KLIRE MENTHYLATED SPIRIT

Indications

• Skin disinfection
• Preparation of skin before injections
• Cleansing minor wounds

Dosage

Children: Apply to the skin as required; consult product literature for specific guidance.

Adults: Apply to the skin as required for disinfection.

Mechanism of action

Alcohol exerts its antiseptic effect by denaturing proteins, disrupting cell membranes, and dehydrating microbial cells, leading to cell lysis and death.

Pharmacodynamics

Alcohol has broad-spectrum antimicrobial activity, effective against bacteria, fungi, and viruses. Its efficacy is influenced by concentration, with higher concentrations generally being more effective.

Pharmacokinetics

Alcohol is rapidly absorbed through the skin and mucous membranes. It is metabolized primarily in the liver, with a half-life that varies based on the individual's metabolic rate and the amount consumed.

Contra-indications

• Concomitant use with lithium
• Regular use in neonates
• Patients with severe burns when diathermy has been preceded by application of alcoholic skin disinfectants

Adverse effects

• Eye erythema
• Punctate keratitis
• Cytotoxicity
• Eye discolouration

Interactions

• Increases risk of visual disturbances with antiepileptics
• Increases concentration with methylphenidate
• Increases risk of facial flushing and skin irritation with topical pimecrolimus
• Increases concentration with retinoids
• Increases concentration with acitretin
• Increases risk of facial flushing and skin irritation with topical tacrolimus
• Decreases antidiuretic effect with vasopressin

Precautions

• Avoid regular application to inflamed or broken skin or mucosa
• Avoid broken skin
• Flammable

Pregnancy

Sufficient iodine may be absorbed to affect the fetal thyroid in the second and third trimester.

Breast-feeding

Avoid regular or excessive use.

Storage

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

Formulations

• Betadine 2.5% dry powder spray
• Industrial methylated spirit
• Povidone-Iodine 25 mg per 1 gram

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.

Dosage

Children: Refer to the BNF for Children for specific dosing guidelines in cases of methanol poisoning in pediatric patients.

Adults: In cases of methanol poisoning, immediate medical attention is required. Treatment typically involves the administration of fomepizole or ethanol as antidotes, along with supportive care and correction of metabolic acidosis. Dosing should be guided by clinical protocols.

Mechanism of action

Methanol is metabolized in the liver by alcohol dehydrogenase to formaldehyde, which is further oxidized to formic acid. Formic acid is responsible for many of the toxic effects of methanol, including metabolic acidosis and visual impairment. The severity of toxicity can depend on individual susceptibility and the activity of metabolic pathways, particularly those involving folic acid metabolism, which is necessary for formate metabolism.

Pharmacodynamics

Methanol toxicity manifests through its metabolic products, primarily formic acid, which decreases blood pH, leading to metabolic acidosis. This acidosis can cause complications such as respiratory distress and cardiovascular instability. The accumulation of formic acid also impacts mitochondrial function and can lead to cellular hypoxia and damage, particularly in the optic nerve, resulting in visual impairment or blindness.

Pharmacokinetics

Methanol is rapidly absorbed through the gastrointestinal tract and can cross the blood-brain barrier. It is metabolized primarily in the liver, with a significant portion converted to formaldehyde and then to formic acid. The elimination half-life of methanol varies and can be prolonged in cases of intoxication due to saturation of metabolic pathways. The time to peak concentrations can vary significantly; toxicity can develop long after initial ingestion, complicating management.

Adverse effects

• Metabolic acidosis
• Visual impairment
• Headaches
• Nausea
• Vomiting
• Dizziness
• Coma
• Death

Precautions

• Use with caution in individuals with liver impairment
• Monitor for signs of toxicity, especially in cases of suspected overdose

Pregnancy

Methanol is classified as a teratogen and should be avoided during pregnancy due to the risk of fetal toxicity and developmental harm.

