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.

Based on the results of worldwide screening of biotinidase deficiency in 1991, the incidence of the disorder is:

5 in 137,401 for profound biotinidase deficiency

- One in 109,921 for partial biotinidase deficiency

- One in 61,067 for the combined incidence of profound and partial biotinidase deficiency

- Carrier frequency in the general population is approximately one in 120.

A triplex tetra-primer ARMS-PCR method was developed for the simultaneous detection of C677T and A1298C polymorphisms with the A66G MTRR polymorphism in a single PCR reaction.

Methylene tetrahydrofolate reductase (MTHFR) is the rate-limiting enzyme in the methyl cycle, and it is encoded by the "MTHFR" gene. Methylenetetrahydrofolate reductase catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a cosubstrate for homocysteine remethylation to methionine. Natural variation in this gene is common in healthy people. Although some variants have been reported to influence susceptibility to occlusive vascular disease, neural tube defects, Alzheimer's disease and other forms of dementia, colon cancer, and acute leukemia, findings from small early studies have not been reproduced. Some mutations in this gene are associated with methylenetetrahydrofolate reductase deficiency.

Bile excretion is different from kidney excretion as it is always involves energy expenditure in active transport across the epithelium of the bile duct against a concentration gradient. This transport system can also be saturated if the plasma concentrations of the drug are high. Bile excretion of drugs mainly takes place where their molecular weight is greater than 300 and they contain both polar and lipophilic groups. The glucuronidation of the drug in the kidney also facilitates bile excretion. Substances with similar physicochemical properties can block the receptor, which is important in assessing interactions. A drug excreted in the bile duct can occasionally be reabsorbed by the intestines (in the entero-hepatic circuit), which can also lead to interactions with other drugs.

The risk of chemotherapy-induced nausea and vomiting varies based on the type of treatment received, as well as several outside factors. Some types of chemotherapy are more prone to causing nausea and vomiting than others. Some chemotheraputic agents may not cause nausea and vomiting on their own, but may when used in combination with other agents. Regimens that are linked to a high incidence (90% or higher) of nausea and vomiting are referred to as "highly emetogenic chemotherapy", and those causing a moderate incidence (30–90%) of nausea and vomiting are referred to as "moderately emetogenic chemotherapy".

Some highly emetogenic agents and chemotherapy regimens include:

- Cisplatin

- Dacarbazine

- Cyclophosphamide (>1500 mg/m)

- Carmustine (>250 mg/m)

- Mechlorethamine

- Streptozocin

- ABVD

- MOPP/COPP/BEACOPP

- CBV

- VIP

- BEP

- AC

Some moderately emetogenic agents and regimens include:

- Carboplatin

- Methotrexate

- Doxorubicin/Adriamycin

- Docetaxel

- Paclitaxel

- Etoposide

- Ifosfamide

- Cyclophosphamide (≤1500 mg/m)

- CHOP/CHOP-R

Besides the type of treatment, personal factors may put a patient at greater risk for CINV. Other risk factors include:

- Female sex

- Patient age (under 55 years old)

- History of light alcohol use

- History of previous CINV

- History of nausea and vomiting during pregnancy

- History of motion sickness

- Anxiety or depression

- Anticipation of CINV

Raw eggs should be avoided in those with biotin deficiency, because egg whites contain high levels of the anti-nutrient avidin. The name avidin literally means that this protein has an "avidity" (Latin: "to eagerly long for") for biotin. Avidin binds irreversibly to biotin and this compound is then excreted in the urine.

The gene NT5E is related to the gene ENPP1, which when mutated is known to cause arterial calcification in infants. Treatments for the ENPP1 mutation, such as bisphosphonates, which are similar to phosphatase, and adenosine reuptake inhibitors, provide possible routes of treatment for the NT5E mutation, as the mechanism of both disorders are very similar.

In ACDC, the gene NT5E, which produces the enzyme CD73, is mutated. A mutation in NT5E causes CD73 to form incorrectly. A nonsense mutation, a single nucleotide insertion, and a missense mutation have all been found to produce essentially the same inactivation of CD73. Normally, CD73 binds to adenosine monophosphate, a nucleotide in DNA, and converts it to adenosine. In affected patients, little to no CD73 was functional. The calcification of cells is caused in part by a lack of pyrophosphate, which is broken down throughout the body by tissue-nonspecific alkaline phosphatase (TNAP). Without pyrophosphate, calcium phosphate crystals cannot be broken down. Since the inactive CD73 is unable to produce adenosine, which inhibits TNAP, there is an increase in TNAP levels and a decrease in pyrophosphate levels.

