ALESOF

Indications

• Fluid and electrolyte imbalances
• Hypoglycemia
• Nutritional supplementation
• Diabetic emergencies

Dosage

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

Adults: The dosage varies based on the clinical condition and specific formulation used. For intravenous administration, consult product literature for precise dosing.

Mechanism of action

Glucose supplies energy to tissues by undergoing glycolysis, which begins with its phosphorylation by hexokinase to form glucose 6-phosphate. This activates glucose for breakdown, ultimately generating ATP and NADH. The aerobic metabolism of glucose can yield up to 36 ATP molecules. Glucose also serves as a precursor for other biomolecules and regulates various physiological processes including gene transcription and hormone secretion.

Pharmacodynamics

Glucose is an obligatory energy source for cellular activities and plays a significant role in metabolic signaling. It is oxidized to yield energy through glycolysis, the citric acid cycle, and oxidative phosphorylation. Glucose can be converted into fat for energy storage and is stored as glycogen in the liver and muscles. Its administration increases blood glucose levels and stimulates insulin secretion, particularly through oral routes that activate gut incretin hormones.

Pharmacokinetics

Glucose is rapidly absorbed from the gastrointestinal tract or directly into the bloodstream when administered intravenously. It is distributed widely throughout the body and metabolized primarily in tissues requiring energy. The body maintains glucose homeostasis through regulatory mechanisms involving insulin and glucagon. Excess glucose can be stored as glycogen or converted to triglycerides for long-term energy storage.

Adverse effects

• Hyperglycemia
• Increased osmolarity
• Fluid overload
• Electrolyte imbalances

Interactions

• Insulin - may require dose adjustments

Precautions

• Use with caution in patients with diabetes mellitus
• Monitor blood glucose levels in patients receiving parenteral glucose
• Adjust dosage in renal impairment

Pregnancy

Glucose is generally considered safe in pregnancy; however, monitoring is advised, especially in diabetic patients.

Breast-feeding

Glucose is considered safe during breastfeeding, as it is a natural sugar found in breast milk.

Storage

Store at room temperature, away from light. Avoid freezing.

Formulations

• Glucose 5% solution for infusion
• Glucose 10% solution for infusion
• Glucose 0.9% solution for injection
• Glucose sodium chloride combination solutions

Indications

• Symptomatic relief of allergic rhinoconjunctivitis (hay fever)
• Chronic idiopathic urticaria (hives)

Dosage

Children: For children aged 6 to 12 years, the typical dose is 5 mg once daily for children weighing less than 30 kg, and 10 mg once daily for those weighing 30 kg or more. For children aged 2 to 5 years, 2.5 mg once daily is recommended

Adults: The usual adult dose is 10 mg once daily. In some cases, this can be adjusted based on individual response and tolerability.

Mechanism of action

Cetirizine selectively inhibits the H1 receptor, preventing the action of histamine, which is released during allergic reactions. By blocking these receptors, cetirizine reduces symptoms associated with allergic responses, including itching, sneezing, and runny nose. It also exhibits mild anticholinergic properties, which contribute to its effectiveness in alleviating symptoms.

Pharmacodynamics

Cetirizine has a faster onset of action compared to older antihistamines, providing relief from allergy symptoms within 1 hour of administration. Its effects can last for up to 24 hours, allowing for once-daily dosing. The drug is generally well-tolerated, with sedation being less common than with first-generation antihistamines due to its reduced penetration across the blood-brain barrier.

Pharmacokinetics

Cetirizine is rapidly absorbed after oral administration, with peak plasma concentrations occurring within 1-2 hours. It is approximately 93% bound to plasma proteins. The elimination half-life is about 8 hours in healthy adults, but may be prolonged in individuals with renal impairment. Cetirizine is primarily excreted unchanged in the urine, and dose adjustments may be necessary for patients with significant renal dysfunction.

Contra-indications

• Acute porphyrias
• Severe renal impairment

Adverse effects

• Drowsiness
• Headache
• Anxiety
• Increased appetite
• Asthenia
• Diarrhoea
• Dry mouth
• Dyspnoea
• Fever
• Gastritis
• Gastrointestinal discomfort
• Insomnia
• Nasal complaints
• Nausea
• Oral herpes

Interactions

• Other antihistamines (non-sedating)

Precautions

• Drowsiness may occur and affect performance of skilled tasks, such as cycling or driving
• Alcohol should be avoided

Pregnancy

Most manufacturers of antihistamines advise avoiding their use during pregnancy; however, there is no evidence of teratogenicity.

Breast-feeding

Most antihistamines are present in breast milk in varying amounts; although not known to be harmful, most manufacturers advise avoiding their use in mothers who are breast-feeding.

Storage

Store in a cool, dry place away from light.

Formulations

• Cetirizine hydrochloride 10 mg tablets
• Cetirizine hydrochloride 10 mg oral solution

Indications

• Food preservative
• Treatment of urea cycle disorders
• Metabolic disorders involving benzoyl-CoA

Dosage

Children: Refer to the BNF for Children for specific dosing guidelines based on condition.

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

Mechanism of action

Benzoate acts mainly by inhibiting the growth of bacteria and fungi through its ability to lower the pH, creating an environment that is less favorable for microbial growth. It is also involved in metabolic pathways where it helps in the conjugation of toxic substances, facilitating their excretion from the body.

