Revac-B

Indications

• Dyspepsia
• Peptic ulcer disease
• Gastroesophageal reflux disease (GERD)
• Heartburn
• Diarrhea
• Mucosal irritations

Dosage

Children: Refer to the BNF for Children for appropriate dosing guidelines.

Adults: Refer to the BNF for specific dosing recommendations based on the condition being treated.

Mechanism of action

Aluminum acts as an astringent, causing local shrinkage or constriction of body tissues through osmotic flow of fluids away from the area of application. This mechanism assists in reducing mucous secretions and managing conditions such as peptic ulcers and diarrhea. Additionally, it can help in drying and hardening of tissues when applied topically.

Pharmacodynamics

Aluminum-based antacids work by neutralizing gastric acid, leading to an increase in gastric pH. This action helps to alleviate symptoms associated with excess gastric acid, such as heartburn and discomfort. The astringent properties of aluminum also contribute to its therapeutic effects in managing mucosal irritations and secretions.

Pharmacokinetics

Aluminum is absorbed minimally when taken orally, with a bioavailability of about 0.1 to 0.5%. The majority of aluminum is excreted renally, and its half-life can be prolonged in individuals with renal impairment. Long-term use may lead to accumulation and potential toxicity, particularly impacting bone and neurological health.

Interactions

• aluminiumhydroxide+deferasirox: Severe (decreases exposure)
• aluminiumhydroxide+enteralfeeds: Unknown (increases risk of blocked enteral or nasogastric tubes)
• aluminiumhydroxide+roxadustat: Unknown (decreases exposure)

Pregnancy

Aluminum compounds are generally considered safe in pregnancy when used as directed. However, excessive exposure should be avoided.

Breast-feeding

Aluminum is excreted in breast milk; caution is advised when administered to nursing mothers.

Storage

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

Formulations

• aluminium hydroxide suspension
• aluminium hydroxide tablets

Indications

• Vaccination against infectious diseases
• Allergy testing and immunotherapy
• Monoclonal antibody production
• Transplantation to prevent organ rejection

Dosage

Children: Dosing of antigens in children also depends on the specific antigen and the clinical indication. For pediatric vaccinations, refer to the BNF for Children.

Adults: Dosing of antigens is highly variable and depends on the specific antigen and the clinical indication. For vaccine administration, refer to national immunization guidelines.

Mechanism of action

Antigens work by binding to specific receptors on the surface of immune cells, such as B cells and T cells. This binding triggers a cascade of immune responses, including the proliferation of specific immune cell populations and the production of antibodies that target the antigen. This process is crucial for the development of adaptive immunity, allowing the body to remember and respond more effectively to future encounters with the same antigen.

Pharmacodynamics

The pharmacodynamics of antigens involve the interaction with the immune system to elicit a response. The magnitude and quality of this response can vary based on several factors, including the nature of the antigen, the route of exposure, and the host's immune status. Antigens can be classified as T-cell dependent or T-cell independent, influencing the type of immune response generated.

Pharmacokinetics

Antigens are processed by antigen-presenting cells (APCs) that present peptide fragments to T cells. The pharmacokinetics of antigens can vary widely depending on their form (e.g., live attenuated, inactivated, or subunit vaccines). Generally, once introduced into the body, antigens are taken up by APCs, which then migrate to lymph nodes to activate T and B cells. The duration of immune response can be influenced by the type of antigen and the presence of adjuvants.

Pregnancy

Safety during pregnancy depends on the specific type of antigen. Consult relevant guidelines for specific antigens.

Breast-feeding

Safety during breastfeeding varies by antigen type. Consult relevant guidelines for specific antigens.

Storage

Store at controlled room temperature, away from light and moisture. Specific storage conditions may vary based on the type of antigen.

Indications

• Hydration therapy
• Solvent for intravenous medications
• Diluent for oral medications
• Rehydration in cases of fluid loss
• Topical applications for wound care

Dosage

Children: Refer to specific drug formulations for appropriate dosing, as the dosage will vary depending on the active ingredient in the aqueous solution.

