TRIZACET

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

• Bacterial infections
• Fungal infections
• Protozoal infections

Dosage

Children: Refer to the BNF for Children for appropriate dosage guidelines for paediatric patients.

Adults: Refer to the BNF for specific dosing information as this varies based on the condition being treated.

Mechanism of action

Bronopol exerts its bactericidal effects by generating biocide-induced bacteriostasis, followed by a growth inhibition in bacteria through reactions with essential thiols. Aerobically, it catalyzes the oxidation of thiol groups like cysteine to disulfides, producing reactive oxygen species such as superoxide and peroxide that directly kill bacteria. The oxidation alters the redox state, creating anoxic conditions that slow thiol oxidation and allow for eventual bacterial regrowth once bronopol is consumed.

Pharmacodynamics

At concentrations of 12.5 to 50 μg/mL, bronopol displays significant inhibitory activity against various strains of both Gram-negative and Gram-positive bacteria in vitro, with a stronger effect observed against Gram-negative strains. It also shows limited antifungal activity and anti-protozoal effects against _Ichthyophthirius multifiliis_. Its efficacy decreases with increasing pH levels in the medium.

Pharmacokinetics

The pharmacokinetics of bronopol, including absorption, distribution, metabolism, and excretion parameters, are not well-documented. However, its mode of action suggests that it acts locally at the site of application, and its biocidal properties may vary based on environmental conditions such as pH.

Adverse effects

• Skin irritation
• Allergic reactions
• Respiratory distress
• Nausea
• Vomiting

Precautions

• Use with caution in patients with known allergies to brominated compounds
• Avoid contact with eyes and skin
• Ensure proper ventilation when used in confined spaces

Pregnancy

There are no adequate and well-controlled studies in pregnant women. Use only if clearly needed.

Breast-feeding

It is unknown whether bronopol is excreted in human milk. Caution is advised when administering to nursing mothers.

Storage

Store in a cool, dry place, away from direct sunlight. Keep container tightly closed.

Formulations

• Bronopol solution
• Bronopol powder

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

Mechanism of action

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

Pharmacodynamics

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

Pharmacokinetics

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

Pregnancy

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

Breast-feeding

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

Storage

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

Indications

• Enhancement of taste in food and beverages
• Improvement of palatability in nutritional products
• Masking undesirable flavors in medications

Dosage

Children: There is no specific pediatric dosage for flavor agents as they are used as needed to improve the taste of food and beverages.

Adults: There is no specific dosage for flavor agents as they are used as needed to achieve the desired taste and aroma in food and beverages.

Mechanism of action

Flavor compounds interact with taste receptors on the tongue, stimulating the sensory neurons responsible for taste perception. This interaction influences the overall flavor profile of food and beverages, enhancing the eating experience. Some flavors may also have a psychological effect, stimulating appetite or evoking pleasant memories associated with certain tastes.

Pharmacodynamics

While flavor agents are primarily used for sensory enhancement in food, their pharmacodynamic effects are minimal as they are not designed to elicit a pharmacological response. However, certain flavors may influence digestion and metabolism indirectly by enhancing saliva production or affecting gut motility. The enjoyment of flavored products can also lead to increased food intake and satisfaction.

Pharmacokinetics

Flavour compounds are typically ingested and metabolized by the body. Their absorption rates can vary depending on their chemical structure and formulation. Once ingested, they may be rapidly metabolized in the liver and other tissues, with excretion primarily via urine. The specific pharmacokinetic profiles of flavor agents can vary significantly based on their source and chemical properties.

Pregnancy

Flavours are generally considered safe for use during pregnancy, but specific assessments should be made based on the type of flavouring agent.

Breast-feeding

Most flavouring agents are deemed safe during breastfeeding, although it's advisable to consult healthcare professionals regarding specific ingredients.

Storage

Store in a cool, dry place away from direct sunlight and heat sources. Ensure that the container is tightly sealed to prevent contamination.

Indications

• Nutritional support
• Prevention of chronic diseases
• Support for digestive health
• Antioxidant support
• Hydration

Dosage

Children: In children, the recommendation for fruit intake varies by age, with guidelines typically suggesting 1 to 2 servings per day, depending on age and dietary requirements.

Adults: Fruits are generally consumed as part of a balanced diet, with recommendations often suggesting 5 portions of fruits and vegetables per day, though specific amounts may vary based on individual dietary needs.

