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.

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.

Grapefruit is not the only citrus fruit that can interact with medications; one medical review advised patients to avoid all citrus.

There are three ways to test if a fruit interacts with drugs:

1. Test a drug-fruit combination in humans

2. Test a fruit chemically for the presence of the interacting polyphenol compounds

3. Test a fruit genetically for the genes needed to make the interacting polyphenol compounds

The first approach involves risk to trial volunteers. The first and second approaches have another problem: the same fruit cultivar could be tested twice with different results. Depending on growing and processing conditions, concentrations of the interacting polyphenol compounds can vary dramatically. The third approach is hampered by a paucity of knowledge of the genes in question.

For medications that interact due to inhibition of OATP (organic anion-transporting polypeptides), a relative short period of time is needed to avoid this interaction, and a 4-hour interval between grapefruit consumption and the medication should suffice. For drugs recently sold on the market, drugs have information pages (monographs) that provide information on any potential interaction between a medication and grapefruit juice. Because there is a growing number of medications that are known to interact with citrus, patients should consult a pharmacist or physician before consuming citrus while taking their medications.

Hippuric acid has long been used as an indicator of toluene exposure; however, there appears to be some doubt about its validity. There is significant endogenous hippuric acid production by humans; which shows inter- and intra-individual variation influenced by factors such as diet, medical treatment, alcohol consumption, etc. This suggests that hippuric acid may be an unreliable indicator of toluene exposure. It has been suggested that urinary hippuric acid, the traditional marker of toluene exposure is simply not sensitive enough to separate the exposed from the non-exposed. This has led to the investigation of other metabolites as markers for toluene exposure.

Urinary "o"-cresol may be more reliable for the biomonitoring of toluene exposure because, unlike hippuric acid, "o"-cresol is not found at detectable levels in unexposed subjects. o-Cresol may be a less sensitive marker of toluene exposure than hippuric acid. o-Cresol excretion may be an unreliable method for measuring toluene exposure because o-cresol makes up <1% of total toluene elimination.

Benzylmercapturic acid, a minor metabolite of toluene, is produced from benzaldehyde. In more recent years, studies have suggested the use of urinary benzylmercapturic acid as the best marker for toluene exposure, because: it is not detected in non-exposed subjects; it is more sensitive than hippuric acid at low concentrations; it is not affected by eating or drinking; it can detect toluene exposure down to approximately 15 ppm; and it shows a better quantitative relationship with toluene than hippuric acid or "o"-cresol.

Serious adverse behavioural effects are often associated with chronic occupational exposure and toluene abuse related to the deliberate inhalation of solvents. Long-term toluene exposure is often associated with effects such as: psychoorganic syndrome; visual evoked potential (VEP) abnormality; toxic polyneuropathy, cerebellar, cognitive, and pyramidal dysfunctions; optic atrophy; and brain lesions.

The neurotoxic effects of long-term use (in particular repeated withdrawals) of toluene may cause postural tremors by upregulating GABA receptors within the cerebellar cortex. Treatment with GABA agonists such as benzodiazepines provide some relief from toluene-induced tremor and ataxia. An alternative to drug treatment is vim thalamotomy. The tremors associated with toluene misuse do not seem to be a transient symptom, but an irreversible and progressive symptom which continues after solvent abuse has been discontinued.

There is some evidence that low-level toluene exposure may cause disruption in the differentiation of astrocyte precursor cells. This does not appear to be a major hazard to adults; however, exposure of pregnant women to toluene during critical stages of fetal development could cause serious disruption to neuronal development.

Caffeine is used in:

- Bronchopulmonary dysplasia in premature infants for both prevention and treatment. It may improve weight gain during therapy and reduce the incidence of cerebral palsy as well as reduce language and cognitive delay. On the other hand, subtle long-term side effects are possible.

- Apnea of prematurity as a primary treatment, but not prevention.

- Orthostatic hypotension treatment.

Health Canada has not developed advice for adolescents because of insufficient data. However, they suggest that daily caffeine intake for this age group be no more than 2.5 mg/kg body weight. This is because the maximum adult caffeine dose may not be appropriate for light weight adolescents or for younger adolescents who are still growing. The daily dose of 2.5 mg/kg body weight would not cause adverse health effects in the majority of adolescent caffeine consumers. This is a conservative suggestion since older and heavier weight adolescents may be able to consume adult doses of caffeine without suffering adverse effects.

Education and counselling by physicians of children and adolescents has been found to be effective in decreasing the risk of tobacco use.

Dipping tobacco, commonly referred to as snuff, is also put in the mouth, but it is a flavored powder. it is placed between the cheek and gum. Dipping tobacco doesn't need to be chewed for the nicotine to be absorbed into your body. First-time users of these products often become nauseated and dizzy. Long-term effects include bad breath, yellowed teeth, and an increased risk of oral cancer.

Users of dipping tobacco are believed to face less risk of some cancers than smokers but are still at greater risk than people who do not use any tobacco products. They also have an equal risk of other health problems directly linked to nicotine such as increased rate of atherosclerosis.

This remains a challenge in clinical practice due to a lack of reliable markers. Many other conditions lead to similar clinical as well as pathological pictures. To diagnose hepatotoxicity, a causal relationship between the use of the toxin or drug and subsequent liver damage has to be established, but might be difficult, especially when idiosyncratic reaction is suspected. Simultaneous use of multiple drugs may add to the complexity. As in acetaminophen toxicity, well established, dose-dependent, pharmacological hepatotoxicity is easier to spot. Several clinical scales such as CIOMS/RUCAM scale and Maria and Victorino criteria have been proposed to establish causal relationship between offending drug and liver damage. CIOMS/RUCAM scale involves a scoring system that categorizes the suspicion into "definite or highly probable" (score > 8), “probable” (score 6-8), “possible” (score 3-5), “unlikely” (score 1-2) and “excluded” (score ≤ 0). In clinical practice, physicians put more emphasis on the presence or absence of similarity between the biochemical profile of the patient and known biochemical profile of the suspected toxicity (e.g., cholestatic damage in amoxycillin-clauvonic acid ).

