pharmaceutical sciences 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 healt ...

, drug interactions occur when a drug's

mechanism of action In pharmacology, the term mechanism of action (MOA) refers to the specific biochemical Drug interaction, interaction through which a Medication, drug substance produces its pharmacological effect. A mechanism of action usually includes mention o ...

is affected by the

concomitant Concomitance is the condition of accompanying or coexisting. A concomitant is something that accompanies something else. Concomitant or concomitance may refer to: * Concomitance (doctrine) The Doctrine of Concomitance is a Eucharistic theologica ...

administration of substances such as foods, beverages, or other drugs. A popular example of drug–food interaction is the effect of grapefruit on the metabolism of drugs. Interactions may occur by simultaneous targeting of

receptors Receptor may refer to: *Sensory receptor, in physiology, any neurite structure that, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds ...

, directly or indirectly. For example, both

Zolpidem Zolpidem, sold under the brand name Ambien among others, is a medication primarily used for the short-term treatment of sleeping problems. Guidelines recommend that it be used only after cognitive behavioral therapy for insomnia and after beh ...

and alcohol affect GABA_A receptors, and their simultaneous consumption results in the overstimulation of the receptor, which can lead to loss of consciousness. When two drugs affect each other, it is a drug–drug interaction (DDI). The risk of a DDI increases with the number of drugs used. A large share of

elderly Old age is the range of ages for people nearing and surpassing life expectancy. People who are of old age are also referred to as: old people, elderly, elders, senior citizens, seniors or older adults. Old age is not a definite biological sta ...

people regularly use five or more medications or supplements, with a significant risk of side-effects from drug–drug interactions. Drug interactions can be of three kinds: * additive (the result is what you expect when you add together the effect of each drug taken independently), *

synergistic Synergy is an interaction or cooperation giving rise to a whole that is greater than the simple sum of its parts (i.e., a non-linear addition of force, energy, or effect). The term ''synergy'' comes from the Attic Greek word συνεργία ' f ...

(combining the drugs leads to a larger effect than expected), or * antagonistic (combining the drugs leads to a smaller effect than expected). It may be difficult to distinguish between synergistic or additive interactions, as individual effects of drugs may vary. Direct interactions between drugs are also possible and may occur when two drugs are mixed before

intravenous injection 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 ...

. For example, mixing

thiopentone Sodium thiopental, also known as Sodium Pentothal (a trademark of Abbott Laboratories), thiopental, thiopentone, or Trapanal (also a trademark), is a rapid-onset short-acting barbiturate general anesthetic. It is the thiobarbiturate analog ...

and

suxamethonium Suxamethonium chloride (brand names Scoline and Sucostrin, among others), also known as suxamethonium or succinylcholine, or simply sux in medical abbreviation, is a medication used to cause short-term paralysis as part of general anesthesia. T ...

can lead to the

precipitation In meteorology, precipitation is any product of the condensation of atmospheric water vapor that falls from clouds due to gravitational pull. The main forms of precipitation include drizzle, rain, rain and snow mixed ("sleet" in Commonwe ...

of thiopentone.

Interactions based on pharmacodynamics

Pharmacodynamic Pharmacodynamics (PD) is the study of the biochemistry, biochemical and physiology, physiologic effects of drugs (especially pharmaceutical drugs). The effects can include those manifested within animals (including humans), microorganisms, or comb ...

interactions are the drug–drug interactions that occur at a

biochemical Biochemistry, or biological chemistry, is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be divided into three fields: structural biology, enzymology, ...

level and depend mainly on the biological processes of organisms. These interactions occur due to action on the same targets; for example, the same receptor or

signaling pathway In biology, cell signaling (cell signalling in British English) is the process by which a cell interacts with itself, other cells, and the environment. Cell signaling is a fundamental property of all cellular life in both prokaryotes and eukary ...

Pharmacodynamic interactions can occur on protein

. Two drugs can be considered to be ''homodynamic'', if they act on the same receptor. Homodynamic effects include drugs that act as (1) pure

agonists An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the agon ...

