Cancer and nausea

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Cancer_and_nausea 

 

A painting from 1681 depicting a person affected by nausea and vomiting

Cancer and nausea are associated in about fifty percent of people affected by cancer. This may be as a result of the cancer itself, or as an effect of the treatment such as chemotherapy, radiation therapy, or other medication such as opiates used for pain relief. About 70 to 80% of people undergoing chemotherapy experience nausea or vomiting. Nausea and vomiting may also occur in people not receiving treatment, often as a result of the disease involving the gastrointestinal tract, electrolyte imbalance, or as a result of anxiety. Nausea and vomiting may be experienced as the most unpleasant side effects of cytotoxic drugs and may result in patients delaying or refusing further radiotherapy or chemotherapy.

The strategies of management or therapy of nausea and vomiting depend on the underlying causes. Medical treatments or conditions associated with a high risk of nausea and/or vomiting include chemotherapy, radiotherapy and malignant bowel obstruction. Anticipatory nausea and vomiting may also occur. Nausea and vomiting may lead to further medical conditions and complications including: dehydration, electrolyte imbalance, malnutrition, and a decrease in quality of life.

Nausea may be defined as an unpleasant sensation of the need to vomit. It may be accompanied by symptoms such as salivation, feeling faint, and a fast heart rate. Vomiting is the forceful ejection of stomach contents through the mouth. Although nausea and vomiting are closely related, some patients experience one symptom without the other and it may be easier to eliminate vomiting than nausea. The vomiting reflex (also called emesis) is thought to have evolved in many animal species as a protective mechanism against ingested toxins. In humans, the vomiting response may be preceded by an unpleasant sensation termed nausea, but nausea may also occur without vomiting. The central nervous system is the primary site where a number of emetic stimuli (input) are received, processed and efferent signals (output) are generated as a response and sent to various effector organs or tissues, leading to processes that eventually end in vomiting. The detection of emetic stimuli, the central processing by the brain and the resulting response by organs and tissues that lead to nausea and vomiting are referred to as the emetic pathway or emetic arch.

Causes

Some medical conditions that arise as a result of cancer or as a complication of its treatment are known to be associated with a high risk of nausea and/or vomiting. These include malignant bowel obstruction (MBO), chemotherapy-induced nausea and vomiting (CINV), anticipatory nausea and vomiting (ANV), and radiotherapy-induced nausea and vomiting (RINV).

Malignant bowel obstruction

Main article: Bowel obstruction

Malignant bowel obstruction (MBO) of the gastrointestinal tract is a common complication of advanced cancer, especially in patients with bowel or gynaecological cancer. These include colorectal cancer, ovarian cancer, breast cancer, and melanoma. Three percent of all advanced cancers lead to malignant bowel obstruction and 25 to 50 percent of patients with ovarian cancer experience at least one episode of malignant bowel obstruction. The mechanisms of action that may lead to nausea in MBO include mechanical compression of the gut, motility disorders, gastrointestinal secretion accumulation, decreased gastrointestinal absorption, and inflammation. Bowel obstruction and the resulting nausea may also occur as a result of anti-cancer therapy such as radiation, or adhesion after surgery. Impaired gastric emptying as a result of bowel obstruction may not respond to drugs alone, and surgical intervention is sometimes the only means of symptom relief. Some constipating drugs used in cancer therapy such as opioids may cause a slowing of peristalsis of the gut, which may lead to a functional bowel obstruction.

Chemotherapy

Main article: Chemotherapy-induced nausea and vomiting

Chemotherapy-induced nausea and vomiting (CINV) is one of the most feared side effects of chemotherapy and is associated with a significant deterioration in quality of life. CINV is classified into three categories:

• early onset (occurring within 24 hours of initial exposure to chemotherapy)
• delayed onset (occurring 24 hours to several days after treatment)
• anticipatory (triggered by taste, odor, sight, thoughts, or anxiety)

Risk factors that predict the occurrence and severity of CINV include sex and age, with females, younger people and people who have a high pretreatment expectation of nausea being at a higher risk, while people with a history of high alcohol consumption being at a lower risk. Other person-related variables, such as chemotherapy dose, rate and route of administration, hydration status, prior history of CINV, emesis during pregnancy or motion sickness, tumour burden, concomitant medication and medical conditions also play a role in the degree of CINV experienced by a person. By far the most important factor which determines the degree of CINV is the emetogenic potential of the chemotherapeutic agents used. Chemotherapeutic agents are classified into four groups according to their degree of emetogenicity: high, moderate, low and minimal.

Chemotherapeutic agents associated with vomiting

Association with vomiting	Examples
Highly emetogenic (>90%) Intravenous agents	Cisplatin, Mechlorethamine, Streptozotocin, Cyclophosphamide > 1500 mg/m2, Carmustine, Dacarbazine, Anthracycline
Highly emetogenic (>90%) oral agents	Hexamethylmelamine, Procarbazine
Moderately emetogenic (30-90%) intravenous agents	Oxaliplatin, Cytarabine > 1g/m2, Carboplatin, Ifosfamide, Cyclophosphamide < 1500 mg/m2, Doxorubicin, Daunorubicin, Epirubicin, Idarubicin, Irinotecan, Azacitidine, Bendamustine, Clofarabine, Alemtuzumab
Moderately emetogenic (30-90%) oral agents	Cyclophosphamide, Temozolomide, Vinorelbine, Imatinib

The European Society of Medical Oncology (ESMO) and the Multinational Association of Supportive Care in Cancer (MASCC) in 2010 as well as the American Society of Clinical Oncology (ASCO) (2011) recommend a prophylaxis to prevent acute vomiting and nausea following chemotherapy with high emetic risk drugs by using a three-drug regimen including a 5-HT3 receptor antagonist, dexamethasone and aprepitant (a neurokinin-1 antagonist) given before chemotherapy.

Anticipatory

A common consequence of cancer treatment is the development of anticipatory nausea and vomiting (ANV). This kind of nausea is usually elicited by the re-exposure of the patients to the clinical context they need to attend to be treated. Approximately 20% of people undergoing chemotherapy are reported to develop anticipatory nausea and vomiting. Once developed, ANV is difficult to control by pharmacological means. Benzodiazepines are the only drugs that have been found to reduce the occurrence of ANV but their efficacy decreases with time. Recently, clinical trials suggests that cannabidiolic acid suppresses conditioned gaping (ANV) in shrews. Because ANV is widely believed to be a learned response, the best approach is to avoid the development of ANV by adequate prophylaxis and treatment of acute vomiting and nausea from the first exposure to therapy. Behavioral treatment techniques, such as systematic desensitization, progressive muscle relaxation and hypnosis have been shown to be effective against ANV.