In most cases, liver function will return to normal if the offending drug is stopped early. Additionally, the patient may require supportive treatment. In acetaminophen toxicity, however, the initial insult can be fatal. Fulminant hepatic failure from drug-induced hepatotoxicity may require liver transplantation. In the past, glucocorticoids in allergic features and ursodeoxycholic acid in cholestatic cases had been used, but there is no good evidence to support their effectiveness.

An elevation in serum bilirubin level of more than 2 times ULN with associated transaminase rise is an ominous sign. This indicates severe hepatotoxicity and is likely to lead to mortality in 10% to 15% of patients, especially if the offending drug is not stopped (Hy's Law). This is because it requires significant damage to the liver to impair bilirubin excretion, hence minor impairment (in the absence of biliary obstruction or Gilbert syndrome) would not lead to jaundice. Other poor predictors of outcome are old age, female sex, high AST.

A literature review of 2014 found that non-coeliac gluten sensitivity diagnosis can be reached only by excluding celiac disease (CD) and wheat allergy.

Persons suspected of having celiac disease may undergo serological testing for IgA anti-tissue transglutaminase antibodies (abbreviated anti-tTG antibodies or anti-TG2 antibodies) and anti-endomysial antibodies (abbreviated EMA) provided the IgA-level is high, and if IgA is low, testing for certain IgG antibodies; in case of positive serological indication, a duodenal biopsy may confirm active celiac disease.

Eliminating the possibility of CD can generally also be done by adding HLA-DQ typing. The absence of HLA-DQ2 and HLA-DQ8 has a very high negative predictive value for CD, and the predictive value can be further enhanced by including HLA-DQ7.5 (HLA-DQ2 and HLA-DQ8 are found in coeliac disease 98% of the time in Caucasians, HLA-DQ7.5 present in the remaining 1.6% and only 0.4% of Caucasians are missed with the combination of these 3). Without serological or HLA-DQ2/8 positivity, celiac disease is likely not present. HLA-DQ typing has a practical advantage in that it is the only diagnostic test that allows to exclude CD when a patient is already on a gluten-free diet; however, as not only celiacs are HLA-DQ2/HLA-DQ8 positive, this method has a higher false positive rate than anti-TG2 and EMA antibody testing.

A four-of-five rule was proposed 2010 for confirming celiac disease, with the disease confirmed if at least four of the following five criteria are satisfied:

- typical symptoms of celiac disease;

- positivity of serum celiac disease immunoglobulin, A class autoantibodies at high titer;

- human leukocyte antigen (HLA)-DQ2 or DQ8 genotypes;

- celiac enteropathy at the small bowel biopsy; and

- response to the gluten-free diet.

For diagnosis of wheat allergy, allergy tests are available.

For patients with celiac disease, a lifelong strict gluten-free diet is the only effective treatment to date; for patients diagnosed with NCGS, there are still open questions concerning for example the duration of such a diet; for patients with wheat allergy, the individual average is six years of gluten-free diet, excepting persons with anaphylaxis, for whom the diet is to be wheat-free for life.

A gluten-free diet should not be started before the tests for excluding celiac disease have been performed, for the reason that the serological and biopsy tests for celiac disease are reliable only if the patient is consuming gluten.

Preferably, newly diagnosed celiacs seek the help of a dietician to receive support for identifying hidden sources of gluten, planning balanced meals, reading labels, food shopping, dining out, and dining during travel. Knowledge of hidden sources of gluten is important for celiac disease patients as they need to be very strict regarding eating only gluten-free food; for NCGS patients, it is not certain how strict the diet needs to be. Balanced eating is important because unless particular care is taken, a gluten-free diet can be lacking in vitamins, minerals, and fiber, and be too high in fat and calories.

The inclusion of oats in gluten-free diets remains controversial. Avenin present in oats may also be toxic for coeliac sufferers. Its toxicity depends on the cultivar consumed. Furthermore, oats are frequently cross-contaminated with gluten-containing cereals.

Lichen planus has a unique microscopic appearance that is similar between cutaneous, mucosal and oral. A Periodic acid-Schiff stain of the biopsy may be used to visualise the specimen. Histological features seen include:

- thickening of the stratum corneum both with nuclei present (parakeratosis) and without (orthokeratosis). Parakeratosis is more common in oral variants of lichen planus.

- thickening of the stratum granulosum

- thickening of the stratum spinosum (acanthosis) with formation of colloid bodies (also known as Civatte bodies, Sabouraud bodies) that may stretch down to the lamina propria.

- liquefactive degeneration of the stratum basale, with separation from the underlying lamina propria, as a result of desmosome loss, creating small spaces (Max Joseph spaces).

- Infiltration of T cells in a band-like pattern into the dermis "hugging" the basal layer.

- Development of a "saw-tooth" appearance of the rete pegs, which is much more common in non-oral forms of lichen planus.

The differential diagnosis for OLP includes:

- Other oral vesiculo-ulcerative conditions such as Pemphigus vulgaris and Benign mucous membrane pemphigoid

- Lupus erythematosus, with lesions more commonly occur on the palate and appear as centrally ulcerated or erythematous with radiating white striae. In contrast, OLP and lichenoid reactions rarely occur on the palate, and the striae are randomly arranged rather than radial.

- Chronic ulcerative stomatitis

- Frictional keratosis and Morsicatio buccarum (chronic cheek biting)

- Oral leukoplakia

- Oral candidiasis