Pharmacodynamics

Benzoate is known for its antimicrobial properties, which are particularly effective against a wide range of fungi and bacteria. Its efficacy as a preservative is due to its ability to penetrate microbial cell membranes and disrupt their metabolic processes. Additionally, it has been observed to modulate various metabolic pathways, particularly those associated with aromatic compound degradation.

Pharmacokinetics

After ingestion, benzoate is rapidly absorbed in the gastrointestinal tract. It is metabolized primarily in the liver, where it undergoes conjugation with glycine to form hippurate, which is then excreted in the urine. The half-life of benzoate varies depending on individual metabolic rates but is generally short due to its efficient conversion and excretion.

Pregnancy

There is limited data on the use of benzoate in pregnancy. Consultation with healthcare professionals is advised before use.

Breast-feeding

Limited data is available on the excretion of benzoate in breast milk. Caution is recommended when administering to nursing mothers.

Storage

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

Indications

• Allergic rhinitis (seasonal and perennial)
• Chronic idiopathic urticaria
• Allergic asthma
• Physical urticaria
• Atopic dermatitis

Dosage

Children: For children aged 6 to 12 years, the usual dose is 5 mg twice daily or 10 mg once daily. For children aged 2 to 5 years, the usual dose is 2.5 mg twice daily or 5 mg once daily

Adults: The usual adult dose is 10 mg once daily, which can be taken with or without food.

Mechanism of action

Cetirizine selectively inhibits peripheral H1 receptors, leading to a reduction in the effects of histamine, a chemical responsible for allergic symptoms. The drug demonstrates negligible anticholinergic and antiserotonergic activity. It has shown to have minimal penetration into the central nervous system, thereby reducing the likelihood of sedation, a common side effect associated with antihistamines.

Pharmacodynamics

Cetirizine exhibits antihistaminic and anti-inflammatory effects that are beneficial in managing allergic conditions. It effectively alleviates symptoms of chronic idiopathic urticaria and both perennial and seasonal allergic rhinitis. Clinical trials have established its efficacy in improving symptoms of allergic respiratory diseases, and it significantly inhibits wheal and flare responses within 20 minutes of administration, with effects lasting for up to 24 hours.

Pharmacokinetics

Cetirizine is well absorbed after oral administration, with peak plasma concentrations typically occurring within 1 hour. It has a long half-life, allowing for once-daily dosing. The drug is primarily eliminated via the kidneys, with a portion being excreted unchanged. Its pharmacokinetic profile demonstrates low potential for significant central nervous system penetration, contributing to its reduced sedation compared to first-generation antihistamines.

Adverse effects

• dry mouth
• drowsiness
• fatigue
• headache
• nausea
• dizziness

Precautions

• Caution in patients with renal impairment
• Caution when driving or operating machinery due to potential drowsiness

Pregnancy

Cetirizine should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus. Consult relevant guidelines.

Breast-feeding

Cetirizine is excreted in breast milk. Caution is advised when administering to nursing mothers.

Storage

Store below 25°C. Protect from light and moisture. Keep out of reach of children.

Formulations

• tablets
• oral solution
• chewable tablets

Indications

• Acidulant in food and beverages
• Preservative in pharmaceutical formulations
• pH adjuster in various chemical preparations

Dosage

Children: Refer to product-specific guidelines for appropriate dosing based on formulation and indication.

Adults: Refer to product-specific guidelines for appropriate dosing based on formulation and indication.

Mechanism of action

Citric acid acts by chelating metal ions, which can enhance the solubility of certain compounds and improve their bioavailability. It also contributes to the acidity of the environment, which can influence enzymatic activity and metabolic pathways, particularly in the degradation of citronellol.

Pharmacodynamics

Citric acid exhibits mild pharmacological effects primarily attributed to its role in metabolic processes. It aids in the regulation of pH levels, which can impact enzymatic reactions and biochemical pathways. The acid's chelating properties may help to reduce the toxicity of certain metal ions in biological systems.

Pharmacokinetics

Citric acid is rapidly absorbed after oral administration and is metabolized in the liver. It undergoes conversion to various metabolites in the citric acid cycle, contributing to energy production. The elimination primarily occurs through urine, with minimal accumulation in the body.

Pregnancy

Citric acid is generally regarded as safe during pregnancy when used in food amounts. However, consult a healthcare provider for advice on medicinal use.

Breast-feeding

Citric acid is considered safe during breastfeeding when consumed in food amounts. For medicinal use, consult a healthcare provider.

Storage

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

Indications

• Dehydration
• Hypovolemia
• Electrolyte imbalance
• Fluid resuscitation in shock
• Maintenance fluid therapy

Dosage

Children: Dosage should be determined based on the individual child's condition and specific guidelines. Refer to the BNF for Children for detailed dosing information.

Adults: Dosage varies based on clinical condition and patient needs. Refer to specific clinical guidelines and protocols for detailed dosing information.

Mechanism of action

Crystalloids work primarily by increasing the intravascular volume and improving tissue perfusion. They help restore fluid balance by distributing into the extracellular compartment, effectively replenishing lost fluids and electrolytes. The exact mechanism depends on the specific type of crystalloid solution used, but generally, they contribute to osmotic pressure and fluid movement across cell membranes.

Pharmacodynamics

The pharmacodynamics of crystalloids involve their ability to quickly expand the intravascular volume and maintain blood pressure during hypovolemic states. The effectiveness of crystalloids in volume replacement is influenced by their osmolarity and electrolyte composition. Isotonic crystalloids are particularly effective in treating dehydration and shock, as they mimic the body's extracellular fluid composition.