Adults: Refer to specific drug formulations for appropriate dosing, as the dosage will vary depending on the active ingredient in the aqueous solution.

Mechanism of action

Aqueous solutions serve primarily as a medium for drug solubility and absorption. The mechanism of action depends on the active ingredient dissolved within the aqueous solution. For many drugs, the aqueous environment enhances bioavailability by allowing the active ingredients to dissolve and interact with biological membranes, facilitating their transport across cell barriers.

Pharmacodynamics

The pharmacodynamics of aqueous solutions are influenced by the solutes they contain. Generally, the dissolution of drugs in an aqueous medium can enhance their effectiveness by improving absorption rates, increasing peak plasma concentrations, and allowing for more predictable pharmacological effects. The specific pharmacodynamic response will depend on the nature of the solute and its interaction with the body’s receptors or enzymes.

Pharmacokinetics

The pharmacokinetics of aqueous solutions largely pertain to the dissolved substances. They are absorbed through various routes, such as gastrointestinal tract, intravenous administration, or topical application, depending on the formulation. The rate of absorption can vary based on the solute’s properties, such as molecular weight, lipophilicity, and the presence of other excipients. Distribution, metabolism, and excretion will also depend on the active ingredient within the aqueous solution.

Pregnancy

Aqueous solutions are generally regarded as safe for use during pregnancy, but the specific context and formulation should be considered.

Breast-feeding

Aqueous solutions are typically considered safe during breastfeeding, but caution is advised depending on the specific formulation.

Storage

Store at room temperature, away from direct sunlight and moisture. Ensure containers are tightly sealed.

Formulations

• Aqueous solution
• Aqueous gel
• Aqueous suspension

Indications

• pH stabilization in laboratory experiments
• buffering during physiological studies
• preparation of samples for biochemical assays
• maintenance of pH in parenteral fluids

Dosage

Children: Refer to specific buffer formulations for detailed dosing guidance.

Adults: Refer to specific buffer formulations for detailed dosing guidance.

Mechanism of action

Buffers work by neutralizing added acids or bases through chemical reactions. For example, a buffer composed of acetic acid and sodium acetate can absorb excess hydrogen ions (from added acids) or donate hydrogen ions (to neutralize added bases), thus stabilizing the pH of the solution. This equilibrium is governed by the Henderson-Hasselbalch equation, which relates pH to the concentrations of the acidic and basic components of the buffer.

Pharmacodynamics

The pharmacodynamics of buffers involves their capacity to maintain pH levels within a target range, which is essential for various physiological processes. For instance, physiological buffers such as bicarbonate and phosphate play critical roles in maintaining the acid-base balance in the body, ensuring proper cellular function, enzyme activity, and metabolic processes.

Pharmacokinetics

The pharmacokinetics of buffer components depends on their specific chemical nature. Weak acids and bases used in buffers are typically absorbed and metabolized according to their molecular characteristics. For instance, bicarbonate can be reabsorbed in the kidneys and plays a significant role in systemic pH regulation. However, since buffer solutions are not typically absorbed in the same way as pharmaceutical drugs, their pharmacokinetic profiles are less relevant in a conventional sense.

Pregnancy

Buffering agents are generally considered safe during pregnancy; however, specific formulations should be evaluated for safety and efficacy.

Breast-feeding

Most buffering agents are considered safe during breastfeeding, but it is advisable to consult healthcare providers regarding specific formulations.

Storage

Store in a cool, dry place, away from direct sunlight and moisture. Follow specific storage instructions on the product label.

Indications

• Constipation
• Irritable bowel syndrome
• Diverticular disease
• Prevention of straining during defecation post-surgery
• Management of stool consistency in patients with fecal incontinence

Dosage

Children: Refer to specific product guidelines for dosing information, as doses may vary depending on the formulation and the child's age and condition.

Adults: Refer to specific product guidelines for dosing information, as doses may vary depending on the formulation and the patient's condition.