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. For example, St. John's Wort has been shown to induce CYP3A4 and P-glycoprotein in vitro and in vivo.

Antineoplastic resistance, synonymous with chemotherapy resistance, is the ability of cancer cells to survive and grow despite different anti-cancer therapies, i.e. their multiple drug resistance. There are two general causes of antineoplastic therapy failure:

Inherent resistance, such as genetic characteristics, giving cancer cells their resistance from the beginning, which is rooted in the concept of cancer cell heterogeneity and acquired resistance after drug exposure.

Elevated levels of the alkaline phosphatase enzyme are reported with those who have obesity. A study reported there were higher serum levels of alkaline phosphatase in obese than in the non obese. With elevated alkaline phosphatase levels there is an increase in disproportionate intracellular fat depots and thereby releasing itself into the bloodstream. The relationship between alkaline phosphatase and obesity is still being tested.

Elevated serum levels of alkaline phosphatase has been associated with Chronic Kidney Disease (CKD). Recently, studies have shown that elevated levels may predict mortality independent of bone metabolism factors and liver function tests in CKD. This distinction is indicated by the markers of inflammations specifically from C-reactive protein (CRP) with elevated levels of alkaline phosphatase. Hence, elevated serum alkaline phosphatase activity may be a marker for inflammation because of its association with elevated levels of CRP.

- Chronic kidney disease

Genetic models of SLOS are created by knocking out the "DHCR7" gene. One study used homologous recombination to disrupt "DCHR7" in mouse embryonic stem cells. Similar to what is found in humans, heterozygous mice (having only one mutated allele) were phentoypically normal, and were crossed to produce pups (young mice) homozygous for the mutated allele. Although these pups died within the first day of life due to their inability to feed, they showed characteristics similar to humans with SLOS. They had decreased levels of cholesterol, increased levels of 7- and 8DHC, showed less growth and smaller birth weights, had craniofacial malformations, and less movement. Many also had a cleft palate, and decreased neuronal responses to glutamate. Overall however, the pups had fewer dysmorphic features than human patients with SLOS; they did not present limb, renal, adrenal or central nervous system malformations. This is explained by the fact that in rodents, maternal cholesterol can cross the placenta, and actually appears to be essential for the development of the fetus. In humans, very little maternal cholesterol is transferred to the fetus. In sum, the genetic mouse model is helpful to explain the neuropathophysiology of SLOS.

Inhalation of an agonist for the beta-2 adrenergic receptor, such as Salbutamol, Albuterol (US), is the most common treatment for asthma. Polymorphisms of the beta-2 receptor play a role in tachyphylaxis. Expression of the Gly-16 allele (glycine at position 16) results in greater receptor downregulation by endogenous catecholamines at baseline compared to Arg-16. This results in a greater single-use bronchodilator response in individuals homozygous for Arg-16 compared to Gly-16 homozygotes. However, with regular beta-2 agonist use, asthmatic Arg-16 individuals experience a significant decline in bronchodilator response. This decline does not occur in Gly-16 individuals. It has been proposed that the tachyphylactic effect of regular exposure to exogenous beta-2 agonists is more apparent in Arg-16 individuals because their receptors have not been downregulated prior to agonist administration.

Teratogenic models are induced by feeding pregnant rats or mice inhibitors of DCHR7. Two common inhibitors are BM15766 (4-(2-[1-(4-chlorocinnamyl)piperazin-4-yl]ethyl)-benzoic acid) and AY9944 (truns-l,4-bis(2-chlorobenzylaminomethy1)cyclohexane dihydrochloride). These compounds have different chemical and physical properties, but induce similar effects. AY9944 has been shown to induce holoprosencephaly and sexual malformations similar to those seen in humans with SLOS. It is also known to cause impairments in the serotonin receptor, another defect commonly seen in SLOS patients. BM15766 has produced the lack of cholesterol and bile acid synthesis that is seen in SLOS patients with homozygous mutations. All teratogenic models can be effectively used to study SLOS; however, they present lower levels of 7-DHC and 8-DHC than are seen in humans. This can be explained by the fact that humans experience a permanent block in their DHCR7 activity, where mice and rats treated with inhibitors experience only transient blocks. Furthermore, different species of mice and rats are more resistant to teratogens, and may be less effective as models of SLOS. Teratogenic models are most commonly used to study more long-term effects of SLOS, because they survive longer than genetic models. For example, one study examined the retinal degeneration of SLOS, which in rats does not occur until at least one month after birth.