Breast-feeding

Methanol is not recommended while breastfeeding due to potential harmful effects in the nursing infant.

Storage

Store in a cool, dry place away from light and heat. Keep container tightly closed and out of reach of children.

Mechanism of action

Ethanol affects the brain’s neurons in several ways. It alters their membranes as well as their ion channels, enzymes, and receptors. Alcohol also binds directly to the receptors for acetylcholine, serotonin, GABA, and the NMDA receptors for glutamate. The sedative effects of ethanol are mediated through binding to GABA receptors and glycine receptors (alpha 1 and alpha 2 subunits). It also inhibits NMDA receptor functioning. In its role as an anti-infective, ethanol acts as an osmolyte or dehydrating agent that disrupts the osmotic balance across cell membranes. ... Ethanol is known to affect a large number of membrane proteins that participate in signaling pathways such as neurotransmitter receptors, enzymes, and ion channels, and there is extensive evidence that ethanol interacts with a variety of neurotransmitters. The major actions of ethanol involve enhancing the inhibitory effects of gamma-aminobutyric acid (GABA) at GABAa receptors and blockade of the N-methyl-D-aspartate (NMDA) subtype of glutamate, an excitatory amine acid (EAA) receptor. Animal studies indicate that the acute effects of ethanol result from competitive inhibition of glycine binding to NMDA receptor and disruption of glutamatergic neurotransmission by inhibiting the response of the NMDA receptor. Persistent glycine antagonism and attenuation of glutamatergic neurotransmission by chronic ethanol exposure results in tolerance to ethanol by enhancing EAA neurotransmission and NMDA receptor upregulation. The latter appears to involve selective increases in NMDA R2B subunit concentrations and other molecular changes in specific brain loci. The abrupt withdrawal of ethanol thus produces a hyperexcitable state that leads to the ethanol withdrawal syndrome and excitotoxic neuronal death. GABA-mediated inhibition, which normally acts to limit excitation, is eliminated during ethanol withdrawal syndrome and further intensifies this excitation. In addition, NMDA receptors function to inhibit the release of dopamine in the nucleus accumbens and mesolimbic structures, which modulate the reinforcing action of addictive xenobiotics such as ethanol. By inhibiting NMDA receptor activity, ethanol could increase dopamine release from the nucleus accumbens and ventral tegmental area and could thus create dependence. Chronic ethanol administration also results in tolerance, dependence, and an ethanol withdrawal syndrome, mediated, in part, by desensitization and or downregulation of GABAa receptors. The development of alcoholic ketoacidosis (AKA) requires that a combination of physical and physiologic events occur. The normal response to starvation and depletion of hepatic glycogen stores is for amino acids to be converted to pyruvate. Pyruvate can serve as a substrate for gluconeogenesis, be converted to acetyl-CoA, which can enter the Krebs cycle or can be utilized in various biosynthetic pathways (eg, fatty acid, ketone bodies, cholesterol, and acetylcholine) ... Ethanol metabolism generates NADH, resulting in an excess of reducing potential. This high redox state favors the conversion of pyruvate to lactate, diverting pyruvate from being a substrate for gluconeogenesis. To compensate for the lack of normal metabolic substrates, the body mobilizes fat from adipose tissue and increased fatty acid metabolism as an alternative source of energy. This response is mediated by a decrease in insulin and an increased secretion of glucagon, catecholamines, growth hormone, and cortisol. Fatty acid metabolism results in the formation of acetyl-CoA and it combines with the excess acetate that is generated from ethanol metabolism to form acetoacetate. Most of the acetoacetate is reduced to beta-hydroxybutyrate due to the excess reducing potential or high redox state of the cell. Volume depletion interferes with the renal elimination of acetoacetate and beta-hydroxybutyrate, and contributes to the acidosis. An elevated lactate concentration may result from shunting from pyruvate or

Pharmacodynamics

Alcohol produces injury to cells by dehydration and precipitation of the cytoplasm or protoplasm. This accounts for its bacteriocidal and antifungal action. When alcohol is injected in close proximity to nerve tissues, it produces neuritis and nerve degeneration (neurolysis). Ninety to 98% of ethanol that enters the body is completely oxidized. Ethanol is also used as a cosolvent to dissolve many insoluble drugs and to serve as a mild sedative in some medicinal formulations. Ethanol also binds to GABA, glycine, NMDA receptors and modulates their effects. Ethanol is also metabolised by the hepatic enzyme alcohol dehydrogenase.