Radiation therapy

The incidence and severity of radiation therapy-induced nausea and vomiting (RINV) depends on a number of factors including therapy related factors such as irradiated site, single and total dose, fractionation, irradiated volume and radiotherapy techniques. Also involved are person related factors such as gender, general health of the person, age, concurrent or recent chemotherapy, alcohol consumption, previous experience of nausea, vomiting, anxiety as well as the tumor stage. The emetogenic potential of radiotherapy is classified into high, moderate, low and minimal risk depending on the site of irradiation:

• High risk: total body irradiation (TBI) is associated with a high risk of RINV
• Moderate risk: radiation of the upper abdomen, half body irradiation and upper body irradiation
• Low risk: radiation of the cranium, spine, head and neck, lower thorax region and pelvis
• Minimal risk: radiation of extremities and breast

Pathophysiology

Nausea and vomiting may have a number of causes in people with cancer. While more than one cause may exist in the same person stimulating symptoms via more than one pathway, the actual cause of nausea and vomiting may be unknown in some people. The underlying causes of nausea and vomiting may in some cases not be directly related to the cancer. The causes may be categorized as disease-related and treatment-related.

The stimuli which lead to emesis are received and processed in the brain. It is thought that a number of loosely organized neuronal networks within the medulla oblongata probably interact to coordinate the emetic reflex. Some of the brain stem nuclei which have been identified as important in the coordination of the emetic reflex include the parvicellular reticular formation, the Bötzinger complex and the nucleus tractus solitarii. The nuclei coordinating emesis had formerly been referred to as the vomiting complex, but it is no longer thought to represent a single anatomical structure.

Efferent outputs which transmit the information from the brain leading to the motoric response of retching and vomiting include vagal efferents to the esophagus, stomach and intestine as well as spinal somatomotor neurones to the abdominal muscles and phrenic motor neurones (C3–C5) to the diaphragm. Autonomic efferents also supply the heart and airways (vagus), salivary glands (chorda tympani) and skin and are responsible for many of the prodromal signs such as salivation and skin pallor.

Nausea and vomiting may be initiated by various stimuli, through different neuronal pathways. A stimulus may act on more than one pathway. Stimuli and pathways include:

• Toxic substances in the gastrointestinal tract: toxic substances (including drugs which are used in the treatment of cancer) in the lumen of the gastrointestinal tract stimulate vagal afferent nerves in the gut mucosa which communicate to the nucleus tractus solitarii and the area postrema to initiate vomiting and nausea. A number of receptors on the terminal ends of the vagal afferent nerves have been identified as being involved in this process, including the 5-hydroxytryptamine3 (5-HT3), neurokinin-1, and cholecystokinin-1 receptors. Various local mediators located in enterochromaffin cells of the gut mucosa play a role in stimulating these receptors. Of these 5-hydroxytryptamine seems to play the dominating role. This pathway has been postulated to be the mechanism by which some anti-cancer drugs such as cisplatin induce emesis.
• Toxic substances in the blood: toxic substances which have been absorbed into the blood (including cytostatics) or endogenous toxic (waste) material released by body or cancer cells into the blood can be detected directly in the area postrema of the brain and trigger the emetic reflex. The area postrema is a structure located on the floor of the fourth ventricle around which the blood–brain barrier is permeable, thus allowing for the detection of humoral or pharmacological stimuli in the blood or cerebrospinal fluid. This structure contains receptors which form a chemoreceptor trigger zone. Some of the receptors and neurotransmitters involved in the regulation of this emetic pathway include dopamine type D2, serotonin types 2–4 (5HT2–4), histamine type 1(H1), and acetylcholine (muscarinic receptors type 1 to 5, M1–5). Some other receptors such as substance P, cannabinoid type 1 (CB1) and the endogenous opioids may also be involved.
• Pathological conditions of the gastrointestinal tract: diseases and pathological conditions of the GIT may also lead to nausea and vomiting through direct or indirect stimulation of the above named pathways. Such conditions may include malignant bowel obstruction, hypertrophic pyloric stenosis and gastritis. Pathological conditions in other organs which are linked to the above named emetic pathways may also lead to nausea and vomiting, such as the myocardial infarction (through stimulation of cardiac vagal afferents) and kidney failure.
• Stimulation of the central nervous system: certain stimuli of the central nervous system may induce the emetic reflex. These include fear, anticipation, brain trauma and increased intra-cranial pressure. Of particular relevance to cancer patients in this regard are the stimuli of fear and anticipation. Evidence suggests that cancer patients may develop the side effects of nausea and vomiting in anticipation of chemotherapy. In some patients, re-exposure to cues such as smell, sounds or sight associated with the clinic or previous treatment may evoke anticipatory nausea and vomiting.
• Pathological conditions of the vestibular system: a disturbance of the vestibular system such as in motion sickness or Ménière's disease can induce the emetic reflex. Such disturbances of the vestibular system could also be cancer related such as in cerebral or vestibular secondaries (metastasis), or cancer treatment related such as the use of opioids.

Management

The strategies of management or prevention of nausea and vomiting depend on the underlying causes, whether they are reversible or treatable, stage of the illness, the person's prognosis and other person specific factors. Anti emetic drugs are chosen according to previous effectiveness and side effects.

Medication

Drugs that are used in the prophylaxis and therapy of nausea and vomiting in cancer include:

