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Examples of herb-drug interactions include, but are not limited to:
- St. John's wort affects the clearance of numerous drugs, including cyclosporin, SSRI antidepressants, digoxin, indinavir, and phenprocoumon. It may also interact with the anti-cancer drugs irinotecan and imatinib.
- Salvia miltiorrhiza may enhance anticoagulation and bleeding among people taking warfarin.
- Allium sativum has been found to decrease the plasma concentration of saquinavir, and may cause hypoglycemia when taken with chlorpropamide.
- Ginkgo biloba can cause bleeding when combined with warfarin or aspirin.
- Concomitant ephedra and caffeine use has been reported to, in rare cases, cause fatalities.
Some fruit juices and fruits can interact with numerous drugs, in many cases causing adverse effects. The effect was first discovered by accident, when a test of drug interactions with alcohol used grapefruit juice to hide the taste of the ethanol.
It is still best-studied with grapefruit and grapefruit juice, but similar effects have more recently been seen with some (not all) other citrus fruits. One medical review advises patients to avoid all citrus juices until further research clarifies the risks. The interacting chemicals are found in many plants, and so many other foods may be affected; effects have been observed with apple juice, but their clinical significance is not yet known.
Normal amounts of food and drink, such as one whole grapefruit or a small glass () of grapefruit juice, can cause drug overdose toxicity. Fruit consumed three days before the medicine can still have an effect. The relative risks of different types of citrus fruit have not been systematically studied. Affected drugs typically have an auxiliary label saying “Do not take with grapefruit” on the container, and the interaction is elaborated on in the package insert. People are also advised to ask their physician or pharmacist about drug interactions.
The effects are caused by furanocoumarins (and, to a lesser extent, flavonoids). These chemicals inhibit key drug metabolizing enzymes, such as cytochrome P450 3A4 (CYP3A4). CYP3A4 is a metabolizing enzyme for almost 50% of drugs, and is found in the liver and small intestinal epithelial cells. As a result, many drugs are affected. Inhibition of enzymes can have two different effects, depending on whether the drug is either
1. metabolized by the enzyme to an inactive metabolite, "or"
2. activated by the enzyme to an active metabolite.
If the active drug is metabolized by the inhibited enzyme, then the fruit will stop the drug being metabolized, leaving elevated concentrations of the medication in the body, which can cause adverse effects. Conversely, if the medication is a prodrug, it needs to be metabolised to be converted to the active drug. Compromising its metabolism lowers concentrations of the active drug, reducing its therapeutic effect, and risking therapeutic failure.
Low drug concentrations can also be caused when the fruit suppresses drug absorption from the intestine.
A drug interaction is a situation in which a substance (usually another drug) affects the activity of a drug when both are administered together. This action can be synergistic (when the drug's effect is increased) or antagonistic (when the drug's effect is decreased) or a new effect can be produced that neither produces on its own. Typically, interactions between drugs come to mind (drug-drug interaction). However, interactions may also exist between drugs and foods (drug-food interactions), as well as drugs and medicinal plants or herbs (drug-plant interactions). People taking antidepressant drugs such as monoamine oxidase inhibitors should not take food containing tyramine as hypertensive crisis may occur (an example of a drug-food interaction). These interactions may occur out of accidental misuse or due to lack of knowledge about the active ingredients involved in the relevant substances.
It is therefore easy to see the importance of these pharmacological interactions in the practice of medicine. If a patient is taking two drugs and one of them increases the effect of the other it is possible that an overdose may occur. The interaction of the two drugs may also increase the risk that side effects will occur. On the other hand, if the action of a drug is reduced it may cease to have any therapeutic use because of under dosage. Notwithstanding the above, on occasion these interactions may be sought in order to obtain an improved therapeutic effect. Examples of this include the use of codeine with paracetamol to increase its analgesic effect. Or the combination of clavulanic acid with amoxicillin in order to overcome bacterial resistance to the antibiotic. It should also be remembered that there are interactions that, from a theoretical standpoint, may occur but in clinical practice have no important repercussions.
