DTPHH

Indications

• Poisoning
• Drug overdose
• Gastrointestinal decontamination

Dosage

Children: Refer to specific guidelines for the substance involved in poisoning or overdose, as doses vary widely based on the clinical scenario.

Adults: Refer to specific guidelines for the substance involved in poisoning or overdose, as doses vary widely based on the clinical scenario.

Mechanism of action

Adsorption occurs when molecules from a liquid or gas phase adhere to the surface of a solid, forming a film. This interaction can be influenced by various forces, including van der Waals forces, hydrogen bonding, and electrostatic interactions. In the context of activated charcoal, for example, it binds to various substances in the gut, preventing their absorption into the bloodstream and facilitating their excretion.

Pharmacodynamics

The pharmacodynamic effects of adsorbed substances depend on the specific material and its intended use. In general, adsorbents can reduce the bioavailability of certain drugs and toxins by binding them within the gastrointestinal tract and thus decreasing their systemic effects. This can be particularly advantageous in cases of poisoning or overdose, where rapid removal of the substance is desired.

Pharmacokinetics

The pharmacokinetics of adsorbed substances are complex and vary significantly depending on the specific adsorbent used. For instance, activated charcoal does not undergo metabolism and is excreted unchanged in the feces. The onset of action is rapid, as the adsorption occurs immediately upon contact in the gastrointestinal tract. The duration of effect depends on the concentration of the adsorbent and the presence of the substance to be adsorbed.

Pregnancy

Adsorbed is generally considered safe during pregnancy, but it should be used only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is not known whether adsorbed is excreted in human milk. Caution should be exercised when administering to nursing mothers.

Storage

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

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

• 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

Dosage

Children: Refer to the specific drug contained within the capsule for appropriate dosing guidelines.

Adults: Refer to the specific drug contained within the capsule for appropriate dosing guidelines.

Mechanism of action

Capsules themselves do not have a specific mechanism of action, as they are a form of drug delivery. The active pharmaceutical ingredient contained within the capsule will exert its pharmacological effects upon dissolution and absorption in the gastrointestinal tract, engaging specific receptors or pathways depending on the nature of the drug.

Pharmacodynamics

The pharmacodynamics of a drug encapsulated in a capsule will depend on the specific drug contained within. Generally, once the capsule dissolves, the active ingredient is released and absorbed into the bloodstream, where it can exert its effects, such as altering physiological functions, inhibiting or stimulating biological processes, or affecting cell signaling pathways. The onset of action, therapeutic effects, and side effects will vary widely based on the pharmacological class of the drug.

Pharmacokinetics

The pharmacokinetics of a drug in capsule form will vary depending on the active ingredient. In general, the pharmacokinetics include absorption, distribution, metabolism, and excretion (ADME). After oral administration, capsules dissolve in the stomach or intestines, releasing the active ingredient for absorption into the systemic circulation. The drug may then be distributed throughout the body, metabolized primarily by the liver, and excreted via urine or feces. The rate of absorption and bioavailability will depend on factors such as the solubility of the drug, the presence of food, and the formulation of the capsule.

Pregnancy

The safety of capsular during pregnancy has not been established. It should be used only if clearly needed and the potential benefits outweigh the risks.

Breast-feeding

It is not known whether capsular is excreted in human milk. Caution should be exercised when administering to nursing mothers.

Storage

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

Indications

• Menopausal symptoms
• Vulvar and vaginal atrophy
• Prevention of osteoporosis in postmenopausal women
• Hypoestrogenism due to hypogonadism or castration

Dosage

Children: Conjugated estrogens are not typically indicated for use in the pediatric population. Refer to specialized resources for any off-label use.

Adults: Refer to the BNF for specific dosing guidelines, as doses may vary based on the indication and patient-specific factors.

Mechanism of action

Conjugated estrogens exert their effects primarily through binding to estrogen receptors, leading to the activation of estrogen-responsive genes. This binding triggers a cascade of biological responses that promote the development and maintenance of female reproductive tissues, regulation of the menstrual cycle, and other systemic effects such as bone density maintenance and modulation of cholesterol levels.