Mechanism of action

Bulk-forming agents function by absorbing water in the intestinal lumen, which increases the stool volume. This mechanical effect stretches the intestinal walls, stimulating peristalsis and facilitating bowel movement. Additionally, the hydrated bulk can help to improve stool consistency and reduce the incidence of straining during defecation.

Pharmacodynamics

The pharmacodynamic effects of bulk-forming agents are primarily localized to the gastrointestinal tract. They increase stool bulk and moisture content, which can help to alleviate constipation. The onset of action typically occurs within 12 to 72 hours after ingestion, depending on the specific agent and individual patient factors.

Pharmacokinetics

Bulk-forming agents are not absorbed into the bloodstream and remain within the gastrointestinal tract. They exert their effects locally and are eliminated in the feces. The hydration of the bulk-forming agent occurs within the intestinal lumen, which helps to form a gel-like substance that enhances stool passage without systemic absorption.

Adverse effects

• Gastrointestinal discomfort
• Bloating
• Flatulence
• Diarrhea
• Nausea

Precautions

• Ensure adequate fluid intake to prevent gastrointestinal obstruction.
• Monitor for signs of allergic reactions in sensitive individuals.
• Use cautiously in patients with gastrointestinal disorders.

Pregnancy

Generally considered safe, but consult a healthcare provider for individual assessment.

Breast-feeding

Considered safe, but consult a healthcare provider for individual assessment.

Storage

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

Formulations

• Powder
• Capsules
• Tablets
• Granules

Indications

• Diagnosis of acute hepatitis B infection
• Diagnosis of chronic hepatitis B infection
• Screening for hepatitis B in blood donors
• Monitoring hepatitis B infection status

Dosage

Children: Refer to BNF for Children for appropriate clinical context and testing protocols.

Adults: Refer to BNF for appropriate clinical context and testing protocols.

Mechanism of action

HBsAg is a component of the hepatitis B virus that triggers an immune response. When introduced into the body, HBsAg is recognized by the immune system, leading to the production of antibodies. This immune response helps to clear the virus from the body and can also provide protection against future infections.

Pharmacodynamics

The detection of HBsAg is used to assess the presence of an active HBV infection. The antigen is produced in large quantities during the acute and chronic phases of infection. The level of HBsAg in the blood can indicate the severity and duration of the infection, as well as the likelihood of developing chronic hepatitis.

Pharmacokinetics

HBsAg is typically detected in the serum of infected individuals. Its levels can vary depending on the phase of the infection, with higher concentrations observed in acute infections. The antigen can persist in chronic infections, and its clearance from the bloodstream is often associated with the resolution of the infection and the development of antibodies against HBV.

Pregnancy

Hepatitis B surface antigen (HBsAg) is a marker for hepatitis B infection and does not have a direct implication for pregnancy. However, management of hepatitis B in pregnant women is crucial to prevent vertical transmission of the virus to the infant.

Breast-feeding

The presence of HBsAg indicates a hepatitis B infection, which may pose a risk of transmission through breast milk. However, breastfeeding is generally considered safe for mothers who are HBsAg positive, provided the infant receives appropriate immunization.

Storage

HBsAg testing kits should be stored according to the manufacturer's guidelines, typically in a cool, dry place away from direct sunlight. Specific storage conditions may vary based on the type of assay used.

Indications

• Acute viral hepatitis
• Chronic hepatitis B
• Chronic hepatitis C
• Autoimmune hepatitis
• Alcoholic hepatitis
• Non-alcoholic fatty liver disease

Dosage

Children: Paediatric dosing also varies significantly based on the specific condition and medication. As with adult dosing, it is important to refer to the BNF for Children for specific recommendations.

Adults: Dosing for adult patients varies widely depending on the specific antiviral agent used and the type of hepatitis. It is essential to refer to specific guidelines or the BNF for precise dosing.

Mechanism of action

In viral hepatitis, the viruses typically enter liver cells and replicate, leading to cellular injury and inflammation. The immune response to the infection contributes to liver damage. Antiviral therapies aim to inhibit viral replication, either by directly targeting viral enzymes or by modulating the host immune response.

