SILVERINE

Indications

• Bacterial infections
• Toxoplasmosis in pregnancy (in combination with pyrimethamine and folinic acid)
• Congenital toxoplasmosis (in combination with pyrimethamine and folinic acid)

Dosage

Children: For children aged 12–17 years, the recommended dose is 1 g three times a day until delivery for toxoplasmosis in pregnancy. For other specific conditions, refer to the BNF for Children for detailed dosing guidelines.

Adults: For adults, the typical dosing for bacterial infections can vary, and it is essential to refer to the BNF for specific recommendations based on the condition being treated. Generally, dosage adjustments may be necessary in renal impairment.

Mechanism of action

Sulfadiazine acts as a competitive inhibitor of the bacterial enzyme dihydropteroate synthetase, blocking the conversion of para-aminobenzoic acid (PABA) to folic acid. This inhibition is crucial for bacterial growth and reproduction, as folic acid is vital for nucleic acid synthesis.

Pharmacodynamics

Sulfadiazine is a synthetic bacteriostatic antibiotic effective against many gram-positive and some gram-negative organisms. It inhibits bacterial multiplication by interfering with folic acid metabolism. Resistance to sulfadiazine usually implies resistance to all sulfonamides, as they share similar mechanisms of action.

Pharmacokinetics

Sulfadiazine is well absorbed when administered orally, with high tissue distribution. It achieves significant concentrations in various bodily fluids, including pleural and synovial fluids. While it is effective, its absorption can be affected by the presence of pus, which can inhibit its antibacterial action. Renal function can influence its clearance, necessitating dose adjustments in cases of impaired renal function.

Contra-indications

• Acute porphyrias

Adverse effects

• Agranulocytosis
• Aplastic anaemia
• Haemolytic anaemia
• Decreased appetite
• Ataxia
• Back pain
• Blood disorders
• Cough
• Crystaluria
• Cyanosis
• Depression
• Diarrhoea
• Dizziness
• Drowsiness
• Dyspnoea
• Eosinophilia
• Erythema nodosum
• Fatigue
• Fever
• Haematuria
• Hallucination
• Headache
• Hepatic disorders
• Hypoglycaemia
• Neutropenia
• Oral disorders
• Pancreatitis
• Photosensitivity reaction
• Skin reactions
• Thrombocytopenia
• Tinnitus
• Vertigo
• Vomiting

Interactions

• Sulfadiazine + antiepileptics: Moderate (increases concentration)
• Sulfadiazine + fosphenytoin: Moderate (increases concentration)
• Sulfadiazine + phenytoin: Moderate (increases concentration)

Precautions

• Caution in asthma
• Caution in blood disorders
• Caution in elderly patients
• Monitor blood counts on prolonged treatment
• Plasma concentration monitoring may be required in moderate to severe renal impairment

Pregnancy

Risk of neonatal haemolysis and methaemoglobinaemia in the third trimester; fear of increased risk of kernicterus in neonates appears to be unfounded.

Breast-feeding

Small risk of kernicterus in jaundiced infants and of haemolysis in G6PD-deficient infants.

Storage

Store in a cool, dry place away from light.

Formulations

• Solution for infusion
• Oral suspension

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

• Dry skin conditions
• Atopic dermatitis
• Psoriasis
• Eczema
• Skin hydration enhancement

Dosage

Children: Refer to the BNF for Children for specific dosing recommendations based on age and condition.

Adults: Refer to the specific product monograph, as dosing may vary based on formulation and condition being treated.

Mechanism of action

Cetomacrogol acts as a surfactant, reducing the surface tension between different substances. This property facilitates the formation of emulsions and enhances the solubility of hydrophobic substances in aqueous solutions. By providing a barrier on the skin, it helps to prevent transepidermal water loss, thereby maintaining skin hydration.

Pharmacodynamics

The pharmacodynamic properties of cetomacrogol are characterized by its ability to improve the consistency and stability of emulsions, allowing for better delivery of topical agents. Its moisturizing effects help to alleviate symptoms associated with dry skin conditions, such as scaling, itching, and cracking.

