elimination (pharmacology)
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pharmacology Pharmacology is a branch of medicine, biology and pharmaceutical sciences concerned with drug or medication action, where a drug may be defined as any artificial, natural, or endogenous (from within the body) molecule which exerts a biochemica ...
the elimination or excretion of a drug is understood to be any one of a number of processes by which a drug is eliminated (that is, cleared and
excreted Excretion is a process in 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 lea ...
) from an organism either in an unaltered form (unbound molecules) or modified as a metabolite. The
kidney The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blood ...
is the main excretory organ although others exist such as the
liver The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...
, the
skin Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other cuticle, animal coverings, such as the arthropod exoskeleton, have diffe ...
, the
lungs The lungs are the primary organs of the respiratory system in humans and most other animals, including some snails and a small number of fish. In mammals and most other vertebrates, two lungs are located near the backbone on either side of th ...
or
gland In animals, a gland is a group of cells in an animal's body that synthesizes substances (such as hormones) for release into the bloodstream (endocrine gland) or into cavities inside the body or its outer surface (exocrine gland). Structure De ...
ular structures, such as the
salivary gland The salivary glands in mammals are exocrine glands that produce saliva through a system of ducts. Humans have three paired major salivary glands (parotid, submandibular, and sublingual), as well as hundreds of minor salivary glands. Salivary gla ...
s and the
lacrimal gland The lacrimal glands are paired exocrine glands, one for each eye, found in most terrestrial vertebrates and some marine mammals, that secrete the aqueous layer of the tear film. In humans, they are situated in the upper lateral region of each or ...
s. These organs or structures use specific routes to expel a drug from the body, these are termed elimination pathways: *
Urine Urine is a liquid by-product of metabolism in humans and in many other animals. Urine flows from the kidneys through the ureters to the urinary bladder. Urination results in urine being excretion, excreted from the body through the urethra. Cel ...
*
Tears Tears are a clear liquid secreted by the lacrimal glands (tear gland) found in the eyes of all land mammals. Tears are made up of water, electrolytes, proteins, lipids, and mucins that form layers on the surface of eyes. The different types of ...
*
Perspiration Perspiration, also known as sweating, is the production of fluids secreted by the sweat glands in the skin of mammals. Two types of sweat glands can be found in humans: eccrine glands and apocrine glands. The eccrine sweat glands are distrib ...
*
Saliva Saliva (commonly referred to as spit) is an extracellular fluid produced and secreted by salivary glands in the mouth. In humans, saliva is around 99% water, plus electrolytes, mucus, white blood cells, epithelial cells (from which DNA can be ...
*
Respiration Respiration may refer to: Biology * Cellular respiration, the process in which nutrients are converted into useful energy in a cell ** Anaerobic respiration, cellular respiration without oxygen ** Maintenance respiration, the amount of cellul ...
*
Milk Milk is a white liquid food produced by the mammary glands of mammals. It is the primary source of nutrition for young mammals (including breastfed human infants) before they are able to digestion, digest solid food. Immune factors and immune ...
*
Faeces Feces ( or faeces), known colloquially and in slang as poo and poop, are the solid or semi-solid remains of food that was not digested in the small intestine, and has been broken down by bacteria in the large intestine. Feces contain a relati ...
*
Bile Bile (from Latin ''bilis''), or gall, is a dark-green-to-yellowish-brown fluid produced by the liver of most vertebrates that aids the digestion of lipids in the small intestine. In humans, bile is produced continuously by the liver (liver bile ...
Drugs are excreted from the kidney by
glomerular filtration Renal functions include maintaining an acid–base balance; regulating fluid balance; regulating sodium, potassium, and other electrolytes; clearing toxins; absorption of glucose, amino acids, and other small molecules; regulation of blood pre ...
and by active
tubular secretion Renal physiology (Latin language, Latin ''rēnēs'', "kidneys") is the study of the physiology of the kidney. This encompasses all functions of the kidney, including maintenance of acid-base balance; regulation of fluid balance; regulation of sod ...
following the same steps and mechanisms as the products of intermediate metabolism. Therefore, drugs that are filtered by the
glomerulus ''Glomerulus'' () is a common term used in anatomy to describe globular structures of entwined vessels, fibers, or neurons. ''Glomerulus'' is the diminutive of the Latin ''glomus'', meaning "ball of yarn". ''Glomerulus'' may refer to: * the filter ...
are also subject to the process of passive
tubular reabsorption In renal physiology, reabsorption or tubular reabsorption is the process by which the nephron removes water and solutes from the tubular fluid (pre-urine) and returns them to the circulating blood. It is called ''reabsorption'' (and not ''absorpt ...
. Glomerular filtration will only remove those drugs or metabolites that are not bound to proteins present in blood plasma (free fraction) and many other types of drugs (such as the organic acids) are actively secreted. In the
proximal Standard anatomical terms of location are used to unambiguously describe the anatomy of animals, including humans. The terms, typically derived from Latin or Greek roots, describe something in its standard anatomical position. This position pro ...
and
distal convoluted tubule The distal convoluted tubule (DCT) is a portion of kidney nephron between the loop of Henle and the collecting tubule. Physiology It is partly responsible for the regulation of potassium, sodium, calcium, and pH. On its apical surface (lumen ...
s non-ionised acids and weak bases are reabsorbed both actively and passively. Weak acids are excreted when the tubular fluid becomes too alkaline and this reduces passive reabsorption. The opposite occurs with weak bases. Poisoning treatments use this effect to increase elimination, by alkalizing the urine causing
forced diuresis Diuresis () is increased urination (polyuria) or, in the related word senses more often intended, the physiological process that produces such an increase or the administration of medications to encourage that process. It involves extra urine pro ...
which promotes excretion of a weak acid, rather than it getting reabsorbed. As the acid is
ionised Ionization, or Ionisation is the process by which an atom or a molecule acquires a negative or positive charge by gaining or losing electrons, often in conjunction with other chemical changes. The resulting electrically charged atom or molecule ...
, it cannot pass through the
plasma membrane The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment (t ...
back into the blood stream and instead gets excreted with the urine. Acidifying the urine has the same effect for weakly basic drugs. On other occasions drugs combine with bile juices and enter the intestines. In the intestines the drug will join with the unabsorbed fraction of the administered dose and be eliminated with the faeces or it may undergo a new process of absorption to eventually be eliminated by the kidney. The other elimination pathways are less important in the elimination of drugs, except in very specific cases, such as the respiratory tract for alcohol or anaesthetic gases. The case of mother's milk is of special importance. The liver and kidneys of newly born
infant An infant or baby is the very young offspring of human beings. ''Infant'' (from the Latin word ''infans'', meaning 'unable to speak' or 'speechless') is a formal or specialised synonym for the common term ''baby''. The terms may also be used to ...
s are relatively undeveloped and they are highly sensitive to a drug's toxic effects. For this reason it is important to know if a drug is likely to be eliminated from a woman's body if she is breast feeding in order to avoid this situation.


