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Sunday, September 8, 2024

Bad breath

From Wikipedia, the free encyclopedia
https://en.wikipedia.org/wiki/Bad_breath
Bad breath
Other namesHalitosis, fetor oris, oral malodour, putrid breath
SpecialtyGastroenterology, otorhinolaryngology, dentistry
SymptomsUnpleasant smell present on breath
ComplicationsAnxiety, depression, obsessive compulsive disorder
TypesGenuine, non-genuine
CausesUsually from inside the mouth
TreatmentDepends on cause, tongue cleaning, mouthwash, flossing
MedicationMouthwash containing chlorhexidine or cetylpyridinium chloride
Frequency~30% of people

Bad breath, also known as halitosis, is a symptom in which a noticeably unpleasant breath odour is present. It can result in anxiety among those affected. It is also associated with depression and symptoms of obsessive compulsive disorder.

The concerns of bad breath may be divided into genuine and non-genuine cases. Of those who have genuine bad breath, about 85% of cases come from inside the mouth. The remaining cases are believed to be due to disorders in the nose, sinuses, throat, lungs, esophagus, or stomach. Rarely, bad breath can be due to an underlying medical condition such as liver failure or ketoacidosis. Non-genuine cases occur when someone complains of having bad breath but other people cannot detect it. This is estimated to make up between 5% and 72% of cases.

The treatment depends on the underlying cause. Initial efforts may include tongue cleaning, mouthwash, and flossing. Tentative evidence supports the use of mouthwash containing chlorhexidine or cetylpyridinium chloride. While there is tentative evidence of benefit from the use of a tongue cleaner it is insufficient to draw clear conclusions. Treating underlying disease such as gum disease, tooth decay, tonsil stones, or gastroesophageal reflux disease may help. Counselling may be useful in those who falsely believe that they have bad breath.

Estimated rates of bad breath vary from 6% to 50% of the population. Concern about bad breath is the third most common reason people seek dental care, after tooth decay and gum disease. It is believed to become more common as people age. Bad breath is viewed as a social taboo and those affected may be stigmatized. People in the United States spend more than $1 billion per year on mouthwash to treat it.

Signs and symptoms

Bad breath is when a noticeably unpleasant odour is believed to be present on the breath. It can result in anxiety among those affected. It is also associated with depression and symptoms of obsessive compulsive disorder.

Causes

Mouth

In about 90% of genuine halitosis cases, the origin of the odour is in the mouth itself. This is known as intra-oral halitosis, oral malodour or oral halitosis.

The most common causes are odour producing biofilm on the back of the tongue or other areas of the mouth due to poor oral hygiene. This biofilm results in the production of high levels of foul odours. The odours are produced mainly due to the breakdown of proteins into individual amino acids, followed by the further breakdown of certain amino acids to produce detectable foul gases. Volatile sulfur compounds are associated with oral malodour levels, and usually decrease following successful treatment. Other parts of the mouth may also contribute to the overall odour, but are not as common as the back of the tongue. These locations are, in order of descending prevalence, inter-dental and sub-gingival niches, faulty dental work, food-impaction areas in between the teeth, abscesses, and unclean dentures. Oral based lesions caused by viral infections like herpes simplex and HPV may also contribute to bad breath.

The intensity of bad breath may differ during the day, due to eating certain foods (such as garlic, onions, meat, fish, and cheese), smoking, and alcohol consumption. Since the mouth is exposed to less oxygen and is inactive during the night, the odour is usually worse upon awakening ("morning breath"). Bad breath may be transient, often disappearing following eating, drinking, tooth brushing, flossing, or rinsing with specialized mouthwash. Bad breath may also be persistent (chronic bad breath), which affects some 25% of the population in varying degrees.

Tongue

Normal appearance of the tongue, showing a degree of visible white coating and normal irregular surface on the posterior dorsum.

The most common location for mouth-related halitosis is the tongue. Tongue bacteria produce malodourous compounds and fatty acids, and account for 80 to 90% of all cases of mouth-related bad breath. Large quantities of naturally occurring bacteria are often found on the posterior dorsum of the tongue, where they are relatively undisturbed by normal activity. This part of the tongue is relatively dry and poorly cleansed, and the convoluted microbial structure of the tongue dorsum provides an ideal habitat for anaerobic bacteria, which flourish under a continually-forming tongue coating of food debris, dead epithelial cells, postnasal drip and overlying bacteria, living and dead. When left on the tongue, the anaerobic respiration of such bacteria can yield either the putrescent smell of indole, skatole, polyamines, or the "rotten egg" smell of volatile sulfur compounds (VSCs) such as hydrogen sulfide, methyl mercaptan, allyl methyl sulfide, and dimethyl sulfide. The presence of halitosis-producing bacteria on the back of the tongue is not to be confused with tongue coating. Bacteria are invisible to the naked eye, and degrees of white tongue coating are present in most people with and without halitosis. A visible white tongue coating does not always equal the back of the tongue as an origin of halitosis, however a "white tongue" is thought to be a sign of halitosis. In oral medicine generally, a white tongue is considered a sign of several medical conditions. Patients with periodontal disease were shown to have sixfold prevalence of tongue coating compared with normal subjects. Halitosis patients were also shown to have significantly higher bacterial loads in this region compared to individuals without halitosis.