Pharmacokinetics

Crystalloids are characterized by rapid distribution within the extracellular space after administration. They are distributed throughout the interstitial and intravascular compartments within minutes. The half-life of crystalloids is relatively short, as they are rapidly eliminated from the body, with a significant portion excreted via the kidneys. The duration of action can be brief, often necessitating repeated administration in cases of ongoing fluid loss.

Pregnancy

Consult relevant guidelines as data on safety in pregnancy is limited.

Breast-feeding

Consult relevant guidelines as data on safety during breastfeeding is limited.

Storage

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

Indications

• Lead poisoning
• Zinc toxicity
• Cadmium poisoning
• Iron overload disorders

Dosage

Adults: Refer to the BNF for specific dosing recommendations for adults, as it may vary based on the condition being treated and the severity of metal poisoning.

Mechanism of action

The pharmacologic effects of edetate calcium disodium are due to the formation of chelates with divalent and trivalent metals. A stable chelate forms with any metal that can displace calcium from the molecule, which includes lead, zinc, cadmium, and iron. The excretion of zinc is significantly increased, while the effect on calcium excretion is minimal. The chelation process helps to reduce the toxicity of heavy metals in the body by promoting their urinary excretion.

Pharmacodynamics

Edetate calcium acts as a heavy metal chelating agent, forming stable, water-soluble complexes with metal ions that can be excreted in urine. One gram of edetate calcium can theoretically bind up to 620 mg of lead, though actual urinary excretion rates are lower, with approximately 5 mg of lead excreted per gram of EDTA in lead-poisoned patients. It is relatively ineffective against mercury, gold, or arsenic poisoning but can mobilize and eliminate zinc, cadmium, copper, iron, and manganese.

Pharmacokinetics

After intravenous administration, edetate calcium disodium is rapidly distributed in the blood and has a half-life that can vary based on the patient's condition and the presence of heavy metals. The drug is primarily excreted unchanged in the urine. Calcium levels may be transiently lowered during infusion, but significant mobilization of body calcium stores is usually not observed unless very slow infusions are administered. The effects on metal ion excretion are dose-dependent and vary according to the specific metal involved.

Contra-indications

• Hypersensitivity to edetate calcium disodium or any component of the formulation
• Pre-existing renal impairment
• Calcium deficiency states

Adverse effects

• Hypocalcemia
• Renal impairment
• Gastrointestinal disturbances such as nausea and vomiting
• Headache
• Hypotension
• Electrolyte imbalances

Interactions

• Increased risk of toxicity when used with nephrotoxic agents
• May interfere with the absorption of certain minerals and vitamins
• Should not be mixed with other intravenous drugs due to potential chemical interactions

Precautions

• Monitor renal function during treatment
• Use caution in patients with cardiovascular disease due to potential hypotensive effects
• Evaluate calcium levels periodically in patients receiving prolonged therapy
• Use with caution in patients with a history of seizures

Pregnancy

Limited data available on the use of edetate calcium disodium in pregnant women. Use only if clearly needed.

Breast-feeding

It is not known whether edetate calcium disodium is excreted in human milk. Caution is advised.

Storage

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

Formulations

• Edetate calcium disodium injection

Indications

• Aromatherapy
• Anxiety relief
• Mood enhancement
• Antimicrobial applications
• Pain management
• Anti-inflammatory treatments

Dosage

Children: Dosage for paediatric use of essences should be approached with caution and tailored to the child's age, weight, and condition. Refer to specific pediatric guidelines or consult a healthcare provider for appropriate dosing information.

Adults: Dosage for essences varies widely based on the specific type of essence and the intended use. It is essential to refer to specific guidelines or consult a healthcare provider for appropriate dosing information.

Mechanism of action

The mechanism of action of essences can vary depending on the specific substance in question. Generally, essential oils and herbal extracts act through a combination of phytochemical interactions, influencing neurotransmitter systems, modulating inflammation, and exhibiting antimicrobial properties. These compounds may interact with various receptors in the body, including G-protein coupled receptors and ion channels, leading to physiological responses.

Pharmacodynamics

Pharmacodynamics of essences is largely dependent on their chemical composition. Many essential oils contain terpenes, phenols, and other bioactive compounds that exhibit a range of effects such as antibacterial, antifungal, anti-inflammatory, and analgesic properties. The effects can vary based on concentration, route of administration, and individual patient factors, influencing their efficacy and safety.

Pharmacokinetics

The pharmacokinetics of essences involves absorption, distribution, metabolism, and excretion. Essential oils are typically absorbed through the skin or via inhalation and can be distributed throughout the body via the bloodstream. They are often metabolized by the liver, with various pathways leading to the formation of active or inactive metabolites. Excretion mostly occurs through urine, but some components may also be eliminated through bile or exhalation.

Pregnancy

The safety of essence during pregnancy has not been established. Consultation with a healthcare provider is recommended before use.

Breast-feeding

It is unclear whether essence is excreted in breast milk. Caution is advised, and it is best to consult a healthcare provider.