, if they bind to the main locus of the

receptor Receptor may refer to: * Sensory receptor, in physiology, any neurite structure that, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and respond ...

, causing a similar effect to that of the main drug, (2) partial

if, on binding to a secondary site, they have the same effect as the main drug, but with a lower intensity and (3)

antagonist An antagonist is a character in a story who is presented as the main enemy or rival of the protagonist and is often depicted as a villain.downstream pathways. The interaction my also occur via signal transduction mechanisms.''Curso de Farmacología Clínica Aplicada'', in El Médico Interactivo
For example, low blood glucose leads to a release of

catecholamine A catecholamine (; abbreviated CA), most typically a 3,4-dihydroxyphenethylamine, is a monoamine neurotransmitter, an organic compound that has a catechol (benzene with two hydroxyl side groups next to each other) and a side-chain amine. Cate ...

s, triggering

symptom Signs and symptoms are diagnostic indications of an illness, injury, or condition. Signs are objective and externally observable; symptoms are a person's reported subjective experiences. A sign for example may be a higher or lower temperature ...

s that hint the organism to take action, like consuming sugary foods. If a patient is on

insulin Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the insulin (''INS)'' gene. It is the main Anabolism, anabolic hormone of the body. It regulates the metabol ...

, which reduces blood sugar, and also

beta-blockers Beta blockers, also spelled β-blockers, are a class of medications that are predominantly used to manage abnormal heart rhythms (arrhythmia), and to protect the heart from a second heart attack after a first heart attack (secondary prevention). ...

, the body is less able to cope with an insulin overdose.

Interactions based on pharmacokinetics

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 describing how the body affects a specific su ...

is the field of research studying the chemical and biochemical factors that directly affect dosage and the

half-life Half-life is a mathematical and scientific description of exponential or gradual decay. Half-life, half life or halflife may also refer to: Film * Half-Life (film), ''Half-Life'' (film), a 2008 independent film by Jennifer Phang * ''Half Life: ...

of drugs in an organism, including absorption, transport, distribution, metabolism and excretion. Compounds may affect any of those process, ultimately interfering with the flux of drugs in the

human body The human body is the entire structure of a Human, human being. It is composed of many different types of Cell (biology), cells that together create Tissue (biology), tissues and subsequently Organ (biology), organs and then Organ system, org ...

, increasing or reducing drug availability.

Based on absorption

Drugs that change intestinal motility may impact the level of other drugs taken. For example, prokinetic agents increase the

intestinal motility Gastrointestinal physiology is the branch of human physiology that addresses the physical function of the gastrointestinal (GI) tract. The function of the GI tract is to process ingested food by mechanical and chemical means, extract nutrients an ...

, which may cause drugs to go through the digestive system too fast, reducing absorption. The pharmacological modification of pH can affect other compounds. Drugs can be present in ionized or non-ionized forms depending on

pKa In chemistry, an acid dissociation constant (also known as acidity constant, or acid-ionization constant; denoted ) is a quantitative measure of the strength of an acid in solution. It is the equilibrium constant for a chemical reaction :H ...

, and neutral compounds are usually better absorbed by membranes.Malgor — Valsecia, ''Farmacología general: Farmacocinética.''Cap. 2. en Revised 25 September 2008 Medication like

antacid An antacid is a substance which neutralization (chemistry), neutralizes gastric acid, stomach acidity and is used to relieve heartburn, indigestion, or an upset stomach. Some antacids have been used in the treatment of constipation and diarrhe ...

s can increase pH and inhibit the absorption of other drugs such as

zalcitabine Zalcitabine (2′-3′-di deoxycytidine, ddC), also called dideoxycytidine, is a nucleoside analog reverse-transcriptase inhibitor (NRTI) sold under the trade name Hivid. Zalcitabine was the third antiretroviral to be approved by the Food and Dru ...

, tipranavir and

amprenavir Amprenavir (original brand name Agenerase, GlaxoSmithKline) is a protease inhibitor used to treat HIV infection. It was approved by the Food and Drug Administration on April 15, 1999, for twice-a-day dosing instead of needing to be taken every ...