Pharmacodynamics

The pharmacodynamics of antiviral agents used in hepatitis treatment involve the inhibition of viral replication, reduction of viral load, and improvement of liver function. This can lead to a decrease in serum liver enzymes (ALT and AST) and an improvement in clinical symptoms. In chronic hepatitis B and C, sustained virologic response is the goal, indicating effective viral suppression.

Pharmacokinetics

The pharmacokinetics of antiviral medications used for hepatitis can vary significantly depending on the specific drug. Generally, these agents are absorbed from the gastrointestinal tract, metabolized in the liver, and excreted through urine or feces. The half-lives of these drugs can vary, influencing dosing schedules.

Pregnancy

Consult medical guidelines as hepatitis can pose risks during pregnancy; specific management depends on the type of hepatitis.

Breast-feeding

Consult healthcare providers, as the safety of certain hepatitis medications during breastfeeding varies.

Storage

Store in a cool, dry place away from direct sunlight; specific storage conditions may vary based on the medication used.

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.

Dosage

Children: Paediatric dosing in micrograms is also highly variable based on the drug and the condition being treated. Refer to the BNF for Children for detailed dosing recommendations.

Adults: Dosage in micrograms varies widely depending on the specific medication and its indication. Consult relevant clinical guidelines or the BNF for precise dosing information.

Mechanism of action

The mechanism of action varies depending on the specific drug being measured in micrograms. For example, many drugs operate by binding to specific receptors or enzymes, leading to a physiological response. This can include agonistic or antagonistic effects on neurotransmitter systems, modulation of immune responses, or alteration of metabolic pathways.

Pharmacodynamics

Pharmacodynamics refers to the effects of the drug on the body, including the relationship between drug concentration and effect. Drugs measured in micrograms often have a steep dose-response curve, meaning small changes in dosage can lead to significant changes in therapeutic and adverse effects. The potency of such drugs is typically high, necessitating careful dosing and monitoring.

Pharmacokinetics

Pharmacokinetics involves the study of how the body absorbs, distributes, metabolizes, and excretes a drug. Drugs administered in microgram doses may exhibit rapid absorption and distribution, especially if given intravenously or sublingually. Metabolism often occurs in the liver, and excretion can be renal or via bile, depending on the drug's chemical properties. Understanding the pharmacokinetics is essential for optimizing therapeutic regimens and minimizing side effects.

Pregnancy

Consult a healthcare professional before use. Safety and efficacy during pregnancy have not been established.

Breast-feeding

Consult a healthcare professional before use. It is not known if this drug is excreted in human milk.

Storage

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

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

• Fluid replacement therapy in dehydration
• Electrolyte replenishment
• As a diluent for intravenous medications
• Wound irrigation
• Intra-amniotic instillation for abortion procedures

Dosage

Children: Paediatric dosing of saline is dependent

Adults: The dosage of saline varies depending on the clinical indication. For fluid resuscitation, isotonic saline (0.9% NaCl) is typically administered at a rate determined by the patient's condition and response to therapy. Refer to specific clinical guidelines for detailed dosing.

Mechanism of action

Sodium and chloride, the major electrolytes in extracellular fluid, control extracellular volume and blood pressure. Changes in sodium concentrations are linked to water balance disorders. Intra-amniotic instillation of hypertonic sodium chloride injection may induce abortion, potentially mediated by prostaglandins released from damaged decidual cells, resulting in uterine contractions that lead to evacuation of the fetus and placenta.

Pharmacodynamics

Sodium, as the principal cation in extracellular fluid, regulates water distribution, fluid balance, and osmotic pressure. It plays a crucial role in maintaining acid-base equilibrium in conjunction with chloride and bicarbonate. Chloride, the major extracellular anion, closely follows sodium metabolism, with fluctuations in acid-base balance reflected in chloride concentrations.