• 5-HT3 antagonists: 5-HT3 antagonists produce their anti emetic effect by blocking of the amplifying effect of serotonin on peripheral and central 5-HT3 receptors located on the various vagal afferent nerve endings and the chemoreceptor trigger zone. They are effective in the treatment and prophylaxis of CINV as well as in malignant bowel obstruction and kidney failure which are associated with elevated serotonin levels. These substances include Dolasetron, Granisetron, Ondansetron, Palonosetron, and Tropisetron. They are often used in combination with other anti emetic drugs in people with high risk of emesis or nausea and are recommended as the most effective anti emetics in the prophylaxis of acute CINV.
• Corticosteroids: such as Dexamethasone are used in the treatment of emesis as a result of chemotherapy, malignant bowel obstruction, raised intracranial pressure and in the chronic nausea of advanced cancer, though their exact mode of action remain unclear. Dexamethason is recommended for use in the acute prevention of highly, moderately, and low emetogenic chemotherapy and in combination with aprepitant for the prevention of delayed emesis in highly emetogenic chemotherapy.
• NK1 receptor antagonists: such as Aprepitant block the NK1 receptor in the brainstem and gastrointestinal tract. Their antiemetic activity when added to a 5-HT3 receptor antagonist plus dexametasone has been shown in several phase II double-blind studies.
• Cannabinoids: are a useful adjunct to modern anti emetic therapy in selected patients. They show a combination of weak anti emetic efficacy with potentially beneficial side effects such as sedation and euphoria. However, their usefulness is generally limited by the high incidence of toxic effects, such as dizziness, dysphoria, and hallucinations. Some studies have shown that cannabinoids are slightly better than conventional anti emetics such as metoclopramide, phenothiazines and haloperidol in the prevention of nausea and vomiting. Cannabinoids are an option in affected people who are intolerant or refractory to 5-HT3 antagonists or steroids and aprepitant as well as in refractory nausea and vomiting and rescue anti emetic therapy.
• Prokinetic agents such as Metoclopramide
• Dopamine receptor antagonists such as Phenothiazines (Prochlorperazine and chlorpromazine), haloperidol, olanzapine, and Levomepromazine, block D2 receptors found in the chemoreceptor trigger zone
• Antihistaminic agents like Promethazine block H1 receptors in the vomiting center of the medulla, the vestibular nucleus, and the chemoreceptor trigger zone
• Anticholinergic agents such as Scopolamine (Hyoscine) are used as anti emetics as they relax smooth muscle and reduce gastrointestinal secretions by blockade of muscarinic receptors. They may be useful in the management of terminal bowel obstruction
• Somatostatin analoga such as Octreotide are used for the palliation of malignant bowel obstruction, especially when there is high output vomiting not responding to other measures
• Cannabidiol is used as a palliative treatment (non-curative symptomatic treatment) and improves numerous symptoms that frequently appear during chemotherapy like nausea, vomiting, loss of appetite, physical pain or insomnia. Due to the large number of cannabinoid receptors ( CB1 and CB2 ) distributed throughout the gastrointestinal tract ( GI ), these substances can help to control and treat many GI diseases where vomiting and nausea are frequent.

Other measures

Other non-drug measures may include:

• Diet: Small palatable meals are normally tolerated better than big meals in people affected by nausea and vomiting in cancer. Carbohydrate meals are better tolerated than spicy, fatty and sweet foods. Cool, fizzy drinks are found to be more palatable than still or hot drinks.
• The avoidance of environmental stimuli, such as sights, sounds, or smells that may initiate nausea.
• Behavioral approaches, such as distraction, relaxation training and Cognitive behavioural therapy may also be useful.
• Alternative medicine: Acupuncture and ginger have been shown to have some anti emetic effects on chemotherapy-induced emesis and anticipatory nausea, but have not been evaluated in the nausea of far advanced disease.

Palliative surgery

Palliative care is the active care of people with advanced, progressive illness such as cancer. The World Health Organization (WHO) defines it as an approach that improves the quality of life of patients and their families facing the problems associated with life-threatening illness, through the prevention and relief of suffering by means of early identification and impeccable assessment and treatment of pain and other problems (such as nausea or vomiting), physical, psychosocial, and spiritual.

Sometimes it is possible or necessary to provide relief for cancer caused nausea and vomiting through palliative surgical intervention. Surgery is however not routinely carried out when there are poor prognostic criteria for surgical intervention such as intra-abdominal carcinomatosis, poor performance status and massive ascites. The surgical approach proves beneficial in affected people with operable lesions, a life expectancy greater than 2 months and good performance status. Often a malignant bowel obstruction is the cause of the symptoms in which case the purpose of palliative surgery is to relieve the symptoms of bowel obstruction by means of several procedures including:

• Stoma formation
• Bypass of the obstruction
• Resection of bowel segments
• Placement of stents.
• Percutaneous endoscopic gastrostomy (PEG) tube placement to enable gastric venting.
• Gastric venting through a nasogastric tube is a semi-invasive possibility for palliation of nausea and vomiting due to gastrointestinal obstruction in people with abdominal malignancies who decline surgery or where surgery may not be indicated. However nasogastric tubes are not recommended to be used over a long period of time because of the high risk of displacement, poor tolerance, restrictions in daily routine activities, coughing, clearing pulmonary secretions and can be cosmetically unacceptable and confining. Complications of nasogastric tubes include aspiration, hemorrhage, gastric erosion, necrosis, sinusitis and otitis.

Epidemiology

12.7 million new cancer cases and 7.6 million cancer deaths were estimated worldwide in 2008.

• Nausea or vomiting occur in 50 to 70% of people with advanced cancer.
• 50 to 80% of people undergoing radiotherapy experience nausea and/or vomiting, depending on the site of irradiation.
• Anticipatory nausea and vomiting is experienced by approximately 20 to 30% of people undergoing chemotherapy.
• Chemotherapy-induced nausea and vomiting resulting from treatment with highly emetogenic cytotoxic drugs can be prevented or effectively treated in 70 to 80% of affected people.

Cannabinoid

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Cannabinoid

Cannabinoids (/kəˈnæbənɔɪdzˌ ˈkænəbənɔɪdz/) are several structural classes of compounds found in the cannabis plant primarily and most animal organisms (although insects lack such receptors) or as synthetic compounds. The most notable cannabinoid is the phytocannabinoid tetrahydrocannabinol (THC) (delta-9-THC), the primary intoxicating compound in cannabis. Cannabidiol (CBD) is also a major constituent of temperate Cannabis plants and a minor constituent in tropical varieties. At least 113 distinct phytocannabinoids have been isolated from cannabis, although only four (i.e., THCA, CBDA, CBCA and their common precursor CBGA) have been demonstrated to have a biogenetic origin. It was reported in 2020 that phytocannabinoids can be found in other plants such as rhododendron, licorice and liverwort, and earlier in Echinacea.

Phytocannabinoids are multi-ring phenolic compounds structurally related to THC, but endocannabinoids are fatty acid derivatives. Nonclassical synthetic cannabinoids (cannabimimetics) include aminoalkylindoles, 1,5-diarylpyrazoles, quinolines, and arylsulfonamides as well as eicosanoids related to endocannabinoids.

Uses

Medical uses include the treatment of nausea due to chemotherapy, spasticity, and possibly neuropathic pain. Common side effects include dizziness, sedation, confusion, dissociation, and "feeling high".

Cannabinoid receptors

Before the 1980s, cannabinoids were speculated to produce their physiological and behavioral effects via nonspecific interaction with cell membranes, instead of interacting with specific membrane-bound receptors. The discovery of the first cannabinoid receptors in the 1980s helped to resolve this debate. These receptors are common in animals. Two known cannabinoid receptors are termed CB₁ and CB₂, with mounting evidence of more. The human brain has more cannabinoid receptors than any other G protein-coupled receptor (GPCR) type.

The Endocannabinoid System (ECS) regulates many functions of the human body. The ECS plays an important role in multiple aspects of neural functions, including the control of movement and motor coordination, learning and memory, emotion and motivation, addictive-like behavior and pain modulation, among others.

