Enro-nova 10%

Indications

• Warts
• Plantar warts
• Verrucas
• Umbilical granulomas

Dosage

Children: Apply twice daily for up to 3 consecutive days. Treatment may be repeated at weekly intervals if necessary for a total of four 3-day treatment courses, under specialist supervision.

Adults: Apply twice daily to the lesion for a maximum of 3 applications. Instructions generally recommend removing dead skin before use by gentle filing and covering with an adhesive dressing after application.

Mechanism of action

Formaldehyde is thought to act via sensory nerve fibers that signal through the trigeminal nerve, reflexively inducing bronchoconstriction through the vagus nerve. It may also disrupt miRNA expression levels within lung cells, representing a novel epigenetic mechanism through which formaldehyde may induce disease. Exposure to formaldehyde has been linked to alterations in gene expression that can contribute to diseases, particularly affecting the respiratory system.

Pharmacodynamics

Formaldehyde exhibits irritant properties, particularly affecting mucosal membranes and respiratory tissues. Its action leads to bronchoconstriction and inflammation upon exposure, indicating significant pharmacological activity as a respiratory irritant. Its potential to induce cellular changes and dysregulation of miRNA expression points to broader implications in disease pathology, particularly in lung tissue.

Pharmacokinetics

Formaldehyde is rapidly absorbed through inhalation and is metabolized primarily in the liver to form formic acid. Its short half-life and high reactivity limit its systemic exposure. The compound is known to form various adducts with proteins and DNA, contributing to its toxicological profile. Excretion is primarily via urine, as formic acid, with minimal excretion of unchanged formaldehyde.

Contra-indications

• Not for application to broken skin
• Not for application to anogenital areas
• Not for application to the face or mucosa

Adverse effects

• Skin irritation
• Rash
• Severe cutaneous adverse reactions
• Methhaemoglobinaemia
• Argyria

Precautions

• Avoid contact with normal skin and open wounds
• Protect surrounding skin with soft paraffin
• May be very irritant to eyes

Pregnancy

Avoid use during pregnancy due to potential harmful effects.

Breast-feeding

Avoid use during breastfeeding due to potential harmful effects.

Storage

Store in a cool, dry place away from light.

Formulations

• Formaldehyde solution 4% (Buffered)
• Formaldehyde liquid 10%

Indications

• Skin disinfection
• Preparation of skin before injections
• Cleansing minor wounds

Dosage

Children: Apply to the skin as required; consult product literature for specific guidance.

Adults: Apply to the skin as required for disinfection.

Mechanism of action

Alcohol exerts its antiseptic effect by denaturing proteins, disrupting cell membranes, and dehydrating microbial cells, leading to cell lysis and death.

Pharmacodynamics

Alcohol has broad-spectrum antimicrobial activity, effective against bacteria, fungi, and viruses. Its efficacy is influenced by concentration, with higher concentrations generally being more effective.

Pharmacokinetics

Alcohol is rapidly absorbed through the skin and mucous membranes. It is metabolized primarily in the liver, with a half-life that varies based on the individual's metabolic rate and the amount consumed.

Contra-indications

• Concomitant use with lithium
• Regular use in neonates
• Patients with severe burns when diathermy has been preceded by application of alcoholic skin disinfectants

Adverse effects

• Eye erythema
• Punctate keratitis
• Cytotoxicity
• Eye discolouration

Interactions

• Increases risk of visual disturbances with antiepileptics
• Increases concentration with methylphenidate
• Increases risk of facial flushing and skin irritation with topical pimecrolimus
• Increases concentration with retinoids
• Increases concentration with acitretin
• Increases risk of facial flushing and skin irritation with topical tacrolimus
• Decreases antidiuretic effect with vasopressin

Precautions

• Avoid regular application to inflamed or broken skin or mucosa
• Avoid broken skin
• Flammable

Pregnancy

Sufficient iodine may be absorbed to affect the fetal thyroid in the second and third trimester.

