Context-sensitive half-life

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Context-sensitive half-life or context sensitive half-time is defined as the time taken for blood plasma concentration of a drug to decline by one half after an infusion designed to maintain a steady state (i.e. a constant plasma concentration) has been stopped. The "context" is the duration of infusion.

Blood plasma liquid component of blood

Blood plasma is a yellowish liquid component of blood that normally holds the blood cells in whole blood in suspension. In other words, it is the liquid part of the blood that carries cells and proteins throughout the body. It makes up about 55% of the body's total blood volume. It is the intravascular fluid part of extracellular fluid (all body fluid outside cells). It is mostly water (up to 95% by volume), and contains dissolved proteins (6–8%) (e.g. serum albumins, globulins, and fibrinogen), glucose, clotting factors, electrolytes (Na+, Ca2+, Mg2+, HCO3−, Cl−, etc.), hormones, carbon dioxide (plasma being the main medium for excretory product transportation) and oxygen. It plays a vital role in an intravascular osmotic effect that keeps electrolyte concentration balanced and protects the body from infection and other blood disorders.

In systems theory, a system or a process is in a steady state if the variables which define the behavior of the system or the process are unchanging in time. In continuous time, this means that for those properties p of the system, the partial derivative with respect to time is zero and remains so:

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When a drug which has a multicompartmental pharmacokinetic model is given by intravenous infusion it initially will distribute to the central compartment and then move out of this compartment into one or two peripheral compartments. Once this infusion is discontinued, drug continues to move into the peripheral compartments until an equilibrium is reached. At this time, the only way drug may leave plasma is by metabolism or excretion. As the plasma concentration falls, the concentration gradient of drug reverses and drug moves from peripheral compartments back into plasma, maintaining the plasma concentration of the drug, often prolonging the pharmacological effect. If an infusion has reached steady state then the context-sensitive half-life is equal to the terminal plasma half-life of the drug. Otherwise it will be shorter than the terminal elimination half-life.

Infusion process of extracting chemical compounds or flavors from plant material in a solvent

Infusion is the process of extracting chemical compounds or flavors from plant material in a solvent such as water, oil or alcohol, by allowing the material to remain suspended in the solvent over time. An infusion is also the name for the resultant liquid. The process of infusion is distinct from both decoction—a method of extraction involving boiling the plant material—and percolation, in which water is passed through the material.

Metabolism The set of life-sustaining chemical transformations within the cells of organisms

Metabolism is the set of life-sustaining chemical reactions in organisms. The three main purposes of metabolism are: the conversion of food to energy to run cellular processes; the conversion of food/fuel to building blocks for proteins, lipids, nucleic acids, and some carbohydrates; and the elimination of nitrogenous wastes. These enzyme-catalyzed reactions allow organisms to grow and reproduce, maintain their structures, and respond to their environments..

Excretion elimination by an organism of the waste products that arise as a result of metabolic activity

Excretion is a process by which metabolic waste is eliminated from an organism. 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 tasks after leaving the cell. Excretion is an essential process in all forms of life. For example, in mammals urine is expelled through the urethra, which is part of the excretory system. In unicellular organisms, waste products are discharged directly through the surface of the cell.

Remifentanil is relatively context insensitive whilst fentanyl and thiopentone are examples of drugs which have significant context-sensitive changes in their half-life. [1]

Remifentanil chemical compound

Remifentanil is a potent, short-acting synthetic opioid analgesic drug. It is given to patients during surgery to relieve pain and as an adjunct to an anaesthetic. Remifentanil is used for sedation as well as combined with other medications for use in general anesthesia. The use of remifentanil has made possible the use of high-dose opioid and low-dose hypnotic anesthesia, due to synergism between remifentanil and various hypnotic drugs and volatile anesthetics.

Fentanyl chemical compound

Fentanyl, also spelled fentanil, is an opioid used as a pain medication and together with other medications for anesthesia. Fentanyl is also used as a recreational drug, often mixed with heroin or cocaine. It has a rapid onset and effects generally last less than two hours. Medically, fentanyl is used by injection, as a patch on the skin, as a nasal spray, or in the mouth.

