ARTOM 80

Indications

• Uncomplicated malaria caused by Plasmodium falciparum
• Malaria treatment in combination with lumefantrine

Dosage

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

Adults: Refer to specific guidelines; typically, artemether is administered in a combination therapy regimen with lumefantrine.

Mechanism of action

Artemether interacts with ferriprotoporphyrin IX (heme) in the acidic vacuole of malaria parasites, leading to the generation of cytotoxic radical species. This interaction involves the activation of the drug by reduced heme or ferrous iron, resulting in the formation of oxygen-centered radicals that subsequently convert into carbon-centered radicals. These radicals are toxic to the parasites, thereby inhibiting their growth and reproduction.

Pharmacodynamics

Artemether is rapidly metabolized to its active metabolite, dihydroartemisinin. It primarily targets the erythrocytic stages of Plasmodium falciparum by inhibiting nucleic acid and protein synthesis. The drug has a rapid onset of action, providing quick symptomatic relief by significantly reducing the number of circulating malarial parasites. In combination therapy with lumefantrine, artemether enhances overall treatment effectiveness and contributes to a higher clinical cure rate.

Pharmacokinetics

Artemether is absorbed quickly, with a rapid onset of action. It is metabolized in the liver to dihydroartemisinin, which is the active form responsible for its antimalarial effects. The drug is eliminated from the body relatively quickly, while lumefantrine, which has a longer half-life, aids in clearing any residual parasites. This pharmacokinetic profile supports the use of artemether in combination therapies for malaria.

Adverse effects

• nausea
• vomiting
• dizziness
• headache
• fatigue
• abdominal pain
• anemia
• QT prolongation

Interactions

• mitotane+artemether with lumefantrine: Severe (decreases exposure)
• mitotane+artemether: Severe (decreases exposure)
• rifampicin+artemether: Severe (decreases exposure)
• grapefruit juice+artemether: Unknown (increases exposure)
• efavirenz+artemether: Unknown (decreases concentration)
• etravirine+artemether: Unknown (decreases exposure)

Precautions

• Monitor for signs of hypersensitivity reactions
• Use with caution in patients with pre-existing QT prolongation
• Assess liver function before use, as hepatic impairment may alter drug metabolism

Pregnancy

Artemether is categorized as pregnancy category C. It should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Artemether is excreted in breast milk. Caution should be exercised when administering to nursing mothers.

Storage

Store at room temperature, away from moisture and heat. Protect from light.

Formulations

• artemether/lumefantrine combination tablets
• artemether oral solution

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

• Alcohol use disorder
• Anxiety disorders
• Sedation
• Muscle relaxation

Dosage

Children: Refer to the BNF for Children for specific dosing guidelines in paediatric populations.

Adults: Refer to the specific BNF guidelines for dosing related to alcohol use disorder and other indications.

Mechanism of action

Ethyl groups serve primarily as substituents in organic chemistry, influencing the properties and reactivity of the parent molecules. In the context of ethanol, which contains an ethyl group, its mechanism of action involves the enhancement of gamma-aminobutyric acid (GABA) receptor activity, leading to increased inhibitory neurotransmission. This results in its sedative, anxiolytic, and muscle relaxant effects.

Pharmacodynamics

The pharmacodynamics of compounds containing the ethyl group, particularly ethanol, include its effects on the central nervous system, where it acts as a depressant. Ethanol enhances the effects of GABA, resulting in sedation, impaired motor function, and decreased anxiety. It can also affect the dopaminergic pathways, leading to the release of dopamine, which contributes to its reinforcing properties.

Pharmacokinetics

Ethanol is rapidly absorbed from the gastrointestinal tract, with peak blood concentrations typically reached within 30 to 90 minutes after consumption. It is metabolized primarily in the liver by alcohol dehydrogenase and aldehyde dehydrogenase, with a first-order elimination kinetics, typically at a rate of 10 to 15 mL of pure alcohol per hour. Ethanol is also known to exhibit a volume of distribution of approximately 0.5 to 0.7 L/kg in adults.

Indications

• Anxiety disorders
• Nausea and vomiting
• Allergic conditions
• Preoperative sedation
• Pruritus

Dosage

Children: Refer to the BNF for Children for appropriate dosing recommendations based on age and weight.

Adults: Refer to the BNF for specific dosing guidelines based on the indication and patient characteristics.

Mechanism of action

Hydroxyzine works by antagonizing the H1 histamine receptors, leading to a reduction in the effects of histamine in the body. This action helps alleviate symptoms of allergic reactions and promotes sedation. Additionally, it may exert effects on serotonin and adrenergic receptors, which could contribute to its anxiolytic properties. Hydroxyzine is also involved in various metabolic pathways, including selenium metabolism and the degradation of reactive oxygen species.

Pharmacodynamics

The pharmacodynamic effects of hydroxyzine include sedation, anxiolysis, and reduction of allergic symptoms. Its sedative effects can make it useful in managing anxiety and inducing sleep, while its antihistaminic properties help to relieve symptoms such as itching and rashes associated with allergic reactions. The onset of action is typically within 15 to 30 minutes when taken orally, with peak effects occurring within 1 to 2 hours.