Pharmacokinetic parameters of elimination

Pharmacokinetics studies the manner and speed with which drugs and their metabolites are eliminated by the various excretory organs. This elimination will be proportional to the drug's plasmatic concentrations. In order to model these processes a working definition is required for some of the concepts related to excretion.


Half life

The plasma half-life or ''half life of elimination'' is the time required to eliminate 50% of the absorbed dose of a drug from an organism. Or put another way, the time that it takes for the plasma concentration to fall by half from its maximum levels.


Clearance

The difference in a drug's concentration in arterial blood (before it has circulated around the body) and venous blood (after it has passed through the body's organs) represents the amount of the drug that the body has eliminated or ''cleared''. Although clearance may also involve other organs than the kidney, it is almost synonymous with renal clearance or renal plasma clearance. Clearance is therefore expressed as the plasma volume totally free of the drug per unit of time, and it is measured in units of volume per units of time. Clearance can be determined on an overall, organism level («systemic clearance») or at an organ level (hepatic clearance, renal clearance etc.). The equation that describes this concept is:
CL_o = Q \cdot \frac
Where: CL_o is the organ's clearance rate, C_A is the drug's plasma concentration in arterial blood, C_V is the drug's plasma concentration in venous blood and Q an organ's blood flow. Each organ will have its own specific clearance conditions, which will relate to its mode of action. The «renal clearance» rate will be determined by factors such as the degree of
plasma protein binding 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 or diffuse th ...
as the drug will only be filtered out if it is in the unbound free form, the degree of
saturation Saturation, saturated, unsaturation or unsaturated may refer to: Chemistry * Saturation, a property of organic compounds referring to carbon-carbon bonds **Saturated and unsaturated compounds ** Degree of unsaturation **Saturated fat or fatty aci ...
of the transporters (active secretion depends on transporter proteins that can become saturated) or the number of functioning
nephron The nephron is the minute or microscopic structural and functional unit of the kidney. It is composed of a renal corpuscle and a renal tubule. The renal corpuscle consists of a tuft of capillaries called a glomerulus and a cup-shaped structure ca ...
s (hence the importance of factors such as
kidney failure Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...
). As «hepatic clearance» is an active process it is therefore determined by factors that alter an organism's metabolism such as the number of functioning
hepatocyte A hepatocyte is a cell of the main parenchymal tissue of the liver. Hepatocytes make up 80% of the liver's mass. These cells are involved in: * Protein synthesis * Protein storage * Transformation of carbohydrates * Synthesis of cholesterol, ...
s, this is the reason that liver failure has such clinical importance.