Gums

Gingival crevices are the small grooves between teeth and gums, and they are present in health, although they may become inflamed when gingivitis is present. The difference between a gingival crevice and periodontal pocket is that former is <3mm in depth and the latter is >3mm. Periodontal pockets usually accompany periodontal disease (gum disease). There is some controversy over the role of periodontal diseases in causing bad breath. However, advanced periodontal disease is a common cause of severe halitosis. People with uncontrolled diabetes are more prone to have multiple gingival and periodontal abscess. Their gums are evident with large pockets, where pus accumulation occurs. This nidus of infection can be a potential source for bad breath. Removal of the subgingival calculus (i.e. tartar or hard plaque) and friable tissue has been shown to improve mouth odour considerably. This is accomplished by subgingival scaling and root planing and irrigation with an antibiotic mouth rinse. The bacteria that cause gingivitis and periodontal disease (periodontopathogens) are invariably gram negative and capable of producing VSC. Methyl mercaptan is known to be the greatest contributing VSC in halitosis that is caused by periodontal disease and gingivitis. The level of VSC on breath has been shown to positively correlate with the depth of periodontal pocketing, the number of pockets, and whether the pockets bleed when examined with a dental probe. Indeed, VSC may themselves have been shown to contribute to the inflammation and tissue damage that is characteristic of periodontal disease. However, not all patients with periodontal disease have halitosis, and not all patients with halitosis have periodontal disease. Although patients with periodontal disease are more likely to develop halitosis than the general population, the halitosis symptom was shown to be more strongly associated with degree of tongue coating than with the severity of periodontal disease. Another possible symptom of periodontal disease is a bad taste, which does not necessarily accompany a malodour that is detectable by others.

Other causes

Other less common reported causes from within the mouth include:

  • Deep carious lesions (dental decay) – which cause localized food impaction and stagnation
  • Recent dental extraction sockets – fill with blood clot, and provide an ideal habitat for bacterial proliferation
  • Interdental food packing – (food getting pushed down between teeth) – this can be caused by missing teeth, tilted, spaced or crowded teeth, or poorly contoured approximal dental fillings. Food debris becomes trapped, undergoes slow bacterial putrefaction and release of malodourous volatiles. Food packing can also cause a localized periodontal reaction, characterized by dental pain that is relieved by cleaning the area of food packing with interdental brush or floss.
  • Acrylic dentures (plastic false teeth) – inadequate denture hygiene practises such as failing to clean and remove the prosthesis each night, may cause a malodour from the plastic itself or from the mouth as microbiota responds to the altered environment. The plastic is actually porous, and the fitting surface is usually irregular, sculpted to fit the edentulous oral anatomy. These factors predispose to bacterial and yeast retention, which is accompanied by a typical smell.
  • Oral infections
  • Oral ulceration
  • Fasting
  • Stress or anxiety
  • Menstrual cycle – At mid cycle and during menstruation, increased breath VSC were reported in women.
  • Smoking – Smoking is linked with periodontal disease, which is the second most common cause of oral malodour. Smoking also has many other negative effects on the mouth, from increased rates of dental decay to premalignant lesions and even oral cancer.
  • Alcohol
  • Volatile foods – e.g. onion, garlic, durian, cabbage, cauliflower and radish. Volatile foodstuffs may leave malodourous residues in the mouth, which are the subject to bacterial putrefaction and VSC release. However, volatile foodstuffs may also cause halitosis via the blood borne halitosis mechanism.
  • Medication – often medications can cause xerostomia (dry mouth) which results in increased microbial growth in the mouth.

Nose and sinuses

In this occurrence, the air exiting the nostrils has a pungent odour that differs from the oral odour. Nasal odour may be due to sinus infections or foreign bodies.

Halitosis is often stated to be a symptom of chronic rhinosinusitis, however gold standard breath analysis techniques have not been applied. Theoretically, there are several possible mechanisms of both objective and subjective halitosis that may be involved.

Tonsils

There is disagreement as to the proportion of halitosis cases that are caused by conditions of the tonsils. Some claim that the tonsils are the most significant cause of halitosis after the mouth. According to one report, approximately 3% of halitosis cases were related to the tonsils. Conditions of the tonsils that may be associated with halitosis include chronic caseous tonsillitis (cheese-like material can be exuded from the tonsillar crypt orifi), tonsillolithiasis (tonsil stones), and less commonly peritonsillar abscess, actinomycosis, fungating malignancies, chondroid choristoma, and inflammatory myofibroblastic tumor.

Esophagus

The lower esophageal sphincter, which is the valve between the stomach and the esophagus, may not close properly due to a hiatal hernia or GERD, allowing acid to enter the esophagus and gases to escape to the mouth. A Zenker's diverticulum may also result in halitosis due to aging food retained in the esophagus.

Stomach

The stomach is considered by most researchers as a very uncommon source of bad breath. The esophagus is a closed and collapsed tube, and continuous flow of gas or putrid substances from the stomach indicates a health problem—such as reflux serious enough to be bringing up stomach contents or a fistula between the stomach and the esophagus—which will demonstrate more serious manifestations than just foul odour.

In the case of allyl methyl sulfide (the byproduct of garlic's digestion), odour does not come from the stomach, since it does not get metabolized there.

Systemic diseases

There are a few systemic (non-oral) medical conditions that may cause foul breath odour, but these are infrequent in the general population. Such conditions are:

  1. Fetor hepaticus: an example of a rare type of bad breath caused by chronic liver failure.
  2. Lower respiratory tract infections (bronchial and lung infections).
  3. Kidney infections and kidney failure.
  4. Carcinoma.
  5. Trimethylaminuria ("fish odour syndrome").
  6. Diabetes mellitus.
  7. Metabolic conditions, e.g. resulting in elevated blood dimethyl sulfide.

Individuals affected by the above conditions often show additional, more diagnostically conclusive symptoms than bad breath alone.

Delusional halitosis

One quarter of the people seeking professional advice on bad breath have an exaggerated concern of having bad breath, known as halitophobia, delusional halitosis, or as a manifestation of the olfactory reference syndrome. They are sure that they have bad breath, although many have not asked anyone for an objective opinion. Bad breath may severely affect the lives of some 0.5–1.0% of the adult population.

Diagnosis

Self diagnosis

Scientists have long thought that smelling one's own breath odour is often difficult due to acclimatization, although many people with bad breath are able to detect it in others. Research has suggested that self-evaluation of halitosis is not easy because of preconceived notions of how bad we think it should be. Some people assume that they have bad breath because of bad taste (metallic, sour, fecal, etc.), however bad taste is considered a poor indicator.

