Hexigold Hospital Concentrate

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

• Oral hygiene
• Skin antisepsis
• Bladder irrigation
• Urological surgery
• Management of infections associated with indwelling urinary catheters

Mechanism of action

Chlorhexidine's antimicrobial effects arise from its ability to disrupt microbial cell membranes. The positively charged chlorhexidine molecule interacts with negatively charged phosphate groups on microbial surfaces, compromising cell integrity and causing leakage of intracellular materials. This interaction allows chlorhexidine to enter the cell, precipitate cytoplasmic components, and ultimately induce cell death. At lower concentrations, chlorhexidine acts as a bacteriostatic agent, causing leakage of substances like potassium and phosphorus, while at higher concentrations, it exerts bactericidal effects.

Pharmacodynamics

Chlorhexidine exhibits broad-spectrum antimicrobial activity, effective against a variety of bacteria, yeasts, and viruses. Its action is dose-dependent, with lower concentrations (0.02%-0.06%) providing bacteriostatic effects, while higher concentrations (>0.12%) are bactericidal. Pharmacokinetic studies indicate that about 30% of chlorhexidine remains in the mouth after rinsing, allowing for slow release into oral fluids. This property, known as 'substantivity', helps prevent microbial colonization on surfaces like dentine, although prolonged use can lead to staining of oral surfaces.

Pharmacokinetics

Chlorhexidine is retained in the oral cavity at approximately 30% following rinsing, with a slow release into saliva. The pharmacokinetics of chlorhexidine indicate a high affinity for binding to tissues, which prolongs its antimicrobial action. The systemic absorption of chlorhexidine is minimal when used topically or as a rinse, making it safe for localized use. The elimination half-life and metabolism details are not well documented due to its primarily topical application.

Adverse effects

• Mucosal irritation
• Burning sensation
• Staining of teeth and oral surfaces
• Allergic reactions

Precautions

• Use with caution in patients with a history of hypersensitivity to chlorhexidine
• May cause irritation; discontinue if severe irritation occurs
• Staining may occur with prolonged use, particularly with oral formulations

Pregnancy

Chlorhexidine is generally considered safe for use during pregnancy; however, caution is advised and pregnant individuals should consult healthcare providers.

Breast-feeding

Chlorhexidine is considered safe during breastfeeding, but it is advisable to consult a healthcare provider.

Storage

Store at room temperature, away from light and moisture. Keep out of reach of children.

Formulations

• Irrigation solution (0.02% and 0.05%)
• Capsules (various strengths)
• Catheter maintenance solution (1:5000)
• Topical solutions for oral hygiene

Indications

• Hepatic encephalopathy
• Urea cycle disorders
• Acid-base disturbances

Dosage

Children: Refer to the BNF for Children for specific pediatric dosing information.

Adults: Refer to the BNF for specific dosing information based on condition and clinical guidelines.

Mechanism of action

Ammonia is crucial for renal excretion and metabolism, which aids in the regulation of acid-base balance by generating bicarbonate ions and promoting renal net acid excretion. Acute exposure to ammonia can activate NMDA receptor signaling pathways, while high concentrations resulting from urea cycle enzyme deficiencies can cause alterations in astrocyte morphology and increased neuroactive metabolites. This includes oxidative/nitrosative stress that impacts neuronal and astrocytic function, contributing to cerebral ammonia toxicity and related neuropsychiatric effects.

Pharmacodynamics

As a gas, ammonia acts as a natural respiratory stimulant. Its renal metabolism contributes to whole body acid-base balance, while its toxic effects at elevated levels can lead to significant neurophysiological changes, particularly in the context of liver dysfunction. Ammonia's role in stimulating oxidative stress responses in brain cells can lead to cellular damage and altered signaling pathways.

Pharmacokinetics

Ammonia is primarily metabolized in the liver, where it is converted to urea through the urea cycle, facilitating its excretion. The balance of ammonia production and clearance is critical for maintaining normal physiological functions. Following inhalation, ammonia is rapidly absorbed and can cause irritation in the respiratory tract. Renal function significantly influences ammonia levels in the body, with changes in kidney function affecting its excretion and thus systemic concentrations.

