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.

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.

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.

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.

Multiple chemical sensitivity (MCS), also known as idiopathic environmental intolerances (IEI), is a disputed chronic condition characterized by symptoms that the affected person attributes to low-level exposures to commonly used chemicals. Symptoms are typically vague and non-specific. They may include fatigue, headaches, nausea, and dizziness.

Commonly attributed substances include scented products, pesticides, plastics, synthetic fabrics, smoke, petroleum products, and paint fumes.

Although the symptoms themselves are real, and can be disabling, MCS is not recognized as an organic, chemical-caused illness by the World Health Organization, American Medical Association, or any of several other professional medical organizations. Blinded clinical trials show that people with MCS react as often and as strongly to placebos as they do to chemical stimuli; the existence and severity of symptoms is related to perception that a chemical stimulus is present. Some attribute the symptoms to depression, somatoform disorders, or anxiety disorders.

Symptoms range in severity from mild to disabling.

Symptoms are common, but vague and non-specific for the condition. The most common are feeling tired, "brain fog" (short-term memory problems, difficulty concentrating), gastrointestinal problems, headaches, and muscle pain.

A partial list of other symptoms patients have attributed to MCS include: difficulty breathing, pains in the throat, chest, or abdominal region, skin irritation, headaches, neurological symptoms (nerve pain, pins and needles feelings, weakness, trembling, restless leg syndrome), tendonitis, seizures, visual disturbances (blurring, halo effect, inability to focus), anxiety, panic and/or anger, sleep disturbance, suppression of immune system, digestive difficulties, nausea, indigestion/heartburn, vomiting, diarrhea, joint pains, vertigo/dizziness, abnormally acute sense of smell (hyperosmia), sensitivity to natural plant fragrance or natural pine terpenes, dry mouth, dry eyes, and an overactive bladder.

Hepatotoxicity (from "hepatic toxicity") implies chemical-driven liver damage. Drug-induced liver injury is a cause of acute and chronic liver disease.

The liver plays a central role in transforming and clearing chemicals and is susceptible to the toxicity from these agents. Certain medicinal agents, when taken in overdoses and sometimes even when introduced within therapeutic ranges, may injure the organ. Other chemical agents, such as those used in laboratories and industries, natural chemicals (e.g., microcystins) and herbal remedies can also induce hepatotoxicity. Chemicals that cause liver injury are called hepatotoxins.

More than 900 drugs have been implicated in causing liver injury (see LiverTox, external link, below) and it is the most common reason for a drug to be withdrawn from the market. Hepatotoxicity and drug-induced liver injury also account for a substantial number of compound failures, highlighting the need for drug screening assays, such as stem cell-derived hepatocyte-like cells, that are capable of detecting toxicity early in the drug development process. Chemicals often cause subclinical injury to the liver, which manifests only as abnormal liver enzyme tests.

Drug-induced liver injury is responsible for 5% of all hospital admissions and 50% of all acute liver failures.

Isoniazide (INH) is one of the most commonly used drugs for tuberculosis; it is associated with mild elevation of liver enzymes in up to 20% of patients and severe hepatotoxicity in 1-2% of patients.

Dermatitis herpetiformis (DH), or Duhring-Brocq disease, is a chronic blistering skin autoimmune condition, characterized by the presence of skin lesions that have an extensive and symmetrical distribution, predominating in areas of greater friction, and affecting mainly both elbows, knees, buttocks, ankles, and may also affect the scalp and other parts of the body, and non-symmetrical occasionally. The lesions are vesicular-crusted and when flake off, they evolve to pigmented areas or achromic an intense burning, itchy and blistering rash. Despite its name, DH is neither related to nor caused by herpes virus: the name means that it is a skin inflammation having an appearance similar to herpes.

The age of onset is variable starting in children and adolescence but can also affect individuals of both sexes indistinctly at any age of their lives.

A fact that difficults its diagnosis is the relatively common presentation with atypical manifestations. Some patients may show erythema or severe pruritus alone, wheals of chronic urticaria, purpuric lesions resembling petechiae on hands and feet, palmo-plantar keratosis, leukocytoclastic vasculitis-like appearance, and/or lesions mimicking prurigo pigmentosa. DH may be confused with many different cutaneous lesions, such as atopic dermatitis, eczema, urticaria, scabies, impetigo, polymorphic erythema and other autoimmune blistering diseases.