Patients often self-diagnose by asking a close friend.

One popular home method to determine the presence of bad breath is to lick the back of the wrist, let the saliva dry for a minute or two, and smell the result. This test results in overestimation, as concluded from research, and should be avoided. A better way would be to lightly scrape the posterior back of the tongue with a plastic disposable spoon and to smell the drying residue. Home tests that use a chemical reaction to test for the presence of polyamines and sulfur compounds on tongue swabs are now available, but there are few studies showing how well they actually detect the odour. Furthermore, since breath odour changes in intensity throughout the day depending on many factors, multiple testing sessions may be necessary.

Testing

If bad breath is persistent, and all other medical and dental factors have been ruled out, specialized testing and treatment is required. Hundreds of dental offices and commercial breath clinics now claim to diagnose and treat bad breath. They often use some of several laboratory methods for diagnosis of bad breath:

  • Halimeter: a portable sulfide monitor used to test for levels of sulfur emissions (to be specific, hydrogen sulfide) in the mouth air. When used properly, this device can be very effective at determining levels of certain VSC-producing bacteria. However, it has drawbacks in clinical applications. For example, other common sulfides (such as mercaptan) are not recorded as easily and can be misrepresented in test results. Certain foods such as garlic and onions produce sulfur in the breath for as long as 48 hours and can result in false readings. The Halimeter is also very sensitive to alcohol, so one should avoid drinking alcohol or using alcohol-containing mouthwashes for at least 12 hours prior to being tested. This analog machine loses sensitivity over time and requires periodic recalibration to remain accurate.
  • Gas chromatography: portable machines are being studied. This technology is designed to digitally measure molecular levels of major VSCs in a sample of mouth air (such as hydrogen sulfide, methyl mercaptan, and dimethyl sulfide). It is accurate in measuring the sulfur components of the breath and produces visual results in graph form via computer interface.
  • BANA test: this test is directed to find the salivary levels of an enzyme indicating the presence of certain halitosis-related bacteria.
  • β-galactosidase test: salivary levels of this enzyme were found to be correlated with oral malodour.

Although such instrumentation and examinations are widely used in breath clinics, the most important measurement of bad breath (the gold standard) is the actual sniffing and scoring of the level and type of the odour carried out by trained experts ("organoleptic measurements"). The level of odour is usually assessed on a six-point intensity scale.

Classification

Several classification schemes have been proposed to define halitosis.

Miyazaki et al.

The Miyazaki et al. classification was originally described in 1999 in a Japanese scientific publication, and has since been adapted to reflect North American society, especially with regards halitophobia. The classification assumes three primary divisions of the halitosis symptom, namely genuine halitosis, pseudohalitosis and halitophobia.

  • Genuine halitosis
    • A. Physiologic halitosis
    • B. Pathologic halitosis
      • (i) Oral
      • (ii) Extra-oral
  • Pseudohalitosis
  • Halitophobia

This classification has been criticized for being inflexible, and that the pseudohalitosis and halitophbia categories contain psychopathologic connotations.

Tangerman and Winkel

The Tangerman and Winkel classification was suggested in Europe in 2002. This classification focuses only on those cases where there is genuine halitosis, and has therefore been criticized for being less clinically useful for dentistry when compared to the Miyazaki et al. classification.

  • Intra-oral halitosis
  • Extra-oral halitosis
    • A. Blood borne halitosis
      • (i) Systemic diseases
      • (ii) Metabolic diseases
      • (iii) Food
      • (iv) Medication
    • B. Non-blood borne halitosis
      • (i) Upper respiratory tract
      • (ii) Lower respiratory tract

The same authors also suggested that halitosis can be divided according to the character of the odour into 3 groups:

Aydin and Harvey-Woodworth

Based on the strengths and weaknesses of previous attempts at classification, Aydin and Harvey-Woodworth proposed a cause-based classification.

  • Type 0 (physiologic)
  • Type 1 (oral)
  • Type 2 (airway)
  • Type 3 (gastroesophageal)
  • Type 4 (blood-borne)
  • Type 5 (subjective)

Any halitosis symptom is potentially the sum of these types in any combination, superimposed on the physiologic odour present in all healthy individuals.

Management

Approaches to improve bad breath may include physical or chemical means to decrease bacteria in the mouth, products to mask the smell, or chemicals to alter the odour creating molecules. Many different interventions have been suggested and trialed such as toothpastes, mouthwashes, lasers, tongue scraping, and mouth rinses. There is no strong evidence to indicate which interventions work and which are more effective. It is recommended that in those who use tobacco products stop. Evidence does not support the benefit of dietary changes or chewing gum.

Mechanical measures

Brushing the teeth may help. While there is evidence of tentative benefit from tongue cleaning it is insufficient to draw clear conclusions. Flossing may be useful.

Mouthwashes

Mouthwashes often contain antibacterial agents including cetylpyridinium chloride, chlorhexidine, zinc gluconate, zinc chloride, zinc lactate, hydrogen peroxide, chlorine dioxide, amine fluorides, stannous fluoride, hinokitiol, and essential oils. Listerine is one of the well-known mouthwash products composed of different essential oils. Other formulations containing herbal products and probiotics have also been proposed. Cetylpyridinium chloride and chlorhexidine can temporarily stain teeth.

Underlying disease

If gum disease and cavities are present, it is recommended that these be treated.

If diseases outside of the mouth are believed to be contributing to the problem, treatment may result in improvements.

Counselling may be useful in those who falsely believe that they have bad breath.

