TETRANOR WOUND SPRAY

Indications

• Bacterial infections (e.g. Chlamydia, Rickettsia, Mycoplasma)
• Acne
• Prophylaxis of asymptomatic meningococcal carrier state (not recommended)

Dosage

Adults: For adult patients, the typical dosage of oxytetracycline for susceptible infections is 100 mg twice daily for 5 days. For other conditions, such as acne, the dosage may be 500 mg twice daily, usually for a duration of 6 to 12 weeks, with the possibility of repeating the course intermittently.

Mechanism of action

Oxytetracycline exerts its antibacterial effects by binding to the 30S ribosomal subunit of bacteria, inhibiting the binding of aminoacyl-tRNA to the mRNA-ribosome complex. This action prevents the synthesis of proteins essential for bacterial growth and replication, leading to the bacteriostatic effect of the drug.

Pharmacodynamics

The pharmacodynamics of oxytetracycline involve its ability to inhibit bacterial protein synthesis, which is critical for the growth and reproduction of bacteria. The drug demonstrates a broad spectrum of activity against both Gram-positive and Gram-negative organisms, as well as some atypical pathogens. Its effectiveness can be influenced by the presence of tetracycline resistance mechanisms in certain bacterial strains.

Pharmacokinetics

Oxytetracycline is well absorbed from the gastrointestinal tract, with peak plasma concentrations occurring approximately 1-2 hours after oral administration. It has a relatively long half-life of about 8-10 hours, allowing for twice-daily dosing. The drug is widely distributed in body tissues and fluids, including the liver, kidneys, and lungs, but is less effective in central nervous system infections due to limited penetration. It is primarily excreted via urine, and dosage adjustments may be necessary in patients with renal impairment.

Contra-indications

• Children under 12 years due to deposition in growing bone and teeth, causing staining and occasionally dental hypoplasia

Adverse effects

• Gastrointestinal disturbances
• Photosensitivity
• Dental discoloration
• Hepatotoxicity
• Renal impairment
• Skin reactions including rash and urticaria
• Ataxia
• Hearing impairment
• Colitis
• Systemic lupus erythematosus exacerbation

Interactions

• Antacids and supplements containing calcium, magnesium, or iron may reduce absorption
• Oral contraceptives may be less effective
• Other tetracyclines
• Warfarin (may increase anticoagulant effect)

Precautions

• Use with caution in patients with renal impairment
• Monitor for hepatic toxicity in long-term use
• Patients should be advised to avoid excessive sunlight exposure
• Discontinue if systemic lupus erythematosus develops or worsens

Pregnancy

Oxytetracycline is contraindicated during pregnancy due to potential harm to fetal development, particularly affecting bone and dental health.

Breast-feeding

Use with caution; oxytetracycline is excreted in breast milk and may affect the infant's dental health.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Formulations

• Oxytetracycline 250 mg tablets
• Oxytetracycline oral suspension
• Oxytetracycline oral solution

Indications

• Multiple sclerosis
• Psoriasis (under expert supervision)

Dosage

Children: There is limited evidence regarding the use of dimethyl fumarate in pediatric populations. For pediatric dosing

Adults: The dosing regimen for adults is typically initiated at a lower dose, gradually increased based on tolerance and clinical response. For specific dosing information, please refer to the BNF.

Mechanism of action

The mechanism of action of dimethyl fumarate involves its conversion to monomethyl fumarate (MMF). MMF up-regulates the Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway, which is activated in response to oxidative stress, and suppresses pro-inflammatory gene expression through the inhibition of nuclear factor kappa B. Additionally, MMF acts as a nicotinic acid receptor agonist, influencing immune cell composition and function, leading to a reduction in central nervous system infiltration and a shift from a pro-inflammatory to an anti-inflammatory immune phenotype.

Pharmacodynamics

Dimethyl fumarate exhibits anti-inflammatory and cytoprotective effects, which are particularly relevant in the context of multiple sclerosis. Although its precise physiological effects are not fully understood, it has been associated with the modulation of immune responses, potentially lowering the risk of relapse in multiple sclerosis patients. However, treatment with dimethyl fumarate can lead to serious adverse effects, including progressive multifocal leukoencephalopathy (PML), opportunistic infections, and severe lymphopenia.