Cannabinoid receptor type 1

Main article: Cannabinoid receptor type 1

CB₁ receptors are found primarily in the brain, more specifically in the basal ganglia and in the limbic system, including the hippocampus and the striatum. They are also found in the cerebellum and in both male and female reproductive systems. CB₁ receptors are absent in the medulla oblongata, the part of the brain stem responsible for respiratory and cardiovascular functions. CB1 is also found in the human anterior eye and retina.

Cannabinoid receptor type 2

Main article: Cannabinoid receptor type 2

CB₂ receptors are predominantly found in the immune system, or immune-derived cells with varying expression patterns. While found only in the peripheral nervous system, a report does indicate that CB₂ is expressed by a subpopulation of microglia in the human cerebellum. CB₂ receptors appear to be responsible for immunomodulatory and possibly other therapeutic effects of cannabinoid as seen in vitro and in animal models.

Phytocannabinoids

See also: Comparison of phytocannabinoids

 

The bracts surrounding a cluster of Cannabis sativa flowers are coated with cannabinoid-laden trichomes.

 

Cannabis indica plant

The classical cannabinoids are concentrated in a viscous resin produced in structures known as glandular trichomes. At least 113 different cannabinoids have been isolated from the Cannabis plant. To the right, the main classes of cannabinoids from Cannabis are shown.

All classes derive from cannabigerol-type (CBG) compounds and differ mainly in the way this precursor is cyclized. The classical cannabinoids are derived from their respective 2-carboxylic acids (2-COOH) by decarboxylation (catalyzed by heat, light, or alkaline conditions).

Well known cannabinoids

The best studied cannabinoids include tetrahydrocannabinol (THC), cannabidiol (CBD) and cannabinol (CBN).

Tetrahydrocannabinol

Main article: Tetrahydrocannabinol

Tetrahydrocannabinol (THC) is the primary psychoactive component of the Cannabis plant. Delta-9-tetrahydrocannabinol (Δ⁹-THC, THC) and Delta-8-Tetrahydrocannabinol (Δ⁸-THC), through intracellular CB₁ activation, induce anandamide and 2-arachidonoylglycerol synthesis produced naturally in the body and brain. These cannabinoids produce the effects associated with cannabis by binding to the CB₁ cannabinoid receptors in the brain.

Cannabidiol

Main article: Cannabidiol

Cannabidiol (CBD) is mildly psychotropic. Evidence shows that the compound counteracts cognitive impairment associated with the use of cannabis. Cannabidiol has little affinity for CB₁ and CB₂ receptors but acts as an indirect antagonist of cannabinoid agonists. It was found to be an antagonist at the putative new cannabinoid receptor, GPR55, a GPCR expressed in the caudate nucleus and putamen. Cannabidiol has also been shown to act as a 5-HT_1A receptor agonist. CBD can interfere with the uptake of adenosine, which plays an important role in biochemical processes, such as energy transfer. It may play a role in promoting sleep and suppressing arousal.

CBD shares a precursor with THC and is the main cannabinoid in CBD-dominant Cannabis strains. CBD has been shown to play a role in preventing the short-term memory loss associated with THC.

There is tentative evidence that CBD has an anti-psychotic effect, but research in this area is limited.

Cannabinol

Main article: Cannabinol

Cannabinol (CBN) is a mildly psychoactive cannabinoid that acts as a low affinity partial agonist at both CB1 and CB2 receptors. Through its mechanism of partial agonism at the CB1R, CBN is thought to interact with other kinds of neurotransmission (e.g., dopaminergic, serotonergic, cholinergic, and noradrenergic).

CBN was the first cannabis compound to be isolated from cannabis extract in the late 1800s. Its structure and chemical synthesis were achieved by 1940, followed by some of the first pre-clinical research studies to determine the effects of individual cannabis-derived compounds in vivo. Although CBN shares the same mechanism of action as other more well-known phytocannabinoids (e.g., delta-9 tetrahydrocannabinol or D9THC), it has a lower affinity for CB1 receptors, meaning that much higher doses of CBN are required in order to experience physiologic effects (e.g., mild sedation) associated with CB1R agonism. Although scientific reports are conflicting, the majority of findings suggest that CBN has a slightly higher affinity for CB2 as compared to CB1. Although CBN has been marketed as a sleep aid in recent years, there is a lack of scientific evidence to support these claims, warranting skepticism on the part of consumers.

Biosynthesis

Cannabinoid production starts when an enzyme causes geranyl pyrophosphate and olivetolic acid to combine and form CBGA. Next, CBGA is independently converted to either CBG, THCA, CBDA or CBCA by four separate synthase, FAD-dependent dehydrogenase enzymes. There is no evidence for enzymatic conversion of CBDA or CBD to THCA or THC. For the propyl homologues (THCVA, CBDVA and CBCVA), there is an analogous pathway that is based on CBGVA from divarinolic acid instead of olivetolic acid.

Double bond position

In addition, each of the compounds above may be in different forms depending on the position of the double bond in the alicyclic carbon ring. There is potential for confusion because there are different numbering systems used to describe the position of this double bond. Under the dibenzopyran numbering system widely used today, the major form of THC is called Δ⁹-THC, while the minor form is called Δ⁸-THC. Under the alternate terpene numbering system, these same compounds are called Δ¹-THC and Δ⁶-THC, respectively.

Length

Most classical cannabinoids are 21-carbon compounds. However, some do not follow this rule, primarily because of variation in the length of the side-chain attached to the aromatic ring. In THC, CBD, and CBN, this side-chain is a pentyl (5-carbon) chain. In the most common homologue, the pentyl chain is replaced with a propyl (3-carbon) chain. Cannabinoids with the propyl side chain are named using the suffix varin and are designated THCV, CBDV, or CBNV, while those with the heptyl side chain are named using the suffix phorol and are designated THCP and CBDP.

Cannabinoids in other plants

Phytocannabinoids are known to occur in several plant species besides cannabis. These include Echinacea purpurea, Echinacea angustifolia, Acmella oleracea, Helichrysum umbraculigerum, and Radula marginata. The best-known cannabinoids that are not derived from Cannabis are the lipophilic alkamides (alkylamides) from Echinacea species, most notably the cis/trans isomers dodeca-2E,4E,8Z,10E/Z-tetraenoic-acid-isobutylamide. At least 25 different alkylamides have been identified, and some of them have shown affinities to the CB₂-receptor. In some Echinacea species, cannabinoids are found throughout the plant structure, but are most concentrated in the roots and flowers. Yangonin found in the Kava plant has significant affinity to the CB1 receptor. Tea (Camellia sinensis) catechins have an affinity for human cannabinoid receptors. A widespread dietary terpene, beta-caryophyllene, a component from the essential oil of cannabis and other medicinal plants, has also been identified as a selective agonist of peripheral CB₂-receptors, in vivo. Black truffles contain anandamide. Perrottetinene, a moderately psychoactive cannabinoid, has been isolated from different Radula varieties.