The Context-Sensitive Half-Time describes the time required for the plasma drug concentration to decline by 50% after terminating an infusion of a particular duration. [2]

Definition

It is the time required for drug plasma concentration to decrease by 50% after stopping administration. The drug is administered continuously.

Context-sensitive half-life of fentanyl

Remifentanil is relatively context insensitive. Fentanyl and thiopental are examples of drugs which have significant context-sensitive changes in their half-life.

Related Research Articles

General anaesthetics are often defined as compounds that induce a loss of consciousness in humans or loss of righting reflex in animals. Clinical definitions are also extended to include the lack of awareness to painful stimuli, sufficient to facilitate surgical applications in clinical and veterinary practice. General anaesthetics do not act as analgesics and should also not be confused with sedatives. General anaesthetics are a structurally diverse group of compounds whose mechanisms encompasses multiple biological targets involved in the control of neuronal pathways. The precise workings are the subject of some debate and ongoing research.

Local anesthetic medication that causes reversible absence of pain sensation

A local anesthetic (LA) is a medication that causes absence of pain sensation. When it is used on specific nerve pathways, paralysis also can be achieved.

Kolokol-1 is a synthetic opioid developed for use as an aerosolizable incapacitating agent. The exact chemical structure has not yet been revealed by the Russian government. It was originally thought by some sources to be a derivative of the potent opioid fentanyl, most probably 3-methylfentanyl dissolved in an inhalational anaesthetic as an organic solvent. However, independent analysis of residues on the Barricade Theater hostage crisis hostages' clothing or in one hostage's urine found no fentanyl or 3-methyl fentanyl. Two much more potent and shorter-acting agents, carfentanil and remifentanil, were found in the samples. They concluded that the agent used in the Barricade Theater hostage rescue contained two fentanyl derivatives much stronger than fentanyl itself, sprayed in an aerosol mist.

In pharmacology, the clearance is a pharmacokinetic measurement of the volume of plasma from which a substance is completely removed per unit time; the usual units are mL/min. The quantity reflects the rate of drug elimination divided by plasma concentration.

The biological half-life of a biological substance is the time it takes for half to be removed by biological processes when the rate of removal is roughly exponential. It is often denoted by the abbreviation . Examples include metabolites, drugs, and signalling molecules. Typically, this refers to the body's cleansing through the function of kidneys and liver in addition to excretion functions to eliminate a substance from the body. In a medical context, half-life may also describe the time it takes for the blood plasma concentration of a substance to halve its steady-state. The relationship between the biological and plasma half-lives of a substance can be complex depending on the substance in question, due to factors including accumulation in tissues, active metabolites, and receptor interactions.

Cinnarizine chemical compound

Cinnarizine is an antihistamine and calcium channel blocker of the diphenylmethylpiperazine group. It is also known to promote cerebral blood flow, and so is used to treat cerebral apoplexy, post-trauma cerebral symptoms, and cerebral arteriosclerosis. However, it is more commonly prescribed for nausea and vomiting due to motion sickness or other sources such as chemotherapy, vertigo, or Ménière's disease.

Distribution in pharmacology is a branch of pharmacokinetics which describes the reversible transfer of a drug from one location to another within the body.


The initial volume of distribution is a pharmacological term used to quantify the distribution of a drug throughout the body relatively soon after oral or intravenous dosing of a drug and prior to the drug reaching a steady state equilibrium. Following distribution of the drug, measurement of blood levels indicate the apparent volume of distribution. Calculation of the initial volume of distribution is the same calculation as that for the apparent volume of distribution, given by the equation:

Plasma protein binding refers to the degree to which medications attach to proteins within the blood. A drug's efficiency may be affected by the degree to which it binds. The less bound a drug is, the more efficiently it can traverse cell membranes or diffuse. Common blood proteins that drugs bind to are human serum albumin, lipoprotein, glycoprotein, and α, β‚ and γ globulins.

Flunarizine chemical compound

Flunarizine, sold under the brand name Sibelium among others, is a drug classified as a calcium antagonist which is used for various indications. It is not available by prescription in the United States or Japan. The drug was discovered at Janssen Pharmaceutica (R14950) in 1968.