Pharmacokinetics

Cetomacrogol is not systemically absorbed when applied topically, as it primarily acts at the site of application. Its pharmacokinetic profile is characterized by local action with minimal risk of systemic effects. Due to its emulsifying properties, it enhances the penetration of active ingredients in topical formulations without significant metabolic transformation.

Pregnancy

There are no known adverse effects in pregnancy. However, it is advisable to use only when clearly needed.

Breast-feeding

Cetomacrogol is generally considered safe to use during breastfeeding, but consult a healthcare professional before use.

Storage

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

Formulations

• Cream
• Ointment
• Emulsion

Indications

• Dry skin conditions
• Eczema
• Psoriasis
• Irritated or inflamed skin
• As a base in topical formulations

Dosage

Children: Refer to specific product guidelines for paediatric use.

Adults: Apply as needed as a topical formulation. Refer to specific product guidelines for details.

Mechanism of action

Cetostearyl alcohol acts primarily as an emollient and emulsifying agent. It forms a barrier on the skin's surface, which helps to retain moisture and prevent transepidermal water loss. As an emulsifier, it stabilizes oil-in-water mixtures, allowing for the uniform distribution of active ingredients in topical formulations. Its fatty alcohol structure contributes to its ability to soften and soothe the skin.

Pharmacodynamics

The pharmacodynamic properties of cetostearyl alcohol are primarily related to its emollient and emulsifying actions. By forming a protective barrier on the skin, it enhances the hydration and overall integrity of the skin barrier. It also contributes to the consistency and feel of topical formulations, which can improve patient adherence to treatment regimens.

Pharmacokinetics

Cetostearyl alcohol is not systemically absorbed when applied topically; it remains primarily on the skin surface to exert its effects. Due to its large molecular size and hydrophobic properties, it does not penetrate deeply into systemic circulation. The metabolism and excretion pathways are not well-defined due to its minimal systemic exposure.

Pregnancy

Cetostearyl alcohol is generally considered safe for use during pregnancy, but it is recommended to consult a healthcare professional.

Breast-feeding

Cetostearyl alcohol is unlikely to pose a risk to breastfeeding infants when used in topical formulations.

Storage

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

Formulations

• Creams
• Lotions
• Ointments
• Emulsions

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

Indications

• Insecticide for agricultural use
• Research tool in toxicology

Dosage

Children: Refer to the BNF for Children for specific dosing and administration guidelines.

Adults: Refer to the BNF for specific dosing and administration guidelines.

Mechanism of action

Methyl parathion acts primarily by inhibiting the enzyme acetylcholinesterase, which is essential for the breakdown of the neurotransmitter acetylcholine. Its active metabolite, methyl paraoxon, is a potent inhibitor of both acetylcholinesterase and butyrylcholinesterase. The inhibition of these enzymes results in the accumulation of acetylcholine at synapses, leading to overstimulation of cholinergic receptors and resultant toxic effects.

Pharmacodynamics

The pharmacodynamics of methyl parathion involve its action as a noncompetitive inhibitor of acetylcholinesterase, causing prolonged effects of acetylcholine due to its inability to be hydrolyzed. The resultant cholinergic toxicity can lead to symptoms such as muscle twitching, respiratory distress, and potentially fatal outcomes if not treated promptly. The extent of inhibition is dose-dependent, with significant toxicity occurring after substantial enzyme inhibition.

Pharmacokinetics

Methyl parathion is absorbed through the gastrointestinal tract and can also be absorbed through the skin and respiratory tract. It is metabolized in the liver to form methyl paraoxon, which is responsible for the majority of its toxic effects. The distribution of methyl parathion in body tissues is influenced by its lipophilicity, and it is primarily excreted as metabolites in the urine. The elimination half-life and specific pharmacokinetic parameters can vary based on individual metabolism and exposure levels.

Pregnancy

There are no adequate and well-controlled studies in pregnant women. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is not known whether this drug is excreted in human milk. Caution is advised when administering to nursing women.