Mechanism of action

... The metabolic mechanisms of methanol toxicity /are/ reviewed. ... It is noted that the most severe toxicity occurs many hours following peak blood and tissue methanol concentrations so that these do not necessarily provide an accurate indication of toxicity. Individual differences are seen both in this latent period and in individual susceptibility to methanol. This susceptibility may depend on the activity of folic acid requiring metabolic reactions involved in formate metabolism, formate being an intermediate produced during methanol oxidation and responsible for many toxic effects of methanol. Studies of the characteristics of methanol poisoning in non-primates and monkeys are examined. Despite the ingestion of lethal doses of methanol, non-primates generally do not develop significant metabolic acidosis nor impairment of vision, and no consistent histopathology has been demonstrated in these species. In monkeys, results suggest that the latent period represents a period of compensated metabolic acidosis; when compensatory mechanisms are exhausted, blood pH begins to drop. Formate accumulates and produces acidosis in the methanol poisoned monkey, but not in the rat, apparently due to a slower rate of formate metabolism to carbon dioxide in the monkey. ... Studies demonstrating the role of alcohol dehydrogenase in methanol metabolism in the monkey are reported; however, the catalase/peroxidative system which participates in methanol metabolism in rats apparently does not function in the monkey. Formaldehyde and formate metabolism are also examined. The regulation of the rate of formate metabolism is governed by regulation of the hepatic tetrahydrofolate concentrations. ... Further research is needed to determine what step or process it is which places the primate at a distinct liability in the metabolic disposition of one carbon moieties. Methanol toxicity is observed in monkeys and humans but is not seen in rats or mice. The expression of methanol poisoning is related to the ability of an animal to metabolize formate to carbon dioxide. Since the rate of formate oxidation is related to hepatic tetrahydrofolate content and the activites of folate dependent enzymes, studies were designed to determine hepatic concentrations of hepatic tetrahydrofolate and activites of folate dependent enzymes of human liver and livers of species considered insensitive to methanol poisoning. An excellent correlation between hepatic tetrahydrofolate and maximal rates of formate oxidation has been observed. In human liver, levels were only 50% of those observed for rat liver and similar to those found in monkey liver. Total folate was also lower (60% decreased) in human liver than that found in rat or monkey liver. Interestingly, mouse liver contains much higher hepatic tetrahydrofolate and total folate than rat or monkey liver. This is consistent with higher formate oxidation rates in this species. A second important observation has been made. 10-Formyltetrahydrofolate dehydrogenase activity, the enzyme catalyzing the final step of formate oxidation to carbon dioxide, was markedly reduced in both monkey and human liver. Thus, two mechanisms may be operative in explaining low formate oxidation in species susceptible to methanol toxicity, low hepatic tetahydrofolate levels and reduced hepatic 10-formyltetrahydrofolate dehydrogenase activity. Formic acid, the toxic metabolite of methanol, has been hypothesized to produce retinal and optic nerve toxicity by disrupting mitochondrial energy production. It has been shown in vitro to inhibit the activity of cytochrome oxidase, a vital component of the mitochondrial electron transport chain involved in ATP synthesis. Inhibition occurs subsequent to the binding of formic acid to the ferric heme iron of cytochrome oxidase, and the apparent inhibition constant is between 5 and 30 mM. Concentrations of formate present in the blood and tissues of methanol-intoxicated humans, non-human primates and rodent m