The pharmaceutical interactions that are of special interest to the practice of medicine are primarily those that have negative effects for an organism. The risk that a pharmacological interaction will appear increases as a function of the number of drugs administered to a patient at the same time. Over a third (36%) of older adults in the U.S. regularly use 5 or more medications or supplements and 15% are potentially at risk for a major drug-drug interaction. Both the use of medications and subsequent adverse drug interactions have increased significantly between 2005-2011.
It is possible that an interaction will occur between a drug and another substance present in the organism (i.e. foods or alcohol). Or in certain specific situations a drug may even react with itself, such as occurs with dehydration. In other situations, the interaction does not involve any effect on the drug. In certain cases, the presence of a drug in an individual's blood may affect certain types of laboratory analysis (analytical interference).
It is also possible for interactions to occur outside an organism before administration of the drugs has taken place. This can occur when two drugs are mixed, for example, in a saline solution prior to intravenous injection. Some classic examples of this type of interaction include that thiopentone and suxamethonium should not be placed in the same syringe and same is true for benzylpenicillin and heparin. These situations will all be discussed under the same heading due to their conceptual similarity.
Drug interactions may be the result of various processes. These processes may include alterations in the pharmacokinetics of the drug, such as alterations in the absorption, distribution, metabolism, and excretion (ADME) of a drug. Alternatively, drug interactions may be the result of the pharmacodynamic properties of the drug, e.g. the co-administration of a receptor antagonist and an agonist for the same receptor.
Herb-drug interactions are drug interactions that occur between herbal medicines 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, although most herbal remedies are not associated with drug interactions causing serious consequences. Most herb-drug interactions are moderate in severity. The most commonly implicated conventional drugs in herb-drug interactions are warfarin, insulin, aspirin, digoxin, and ticlopidine, 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.
The effect of grapefruit juice with regard to drug absorption was originally discovered in 1989. The first published report on grapefruit drug interactions was in 1991 in the Lancet entitled "Interactions of Citrus Juices with Felodipine and Nifedipine," and was the first reported food-drug interaction clinically. However, the effect only became well-publicized after being responsible for a number of bad interactions with medication.
Tachyphylaxis (Greek ταχύς, "tachys", "rapid", and φύλαξις, "phylaxis", "protection") is a medical term describing an acute, sudden decrease in response to a drug after its administration, i.e. a rapid and short-term onset of drug tolerance. It can occur after an initial dose or after a series of small doses. Increasing the dose of the drug may be able to restore the original response.
The U.S Food and Drug Administration defines a serious adverse event as one when the patient outcome is one of the following:
- Death
- Life-threatening
- Hospitalization (initial or prolonged)
- Disability - significant, persistent, or permanent change, impairment, damage or disruption in the patient's body function/structure, physical activities or quality of life.
- Congenital anomaly
- Requires intervention to prevent permanent impairment or damage
Severity is a point on an arbitrary scale of intensity of the adverse event in question. The terms "severe" and "serious" when applied to adverse events are technically very different. They are easily confused but can not be used interchangeably, requiring care in usage.
A headache is severe, if it causes intense pain. There are scales like "visual analog scale" that help clinicians assess the severity. On the other hand, a headache is not usually serious (but may be in case of subarachnoid haemorrhage, subdural bleed, even a migraine may temporally fit criteria), unless it also satisfies the criteria for seriousness listed above.
Types A and B were proposed in the 1970s, and the other types were proposed subsequently when the first two proved insufficient to classify ADRs.
Among US adults older than 55, 4% are 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 low educated elderly even after controlling for age, sex, place of residence, and comorbidity.
Tachyphylaxis is characterized by the rate sensitivity: the response of the system depends on the rate with which a stimulus is presented. To be specific, a high-intensity prolonged stimulus or often-repeated stimulus may bring about a diminished response also known as desensitization.