Most of the phytocannabinoids are nearly insoluble in water but are soluble in lipids, alcohols, and other non-polar organic solvents.

Cannabis plant profile

Cannabis plants can exhibit wide variation in the quantity and type of cannabinoids they produce. The mixture of cannabinoids produced by a plant is known as the plant's cannabinoid profile. Selective breeding has been used to control the genetics of plants and modify the cannabinoid profile. For example, strains that are used as fiber (commonly called hemp) are bred such that they are low in psychoactive chemicals like THC. Strains used in medicine are often bred for high CBD content, and strains used for recreational purposes are usually bred for high THC content or for a specific chemical balance.

Quantitative analysis of a plant's cannabinoid profile is often determined by gas chromatography (GC), or more reliably by gas chromatography combined with mass spectrometry (GC/MS). Liquid chromatography (LC) techniques are also possible and, unlike GC methods, can differentiate between the acid and neutral forms of the cannabinoids. There have been systematic attempts to monitor the cannabinoid profile of cannabis over time, but their accuracy is impeded by the illegal status of the plant in many countries.

Pharmacology

Cannabinoids can be administered by smoking, vaporizing, oral ingestion, transdermal patch, intravenous injection, sublingual absorption, or rectal suppository. Once in the body, most cannabinoids are metabolized in the liver, especially by cytochrome P450 mixed-function oxidases, mainly CYP 2C9. Thus supplementing with CYP 2C9 inhibitors leads to extended intoxication.

Some is also stored in fat in addition to being metabolized in the liver. Δ⁹-THC is metabolized to 11-hydroxy-Δ⁹-THC, which is then metabolized to 9-carboxy-THC. Some cannabis metabolites can be detected in the body several weeks after administration. These metabolites are the chemicals recognized by common antibody-based "drug tests"; in the case of THC or others, these loads do not represent intoxication (compare to ethanol breath tests that measure instantaneous blood alcohol levels), but an integration of past consumption over an approximately month-long window. This is because they are fat-soluble, lipophilic molecules that accumulate in fatty tissues.

Research shows the effect of cannabinoids might be modulated by aromatic compounds produced by the cannabis plant, called terpenes. This interaction would lead to the entourage effect.

Cannabinoid-based pharmaceuticals

Nabiximols (brand name Sativex) is an aerosolized mist for oral administration containing a near 1:1 ratio of CBD and THC. Also included are minor cannabinoids and terpenoids, ethanol and propylene glycol excipients, and peppermint flavoring. The drug, made by GW Pharmaceuticals, was first approved by Canadian authorities in 2005 to alleviate pain associated with multiple sclerosis, making it the first cannabis-based medicine. It is marketed by Bayer in Canada. Sativex has been approved in 25 countries; clinical trials are underway in the United States to gain FDA approval. In 2007, it was approved for treatment of cancer pain. In Phase III trials, the most common adverse effects were dizziness, drowsiness and disorientation; 12% of subjects stopped taking the drug because of the side effects.

Dronabinol (brand name Marinol) is a THC drug used to treat poor appetite, nausea, and sleep apnea. It is approved by the FDA for treating HIV/AIDS induced anorexia and chemotherapy induced nausea and vomiting.

The CBD drug Epidiolex has been approved by the Food and Drug Administration for treatment of two rare and severe forms of epilepsy,^[59] Dravet and Lennox-Gastaut syndromes.

Separation

Cannabinoids can be separated from the plant by extraction with organic solvents. Hydrocarbons and alcohols are often used as solvents. However, these solvents are flammable and many are toxic. Butane may be used, which evaporates extremely quickly. Supercritical solvent extraction with carbon dioxide is an alternative technique. Once extracted, isolated components can be separated using wiped film vacuum distillation or other distillation techniques. Also, techniques such as SPE or SPME are found useful in the extraction of these compounds.

History

The first discovery of an individual cannabinoid was made, when British chemist Robert S. Cahn reported the partial structure of Cannabinol (CBN), which he later identified as fully formed in 1940.

Two years later, in 1942, American chemist, Roger Adams, made history when he discovered Cannabidiol (CBD). Progressing from Adams research, in 1963 Israeli professor Raphael Mechoulam later identified the stereochemistry of CBD. The following year, in 1964, Mechoulam and his team identified the stereochemistry of Tetrahydrocannabinol (THC).

Due to molecular similarity and ease of synthetic conversion, CBD was originally believed to be a natural precursor to THC. However, it is now known that CBD and THC are produced independently in the Cannabis plant from the precursor CBG.

Endocannabinoids

Further information on the functions and regulation of the endocannabinoids: Endocannabinoid system

Anandamide, an endogenous ligand of CB₁ and CB₂

Endocannabinoids are substances produced from within the body that activate cannabinoid receptors. After the discovery of the first cannabinoid receptor in 1988, scientists began searching for endogenous ligand for the receptors.

Types of endocannabinoid ligands

Arachidonoylethanolamine (Anandamide or AEA)

Main article: Arachidonoylethanolamine

Anandamide was the first such compound identified as arachidonoyl ethanolamine. The name is derived from the Sanskrit word for bliss and -amide. It has a pharmacology similar to THC, although its structure is quite different. Anandamide binds to the central (CB₁) and, to a lesser extent, peripheral (CB₂) cannabinoid receptors, where it acts as a partial agonist. Anandamide is about as potent as THC at the CB₁ receptor. Anandamide is found in nearly all tissues in a wide range of animals. Anandamide has also been found in plants, including small amounts in chocolate.

Two analogs of anandamide, 7,10,13,16-docosatetraenoylethanolamide and homo-γ-linolenoylethanolamine, have similar pharmacology. All of these compounds are members of a family of signalling lipids called N-acylethanolamines, which also includes the noncannabimimetic palmitoylethanolamide and oleoylethanolamide, which possess anti-inflammatory and anorexigenic effects, respectively. Many N-acylethanolamines have also been identified in plant seeds and in molluscs.

2-Arachidonoylglycerol (2-AG)

Main article: 2-Arachidonoylglycerol

Another endocannabinoid, 2-arachidonoylglycerol, binds to both the CB₁ and CB₂ receptors with similar affinity, acting as a full agonist at both. 2-AG is present at significantly higher concentrations in the brain than anandamide, and there is some controversy over whether 2-AG rather than anandamide is chiefly responsible for endocannabinoid signalling in vivo. In particular, one in vitro study suggests that 2-AG is capable of stimulating higher G-protein activation than anandamide, although the physiological implications of this finding are not yet known.