Pharmacodynamics

The pharmacodynamics of conjugated estrogens involve their role in modulating gene expression within estrogen-responsive tissues. They help to alleviate symptoms associated with menopause, such as hot flashes and vaginal dryness, and play a critical role in bone health by inhibiting osteoclast activity, thus reducing bone resorption and helping to prevent osteoporosis.

Pharmacokinetics

Following oral administration, conjugated estrogens are absorbed through the gastrointestinal tract. They undergo first-pass metabolism in the liver, which can affect their bioavailability. The half-life of conjugated estrogens varies, but they generally have a half-life of several hours. They are metabolized primarily in the liver and excreted in urine. The pharmacokinetics can be influenced by factors such as age, liver function, and concurrent medications.

Contra-indications

• Known hypersensitivity to conjugated estrogens or any of the excipients
• Estrogen-dependent neoplasms, including breast cancer
• Undiagnosed abnormal genital bleeding
• Active or past venous thromboembolic disorders
• Severe liver dysfunction or disease
• Pregnancy

Adverse effects

• Nausea
• Headache
• Breast tenderness
• Abdominal cramps
• Bloating
• Mood changes
• Increased risk of thromboembolic events
• Hypertension
• Cholestatic jaundice
• Gallbladder disease

Interactions

• Anticoagulants may have altered effects
• Certain anticonvulsants may reduce efficacy of estrogen therapy
• Rifampicin and other enzyme inducers may decrease effectiveness
• St. John's Wort may decrease hormone levels

Precautions

• Monitor patients for signs of thromboembolic disorders
• Assess risk factors for cardiovascular disease
• Evaluate liver function before and during treatment
• Consider individual patient history of breast cancer or other estrogen-sensitive conditions

Pregnancy

Conjugated estrogens are contraindicated in pregnancy due to risk of fetal harm.

Breast-feeding

Conjugated estrogens may be excreted in breast milk; use with caution in breastfeeding women.

Storage

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

Formulations

• Oral tablets
• Injectable forms

Indications

• Prevention of diphtheria through vaccination
• Treatment of diphtheria infection
• Management of respiratory obstruction due to pseudomembrane

Dosage

Children: Refer to specific

Adults: Refer to specific guidelines for the treatment of diphtheria. Antitoxin and antibiotics are typically used in treatment.

Mechanism of action

The pathogenicity of Corynebacterium diphtheriae is largely due to its production of diphtheria toxin, an A-B toxin that inhibits protein synthesis in host cells. The toxin is composed of two subunits: the A subunit, which enters the cytoplasm of the cell and catalyzes the ADP-ribosylation of elongation factor 2 (EF-2), leading to cell death, and the B subunit, which binds to the cell surface receptor, facilitating the entry of the A subunit. This results in local tissue damage and systemic effects, including myocarditis and neuropathy.

Pharmacodynamics

Diphtheria toxin exerts its effects primarily through inhibiting protein synthesis, causing cell death in susceptible tissues. The resulting necrosis can lead to the characteristic pseudomembrane formation in the throat and can affect other organs, including the heart and nervous system. The immune response to the toxin and the bacteria provides some level of protection, which is the basis for vaccination strategies.

Pharmacokinetics

The pharmacokinetics of the diphtheria toxin itself are not typically described in terms of absorption, distribution, metabolism, and excretion, as it is a potent toxin rather than a conventional drug. However, the body’s immune response to the toxin is crucial for recovery. After vaccination, the body generates antibodies against the toxin, which can neutralize its effects upon exposure to the bacterium.

Pregnancy

Diphtheria vaccination is recommended during pregnancy to protect the mother and fetus. The vaccine is inactivated and poses no risk.

Breast-feeding

Diphtheria vaccination is safe during breastfeeding. Antibodies may be transferred to the infant through breast milk.

Storage

Store in a refrigerator at 2-8 degrees Celsius. Do not freeze.