Storage

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

Formulations

• Liquid formulation

Indications

• Used as an emulsifying agent in pharmaceutical formulations
• Used in food products for texture and stability
• May be indicated in topical preparations to enhance drug absorption

Dosage

Children: Refer to specific product guidelines as doses can vary widely based on formulation and intended use.

Adults: Refer to specific product guidelines as doses can vary widely based on formulation and intended use.

Mechanism of action

Monostearate functions primarily as a surfactant. It reduces the surface tension between components in a mixture, allowing for better emulsification of oils and water. This action enhances the dispersion of active ingredients and improves their absorption in the gastrointestinal tract.

Pharmacodynamics

As an emulsifier, monostearate facilitates the formation of stable emulsions, which can lead to improved drug delivery and absorption. Its ability to enhance solubility of lipophilic compounds can result in increased bioavailability of certain drugs, making them more effective.

Pharmacokinetics

Monostearate is generally considered non-toxic and is metabolized by the body through hydrolysis into glycerol and stearic acid. It is poorly absorbed in the gastrointestinal tract due to its large molecular structure, and any absorbed amounts may be further metabolized or excreted. The onset and duration of action depend on the formulation in which it is used.

Pregnancy

Monostearate is generally considered safe for use during pregnancy, but it is important to consult with a healthcare provider for personalized advice.

Breast-feeding

Monostearate is typically regarded as safe during breastfeeding, but a healthcare provider should be consulted to ensure no adverse effects on the infant.

Storage

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

Formulations

• Monostearate powder
• Monostearate capsules
• Monostearate ointment

Indications

• Constipation
• Dry skin
• Skin irritation

Dosage

Children: Refer to specific guidelines and prescribing information for paediatric dosing.

Adults: Refer to specific guidelines and prescribing information for adult dosing.

Mechanism of action

Paraffin acts as a lubricating agent in the gastrointestinal tract. It coats the stool and the intestinal walls, which helps to ease the passage of feces by reducing friction. This action promotes bowel movements and alleviates constipation. When used topically, it forms a barrier on the skin, which helps to retain moisture and protect against irritants.

Pharmacodynamics

Paraffin has a low viscosity and surface tension, which allows it to spread easily over surfaces. Its lubricating properties facilitate the movement of stool through the intestines, while its emollient properties help in maintaining skin hydration and barrier function. The onset of action for oral administration typically occurs within 6 to 8 hours, making it effective in treating occasional constipation.

Pharmacokinetics

Paraffin is not absorbed systemically when ingested; it remains in the gastrointestinal tract and is excreted unchanged in the feces. After oral administration, it acts locally in the intestines without significant systemic effects. When used topically, it remains on the skin surface and does not penetrate deeply, providing a protective layer without altering systemic pharmacokinetics.

Adverse effects

• Abdominal cramps
• Diarrhea
• Nausea
• Vomiting
• Lipid pneumonia (when aspirated)
• Electrolyte imbalances

Precautions

• Use with caution in patients with gastrointestinal obstruction
• Avoid in patients with a history of aspiration
• Monitor for signs of dehydration with prolonged use

Pregnancy

Use only if clearly needed. Consult a healthcare provider for advice.

Breast-feeding

Paraffin can be excreted in breast milk, use with caution.

Storage

Store at room temperature away from moisture and heat.

Formulations

• Liquid paraffin
• Soft paraffin (for topical use)

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

• Management of wounds
• Burn treatment
• Dental caries prevention
• Topical antiseptic
• Infection control in medical devices

Dosage

Children: Refer to BNF for Children for age-appropriate dosing recommendations.

Adults: Refer to BNF for specific dosing guidelines depending on the clinical context and formulation used.