2-Arachidonyl glyceryl ether (noladin ether)

Main article: 2-Arachidonyl glyceryl ether

In 2001, a third, ether-type endocannabinoid, 2-arachidonyl glyceryl ether (noladin ether), was isolated from porcine brain. Prior to this discovery, it had been synthesized as a stable analog of 2-AG; indeed, some controversy remains over its classification as an endocannabinoid, as another group failed to detect the substance at "any appreciable amount" in the brains of several different mammalian species. It binds to the CB₁ cannabinoid receptor (K_i = 21.2 nmol/L) and causes sedation, hypothermia, intestinal immobility, and mild antinociception in mice. It binds primarily to the CB₁ receptor, and only weakly to the CB₂ receptor.

N-Arachidonoyl dopamine (NADA)

Main article: N-Arachidonoyl dopamine

Discovered in 2000, NADA preferentially binds to the CB₁ receptor. Like anandamide, NADA is also an agonist for the vanilloid receptor subtype 1 (TRPV1), a member of the vanilloid receptor family.

Virodhamine (OAE)

Main article: Virodhamine

A fifth endocannabinoid, virodhamine, or O-arachidonoyl-ethanolamine (OAE), was discovered in June 2002. Although it is a full agonist at CB₂ and a partial agonist at CB₁, it behaves as a CB₁ antagonist in vivo. In rats, virodhamine was found to be present at comparable or slightly lower concentrations than anandamide in the brain, but 2- to 9-fold higher concentrations peripherally.

Lysophosphatidylinositol (LPI)

Lysophosphatidylinositol is the endogenous ligand to novel endocannabinoid receptor GPR55, making it a strong contender as the sixth endocannabinoid.

Function

Endocannabinoids serve as intercellular 'lipid messengers', signaling molecules that are released from one cell and activating the cannabinoid receptors present on other nearby cells. Although in this intercellular signaling role they are similar to the well-known monoamine neurotransmitters such as dopamine, endocannabinoids differ in numerous ways from them. For instance, they are used in retrograde signaling between neurons. Furthermore, endocannabinoids are lipophilic molecules that are not very soluble in water. They are not stored in vesicles and exist as integral constituents of the membrane bilayers that make up cells. They are believed to be synthesized 'on-demand' rather than made and stored for later use.

As hydrophobic molecules, endocannabinoids cannot travel unaided for long distances in the aqueous medium surrounding the cells from which they are released and therefore act locally on nearby target cells. Hence, although emanating diffusely from their source cells, they have much more restricted spheres of influence than do hormones, which can affect cells throughout the body.

The mechanisms and enzymes underlying the biosynthesis of endocannabinoids remain elusive and continue to be an area of active research.

The endocannabinoid 2-AG has been found in bovine and human maternal milk.

A review by Matties et al. (1994) summed up the phenomenon of gustatory enhancement by certain cannabinoids. The sweet receptor (Tlc1) is stimulated by indirectly increasing its expression and suppressing the activity of leptin, the Tlc1 antagonist. It is proposed that the competition of leptin and cannabinoids for Tlc1 is implicated in energy homeostasis.

Retrograde signal

Conventional neurotransmitters are released from a ‘presynaptic’ cell and activate appropriate receptors on a ‘postsynaptic’ cell, where presynaptic and postsynaptic designate the sending and receiving sides of a synapse, respectively. Endocannabinoids, on the other hand, are described as retrograde transmitters because they most commonly travel ‘backward’ against the usual synaptic transmitter flow. They are, in effect, released from the postsynaptic cell and act on the presynaptic cell, where the target receptors are densely concentrated on axonal terminals in the zones from which conventional neurotransmitters are released. Activation of cannabinoid receptors temporarily reduces the amount of conventional neurotransmitter released. This endocannabinoid-mediated system permits the postsynaptic cell to control its own incoming synaptic traffic. The ultimate effect on the endocannabinoid-releasing cell depends on the nature of the conventional transmitter being controlled. For instance, when the release of the inhibitory transmitter GABA is reduced, the net effect is an increase in the excitability of the endocannabinoid-releasing cell. On the converse, when release of the excitatory neurotransmitter glutamate is reduced, the net effect is a decrease in the excitability of the endocannabinoid-releasing cell.

"Runner's high"

The runner's high, the feeling of euphoria that sometimes accompanies aerobic exercise, has often been attributed to the release of endorphins, but newer research suggests that it might be due to endocannabinoids instead.

Synthetic cannabinoids

Main article: Synthetic cannabinoid

Historically, laboratory synthesis of cannabinoids was often based on the structure of herbal cannabinoids, and a large number of analogs have been produced and tested, especially in a group led by Roger Adams as early as 1941 and later in a group led by Raphael Mechoulam. Newer compounds are no longer related to natural cannabinoids or are based on the structure of the endogenous cannabinoids.

Synthetic cannabinoids are particularly useful in experiments to determine the relationship between the structure and activity of cannabinoid compounds, by making systematic, incremental modifications of cannabinoid molecules.

When synthetic cannabinoids are used recreationally, they present significant health dangers to users. In the period of 2012 through 2014, over 10,000 contacts to poison control centers in the United States were related to use of synthetic cannabinoids.

Medications containing natural or synthetic cannabinoids or cannabinoid analogs:

• Dronabinol (Marinol), is Δ⁹-tetrahydrocannabinol (THC), used as an appetite stimulant, anti-emetic, and analgesic
• Nabilone (Cesamet, Canemes), a synthetic cannabinoid and an analog of Marinol. It is Schedule II unlike Marinol, which is Schedule III
• Rimonabant (SR141716), a selective cannabinoid (CB₁) receptor inverse agonist once used as an anti-obesity drug under the proprietary name Acomplia. It was also used for smoking cessation

Other notable synthetic cannabinoids include:

• JWH-018, a potent synthetic cannabinoid agonist discovered by John W. Huffman at Clemson University. It was often sold in legal smoke blends collectively known as "spice". Several countries and states have moved to ban it legally.
• JWH-073
• CP-55940, produced in 1974, this synthetic cannabinoid receptor agonist is many times more potent than THC.
• Dimethylheptylpyran
• HU-210, about 100 times as potent as THC
• HU-211, a synthetic cannabinoid derived drug that acts on NMDA instead of endocannabinoid system
• HU-331 a potential anti-cancer drug derived from cannabidiol that specifically inhibits topoisomerase II.
• SR144528, a CB₂ receptor antagonist/ inverse agonist
• WIN 55,212-2, a potent cannabinoid receptor agonist
• JWH-133, a potent selective CB₂ receptor agonist
• Levonantradol (Nantrodolum), an anti-emetic and analgesic but not currently in use in medicine
• AM-2201, a potent cannabinoid receptor agonist

Recently, the term "neocannabinoid" has been introduced to distinguish these designer drugs from synthetic phytocannabinoids (THC or CBD obtained by chemical synthesis) or synthetic endocannabinoids.