Verticillium wilt is a wilt disease of over 350 species of eudicot plants caused by six species of Verticillium genus, "V. dahliae", "V. albo-atrum", "V. longisporum", V. nubilum, V. theobromae and
V. tricorpus. (See, for example, Barbara, D.J. & Clewes, E. (2003). "Plant pathogenic Verticillium species: how many of them are there?" Molecular Plant Pathology 4(4).297-305. Blackwell Publishing.) Many economically important plants are susceptible including cotton, tomatoes, potatoes, oilseed rape, eggplants, peppers and ornamentals, as well as others in natural vegetation communities. Many eudicot species and cultivars are resistant to the disease and all monocots, gymnosperms and ferns are immune.
Symptoms are superficially similar to "Fusarium" wilts. There is no chemical control for the disease but crop rotation, the use of resistant varieties and deep plowing may be useful in reducing the spread and impact of the disease.
Glyceraldehyde 3-phosphate dehydrogenase (abbreviated as GAPDH or less commonly as G3PDH) () is an enzyme of ~37kDa that catalyzes the sixth step of glycolysis and thus serves to break down glucose for energy and carbon molecules. In addition to this long established metabolic function, GAPDH has recently been implicated in several non-metabolic processes, including transcription activation, initiation of apoptosis, ER to Golgi vesicle shuttling, and fast axonal, or axoplasmic transport. In sperm, a testis-specific isoenzyme GAPDHS is expressed.
Developmental toxicity is any structural or functional alteration, reversible or irreversible, which interferes with homeostasis, normal growth, differentiation, development or behavior, and which is caused by environmental insult (including drugs, lifestyle factors such as alcohol, diet, and environmental toxic chemicals or physical factors). It is the study of adverse effects on the development of the organism resulting from exposure to toxic agents before conception (either parent), during prenatal development, or post-natally until puberty. The substance that causes developmental toxicity from embryonic stage to birth is called teratogens. The effect of the developmental toxicants depends on the type of substance, dose and duration and time of exposure.
Certain Pathogens are also included since the toxins they secrete are known to cause adverse effects on the development of the organism when the mother or fetus is infected. Developmental toxicology is a science studying adverse developmental outcomes. This term has widely replaced the early term for the study of primarily structural congenital abnormalities, teratology, to enable inclusion of a more diverse spectrum of congenital disorders. Typical factors causing developmental toxicity are radiation, infections (e.g. rubella), maternal metabolic imbalances (e.g. alcoholism, diabetes, folic acid deficiency), drugs (e.g. anticancer drugs, tetracyclines, many hormones, thalidomide), and environmental chemicals (e.g. mercury, lead, dioxins, PBDEs, HBCD, tobacco smoke). The first-trimester exposure is considered the most potential for developmental toxicity.
Once fertilization has taken place, the toxicants in the environment can pass through the mother to the developing embryo or fetus across the placental barrier. The fetus is at greatest risk during the first 14th to 60th day of the pregnancy when the major organs are being formed. However, depending on the type of toxicant and amount of exposure, a fetus can be exposed toxicant at any time during pregnancy. For example, exposure to a particular toxicant at one time in the pregnancy may result in organ damage and at another time in the pregnancy could cause death of the fetus and miscarriage. There are a number of chemicals, biological agents (such as bacteria and viruses), and physical agents (such as radiation) used in a variety of workplaces that are known to cause developmental disorders. Developmental disorders can include a wide range of physical abnormalities, such as bone or organ deformities, or behavioral and learning problems, such as a mental retardation. Exposures to some chemicals during pregnancy can lead to the development of cancer later in the life of the child and are called transgenerational carcinogens. Exposure to toxicants during the second and the third trimester of a pregnancy can lead to slow fetal grown and result in low birth weight.
Citrus Black Spot is a fungal disease caused by Guignardia citricarpa. This Ascomycete fungus affects citrus plants throughout subtropical climates, causing a reduction in both fruit quantity and quality. Symptoms include both fruit and leaf lesions, the latter being critical to inter-tree dispersal. Strict regulation and management is necessary to control this disease since there are currently no citrus varieties that are resistant.