Mechanism of action

Fruits contain various bioactive compounds, including vitamins (such as vitamin C and folate), minerals (like potassium), dietary fiber, and phytochemicals (such as flavonoids and carotenoids). These components contribute to their health benefits through various mechanisms, including antioxidant activity, modulation of inflammation, and enhancement of immune function.

Pharmacodynamics

The pharmacodynamic effects of fruits are largely attributed to their phytochemical content, which can influence metabolic pathways, reduce oxidative stress, and improve cardiovascular health. The fiber content aids in digestion and can contribute to maintaining healthy cholesterol levels. The vitamins and minerals support various physiological functions, including immune response and cellular repair.

Pharmacokinetics

The bioavailability of nutrients from fruits can vary based on the composition of the fruit and the individual's digestive health. Vitamins and antioxidants are typically absorbed in the small intestine, while dietary fiber is fermented in the colon. The metabolism of fruit-derived nutrients occurs through various pathways, with some compounds undergoing conjugation and excretion via the kidneys.

Pregnancy

Fruits are generally safe to consume during pregnancy and provide essential nutrients. However, certain fruits may need to be limited due to sugar content or potential allergies.

Breast-feeding

Fruits are safe to consume while breastfeeding and can contribute to the nutritional needs of both the mother and the infant. Some fruits may help with lactation.

Storage

Fruits should be stored in a cool, dry place, and refrigeration can help prolong freshness. Some fruits may require specific storage conditions to maintain quality.

Formulations

• whole fruit
• dried fruit
• fruit juice
• fruit puree
• fruit smoothie

Indications

• Constipation
• Preparation for surgical or diagnostic procedures involving the rectum
• Decreasing intraocular pressure in certain ocular conditions

Dosage

Children: For children aged 2 to 6 years, 2 g to 5 g of glycerin may be used as a suppository. Children aged 6 to 12 years may use 5 g to 10 g as needed. For specific pediatric dosing, please refer to the BNF for Children.

Adults: For rectal use, 4 g to 10 g of glycerin may be administered as a suppository as needed.

Mechanism of action

When administered rectally, glycerin draws water from the tissues into the feces due to its hygroscopic action, which reflexively stimulates bowel evacuation. Additionally, glycerin creates an osmotic gradient that leads to a decrease in intraocular pressure by facilitating fluid movement from the aqueous and vitreous humors into the bloodstream.

Pharmacodynamics

Glycerin is classified as an osmotic laxative, which acts to retain water in the fecal matter, softening stools and making them easier to pass. Its local irritant effects also contribute to its laxative properties. Glycerin suppositories typically produce a bowel movement within 15 to 30 minutes of administration.

Pharmacokinetics

Glycerin is readily absorbed from the gastrointestinal tract when taken orally and is metabolized primarily in the liver. It is distributed widely throughout the body, with excretion occurring primarily via the kidneys. The onset of action for glycerin when used as a laxative is relatively quick, particularly when used rectally.

Contra-indications

• Severe dehydration
• Severe renal impairment
• Intestinal obstruction
• Appendicitis

Adverse effects

• Abdominal cramps
• Diarrhea
• Nausea
• Vomiting
• Electrolyte imbalance

Interactions

• May enhance the effects of other laxatives
• Caution with concurrent use of diuretics due to potential electrolyte imbalance

Precautions

• Use with caution in patients with renal impairment
• Monitor electrolytes in patients with prolonged use
• Not recommended for long-term use

Pregnancy

Glycerin is generally considered safe during pregnancy but should be used under medical advice.

Breast-feeding

Glycerin is excreted in breast milk in small amounts and is considered safe for use while breastfeeding.

Storage

Store at room temperature, away from moisture and heat.

Formulations

• Glycerin suppositories
• Glycerin oral solution

Dosage

Children: Refer to specific drug guidelines as paediatric dosing must be determined based on the individual drug and condition being treated.

Adults: Refer to specific drug guidelines as dosing can vary widely based on the exact medication and its intended use.

Mechanism of action

The mechanism of action of mixed drugs can vary widely, often involving multiple pathways. For example, some may act as agonists or antagonists at certain receptors, while others may inhibit enzymes or modulate neurotransmitter levels. This complexity allows mixed drugs to have a broad spectrum of effects, which can be beneficial in treating conditions that require multifaceted approaches.