Pharmacokinetics

Saline is administered intravenously or through other routes depending on clinical needs. Once in the body, sodium and chloride are distributed in the extracellular fluid compartment. The elimination of sodium occurs primarily through renal excretion, while chloride follows similar pathways. The pharmacokinetic properties can vary based on the concentration of the saline solution and the physiological state of the patient.

Pregnancy

Saline is generally considered safe for use during pregnancy, but its use should be justified based on the clinical situation.

Breast-feeding

Saline is considered safe to use during breastfeeding, as it is not expected to affect the milk or nursing infant.

Storage

Store at room temperature, away from light and moisture. Do not freeze.

Formulations

• 0.9% Sodium Chloride Injection
• 20% Sodium Chloride Injection

Indications

• Topical treatment of skin conditions
• Emulsifying agents in pharmaceutical formulations
• Wound healing applications
• Delivery of poorly soluble drugs

Dosage

Children: Refer to specific product guidelines and BNF for appropriate dosing regimens.

Adults: Refer to specific product guidelines and BNF for appropriate dosing regimens.

Mechanism of action

Surface-active agents, or surfactants, lower the surface tension between two substances, such as between a liquid and a solid or between two liquids. This property enables them to spread easily and improve the solubility of drugs in various formulations. In the context of drug delivery, surfactants can facilitate the absorption of medications across biological membranes by disrupting lipid bilayers, thus enhancing bioavailability.

Pharmacodynamics

Pharmacodynamics refers to the effects of drugs on the body and their mechanisms of action. For surface-active agents, the pharmacodynamic properties include their ability to alter surface tension and enhance wetting, spreading, and emulsification. These properties allow for improved penetration of active ingredients into tissues and can enhance the therapeutic effects of topically applied drugs.

Pharmacokinetics

Pharmacokinetics involves the absorption, distribution, metabolism, and excretion (ADME) of drugs. Surface-active agents typically exhibit limited systemic absorption when applied topically, leading to localized effects. The rate of absorption can be influenced by the formulation, the presence of other excipients, and the condition of the skin or mucosal surface. Metabolism may occur to a minimal extent, and excretion primarily happens through the skin or via the lymphatic system.

Pregnancy

Consult healthcare professional before use.

Breast-feeding

Consult healthcare professional before use.

Storage

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

Indications

• Preservative in vaccines
• Antibacterial agent
• Antifungal agent

Dosage

Children: Refer to the BNF for Children for specific dosage guidelines, especially in

Adults: Refer to specific product guidelines or the BNF for detailed dosage information, as thimerosal is primarily used as a preservative in vaccines rather than in therapeutic doses.

Mechanism of action

Thimerosal inhibits sulfhydryl-containing active sites of various enzymes and binds to sulfhydryl compounds, including glutathione and cysteine. It activates the InsP3 calcium channel on the endoplasmic reticulum, leading to the release of intracellular calcium and subsequent cellular functions dependent on calcium signaling. Ethylmercury, the metabolite of thimerosal, is lipophilic and can cross the blood-brain barrier, contributing to its biological effects.

Pharmacodynamics

Thimerosal exhibits antibacterial and antifungal properties, functioning as a preservative in vaccines. Its pharmacological effects are mediated through interactions with cellular thiols and modulation of calcium signaling pathways. The toxic effects of high doses of thimerosal, such as oxidative stress and apoptosis, have been observed in vitro, although the effects of low-dose exposure remain less understood.

Pharmacokinetics

Thimerosal is rapidly metabolized to ethylmercury, which is eliminated from the body more quickly than methylmercury. Ethylmercury has a shorter half-life, leading to limited accumulation and toxic potential when used in vaccine formulations. The octanol/water partition coefficients indicate that both organomercury compounds, including ethylmercury, can primarily exist within cells, allowing them to cross cellular membranes effectively.

Adverse effects

• Hypersensitivity reactions
• Local reactions at injection site
• Neurotoxic effects at high doses
• Possible kidney pathology with toxic quantities

Precautions

• Use with caution in individuals with known hypersensitivity to thimerosal or other mercury compounds
• Monitoring for adverse effects in patients receiving multiple vaccines containing thimerosal

Pregnancy

Thimerosal should be used in pregnant women only if clearly needed, as the effects on fetal development are not fully established.