Epidemiology

It is difficult for researchers to make estimates of the prevalence of halitosis in the general population for several reasons. Firstly, halitosis is subject to societal taboo and stigma, which may impact individuals' willingness to take part in such studies or to report accurately their experience of the condition. Secondly, there is no universal agreement about what diagnostic criteria and what detection methods should be used to define which individuals have halitosis and which do not. Some studies rely on self reported estimation of halitosis, and there is contention as to whether this is a reliable predictor of actual halitosis or not. In reflection of these problems, reported epidemiological data are widely variable.

History, society and culture

The earliest known mention of bad breath occurs in ancient Egypt, where detailed recipes for toothpaste are made before the Pyramids are built. The 1550 BC Ebers Papyrus describes tablets to cure bad breath based on incense, cinnamon, myrrh and honey. Hippocratic medicine advocated a mouthwash of red wine and spices to cure bad breath. Alcohol-containing mouthwashes are now thought to exacerbate bad breath as they dry the mouth, leading to increased microbial growth. The Hippocratic Corpus also describes a recipe based on marble powder for females with bad breath. The Ancient Roman physician Pliny wrote about methods to sweeten the breath.

Ancient Chinese emperors required visitors to chew clove before an audience. The Talmud describes bad breath as a disability, which could be grounds for legal breaking of a marriage license. Early Islamic theology stressed that the teeth and tongue should be cleaned with a siwak, a stick from the plant Salvadora persica tree. This traditional chewing stick is also called a Miswak, especially used in Saudi Arabia, an essentially is like a natural toothbrush made from twigs. During the Renaissance era, Laurent Joubert, doctor to King Henry III of France stated that bad breath is "caused by dangerous miasma that falls into the lungs and through the heart, causing severe damages".

In B. G. Jefferis and J. L. Nichols' "Searchlights on Health" (1919), the following recipe is offered: "[One] teaspoonful of the following mixture after each meal: One ounce chloride of soda, one ounce liquor of potassa, one and one-half ounces phosphate of soda, and three ounces of water."

In the present day, bad breath is one of the biggest social taboos. The general population places great importance on the avoidance of bad breath, illustrated by the annual $1 billion that consumers in the United States spend on deodorant-type mouth (oral) rinses, mints, and related over-the-counter products. Many of these practices are merely short term attempts at masking the odour. Some authors have suggested that there is an evolutionary basis to concern over bad breath. An instinctive aversion to unpleasant odours may function to detect spoiled food sources and other potentially invective or harmful substances. Body odours in general are thought to play an important role in mate selection in humans, and unpleasant odour may signal disease, and hence a potentially unwise choice of mate. Although reports of bad breath are found in the earliest medical writings known, the social stigma has likely changed over time, possibly partly due to sociocultural factors involving advertising pressures. As a result, the negative psychosocial aspects of halitosis may have worsened, and psychiatric conditions such as halitophobia are probably more common than historically. There have been rare reports of people committing suicide because of halitosis, whether there is genuine halitosis or not.

Etymology

The word halitosis is derived from the Latin word halitus, meaning 'breath', and the Greek suffix -osis meaning 'diseased' or 'a condition of'. With modern consumerism, there has been a complex interplay of advertising pressures and the existing evolutionary aversion to malodour. Contrary to the popular belief that Listerine coined the term halitosis, its origins date to before the product's existence, being coined by physician Joseph William Howe in his 1874 book The Breath, and the Diseases Which Give It a Fetid Odor, although it only became commonly used in the 1920s when a marketing campaign promoted Listerine as a solution for "chronic halitosis". The company was the first to manufacture mouth washes in the United States. According to Freakonomics:

Listerine "...was invented in the nineteenth century as powerful surgical antiseptic. It was later sold, in distilled form, as both a floor cleaner and a cure for gonorrhea. But it wasn't a runaway success until the 1920s, when it was pitched as a solution for "chronic halitosis"— a then obscure medical term for bad breath. Listerine's new ads featured forlorn young women and men, eager for marriage but turned off by their mate's rotten breath. "Can I be happy with him in spite of that?" one maiden asked herself. Until that time, bad breath was not conventionally considered such a catastrophe, but Listerine changed that. As the advertising scholar James B. Twitchell writes, "Listerine did not make mouthwash as much as it made halitosis." In just seven years, the company's revenues rose from $115,000 to more than $8 million."

Alternative medicine

According to traditional Ayurvedic medicine, chewing areca nut and betel leaf is a remedy for bad breath. In South Asia, it was a custom to chew areca or betel nut and betel leaf among lovers because of the breath-freshening and stimulant drug properties of the mixture. Both the nut and the leaf are mild stimulants and can be addictive with repeated use. The betel nut will also cause dental decay and red or black staining of teeth when chewed. Both areca nut and betel leaf chewing, however, can cause premalignant lesions such as leukoplakia and submucous fibrosis, and are recognized risk factors for oral and oropharyngeal squamous cell carcinoma (oral cancer).

Practitioners and purveyors of alternative medicine sell a vast range of products that claim to be beneficial in treating halitosis, including dietary supplements, vitamins, and oral probiotics. Halitosis is often claimed to be a symptom of "candida hypersensitivity syndrome" or related diseases, and is claimed to be treatable with antifungal medications or alternative medications to treat fungal infections.

Research

In 1996, the International Society for Breath Odor Research (ISBOR) was formed to promote multidisciplinary research on all aspects of breath odours.

Dysphagia

From Wikipedia, the free encyclopedia
 
Dysphagia
The digestive tract, with the esophagus marked in red
SpecialtyGastroenterology, phoniatrics
SymptomsInability or difficulty swallowing
ComplicationsPulmonary aspiration, malnutrition, starvation
CausesEsophageal cancer, Esophagitis, Stomach cancer, mental illness, alcoholism, refeeding syndrome, starvation, infection, gastritis, malnutrition

Dysphagia is difficulty in swallowing. Although classified under "symptoms and signs" in ICD-10, in some contexts it is classified as a condition in its own right.