Storage

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

Indications

• Insecticide for agricultural use
• Research tool in toxicology

Dosage

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

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

Mechanism of action

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

Pharmacodynamics

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

Pharmacokinetics

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

Pregnancy

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

Breast-feeding

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

Storage

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

Formulations

• Liquid formulation

Indications

• Allergic conditions
• Autoimmune diseases
• Asthma and chronic obstructive pulmonary disease (COPD)
• Certain cancers (e.g., leukemia, lymphoma)
• Skin conditions (e.g., dermatitis)
• Inflammatory bowel disease
• Multiple sclerosis exacerbations
• Severe infections requiring immunosuppression

Dosage

Children: Refer to BNF for Children for specific dosing; doses vary significantly based on the child's age, weight, and condition being treated.

Adults: Refer to BNF for specific dosing; typically, initial doses range from 4 to 48 mg depending on the severity of the condition.

Mechanism of action

Methylprednisolone exerts its effects by binding to glucocorticoid receptors, leading to the modulation of gene expression. This interaction influences the transcription of anti-inflammatory proteins while suppressing the expression of pro-inflammatory genes, ultimately resulting in reduced inflammation and immune response.

Pharmacodynamics

The pharmacodynamic effects of methylprednisolone are characterized by its ability to decrease inflammation, suppress the immune response, and affect carbohydrate metabolism. Therapeutic doses lead to various systemic effects, including modification of leukocyte distribution and inhibition of cytokine production.

Pharmacokinetics

Methylprednisolone is well absorbed after oral administration, with a bioavailability of approximately 50%. It has a volume of distribution that reflects extensive tissue binding. The drug is metabolized primarily in the liver through conjugation and reduction, and its metabolites are excreted in urine. The half-life varies based on the route of administration but is generally around 18 to 36 hours.

Adverse effects

• Increased blood pressure
• Hyperglycemia
• Weight gain
• Mood changes
• Insomnia
• Gastrointestinal disturbances
• Increased susceptibility to infections

Interactions

• methylphenidate+apraclonidine: Severe (decreases effects)
• methylthioninium chloride+bupropion: Severe (increases risk of severe hypertension)
• methylphenidate+linezolid: Severe (increases risk of elevated blood pressure)
• rasagiline+methylphenidate: Severe (increases risk of a hypertensive crisis)
• mao-inhibitors+methylphenidate: Severe (increases risk of a hypertensive crisis)
• dronedarone+methylprednisolone: Moderate (increases exposure)
• miconazole+methylprednisolone: Moderate (increases concentration)
• antifungals, azoles+methylprednisolone: Moderate (increases exposure)
• crizotinib+methylprednisolone: Moderate (increases exposure)

Precautions

• Use with caution in patients with hypertension
• Monitor blood glucose levels in diabetic patients
• Consider potential for infection risk due to immunosuppression
• Evaluate for psychiatric effects in susceptible individuals

Pregnancy

Corticosteroids may be used during pregnancy if the potential benefit justifies the risk to the fetus. Careful monitoring is advised.

Breast-feeding

Corticosteroids are excreted in breast milk; caution is advised. Monitor the infant for potential effects.

Storage

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

Formulations

• Tablets
• Injectable solutions
• Topical preparations

Mechanism of action

Methylsulphate functions as a methylating agent, transferring a methyl group to nucleophiles. This process involves the formation of a sulfonium ion, which is highly reactive and can readily react with nucleophilic sites on various substrates, leading to methylation reactions.

Pharmacodynamics

The pharmacodynamics of methylsulphate is primarily related to its role as a methylating agent in biochemical reactions. It can alter the structure and function of biological molecules, potentially affecting cellular processes and signaling pathways. However, detailed pharmacodynamic studies specific to therapeutic use are limited.

Pharmacokinetics

There is limited information on the pharmacokinetics of methylsulphate, given its typical use as a reagent in laboratory settings rather than a clinical drug. When used in chemical reactions, its reactivity and transformation into other compounds would dictate its pharmacokinetic profile, which could vary significantly based on the specific context of use.

Pregnancy

There is limited data on the use of methylsulphate in pregnancy. Consult relevant guidelines.

Breast-feeding

Data on the excretion of methylsulphate in human milk is not available. Caution is advised.

Storage

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

Dosage

Children: Refer to BNF for Children for specific recommendations regarding the consumption of orange juice in children.

Adults: There is no standard dosage for orange juice as it is typically consumed as a beverage. Moderation is advised, especially for individuals on certain medications.

Mechanism of action

The exact mechanism of action of orange juice is not fully understood, but it is known to contain compounds that can influence the metabolism of certain drugs. For instance, it may affect the activity of cytochrome P450 enzymes, particularly CYP3A4, which can alter the pharmacokinetics of medications.

Pharmacodynamics

Orange juice is known to enhance the bioavailability of certain nutrients and may influence the pharmacological effects of some drugs. Its high vitamin C content contributes to various physiological functions, including antioxidant activity, which may indirectly support overall health.

Pharmacokinetics

The pharmacokinetics of orange juice itself are not extensively studied, but it is generally absorbed well through the gastrointestinal tract. The compounds in orange juice can affect the absorption and metabolism of medications, leading to varied clinical effects depending on the drug in question.

Interactions

• orange juice + celiprolol: Unknown (decreases exposure)

Formulations

• juice
• whole fruit

Indications

• Preservative in cosmetics
• Preservative in pharmaceuticals
• Preservative in food products

Dosage

Children: Refer to specific product guidelines as dosing varies based on formulation and concentration used.

Adults: Refer to specific product guidelines as dosing varies based on formulation and concentration used.