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.

Antineoplastic resistance, often used interchangeably with chemotherapy resistance, is the multiple drug resistance of neoplastic (cancerous) cells, or the ability of cancer cells to survive and grow despite anti-cancer therapies.

There are two general causes of antineoplastic therapy failure: Inherent genetic characteristics, giving cancer cells their resistance, which is rooted in the concept of cancer cell heterogeneity and acquired resistance after drug exposure. Altered membrane transport, enhanced DNA repair, apoptotic pathway defects, alteration of target molecules, protein and pathway mechanisms, such as enzymatic deactivation.

Since cancer is a genetic disease, two genomic events underlie acquired drug resistance: Genome alterations (e.g. gene amplification and deletion) and epigenetic modifications.

Cancer cells are constantly using a variety of tools, involving genes, proteins and altered pathways, to ensure their survival against antineoplastic drugs.

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.

Cortisol inhibition, and as a result, excess androgen release can lead to a variety of symptoms. Other symptoms come about as a result of increased levels of circulating androgen. Androgen is a steroid hormone, generally associated with development of male sex organs and secondary male sex characteristics The symptoms associated with Cortisone Reductase Deficiency are often linked with Polycystic Ovary Syndrome (PCOS) in females. The symptoms of PCOS include excessive hair growth, oligomenorrhea, amenorrhea, and infertility. In men, cortisone reductase deficiency results in premature pseudopuberty, or sexual development before the age of nine.

Cortisone reductase deficiency is caused by dysregulation of the 11β-hydroxysteroid dehydrogenase type 1 enzyme (11β-HSD1), otherwise known as cortisone reductase, a bi-directional enzyme, which catalyzes the interconversion of cortisone to cortisol in the presence of NADH as a co-factor. If levels of NADH are low, the enzyme catalyses the reverse reaction, from cortisol to cortisone, using NAD+ as a co-factor.

Cortisol is a glucocorticoid that plays a variety of roles in many different biochemical pathways, including, but not limited to: gluconeogenesis, suppressing immune system responses and carbohydrate metabolism.

One of the symptoms of cortisone reductase deficiency is hyperandrogenism, resulting from activation of the Hypothalamic–pituitary–adrenal axis.

The deficiency has been known to exhibit symptoms of other disorders such as Polycystic Ovary Syndrome in women. Cortisone Reductase Deficiency alone has been reported in fewer than ten cases in total, all but one case were women. Elevated activity of 11β-HSD1 can lead to obesity or Type II Diabetes, because of the role of cortisol in carbohydrate metabolism and gluconeogenesis.

Increased consumption of zinc is another cause of copper deficiency. Zinc is often used for the prevention or treatment of common colds and sinusitis (inflammation of sinuses due to an infection), ulcers, sickle cell disease, celiac disease, memory impairment and acne. Zinc is found in many common vitamin supplements and is also found in denture creams. Recently, several cases of copper deficiency myeloneuropathy were found to be caused by prolonged use of denture creams containing high quantities of zinc.

Metallic zinc is the core of all United States currency coins, including copper coated pennies. People who ingest a large number of coins will have elevated zinc levels, leading to zinc-toxicity-induced copper deficiency and the associated neurological symptoms. This was the case for a 57-year-old woman diagnosed with schizophrenia. The woman consumed over 600 coins, and started to show neurological symptoms such as unsteady gait and mild ataxia.

Several treatment methods are available to help prevent CINV. Pharmaceutical treatment is generally separated into two types: prophylactic (preventative) treatment, given before the dose of chemotherapy agents, and rescue treatment, given to treat breakthrough nausea and vomiting.

Porphyria cutanea tarda has a prevalence estimated at approximately 1 in 10,000. An estimated 80% of porphyria cutanea tarda cases are sporadic. The exact frequency is not clear because many people with the condition never experience symptoms and those that do are often misdiagnosed with anything ranging from idiopathic photodermatitis and seasonal allergies to hives.