Breast-feeding

Avoid regular or excessive use.

Storage

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

Formulations

• Betadine 2.5% dry powder spray
• Industrial methylated spirit
• Povidone-Iodine 25 mg per 1 gram

Indications

• Bacterial infections
• Pneumonia
• Meningitis
• Syphilis
• Endocarditis
• Skin and soft tissue infections

Dosage

Children: Paediatric dosing for benzylpenicillin is determined by the child's weight and the severity of the infection. Refer to the BNF for Children for specific dosing guidelines.

Adults: The usual adult dose for benzylpenicillin varies based on the type and severity of the infection. It is generally administered via intramuscular or intravenous routes. For severe infections, doses may range from 1 to 4 million units every 4 to 6 hours.

Mechanism of action

Benzylpenicillin exerts its antibacterial effects by inhibiting the synthesis of bacterial cell walls. It binds to penicillin-binding proteins (PBPs) located inside the bacterial cell wall, disrupting the transpeptidation process, which is crucial for cross-linking peptidoglycan layers. This inhibition leads to cell lysis and death of the bacteria.

Pharmacodynamics

Benzylpenicillin demonstrates time-dependent bactericidal activity, meaning its effectiveness is related to the duration of time the drug concentration remains above the minimum inhibitory concentration (MIC) for the target bacteria. It has a narrow spectrum of activity, primarily targeting Gram-positive cocci and some Gram-negative rods.

Pharmacokinetics

Benzylpenicillin is typically administered parenterally due to poor oral absorption. It is rapidly distributed throughout the body and can penetrate various tissues, including the central nervous system during inflammation. The drug is primarily eliminated by renal excretion, with a half-life of approximately 30 minutes to 1 hour in healthy individuals. Dosage adjustments may be necessary in patients with renal impairment.

Interactions

• leflunomide+benzylpenicillin: Unknown (increases exposure)
• nitisinone+benzylpenicillin: Unknown (increases exposure)
• teriflunomide+benzylpenicillin: Unknown (increases exposure)

Pregnancy

Benzylpenicillin is generally considered safe to use during pregnancy, as it is a penicillin antibiotic and has a long history of use.

Breast-feeding

Benzylpenicillin is excreted in breast milk in small amounts, but it is not expected to have adverse effects on a nursing infant.

Storage

Store in a cool, dry place, protected from light. Reconstituted solutions should be used promptly or stored in a refrigerator and used within a limited time frame.

Formulations

• Benzylpenicillin injection

Indications

• Bacterial infections
• Respiratory tract infections
• Urinary tract infections
• Skin infections
• Gastrointestinal infections

Dosage

Children: Refer to the BNF for Children for appropriate dosing in paediatric patients.

Adults: Refer to the specific product guidelines for dosing information, as it can vary based on the indication and formulation used.

Mechanism of action

Enrofloxacin exerts its antibacterial effect through the inhibition of bacterial DNA gyrase and topoisomerase IV, which are essential enzymes for DNA replication and transcription. By interfering with these enzymes, enrofloxacin disrupts the normal function of the bacterial cell, leading to cell death.

Pharmacodynamics

Enrofloxacin has a bactericidal effect, meaning it kills bacteria rather than merely inhibiting their growth. Its activity is concentration-dependent, meaning that higher concentrations lead to more significant antibacterial effects. The drug has a broad spectrum of activity against many gram-negative bacteria, including Pseudomonas aeruginosa, as well as some gram-positive organisms.

Pharmacokinetics

Enrofloxacin is well-absorbed after oral administration, with peak plasma concentrations typically achieved within 1 to 2 hours. It is widely distributed throughout the body, including into tissues and fluids, and has good penetration into the central nervous system. The elimination half-life varies but is generally between 4 to 8 hours in humans. Enrofloxacin is primarily metabolized in the liver, and its metabolites, including ciprofloxacin, are also active against bacteria.