. The opposite is more common, with, for example, the antacid

cimetidine Cimetidine, sold under the brand name Tagamet among others, is a histamine H2 receptor antagonist that inhibits stomach acid production. It is mainly used in the treatment of heartburn and peptic ulcers. With the development of proton pump ...

''stimulating'' the absorption of

didanosine Didanosine, sold under the brand name Videx among others, is a medication used to treat HIV/AIDS. It is used in combination with other medications as part of highly active antiretroviral therapy (HAART). It is of the reverse-transcriptase inhib ...

. Some resources describe that a gap of two to four hours between taking the two drugs is needed to avoid the interaction. Factors such as food with high-fat content may also alter the solubility of drugs and impact its absorption. This is the case for oral

anticoagulant An anticoagulant, commonly known as a blood thinner, is a chemical substance that prevents or reduces the coagulation of blood, prolonging the clotting time. Some occur naturally in blood-eating animals, such as leeches and mosquitoes, which ...

s and

avocado The avocado, alligator pear or avocado pear (''Persea americana'') is an evergreen tree in the laurel family (Lauraceae). It is native to Americas, the Americas and was first domesticated in Mesoamerica more than 5,000 years ago. It was priz ...

. The formation of non-absorbable complexes may occur also via

chelation Chelation () is a type of bonding of ions and their molecules to metal ions. It involves the formation or presence of two or more separate coordinate bonds between a polydentate (multiple bonded) ligand and a single central metal atom. These l ...

, when

cation An ion () is an atom or molecule with a net electrical charge. The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by convent ...

s can make certain drugs harder to absorb, for example between

tetracycline Tetracycline, sold under various brand names, is an antibiotic in the tetracyclines family of medications, used to treat a number of infections, including acne, cholera, brucellosis, plague, malaria, and syphilis. It is available in oral an ...

or the

fluoroquinolone Quinolone antibiotics constitute a large group of broad-spectrum bacteriocidals that share a bicyclic core structure related to the substance 4-quinolone. They are used in human and veterinary medicine to treat bacterial infections, as well ...

s and dairy products, due to the presence of

calcium ions Calcium ions (Ca2+) contribute to the physiology and biochemistry of organisms' cells. They play an important role in signal transduction pathways, where they act as a second messenger, in neurotransmitter release from neurons, in contraction ...

. . Other drugs bind to proteins. Some drugs such as

sucralfate Sucralfate, sold under various brand names, is a medication used to treat stomach ulcers, gastroesophageal reflux disease (GERD), radiation proctitis, and stomach inflammation and to prevent stress ulcers. Its usefulness in people infected b ...

bind to proteins, especially if they have a high

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 ...

. For this reason its administration is

contraindicated In medicine, a contraindication is a condition (a situation or factor) that serves as a reason not to take a certain medical treatment due to the harm that it would cause the patient. Contraindication is the opposite of indication, which is a rea ...

enteral feeding A feeding tube is a medical device used to provide nutrition to people who cannot obtain nutrition by mouth, are unable to swallow safely, or need nutritional supplementation. The state of being fed by a feeding tube is called gavage, enteral fee ...

.Marduga Sanz, Mariano. ''Interacciones de los alimentos con los medicamentos''. o

Some drugs also alter absorption by acting on the

P-glycoprotein P-glycoprotein 1 (permeability glycoprotein, abbreviated as P-gp or Pgp) also known as multidrug resistance protein 1 (MDR1) or ATP-binding cassette sub-family B member 1 (ABCB1) or cluster of differentiation 243 (CD243) is an important protein ...

of the

enterocyte Enterocytes, or intestinal absorptive cells, are simple columnar epithelial cells which line the inner surface of the small and large intestines. A glycocalyx surface coat contains digestive enzymes. Microvilli on the apical surface increase ...

s. This appears to be one of the mechanisms by which

grapefruit The grapefruit (''Citrus'' × ''paradisi'') is a subtropical citrus tree known for its relatively large, sour to semi-sweet, somewhat bitter fruit. The flesh of the fruit is segmented and varies in color from pale yellow to dark red. Grapefru ...

juice increases the

of various drugs beyond its inhibitory activity on

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 ...