Pharmacokinetics

Dimethyl fumarate is rapidly absorbed after oral administration, with peak plasma concentrations reached within hours. The drug is extensively metabolized to its active form, monomethyl fumarate, which is primarily eliminated via renal excretion. The pharmacokinetics may be influenced by factors such as liver function and concurrent medications. Monitoring of lymphocyte counts is recommended during treatment due to the risk of lymphopenia.

Contra-indications

• Severe lymphopenia (lymphocyte count below 0.5 x 10^9/litre)
• Active infection
• Severe active gastro-intestinal disease

Adverse effects

• Progressive multifocal leukoencephalopathy (PML)
• Lymphopenia
• Serious opportunistic infections
• Liver injury
• Anaphylaxis
• Angioedema
• Decreased leukocyte count
• Constipation
• Diarrhea
• Feeling hot
• Gastrointestinal discomfort
• Fatigue
• Eosinophilia

Interactions

• Live vaccines (unknown interaction, increases risk of generalized infection, possibly life-threatening)

Precautions

• Monitor lymphocyte counts at least every 3 months during treatment
• Re-evaluate treatment in patients with sustained moderate reductions of absolute lymphocyte counts (between 0.5 and 0.8 x 10^9/litre) for longer than 6 months
• Patients should be vigilant for new or worsening neurological or psychiatric symptoms

Pregnancy

There are limited data on the use of dimethyl fumarate in pregnancy. Caution is advised.

Breast-feeding

It is not known whether dimethyl fumarate is excreted in human milk. Caution is advised.

Storage

Store at room temperature, away from moisture and heat.

Formulations

• Dimethyl fumarate 120 mg and 240 mg delayed-release capsules

Indications

• Relapsing forms of multiple sclerosis
• Multiple sclerosis exacerbation

Dosage

Children: Refer to the BNF for Children for specific dosage recommendations for paediatric patients.

Adults: Refer to the BNF for specific dosage recommendations for adults.

Mechanism of action

Dimethyl fumarate is thought to activate the Nrf2 pathway, which leads to the induction of antioxidant proteins and a subsequent reduction in oxidative stress. This activation may also promote an anti-inflammatory response and modulate immune system activity, contributing to its beneficial effects in conditions such as multiple sclerosis.

Pharmacodynamics

Dimethyl fumarate exhibits immunomodulatory properties, influencing T-cell activation and promoting a shift from pro-inflammatory to anti-inflammatory immune responses. This modulation can help reduce the inflammatory processes associated with autoimmune diseases like multiple sclerosis. Additionally, the drug is associated with increased production of neuroprotective factors and a decrease in neuroinflammation.

Pharmacokinetics

Dimethyl fumarate is rapidly absorbed after oral administration, with peak plasma concentrations occurring within a few hours. It undergoes extensive first-pass metabolism, primarily converting to its active metabolite, monomethyl fumarate. The elimination half-life is approximately 30 minutes to 2 hours. Dimethyl fumarate and its metabolites are primarily excreted in the urine. Its pharmacokinetics may be influenced by food intake, with higher bioavailability observed when taken with meals.

Interactions

• live vaccines + dimethylfumarate: Unknown (increases risk of generalised infection (possibly life-threatening))

Indications

• Alcohol use disorder
• Acute alcohol intoxication
• Antiseptic for skin disinfection

Mechanism of action

Ethanol affects the brain’s neurons in several ways. It alters their membranes, ion channels, enzymes, and receptors. Ethanol binds directly to the receptors for acetylcholine, serotonin, GABA, and NMDA receptors for glutamate. The sedative effects are mediated through binding to GABA receptors and glycine receptors, while also inhibiting NMDA receptor functioning. As an anti-infective, ethanol acts as an osmolyte, disrupting the osmotic balance across cell membranes. The acute effects result from competitive inhibition of glycine binding to NMDA receptors, leading to disrupted glutamatergic neurotransmission.

Pharmacodynamics

Ethanol produces cellular injury through dehydration and precipitation of cytoplasm, contributing to its bactericidal and antifungal actions. It can lead to neuritis and nerve degeneration when injected near nerve tissues. Up to 98% of ethanol in the body is oxidized, primarily by the hepatic enzyme alcohol dehydrogenase. Its modulation of neurotransmitter receptors, particularly GABA and NMDA, leads to its sedative properties and potential for developing tolerance with chronic use.

