Farmectin 1 %

Indications

• Onchocerciasis (river blindness)
• Strongyloidiasis
• Scabies (especially hyperkeratotic or crusted scabies)
• Lymphatic filariasis
• Other helminth infections

Dosage

Children: Child 6 months–17 years: 100 mg for 1 dose;

Adults: Adult: Initially 1 mg/kg daily on the first day, then increased to 6 mg/kg daily in divided doses, gradually increased over 3 days. Maximum 9 mg/kg per day. For scabies, 100 mg for 1 dose; if reinfection occurs, a second dose may be given after 2 weeks.

Mechanism of action

Ivermectin binds selectively to glutamate-gated chloride channels, leading to increased permeability of the cell membrane to chloride ions. This results in hyperpolarization of the nerve or muscle cells in the parasites, causing paralysis and death. It also interacts with other chloride channels, which may contribute to its antiparasitic effects.

Pharmacodynamics

Ivermectin exhibits broad-spectrum activity against a variety of parasites, including nematodes and arthropods. Its effectiveness is attributed to its ability to paralyze and kill parasites, thus facilitating their expulsion from the host. The drug has a long half-life, allowing for effective dosing regimens, and it is generally well-tolerated in patients.

Pharmacokinetics

Ivermectin is rapidly absorbed following oral administration, with peak plasma concentrations occurring within 4 to 6 hours. It is extensively distributed throughout the body, including the central nervous system. The drug undergoes hepatic metabolism, primarily via cytochrome P450, and is eliminated with a half-life of approximately 18 hours. Excretion occurs mainly in the feces, with a smaller proportion eliminated in urine.

Contra-indications

• Blood disorders
• Epilepsy
• Sjögren’s syndrome

Adverse effects

• Diarrhoea
• Dizziness
• Headache
• Influenza-like illness
• Insomnia
• Myalgia
• Nausea
• Rash
• Seizure
• Taste alteration
• Vomiting
• Skin reactions
• Abnormal sensation in eye
• Anaemia
• Appetite decrease
• Asthenia
• Asthma exacerbated
• Chest discomfort
• Confusion
• Conjunctival haemorrhage
• Constipation
• Gastrointestinal discomfort
• Headache
• Hepatitis
• Hypotension
• Joint disorders
• Leukopenia
• Myalgia
• Nausea
• Oedema
• Pain
• Psychiatric disorder
• Severe cutaneous adverse reactions
• Stupor
• Tachycardia
• Tremor
• Urinary incontinence
• Vertigo

Interactions

• Coumarins: Unknown (increases anticoagulant effect)
• Levamisole: Unknown (increases exposure)

Precautions

• Use with caution in hepatic impairment
• Avoid sun exposure when using topical formulations

Pregnancy

Embryotoxic in animal studies, avoid if possible.

Breast-feeding

Manufacturer advises avoid-limited information available; ensure infant does not come in contact with treated areas.

Storage

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

Formulations

• Tablets
• Topical formulation

Dosage

Children: Refer to specific formulations and usages, as dosing can vary widely depending on the application and regulatory guidelines.

Adults: Refer to specific formulations and usages, as dosing can vary widely depending on the application and regulatory guidelines.

Mechanism of action

Butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) act as antioxidants by inhibiting the oxidation of lipids. They scavenge free radicals and donate hydrogen atoms to reactive species, thus stabilizing and preventing oxidative damage to cellular components. This action helps to protect the integrity of cell membranes and prevent the formation of harmful peroxides.

Pharmacodynamics

The pharmacodynamic properties of butylated compounds are primarily related to their antioxidant activity. They exhibit a dose-dependent ability to inhibit lipid peroxidation, which is crucial in protecting cells from oxidative stress. Furthermore, they may modulate certain biochemical pathways involved in cell signaling and apoptosis, although these effects are less well-characterized.

Pharmacokinetics

Butylated compounds are absorbed from the gastrointestinal tract following oral ingestion. They undergo metabolic processing primarily in the liver, where they are conjugated and excreted in urine. The half-life of butylated compounds in humans is variable, influenced by factors such as dosage and individual metabolism. Accumulation in tissues is generally low, but prolonged exposure may lead to higher tissue concentrations.

Adverse effects

• Gastrointestinal disturbances
• Allergic reactions
• Potential carcinogenic effects with prolonged exposure

Precautions

• Use with caution in patients with a history of hypersensitivity to butylated compounds
• Avoid prolonged exposure due to potential toxicity

Pregnancy

Limited data available, use only if the benefits outweigh the risks.

Breast-feeding

Unknown, exercise caution and consult a healthcare provider.

Storage

Store in a cool, dry place away from light.