Combined drug intoxication (CDI), also known as multiple drug intake (MDI) or lethal polydrug/polypharmacy intoxication, is an unnatural cause of human death. CDI is often confused with drug overdose, but it is a completely different phenomenon. It is distinct in that it is due to the simultaneous use of multiple drugs, whether the drugs are prescription, over-the-counter, recreational, or some other combination. Alcohol can exacerbate the symptoms and may directly contribute to increased severity of symptoms. The reasons for toxicity vary depending on the mixture of drugs. Usually, most victims die after using two or more drugs in combination that suppress breathing, and the low blood oxygen level causes brain death.
The CDI/MDI phenomenon seems to be becoming more common in recent years. In December 2007, according to Dr. John Mendelson, a pharmacologist at the California Pacific Medical Center Research Institute, deaths by combined drug intoxication were relatively "rare" ("one in several million"), though they appeared then to be "on the rise". In July 2008, the Associated Press and CNN reported on a medical study showing that over two decades, from 1983 to 2004, such deaths have soared. It has also become a prevalent risk for older patients.
Patients affected by ADT tachyphylaxis experience a noticeably sudden progressive decrease in response to SSRIs. The reported rates of this condition vary from 9% to 33% of SSRI users, and the majority of those affected are less responsive to subsequent treatments. In most observational studies, these individuals suffer a recurrence or relapse of depression without changing the previously effective dose.
ADT tachyphylaxis incorporates drug sensitivity as a potential causal factor for the decreased response. However, tolerance provides a more accurate explanation. While the exact cause of ADT tachyphylaxis in individual cases is unknown, drug tolerance is a more comprehensive model, as it includes mechanisms of pharmacodynamic tolerance, metabolic tolerance, and others.
Overmedication is an inappropriate medical treatment that occurs when a patient takes unnecessary or excessive medications. This may happen because the prescriber is unaware of other medications the patient is already taking, because of drug interactions with another chemical or target population, because of human error, because of undiagnosed medical conditions or because of conflicts of interest in the pharmaceutical industry, creating-over promotion (via advertising campaigns, sales to private practice Doctors, or biased or altered medical studies) causing widespread unnecessary use of a specific medicine, or unnecessary dosage of a medicine, due to excessive profit motives in the pharmaceutical industry. This is also sometimes described as the "commercialization of medicine".
Overmedication can also occur when consumers take more medication than is prescribed or as labeled on over-the-counter (OTC) products—either intentionally or unintentionally—or when consumers unknowingly take both prescription and nonprescription drug products containing the same active ingredients. For example, overmedication (in the form of acute overdose) can occur when a prescription drug like Vicodin, which contains both hydrocodone and acetaminophen, is taken along with the nonprescription product Tylenol, which contains acetaminophen as the active ingredient. In other words, overmedication can be caused by both prescribers and consumers or their caretakers.
Another important instance of overmedication occurs when consumers are either prescribed or take additional prescribed or OTC drugs which produce the same or similar therapeutic effects. For instance, if a patient is taking a prescription strength ibuprofen product and also uses a naprosyn product—whether prescription or OTC strength—this, too, can constitute overmedication, can be dangerous, and can be costly to the patient in overall health care costs. Often consumers/patients overmedicate themselves by taking their medications at shorter intervals than prescribed or than container labels specify. As a result, medications may accumulate at higher levels, causing undesired side effects, sometimes serious, or even fatal. Such situations are often reversed through targeted deprescribing by members of the medical team.
Persons who feel that they are overmedicated tend to not to follow their physician's instructions for taking their medication.
Hard spots are the most common lesions. They are small, round, and sunken. The average diameter of hard spot lesions ranges from 3–10 mm (.12-.4 in).
They have dark red to chocolate brown margins and often have pycnidia in the gray-colored centers. A green halo may be present around the lesion.