Pharmacokinetics

Ethanol is readily absorbed from the gastrointestinal tract and distributed throughout the body. It has a volume of distribution of approximately 0.5 to 0.6 L/kg. Ethanol is metabolized predominantly in the liver by alcohol dehydrogenase to acetaldehyde, which is further oxidized to acetic acid by aldehyde dehydrogenase. The elimination half-life of ethanol varies but is generally around 4 to 5 hours. Factors such as age, sex, body weight, and genetic variability can influence ethanol metabolism.

Contra-indications

• Hypersensitivity to ethanol
• Acute alcohol intoxication
• Severe liver disease
• Pregnancy (in non-medicinal use)
• Severe pancreatitis
• Severe head injury or intracranial bleeding

Adverse effects

• Dizziness
• Nausea
• Vomiting
• Headache
• Sedation
• Cognitive impairment
• Respiratory depression
• Hypotension
• Gastrointestinal bleeding
• Alcohol withdrawal syndrome

Interactions

• CNS depressants (e.g., benzodiazepines, opioids) may enhance sedative effects
• Disulfiram may cause unpleasant reactions when taken with ethanol
• Acetaminophen may increase hepatic toxicity when used with ethanol
• Warfarin may have altered effects when used with ethanol

Precautions

• Caution in patients with a history of alcohol abuse
• Use with caution in patients with hepatic impairment
• Monitor for signs of respiratory depression
• Consider potential for addiction and withdrawal symptoms
• Use in moderation in older adults due to increased sensitivity

Pregnancy

Ethanol should be avoided during pregnancy due to the risk of fetal alcohol spectrum disorders.

Breast-feeding

Ethanol can pass into breast milk; breastfeeding should be avoided for a minimum of 2 hours after consumption.

Storage

Store in a cool, dry place away from light. Keep tightly closed and out of reach of children.

Formulations

• Oral solutions
• Topical antiseptics
• Intravenous formulations
• Medicinal tinctures

Indications

• Loss of appetite
• Dyspepsia
• Gastrointestinal disorders
• Digestive aid
• Bloating

Dosage

Children: Refer to established herbal guidelines, as specific dosing may vary based on preparation and indication.

Adults: Refer to established herbal guidelines, as specific dosing may vary based on preparation and indication.

Mechanism of action

The primary mechanism of action of gentian is attributed to its bitter compounds, which stimulate the taste receptors in the mouth and gastrointestinal tract. This stimulation increases the secretion of digestive juices, including saliva, gastric acid, and bile, thereby enhancing digestion and appetite. The presence of secoiridoids may also exert anti-inflammatory and antioxidant effects, contributing to its overall benefits.

Pharmacodynamics

Gentian exhibits pharmacodynamic effects primarily through its bitter principles that promote digestive processes. These compounds increase gastrointestinal motility and enhance nutrient absorption by stimulating the secretion of digestive enzymes. Gentian's potential effects on appetite regulation may also involve central nervous system pathways, although this mechanism is less well understood.

Pharmacokinetics

The pharmacokinetics of gentian are not extensively characterized due to its herbal nature. However, it is generally assumed that the active compounds are absorbed in the gastrointestinal tract after oral administration. The metabolism and excretion pathways remain largely undefined, given the complexity of the herbal preparation and the variability in individual responses.

Pregnancy

The safety of gentian during pregnancy has not been established. Use should be avoided unless deemed necessary by a healthcare professional.

Breast-feeding

Limited information is available on the excretion of gentian in breast milk. Caution is advised when administering to breastfeeding mothers.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Indications

• Severe infections caused by gram-negative bacteria
• Complicated urinary tract infections
• Bacterial sepsis
• Endocarditis caused by susceptible organisms

Dosage

Children: Dosing in children is also weight-based and varies by indication. Refer to the BNF for Children for specific dosing recommendations.

Adults: Dosage varies significantly based on the infection severity and type, renal function, and the specific bacterial susceptibility. Refer to clinical guidelines or the BNF for precise dosing.

Mechanism of action

Gram works by inhibiting bacterial protein synthesis. It binds to the 30S ribosomal subunit of the bacteria, causing misreading of the mRNA and ultimately preventing the synthesis of essential proteins necessary for bacterial growth and replication.