Pregnancy

Ammonia is generally considered unsafe during pregnancy due to potential risks to fetal development.

Breast-feeding

Ammonia may be present in breast milk; caution is advised.

Storage

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

Indications

• Topical antiseptic for wound care
• Disinfection of skin and mucous membranes
• Cleaning and preparation of the skin prior to surgery
• Management of minor cuts, abrasions, and burns

Dosage

Children: Refer to specific product guidelines for concentration and application frequency, as doses may vary based on formulation.

Adults: Refer to specific product guidelines for concentration and application frequency, as doses may vary based on formulation.

Mechanism of action

Cetrimide works by disrupting the cell membrane of microorganisms, leading to cell lysis and death. It is a surfactant that decreases surface tension and facilitates the penetration of the antiseptic into the microbial cell wall, ultimately causing cell disruption. This mechanism contributes to its broad-spectrum antimicrobial efficacy.

Pharmacodynamics

Cetrimide exhibits bactericidal and fungicidal activity. It is particularly effective against Gram-positive bacteria, with variable activity against Gram-negative organisms. Its surfactant properties enhance its ability to cleanse and disinfect wounds, reducing the risk of infection. Cetrimide's effectiveness is influenced by concentration, contact time, and the presence of organic matter.

Pharmacokinetics

When applied topically, cetrimide is minimally absorbed into systemic circulation, resulting in localized action at the site of application. Its distribution is primarily limited to the skin and mucous membranes. The metabolism and excretion pathways of cetrimide are not well characterized due to its low systemic absorption; however, it is predominantly eliminated through topical use without significant systemic effects.

Adverse effects

• Skin irritation
• Allergic reactions
• Contact dermatitis
• Systemic toxicity if absorbed in large amounts

Precautions

• Avoid contact with eyes
• Use with caution in individuals with sensitive skin
• Not for internal use

Pregnancy

Cetrimide should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus, as there are limited studies on its safety in pregnant women.

Breast-feeding

Cetrimide is not known to be harmful when used topically during breastfeeding; however, it is advisable to avoid application on the breast area to prevent accidental ingestion by the infant.

Storage

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

Formulations

• Topical solution
• Cream
• Ointment
• Wipes

Mechanism of action

The precise mechanism of action is not well-documented in the provided resources. However, compounds with similar molecular structures often interact with biological pathways through modulation of neurotransmitter systems or receptor activity.

Pharmacodynamics

Pharmacodynamics for compounds like Colour typically involve interactions at the cellular level, influencing physiological responses through receptor binding and modulation of signaling pathways. The specific effects and potency would depend on the context of use and formulation.

Pharmacokinetics

Information on the pharmacokinetics of Colour, including absorption, distribution, metabolism, and excretion, is not provided in the available resources. Generally, pharmacokinetic properties will vary significantly based on formulation and route of administration.

Pregnancy

Safety in pregnancy has not been established. Use only if the benefits outweigh the risks.

Breast-feeding

Caution is advised. There are no adequate studies in breastfeeding women.

Storage

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

Indications

• Perfumes and colognes
• Aromatherapy
• Personal care products (e.g., lotions, shampoos)
• Household cleaning products
• Food flavoring

Dosage

Children: Refer to specific product guidelines; use caution in children as sensitivities may vary.

Adults: Refer to specific product guidelines as fragrance concentrations vary widely; no standard dosage exists.

Mechanism of action

Fragrance molecules interact with olfactory receptors in the nasal cavity, which send signals to the brain's olfactory bulb. This interaction triggers a sensory response, influencing emotions and memories through the limbic system, which is associated with emotional regulation and memory.

Pharmacodynamics

Fragrances can evoke various psychological and physiological responses. Some fragrance compounds may have calming effects, while others may stimulate energy or alertness. The specific effects depend on the individual’s perception and the context of use, as well as the chemical composition of the fragrance. Commonly used fragrance compounds include linalool, limonene, and vanillin, each associated with distinct sensory profiles.

Pharmacokinetics

The pharmacokinetics of fragrance compounds can vary widely based on their chemical structure. Generally, these compounds are absorbed through the skin or inhaled, leading to systemic circulation. Metabolism primarily occurs in the liver, where they are converted to various metabolites that may be excreted via urine. The elimination half-life can differ significantly among individual compounds.