Mechanism of action

Parabens work by inhibiting the growth of microorganisms through their ability to disrupt the cellular processes of bacteria and fungi. They penetrate the microbial cell membrane and disrupt enzyme and protein functions, leading to cell death. Parabens are known to have low toxicity and are metabolized by the body, subsequently being excreted in urine.

Pharmacodynamics

Parabens demonstrate broad-spectrum antimicrobial activity, making them effective preservatives in various formulations. Their efficacy is influenced by factors such as concentration, pH, and the presence of other ingredients in the formulation. Due to their structural similarity to estrogen, there has been concern regarding their potential endocrine-disrupting effects, although the clinical significance of this is still debated.

Pharmacokinetics

Parabens are readily absorbed through the skin and gastrointestinal tract. Once absorbed, they are rapidly metabolized primarily in the liver. They undergo hydrolysis to form para-hydroxybenzoic acid, which is then conjugated with glucuronic acid and excreted in urine. The half-life of parabens in the human body is relatively short, and they are eliminated rapidly.

Adverse effects

• Allergic reactions, such as skin rashes
• Irritation at the site of application
• Endocrine disruption (in high concentrations)

Precautions

• Use with caution in individuals with known sensitivities or allergies to parabens
• Consider potential endocrine effects with prolonged exposure

Pregnancy

Parabens are generally considered safe in cosmetics and personal care products during pregnancy, although caution is advised due to potential endocrine disruption.

Breast-feeding

Parabens are considered safe in breastfeeding, but it is recommended to use products with minimal or no parabens when possible.

Storage

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

Formulations

• Topical creams
• Lotions
• Shampoos
• Conditioners
• Makeup products
• Pharmaceutical preparations

Indications

• Hyperthyroidism
• Graves' disease
• Thyroid storm

Dosage

Children: Refer to the BNF

Adults: The usual initial dose of propylthiouracil in adults is 300 mg per day, divided into 3 doses. The maintenance dose is typically 100-150 mg per day, adjusted based on thyroid function tests.

Mechanism of action

Propylthiouracil acts by inhibiting the enzyme thyroid peroxidase, which is involved in the iodination of tyrosine residues in thyroglobulin, a precursor of thyroid hormones. By blocking this enzyme, PTU reduces the production of thyroxine (T4) and triiodothyronine (T3), leading to decreased thyroid hormone levels in circulation. Additionally, PTU inhibits the conversion of T4 to T3 in peripheral tissues, further contributing to its antithyroid effects.

Pharmacodynamics

The pharmacodynamic effects of propylthiouracil are primarily centered around its ability to lower thyroid hormone levels, which helps alleviate symptoms of hyperthyroidism such as increased heart rate, weight loss, and anxiety. The onset of action can vary, but therapeutic effects may be observed within several weeks of initiation. Monitoring thyroid function tests is essential to assess the efficacy and adjust dosing as needed.

Pharmacokinetics

Propylthiouracil is well absorbed from the gastrointestinal tract, though its bioavailability can be affected by factors such as food intake. The drug is extensively metabolized in the liver, and its elimination half-life averages around 1-2 hours. Most of the drug is excreted in urine as metabolites. It is important to note that due to its rapid metabolism, multiple daily doses may be required to maintain therapeutic levels.

Interactions

• propylthiouracil+metyrapone: Severe (decreases effects)

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.

Dosage

Children: Refer to specific product guidelines for dosing information.

Adults: Refer to specific product guidelines for dosing information.

Adverse effects

• Nausea
• Vomiting
• Diarrhea
• Abdominal pain
• Headache
• Dizziness
• Fatigue

Precautions

• Use with caution in patients with a history of gastrointestinal disorders.
• Monitor for signs of allergic reactions.

Pregnancy

Safety in pregnancy has not been established, use only if clearly needed.

Breast-feeding

Consult a healthcare provider before use while breastfeeding.

Storage

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

Indications

• Constipation
• Diagnostic aid in colonoscopy preparation
• Management of hyperosmolality in various conditions

Dosage

Children: For children, the dosage should be determined based on age and condition, and it is advised to refer to the BNF for Children for specific dosing guidelines.

Adults: The typical dose for adults is 30 to 150 mL of sorbitol solution (70%) taken orally, as needed, usually before bedtime.

Mechanism of action

Sorbitol exerts its laxative effect by drawing water into the large intestine, thereby stimulating bowel movements. It acts as a hygroscopic agent, pulling water from tissues into the feces, which reflexively stimulates evacuation. In metabolic pathways, sorbitol is produced from glucose via aldose reductase and is converted to fructose by sorbitol dehydrogenase, with implications in diabetic complications such as retinopathy.

Pharmacodynamics

Sorbitol's laxative effect results from its osmotic properties, which increase the water content of the stool and soften it, facilitating easier passage. Additionally, sorbitol can induce apoptosis in certain cancer cell lines, indicating potential therapeutic implications beyond its laxative use. The modulation of intracellular signaling pathways through the regulation of proteins such as Bax and Bcl-2 suggests a complex role in cellular health and disease.

Pharmacokinetics

Sorbitol is poorly absorbed in the gastrointestinal tract, which contributes to its efficacy as a laxative. It is metabolized in the liver, primarily through the polyol pathway. The absorption and distribution of sorbitol are affected by its osmotic properties, leading to increased intestinal water retention. Its elimination is primarily via renal excretion, with minimal systemic absorption, thus reducing the risk of systemic side effects.

