route of administration whereby a substance is taken through the Human mouth, mouth, swallowed, and then processed via the digestive system. This is a common route of administration for many medications. Oral administ ...

, but is also available as an

injectable An injection (often and usually referred to as a "shot" in US English, a "jab" in UK English, or a "jag" in Scottish English and Scots) is the act of administering a liquid, especially a drug, into a person's body using a needle (usually a hyp ...

Side effect In medicine, a side effect is an effect of the use of a medicinal drug or other treatment, usually adverse but sometimes beneficial, that is unintended. Herbal and traditional medicines also have side effects. A drug or procedure usually use ...

s of etilefrine include

nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. It can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the throat. Over 30 d ...

tremor A tremor is an involuntary, somewhat rhythmic muscle contraction and relaxation involving neural oscillations, oscillations or twitching movements of one or more body parts. It is the most common of all involuntary movements and can affect the h ...

s, and

palpitation Palpitations occur when a person becomes aware of their heartbeat. The heartbeat may feel hard, fast, or uneven in their chest. Symptoms include a very fast or irregular heartbeat. Palpitations are a sensory symptom. They are often described as ...

s, among others. Etilefrine is an

agonist An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an R ...

of the α- and

β-adrenergic receptor The adrenergic receptors or adrenoceptors are a class of G protein-coupled receptors that are targets of many catecholamines like norepinephrine (noradrenaline) and epinephrine (adrenaline) produced by the body, but also many medications like bet ...

s. It is a

substituted phenethylamine Substituted phenethylamines (or simply phenethylamines) are a chemical class of organic compounds that are based upon the phenethylamine structure; the class is composed of all the derivative (chemistry), derivative compounds of phenethylamine ...

and is related to

epinephrine Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions (e.g., respiration). It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands a ...

phenylephrine Phenylephrine, sold under the brand names Neosynephrine and Sudafed PE among others, is a medication used as a decongestant for uncomplicated nasal congestion in the form of a nasal spray or oral tablet, to dilate the pupil, to increase bloo ...

, and

norfenefrine Norfenefrine, also known as ''meta''-octopamine or norphenylephrine and sold under the brand name Novadral among others, is a sympathomimetic medication which is used in the treatment of hypotension (low blood pressure). Along with its structura ...

. Etilefrine was first described and introduced for medical use by 1949.

Medical uses

Etilefrine is used to treat

and as a

nasal decongestant A decongestant, or nasal decongestant, is a type of pharmaceutical drug that is used to relieve nasal congestion in the upper respiratory tract. The active ingredient in most decongestants is either pseudoephedrine or phenylephrine (the latter o ...

. It has also been used

off-label Off-label use is the use of pharmaceutical drugs for an unapproved indication (medicine), indication or in an unapproved age group, dose (biochemistry), dosage, or route of administration. Both prescription drugs and over-the-counter drugs (OTCs) ca ...

to treat

priapism Priapism is a condition in which a penis remains erect for hours in the absence of stimulation or after stimulation has ended. There are three types: ischemic (low-flow), nonischemic (high-flow), and recurrent ischemic (intermittent). Most cases ...

Side effects

s of etilefrine include

s, and

s, among others.

Pharmacology

Pharmacodynamics

Etilefrine is an

of the α₁-adrenergic receptor. It is a

vasoconstrictor Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, in particular the large arteries and small arterioles. The process is the opposite of vasodilation, the widening of blood vesse ...

and

. It has also been described as a β₁-adrenergic receptor agonist with some agonistic actions at the α- and β₂-adrenergic receptors.

Intravenous infusion Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutr ...

of this compound increases

cardiac output In cardiac physiology, cardiac output (CO), also known as heart output and often denoted by the symbols Q, \dot Q, or \dot Q_ , edited by Catherine E. Williamson, Phillip Bennett is the volumetric flow rate of the heart's pumping output: tha ...

stroke volume In cardiovascular physiology, stroke volume (SV) is the volume of blood pumped from the ventricle (heart), ventricle per beat. Stroke volume is calculated using measurements of ventricle volumes from an Echocardiography, echocardiogram and subtra ...

venous return Venous return is the rate of blood flow back to the heart. It normally limits cardiac output. Superposition of the cardiac function curve and venous return curve is used in one hemodynamic model. __TOC__ Physiology Venous return (VR) is the flow ...