Pharmacodynamics

Pharmacodynamics of mixed drugs also varies significantly. Their effects can be dose-dependent, with lower doses potentially providing different therapeutic effects than higher doses. The interactions with various receptors and pathways can lead to synergistic or antagonistic effects, influencing the overall therapeutic outcome. Side effects and therapeutic efficacy must be carefully monitored.

Pharmacokinetics

Pharmacokinetics of mixed drugs includes absorption, distribution, metabolism, and excretion, which are influenced by the drug's chemical structure and route of administration. Many mixed drugs are absorbed rapidly and have wide distribution in body tissues. Metabolism can occur in the liver, often involving cytochrome P450 enzymes, and excretion may be renal or hepatic, depending on the drug's properties. The half-life can vary, affecting dosing schedules and potential for drug interactions.

Pregnancy

Consult with a healthcare provider regarding use during pregnancy, as the safety profile may vary depending on the specific components involved in the mixed formulation.

Breast-feeding

Consult with a healthcare provider regarding use during breastfeeding, as the safety profile may vary depending on the specific components involved in the mixed formulation.

Storage

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

Dosage

Children: Refer to specific formulations and guidelines, as ponceau is primarily a colorant and not used therapeutically.

Adults: Refer to specific formulations and guidelines, as ponceau is primarily a colorant and not used therapeutically.

Mechanism of action

Ponceau exerts its color properties through the presence of azo groups (-N=N-), which absorb specific wavelengths of light, thereby producing a bright red color. The mechanism of action in terms of pharmacological effects is not well-defined, as ponceau is primarily a colorant rather than a pharmacologically active agent.

Pharmacodynamics

Ponceau does not have pharmacodynamic effects traditionally associated with therapeutic drugs, as it is not intended to exert a pharmacological effect. Its primary role is as a color additive, and any physiological response is typically limited to allergic reactions in susceptible individuals. The dye's interaction with biological systems is largely related to its structural properties rather than specific pharmacological activity.

Pharmacokinetics

The pharmacokinetics of ponceau are not well-studied, as it is mainly used as a colorant rather than a therapeutic agent. Generally, colorants like ponceau are not absorbed significantly in the gastrointestinal tract and are excreted unchanged. However, in cases of hypersensitivity or allergic reactions, the body's response may vary based on individual metabolism and immune response.

Pregnancy

There is limited data on the safety of ponceau in pregnancy. It should only be used if clearly needed and the potential benefits outweigh the risks.

Breast-feeding

It is unknown if ponceau is excreted in human milk. Caution should be exercised when administering to breastfeeding women.

Storage

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

Dosage

Children: Refer to specific drug formulations and product labels as purified substances can vary widely in their use and dosing.

Adults: Refer to specific drug formulations and product labels as purified substances can vary widely in their use and dosing.

Mechanism of action

The mechanism of action for purified compounds varies widely depending on the specific substance. Generally, purified drugs exert their effects by interacting with specific biological targets, such as receptors, enzymes, or ion channels, leading to a desired therapeutic effect. This interaction can involve binding to receptors to activate or inhibit signaling pathways, modulating enzymatic activity, or altering physiological processes.

Pharmacodynamics

Pharmacodynamics describes the effects of a drug on the body and the relationship between drug concentration and effect. For purified drugs, this can involve dose-response relationships and the time course of their action. The purified form often enhances potency and reduces variability in response among patients, which can lead to more predictable therapeutic outcomes. The overall effect is determined by the drug's affinity for its target, the efficacy of the drug-receptor interaction, and the downstream signaling pathways activated as a result of this interaction.

Pharmacokinetics

Pharmacokinetics involves the absorption, distribution, metabolism, and excretion (ADME) of a drug. For purified substances, absorption can be more efficient due to the absence of impurities that may affect solubility or stability. Distribution may also be enhanced, leading to higher bioavailability. Metabolism can be influenced by the structure of the purified compound, as it may be metabolized more readily by liver enzymes. Excretion typically occurs through the kidneys or liver, depending on the molecular characteristics of the purified drug.

Pregnancy

Consult with a healthcare professional, as the safety of purified forms of medications during pregnancy may vary depending on the specific substance.

Breast-feeding

Consult with a healthcare professional, as the safety of purified forms of medications during breastfeeding may vary depending on the specific substance.