Adverse effects

• Diarrhea
• Abdominal cramps
• Nausea
• Vomiting
• Electrolyte imbalances

Precautions

• Use with caution in patients with renal impairment
• May exacerbate gastrointestinal conditions

Pregnancy

Sorbitol is generally considered safe during pregnancy, but should be used under medical supervision.

Breast-feeding

Sorbitol is excreted in breast milk in small amounts; consult a healthcare provider before use.

Storage

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

Formulations

• Oral solution
• Syrup

Indications

• Providing energy in dietary supplementation
• Enhancing flavor in food products
• Replacement of carbohydrates in certain medical nutrition therapies

Dosage

Children: Refer to general dietary guidelines for carbohydrate intake in children. No specific dosing guidelines provided.

Adults: Refer to general dietary guidelines for carbohydrate intake. No specific dosing guidelines provided.

Mechanism of action

Sugar is metabolized in the body to provide energy. Upon ingestion, sucrose is broken down by the enzyme sucrase into its constituent monosaccharides, glucose and fructose, which are then absorbed into the bloodstream. These monosaccharides can be utilized by cells for energy or stored as glycogen in the liver and muscles.

Pharmacodynamics

As a simple carbohydrate, sugar elevates blood glucose levels rapidly after consumption, leading to increased insulin secretion from the pancreas. This insulin facilitates the uptake of glucose by tissues, promoting energy production. The rapid increase in blood sugar can provide quick energy but may also lead to potential negative effects on metabolism and weight if consumed in excess.

Pharmacokinetics

After oral administration, sugar is quickly hydrolyzed in the gastrointestinal tract. Peak plasma glucose concentrations typically occur within 30 minutes to 2 hours post-ingestion, depending on the amount consumed and individual metabolism. The half-life of glucose in the bloodstream is relatively short, as it is rapidly taken up by tissues or converted into glycogen.

Pregnancy

Sugar is generally considered safe for use during pregnancy, but excessive intake should be avoided to prevent gestational diabetes and excessive weight gain.

Breast-feeding

Sugar is safe during breastfeeding; however, excessive consumption should be avoided.

Storage

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

Formulations

• Granulated sugar
• Brown sugar
• Powdered sugar
• Liquid sugar

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

• Diabetes management
• Weight management
• Flavor enhancement in food and beverages
• Dietary restrictions

Dosage

Children: Paediatric dosing for sweet substances should be determined based on age, weight

Adults: Dosage for sweet substances varies widely depending on the specific compound and its intended use. For example, in diabetic patients, artificial sweeteners may be substituted for sugar based on individual dietary needs and preferences. It is recommended to refer to specific product guidelines for appropriate dosing.

Mechanism of action

Sugars and sweeteners activate taste receptors on the tongue, primarily the T1R2 and T1R3 receptor heterodimers, which are responsible for the sweet taste perception. This stimulation leads to a cascade of intracellular signaling that results in the sensation of sweetness. Artificial sweeteners often have a higher affinity for these receptors, providing a sweet taste without significant caloric intake.

Pharmacodynamics

The pharmacodynamic properties of sweet substances vary significantly. Natural sugars are metabolized to glucose, which is utilized by the body for energy, influencing insulin secretion and blood glucose levels. Artificial sweeteners, on the other hand, are not metabolized in the same way and do not contribute to blood glucose levels, making them useful for individuals managing diabetes. The perception of sweetness can also influence appetite and food intake, potentially affecting weight management.

Pharmacokinetics

Natural sugars are absorbed in the gastrointestinal tract, with glucose rapidly entering the bloodstream, leading to a quick increase in blood sugar levels. They are metabolized primarily in the liver and utilized by various tissues. In contrast, many artificial sweeteners are poorly absorbed and may pass through the gastrointestinal tract unchanged, or they can be partially metabolized by gut bacteria. The elimination half-lives and metabolic pathways for these substances vary widely based on the specific compound.

Pregnancy

There is limited data on the effects of sweeteners during pregnancy. It is advisable to use them in moderation and consult a healthcare provider.

Breast-feeding

Generally considered safe in moderation, but it is advisable to consult a healthcare provider.

Storage

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

Indications

• Hyperthyroidism
• Graves' disease

Dosage

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

Adults: Refer to the BNF for specific dosing guidance based on the patient's condition and clinical response.

Mechanism of action

Thiourea acts by inhibiting the enzyme thyroid peroxidase, which is essential for the synthesis of thyroid hormones. This inhibition prevents the iodination of tyrosine residues in thyroglobulin, thereby reducing the production of thyroxine (T4) and triiodothyronine (T3). Additionally, thiourea may influence protein citrullination and impact pathways involved in thyroid hormone biosynthesis.

Pharmacodynamics

The pharmacodynamic effects of thiourea include a decrease in the levels of circulating thyroid hormones, resulting in an overall reduction in metabolic rate. This leads to alleviation of symptoms associated with hyperthyroidism. The onset of action may vary, with some patients experiencing improvement within weeks of starting therapy.

Pharmacokinetics

Thiourea is absorbed well from the gastrointestinal tract, with peak plasma concentrations occurring within 1 to 2 hours after oral administration. The drug is metabolized in the liver, with a half-life that can vary based on individual metabolic rates. It is primarily excreted in urine, with renal function playing a significant role in its clearance.