Mechanism of action

Silver ions precipitate with chloride or phosphate anions and bind to proteins, leading to antibacterial effects by disrupting cell membranes. They can bind to peptidoglycans in bacterial cell walls, causing loss of structural integrity and function. Silver also binds to and oxidizes sulphydryl groups in enzymes, inhibiting metabolic processes. Additionally, silver ions may attach to bacterial DNA, inhibiting replication, and silver nanoparticles can generate reactive oxygen species, causing oxidative stress.

Pharmacodynamics

Silver exhibits broad-spectrum antimicrobial activity, effective against both Gram-positive and Gram-negative bacteria, including _Streptococcus mutans_, _Staphylococcus aureus_, and _Escherichia coli_. It has shown dose-dependent effects against methicillin-resistant Staphylococcus aureus (MRSA). Furthermore, silver compounds have demonstrated anti-inflammatory properties in models of skin inflammation and ulcerative colitis, suppressing pro-inflammatory cytokines and matrix metalloproteinases.

Pharmacokinetics

Silver does not have a well-defined pharmacokinetic profile due to its nature as a metal; however, it is known to bind extensively to proteins and tissues. Chronic exposure to silver can lead to accumulation and potential toxicity. The absorption and distribution of silver ions can vary based on the form of silver administered, with nanoparticles showing different properties compared to ionic silver.

Pregnancy

Safety during pregnancy has not been established. Use only if clearly needed.

Breast-feeding

Caution is advised as it is not known whether silver is excreted in human milk.

Storage

Store in a well-closed container, protected from light, at room temperature.

Formulations

• Silver nitrate
• Nanocrystalline silver

Dosage

Children: Refer to specific product information for dosing guidelines.

Adults: Refer to specific product information for dosing guidelines.

Pregnancy

Consult a healthcare professional before use. The effects of Soft during pregnancy are not well-documented.

Breast-feeding

Consult a healthcare professional before use. The safety of Soft during breastfeeding is not well-established.

Storage

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

Indications

• Emulsifying agent in topical formulations
• Stabilizing agent in oral drug formulations
• Food industry applications as an emulsifier
• Cosmetic formulations

Dosage

Children: Refer to specific formulation guidelines for dosage recommendations.

Adults: Refer to specific formulation guidelines for dosage recommendations.

Mechanism of action

Sorbitan acts primarily as a surfactant and emulsifier. Its amphiphilic nature allows it to reduce the surface tension between oil and water, thereby facilitating the formation and stabilization of emulsions. The hydrophilic part of the sorbitan molecule interacts with water, while the lipophilic part interacts with oils, promoting the mixing of immiscible liquids.

Pharmacodynamics

As an emulsifier, sorbitan enhances the bioavailability of lipophilic drugs by aiding their dispersion in aqueous environments. This property is particularly valuable in formulations where uniform distribution of active ingredients is critical for efficacy. Sorbitan may also impact the release profiles of drugs from emulsified formulations, potentially affecting the onset of action.

Pharmacokinetics

Sorbitan is generally considered to be poorly absorbed when administered orally, leading to minimal systemic exposure. Its primary role is local, serving as an excipient in formulations rather than as an active therapeutic agent. Due to its emulsifying properties, it may enhance the solubility and absorption of other drugs in the gastrointestinal tract, but the absorption characteristics of sorbitan itself are limited. Metabolism and excretion details specific to sorbitan are not well-documented, as it typically functions in a non-systemic capacity.

Pregnancy

Sorbitan has not been well studied in pregnant women. Use during pregnancy should be based on a risk-benefit assessment.

Breast-feeding

Sorbitan is generally considered safe during breastfeeding, however, there is limited data available.

Storage

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

Formulations

• Sorbitan monooleate
• Sorbitan monostearate
• Sorbitan tristearate

Dosage

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

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

Mechanism of action

The mechanism of action for White involves its interaction with specific biological pathways, leading to the desired pharmacological effects. The precise pathways may include modulation of receptor activity or alteration of enzyme function, although specific details are not provided.

Pharmacodynamics

Pharmacodynamics of White includes its effects on the body, including therapeutic effects and potential side effects. As a compound, it may exert its influence on multiple physiological systems, which can lead to changes in symptoms or disease progression.