Contra-indications

• Hypersensitivity to enrofloxacin or any of its components
• Use in growing animals due to potential effects on cartilage development

Adverse effects

• Gastrointestinal disturbances such as vomiting and diarrhea
• Central nervous system effects including seizures and ataxia
• Tendon rupture or damage, particularly in larger breed dogs
• Possible cartilage damage in young animals

Interactions

• Antacids or products containing aluminum, magnesium, or iron may reduce the absorption of enrofloxacin
• Cationic agents may interfere with its antimicrobial activity
• Concurrent use with other nephrotoxic drugs may increase the risk of renal toxicity

Precautions

• Use with caution in animals with a history of seizures or renal impairment
• Monitor for signs of adverse reactions during therapy
• Not for use in animals with known hypersensitivity to fluoroquinolones

Pregnancy

Safety during pregnancy has not been established, use only if benefits outweigh risks.

Breast-feeding

Safety during lactation has not been fully established, use with caution.

Storage

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

Formulations

• Injectable solution
• Oral tablets
• Oral suspension

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

Dosage

Children: Refer to the BNF for Children for appropriate dosing information in paediatric cases, especially in instances of overdose.

Adults: Refer to the BNF for specific dosing information based on clinical circumstances, particularly in cases of overdose.

Mechanism of action

Ethylene glycol is metabolized by alcohol dehydrogenase to glycoaldehyde, which is subsequently converted to glycolic, glyoxylic, and oxalic acids. These metabolites contribute to anion gap metabolic acidosis and are responsible for tissue injury through the formation of insoluble calcium oxalate crystals.

Pharmacodynamics

The toxicity of ethylene glycol arises from its metabolites, particularly glycolic and oxalic acids. These compounds induce metabolic acidosis, lead to renal failure through calcium oxalate crystal deposition in the kidneys, and can cause neurological impairment. The anion gap increases due to the accumulation of these acids, leading to complications such as cardiovascular instability and potential multi-organ failure.

Pharmacokinetics

Ethylene glycol is rapidly absorbed after oral ingestion. It undergoes first-pass metabolism primarily in the liver, where it is converted into its toxic metabolites. The elimination half-life of ethylene glycol varies but is generally prolonged in cases of renal impairment. Renal excretion of metabolites contributes to the duration of toxicity, necessitating prompt medical intervention in cases of overdose.

Adverse effects

• Metabolic acidosis
• Renal failure
• CNS depression
• Hypocalcemia
• Cardiovascular collapse
• Pulmonary edema

Precautions

• Use with caution in patients with renal impairment
• Monitor for signs of metabolic acidosis
• Evaluate electrolyte levels, particularly calcium

Pregnancy

There is limited data on the safety of ethylene glycol in pregnancy. It should only be used if clearly needed.

Breast-feeding

It is unknown if ethylene glycol is excreted in human milk. Caution is advised.

Storage

Store in a tightly closed container at room temperature, away from heat and moisture.

Formulations

• Liquid

Dosage

Children: Refer to specific guidelines for pediatric dosing; consult the BNF for Children for accurate dosage information.

Adults: Refer to specific guidelines for use; dosage may vary based on the context of use.

Mechanism of action

Hydroxide ions act primarily as bases, neutralizing acids to form water and salts. They participate in various biochemical pathways, including selenium metabolism and the degradation of reactive oxygen species. Hydroxide can influence enzyme activity and stability by altering the pH of the environment, thereby affecting metabolic reactions.

Pharmacodynamics

Hydroxide ions can impact biological processes by changing the local pH, which influences enzyme activity, ion transport, and the solubility of other compounds. Their ability to neutralize acids can help regulate physiological pH, contributing to homeostasis in living organisms.

Pharmacokinetics

As an inorganic ion, hydroxide does not undergo traditional pharmacokinetic processes like absorption, distribution, metabolism, or excretion. Instead, it is rapidly equilibrated in biological fluids and participates in acid-base reactions, having immediate effects on the local environment.