Breast-feeding

Thimerosal is considered compatible with breastfeeding, but caution is advised due to potential mercury exposure.

Storage

Store in a cool, dry place away from light. Protect from freezing. Ensure proper disposal of any unused or expired vaccine containing thimerosal.

Formulations

• Thimerosal-containing vaccines (various formulations)

Mechanism of action

Aluminum Acetate is an astringent. An astrignent is a chemical that tends to shrink or constrict body tissues, usually locally after topical medicinal application. The shrinkage or constriction is through osmotic flow of water (or other fluids) away from the area where the astringent was applied. Astringent medicines cause shrinkage of mucous membranes or exposed tissues and are often used internally to check discharge of blood serum or mucous secretions. This can happen with a sore throat, hemorrhages, diarrhea, or with peptic ulcers. Externally applied astringents, which cause mild coagulation of skin proteins, dry, harden, and protect the skin. Acne sufferers are often advised to use astringents if they have oily skin. Astringents also help heal stretch marks and other scars. Mild astringent solutions are used in the relief of such minor skin irritations as those resulting from superficial cuts, allergies, insect bites, or fungal infections such as athlete's foot. Excessive dietary aluminum has been proposed to be a factor contributing to several neurological disorders in humans. Six 8-week-old female Swiss Webster mice were fed for 10 wk purified diets containing 100 (control), 500 or 1000 ug aluminum/g diet. Brain and liver lipid peroxidation was determined by evaluating the production of 2-thiobarbituric acid reactive substances in brain and liver homogenates in the presence or absence of 50 uM ferrous iron. 2-Thiobarbituric acid reactive substances production in the absence of iron in brain homogenates from mice fed the 1000 ug/g diet was higher (30%) than that in the 100 ug/g control group (3.1 vs 2.4 nmol 2-thiobarbituric acid reactive substances/mg protein). The addition of ferrous iron increased 2-thiobarbituric acid reactive substances production in brain homogenates from all 3 dietary groups. The iron induced 2-thiobarbituric acid reactive substances production was 26% higher in the 1000 ug/g brain homogenates than in the 100 ug/g group (4.9 vs 3.9 nmol 2-thiobarbituric acid reactive substances/mg protein). Brain 2-thiobarbituric acid reactive substances production in the presence and absence of iron was similar between the 100 and 500 ug/g aluminum groups. 2-Thiobarbituric acid reactive substances production in liver homogenates measured either with or without iron was similar for the 3 groups. These results show that, in mice, dietary aluminum intoxication leads to increased brain 2-thiobarbituric acid reactive substance production, suggesting that enhanced lipid peroxidation may be one possible mechanism underlying the neurological damage associated with increased tissue aluminum. Evidence is presented indicating that dementias are associated with a relative insufficiency of magnesium in the brain. Such insufficiency may be attributable to low intake or retention of magnesium; high intake of a neurotoxic metal, such as aluminum, which inhibits activity of magnesium requiring enzymes; or impaired transport of magnesium and/or enhanced transport of the neurotoxic metal into brain tissue. It is proposed that Alzheimer's disease involves a defective transport process, characterized by both an abnormally high incorporation of aluminum and an abnormally low incorporation that an altered serum protein contributes to the progression of Alzheimer's disease by having a greater affinity for aluminum than for magnesium, in contrast to the normal protein, which binds magnesium better than aluminum. The altered protein crosses the blood-brain barrier more efficiently than the normal protein and competes with the normal protein in binding to brain neurons. Binding of the altered protein to the target neurons would both facilitate aluminum uptake and impede magnesium uptake. Evidence suggests that albumin is the serum protein that is altered. Aluminum is established as a neurotoxin, although the basis for its toxicity is unknown. It recently has been shown to alter the function of the blood-brain barrier, which regulates ex