Pharmacodynamics

The pharmacodynamics of Gram include its bactericidal activity against susceptible bacteria. The drug shows concentration-dependent killing, meaning that higher drug concentrations correlate with greater bactericidal effects. The post-antibiotic effect is noted, where bacterial growth is inhibited even after the drug concentration falls below the minimum inhibitory concentration (MIC).

Pharmacokinetics

Gram is usually administered parenterally (intravenously or intramuscularly), and its absorption can vary based on the route of administration. It is distributed widely in body fluids and tissues, although it does not penetrate well into the central nervous system. The drug is primarily eliminated through the kidneys, and its half-life may be prolonged in patients with renal impairment. Monitoring of drug levels may be necessary to avoid toxicity.

Adverse effects

• Nausea
• Vomiting
• Diarrhea
• Abdominal pain
• Allergic reactions
• Rash
• Renal dysfunction

Precautions

• Use with caution in patients with renal impairment
• Monitor renal function during therapy
• Assess for potential allergic reactions

Pregnancy

Use only if the potential benefit justifies the potential risk to the fetus. Consult with a healthcare provider.

Breast-feeding

Use with caution, as it may be excreted in breast milk. Consult with a healthcare provider.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Dosage

Children: Refer to specific medication guidelines for appropriate dosing in paediatric patients, as this can vary based on the active ingredient and therapeutic indication.

Adults: Refer to specific medication guidelines for appropriate dosing, as this can vary based on the active ingredient and therapeutic indication.

Mechanism of action

Liquified formulations may enhance the solubility and bioavailability of the active pharmaceutical ingredients (APIs), allowing for quicker absorption in the gastrointestinal tract. This mechanism is particularly beneficial for drugs with poor water solubility, improving their overall therapeutic effects.

Pharmacodynamics

The pharmacodynamic effects of liquified medications depend on the specific active ingredients within the formulation. Generally, liquified forms can lead to faster onset of action due to enhanced absorption rates. The therapeutic effects will vary based on the drug's mechanism of action, receptor interaction, and physiological pathways it influences.

Pharmacokinetics

The pharmacokinetics of liquified medications are influenced by the formulation's liquid state, which may lead to improved dissolution and absorption rates compared to solid forms. The distribution, metabolism, and excretion of the active ingredients will depend on their chemical properties and the body's physiological processes. Liquified medications may exhibit altered half-lives and bioavailability profiles compared to their solid counterparts.

Pregnancy

Safety during pregnancy has not been established. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Caution is advised when administering to breastfeeding mothers, as the effects on a nursing infant are unknown.

Storage

Store in a cool, dry place away from light. Ensure that the container is tightly closed.

Indications

• Dry skin
• Chapped lips
• Minor skin irritations
• Eczema
• Psoriasis
• Protection of minor cuts and abrasions

Dosage

Children: Apply as needed to affected area, typically 1-3 times daily depending on the severity of the condition.

Adults: Apply as needed to affected area, typically 1-3 times daily depending on the severity of the condition.

Mechanism of action

Petroleum acts as an occlusive agent when applied to the skin, creating a barrier that reduces water evaporation. This helps to maintain skin hydration and protect damaged or irritated skin. The hydrocarbons in petroleum can also have a soothing effect on the skin and may help in the healing of minor abrasions.

Pharmacodynamics

The primary pharmacodynamic action of petroleum is its ability to form a protective film over the skin, which aids in moisture retention. It does not penetrate deeply into the skin and primarily acts at the stratum corneum level. This mechanism makes it effective for treating dry skin conditions and preventing transepidermal water loss.

Pharmacokinetics

Petroleum is not systemically absorbed through the skin when used topically, hence it has a low bioavailability. Its effects are localized to the area of application. The onset of action is immediate upon application, and the duration of effect can last for several hours, depending on the surface area covered and the amount applied.

Adverse effects

• Skin irritation
• Allergic reactions
• Gastrointestinal disturbances if ingested

Precautions

• Avoid contact with open wounds or mucous membranes
• Use with caution in patients with a history of skin sensitivities

Pregnancy

Considered safe when used topically, but ingestion should be avoided.

Breast-feeding

Generally regarded as safe for topical use, but ingestion should be avoided.

Storage

Store in a cool, dry place away from direct sunlight and heat sources.