Pharmacokinetics

Hydroxyzine is well absorbed from the gastrointestinal tract, with peak plasma concentrations occurring approximately 2 hours after oral administration. It is extensively metabolized in the liver, with metabolites, including cetirizine, possessing their own therapeutic effects. Hydroxyzine has a half-life of approximately 20 hours, allowing for once or twice daily dosing. It is primarily excreted in the urine, with less than 1% of the unchanged drug found in urine.

Interactions

• hydroxyzine+antiepileptics: Severe (increases risk of overheating and dehydration)
• hydroxyzine+zonisamide: Severe (increases risk of overheating and dehydration)
• hydroxychloroquine+penicillamine: Severe (increases risk of haematological toxicity)
• hydroxychloroquine+agalsidase alfa: Unknown (decreases effects)
• hydroxychloroquine+agalsidase beta: Unknown (decreases exposure)
• hydroxychloroquine+oral cholera vaccine: Unknown (decreases efficacy)
• live vaccines+hydroxy carbamide: Unknown (increases risk of generalised infection (possibly life-threatening))
• lanthanum+hydroxychloroquine: Unknown (decreases absorption)
• macrolides+hydroxychloroquine: Unknown (increases risk of serious cardiovascular adverse effects)
• hydroxychloroquine+remdesivir: Unknown (decreases effects)

Pregnancy

Safety in pregnancy has not been established. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Use with caution. Hydroxychloroquine is excreted in breast milk, and effects on the infant are unknown.

Storage

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

Formulations

• Tablets
• Oral solution

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

• Fatty acid supplementation
• Dietary management of hyperlipidemia
• Support in lipid metabolism disorders

Dosage

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

Adults: Refer to the BNF for specific dosing guidelines.

Mechanism of action

Oleate functions as a signaling molecule that can influence various metabolic pathways, including phospholipid remodeling and choline biosynthesis. It is involved in the regulation of cellular functions through its incorporation into phospholipids and modulation of enzyme activity, particularly phospholipases.

Pharmacodynamics

Oleate exhibits effects on lipid metabolism, insulin sensitivity, and inflammation. It has been shown to influence the composition of cell membranes, affecting their fluidity and functionality. Oleate may also play a role in the regulation of gene expression related to fat metabolism and inflammation.

Pharmacokinetics

Oleate is absorbed through the gastrointestinal tract and transported in the bloodstream as part of lipoproteins. It is metabolized primarily in the liver and can be oxidized for energy production or esterified for storage in adipose tissue. The metabolism of oleate can influence the levels of other fatty acids and lipid profiles in the body.

Pregnancy

Oleate is generally considered safe during pregnancy; however, it is advisable to consult a healthcare professional before use.

Breast-feeding

Oleate is typically regarded as safe during breastfeeding, but it is important to seek guidance from a healthcare provider.

Storage

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

Formulations

• Oleate solution
• Oleate emulsion

Dosage

Children: There are no established therapeutic doses for toluene in pediatric populations due to its potential for abuse and toxicity. Exposure should be avoided.

Adults: There are no established therapeutic doses for toluene due to its potential for abuse and toxicity. Exposure should be minimized as per occupational safety guidelines.

Mechanism of action

Toluene primarily affects the dopaminergic mechanisms of the basal ganglia, leading to alterations in sensory-motor integration. At low concentrations, it reduces dopamine turnover in the anterior nucleus caudate, while at higher concentrations, it increases dopamine turnover in the cholecystokinin-dopamine terminals of the limbic system, contributing to its euphoric effects. Toluene also influences various neurotransmitter systems, including glutamate and GABA, and alters the activities of neurotransmitter synthesizing enzymes, which can indicate permanent loss of neuronal activity.

Pharmacodynamics

Toluene exhibits central nervous system depressant effects, which can lead to symptoms such as euphoria, dizziness, and cognitive impairment. Chronic exposure may result in neurotoxic effects, including potential damage to catecholaminergic neurons and changes in neurotransmitter levels. The drug's psychoactive effects are associated with its ability to modulate dopamine pathways, ultimately affecting mood, perception, and motor coordination.

Pharmacokinetics

Toluene is rapidly absorbed through inhalation and can distribute throughout the body, with a high affinity for fatty tissues. It undergoes metabolic degradation primarily in the liver, where it is converted into various metabolites. The elimination half-life of toluene varies depending on the route of exposure and the concentration, with significant excretion occurring through urine as metabolites, including hippuric acid.

Adverse effects

• CNS depression
• Dizziness
• Headaches
• Nausea
• Vomiting
• Respiratory irritation
• Cognitive impairment
• Potential for addiction and euphoric effects

Precautions

• Use with caution in individuals with pre-existing neurological disorders
• Avoid exposure in pregnant women due to potential risks to fetal development
• Monitor for signs of abuse in individuals with a history of substance misuse

Pregnancy

Toluene exposure during pregnancy may pose risks to fetal development, including potential teratogenic effects. Caution is advised.