Medical microbiology

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Medical_microbiology 

 

A microbiologist examining cultures under a dissecting microscope.

Medical microbiology, the large subset of microbiology that is applied to medicine, is a branch of medical science concerned with the prevention, diagnosis and treatment of infectious diseases. In addition, this field of science studies various clinical applications of microbes for the improvement of health. There are four kinds of microorganisms that cause infectious disease: bacteria, fungi, parasites and viruses, and one type of infectious protein called prion.

A medical microbiologist studies the characteristics of pathogens, their modes of transmission, mechanisms of infection and growth. The academic qualification as a clinical/Medical Microbiologist in a hospital or medical research centre generally requires a Bachelors degree while in some countries a Masters in Microbiology along with Ph.D. in any of the life-sciences (Biochem, Micro, Biotech, Genetics, etc.). Medical microbiologists often serve as consultants for physicians, providing identification of pathogens and suggesting treatment options. Using this information, a treatment can be devised. Other tasks may include the identification of potential health risks to the community or monitoring the evolution of potentially virulent or resistant strains of microbes, educating the community and assisting in the design of health practices. They may also assist in preventing or controlling epidemics and outbreaks of disease. Not all medical microbiologists study microbial pathology; some study common, non-pathogenic species to determine whether their properties can be used to develop antibiotics or other treatment methods.

Epidemiology, the study of the patterns, causes, and effects of health and disease conditions in populations, is an important part of medical microbiology, although the clinical aspect of the field primarily focuses on the presence and growth of microbial infections in individuals, their effects on the human body, and the methods of treating those infections. In this respect the entire field, as an applied science, can be conceptually subdivided into academic and clinical sub-specialties, although in reality there is a fluid continuum between public health microbiology and clinical microbiology, just as the state of the art in clinical laboratories depends on continual improvements in academic medicine and research laboratories.

History

Anton van Leeuwenhoek was the first to observe microorganisms using a microscope.

 

Statue of Robert Koch, father of medical bacteriology, at Robert-Koch-Platz (Robert Koch square) in Berlin

In 1676, Anton van Leeuwenhoek observed bacteria and other microorganisms, using a single-lens microscope of his own design.

In 1796, Edward Jenner developed a method using cowpox to successfully immunize a child against smallpox. The same principles are used for developing vaccines today.

Following on from this, in 1857 Louis Pasteur also designed vaccines against several diseases such as anthrax, fowl cholera and rabies as well as pasteurization for food preservation.

In 1867 Joseph Lister is considered to be the father of antiseptic surgery. By sterilizing the instruments with diluted carbolic acid and using it to clean wounds, post-operative infections were reduced, making surgery safer for patients.

In the years between 1876 and 1884 Robert Koch provided much insight into infectious diseases. He was one of the first scientists to focus on the isolation of bacteria in pure culture. This gave rise to the germ theory, a certain microorganism being responsible for a certain disease. He developed a series of criteria around this that have become known as the Koch's postulates.

A major milestone in medical microbiology is the Gram stain. In 1884 Hans Christian Gram developed the method of staining bacteria to make them more visible and differentiated under a microscope. This technique is widely used today.

In 1910 Paul Ehrlich tested multiple combinations of arsenic based chemicals on infected rabbits with syphilis. Ehrlich then found that arsphenamine was found effective against syphilis spirochetes. The arsphenamines was then made available in 1910, known as Salvarsan.

In 1929 Alexander Fleming developed the most commonly used antibiotic substance both at the time and now: penicillin.

In 1939 Gerhard Domagk found Prontosil red protected mice from pathogenic streptococci and staphylococci without toxicity. Domagk received the Nobel Prize in physiology, or medicine, for the discovery of the sulfa drug.

DNA sequencing, a method developed by Walter Gilbert and Frederick Sanger in 1977, caused a rapid change the development of vaccines, medical treatments and diagnostic methods. Some of these include synthetic insulin which was produced in 1979 using recombinant DNA and the first genetically engineered vaccine was created in 1986 for hepatitis B.

In 1995 a team at The Institute for Genomic Research sequenced the first bacterial genome; Haemophilus influenzae. A few months later, the first eukaryotic genome was completed. This would prove invaluable for diagnostic techniques.

Commonly treated infectious diseases

Bacterial

• Streptococcal pharyngitis
• Chlamydia
• Typhoid fever
• Tuberculosis

Viral

• Rotavirus
• Hepatitis C
• Human papillomavirus (HPV)

Parasitic

• Malaria
• Giardia lamblia
• Toxoplasma gondii

Fungal

• Candida
• Histoplasmosis
• Dandruff

Causes and transmission of infectious diseases

See also: Infection

Infections may be caused by bacteria, viruses, fungi, and parasites. The pathogen that causes the disease may be exogenous (acquired from an external source; environmental, animal or other people, e.g. Influenza) or endogenous (from normal flora e.g. Candidiasis).

The site at which a microbe enters the body is referred to as the portal of entry. These include the respiratory tract, gastrointestinal tract, genitourinary tract, skin, and mucous membranes. The portal of entry for a specific microbe is normally dependent on how it travels from its natural habitat to the host.

There are various ways in which disease can be transmitted between individuals. These include:

• Direct contact - Touching an infected host, including sexual contact
• Indirect contact - Touching a contaminated surface
• Droplet contact - Coughing or sneezing
• Fecal–oral route - Ingesting contaminated food or water sources
• Airborne transmission - Pathogen carrying spores
• Vector transmission - An organism that does not cause disease itself but transmits infection by conveying pathogens from one host to another
• Fomite transmission - An inanimate object or substance capable of carrying infectious germs or parasites
• Environmental - Hospital-acquired infection (Nosocomial infections)

Like other pathogens, viruses use these methods of transmission to enter the body, but viruses differ in that they must also enter into the host's actual cells. Once the virus has gained access to the host's cells, the virus' genetic material (RNA or DNA) must be introduced to the cell. Replication between viruses is greatly varied and depends on the type of genes involved in them. Most DNA viruses assemble in the nucleus while most RNA viruses develop solely in cytoplasm.

The mechanisms for infection, proliferation, and persistence of a virus in cells of the host are crucial for its survival. For example, some diseases such as measles employ a strategy whereby it must spread to a series of hosts. In these forms of viral infection, the illness is often treated by the body's own immune response, and therefore the virus is required to disperse to new hosts before it is destroyed by immunological resistance or host death. In contrast, some infectious agents such as the Feline leukemia virus, are able to withstand immune responses and are capable of achieving long-term residence within an individual host, whilst also retaining the ability to spread into successive hosts.