Formulations

• Topical ointments
• Creams
• Lotions

Dosage

Children: Dosage information for phthalates is not applicable, as they are not intended for therapeutic use in pediatrics.

Adults: Dosage information for phthalates is typically not specified as they are not used therapeutically but rather as industrial chemicals.

Mechanism of action

Phthalates primarily act as plasticizers by interfering with the polymerization process of PVC and other materials. They also have been shown to affect hormone signaling pathways, particularly those involving steroid hormones. The degradation pathways of phthalates in biological systems involve various enzymatic processes, leading to their conversion into less harmful metabolites.

Pharmacodynamics

Phthalates exhibit a range of pharmacodynamic effects, particularly concerning their role as endocrine disruptors. They can bind to hormone receptors, influencing the synthesis and activity of hormones such as testosterone and estrogen. This can lead to developmental and reproductive toxicity, as well as potential impacts on metabolic processes.

Pharmacokinetics

Phthalates are rapidly absorbed in the gastrointestinal tract, and their distribution varies based on their molecular weight and chemical structure. They are metabolized primarily in the liver, where they undergo hydrolysis and oxidation, leading to the formation of monoester metabolites. These metabolites are excreted primarily through urine. The half-life of phthalates can vary significantly depending on the specific compound and the individual's metabolism.

Pregnancy

There is limited information available regarding the safety of phthalates during pregnancy. Caution is advised in use and exposure.

Breast-feeding

Limited data available. Caution is advised regarding exposure.

Storage

Store in a cool, dry place, away from direct sunlight and moisture.

Dosage

Children: Refer to specific drug formulations and product labels as purified substances can vary widely in their use and dosing.

Adults: Refer to specific drug formulations and product labels as purified substances can vary widely in their use and dosing.

Mechanism of action

The mechanism of action for purified compounds varies widely depending on the specific substance. Generally, purified drugs exert their effects by interacting with specific biological targets, such as receptors, enzymes, or ion channels, leading to a desired therapeutic effect. This interaction can involve binding to receptors to activate or inhibit signaling pathways, modulating enzymatic activity, or altering physiological processes.

Pharmacodynamics

Pharmacodynamics describes the effects of a drug on the body and the relationship between drug concentration and effect. For purified drugs, this can involve dose-response relationships and the time course of their action. The purified form often enhances potency and reduces variability in response among patients, which can lead to more predictable therapeutic outcomes. The overall effect is determined by the drug's affinity for its target, the efficacy of the drug-receptor interaction, and the downstream signaling pathways activated as a result of this interaction.

Pharmacokinetics

Pharmacokinetics involves the absorption, distribution, metabolism, and excretion (ADME) of a drug. For purified substances, absorption can be more efficient due to the absence of impurities that may affect solubility or stability. Distribution may also be enhanced, leading to higher bioavailability. Metabolism can be influenced by the structure of the purified compound, as it may be metabolized more readily by liver enzymes. Excretion typically occurs through the kidneys or liver, depending on the molecular characteristics of the purified drug.

Pregnancy

Consult with a healthcare professional, as the safety of purified forms of medications during pregnancy may vary depending on the specific substance.

Breast-feeding

Consult with a healthcare professional, as the safety of purified forms of medications during breastfeeding may vary depending on the specific substance.

Storage

Store in a cool, dry place, away from light and moisture, and keep out of reach of children.

Dosage

Children: Refer to specific product information for details on use as a coloring agent in formulations.

Adults: Refer to specific product information for details on use as a coloring agent in formulations.

Mechanism of action

The mechanism of action for violet dyes generally involves their ability to absorb specific wavelengths of light, which contributes to their coloring properties. In the context of pharmacology, they do not possess therapeutic effects but rather serve a functional role in drug formulation.

Pharmacodynamics

As a coloring agent, violet dyes do not exhibit pharmacodynamic properties associated with therapeutic agents. They do not interact with biological targets in the manner that active pharmaceutical ingredients do, and their primary role is to provide color rather than therapeutic efficacy.

Pharmacokinetics

Violet dyes, being non-active agents, do not undergo typical pharmacokinetic processes such as absorption, distribution, metabolism, and excretion in the same way that active drugs do. Their presence in formulations is primarily for aesthetic purposes, and they are typically excreted unchanged.