Adverse effects

• Allergic reactions
• Skin irritation
• Respiratory issues
• Headaches
• Nausea

Precautions

• May cause sensitivity in individuals with allergies
• Use with caution in patients with asthma or respiratory conditions
• Avoid contact with eyes and mucous membranes

Pregnancy

Safety during pregnancy is not well established; use cautiously and consult a healthcare provider.

Breast-feeding

Limited data available; consult a healthcare provider before use.

Storage

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

Formulations

• Perfumes
• Colognes
• Essential oils
• Scented lotions
• Air fresheners

Indications

• Antiseptic for skin disinfection
• Solvent in pharmaceutical formulations
• Cleaning agent in laboratories and healthcare settings

Dosage

Children: For pediatric use, consult specific guidelines in the BNF for Children, as dosing may vary based on age, weight, and clinical circumstances.

Adults: For skin antisepsis, apply isopropyl alcohol topically in a concentration of 70% to the affected area. Dosage may vary based on clinical indication and setting.

Mechanism of action

Isopropyl alcohol works primarily as an antiseptic by denaturing proteins and disrupting cell membranes of bacteria, viruses, and fungi, leading to cell lysis and death. Its efficacy is enhanced by the presence of water, which facilitates the penetration of the alcohol into microbial cells.

Pharmacodynamics

Isopropyl alcohol exhibits a rapid onset of action against a variety of pathogens, including gram-positive and gram-negative bacteria, fungi, and some viruses. Its antimicrobial activity is concentration-dependent, with higher concentrations generally providing a broader spectrum of activity. It is commonly used in concentrations ranging from 60% to 90%, with 70% being optimal for disinfection due to its ability to penetrate the cell wall effectively.

Pharmacokinetics

Isopropyl alcohol is readily absorbed through the skin and mucous membranes. After absorption, it is metabolized primarily in the liver to acetone, which is then further metabolized and excreted, mostly via urine. The elimination half-life of isopropyl alcohol varies but is typically around 2 to 3 hours. Its effects can be influenced by factors such as dosage, route of exposure, and individual metabolic differences.

Pregnancy

Isopropyl alcohol should be used with caution during pregnancy. It is a category C drug, indicating that risk cannot be ruled out.

Breast-feeding

Caution is advised when using isopropyl alcohol during breastfeeding, as it is not known if it is excreted in human milk.

Storage

Isopropyl alcohol should be stored at room temperature, away from heat and flame. Keep the container tightly closed and in a well-ventilated area.

Formulations

• Isopropyl alcohol 70% solution
• Isopropyl alcohol 99% solution

Indications

• Methylmalonic aciduria
• Homocystinuria
• Vitamin B12 deficiency
• Neurological disorders associated with metabolic dysfunction

Dosage

Children: Refer to the BNF for Children for dosing in paediatric patients, as specific doses depend on age, weight, and severity of the condition.

Adults: Refer to clinical guidelines and appropriate literature for specific dosing recommendations as these can vary based on the severity of the condition and individual patient needs.

Mechanism of action

The mechanism of action in the context of MmrDC involves the supplementation of vitamin B12 (cobalamin), which acts as a cofactor for various enzymatic reactions crucial for metabolizing propionate and certain amino acids. This helps reduce the levels of methylmalonic acid and homocysteine in the body, thereby addressing the underlying metabolic dysfunction.

Pharmacodynamics

The pharmacodynamics of vitamin B12 supplementation in MmrDC involve enhancing the enzymatic activity of methylmalonyl-CoA mutase, which is necessary for converting methylmalonyl-CoA to succinyl-CoA. This conversion is vital for proper energy metabolism and reducing toxic metabolites. Adequate levels of vitamin B12 can improve metabolic balance and alleviate some clinical symptoms associated with the disease.

Pharmacokinetics

Vitamin B12 is absorbed in the intestines, specifically in the terminal ileum, and is stored primarily in the liver. Following absorption, it is transported in the bloodstream bound to transcobalamin II. The half-life of vitamin B12 can vary but is generally long, allowing for sustained effects in the body. The renal excretion of excess vitamin B12 is minimal due to its high storage capacity.