, and blood pressure in humans and animals, suggesting stimulation of both α- and

s. However, ''

in vitro ''In vitro'' (meaning ''in glass'', or ''in the glass'') Research, studies are performed with Cell (biology), cells or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in ...

'' studies indicate that etilefrine has a much higher affinity for β₁ (cardiac) than for β₂

adrenoreceptors The adrenergic receptors or adrenoceptors are a class of G protein-coupled receptors that are targets of many catecholamines like norepinephrine (noradrenaline) and epinephrine (adrenaline) produced by the body, but also many medications like bet ...

. Intravenous etilefrine increases the pulse rate, cardiac output, stroke volume,

central venous pressure Central venous pressure (CVP) is the blood pressure in the venae cavae, near the right atrium of the heart. CVP reflects the amount of blood returning to the heart and the ability of the heart to pump the blood back into the arterial system. CVP ...

, and

mean arterial pressure In medicine, the mean arterial pressure (MAP) is an average calculated blood pressure in an individual during a single cardiac cycle. Although methods of estimating MAP vary, a common calculation is to take one-third of the pulse pressure (the d ...

of healthy individuals.

Peripheral vascular resistance Vascular resistance is the resistance that must be overcome for blood to flow through the circulatory system. The resistance offered by the systemic circulation is known as the systemic vascular resistance or may sometimes be called by another ter ...

falls during the infusion of 1 to 8mg etilefrine but begins to rise at higher dosage. Marked falls in pulse rate, cardiac output, stroke volume, and peripheral blood flow, accompanied by rises in mean arterial pressure, occur when etilefrine is infused after administration of intravenous

propranolol Propranolol is a medication of the beta blocker class. It is used to treat hypertension, high blood pressure, some types of cardiac dysrhythmia, irregular heart rate, thyrotoxicosis, capillary hemangiomas, akathisia, performance anxiety, and ...

2.5mg. These findings indicate that etilefrine has both β₁- and α₁-adrenergic receptor actions in humans.

Pharmacokinetics

Absorption

Etilefrine is rapidly absorbed with

oral administration Oral administration is a route of administration whereby a substance is taken through the Human mouth, mouth, swallowed, and then processed via the digestive system. This is a common route of administration for many medications. Oral administ ...

. The oral

bioavailability In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation. By definition, when a medication is administered intravenously, its bioavailability is 100%. H ...

of etilefrine is approximately 50%.

Peak Peak or The Peak may refer to: Basic meanings Geology * Mountain peak ** Pyramidal peak, a mountaintop that has been sculpted by erosion to form a point Mathematics * Peak hour or rush hour, in traffic congestion * Peak (geometry), an (''n''-3)-d ...

concentrations of etilefrine occur after 30minutes.

Distribution

The

plasma protein binding Plasma protein binding refers to the degree to which medications attach to blood proteins within the blood plasma. A drug's efficacy may be affected by the degree to which it binds. The less bound a drug is, the more efficiently it can traverse o ...

of etilefrine is 23%. About 8.5% is bound to

albumin Albumin is a family of globular proteins, the most common of which are the serum albumins. All of the proteins of the albumin family are water- soluble, moderately soluble in concentrated salt solutions, and experience heat denaturation. Alb ...

. Etilefrine is a

peripherally selective drug Peripherally selective drugs have their primary mechanism of action outside of the central nervous system (CNS), usually because they are excluded from the CNS by the blood–brain barrier. By being excluded from the CNS, drugs may act on the rest o ...

Metabolism

Etilefrine is

metabolized Metabolism (, from ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cellular processes; the co ...

conjugation Conjugation or conjugate may refer to: Linguistics *Grammatical conjugation, the modification of a verb from its basic form *Emotive conjugation or Russell's conjugation, the use of loaded language Mathematics *Complex conjugation, the change o ...

, for instance

glucuronidation Glucuronidation is often involved in drug metabolism of substances such as drugs, pollutants, bilirubin, androgens, estrogens, mineralocorticoids, glucocorticoids, fatty acid derivatives, retinoids, and bile acids. These linkages involve gly ...