Contra-indications

• Hypersensitivity to thiourea or any component of the formulation
• Severe liver dysfunction
• Pregnancy

Adverse effects

• Agranulocytosis
• Hypothyroidism
• Skin rashes
• Nausea and vomiting
• Headache
• Dizziness

Interactions

• Antithyroid drugs may enhance the effects of thiourea
• Concurrent use with other myelosuppressive agents may increase the risk of bone marrow suppression

Precautions

• Monitor blood counts regularly due to the risk of agranulocytosis
• Use with caution in patients with pre-existing liver disease
• Patients should be advised to report any signs of infection or unusual bleeding

Pregnancy

Thiourea is contraindicated in pregnancy due to potential harm to the fetus.

Breast-feeding

It is not known whether thiourea is excreted in human milk. Caution should be exercised.

Storage

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

Formulations

• Tablets
• Oral solution

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

Glucose supplies most of the energy to all tissues by generating energy molecules ATP and NADH during a series of metabolism reactions called glycolysis. Glycolysis can be divided into two main phases where the preparatory phase is initiated by the phosphorylation of glucose by hexokinase to form glucose 6-phosphate. The addition of the high-energy phosphate group activates glucose for the subsequent breakdown in later steps of glycolysis and is the rate-limiting step. Products end up as substrates for following reactions, to ultimately convert C6 glucose molecule into two C3 sugar molecules. These products enter the energy-releasing phase where the total of 4ATP and 2NADH molecules are generated per one glucose molecule. The total aerobic metabolism of glucose can produce up to 36 ATP molecules. These energy-producing reactions of glucose are limited to D-glucose as L-glucose cannot be phosphorylated by hexokinase. Glucose can act as precursors to generate other biomolecules such as vitamin C. It plays a role as a signaling molecule to control glucose and energy homeostasis. Glucose can regulate gene transcription, enzyme activity, hormone secretion, and the activity of glucoregulatory neurons. The types, number, and kinetics of glucose transporters expressed depends on the tissues and fine-tunes glucose uptake, metabolism, and signal generation to preserve cellular and whole body metabolic integrity. Vascular calcification is a hallmark of type 2 diabetes. Glucose stimulates calcification in culture of vascular smooth muscle cells (VSMCs) but the underlying mechanisms remain obscure. We observed that high glucose levels stimulated mouse and human VSMC trans-differentiation into chondrocytes, with increased levels of Sox9, type II collagen, glycosaminoglycan and Runx2 expression, and increased alkaline phosphatase activity and mineralization. These effects were associated with increased expression of IL-1beta, which stimulated alkaline phosphatase and calcification, suggesting that glucose induces chondrocyte differentiation of VSMCs, possibly through IL-1beta activation.

Pharmacodynamics

Blood glucose is an obligatory energy source for humans involved in various cellular activities, and it also acts as a signaling molecule for diverse glucose-sensing molecules and proteins. Glucose undergoes oxidation into carbon dioxide, water, and yields energy molecules in the process of glycolysis and subsequent citric cycle and oxidative phosphorylation. Glucose is readily converted into fat in the body which can be used as a source of energy as required. Under a similar conversion into storage of energy, glucose is stored in the liver and muscles as glycogen. Glucose stores are mobilized in a regulated manner, depending on the tissues' metabolic demands. Oral glucose tablets or injections serve to increase the supply of glucose and oral glucose administration is more effective in stimulating insulin secretion because it stimulates the incretin hormones from the gut, which promotes insulin secretion.

Mechanism of action

Cetirizine, a metabolite of _hydroxyzine_, is an antihistamine drug. Its main effects are achieved through selective inhibition of peripheral H1 receptors. The antihistamine activity of cetirizine has been shown in a variety of animal and human models. _In vivo_ and _ex vivo_ animal models have shown insignificant anticholinergic and antiserotonergic effects. In clinical studies, however, dry mouth was found to be more frequent with cetirizine than with a placebo. In vitro receptor binding studies have demonstrated no detectable affinity of cetirizine for histamine receptors other than the H1 receptors. Studies with radiolabeled cetirizine administration in the rat have demonstrated insignificant penetration into the brain. _Ex vivo_ studies in the mouse have shown that systemically administered cetirizine does not occupy cerebral H1 receptors significantly. Cetirizine, a human metabolite of hydroxyzine, is an antihistamine; its principal effects are mediated via selective inhibition of peripheral H1 receptors. The antihistaminic activity of cetirizine has been clearly documented in a variety of animal and human models. In vivo and ex vivo animal models have shown negligible anticholinergic and antiserotonergic activity. In clinical studies, however, dry mouth was more common with cetirizine than with placebo. In vitro receptor binding studies have shown no measurable affinity for other than H1 receptors. Autoradiographic studies with radiolabeled cetirizine in the rat have shown negligible penetration into the brain. Ex vivo experiments in the mouse have shown that systemically administered cetirizine does not significantly occupy cerebral H1 receptors.

Pharmacodynamics

**General effects and respiratory effects** Cetirizine, the active metabolite of the piperazine H₁-receptor antagonist hydroxyzine, minimizes or eliminates the symptoms of chronic idiopathic urticaria, perennial allergic rhinitis, seasonal allergic rhinitis, allergic asthma, physical urticaria, and atopic dermatitis. The clinical efficacy of cetirizine for allergic respiratory diseases has been well established in numerous trials. **Effects on urticaria/anti-inflammatory effects** It has anti-inflammatory properties that may play a role in asthma management. There is evidence that cetirizine improves symptoms of urticaria. Marked clinical inhibition of a wheal and flare response occurs in infants, children as well as adults within 20 minutes of one oral dose and lasts for 24 h. Concomitant use of cetirizine reduces the duration and dose of topical anti-inflammatory formulas used for the treatment of atopic dermatitis.