Based on transport and distribution

Drugs also may affect each other by competing for transport proteins in plasma, such as

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 ...

. In these cases the drug that arrives first binds with the plasma protein, leaving the other drug dissolved in the plasma, modifying its expected concentration. The organism has mechanisms to counteract these situations (by, for example, increasing plasma clearance), and thus they are not usually clinically relevant. They may become relevant if other problems are present, such as issues with drug excretion.

Based on metabolism

Many drug interactions are due to alterations in

drug metabolism Drug metabolism is the metabolic breakdown of drugs by living organisms, usually through specialized enzymatic systems. More generally, xenobiotic metabolism (from the Greek xenos "stranger" and biotic "related to living beings") is the set o ...

. Further, human drug-metabolizing enzymes are typically activated through the engagement of

nuclear receptor In the field of molecular biology, nuclear receptors are a class of proteins responsible for sensing steroids, thyroid hormones, vitamins, and certain other molecules. These intracellular receptors work with other proteins to regulate the ex ...

s. One notable system involved in metabolic drug interactions is the enzyme system comprising the

cytochrome P450 oxidase Cytochromes P450 (P450s or CYPs) are a superfamily of enzymes containing heme as a cofactor that mostly, but not exclusively, function as monooxygenases. However, they are not omnipresent; for example, they have not been found in ''Escherich ...

CYP450

Cytochrome P450 Cytochromes P450 (P450s or CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that mostly, but not exclusively, function as monooxygenases. However, they are not omnipresent; for examp ...

is a very large family of haemoproteins (hemoproteins) that are characterized by their

enzymatic An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as produc ...

activity and their role in the metabolism of a large number of drugs. Of the various families that are present in humans, the most interesting in this respect are the 1, 2 and 3, and the most important enzymes are

CYP1A2 Cytochrome P450 1A2 (abbreviated CYP1A2), a member of the cytochrome P450 mixed-function oxidase system, is involved in the metabolism of xenobiotics in the human body. In humans, the CYP1A2 enzyme is encoded by the ''CYP1A2'' gene. Function ...

CYP2C9 Cytochrome P450 family 2 subfamily C member 9 (abbreviated CYP2C9) is an enzyme protein. The enzyme is involved in the metabolism, by oxidation, of both xenobiotics, including drugs, and endogenous compounds, including fatty acids. In humans, t ...

CYP2C19 Cytochrome P450 2C19 (abbreviated CYP2C19) is an enzyme protein. It is a member of the CYP2C subfamily of the cytochrome P450 mixed-function oxidase system. This subfamily includes enzymes that catalyze metabolism of xenobiotics, including some ...

CYP2D6 Cytochrome P450 2D6 (CYP2D6) is an enzyme that in humans is encoded by the ''CYP2D6'' gene. ''CYP2D6'' is primarily expressed in the liver. It is also highly expressed in areas of the central nervous system, including the substantia nigra. CYP2 ...

CYP2E1 Cytochrome P450 2E1 (abbreviated CYP2E1, ) is a member of the cytochrome P450 mixed-function oxidase system, which is involved in the metabolism of xenobiotics in the body. This class of enzymes is divided up into a number of subcategories, inclu ...

and

CYP3A4 Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine, which in humans is encoded by ''CYP3A4'' gene. It organic redox reaction, oxidizes small foreign organic molecules ( ...

.Nelson D (2003)
Cytochrome P450s in humans
. Consulted 9 May 2005. The majority of the enzymes are also involved in the metabolism of

endogenous Endogeny, in biology, refers to the property of originating or developing from within an organism, tissue, or cell. For example, ''endogenous substances'', and ''endogenous processes'' are those that originate within a living system (e.g. an ...

substances, such as

steroid A steroid is an organic compound with four fused compound, fused rings (designated A, B, C, and D) arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes t ...

s or

sex hormones Sex hormones, also known as sex steroids, gonadocorticoids and gonadal steroids, are steroid hormones that interact with vertebrate steroid hormone receptors. The sex hormones include the androgens, estrogens, and progestogens. Their effects a ...