Pregnancy

Safety not established; consult healthcare provider.

Breast-feeding

Safety not established; consult healthcare provider.

Storage

Store in a cool, dry place, away from light.

Mechanism of action

The mechanism of action of dimethyl fumarate in multiple sclerosis is not well understood. It is thought to involve dimethyl fumarate degradation to its active metabolite, monomethyl fumarate (MMF). Both dimethyl fumarate and MMF up-regulate the Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway that is activated in response to oxidative stress. Dimethyl fumarate also suppresses pro-inflammatory genes through nuclear factor kappa B inhibition. Additionally, MMF acts as an agonist at the nicotinic acid receptor, but the relevance of this is unknown. It has been suggested that dimethyl fumarate exerts its immunomodulatory effects through changes in the composition and phenotype of immune cells. It reduces CNS infiltration and alters the composition of all lymphocyte subpopulations, especially for cytotoxic and effector T cells. This causes a shift from a mainly pro-inflammatory phenotype to an anti-inflammatory one. Dimethyl fumarate (DMF) is a fumaric acid ester that is used to treat psoriasis and multiple sclerosis. Recently, DMF was found to exhibit anti-tumor effects. However, the molecular mechanisms underlying these effects have not been elucidated. In this study, we investigated the mechanism of DMF-induced apoptosis in different human hematopoietic tumor cell lines. We found that DMF induced apoptosis in different human hematopoietic tumor cell lines but it did not affect the normal human B lymphocyte cell line RPMI 1788. We also observed a concurrent increase in caspase-3 activity and in the number of Annexin-V-positive cells. Furthermore, an examination of the survival signals, which are activated by apoptotic stimuli, revealed that DMF significantly inhibited nuclear factor-kB (NF-kB) p65 nuclear translocation. In addition, DMF suppressed B-cell lymphoma extra-large (Bcl-xL) and X-linked inhibitor of apoptosis (XIAP) expression whereas Bcl-2, survivin, Bcl-2-associated X protein (Bax), and Bim levels did not change. These results indicated that DMF induced apoptosis by suppressing NF-kB activation, and Bcl-xL and XIAP expression. These findings suggested that DMF might have potential as an anticancer agent that could be used in combination therapy with other anticancer drugs for the treatment of human hematopoietic tumors. Oxidative stress plays a crucial role in many neurodegenerative conditions such as Alzheimer's disease, amyotrophic lateral sclerosis and Parkinson's as well as Huntington's disease. Inflammation and oxidative stress are also thought to promote tissue damage in multiple sclerosis (MS). Recent data point at an important role of anti-oxidative pathways for tissue protection in chronic-progressive MS, particularly involving the transcription factor nuclear factor (erythroid-derived 2)-related factor 2 (Nrf2). ... In vitro, application of dimethylfumarate (DMF) leads to stabilization of Nrf2, activation of Nrf2-dependent transcriptional activity and abundant synthesis of detoxifying proteins. Furthermore, application of FAE involves direct modification of the inhibitor of Nrf2, Kelch-like ECH-associated protein 1. On cellular levels, the application of FAE enhances neuronal survival and protects astrocytes against oxidative stress. Increased levels of Nrf2 are detected in the central nervous system of DMF treated mice suffering from experimental autoimmune encephalomyelitis (EAE), an animal model of MS. In EAE, DMF ameliorates the disease course and improves preservation of myelin, axons and neurons. Finally, Nrf2 is also up-regulated in the spinal cord of autopsy specimens from untreated patients with MS, probably as part of a naturally occurring anti-oxidative response. In summary, oxidative stress and anti-oxidative pathways are important players in MS pathophysiology and constitute a promising target for future MS therapies like FAE. Multiple sclerosis (MS) is the most common multifocal inflammatory demyelinating disease of the central nervous system (CNS). Due to the progressive neurodegen

Pharmacodynamics

The physiological effects of dimethyl fumarate on the body are not well understood. It has anti-inflammatory and cytoprotective effects, likely involved in its actions in multiple sclerosis (MS) patients. Dimethyl fumarate does not cause clinically significant QT interval prolongation. However, cases of progressive multifocal leukoencephalopathy, serious opportunistic infections, lymphopenia and liver injury have been reported in MS patients treated with this drug. Dimethyl fumarate may also cause anaphylaxis and angioedema.