Pharmacokinetics

Pharmacokinetics of White involves its absorption, distribution, metabolism, and excretion. Understanding these parameters can help predict how the drug behaves in the body, including onset of action and duration of effect. Detailed pharmacokinetic data is not specified.

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

To elucidate the possible mechanism of initiation of lipid peroxidation in silver nitrate treated erythrocytes, the effect of AgNO3 on Hb catalyzed peroxidation of phospholipid liposomes was studied. Ag+ significantly increases the rate of Hb-catalyzed peroxidation. The inhibition of this effect by superoxide dismutase and catalase suggests that superoxide radical and H2O2 are involved. It was demonstrated also that Ag+ potentiates the Hb autoxidation and increases the binding of Hb to the erythrocyte membrane. Silver nitrate exhibits antiseptic, germicidal, astringent, and caustic or escharotic activity. These effects may result from silver ions readily combining with sulfhydryl, carboxyl, phosphate, amino, and other biologically important chemical groups. When silver ions interact with proteins, physical properties of the protein are usually altered; the protein may be denatured and precipitation usually occurs. Silver ions act on the surface of bacteria causing substantial changes in the cell wall and membrane. The germicidal activity of silver nitrate may be attributed to precipitation of bacterial proteins by liberated silver ions.

Mechanism of action

Sulfadiazine is a competitive inhibitor of the bacterial enzyme dihydropteroate synthetase. This enzyme is needed for the proper processing of para-aminobenzoic acid (PABA) which is essential for folic acid synthesis. The inhibited reaction is necessary in these organisms for the synthesis of folic acid.

Pharmacodynamics

Sulfadiazine is a sulfonamide antibiotic. The sulfonamides are synthetic bacteriostatic antibiotics with a wide spectrum against most gram-positive and many gram-negative organisms. However, many strains of an individual species may be resistant. Sulfonamides inhibit multiplication of bacteria by acting as competitive inhibitors of <i>p</i>-aminobenzoic acid in the folic acid metabolism cycle. Bacterial sensitivity is the same for the various sulfonamides, and resistance to one sulfonamide indicates resistance to all. Most sulfonamides are readily absorbed orally. However, parenteral administration is difficult, since the soluble sulfonamide salts are highly alkaline and irritating to the tissues. The sulfonamides are widely distributed throughout all tissues. High levels are achieved in pleural, peritoneal, synovial, and ocular fluids. Although these drugs are no longer used to treat meningitis, CSF levels are high in meningeal infections. Their antibacterial action is inhibited by pus.

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

Acute poisoning ... is related to ... inhibiting action on enzyme acetylcholinesterase. Toxic manifestations generally occur only after more than 50% of plasma cholinesterase is inhibited. ... Methyl parathion ... depend on oxidative activation by replacement of thiono-sulfur with oxygen for ... toxicity. Methyl parathion has only a slight inhibitory action on acetylcholinesterase and butyrylcholinesterase, but its active metabolite, methyl paraoxon, is a potent inhibitor of both these enzymes. A study was conducted examining the inhibition of (Ca2+ and Mg2+)-ATPase by parathion (56382) and methyl parathion. Enzyme activity was assessed spectrophotometrically in pig erythrocyte membranes containing calcium2+ (Ca2+) and magnesium2+ and in solubilized membrane preparations incubated with the test agents. The enzyme response to ATP was biphasic. Equations expressing the kinetics of the substrate curves described two classes of the ATP binding active site, one with high affinity and low maximum rate and one with low affinity and high maximum rate. High affinity active sites were stimulated by low ATP concentrations (20 uM), whereas low affinity active sites were stimulated by high ATP levels (2 mM). Parathion and methylparathion dose dependently inhibited enzyme activity; parathion had a greater inhibitory effect than methylparathion. Lineweaver-Burke and Dixon plots indicated noncompetitive inhibition. Parathion and methylparathion induced enzyme inhibition occurred over a range of free calcium ion concentrations (0.5 to 5 mM); the inhibition was significantly greater at lower Ca2+ concentrations (1 to 100 uM) than at higher concentrations. The authors conclude that parathion and methylparathion inhibit ATPase activity by binding to a site on the enzyme rather than through an interaction with associated lipids. For more Mechanism of Action (Complete) data for METHYL PARATHION (6 total), please visit the HSDB record page.