, which is also important should there be interference with these substances. The function of the enzymes can either be stimulated (

enzyme induction An enzyme inducer is a type of drug that increases the metabolic activity of an enzyme either by binding to the enzyme and activating it, or by increasing the expression of the gene coding for the enzyme. One of the examples of enzyme inducers can ...

) or inhibited (

enzyme inhibition An enzyme inhibitor is a molecule that binds to an enzyme and blocks its Enzyme activity, activity. Enzymes are proteins that speed up chemical reactions necessary for life, in which Substrate (biochemistry), substrate molecules are converted ...

Through enzymatic inhibition and induction

If a drug is metabolized by a CYP450 enzyme and drug B blocks the activity of these enzymes, it can lead to pharmacokinetic alterations. A. This alteration results in drug A remaining in the bloodstream for an extended duration, and eventually increase in concentration. In some instances, the inhibition may reduce the therapeutic effect, if instead the metabolites of the drug is responsible for the effect. Compounds that increase the efficiency of the enzymes, on the other hand, may have the opposite effect and increase the rate of metabolism.

Examples of metabolism-based interactions

An example of this is shown in the following table for the

enzyme, showing the substrates (drugs metabolized by this enzyme) and some inductors and inhibitors of its activity: Some foods also act as inductors or inhibitors of enzymatic activity. The following table shows the most common:

Based on excretion

Renal and biliary excretion

Drugs tightly bound to proteins (i.e. not in the

free fraction The free fraction is a parameter in pharmacokinetics and receptor-ligand kinetics. One speaks of two different free fractions: * ''Plasma free fraction'', previously referred to as ƒ1, is now referred to as ƒP according to consensus nomenclature ...

) are not available for renal excretion.Gago Bádenas, F. ''Curso de Farmacología General. Tema 6.- Excreción de los fármacos''. e

Filtration depends on a number of factors including the pH of the urine. Drug interactions may affect those points.

With herbal medicines

Herb-drug interactions are drug interactions that occur between

herbal medicines Herbal medicine (also called herbalism, phytomedicine or phytotherapy) is the study of pharmacognosy and the use of medicinal plants, which are a basis of traditional medicine. Scientific evidence for the effectiveness of many herbal treatments ...

and conventional drugs. These types of interactions may be more common than drug-drug interactions because herbal medicines often contain multiple pharmacologically active ingredients, while conventional drugs typically contain only one. Some such interactions are

clinically significant In medicine and psychology, clinical significance is the practical importance of a treatment effect—whether it has a real genuine, palpable, noticeable effect on daily life. Types of significance Statistical significance Statistical significanc ...

, although most herbal remedies are not associated with drug interactions causing serious consequences. Most catalogued herb-drug interactions are moderate in severity. The most commonly implicated conventional drugs in herb-drug interactions are

warfarin Warfarin, sold under the brand name Coumadin among others. It is used as an anticoagulant, anticoagulant medication. It is commonly used to prevent deep vein thrombosis and pulmonary embolism, and to protect against stroke in people who ha ...

aspirin Aspirin () is the genericized trademark for acetylsalicylic acid (ASA), a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and inflammation, and as an antithrombotic. Specific inflammatory conditions that aspirin is ...

digoxin Digoxin (better known as digitalis), sold under the brand name Lanoxin among others, is a medication used to treat various heart disease, heart conditions. Most frequently it is used for atrial fibrillation, atrial flutter, and heart failure. ...

, and

ticlopidine Ticlopidine, sold under the brand name Ticlid, is a medication used to reduce the risk of thrombotic strokes. It is an antiplatelet drug in the thienopyridine family which is an adenosine diphosphate (ADP) receptor inhibitor. Research initially ...