Storage

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

Indications

• 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

Mechanism of action

It is proposed that bronopol generates biocide-induced bacteriostasis followed by a growth at an inhibited rate in bacteria, via two distinct reactions between bronopol and essential thiols within the bacterial cell. Under aerobic conditions, bronopol catalyzes the oxidation of thiol groups, such as cysteine, to disulfides. This reaction is accompanied by rapid consumption of oxygen, where oxygen acts as the final oxidant. During the conversion of cysteine to cystine, radical anion intermediates such as superoxide and peroxide are formed from bronopol to exert a direct bactericidal activity. The oxidation of excess thiols alters the redox state to create anoxic conditions, leading to a second reaction involving the oxidation of intracellular thiols such as glutathione to its disulfide. The resulting effects are inhibition of enzyme function, and reduced growth rate following the bacteriostatic period. Under the anoxic conditions, the reaction between thiol and bronopol decelerates without the involvement of oxygen and the consumption of bronopol predominates. Bronopol is ultimately removed from the reaction via consumption and resumption of bacterial growth occurs. ...Under aerobic conditions, bronopol catalytically oxidizes thiol-containing materials such as cysteine, with atmospheric oxygen as the final oxidant. By-products of this reaction are active oxygen species such as superoxide and peroxide, which are directly responsible for the bactericidal activity of the compound and for the reduced growth rate after the bacteriostatic period.

Pharmacodynamics

At concentrations of 12.5 to 50 μg/mL, bronopol mediated an inhibitory activity against various strains of Gram negative and positive bacteria _in vitro_. The bactericidal activity is reported to be greater against Gram-negative bacteria than against Gram-positive cocci. Bronopol was also demonstrated to be effective against various fungal species, but the inhibitory action is reported to be minimal compared to that of against bacterial species. The inhibitory activity of bronopol decreases with increasing pH of the media. Bronopol also elicits an anti-protozoal activity, as demonstrated with _Ichthyophthirius multifiliis_ _in vitro_ and _in vivo_. It is proposed that bronopol affects the survival of all free-living stages of _I. multifiliis_.

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

When administered rectally, glycerin exerts a hygroscopic and/or local irritant action, drawing water from the tissues into the feces and reflexively stimulating evacuation. Glycerin decreases intraocular pressure by creating an osmotic gradient between the blood and intraocular fluid, causing fluid to move out of the aqueous and vitreous humors into the bloodstream. Glycerin (glycerol) and sorbitol are hyperosmotic laxatives. When administered rectally, glycerin and sorbitol exert a hygroscopic and/or local irritant action, drawing water from the tissues into the feces and reflexly stimulating evacuation. The extent to which the simple physical distention of the rectum and the hygroscopic and/or local irritant actions are responsible for the laxative effects of some of these drugs is not known. Only extremely high oral doses of sorbitol (25 g daily) or glycerin exert laxative action. /Glycerin/ decreases intraocular pressure by creating an osmotic gradient between the blood and intraocular fluid, causing fluid to move out of the aqueous and vitreous humors into the bloodstream. The physicochemical effects of a series of alkanols, alkanediols and glycerol on erythrocyte shape and hemolysis at 4 and 20 degrees C were examined. We calculated the dielectric constant of the incubation medium, Ds, and the dielectric constant of the erythrocyte membrane Dm in the presence of organic solutes. The ratio Ds/Dm = -38.48 at 20 degrees C defines the normal biconcave shape in a medium without hemolytic agents. A decrease in Ds/Dm favors externalization or internalization with consequent hemolysis. Alkanols and alkanediols convert biconcave erythrocytes into echinocytes, which is accompanied by an increase in the projected surface area. Glycerol converts biconcave erythrocytes into stomatocytes, which was accompanied by a marginal decrease in the projected surface area. Progressive externalization in alkanols and alkanediols or internalization in glycerol resulted in a decrease in the projected surface area and the formation of smooth spheres. The degree of shape change induced was related to the degree of hemolysis and the ratio Ds/Dm. A decrease in temperature reduced both the degree of shape change and hemolysis. .../Thus/ physicochemical toxicity may be a result of a temperature dependent hydrophobic interaction between the organic solutes and the membrane and is best interpreted by the ability of the solutes to change Ds and Dm.

Pharmacodynamics

Glycerin is commonly classified as an osmotic laxative but may act additionally or alternatively through its local irritant effects; it may also have lubricating and fecal softening actions. Glycerin suppositories usually work within 15 to 30 minutes.

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."