Formulations

• Butylated hydroxytoluene (BHT)
• Butylated hydroxyanisole (BHA)

Indications

• Solvent in pharmaceutical formulations
• Moisturizer and humectant in topical applications
• Potential use in the management of drug solubility issues

Dosage

Children: Refer to specific formulations and clinical guidelines, as dosing varies widely based on the application and formulation.

Adults: Refer to specific formulations and clinical guidelines, as dosing varies widely based on the application and formulation.

Mechanism of action

Glycols, particularly propylene glycol, act as humectants, which help to retain moisture in formulations. They can also enhance the solubility of drugs, aiding in their absorption when used as excipients. Propylene glycol is metabolized in the liver to lactate and subsequently to glucose, providing a source of energy when utilized in metabolic pathways.

Pharmacodynamics

The pharmacodynamics of glycols involve their ability to modulate the viscosity of solutions and enhance the solubility of other compounds. Propylene glycol can also facilitate the absorption of other drugs when used in formulations. It exhibits a low toxicity profile when used appropriately, but excessive systemic exposure can lead to metabolic acidosis and other adverse effects.

Pharmacokinetics

Glycols are rapidly absorbed when administered intravenously or orally. Propylene glycol is metabolized primarily in the liver, with a half-life varying based on the dose and individual metabolism. Renal excretion plays a role in the elimination of metabolites. Accumulation can occur in individuals with impaired liver or kidney function, necessitating careful monitoring of dosing in such populations.

Pregnancy

The safety of glycol in pregnancy is not well established. Consult healthcare professionals before use.

Breast-feeding

Glycol's effects during breastfeeding are not well characterized. Caution is advised.

Storage

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

Indications

• Solar lentigines
• Hyperpigmented lesions
• Other related skin disorders characterized by increased melanin production

Dosage

Children: Refer to BNF for Children for specific dosage guidance for paediatrics.

Adults: Refer to BNF for specific dosage guidance for adults.

Mechanism of action

Mequinol is considered a melanocytotoxic chemical that, upon oxidation in melanocytes, leads to the formation of toxic compounds such as quinones. These cytotoxic agents can damage and destroy pigment-producing cells (melanocytes), resulting in skin depigmentation. The presence of glutathione and glutathione S-transferase in skin cells offers a protective mechanism against the toxicity, but the combination of mequinol with tretinoin can inhibit this protective response, enhancing the depigmentation effect.

Pharmacodynamics

Mequinol's pharmacodynamic profile reveals its ability to induce cellular toxicity in melanocytes, leading to the destruction of pigment cells and subsequent depigmentation of the skin. The drug's action is characterized by the formation of cytotoxic quinones after oxidation, which, while detrimental to melanocytes, is a primary mechanism for its therapeutic efficacy in addressing hyperpigmentation.

Pharmacokinetics

The pharmacokinetics of hydroxyanisole have not been extensively detailed in the provided sources. Typically, topical agents like mequinol are expected to have limited systemic absorption, with localized action on the skin. The duration of action and specific metabolic pathways for mequinol are not specified, indicating a need for further research to fully understand these aspects.

Pregnancy

Use is not recommended during pregnancy due to potential risks.

Breast-feeding

Caution is advised; the effects on a nursing infant are unknown.

Storage

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

Formulations

• Topical solution
• Cream

Indications

• Plant growth regulation
• Agricultural applications as a growth inhibitor

Dosage

Children: Not applicable.

Adults: Refer to the relevant agricultural guidelines for specific applications.

Mechanism of action

In an in vitro study, propylene acts as a plant growth inhibitor by inhibiting the oxidation of indole-3-acetic acid by peroxidase in the presence of superoxide anion radicals. This inhibition is linked to the activation of an iron complex (compound III) shuttle, which enhances the reaction rate between superoxide and peroxidase, ultimately affecting plant growth processes. Propylene is a less effective inhibitor compared to ethylene.

Pharmacodynamics

The pharmacodynamic effects of propylene are primarily observed in its role as a growth inhibitor in plants. By modulating the oxidation of phytohormones like indole-3-acetic acid, propylene can influence various growth responses in plants, potentially affecting processes such as cell elongation and division.

Pharmacokinetics

Information on the pharmacokinetics of propylene in humans is not well-documented, as its primary uses are industrial and agricultural. Its metabolism may be influenced by environmental factors, and its effects are primarily studied in the context of plant biology rather than human pharmacology.