Formulations

• Diphtheria toxoid vaccine

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

• Whooping cough (pertussis)
• Prevention of pertussis in infants and young children through vaccination

Dosage

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

Adults: Refer to the BNF for specific dosing information.

Mechanism of action

Pertussis toxin, produced by Bordetella pertussis, acts on host cells by ADP-ribosylating a G protein, which disrupts normal signal transduction pathways. This leads to increased production of cyclic AMP, inhibiting immune responses and contributing to the characteristic symptoms of the disease.

Pharmacodynamics

The clinical manifestations of pertussis are largely due to the immune response to the toxin and the bacterium itself. The disease progresses through stages: the catarrhal stage with mild symptoms, the paroxysmal stage with intense coughing fits, and the convalescent stage where symptoms gradually improve. The severity can vary, particularly in infants and young children, who are at higher risk for complications.

Pharmacokinetics

The pharmacokinetics of Bordetella pertussis are not typically described in the same manner as pharmaceutical agents. The organism does not have a traditional pharmacokinetic profile, but it primarily colonizes the ciliated epithelial cells of the upper respiratory tract. The immune clearance of the bacteria can take several weeks, depending on the host's immune response and treatment.

Adverse effects

• Cough
• Vomiting
• Fatigue
• Apnea (especially in infants)
• Weight loss
• Paroxysms of coughing
• Encephalopathy (rare)
• Pneumonia (secondary infection)

Precautions

• Use with caution in individuals with a history of seizures
• Consider potential for severe respiratory distress, especially in infants
• Monitor for complications, particularly in young children

Pregnancy

Pertussis vaccination is recommended during pregnancy to protect the newborn, especially during outbreaks.

Breast-feeding

Vaccination during breastfeeding is safe and can provide passive immunity to the infant.

Storage

Store in a cool, dry place away from direct sunlight. Follow specific storage instructions for vaccines.

Formulations

• DTaP vaccine (Diphtheria, Tetanus, and Pertussis)
• Tdap vaccine (Tetanus, Diphtheria, and Pertussis)

Mechanism of action

Polysaccharides exert their effects through various mechanisms, often involving the modulation of immune responses. For example, certain polysaccharides can act as pathogen-associated molecular patterns (PAMPs) that are recognized by pattern recognition receptors on immune cells, leading to the activation of innate immunity. Additionally, some polysaccharides can enhance the proliferation and activation of lymphocytes, such as T-cells and B-cells, thereby influencing adaptive immune responses. Some polysaccharides also play a role in anticoagulation by inhibiting thrombin and other factors in the coagulation cascade.

Pharmacodynamics

The pharmacodynamics of polysaccharides vary widely depending on their structure and the specific biological pathways they influence. For instance, polysaccharides that act as immunomodulators can increase cytokine production, enhance phagocytosis by macrophages, and promote the differentiation of immune cells, leading to a more robust immune response. Furthermore, polysaccharides can exhibit anti-inflammatory properties by modulating the release of pro-inflammatory cytokines and chemokines. In the case of anticoagulant polysaccharides, their action may involve the binding and inhibition of specific clotting factors, thus preventing thrombus formation.

Pharmacokinetics

The pharmacokinetics of polysaccharides depend on their molecular weight, structure, and route of administration. Generally, polysaccharides are poorly absorbed in the gastrointestinal tract when taken orally due to their large size and complexity. However, certain polysaccharides are designed for parenteral administration, where they can be directly introduced into the bloodstream. Following administration, they may be metabolized by specific enzymes or by gut microbiota. The elimination half-life can vary significantly, influenced by factors such as the degree of sulfation or acetylation, which can affect their

Pregnancy

Polysaccharides are generally considered safe during pregnancy, but specific formulations should be evaluated on a case-by-case basis. Always consult a healthcare provider.

Breast-feeding

Polysaccharides are typically considered safe during breastfeeding, although individual formulations may vary. Consultation with a healthcare provider is recommended.

Storage

Polysaccharides should be stored in a cool, dry place, away from direct sunlight and moisture. Specific storage conditions may vary depending on the formulation.