Pharmacokinetics, sometimes abbreviated as PK, is a branch of pharmacology dedicated to determining the fate of substances administered to a living organism. The substances of interest include any chemical xenobiotic such as: pharmaceutical drugs, pesticides, food additives, cosmetics, etc. It attempts to analyze chemical metabolism and to discover the fate of a chemical from the moment that it is administered up to the point at which it is completely eliminated from the body. Pharmacokinetics is the study of how an organism affects a drug, whereas pharmacodynamics (PD) is the study of how the drug affects the organism. Both together influence dosing, benefit, and adverse effects, as seen in PK/PD models.

Nadifloxacin chemical compound

Nadifloxacin is a topical fluoroquinolone antibiotic for the treatment of acne vulgaris. It is also used to treat bacterial skin infections.

The plateau principle is a mathematical model or scientific law originally developed to explain the time course of drug action. The principle has wide applicability in pharmacology, physiology, nutrition, biochemistry and system dynamics. It applies whenever a drug or nutrient is infused or ingested at a relatively constant rate and when a constant fraction is eliminated during each time interval. Under these conditions, any change in the rate of infusion leads to an exponential increase or decrease until a new level is achieved. This behavior is also called an approach to steady state because rather than causing an indefinite increase or decrease, a natural balance is achieved when the rate of infusion or production is balanced by the rate of loss.

Glucose clamp technique is a method for quantifying insulin secretion and resistance. It is used to measure either how well an individual metabolizes glucose or how sensitive an individual is to insulin.

Macitentan chemical compound

Macitentan is an endothelin receptor antagonist (ERA) approved for the treatment of pulmonary arterial hypertension (PAH). The other two ERAs marketed as of 2014 are bosentan and ambrisentan. Macitentan is a dual ERA, meaning that it acts as an antagonist of two endothelin (ET) receptor subtypes, ETA and ETB. However, macitentan has a 50-fold increased selectivity for the ETA subtype compared to the ETB subtype. The drug received approval from the U.S. Food and Drug Administration (FDA) on October 13, 2013.

Decompression theory Theoretical modelling of decompression physiology

Decompression theory is the study and modelling of the transfer of the inert gas component of breathing gases from the gas in the lungs to the tissues and back during exposure to variations in ambient pressure. In the case of underwater diving and compressed air work, this mostly involves ambient pressures greater than the local surface pressure, but astronauts, high altitude mountaineers, and travellers in aircraft which are not pressurised to sea level pressure, are generally exposed to ambient pressures less than standard sea level atmospheric pressure. In all cases, the symptoms caused by decompression occur during or within a relatively short period of hours, or occasionally days, after a significant pressure reduction.

Elimination (pharmacology)

In pharmacology the elimination or excretion of a drug is understood to be any one of a number of processes by which a drug is eliminated from an organism either in an unaltered form or modified as a metabolite. The kidney is the main excretory organ although others exist such as the liver, the skin, the lungs or glandular structures, such as the salivary glands and the lacrimal glands. These organs or structures use specific routes to expel a drug from the body, these are termed elimination pathways:

Physiology of decompression The physiological basis for decompression theory and practice

The physiology of decompression involves a complex interaction of gas solubility, partial pressures and concentration gradients, diffusion, bulk transport and bubble mechanics in living tissues. Gas is breathed at ambient pressure, and some of this gas dissolves into the blood and other fluids. Inert gas continues to be taken up until the gas dissolved in the tissues is in a state of equilibrium with the gas in the lungs,, or the ambient pressure is reduced until the inert gases dissolved in the tissues are at a higher concentration than the equilibrium state, and start diffusing out again.

Opicapone

Opicapone is a drug which is a catechol-O-methyltransferase (COMT) inhibitor. It is administered together with levodopa in patients with Parkinson's disease. In June 2016 it was authorised for sale – under the trade name Ongentys – in the European Union. In February 2017, its developer Bial sold exclusive marketing rights for the United States and Canada to Neurocrine Biosciences for an initial payment of $30 million.

References

  1. ↑ http://www.openanesthesia.org/context-sensitive_half_time/
  2. ↑ Clinical Anesthesia, 6th Edition. Barash, Cullen, Stoelting, Cahalan, Stock. Lippencott Williams & Wilkins, Philadelphia PA. 2009. Page 818.
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