DH is considered to be as "the coeliac disease of the skin". For this reason, the new guidelines of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition for the diagnosis of coeliac disease conclude that its proven presence, by itself, confirms the diagnosis of coeliac disease. Nevertheless, duodenal biopsy is recommended in doubtful DH cases, or if there are suspected gastrointestinal complications, including lymphoma. People with DH have different degrees of intestinal involvement, ranging from milder mucosal lesions to the presence of villous atrophy.

The main and more efficacious treatment for DH is following a lifelong gluten-free diet, which produces the improvement of skin and gut lesions. Nevertheless, the skin lesions may take several months or even years to disappear. To calm itching, dapsone is often recommended as a temporary treatment, during the time it takes for the diet to work, but it has no effect on the gastrointestinal changes and may have important side effects.

More than 250 symptoms of gluten sensitivity have been reported, including bloating, abdominal discomfort or pain, constipation and diarrhea. Sensitivity may also present with extraintestinal symptoms, including headache, "brain fog", tingling and/or numbness in hands and feet, fatigue, as well as muscular disturbances and bone or joint pain; also neuropsychiatric manifestations ("gluten-sensitive idiopathic neuropathies") have been reported on.

Although lichen planus can present with a variety of lesions, the most common presentation is as a well defined area of purple-coloured, itchy, flat-topped papules with interspersed lacy white lines (Wickham's striae). This description is known as the characteristic "6 Ps" of lichen planus: planar (flat-topped), purple, polygonal, pruritic, papules, and plaques. This rash, after regressing, is likely to leave an area of hyperpigmentation that slowly fades. That said, a variety of other lesions can also occur.

Obsessive–compulsive disorder (OCD) is a mental disorder where people feel the need to check things repeatedly, perform certain routines repeatedly (called "rituals"), or have certain thoughts repeatedly. People are unable to control either the thoughts or the activities for more than a short period of time. Common activities include hand washing, counting of things, and checking to see if a door is locked. Some may have difficulty throwing things out. These activities occur to such a degree that the person's daily life is negatively affected. Often they take up more than an hour a day. Most adults realize that the behaviors do not make sense. The condition is associated with tics, anxiety disorder, and an increased risk of suicide.

The cause is unknown. There appear to be some genetic components with both identical twins more often affected than both non-identical twins. Risk factors include a history of child abuse or other stress inducing event. Some cases have been documented to occur following infections. The diagnosis is based on the symptoms and requires ruling out other drug related or medical causes. Rating scales such as the Yale–Brown Obsessive Compulsive Scale (Y-BOCS) can be used to assess the severity. Other disorders with similar symptoms include anxiety disorder, major depressive disorder, eating disorders, tic disorders, and obsessive–compulsive personality disorder.

Treatment involves counselling, such as cognitive behavioral therapy (CBT), and sometimes medication, typically selective serotonin reuptake inhibitors (SSRIs). CBT for OCD involves increasing exposure to what causes the problems while not allowing the repetitive behavior to occur. While clomipramine appears to work as well as SSRIs, it has greater side effects. Atypical antipsychotics may be useful when used in addition to an SSRI in treatment-resistant cases but are also associated with an increased risk of side effects. Without treatment, the condition often lasts decades.

Obsessive–compulsive disorder affects about 2.3% of people at some point in their life. Rates during a given year are about 1.2% and it occurs worldwide. It is unusual for symptoms to begin after the age of thirty-five, and half of people develop problems before twenty. Males and females are affected about equally. In English the phrase "obsessive–compulsive" is often used in an informal manner unrelated to OCD to describe someone who is excessively meticulous, perfectionistic, absorbed, or otherwise fixated.

Variants of cutaneous lichen planus are distinguished based upon the appearance of the lesions and/or their distribution. Lesions can affect the:

- Extremities (face, dorsal hands, arms, and nape of neck). This is more common in Middle Eastern countries in spring and summer, where sunlight appears to have a precipitating effect.

- Palms and soles

- Intertriginous areas of the skin. This is also known as "Inverse lichen planus."