Mechanism of action

Sodium and chloride - major electrolytes of the fluid compartment outside of cells (i.e., extracellular) - work together to control extracellular volume and blood pressure. Disturbances in sodium concentrations in the extracellular fluid are associated with disorders of water balance. Intra-amniotic instillation of 20% sodium chloride injection induces abortion and fetal death. Although the mechanism has not been conclusively determined, some studies indicate that the drug's abortifacient activity may be mediated by prostaglandins released from decidual cells damaged by hypertonic solutions of sodium chloride. Hypertonic sodium chloride-induced uterine contractions are usually sufficient to cause evacuation of both the fetus and placenta; however, abortion may be incomplete in 25-40% of patients. /20% injection/

Pharmacodynamics

Sodium, the major cation of the extracellular fluid, functions primarily in the control of water distribution, fluid balance, and osmotic pressure of body fluids. Sodium is also associated with chloride and bicarbonate in the regulation of the acid-base equilibrium of body fluid. Chloride, the major extracellular anion, closely follows the metabolism of sodium, and changes in the acid-base balance of the body are reflected by changes in the chloride concentration.

Mechanism of action

Although its mechanism of action is not fully understood, thimerosal inhibits sulfhydryl-containing active site of various enzymes and binds to sulfhydryl compounds, including glutathione, cysteine, and sulfhydryl groups of proteins. In addition, thimerosal activates the InsP3 calcium channel on the endoplasmic reticular membrane, thereby triggering the release of intracellular calcium resulting in a calcium-induced calcium-influx of extracellular calcium. Therefore, thimerosal may induce or inhibit various cellular functions that are dependent on the signaling of calcium. Ethylmercury is metabolized to inorganic mercury more rapidly than methylmercury. This difference in metabolism may account for kidney pathology that can result from toxic quantities. Also, whereas the increase in oxidative stress and induction of apoptosis observed in vitro with large doses (405 μg/L to 101 mg/L) of thimerosal may explain its damaging neurological effects. The effects of low-dose ethylmercury are not completely understood to date. It is known, however, that the shorter half-life of ethylmercury (the metabolite of thimerosal) allows for very limited opportunities of ethylmercury derived from thimerosal in vaccines. Ethylmercury is a lipophilic cation that is capable of crossing the blood-brain barrier. The octanol/water partition coefficients of methyl and ethylmercury are 1.4 to 1.8, at intracellular pH and [Cl−], therefore, both organomercury compounds will primarily exist as intracellular lipophilic cations. It has been demonstrated that lipophilic cations accumulate inside mitochondria, in a Nernstian fashion, driven by the steady state membrane potential. As the typical mitochondrial membrane potential of astrocytes and neurons is between 140–170 mV, one would expect the concentration of these organomercury compounds within mitochondria to be approximately 1000 times greater than the cytosolic concentration.

Pharmacodynamics

Thimerosal is an organomercurial compound and derivative of thiosalicyclic acid with antibacterial and antifungal properties. Thimerosal, which consists of approximately 50% mercury by weight, has been one of the most widely used preservatives in vaccines. It is metabolized/degraded to ethylmercury and thiosalicylate. Ethylmercury is an organomercurial that must be carefully distinguished from methylmercury, a closely related substance that has been the focus of many studies. Methylmercury is the type of mercury found in various species of fish. Experimental data demonstrates that the toxicokinetics of thimerosal (ethylmercury) is vastly different from that of methyl-mercury. Thus, methyl-mercury is not a suitable reference for assessing the risk from exposure to thimerosal-derived mercury. Prior to the recent initiative to reduce or eliminate thimerosal from childhood vaccines, the maximum cumulative exposure to mercury via routine childhood vaccinations during the first 6 months of life was 187.5 micrograms. In the most recently formulated vaccines, the maximum cumulative exposure during the first 6 months of life should now be less than 3 micrograms of mercury. Currently, thimerosal may still be used in the early stages of manufacturing of certain childhood vaccines, however, only a trace remains after a chemical purification process. Note that the dose above is indicated for children 1-6 months of age is applicable only in the United States, and other countries may have varying indications.