, due to their narrow therapeutic indices. The most commonly implicated herbs involved in such interactions are those containing St. John’s Wort, magnesium, calcium, iron, or

ginkgo ''Ginkgo'' is a genus of non-flowering seed plants, assigned to the gymnosperms. The scientific name is also used as the English common name. The order to which the genus belongs, Ginkgoales, first appeared in the Permian, , and ''Ginkgo'' is n ...

Examples

Examples of herb-drug interactions include, but are not limited to: * St. John's wort affects the clearance of numerous drugs, including

cyclosporin Ciclosporin, also spelled cyclosporine and cyclosporin, is a calcineurin inhibitor, used as an immunosuppressant medication. It is taken orally or intravenously for rheumatoid arthritis, psoriasis, Crohn's disease, nephrotic syndrome, ecz ...

SSRI Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions. SSRIs primarily work by ...

antidepressants,

indinavir Indinavir (IDV; trade name Crixivan, made by Merck & Co., Merck) is a Protease inhibitor (pharmacology), protease inhibitor used as a component of management of HIV/AIDS, highly active antiretroviral therapy to treat HIV/AIDS. It is soluble whit ...

, and

phenprocoumon Phenprocoumon (marketed under the brand names Marcoumar, Marcumar and Falithrom) is a long-acting anticoagulant to be taken by mouth, and a coumarin derivative. It acts as a vitamin K antagonist and inhibits blood clotting (coagulation) by blocki ...

. It may also interact with the anti-cancer drugs

irinotecan Irinotecan, sold under the brand name Camptosar among others, is an anti-cancer medication used to treat colon cancer and small cell lung cancer. For colon cancer it is used either alone or with fluorouracil. For small cell lung cancer it is ...

and

imatinib Imatinib, sold under the brand names Gleevec and Glivec (both marketed worldwide by Novartis) among others, is an oral targeted therapy medication used to treat cancer. Imatinib is a small molecule inhibitor targeting multiple tyrosine kinases ...

. *

Salvia miltiorrhiza ''Salvia miltiorrhiza'' (), also known as red sage, redroot sage, Chinese sage, or danshen, is a perennial plant in the genus ''Salvia'', highly valued for its roots in traditional Chinese medicine. Native to China and Japan, it grows at elevat ...

may enhance anticoagulation and bleeding among people taking warfarin. *

Allium sativum Garlic (''Allium sativum'') is a species of bulbous flowering plants in the genus ''Allium''. Its close relatives include the onion, shallot, leek, chives, Allium fistulosum, Welsh onion, and Allium chinense, Chinese onion. Garlic is native to ...

has been found to decrease the plasma concentration of

saquinavir Saquinavir, sold under the brand name Invirase among others, is an antiretroviral medication used together with other medications to treat or prevent HIV/AIDS. Typically it is used with ritonavir or lopinavir/ritonavir to increase its effect. I ...

, and may cause

hypoglycemia Hypoglycemia (American English), also spelled hypoglycaemia or hypoglycæmia (British English), sometimes called low blood sugar, is a fall in blood sugar to levels below normal, typically below 70 mg/dL (3.9 mmol/L). Whipple's tria ...

when taken with

chlorpropamide Chlorpropamide is an antidiabetic drug, belonging to the sulfonylurea class of organic compounds. It is used to treat diabetes mellitus type 2. It is a long-acting first-generation sulfonylurea. Mechanism of action Like other sulfonylureas, ch ...

. *

Ginkgo biloba ''Ginkgo biloba'', commonly known as ginkgo or gingko ( ), also known as the maidenhair tree, is a species of gymnosperm tree native to East Asia. It is the last living species in the order Ginkgoales, which first appeared over 290 million year ...

can cause bleeding when combined with warfarin or

. * Concomitant Ephedra and

caffeine Caffeine is a central nervous system (CNS) stimulant of the methylxanthine chemical classification, class and is the most commonly consumed Psychoactive drug, psychoactive substance globally. It is mainly used for its eugeroic (wakefulness pr ...

use has been reported to, in rare cases, cause fatalities.