Breast-feeding

Due to the potential for adverse effects, breastfeeding is not recommended during exposure to toluene.

Storage

Store in a cool, well-ventilated area away from sources of ignition. Keep container tightly closed.

Formulations

• Inhalation vapors
• Solvent formulations

Mechanism of action

Involves an interaction with ferriprotoporphyrin IX (“heme”), or ferrous ions, in the acidic parasite food vacuole, which results in the generation of cytotoxic radical species. The generally accepted mechanism of action of peroxide antimalarials involves interaction of the peroxide-containing drug with heme, a hemoglobin degradation byproduct, derived from proteolysis of hemoglobin. This interaction is believed to result in the formation of a range of potentially toxic oxygen and carbon-centered radicals. Artemether (AM) is an antimalarial drug derived from artemisinin (Qinghaosu), an extract of the herb Artemisia annua L., sweet wormwood. Its antiparasitic effect is that of a schizontocide and is explained by rapid uptake by parasitized erythrocytes and interaction with a component of hemoglobin degradation resulting in formation of free radicals. It has been shown to exhibit a high clinical cure rate. Two theories have been put forward for the mode of antimalarial action of the artemisinin antimalarials, in accodance with the known properties of peroxides with medicinal activity. The first assumes that the artemisinins must be activated by contact with either reduced haem (ferrous haem, Fe(ll)PPIX) or non-haem ferrous iron (exogenous iron), causing cleavage of the peroxide to generate oxygen-centered radicals (alkoxy radicals') which are then presumed to be converted into carbon-centered radicals by transfer of proximate hydrogen atoms from the periphery of the peroxide molecule. These carbon-centered radicals are then thought to alkylate sensitive, yet unspecified, biomolecules in the parasite. A second theory argues for a process in which the intact artemisinin binds to a site within a vital protein in the parasite. The act of binding causes the peroxide to be converted to hydroperoxide or similar open peroxide, which in accordance with known properties of such compounds, generates one or more active chemical entities, either oxidizing agents or oxygen transfer agents per se, or oxygen-centered free radicals. This would be associated with the binding process. In such a way, the artemisinins might act as (irreversibile) inhibitors. Iron may, or may not, be associated with the activation process. No specific biological target in the parasite has yet been identified in support of this theory, but it may be membrane-bound proteins. A 2025 systematic review notes Artemether's pharmacological activity is antimalarial.

Pharmacodynamics

In the body, artemether is metabolized into the active metabolite metabolite dihydroartemisinin. The drug works against the erythrocytic stages of <i>P. falciparum</i> by inhibiting nucleic acid and protein synthesis. Artemether is administered in combination with lumefantrine for improved efficacy. Artemether has a rapid onset of action and is rapidly cleared from the body. It is thought that artemether provides rapid symptomatic relief by reducing the number of malarial parasites. Lumefantrine has a much longer half life and is believed to clear residual parasites.

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

The present study demonstrates reductions of dopamine (DA) turnover in various areas of the anterior nucleus caudate of rat by toluene at concentrations lower than the current OSHA threshold limit value (100 ppm). Thus, toluene at low concentrations may produce disturbances in dopaminergic mechanisms of the basal ganglia probably leading to functional changes in sensory-motor integration. The increases in DA turnover in the cholecystokinin (CCK)-DA terminals of the subcortical limbic system induced by high concentrations of toluene may be part of the neurochemical basis for its abuse as a euphoric agent in man. Exposure to toluene causes both reversible and irreversible changes in the central nervous system. The effects of toluene inhalation on some specific enzymes and glutamate and GABA receptor binding in defined parts of the rat brain were studied following several exposure schemes. The activities of the transmitter synthesizing enzymes glutamic acid decarboxylase (GAD), choline acetyltransferase (ChAT) and aromatic amino-acid decarboxylase (AAD) were used as markers for permanent loss of neuronal activity. Catecholaminergic neurons showed a 50% reduction in the brain stem after 4 weeks exposure to 250 and 1000 ppm toluene. Following 500 ppm of toluene, 16 hr/day for 3 months, a general increase in the activities was seen. This is most probably due to a reduction in total protein content, to which the activities were related. The neurotransmitters glutamate and GABA had their specific receptor binding increased in most of the brain areas studied, but decreased in some areas. The glial enzyme, glutamine synthetase, has its activity increased in the cerebellar hemisphere following 4 weeks exposure to 1000 ppm. This suggests that glial cells in the area may have proliferated, a frequent phenomenon following CNS damage. The effect on energetic metabolism of rat liver mitochondria (RLM) of styrene and other aliphatic benzene derivatives, i.e. toluene, ethylbenzene, alpha-methylstyrene and butylbenzene, is studied. It is shown that these compounds uncouple oxidative phosphorylation and this effect is connected with the stimulation of passive entry of protons into mitochondria. The relationship between hydrophobicity of these compounds and their biological activity and mechanism of uncoupling effect are discussed.