Pregnancy

Consult a healthcare provider before use, as the safety of MMRDC during pregnancy has not been established.

Breast-feeding

Consult a healthcare provider before use, as the safety of MMRDC during breastfeeding has not been established.

Storage

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

Indications

• Emulsifying agent in drug formulations
• Stabilizer for parenteral preparations
• Solubilizer for hydrophobic drug compounds
• Ingredient in topical formulations

Dosage

Children: Refer to specific product guidelines, as dosing varies based on formulation and intended use.

Adults: Refer to specific product guidelines, as dosing varies based on formulation and intended use.

Mechanism of action

Polysorbate functions primarily as an emulsifying agent. It reduces the surface tension between immiscible liquids, allowing them to mix more easily. This property is particularly useful in stabilizing emulsions and suspensions, facilitating the delivery of active pharmaceutical ingredients in various formulations.

Pharmacodynamics

Polysorbate does not exert pharmacological effects in the traditional sense, as it does not bind to specific receptors to elicit a physiological response. Instead, it plays a crucial role in modifying the physical properties of drug formulations, thereby enhancing drug delivery and absorption. Its ability to solubilize drugs enhances their bioavailability, particularly for poorly soluble compounds.

Pharmacokinetics

Polysorbate is generally considered to be non-toxic and is not absorbed to a significant extent when administered orally. It is metabolized by the liver and excreted primarily through the gastrointestinal tract. The pharmacokinetic profile may vary depending on the route of administration and the specific formulation in which it is used.

Adverse effects

• Allergic reactions
• Skin irritation
• Gastrointestinal disturbances

Precautions

• Use cautiously in patients with known allergies to polysorbates or related compounds
• Monitor for allergic reactions in susceptible individuals

Pregnancy

Polysorbate is generally considered safe for use during pregnancy, but consult with a healthcare provider for specific cases.

Breast-feeding

Polysorbate is considered safe during breastfeeding, but consult with a healthcare provider for individual advice.

Storage

Store at room temperature, away from direct sunlight and moisture.

Formulations

• Polysorbate 20
• Polysorbate 80

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.

Indications

• Severe pain management
• Acute inflammatory conditions
• Chronic pain syndromes
• Postoperative pain relief
• Cancer-related pain
• Severe anxiety or depression (specific agents)

Dosage

Children: Refer to BNF for Children for specific paediatric dosing recommendations based on age, weight

Adults: Refer to specific guidelines or BNF for exact dosing information based on the drug type and condition being treated.

Mechanism of action

The mechanism of action for strong medications can vary significantly. For example, opioids work by binding to specific receptors in the central nervous system (CNS), primarily mu-opioid receptors, which leads to inhibition of pain signaling and modulation of emotional responses to pain. NSAIDs typically exert their effects by inhibiting cyclooxygenase enzymes (COX-1 and COX-2), leading to decreased production of prostaglandins, which are mediators of inflammation and pain. Other strong medications may act through different pathways, such as altering neurotransmitter levels or modulating immune responses.

Pharmacodynamics

Pharmacodynamics of strong medications includes their effects on the body, particularly in terms of analgesia, anti-inflammatory effects, or modulation of various physiological systems. The efficacy of these medications is often assessed through their impact on pain relief, reduction of inflammation, or improvement in mood or anxiety levels. Tolerance and dependence may develop with long-term use of certain strong medications, particularly opioids, necessitating careful management.

Pharmacokinetics

Pharmacokinetics of strong medications encompasses absorption, distribution, metabolism, and excretion (ADME). For example, opioids are typically well-absorbed orally and undergo significant first-pass metabolism in the liver, which can affect bioavailability. The volume of distribution varies, influencing how the drug is distributed throughout the body, while the elimination half-life can differ widely among strong medications, impacting dosing frequency and duration of action.

Pregnancy

Consult a healthcare provider for risk assessment, as safety data may be limited.

Breast-feeding

Consult a healthcare provider, as the effects on nursing infants are not well studied.

Storage

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

Dosage

Children: Refer to product-specific guidelines or consult a healthcare professional.

Adults: Refer to product-specific guidelines or consult a healthcare professional.

Pregnancy

There is limited data on the safety of Sunset during pregnancy, thus it should be used only if clearly needed and prescribed by a healthcare provider.