It may be a sensation that suggests difficulty in the passage of solids or liquids from the mouth to the stomach, a lack of pharyngeal sensation or various other inadequacies of the swallowing mechanism. Dysphagia is distinguished from other symptoms including odynophagia, which is defined as painful swallowing, and globus, which is the sensation of a lump in the throat. A person can have dysphagia without odynophagia (dysfunction without pain), odynophagia without dysphagia (pain without dysfunction) or both together. A psychogenic dysphagia is known as phagophobia.

Classification

Dysphagia is classified into the following major types:

  1. Oropharyngeal dysphagia
  2. Esophageal and obstructive dysphagia
  3. Neuromuscular symptom complexes
  4. Functional dysphagia is defined in some patients as having no organic cause for dysphagia that can be found.

Signs and symptoms

Some patients have limited awareness of their dysphagia, so lack of the symptom does not exclude an underlying disease. When dysphagia goes undiagnosed or untreated, patients are at a high risk of pulmonary aspiration and subsequent aspiration pneumonia secondary to food or liquids going the wrong way into the lungs. Some people present with "silent aspiration" and do not cough or show outward signs of aspiration. Undiagnosed dysphagia can also result in dehydration, malnutrition, and kidney failure.

Some signs and symptoms of oropharyngeal dysphagia include difficulty controlling food in the mouth, inability to control food or saliva in the mouth, difficulty initiating a swallow, coughing, choking, frequent pneumonia, unexplained weight loss, gurgly or wet voice after swallowing, nasal regurgitation, and patient complaint of swallowing difficulty. When asked where the food is getting stuck, patients will often point to the cervical (neck) region as the site of the obstruction. The actual site of obstruction is always at or below the level at which the level of obstruction is perceived.

The most common symptom of esophageal dysphagia is the inability to swallow solid food, which the patient will describe as 'becoming stuck' or 'held up' before it either passes into the stomach or is regurgitated. Pain on swallowing or odynophagia is a distinctive symptom that can be highly indicative of carcinoma, although it also has numerous other causes that are not related to cancer. Achalasia is a major exception to usual pattern of dysphagia in that swallowing of fluid tends to cause more difficulty than swallowing solids. In achalasia, there is idiopathic destruction of parasympathetic ganglia of the Auerbach's (Myenteric) plexus of the entire esophagus, which results in functional narrowing of the lower esophagus, and peristaltic failure throughout its length.

Complications

Complications of dysphagia may include aspiration, pneumonia, dehydration, and weight loss.

Causes

The following table enumerates possible causes of dysphagia:

Difficulty with or inability to swallow may be caused or exacerbated by usage of opiate and/or opioid drugs.

Diagnosis

  • Esophagoscopy and laryngoscopy can give direct view of lumens.
  • Esophageal motility study is useful in cases of esophageal achalasia and diffuse esophageal spasms.
  • Exfoliative cytology can be performed on esophageal lavage obtained by esophagoscopy. It can detect malignant cells in early stage.
  • Ultrasonography and CT scan are not very useful in finding causes of dysphagia, but can detect masses in mediastinum and aortic aneurysms.
  • FEES (Fibreoptic endoscopic evaluation of swallowing), sometimes with sensory evaluation, is done usually by a Medical Speech Pathologist or Deglutologist. This procedure involves the patient eating different consistencies as above.
  • Swallowing sounds and vibrations could be potentially used for dysphagia screening, but these approaches are in the early research stages.

Differential diagnosis

All causes of dysphagia are considered as differential diagnoses. Some common ones are:

Esophageal dysphagia is almost always caused by disease in or adjacent to the esophagus but occasionally the lesion is in the pharynx or stomach. In many of the pathological conditions causing dysphagia, the lumen becomes progressively narrowed and indistensible. Initially, only fibrous solids cause difficulty but later the problem can extend to all solids and later even to liquids. Patients with difficulty swallowing may benefit from thickened fluids if the person is more comfortable with those liquids, although, so far, there is no scientific study that proves that those thickened liquids are beneficial.

Dysphagia may manifest as the result of autonomic nervous system pathologies including stroke and ALS, or due to rapid iatrogenic correction of an electrolyte imbalance.

In older adults, presbyphagia - the normal healthy changes in swallowing associated with age - should be considered as an alternative explanation for symptoms.

Treatments

There are many ways to treat dysphagia, such as swallowing therapy, dietary changes, feeding tubes, certain medications, and surgery. Treatment for dysphagia is managed by a group of specialists known as a multidisciplinary team. Members of the multidisciplinary team include: a speech language pathologist specializing in swallowing disorders (swallowing therapist), primary physician, gastroenterologist, nursing staff, respiratory therapist, dietitian, occupational therapist, physical therapist, pharmacist, and radiologist. The role of the members of the multidisciplinary team will differ depending on the type of swallowing disorder present. For example, the swallowing therapist will be directly involved in the treatment of a patient with oropharyngeal dysphagia, while a gastroenterologist will be directly involved in the treatment of an esophageal disorder.

Treatment strategies

The implementation of a treatment strategy should be based on a thorough evaluation by the multidisciplinary team. Treatment strategies will differ on a patient to patient basis and should be structured to meet the specific needs of each individual patient. Treatment strategies are chosen based on a number of different factors including diagnosis, prognosis, reaction to compensatory strategies, severity of dysphagia, cognitive status, respiratory function, caregiver support, and patient motivation and interest.

Oral vs. nonoral feeding

Adequate nutrition and hydration must be preserved at all times during dysphagia treatment. The overall goal of dysphagia therapy is to maintain or return the patient to, oral feeding. However, this must be done while ensuring adequate nutrition and hydration and a safe swallow (no aspiration of food into the lungs). If oral feeding results in increased mealtimes and increased effort during the swallow, resulting in not enough food being ingested to maintain weight, a supplementary nonoral feeding method of nutrition may be needed. In addition, if the patient aspirates food or liquid into the lungs despite the use of compensatory strategies, and is therefore unsafe for oral feeding, nonoral feeding may be needed. Nonoral feeding includes receiving nutrition through a method that bypasses the oropharyngeal swallowing mechanism including a nasogastric tube, gastrostomy, or jejunostomy. Some people with dysphagia, especially those nearing the end of life, may choose to continue eating and drinking orally even when it has been deemed unsafe. This is known as "risk feeding".