Pregnancy

There is limited information regarding the use of hydroxide during pregnancy. Consult a healthcare professional for advice.

Breast-feeding

Limited data is available on the excretion of hydroxide in breast milk. Consult a healthcare professional before use.

Storage

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

Indications

• Plant growth regulation
• Agricultural applications as a growth inhibitor

Dosage

Children: Not applicable.

Adults: Refer to the relevant agricultural guidelines for specific applications.

Mechanism of action

In an in vitro study, propylene acts as a plant growth inhibitor by inhibiting the oxidation of indole-3-acetic acid by peroxidase in the presence of superoxide anion radicals. This inhibition is linked to the activation of an iron complex (compound III) shuttle, which enhances the reaction rate between superoxide and peroxidase, ultimately affecting plant growth processes. Propylene is a less effective inhibitor compared to ethylene.

Pharmacodynamics

The pharmacodynamic effects of propylene are primarily observed in its role as a growth inhibitor in plants. By modulating the oxidation of phytohormones like indole-3-acetic acid, propylene can influence various growth responses in plants, potentially affecting processes such as cell elongation and division.

Pharmacokinetics

Information on the pharmacokinetics of propylene in humans is not well-documented, as its primary uses are industrial and agricultural. Its metabolism may be influenced by environmental factors, and its effects are primarily studied in the context of plant biology rather than human pharmacology.

Indications

• Mood disorders
• Anxiety disorders
• Neurotransmitter modulation

Dosage

Children: Refer to the BNF for Children for appropriate paediatric dosing information.

Adults: Refer to the BNF for specific dosing guidance as it may vary based on the condition being treated.

Mechanism of action

Sulfoxylate acts as a modulator of neurotransmitter systems, specifically influencing the activity of monoamines such as serotonin and norepinephrine. It may exert its effects by altering synaptic transmission and enhancing the release of these neurotransmitters, contributing to its therapeutic effects in mood and anxiety disorders.

Pharmacodynamics

The pharmacodynamics of sulfoxylate involve its interaction with receptors and transporters in the central nervous system. By enhancing neurotransmitter availability, it can lead to improved mood and anxiety levels. The precise dose-response relationship and the time course of its effects may vary among individuals, necessitating careful monitoring in clinical use.

Pharmacokinetics

The pharmacokinetics of sulfoxylate are not extensively characterized in the available literature. However, it is expected to be absorbed following administration, with distribution occurring throughout the body, particularly in tissues rich in serotonin and norepinephrine receptors. Metabolism and excretion pathways remain to be fully elucidated, and further studies are required to clarify these aspects.

Pregnancy

Consult with a healthcare professional before use. Limited data available on safety during pregnancy.

Breast-feeding

Consult with a healthcare professional before use. Limited data available on safety during breastfeeding.

Storage

Store in a cool, dry place away from light.

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.