, in the

liver The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...

and

gastrointestinal tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the Digestion, digestive system that leads from the mouth to the anus. The tract is the largest of the body's systems, after the cardiovascula ...

. There appears to be significant

first-pass metabolism The first pass effect (also known as first-pass metabolism or presystemic metabolism) is a phenomenon of drug metabolism at a specific location in the body which leads to a reduction in the concentration of the active drug before it reaches the ...

. About 3% is metabolized into hydroxymandelic acid.

Elimination

The elimination of etilefrine is dependent on

route of administration In pharmacology and toxicology, a route of administration is the way by which a medication, drug, fluid, poison, or other substance is taken into the body. Routes of administration are generally classified by the location at which the substance ...

. Regardless of route, about 80% is

excreted Excretion is elimination of metabolic waste, which is an essential process in all organisms. In vertebrates, this is primarily carried out by the lungs, kidneys, and skin. This is in contrast with secretion, where the substance may have specific ...

urine Urine is a liquid by-product of metabolism in humans and many other animals. In placental mammals, urine flows from the Kidney (vertebrates), kidneys through the ureters to the urinary bladder and exits the urethra through the penile meatus (mal ...

within 24hours. With oral administration, 7% is eliminated unchanged in urine and 73% as conjugates. Conversely, with intravenous administration, 28% is eliminated unchanged in urine and 44% as conjugates.

Chemistry

Etilefrine, also known as 3,β-dihydroxy-''N''-ethylphenethylamine, is a

derivative In mathematics, the derivative is a fundamental tool that quantifies the sensitivity to change of a function's output with respect to its input. The derivative of a function of a single variable at a chosen input value, when it exists, is t ...

. It is an analogue of

(3,4,β-trihydroxy-''N''-methylphenethylamine), of

((''R'')-β,3-dihydroxy-''N''-methylphenethylamine), of metaterol (3,β-dihydroxy-''N''-isopropylphenethylamine), and of

(3,β-dihydroxyphenethylamine), as well as of

metaraminol Metaraminol, also known as metaradrine and sold under the brand name Aramine among others, is a sympathomimetic medication which is used in the prevention and treatment of hypotension (low blood pressure), particularly as a complication of an ...

((1''R'',2''S'')-3,β-dihydroxy-α-methylphenethylamine).

Etilefrine pivalate Etilefrine pivalate ; developmental code name K-30052) is a sympathomimetic agent which was never marketed. It is the 3- pivalate ester of etilefrine (ethylnorphenylephrine) and has much greater lipophilicity than etilefrine. Some related compo ...

(K-30052) is the 3- pivalyl

ester In chemistry, an ester is a compound derived from an acid (either organic or inorganic) in which the hydrogen atom (H) of at least one acidic hydroxyl group () of that acid is replaced by an organyl group (R). These compounds contain a distin ...

of etilefrine. In contrast to etilefrine, etilefrine pivalate was never marketed.

History

Etilefrine was first described and introduced for medical use by 1949.

Society and culture

Names

''Etilefrine'' is the generic name of the drug and its and , while ''étiléfrine'' is its and ''etilefrina'' is its . In the case of the

hydrochloride In chemistry, a hydrochloride is an acid salt resulting, or regarded as resulting, from the reaction of hydrochloric acid with an organic base (e.g. an amine). An alternative name is chlorhydrate, which comes from French. An archaic alternati ...

salt In common usage, salt is a mineral composed primarily of sodium chloride (NaCl). When used in food, especially in granulated form, it is more formally called table salt. In the form of a natural crystalline mineral, salt is also known as r ...

, its generic name is ''etilefrine hydrochloride'' and this is its and . Synonyms of etilefrine include ''ethylnorphenylephrine'', ''ethylphenephrine'', ''etiladrianol'', ''aethyladrianol'', and ''M-I-36''. Brand names of the drug include ''Effortil'', ''Circupon'', ''Apocretin'', ''Palsamin'', ''Kertasin'', ''Pressoton'', ''Effoless'', and ''Sanlephrin''.

References

{{Phenethylamines Alpha-1 adrenergic receptor agonists Alpha-2 adrenergic receptor agonists Antihypotensive agents Beta-adrenergic agonists Cardiac stimulants Peripherally selective drugs Phenylethanolamines 3-Hydroxyphenyl compounds Sympathomimetics