Mechanisms

The mechanisms underlying most herb-drug interactions are not fully understood. Interactions between herbal medicines and anticancer drugs typically involve enzymes that metabolize

cytochrome P450 Cytochromes P450 (P450s or CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that mostly, but not exclusively, function as monooxygenases. However, they are not omnipresent; for examp ...

. For example, St. John's Wort has been shown to induce

and

in vitro and in vivo.

Underlying factors

The factors or conditions that predispose the appearance of interactions include factors such as

old age Old age is the range of ages for people nearing and surpassing life expectancy. People who are of old age are also referred to as: old people, elderly, elders, senior citizens, seniors or older adults. Old age is not a definite biological sta ...

. This is where human physiology changing with age may affect the interaction of drugs. For example, liver metabolism, kidney function, nerve transmission, or the functioning of bone marrow all decrease with age. In addition, in old age, there is a sensory decrease that increases the chances of errors being made in the administration of drugs. The elderly are also more vulnerable to

polypharmacy Polypharmacy (polypragmasia) is an umbrella term to describe the simultaneous use of multiple medicines by a patient for their conditions. The term polypharmacy is often defined as regularly taking five or more medicines but there is no standard ...

, and the more drugs a patient takes, the higher is the chance of an interaction.García Morillo, J.S. ''Optimización del tratamiento de enfermos pluripatológicos en atención primaria'' UCAMI HHUU Virgen del Rocio. Sevilla. Spain. Available for members of SEMI at
ponencias de la II Reunión de Paciente Pluripatológico y Edad Avanzada
Genetic factors may also affect the enzymes and receptors, thus altering the possibilities of interactions. Patients with

hepatic 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 ...

renal In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and right in the retrop ...

diseases already may have difficulties metabolizing and excreting drugs, which may exacerbate the effect of interactions. Some drugs present an intrinsic increased risk for a harmful interaction, including drugs with a narrow

therapeutic index The therapeutic index (TI; also referred to as therapeutic ratio) is a quantitative measurement of the relative safety of a drug with regard to risk of overdose. It is a comparison of the amount of a therapeutic agent that causes toxicity to the ...

, where the difference between the effective dose and the

toxic dose In toxicology, the median toxic dose (TD50) of a drug or toxin is the dose at which toxicity occurs in 50% of cases. The ''type'' of toxicity should be specified for this value to have meaning for practical purposes. The median toxic dose encompas ...

is small.The term effective dose is generally understood to mean the minimum amount of a drug that is needed to produce the required effect. The toxic dose is the minimum amount of a drug that will produce a damaging effect. The drug

is an example of this type of drug.Castells Molina, S.; Castells, S. y Hernández Pérez, M. ''Farmacología en enfermería'' Published by Elsevier Spain, 2007 , 9788481749939 Available fro

/ref> Risks are also increased when the drug presents a steep Dose-response relationship, dose-response curve, and small changes in the dosage produce large changes in the drug's concentration in the blood plasma.

Epidemiology

As of 2008, among adults in the

United States of America The United States of America (USA), also known as the United States (U.S.) or America, is a country primarily located in North America. It is a federal republic of 50 states and a federal capital district, Washington, D.C. The 48 contiguo ...

older than 56, 4% were taking medication and/ or supplements that put them at risk of a major drug interaction. Potential drug-drug interactions have increased over time and are more common in the less-educated

even after controlling for age, sex, place of residence, and

comorbidity In medicine, comorbidity refers to the simultaneous presence of two or more medical conditions in a patient; often co-occurring (that is, concomitant or concurrent) with a primary condition. It originates from the Latin term (meaning "sicknes ...

Notes

References

Bibliography

* MA Cos. ''Interacciones de fármacos y sus implicancias clínicas.'' In: ''Farmacología Humana.'' Chap. 10, pp. 165–176. (J. Flórez y col. Eds). Masson SA, Barcelona. 1997.

External links

Drug Interactions: What You Should Know
U.S. Food and Drug Administration, Center for Drug Evaluation and Research, September 2013
COVID 19 Drug interaction check tool
University of Liverpool {{Authority control Clinical pharmacology Pharmacokinetics Prescription of drugs Drug safety