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

• Tetanus prophylaxis
• Treatment of tetanus infection
• Management of tetanus symptoms

Dosage

Children: Refer to the specific guidelines for tetanus immunoglobulin and other supportive treatments as per clinical protocols.

Adults: Refer to the specific guidelines for tetanus immunoglobulin and other supportive treatments as per clinical protocols.

Mechanism of action

The tetanus toxin binds to the presynaptic membrane of motor neurons and is transported retrogradely to the spinal cord, where it interferes with neurotransmitter release, particularly inhibiting the release of glycine and gamma-aminobutyric acid (GABA), leading to unopposed motor neuron activity and resultant muscle rigidity and spasms.

Pharmacodynamics

Tetanus toxin is one of the most potent toxins known, with effects that can manifest within hours of exposure. The toxin's ability to block inhibitory neurotransmitter release results in a state of continuous muscle contraction, known as tetany. The clinical presentation of tetanus includes trismus (lockjaw), muscle rigidity, and autonomic instability, among others.

Pharmacokinetics

The pharmacokinetics of tetanus toxin are complex due to its high potency and the nature of its action. Following entry into the body, the toxin binds to nerve endings and is internalized, leading to its effects on neurotransmitter release. The half-life of the toxin is not well defined as it does not circulate freely in the bloodstream but acts locally at the neuromuscular junction. Recovery from the effects of the toxin may take weeks to months, depending on the severity of the infection and the treatment provided.

Adverse effects

• Pain at the injection site
• Fever
• Fatigue
• Headache
• Nausea

Precautions

• Ensure patient is up to date with vaccinations
• Monitor for allergic reactions post-vaccination
• Consider history of neurological disorders

Pregnancy

Tetanus vaccination is considered safe during pregnancy and is recommended to protect both the mother and the newborn.

Breast-feeding

Tetanus vaccination is safe during breastfeeding and does not affect the nursing infant.

Storage

Store in a refrigerator at 2–8 degrees Celsius. Do not freeze.

Formulations

• Tetanus toxoid vaccine

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)

Indications

• Diphtheria prophylaxis
• Tetanus prophylaxis
• Pertussis prophylaxis (when combined with other vaccines)

Dosage

Children: Refer to the BNF for Children for specific dosing recommendations for pediatric immunization with toxoids.

Adults: Refer to specific guidelines for each toxoid vaccine, as dosing may vary based on the type of vaccine and individual patient factors.

Mechanism of action

Toxoids work by stimulating the immune system to produce antibodies against the toxin without causing disease. When administered, the immune system recognizes the toxoid as a foreign substance and generates a specific immune response. This includes the production of immunoglobulin G (IgG) antibodies that can neutralize the active toxin if the individual is exposed to the bacteria in the future.

Pharmacodynamics

The pharmacodynamics of toxoids involve the activation of the adaptive immune response. After vaccination, dendritic cells present the antigen to T cells, which then help B cells differentiate into plasma cells that produce specific antibodies. The presence of these antibodies provides immunity against the toxin by neutralizing its effects, thereby preventing the disease associated with the original bacterial toxin.

Pharmacokinetics

Toxoids are typically administered via intramuscular or subcutaneous injection. Following administration, they are gradually taken up by antigen-presenting cells, which then process and present the toxoid to T cells. The immunogenic response can develop over several weeks. The duration of immunity can vary, necessitating booster doses to maintain adequate antibody levels over time.

Adverse effects

• Local reactions at the injection site, such as pain, swelling, or redness.
• Fever.
• Fatigue.
• Headache.
• Allergic reactions in rare cases.

Precautions

• Use with caution in individuals with a history of severe allergic reactions to a vaccine component.
• Monitor patients for allergic reactions post-vaccination.

Pregnancy

Toxoids are generally considered safe during pregnancy; however, consultation with a healthcare provider is recommended.

Breast-feeding

Toxoids are considered safe for use during breastfeeding.

Storage

Store in a refrigerator at 2-8°C. Do not freeze. Protect from light.

Formulations

• Diphtheria toxoid
• Tetanus toxoid
• Pertussis toxoid

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

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.