- Nails characterized by irregular longitudinal grooving and ridging of the nail plate, thinning of the nail plate, pterygium formation, shedding of the nail plate with atrophy of the nail bed, subungual keratosis, longitudinal erthronychia (red streaks), and subungual hyperpigmentation. A sand-papered appearance is present in around 10% of individuals with nail lichen planus.

- Hair and Scalp. The scalp is rarely affected by a condition known as lichen planopilaris, acuminatus, follicular lichen planus, and peripilaris, characterised by violaceous, adherent follicular scale with progressive scarring alopecia. While lichen planus and lichen planopilaris may occur together, aside from sharing the term ‘lichen’ and revealing inflammation on skin biopsy, there is neither established data on their co-occurrence nor data to suggest a common etiology. Lichen planopilaris is considered an orphan disease with no definitive prevalence data and no proven effective treatments.

Other variants may include:

- "Lichen planus pemphigoides" characterized by the development of tense blisters atop lesions of lichen planus or the development vesicles de novo on uninvolved skin.

- "Keratosis lichenoides chronica" (also known as "Nekam's disease") is a rare dermatosis characterized by violaceous papular and nodular lesions, often arranged in a linear or reticulate pattern on the dorsal hands and feet, extremities, and buttock, and some cases manifest by sorrheic dermatitis-like eruption on the scalp and face; also palmo plantar keratosis has been reported.

- "Lichenoid keratoses" (also known as "Benign lichenoid keratosis," and "Solitary lichen planus") is a cutaneous condition characterized by brown to red scaling maculopapules, found on sun-exposed skin of extremities. Restated, this is a cutaneous condition usually characterized by a solitary dusky-red to violaceous papular skin lesion.

- "Lichenoid dermatitis" represents a wide range of cutaneous disorders characterized by lichen planus-like skin lesions.

OCD can present with a wide variety of symptoms. Certain groups of symptoms typically occur together. These groups are sometimes viewed as dimensions or clusters that may reflect an underlying process. The standard assessment tool for OCD, the Yale–Brown Obsessive Compulsive Scale (Y-BOCS), has 13 predefined categories of symptoms. These symptoms fit into three to five groupings. A meta analytic review of symptom structures found a four factor structure(grouping) to be most reliable. The observed groups included a "symmetry factor", a "forbidden thoughts factor", a "cleaning factor" and a "hoarding factor". The "symmetry factor" correlated highly with obsessions related to ordering, counting, symmetry as well as repeating compulsions. The "forbidden thoughts factor" correlated highly with intrusive and distressing thoughts of a violent, religious or sexual nature. The "cleaning factor" correlated highly with obsessions about contamination and compulsions related to cleaning. The "hoarding factor" only involved hoarding related obsessions and compulsions, and was identified as being distinct from other symptom groupings.

While OCD has been considered a homogenous disorder from a neuropsychological perspective, many of the putative neuropsychological deficits may be due to comorbid disorders. Furthermore, some subtypes have been associated with improvement in performance on certain tasks such as pattern recognition(washing subtype) and spatial working memory(obsessive thought subtype). Subgroups have also been distinguished by neuroimaging findings and treatment response. Neuroimaging studies on this have been too few, and the subtypes examined have differed too much to draw any conclusions. On the other hand, subtype dependent treatment response has been studied, and the hoarding subtype has consistently responded least to treatment.

The T helper cells (T cells) are a type of T cell that play an important role in the immune system, particularly in the adaptive immune system. They help the activity of other immune cells by releasing T cell cytokines. These cells help suppress or regulate immune responses. They are essential in B cell antibody class switching, in the activation and growth of cytotoxic T cells, and in maximizing bactericidal activity of phagocytes such as macrophages.

Mature T cells express the surface protein CD4 and are referred to as CD4 T cells. Such CD4 T cells are generally treated as having a pre-defined role as helper T cells within the immune system. For example, when an antigen-presenting cell expresses an antigen on MHC class II, a CD4 cell will aid those cells through a combination of cell to cell interactions (e.g. CD40 (protein) and CD40L) and through cytokines.