Breast-feeding

Due to the lack of sufficient studies, it is advised to consult a healthcare professional before using Sunset while breastfeeding.

Storage

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

Indications

• Magnetic resonance imaging (MRI) contrast enhancement
• Drug delivery systems
• Potential therapeutic applications in oncology

Dosage

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

Adults: Refer to the specific guidelines for dosage as per BNF and clinical protocols.

Mechanism of action

The principal uptake mechanism for superparamagnetic iron oxide nanoparticles involves clathrin-mediated endocytosis that is dependent on scavenger receptor A. This process allows phagocytic cells, particularly macrophages, to internalize the nanoparticles effectively. The interaction of these nanoparticles with macrophages is critical for their application in imaging and potential therapeutic interventions.

Pharmacodynamics

Superparamagnetic iron oxide nanoparticles exhibit properties that enhance the visibility of tissues during imaging procedures. Their magnetic properties allow for a significant increase in contrast during MRI scans. Additionally, they may have implications in therapeutic contexts, such as in the targeting of cancer cells, where their uptake by macrophages could facilitate localized drug delivery.

Pharmacokinetics

The pharmacokinetics of superparamagnetic iron oxide nanoparticles are characterized by rapid uptake by phagocytic cells, particularly in the liver and spleen. Following systemic administration, these nanoparticles are primarily cleared by macrophages through endocytosis. The particles tend to accumulate in the reticuloendothelial system, which can influence their distribution and elimination from the body.

Pregnancy

There is limited data on the safety of iron oxide nanoparticles during pregnancy. Caution is advised.

Breast-feeding

Limited data is available regarding the excretion of iron oxide nanoparticles in breast milk. Caution is advised.

Storage

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

Formulations

• Carboxydextran-coated superparamagnetic iron oxide nanoparticles

Pregnancy

No specific data available, consult a healthcare professional.

Breast-feeding

No specific data available, consult a healthcare professional.

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

Chlorhexidine’s broad-spectrum antimicrobial effects are due to its ability to disrupt microbial cell membranes. The positively charged chlorhexidine molecule reacts with negatively charged phosphate groups on microbial cell surfaces - this reaction both destroys the integrity of the cell, allowing leakage of intracellular material, and allows chlorhexidine to enter the cell, causing precipitation of cytoplasmic components and ultimately cell death. The specific means of cell death is dependent on the concentration of chlorhexidine - lower concentrations are bacteriostatic and result in leakage of intracellular substances such as potassium and phosphorous, whereas higher concentrations are bactericidal and cause cytoplasmic precipitation.

Pharmacodynamics

Chlorhexidine is a broad-spectrum antimicrobial with demonstrated activity against both gram-positive and gram-negative bacteria, yeasts, and viruses. Antimicrobial activity is dose-dependent - chlorhexidine is bacteriostatic at lower concentrations (0.02%-0.06%) and bactericidal at higher concentrations (>0.12%). Pharmacokinetic studies of oral chlorhexidine rinses indicate that approximately 30% of the active ingredient is retained in the mouth following rinsing, which is subsequently slowly released into oral fluids. This ability to adsorb to dentine, shared with tetracycline antibiotics such as [doxycycline], is known as "substantivity" and is the result of chlorhexidine's positive charge - it is likely that this substantivity plays at least some role in chlorhexidine's antimicrobial activity, as its persistence on surfaces such as dentine prevent microbial colonization. Dental chlorhexidine rinses may result in staining of oral surfaces, such as teeth. This effect is not ubiquitous and appears to be more significant with extended therapy (i.e. up to 6 months) - nevertheless, patients for whom oral staining is unacceptable should use chlorhexidine rinse with caution and for the shortest effective interval. Allergic reactions to chlorhexidine have been associated with the development of anaphylaxis.