Steady state

The steady state or ''stable concentration'' is reached when the drug's supply to the blood plasma is the same as the rate of elimination from the plasma. It is necessary to calculate this concentration in order to decide the period between doses and the amount of drug supplied with each dose in prolonged treatments.


Other parameters

Other parameters of interest include a drug's
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 ...
and the ''apparent volume of distribution''.


See also

*
Pharmacy Pharmacy is the science and practice of discovering, producing, preparing, dispensing, reviewing and monitoring medications, aiming to ensure the safe, effective, and affordable use of medicines. It is a miscellaneous science as it links heal ...
*
Bioequivalence Bioequivalence is a term in pharmacokinetics used to assess the expected in vivo biological equivalence of two proprietary preparations of a drug. If two products are said to be bioequivalent it means that they would be expected to be, for all i ...
*
Generic drugs A generic drug is a pharmaceutical drug that contains the same chemical substance as a drug that was originally protected by chemical patents. Generic drugs are allowed for sale after the patents on the original drugs expire. Because the active ch ...
*
Pharmacokinetics Pharmacokinetics (from Ancient Greek ''pharmakon'' "drug" and ''kinetikos'' "moving, putting in motion"; see chemical kinetics), sometimes abbreviated as PK, is a branch of pharmacology dedicated to determining the fate of substances administered ...
*
Pharmacodynamics Pharmacodynamics (PD) is the study of the biochemical and physiologic effects of drugs (especially pharmaceutical drugs). The effects can include those manifested within animals (including humans), microorganisms, or combinations of organisms (fo ...
*
ADME ADME is an abbreviation in pharmacokinetics and pharmacology for " absorption, distribution, metabolism, and excretion", and describes the disposition of a pharmaceutical compound within an organism. The four criteria all influence the drug le ...
*
Liberation (pharmacology) Liberation is the first step in the process by which medication enters the body and liberates the active ingredient that has been administered. The pharmaceutical drug must separate from the vehicle or the excipient that it was mixed with during ...
*
Absorption (pharmacokinetics) Absorption is the journey of a drug travelling from the site of administration to the site of action. The drug travels by some route of administration (oral, topical-dermal, etc.) in a chosen dosage form (e.g., tablets, capsules, or in solut ...
*
Distribution (pharmacology) Distribution in pharmacology is a branch of pharmacokinetics which describes the reversible transfer of a drug from one location to another within the body. Once a drug enters into systemic circulation by absorption or direct administration, it m ...
*
Metabolism Metabolism (, from el, μεταβολή ''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 cell ...
*
Countercurrent exchange Countercurrent exchange is a mechanism occurring in nature and mimicked in industry and engineering, in which there is a crossover of some property, usually heat or some chemical, between two flowing bodies flowing in opposite directions to each ...
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Eructation Burping (also called belching and eructation) is the release of gas from the upper digestive tract (esophagus and stomach) of animals through the mouth. It is usually audible. In humans, burping can be caused by normal eating processes, or as ...
*
Homeostasis In biology, homeostasis (British English, British also homoeostasis) Help:IPA/English, (/hɒmɪə(ʊ)ˈsteɪsɪs/) is the state of steady internal, physics, physical, and chemistry, chemical conditions maintained by organism, living systems. Thi ...
*
Osmoregulation Osmoregulation is the active regulation of the osmotic pressure of an organism's body fluids, detected by osmoreceptors, to maintain the homeostasis of the organism's water content; that is, it maintains the fluid balance and the concentration o ...
*
Respiration (physiology) In physiology, respiration is the movement of oxygen from the outside environment to the cells within Tissue (biology), tissues, and the transport, removal of carbon dioxide in the opposite direction that's to the environment. The physiological d ...


References

For elimination via bile please see: Estimation of Biliary Excretion of Foreign Compounds Using Properties of Molecular Structure. 2014. Sharifi M., Ghafourian T. AAPS J. 16(1) 65–78.


External links


UAlberta.ca
Animation of excretion {{Pharmacology Digestive system Excretion Pharmacokinetics Pharmacy