Diagnostic tests

Main article: Diagnostic microbiology

Identification of an infectious agent for a minor illness can be as simple as clinical presentation; such as gastrointestinal disease and skin infections. In order to make an educated estimate as to which microbe could be causing the disease, epidemiological factors need to be considered; such as the patient's likelihood of exposure to the suspected organism and the presence and prevalence of a microbial strain in a community.

Diagnosis of infectious disease is nearly always initiated by consulting the patient's medical history and conducting a physical examination. More detailed identification techniques involve microbial culture, microscopy, biochemical tests and genotyping. Other less common techniques (such as X-rays, CAT scans, PET scans or NMR) are used to produce images of internal abnormalities resulting from the growth of an infectious agent.

Microbial culture

Four nutrient agar plates growing colonies of common Gram negative bacteria.

Microbiological culture is the primary method used for isolating infectious disease for study in the laboratory. Tissue or fluid samples are tested for the presence of a specific pathogen, which is determined by growth in a selective or differential medium.

The 3 main types of media used for testing are:

• Solid culture: A solid surface is created using a mixture of nutrients, salts and agar. A single microbe on an agar plate can then grow into colonies (clones where cells are identical to each other) containing thousands of cells. These are primarily used to culture bacteria and fungi.
• Liquid culture: Cells are grown inside a liquid media. Microbial growth is determined by the time taken for the liquid to form a colloidal suspension. This technique is used for diagnosing parasites and detecting mycobacteria.
• Cell culture: Human or animal cell cultures are infected with the microbe of interest. These cultures are then observed to determine the effect the microbe has on the cells. This technique is used for identifying viruses.

Microscopy

Culture techniques will often use a microscopic examination to help in the identification of the microbe. Instruments such as compound light microscopes can be used to assess critical aspects of the organism. This can be performed immediately after the sample is taken from the patient and is used in conjunction with biochemical staining techniques, allowing for resolution of cellular features. Electron microscopes and fluorescence microscopes are also used for observing microbes in greater detail for research.

Biochemical tests

Fast and relatively simple biochemical tests can be used to identify infectious agents. For bacterial identification, the use of metabolic or enzymatic characteristics are common due to their ability to ferment carbohydrates in patterns characteristic of their genus and species. Acids, alcohols and gases are usually detected in these tests when bacteria are grown in selective liquid or solid media, as mentioned above. In order to perform these tests en masse, automated machines are used. These machines perform multiple biochemical tests simultaneously, using cards with several wells containing different dehydrated chemicals. The microbe of interest will react with each chemical in a specific way, aiding in its identification.

Serological methods are highly sensitive, specific and often extremely rapid laboratory tests used to identify different types of microorganisms. The tests are based upon the ability of an antibody to bind specifically to an antigen. The antigen (usually a protein or carbohydrate made by an infectious agent) is bound by the antibody, allowing this type of test to be used for organisms other than bacteria. This binding then sets off a chain of events that can be easily and definitively observed, depending on the test. More complex serological techniques are known as immunoassays. Using a similar basis as described above, immunoassays can detect or measure antigens from either infectious agents or the proteins generated by an infected host in response to the infection.

Polymerase chain reaction

Polymerase chain reaction (PCR) assays are the most commonly used molecular technique to detect and study microbes. As compared to other methods, sequencing and analysis is definitive, reliable, accurate, and fast. Today, quantitative PCR is the primary technique used, as this method provides faster data compared to a standard PCR assay. For instance, traditional PCR techniques require the use of gel electrophoresis to visualize amplified DNA molecules after the reaction has finished. quantitative PCR does not require this, as the detection system uses fluorescence and probes to detect the DNA molecules as they are being amplified. In addition to this, quantitative PCR also removes the risk of contamination that can occur during standard PCR procedures (carrying over PCR product into subsequent PCRs). Another advantage of using PCR to detect and study microbes is that the DNA sequences of newly discovered infectious microbes or strains can be compared to those already listed in databases, which in turn helps to increase understanding of which organism is causing the infectious disease and thus what possible methods of treatment could be used. This technique is the current standard for detecting viral infections such as AIDS and hepatitis.

Treatments

Once an infection has been diagnosed and identified, suitable treatment options must be assessed by the physician and consulting medical microbiologists. Some infections can be dealt with by the body's own immune system, but more serious infections are treated with antimicrobial drugs. Bacterial infections are treated with antibacterials (often called antibiotics) whereas fungal and viral infections are treated with antifungals and antivirals respectively. A broad class of drugs known as antiparasitics are used to treat parasitic diseases.

Medical microbiologists often make treatment recommendations to the patient's physician based on the strain of microbe and its antibiotic resistances, the site of infection, the potential toxicity of antimicrobial drugs and any drug allergies the patient has.

Antibiotic resistance tests: bacteria in the culture on the left are sensitive to the antibiotics contained in the white, paper discs. Bacteria in the culture on the right are resistant to most of the antibiotics.

In addition to drugs being specific to a certain kind of organism (bacteria, fungi, etc.), some drugs are specific to a certain genus or species of organism, and will not work on other organisms. Because of this specificity, medical microbiologists must consider the effectiveness of certain antimicrobial drugs when making recommendations. Additionally, strains of an organism may be resistant to a certain drug or class of drug, even when it is typically effective against the species. These strains, termed resistant strains, present a serious public health concern of growing importance to the medical industry as the spread of antibiotic resistance worsens. Antimicrobial resistance is an increasingly problematic issue that leads to millions of deaths every year.

Whilst drug resistance typically involves microbes chemically inactivating an antimicrobial drug or a cell mechanically stopping the uptake of a drug, another form of drug resistance can arise from the formation of biofilms. Some bacteria are able to form biofilms by adhering to surfaces on implanted devices such as catheters and prostheses and creating an extracellular matrix for other cells to adhere to. This provides them with a stable environment from which the bacteria can disperse and infect other parts of the host. Additionally, the extracellular matrix and dense outer layer of bacterial cells can protect the inner bacteria cells from antimicrobial drugs.

Medical microbiology is not only about diagnosing and treating disease, it also involves the study of beneficial microbes. Microbes have been shown to be helpful in combating infectious disease and promoting health. Treatments can be developed from microbes, as demonstrated by Alexander Fleming's discovery of penicillin as well as the development of new antibiotics from the bacterial genus Streptomyces among many others. Not only are microorganisms a source of antibiotics but some may also act as probiotics to provide health benefits to the host, such as providing better gastrointestinal health or inhibiting pathogens.