Swallowing difficulties in dementia

A 2018 Cochrane review found no certain evidence about the immediate and long-term effects of modifying the thickness of fluids for swallowing difficulties in people with dementia. While thickening fluids may have an immediate positive effect on swallowing and improving oral intake, the long-term impact on the health of the person with dementia should also be considered.

Treatment procedures

Compensatory treatment procedures are designed to change the flow of the food/liquids and eliminate symptoms but do not directly change the physiology of the swallow.

  • Postural techniques
  • Food consistency (diet) changes
  • Modifying volume and speed of food presentation
  • Technique to improve oral sensory awareness
  • Intraoral prosthetics

Therapeutic treatment procedures – designed to change and/or improve the physiology of the swallow.

  • Oral and pharyngeal range-of-Motion exercises
  • Resistance exercises
  • Bolus control exercises
  • Swallowing maneuvers
    • Supraglottic swallow
    • Super-supraglottic swallow
    • Effortful swallow
    • Mendelsohn maneuver

Patients may need a combination of treatment procedures to maintain a safe and nutritionally adequate swallow. For example, postural strategies may be combined with swallowing maneuvers to allow the patient to swallow in a safe and efficient manner.

The most common interventions used for those with oropharyngeal dysphagia by speech language pathologists are rehabilitation of the swallow through oral motor exercises, texture modification of foods, thickening fluids and positioning changes during swallowing. The effectiveness of modifying food and fluid in preventing aspiration pneumonia has been questioned and these can be associated with poorer nutrition, hydration and quality of life. Also, there has been considerable variability in national approaches to describing different degrees of thickened fluids and food textures.  However, in 2015, the International Dysphagia Diet Standardisation Initiative (IDDSI) group produced an agreed IDDSI framework consisting of a continuum of 8 levels (0–7), where drinks are measured from Levels 0 – 4, while foods are measured from Levels 3 – 7. It is likely that this initiative, which has widespread support among dysphagia practitioners, will improve communication with carers and will lead to greater standardisation of modified diets.

Epidemiology

Swallowing disorders can occur in all age groups, resulting from congenital abnormalities, structural damage, and/or medical conditions. Swallowing problems are a common complaint among older individuals, and the incidence of dysphagia is higher in the elderly, and in patients who have had strokes. Dysphagia affects about 3% of the population.

Etymology

The word "dysphagia" is derived from the Greek dys meaning bad or disordered, and the root phag- meaning "eat".

Amyl nitrite

From Wikipedia, the free encyclopedia
Amyl nitrite
Chemical structure of amyl nitrite
Ball-and-stick model of amyl nitrite
Clinical data
Other namesIsoamyl nitrite,
Isopentyl nitrite,
Nitramyl,
3-methyl-1-nitrosooxybutane,
Pentyl alcohol nitrite (ambiguous),
poppers (ambiguous, colloquial, slang)
ATC code
Legal status
Legal status
Identifiers

CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC5H11NO2
Molar mass117.148 g·mol−1
3D model (JSmol)
Density0.872 g/cm3
Boiling point99 °C (210 °F)
Solubility in waterSlightly soluble mg/mL (20 °C)


Amyl nitrite is a chemical compound with the formula C5H11ONO. A variety of isomers are known, but they all feature an amyl group attached to the nitrite functional group. The alkyl group is unreactive and the chemical and biological properties are mainly due to the nitrite group. Like other alkyl nitrites, amyl nitrite is bioactive in mammals, being a vasodilator, which is the basis of its use as a prescription medicine. As an inhalant, it also has a psychoactive effect, which has led to its recreational use, with its smell being described as that of old socks or dirty feet. It was first documented in 1844 and came into medical use in 1867.

Uses

  • Amyl nitrite was historically employed medically to treat heart diseases as well as angina.
  • Amyl nitrite was sometimes used as an antidote for cyanide poisoning. It was thought to act as an oxidant, to induce the formation of methemoglobin. Methemoglobin in turn can sequester cyanide as cyanomethemoglobin. However, it has been replaced by hydroxocobalamin which had better efficacy, and the use of amyl nitrite has been found to be ineffective and unscientific 
  • Amyl nitrite is used as a cleaning agent and solvent in industrial and household applications. It replaced dichlorodifluoromethane, an industrial chemical universally banned in 1996 due to damage to the ozone layer, as a printed circuit board cleaner. Trace amounts are added to some perfumes.
  • It is also used recreationally as an inhalant drug that induces a brief euphoric state, and when combined with other intoxicant stimulant drugs such as cocaine or MDMA, the euphoric state intensifies and is prolonged. Once some stimulative drugs wear off, a common side effect is a period of depression or anxiety, colloquially called a "come down"; amyl nitrite is sometimes used to combat these negative after-effects. This effect, combined with its dissociative effects, has led to its use as a recreational drug (see poppers).

Nomenclature

The term "amyl nitrite" encompasses several isomers. In older literature, the common non-systematic name amyl was often used for the pentyl group, where the amyl group is a linear or normal (n) alkyl group, and the resulting amyl nitrite would have the structural formula CH3(CH2)3CH2ONO, also referred to as n-amyl nitrite.

A common form of amyl nitrite is the isomer with the formula (CH3)2CHCH2CH2ONO, which may be more specifically referred to as isoamyl nitrite.

The similarly named amyl nitrate has very different properties. At the same time, isopropyl nitrite has a similar structure and similar uses (also called 'poppers') but with worse side-effects.