Mechanism of action

Solar lentigines and related hyperpigmented lesions are localized, pigmented, macular lesions of the skin, usually on the areas of the body which have been chronically exposed to sunlight. These lesions are characterized by increased numbers of active melanocytes and increased melanin production. Although the mechanism of action of mequinol is not fully elucidated, when employed as an active ingredient in combination with other agents like tretinoin in skin depigmentation products, a synergy between a number of potential mechanisms is proposed. Firstly, mequinol is in fact considered a melanocytotoxic chemical which when oxidized in melanocytes results in the formation of toxic compounds like quinones. Such cytotoxic agents are subsequently capable of damaging and destroying pigment cells, which results in skin depigmentation of solar lentigines or other related hyperpigmented lesions. Nevertheless, skin cells are naturally capable of protecting themselves against such cytotoxic entities by endogenous intracellular glutathione (GSH). This protection is elicited through the enzymatic action of glutathione S-transferase (GST), which is responsible for the conjugation of agents toxic to glutathione. Conversely, tretinoin has been observed to serve as a potent inhibitor of mammalian GSTs and to be capable of reducing the level of intracellular GSH in various cells. As a result, the combination of mequinol with tretinoin seemingly allows for a synergistic enhancement of a melanocytotoxic effect that involves the inhibition and impairment of GSH and GST cytoprotection. Secondly, even though mequinol is a substrate for the enzyme tyrosinase and therefore acts as a competitive inhibitor of the formation of melanin precursors by way of tyrosinase facilitated reactions, the clinical significance of this action is unknown. We examined changes in the levels of chaperone proteins to evaluate the toxic effects of environmental chemicals in human cells in vitro. Some chaperones are up-regulated by estrogenic chemicals, but the effect is not necessarily dependent on the receptor. Thus we also investigated whether a chemical-induced change in chaperone protein expression is human estrogen receptor (hER)-dependent or not, using cultured human cell lines transfected with hERalpha cDNA or an empty vector. In the hERalpha-expressed cells, the protein levels of the heat shock protein 27 (HSP27), the glucose-regulated protein 78 (GRP78/BiP), and GRP94 increased after exposure to beta-estradiol (E(2)) (from 10(-9)M to 10(-6)M) and bisphenol A (BPA) (from 10(-6)M to 10(-5)M). On the other hand, the increase was not observed in the cells without hERalpha expression. These results suggest that the E(2)- and BPA-induced increase in the protein levels were hERalpha dependent. We next examined the effect of four phenolic chemicals similar in structure to BPA, and found that among them, 4-methoxyphenol (from 10(-6)M to 10(-5)M) increased the levels of the chaperone proteins with hERalpha dependency. Thus the human cultured cells would be suitable for evaluating whether an increase in chaperone proteins occurs upon exposure to environmental chemicals and whether the effect is ER-dependent. Many of the well-known depigmenting agents such as hydroquinone and 4-hydroxyanisole are, in fact, melanocytotoxic chemicals which are oxidized in melanocytes to produce highly toxic compounds such as quinones. These cytotoxic compounds are responsible for the destruction of pigment cells, which results in skin depigmentation. However, cells are capable of protecting themselves against cytotoxic agents by intracellular glutathione (GSH). This protection takes place under the enzymatic action of the detoxification enzyme glutathione S-transferase (GST), which is responsible for the conjugation of toxic species to GSH. The depigmenting effect of hydroquinone is shown to be potentiated by buthionine sulfoximine (BSO) and cystamine as the result of the reduction of intracel

Pharmacodynamics

Mequinol is in fact considered a melanocytotoxic chemical which when oxidized in melanocytes results in the formation of toxic entities like quinones. Such cytotoxic compounds subsequently have the potential to damage and destroy pigment cells, therefore causing skin depigmentation. In response, skin cells are naturally capable of protecting themselves against such cytotoxic agents with the help of endogenous intracellular glutathione and the detoxification action of glutathione S-transferase on the cytotoxic compounds. Regardless, it is consequently by way of this seemingly negative and damaging pharmacodynamic profile by which the mechanism of action of mequinol is sometimes described.

Mechanism of action

In an in vitro study of the mechanism of action of ethylene as a plant growth inhibitor, the effects of ethylene and some of its analogs, including propylene, on the oxidation of indole-3-acetic acid were examined. Ethylene and its analogs inhibited the oxidation of indole-3-acetic acid by peroxidase under conditions where the iron complex (compound III, an oxy-ferrous complex of peroxidase) shuttle was activated. Inhibition occurred only in the presence of the superoxide anion radical 02(-). Spectral and kinetic data indicated that ethylene and its analogs enhanced the rate of reaction of 02(-) with peroxidase; ie, the iron complex (compound III) shuttle, resulting in the formation of compound III. Propylene was a less effective inhibitor than ethylene.