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.

Mechanism of action

The majority of released silver ions precipitate with chloride or phosphate anions or bind to albumins, macroglobulins, or tissue debris. While bound silver ions do not exert antibacterial actions, they may potentially play a role in silver toxicity in case of chronic exposure. Silver ions mediate antibacterial effects via disrupting the bacterial, fungal, and protozoal cell membranes; they bind to disulphide in membrane proteins, readily allowing penetration through the membranes and intracellular absorption via pinocytosis. They may also bind to negatively-charged peptidoglycans in the cell wall via electrostatic interactions, leading to disruption of membrane transport function and loss of structural integrity. Silver ions also bind to and oxidize sulphydryl groups (SH) in bacterial cytoplasmic enzymes to aberrate their function in metabolic processes. Silver nanoparticles may cause an increase in reactive oxygen species (ROS) inside the microbial cells leading to metal-induced oxidative stress and cell damage. They also modulate cellular signal system via inhibition of phosphorylation of essential bacterial proteins to eventually cause cell death. It is also reported that silver ions also attach to guanine in bacterial DNA, which inhibits DNA replication. While it is not fully understood, the mode of action of silver compounds in preventing and arresting dental caries is thought to involve inhibition of the demineralization process in addition to cytoplasmic and membrane function perturbation mentioned above. Silver compounds may directly interact with hydroxyapatite, a major tooth component. Light catalyzes the reduction of silver salts deposited in skin to metallic silver & it /is/ subsequently oxidized to silver sulfide; it is the deposition of the latter compound which accounts for the gray discoloration pathognomonic of argyria. /Silver and compounds/ Silver nanoparticles (nano-Ag) are potent and broad-spectrum antimicrobial agents. In this study, spherical nano-Ag (average diameter = 9.3 nm) particles were synthesized using a borohydride reduction method and the mode of their antibacterial action against E. coli was investigated by proteomic approaches (2-DE and MS identification), conducted in parallel to analyses involving solutions of Ag(+) ions. The proteomic data revealed that a short exposure of E. coli cells to antibacterial concentrations of nano-Ag resulted in an accumulation of envelope protein precursors, indicative of the dissipation of proton motive force. Consistent with these proteomic findings, nano-Ag were shown to destabilize the outer membrane, collapse the plasma membrane potential and deplete the levels of intracellular ATP. The mode of action of nano-Ag was also found to be similar to that of Ag(+) ions ... however, the effective concentrations of nano-Ag and Ag(+) ions were at nanomolar and micromolar levels, respectively. Nano-Ag appear to be an efficient physicochemical system conferring antimicrobial silver activities.

Pharmacodynamics

Silver exhibits a broad-spectrum antimicrobial activity. Silver ions were shown to mediate an effective antibacterial action against _Streptococcus mutans_, one of major bacteria present in the human oral cavity and one of etiological microorganism of dental caries. A study reported a dose-dependent antimicrobial activity of silver nanoparticles against MRSA and non-MRSA bacteria. Silver nanoparticles were also shown to mediate antibacterial activity against Gram-positive _S. aureus_ and Gram-negative _E. coli_ by inhibiting the growth. In experimental dinitrochlorobenzene-induced inflammatory models in porcine or murine skin, topical application of silver nitrate and nanocrystalline silver were shown to exert anti-inflammatory effects associated with lymphocyte apoptosis, decreased expression of pro-inflammatory cytokines, and reduced gelatinase activity. In a rat model of ulcerative colitis, orally or intracolonically administered nanocrystalline silver were shown to suppress matrix metalloproteinase (MMP-9), tumour necrosis factor (TNF), and interleukin-β (IL-β) and IL-12.