Amyl nitrite is sometimes referred to colloquially as banapple gas.

Synthesis and reactions

Alkyl nitrites are prepared by the reaction of alcohols with nitrous acid:

ROH + HONO → RONO + H2O, where R = alkyl group

The reaction is called esterification. Synthesis of alkyl nitrites is, in general, straightforward and can be accomplished in home laboratories. A common procedure includes the dropwise addition of concentrated sulfuric acid to a cooled mixture of an aqueous sodium nitrite solution and an alcohol. The intermediately-formed stoichiometric mixture of nitrogen dioxide and nitric oxide then converts the alcohol to the alkyl nitrite, which, due to its low density, will form an upper layer that can be easily decanted from the reaction mixture.

Isoamyl nitrite decomposes in the presence of base to give nitrite salts and the isoamyl alcohol:

C5H11ONO + NaOH → C5H11OH + NaNO2

Amyl nitrite, like other alkyl nitrites, reacts with carbanions to give oximes.

Amyl nitrites are also useful as reagents in a modification of the Sandmeyer reaction. The reaction of the alkyl nitrite with an aromatic amine in a halogenated solvent produces a radical aromatic species, this then frees a halogen atom from the solvent. For the synthesis of aryl iodides diiodomethane is used, whereas bromoform is the solvent of choice for the synthesis of aryl bromides.

Physiological effects

An early container of amyl nitrite, Hunterian Museum, Glasgow

Amyl nitrite, in common with other alkyl nitrites, is a potent vasodilator; it expands blood vessels, resulting in lowering of the blood pressure. Amyl nitrite may be used during cardiovascular stress testing in patients with suspected hypertrophic cardiomyopathy to cause vasodilation and thereby reduce afterload and provoke obstruction of blood flow towards the aorta from the ventricle by increasing the pressure gradient, thereby causing left ventricular outflow obstruction. Alkyl nitrites are a source of nitric oxide, which signals for relaxation of the involuntary muscles. Physical effects include decrease in blood pressure, headache, flushing of the face, increased heart rate, dizziness, and relaxation of involuntary muscles, especially the blood vessel walls and the internal and external anal sphincter. There are no withdrawal symptoms. Overdose symptoms include nausea, vomiting, hypotension, hypoventilation, shortness of breath, and fainting. The effects set in very quickly, typically within a few seconds and disappear within a few minutes. Amyl nitrite may also intensify the experience of synesthesia. Amyl nitrite, when given as a medication for patients with angina, can also be administered as an ampule. The ampule is put in a gauze pad and then inhaled by the patient during an angina attack and repeated every fifteen minutes. However, oral dosing of amyl nitrite is ineffective due to poor absorption and extensive hepatic metabolism. Amyl nitrite has been widely replaced by nitroglycerin for the treatment of acute angina.

Toxicity

Although there are case reports of life-threatening toxicity involving unusually large amounts, typical inhaled doses of amyl nitrite are considered relatively safe. However, liquid amyl nitrite is highly toxic when ingested because of the unsafely high concentration it causes in blood. Regardless of the form or route of administration, acute toxicity principally results when the nitrite oxidizes a significant proportion of hemoglobin in the blood without oxygen, forming methemoglobin, which cannot carry oxygen. Severe poisoning cases will progress to methemoglobinemia, characterized by a blue-brown discoloration under the skin which could be mistaken for cyanosis. Treatment with oxygen and intravenous methylene blue frustrates visual confirmation further as methylene blue itself is, as its name suggests, a blue dye; the patient's changes in different shades of blue notwithstanding, it is an effective antidote by way of catalyzing the production of the enzyme responsible for reducing the methemoglobin in the blood back to hemoglobin.

The discoloration does mean that regular near-infrared–based pulse oximetry becomes useless. More fundamentally, blood gas analysis on the whole has limited effectiveness, as the increased methemoglobin level increases the oxygen binding affinity of regular hemoglobin. Therefore, the measurement of actual ratios and levels of methemoglobin and hemoglobin must accompany any blood gas partial pressure sample in these cases.

The Columbo episode titled "Troubled Waters" (1974–1975) features amyl nitrite inhaled by the antagonist Hayden Danziger – played by Robert Vaughn – to help him feign a heart attack for his alibi. However, the episode consistently refers to the substance incorrectly as amyl nitrate.

The 1978 Derek Jarman film Jubilee features a character named Amyl Nitrate (a misspelled reference to amyl nitrite).

The punk band Amyl and the Sniffers reference recreational use of amyl nitrite in their name.

Saturday, September 7, 2024

Nitroglycerin (medication)

From Wikipedia, the free encyclopedia
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
ChEBI
ChEMBL
Chemical and physical data
FormulaC3H5N3O9
Molar mass227.085 g·mol−1
3D model (JSmol)


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Nitroglycerin, also known as glyceryl trinitrate (GTN), is a vasodilator used for heart failure, high blood pressure (hypertension), anal fissures, painful periods, and to treat and prevent chest pain caused by decreased blood flow to the heart (angina) or due to the recreational use of cocaine. This includes chest pain from a heart attack. It is taken by mouth, under the tongue, applied to the skin, or by injection into a vein.

Side effects and mechanism

Common side effects include headache and low blood pressure. The low blood pressure can be severe. It is unclear if use in pregnancy is safe for the fetus. It should not be used together with medications within the PDE5 inhibitor family such as sildenafil due to the risk of low blood pressure. Nitroglycerin is in the nitrate family of medications. While it is not entirely clear how it works, it is believed to function by dilating blood vessels.

History, society and culture

Nitroglycerin was written about as early as 1846 and came into medical use in 1878. The drug nitroglycerin is a dilute form of the same chemical used as the explosive, nitroglycerin. Dilution makes it non-explosive. In 2021, it was the 174th most commonly prescribed medication in the United States, with more than 2 million prescriptions.