Mechanism of action

Ethanol affects the brain’s neurons in several ways. It alters their membranes as well as their ion channels, enzymes, and receptors. Alcohol also binds directly to the receptors for acetylcholine, serotonin, GABA, and the NMDA receptors for glutamate. The sedative effects of ethanol are mediated through binding to GABA receptors and glycine receptors (alpha 1 and alpha 2 subunits). It also inhibits NMDA receptor functioning. In its role as an anti-infective, ethanol acts as an osmolyte or dehydrating agent that disrupts the osmotic balance across cell membranes. ... Ethanol is known to affect a large number of membrane proteins that participate in signaling pathways such as neurotransmitter receptors, enzymes, and ion channels, and there is extensive evidence that ethanol interacts with a variety of neurotransmitters. The major actions of ethanol involve enhancing the inhibitory effects of gamma-aminobutyric acid (GABA) at GABAa receptors and blockade of the N-methyl-D-aspartate (NMDA) subtype of glutamate, an excitatory amine acid (EAA) receptor. Animal studies indicate that the acute effects of ethanol result from competitive inhibition of glycine binding to NMDA receptor and disruption of glutamatergic neurotransmission by inhibiting the response of the NMDA receptor. Persistent glycine antagonism and attenuation of glutamatergic neurotransmission by chronic ethanol exposure results in tolerance to ethanol by enhancing EAA neurotransmission and NMDA receptor upregulation. The latter appears to involve selective increases in NMDA R2B subunit concentrations and other molecular changes in specific brain loci. The abrupt withdrawal of ethanol thus produces a hyperexcitable state that leads to the ethanol withdrawal syndrome and excitotoxic neuronal death. GABA-mediated inhibition, which normally acts to limit excitation, is eliminated during ethanol withdrawal syndrome and further intensifies this excitation. In addition, NMDA receptors function to inhibit the release of dopamine in the nucleus accumbens and mesolimbic structures, which modulate the reinforcing action of addictive xenobiotics such as ethanol. By inhibiting NMDA receptor activity, ethanol could increase dopamine release from the nucleus accumbens and ventral tegmental area and could thus create dependence. Chronic ethanol administration also results in tolerance, dependence, and an ethanol withdrawal syndrome, mediated, in part, by desensitization and or downregulation of GABAa receptors. The development of alcoholic ketoacidosis (AKA) requires that a combination of physical and physiologic events occur. The normal response to starvation and depletion of hepatic glycogen stores is for amino acids to be converted to pyruvate. Pyruvate can serve as a substrate for gluconeogenesis, be converted to acetyl-CoA, which can enter the Krebs cycle or can be utilized in various biosynthetic pathways (eg, fatty acid, ketone bodies, cholesterol, and acetylcholine) ... Ethanol metabolism generates NADH, resulting in an excess of reducing potential. This high redox state favors the conversion of pyruvate to lactate, diverting pyruvate from being a substrate for gluconeogenesis. To compensate for the lack of normal metabolic substrates, the body mobilizes fat from adipose tissue and increased fatty acid metabolism as an alternative source of energy. This response is mediated by a decrease in insulin and an increased secretion of glucagon, catecholamines, growth hormone, and cortisol. Fatty acid metabolism results in the formation of acetyl-CoA and it combines with the excess acetate that is generated from ethanol metabolism to form acetoacetate. Most of the acetoacetate is reduced to beta-hydroxybutyrate due to the excess reducing potential or high redox state of the cell. Volume depletion interferes with the renal elimination of acetoacetate and beta-hydroxybutyrate, and contributes to the acidosis. An elevated lactate concentration may result from shunting from pyruvate or

Pharmacodynamics

Alcohol produces injury to cells by dehydration and precipitation of the cytoplasm or protoplasm. This accounts for its bacteriocidal and antifungal action. When alcohol is injected in close proximity to nerve tissues, it produces neuritis and nerve degeneration (neurolysis). Ninety to 98% of ethanol that enters the body is completely oxidized. Ethanol is also used as a cosolvent to dissolve many insoluble drugs and to serve as a mild sedative in some medicinal formulations. Ethanol also binds to GABA, glycine, NMDA receptors and modulates their effects. Ethanol is also metabolised by the hepatic enzyme alcohol dehydrogenase.