CD154, also called CD40 ligand or CD40L, is a cell surface protein that mediates T cell helper function in a contact-dependent process and is a member of the TNF superfamily of molecules. It binds to CD40 on antigen-presenting cells (APC), which leads to many effects depending on the target cell type. CD154 acts as a costimulatory molecule and is particularly important on a subset of T cells called T follicular helper cells (T cells). On T cells, CD154 promotes B cell maturation and function by engaging CD40 on the B cell surface and therefore facilitating cell-cell communication. A defect in this gene results in an inability to undergo immunoglobulin class switching and is associated with hyper IgM syndrome. Absence of CD154 also stops the formation of germinal centers and therefore prohibiting antibody affinity maturation, an important process in the adaptive immune system.

The importance of helper T cells can be seen from HIV, a virus that primarily infects CD4 T cells. In the advanced stages of HIV infection, loss of functional CD4 T cells leads to the symptomatic stage of infection known as the acquired immunodeficiency syndrome (AIDS). When the HIV virus is detected early in blood or other bodily fluids, continuous therapy can delay the time at which this fall happens. Therapy can also better manage the course of AIDS if and when it occurs. There are other rare disorders such as lymphocytopenia which result in the absence or dysfunction of CD4 T cells. These disorders produce similar symptoms, many of which are fatal.

The immune system must achieve a balance of sensitivity in order to respond to foreign antigens without responding to the antigens of the host itself. When the immune system responds to very low levels of antigen that it usually shouldn't respond to, a hypersensitivity response occurs. Hypersensitivity is believed to be the cause of allergy and some auto-immune disease.

Hypersensitivity reactions can be divided into four types:

- Type 1 hypersensitivity includes common immune disorders such as asthma, allergic rhinitis (hay fever), eczema, urticaria (hives) and anaphylaxis. These reactions all involve IgE antibodies, which require a T2 response during helper T cell development. Preventive treatments, such as corticosteroids and montelukast, focus on suppressing mast cells or other allergic cells; T cells do not play a primary role during the actual inflammatory response. It's important to note that the numeral allocation of hypersensitivity "types" does not correlate (and is completely unrelated) to the "response" in the T model.

- Type 2 and Type 3 hypersensitivity both involve complications from auto-immune or low affinity antibodies. In both of these reactions, T cells may play an accomplice role in generating these auto-specific antibodies, although some of these reactions under Type 2 hypersensitivity would be considered normal in a healthy immune system (for example, Rhesus factor reactions during child-birth is a normal immune response against child antigens). The understanding of the role of helper T cells in these responses is limited but it is generally thought that T2 cytokines would promote such disorders. For example, studies have suggested that lupus (SLE) and other auto-immune diseases of similar nature can be linked to the production of T2 cytokines.

- Type 4 hypersensitivity, also known as delayed type hypersensitivity, are caused via the over-stimulation of immune cells, commonly lymphocytes and macrophages, resulting in chronic inflammation and cytokine release. Antibodies do not play a direct role in this allergy type. T cells play an important role in this hypersensitivity, as they activate against the stimulus itself and promote the activation of other cells; particularly macrophages via T1 cytokines.

Other cellular hypersensitivities include cytotoxic T cell mediated auto-immune disease, and a similar phenomenon; transplant rejection. Helper T cells are required to fuel the development of these diseases. In order to create sufficient auto-reactive killer T cells, interleukin-2 must be produced, and this is supplied by CD4 T cells. CD4 T cells can also stimulate cells such as natural killer cells and macrophages via cytokines such as interferon-gamma, encouraging these cytotoxic cells to kill host cells in certain circumstances.

The mechanism that killer T cells use during auto-immunity is almost identical to their response against viruses, and some viruses have been accused of causing auto-immune diseases such as Type 1 diabetes mellitus. Cellular auto-immune disease occurs because the host antigen recognition systems fail, and the immune system believes, by mistake, that a host antigen is foreign. As a result, the CD8 T cells treat the host cell presenting that antigen as infected, and go on to destroy all host cells (or in the case of transplant rejection, transplant organ) that express that antigen.

Some of this section is a simplification. Many auto-immune diseases are more complex. A well-known example is rheumatoid arthritis, where both antibodies and immune cells are known to play a role in the pathology. Generally the immunology of most auto-immune diseases is not well understood.