Mechanism of action

The pharmacologic effects of edetate calcium disodium are due to the formation of chelates with divalent and trivalent metals. A stable chelate will form with any metal that has the ability to displace calcium from the molecule, a feature shared by lead, zinc, cadmium, manganese, iron and mercury. The amounts of manganese and iron metabolized are not significant. Copper is not mobilized and mercury is unavailable for chelation because it is too tightly bound to body ligands or it is stored in inaccessible body compartments. The excretion of calcium by the body is not increased following intravenous administration of edetate calcium disodium, but the excretion of zinc is considerably increased. Effects on rat liver glucocorticoid receptor in vitro was studied. At 4 °C, 10 mmole EDTA had a stablizing effect on unbound hepatic glucocorticoid receptors. Apparently, endogenous metal ions are involved in the processes of glucocorticoid-receptor complex stabilization and transformation. Edetate disodium injection forms chelates with the cations of calcium and many divalent and trivalent metals. Because of its affinity for calcium, edetate disodium will produce a lowering of the serum calcium level during intravenous infusion. Slow infusion over a protracted period may cause mobilization of extracirculatory calcium stores. Edetate disodium exerts a negative inotropic effect upon the heart. Edetate disodium likewise forms chelates with other polyvalent metals and produces increases in urinary excretion of magnesium, zinc and other trace elements. It does not form a chelate with potassium but may reduce the serum level and increase urinary loss of potassium.

Pharmacodynamics

Edetate calcium is a heavy metal chelating agent. The calcium in edetate calcium can be displaced by divalent or trivalent metals to form a stable water soluble complex that can be excreted in the urine. In theory, 1 g of edetate calcium can theoretically bind 620 mg of lead, but in reality only about 5 mg per gram is actually excreted into the urine in lead poisoned patients. In addition to chelating lead, edetate calcium also chelates and eliminates zinc from the body. Edetate calcium also binds cadmium, copper, iron and manganese, but to a much lesser extent than either lead or zinc. Edetate calcium is relatively ineffective for use in treating mercury, gold or arsenic poisoning.

Mechanism of action

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

Mechanism of action

Sorbitol exerts its laxative effect by drawing water into the large intestine, thereby stimulating bowel movements. ... Sorbitol exerts hygroscopic and/or local irritant action, drawing water from tissues into feces and reflexly stimulating evacuation. The polyol pathway consists of two enzymes aldose reductase (AR) and sorbitol dehydrogenase (SDH); the former is the first enzyme in the polyol pathway, that catalyzes the reduction of glucose to sorbitol, the latter is the second one, that converts sorbitol to fructose using by NAD(+) as a cofactor. ... SDH activity, the second step in the polyol pathway, might make a greater contribution to the etiology of diabetic retinopathy than does the first step involving AR. /This paper proposes/ a novel hypothesis that polymorphisms of SDH gene may be correlated with SDH gene expression levels in diabetic retinas, thus being a valuable genetic marker for diabetic retinopathy. It has been reported that sorbitol induces apoptosis in several cancer cell lines. ... In /this/ study, the intracellular signaling pathways of sorbitol-induced apoptosis in human K562 cells were investigated using both morphological analysis and DNA fragmentation technique. In this study, we demonstrated that sorbitol-induced apoptosis in human K562 cells is a concentration- and time-dependent manner. This sorbitol-induced apoptosis in human K562 cells was also accompanied by the up-regulation of Bax, and down-regulation of p-Bcl-2, but no effect on the levels of Bcl-X(L). Moreover, the sorbitol treatment resulted in a significant reduction of mitochondria membrane potential, increase in the release of mitochondrial cytochrome c (cyt c), and activation of caspase 3. Furthermore, treatment with caspase 3 inhibitor (z-DEVD-fmk) was capable of preventing the sorbitol-induced caspase 3 activity and cell death. These results clearly demonstrate that the induction of apoptosis by sorbitol involves multiple cellular/molecular pathways and strongly suggest that pro- and anti-apoptotic Bcl-2 family proteins, mitochondrial membrane potential, mitochondrial cyt c, and caspase 3, they all participate in sorbitol-induced apoptotic process in human K562 cells. Chronic diabetic complications, in particular, nephropathy, peripheral and autonomic neuropathy, "diabetic foot," retinopathy, and cardiovascular disease, remain the major cause of morbidity and mortality in patients with diabetes mellitus. Growing evidence indicates that both increased activity of the sorbitol pathway of glucose metabolism and enhanced oxidative stress are the leading factors in the pathogenesis of diabetic complications. The relation between the two mechanisms remains the area of controversy. One group has reported that increased sorbitol pathway activity has a protective rather than detrimental role in complication-prone tissues because the pathway detoxifies toxic lipid peroxidation products. Others put forward a so-called "unifying hypothesis" suggesting that activation of several major pathways implicated in diabetic complications (eg, sorbitol pathway) occurs due to increased production of superoxide anion radicals in mitochondria and resulting poly(ADP-ribose) polymerase activation. This review (a) presents findings supporting a key role for the sorbitol pathway in oxidative stress and oxidative stress-initiated downstream mechanisms of diabetic complications, and (b) summarizes experimental evidence against a detoxifying role of the sorbitol pathway, as well as the "unifying concept."