People who engage in polypharmacy and other hypochondriac behaviors are at an elevated risk of death from CDI. Elderly people are at the highest risk of CDI, because of having many age-related health problems requiring many medications combined with age-impaired judgment, leading to confusion in taking medications.
"Verticillium" spp. attack a very large host range including more than 350 species of vegetables, fruit trees, flowers, field crops, and shade or forest trees. Most vegetable species have some susceptibility, so it has a very wide host range. A list of known hosts is at the bottom of this page.
The symptoms are similar to most wilts with a few specifics to "Verticillium". Wilt itself is the most common symptom, with wilting of the stem and leaves occurring due to the blockage of the xylem vascular tissues and therefore reduced water and nutrient flow. In small plants and seedlings, "Verticillium" can quickly kill the plant while in larger, more developed plants the severity can vary. Some times only one side of the plant will appear infected because once in the vascular tissues, the disease migrates mostly upward and not as much radially in the stem. Other symptoms include stunting, chlorosis or yellowing of the leaves, necrosis or tissue death, and defoliation. Internal vascular tissue discoloration might be visible when the stem is cut.
In "Verticillium", the symptoms and effects will often only be on the lower or outer parts of plants or will be localized to only a few branches of a tree. In older plants, the infection can cause death, but often, especially with trees, the plant will be able to recover, or at least continue living with the infection. The severity of the infection plays a large role in how severe the symptoms are and how quickly they develop.
An adrenergic storm is a sudden and dramatic increase in serum levels of the catecholamines adrenalin and noradrenalin (also known as epinephrine and norepinephrine respectively), with a less significant increase in dopamine transmission. It is a life-threatening condition because of extreme tachycardia and hypertension, and is especially dire for those with prior heart problems. If treatment is prompt, prognosis is good; typically large amounts of diazepam or other benzodiazepines are administered alongside beta blockers. Beta blockers are contraindicated in some patients, so other anti-hypertensive medication such as clonidine may be used. It is usually caused by overdose of stimulants, especially cocaine or methamphetamine, or eating foods high in tyramine while taking monoamine oxidase inhibitors. A subarachnoid hemorrhage can also cause an adrenergic storm. A catecholamine storm is part of the normal course of Rabies infection, and is responsible for the severe feelings of agitation, terror, and dysautonomia present in the pre-coma stage of the disease.
Antidepressant treatment tachyphylaxis (ADT tachyphylaxis), also known as Prozac poop-out, is a medical condition in which progressive or acute tolerance effects are seen following chronic administration of a drug. ADT tachyphylaxis specifically refers to a sudden decrease in response to selective serotonin reuptake inhibitors (SSRIs), which are the most commonly prescribed antidepressants. Although less commonly prescribed as antidepressants (having lost popularity following the introduction of SSRIs), monoamine oxidase inhibitors, or MAOIs, have also incurred a "poop-out" effect among depressed patients.
Fructose malabsorption may cause gastrointestinal symptoms such as abdominal pain, bloating, flatulence or diarrhea.
The behavioral symptoms are similar to those of an amphetamine, cocaine or caffeine overdose. Overstimulation of the central nervous system results in a state of hyperkinetic movement and unpredictable mental status including mania, rage and suicidal behavior.
Physical symptoms are more serious and include heart arrhythmias as well as outright heart attack or stroke in people who are at risk of coronary disease. Breathing is rapid and shallow while both pulse and blood pressure are dangerously elevated.
A quinolone antibiotic is any member of a large group of broad-spectrum bactericides that share a bicyclic core structure related to the compound 4-quinolone. They are used in human and veterinary medicine to treat bacterial infections, as well as in animal husbandry.
Nearly all quinolone antibiotics in modern use are fluoroquinolones, which contain a fluorine atom in their chemical structure and are effective against both Gram-negative and Gram-positive bacteria. One example is ciprofloxacin (Cipro), one of the most widely used antibiotics worldwide.