Mechanism of action

Renal excretion and metabolism of ammonia is critical in regulation of acid-base balance by generating bicarbonate ions and promoting renal net acid excretion, both under basal conditions and in response to acid-base disturbances. There is evidence that acute ammonia exposure activates NMDA receptor signalling pathways, and high concentrations of ammonia resulting from urea cycle enzyme deficiencies are associated with changes in astrocyte morphology due to glutamine accumulation, changes in the expression of key astrocyte proteins, and increased concentrations of neuroactive L-tryptophan metabolites. ... Ammonia plays a key role in the pathogenesis of hepatic encephalopathy, which manifests as a neuropsychiatric syndrome accompanying acute and chronic liver failure. One consequence of ammonia action on the brain is astrocyte swelling, which triggers the generation of oxidative/nitrosative stress at the level of NADPH oxidase, nitric oxide synthases and the mitochondria. A self-amplifying signaling loop between oxidative stress and astrocyte swelling has been proposed. Consequences of the ammonia-induced oxidative/nitrosative stress response are protein modifications through nitration of tyrosine residues and oxidation of astrocytic and neuronal RNA. Nitrosative stress also mobilizes zinc from intracellular stores with impact on gene expression. These alterations may at least in part mediate cerebral ammonia toxicity through disturbances of intracellular and intercellular signaling and of synaptic plasticity. Oxidative/nitrosative stress and a low-grade cerebral edema as key events in the pathogenesis of ammonia toxicity and hepatic encephalopathy may offer potential new strategies for treatment. Ammonia-induced oxidation of RNA and proteins may impair postsynaptic protein synthesis, which is critically involved in learning and memory consolidation. RNA oxidation offers a novel explanation for multiple disturbances of neurotransmitter systems and gene expression and the cognitive deficits observed in hepatic encephalopathy. SRP: Ammonia in an aqueous environment exists in equilibrium between ionized ammonium cation and the non-ionized ammonia. This equilibrium can be affected by buffers, pH, temperature, and salinity. Thus in many cases it is not possible to assign the associated toxicity to the ionized or non-ionized form of the ammonia-nitrogen. /Aqueous ammonia/ Mechanisms involved in hepatic encephalopathy (HE) still remain poorly understood. It is generally accepted that ammonia plays a major role in this disorder, and that astrocytes represent the principal target of ammonia neurotoxicity. In recent years, studies from several laboratories have uncovered a number of factors and pathways that appear to be critically involved in the pathogenesis of this disorder. Foremost is oxidative and nitrosative stress (ONS), which is largely initiated by an ammonia-induced increase in intracellular Ca(2+). Such increase in Ca(2+) activates a number of enzymes that promote the synthesis of reactive oxygen-nitrogen species, including constitutive nitric oxide synthase, NADPH oxidase and phospholipase A2. ONS subsequently induces the mitochondrial permeability transition, and activates mitogen-activated protein kinases and the transcription factor, nuclear factor-kappaB (NF-kappaB). These factors act to generate additional reactive oxygen-nitrogen species, to phosphorylate various proteins and transcription factors, and to cause mitochondrial dysfunction. This article reviews the role of these factors in the mechanism of HE and ammonia toxicity with a focus on astrocyte swelling and glutamate uptake, which are important consequences of ammonia neurotoxicity.... A new model for ammonia excretion in freshwater fish and its variable linkage to Na(+) uptake and acid excretion /is proposed/. In this model, /the Rhesus protein/ Rhag facilitates NH(3) flux out of the erythrocyte, Rhbg moves it across the basolateral membrane of the branchial i

Pharmacodynamics

As a gas, ammonia is a natural byproduct and respiratory stimulant. Its renal metabolism plays a role in whole body acid-base balance.

Mechanism of action

Although systemically applied nanoparticles are quickly taken up by phagocytic cells, mainly macrophages, the interactions between engineered nanoparticles and macrophages are still not well defined. ...Therefore ... the uptake of diagnostically used carboxydextran-coated superparamagnetic iron oxide nanoparticles of 60 nm (SPIO) and 20 nm (USPIO) by human macrophages /was analyzed/. By pharmacological and in vitro knockdown approaches, the principal uptake mechanism for both particles was identified as clathrin-mediated, scavenger receptor A-dependent endocytosis... /Iron oxide nanoparticles/ ... /It has been/ suggested that ferric oxide serves as a carcinogenic cofactor either by retarding the clearance of inhaled carcinogens or by inducing cytopathological changes which make the cells of the respiratory tract more prone to develop cancer when exposed to carcinogenic substances.