Snowtraz

Indications

• Acaricide for veterinary use
• Treatment of certain human conditions such as ADHD
• Potential use in obesity management

Dosage

Children: Refer to BNF for Children for specific paediatric dosing guidelines.

Adults: Refer to BNF for specific dosing recommendations, as dosing may vary based on indication and patient factors.

Mechanism of action

Amitraz exerts its pharmacological effects primarily by acting as an agonist at alpha-2 adrenergic receptors in the central nervous system. This action leads to a decrease in norepinephrine release and results in sedation, analgesia, and decreased sympathetic outflow. Additionally, it has been shown to inhibit monoamine oxidase, which may contribute to its effects on neurotransmitter levels. The drug also affects the octopaminergic system in insects, which is critical for their motor function and behavior.

Pharmacodynamics

Amitraz demonstrates sedative and analgesic properties due to its central nervous system activity. Its interaction with alpha-2 adrenergic receptors results in decreased heart rate, reduced blood pressure, and drowsiness. In addition, its role as a monoamine oxidase inhibitor may enhance the levels of certain neurotransmitters, potentially influencing mood and behavior. The overall pharmacodynamic profile indicates a complex interaction with both adrenergic and non-adrenergic pathways.

Pharmacokinetics

Amitraz is absorbed well following administration and can cross the blood-brain barrier due to its lipophilic nature. It undergoes extensive metabolism in the liver, primarily through oxidation and conjugation. The elimination half-life can vary, but metabolites are typically excreted in urine. Factors such as age, liver function, and concurrent medications may influence its pharmacokinetic parameters.

Contra-indications

• Hypersensitivity to amitraz or any of its components
• Pregnancy
• Severe depression of the central nervous system
• Concurrent use with monoamine oxidase inhibitors

Adverse effects

• Sedation
• Ataxia
• Vomiting
• Diarrhoea
• Skin rash
• Hypotension
• Bradycardia

Interactions

• May interact with central nervous system depressants, leading to enhanced sedation
• Concurrent use with monoamine oxidase inhibitors may increase the risk of hypotension and bradycardia

Precautions

• Use with caution in animals with compromised central nervous system function
• Monitor for signs of toxicity, especially in young, elderly or debilitated patients
• Not recommended for use in pregnant or lactating animals

Pregnancy

Amitraz is contraindicated during pregnancy due to potential risks to the fetus.

Breast-feeding

Caution is advised when administering to lactating individuals as it may be excreted in milk.

Storage

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

Formulations

• Topical solution
• Emulsifiable concentrate

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

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.