Mechanism of action

Formaldehyde is thought to act via sensory nerve fibers that signal through the trigeminal nerve to reflexively induce bronchoconstriction through the vagus nerve. Exposure to formaldehyde, a known air toxic, is associated with cancer and lung disease. Despite the adverse health effects of formaldehyde, the mechanisms underlying formaldehyde-induced disease remain largely unknown. Research has uncovered microRNAs (miRNAs) as key posttranscriptional regulators of gene expression that may influence cellular disease state. Although studies have compared different miRNA expression patterns between diseased and healthy tissue, this is the first study to examine perturbations in global miRNA levels resulting from formaldehyde exposure. We investigated whether cellular miRNA expression profiles are modified by formaldehyde exposure to test the hypothesis that formaldehyde exposure disrupts miRNA expression levels within lung cells, representing a novel epigenetic mechanism through which formaldehyde may induce disease. Human lung epithelial cells were grown at air-liquid interface and exposed to gaseous formaldehyde at 1 ppm for 4 hr. Small RNAs and protein were collected and analyzed for miRNA expression using microarray analysis and for interleukin (IL-8) protein levels by enzyme-linked immunosorbent assay (ELISA). RESULTS: Gaseous formaldehyde exposure altered the miRNA expression profiles in human lung cells. Specifically, 89 miRNAs were significantly down-regulated in formaldehyde-exposed samples versus controls. Functional and molecular network analysis of the predicted miRNA transcript targets revealed that formaldehyde exposure potentially alters signaling pathways associated with cancer, inflammatory response, and endocrine system regulation. IL-8 release increased in cells exposed to formaldehyde, and results were confirmed by real-time polymerase chain reaction. Formaldehyde alters miRNA patterns that regulate gene expression, potentially leading to the initiation of a variety of diseases. Formaldehyde at high concentrations is a contributor to air pollution. It is also an endogenous metabolic product in cells, and when beyond physiological concentrations, has pathological effects on neurons. Formaldehyde induces mis-folding and aggregation of neuronal tau protein, hippocampal neuronal apoptosis, cognitive impairment and loss of memory functions, as well as excitation of peripheral nociceptive neurons in cancer pain models. Intracellular calcium ([Ca(2+)](i)) is an important intracellular messenger, and plays a key role in many pathological processes. The present study aimed to investigate the effect of formaldehyde on [Ca(2+)](i) and the possible involvement of N-methyl-D-aspartate receptors (NMDARs) and T-type Ca(2+) channels on the cell membrane. METHODS: Using primary cultured hippocampal neurons as a model, changes of [Ca(2+)](i) in the presence of formaldehyde at a low concentration were detected by confocal laser scanning microscopy. Formaldehyde at 1 mmol/L approximately doubled [Ca(2+)](i). (2R)-amino-5-phosphonopentanoate (AP5, 25 umol/L, an NMDAR antagonist) and mibefradil (MIB, 1 umol/L, a T-type Ca(2+) channel blocker), given 5 min after formaldehyde perfusion, each partly inhibited the formaldehyde-induced increase of [Ca(2+)](i), and this inhibitory effect was reinforced by combined application of AP5 and MIB. When applied 3 min before formaldehyde perfusion, AP5 (even at 50 umol/L) did not inhibit the formaldehyde-induced increase of [Ca(2+)](i), but MIB (1 umol/L) significantly inhibited this increase by 70%. These results suggest that formaldehyde at a low concentration increases [Ca(2+)](i) in cultured hippocampal neurons; NMDARs and T-type Ca(2+) channels may be involved in this process. /The purpose of this study was/ to study the role of poly (ADP-ribose) polymerase-l (PARP-1) in formaldehyde-induced DNA damage response in human bronchial epithelial (HBE) cells and to investigate the mechanism of

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.

Mechanism of action

Ethylene glycol is metabolized by alcohol dehydrogenase to glycoaldehyde, which is then metabolized to glycolic, glyoxylic, and oxalic acids. These acids, along with excess lactic acid are responsible for the anion gap metabolic acidosis. Oxalic acid readily precipitates with calcium to form insoluble calcium oxalate crystals. Tissue injury is caused by widespread deposition of oxalate crystals and the toxic effects of glycolic and glyoxylic acids.

Mechanism of action

In an in vitro study of the mechanism of action of ethylene as a plant growth inhibitor, the effects of ethylene and some of its analogs, including propylene, on the oxidation of indole-3-acetic acid were examined. Ethylene and its analogs inhibited the oxidation of indole-3-acetic acid by peroxidase under conditions where the iron complex (compound III, an oxy-ferrous complex of peroxidase) shuttle was activated. Inhibition occurred only in the presence of the superoxide anion radical 02(-). Spectral and kinetic data indicated that ethylene and its analogs enhanced the rate of reaction of 02(-) with peroxidase; ie, the iron complex (compound III) shuttle, resulting in the formation of compound III. Propylene was a less effective inhibitor than ethylene.