Medical uses

Three different forms of nitroglycerin: intravenous, sublingual spray, and the nitroglycerin patch.

Nitroglycerin is used for the treatment of angina, acute myocardial infarction, severe hypertension, and acute coronary artery spasms. It may be administered intravenously, as a sublingual spray, or as a patch applied to the skin.

Angina

Glyceryl trinitrate is useful in decreasing angina attacks, perhaps more so than reversing angina once started, by supplementing blood concentrations of NO, also called endothelium-derived relaxing factor, before the structure of NO as the responsible agent was known. This led to the development of transdermal patches of glyceryl trinitrate, providing 24-hour release. However, the effectiveness of glyceryl trinitrate is limited by development of tolerance/tachyphylaxis within 2–3 weeks of sustained use. Continuous administration and absorption (such as provided by daily pills and especially skin patches) accelerate onset of tolerance and limit the usefulness of the agent. Thus, glyceryl trinitrate works best when used only in short-term, pulse dosing. Glyceryl trinitrate is useful for myocardial infarction (heart attack) and pulmonary edema, again working best if used quickly, within a few minutes of symptom onset, as a pulse dose. It may also be given as a sublingual or buccal dose in the form of a tablet placed under the tongue or a spray into the mouth for the treatment of an angina attack.

Other uses

Tentative evidence indicates efficacy of glyceryl trinitrate in the treatment of various tendinopathies, both in pain management and acceleration of soft tissue repair.

Glyceryl trinitrate is also used in the treatment of anal fissures, though usually at a much lower concentration than that used for angina treatment.

Glyceryl trinitrate has been used to decrease pain associated with dysmenorrhea.

Glyceryl trinitrate was once researched for the prevention and treatment of osteoporosis; however, the researcher Sophie Jamal was found to have falsified the findings, sparking one of the largest scientific misconduct cases in Canada.

Tolerance

After long-term use for chronic conditions, nitrate tolerance—tolerance to agents such as glyceryl trinitrate— may develop in a patient, reducing its effectiveness. Tolerance is defined as the loss of symptomatic and hemodynamic effects of glyceryl trinitrate and/or the need for higher doses of the drug to achieve the same effects, and was first described soon after the introduction of glyceryl trinitrate in cardiovascular therapy. Studies have shown that nitrate tolerance is associated with vascular abnormalities which have the potential to worsen patients' prognosis. These include endothelial and autonomic dysfunction.

The mechanisms of nitrate tolerance have been investigated over the last 30 years, and several hypotheses to explain tolerance have been offered, including:

  1. plasma volume expansion
  2. impaired transformation of glyceryl trinitrate into NO or related species
  3. counteraction of glyceryl trinitrate vasodilation by neurohormonal activation
  4. oxidative stress

Adverse events

Glyceryl trinitrate can cause severe hypotension, reflex tachycardia, and severe headaches that necessitate analgesic intervention for pain relief, the painful nature of which can have a marked negative effect on patient compliance.

Glyceryl trinitrate also can cause severe hypotension, circulatory collapse, and death if used together with vasodilator drugs that are used for erectile dysfunction, such as sildenafil, tadalafil, and vardenafil.

Glyceryl trinitrate transdermal patches should be removed before defibrillation due to the risk of explosion and/or burns, but investigations have concluded that glyceryl trinitrate patch explosions during defibrillation were due to the breakdown voltage of the metal mesh in some patches.

Mechanism of action

Glyceryl trinitrate is a prodrug which must be denitrated, with the nitrite anion or a related species further reduced to produce the active metabolite nitric oxide (NO). Organic nitrates that undergo these two steps within the body are called nitrovasodilators, and the denitration and reduction occur via a variety of mechanisms. The mechanism by which such nitrates produce NO is widely disputed. Some believe that organic nitrates produce NO by reacting with sulfhydryl groups, while others believe that enzymes such as glutathione S-transferases, cytochrome P450 (CYP), and xanthine oxidoreductase are the primary source of glyceryl trinitrate bioactivation. In recent years, a great deal of evidence has been produced that supports the conclusion that glyceryl trinitrate's clinically relevant denitration and reduction produce 1,2-glyceryl dinitrate (GDN) and NO, and that this reaction is catalysed by mitochondrial aldehyde dehydrogenase (ALDH2 or mtALDH).

The NO produced by this process is a potent activator of guanylyl cyclase (GC) by heme-dependent mechanisms; this activation results in formation of cyclic guanosine monophosphate (cGMP) from guanosine triphosphate (GTP). Among other roles, cGMP serves as a substrate for a cGMP-dependent protein kinase that activates myosin light chain phosphatase. Thus, production of NO from exogenous sources such as glyceryl trinitrate increases the level of cGMP within the cell, and stimulates dephosphorylation of myosin, which initiates relaxation of smooth muscle cells in blood vessels.

History

It was known almost from the time of the first synthesis of glyceryl trinitrate by Ascanio Sobrero in 1846 that handling and tasting of nitroglycerin could cause sudden intense headaches, which suggested a vasodilation effect (as suggested by Sobrero). Constantine Hering developed a form of nitroglycerin in 1847 and advocated for its dosing as a treatment of a number of diseases; however, its use as a specific treatment for blood pressure and chest pain was not among these. This is primarily due to his deep rooted focus in homeopathy.

Following Thomas Brunton's discovery that amyl nitrite could be used to treat chest pain, William Murrell experimented with the use of nitroglycerin to alleviate angina and reduce blood pressure, and showed that the accompanying headaches occurred as a result of overdose. Murrell began treating patients with small doses of glyceryl trinitrate in 1878, and the substance was widely adopted after he published his results in The Lancet in 1879.

The medical establishment used the name "glyceryl trinitrate" or "trinitrin" to avoid alarming patients, because of a general awareness that nitroglycerin was explosive.

Overdoses may generate methemoglobinemia.

Inquiry-based learning

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