MUPISOFT

Indications

• Eradication of nasal carriage of Staphylococcus aureus, including methicillin-resistant Staphylococcus aureus (MRSA)
• Treatment of skin infections caused by susceptible bacteria, including impetigo and folliculitis

Dosage

Adults: For nasal carriage eradication, apply 2-3 times a day for 5 days, with the dose applied to the inner surface of each nostril. For

Mechanism of action

Mupirocin specifically and reversibly binds to bacterial isoleucyl transfer-RNA (tRNA) synthetase, inhibiting the enzyme that converts isoleucine and tRNA to isoleucyl-tRNA. This inhibition leads to decreased bacterial protein and RNA synthesis, resulting in bacteriostatic effects at lower concentrations and bactericidal effects with prolonged exposure, killing 90-99% of susceptible bacteria over 24 hours.

Pharmacodynamics

Mupirocin is effective against susceptible aerobic gram-positive cocci, particularly Staphylococcus aureus, Staphylococcus epidermidis, and beta-hemolytic streptococci such as Streptococcus pyogenes. Its antibacterial activity is attributed to its ability to inhibit protein synthesis, which is crucial for bacterial survival. Clinical studies have shown a therapeutic response rate of 94 to 98% after one week of treatment for conditions like impetigo, with over 90% of patients demonstrating clinical improvement in primary and secondary skin infections.

Pharmacokinetics

Mupirocin is primarily used topically, resulting in minimal systemic absorption. When applied to the skin, it is rapidly absorbed and achieves high local concentrations. The drug is metabolized in the liver and excreted in urine. Its pharmacokinetic profile supports its use for localized infections with minimal risk of systemic side effects.

Adverse effects

• Skin reactions
• Nasal mucosal disorder

Interactions

• Caution in patients with sensitivity to sulfonamides
• Caution with significant hepatic impairment
• Caution with significant renal impairment

Precautions

• Monitor for leucopenia
• Use with caution in patients with G6PD deficiency due to risk of hemolysis
• Avoid use in pregnancy unless potential benefit outweighs risk due to risk of neonatal hemolysis and methaemoglobinaemia in the third trimester

Pregnancy

Manufacturer advises avoiding unless potential benefit outweighs risk-no information available.

Breast-feeding

Small risk of kernicterus in jaundiced infants and of haemolysis in G6PD-deficient infants.

Storage

Store at room temperature, away from moisture and heat.

Formulations

• Mupirocin 20 mg per 1 gram cream
• Mupirocin nasal spray

Indications

• Stabilization of emulsions in pharmaceutical formulations
• Improvement of drug solubility and bioavailability
• Enhancement of texture and stability in food products
• Use in topical formulations for skin hydration

Dosage

Children: Refer to specific product guidelines or consult the manufacturer's information for recommended dosage, as emulsifying agents are often used as excipients rather than active pharmacological agents.

Adults: Refer to specific product guidelines or consult the manufacturer's information for recommended dosage, as emulsifying agents are often used as excipients rather than active pharmacological agents.

Mechanism of action

Emulsifying agents function by accumulating at the interface of the dispersed and continuous phases of an emulsion. They possess both hydrophilic (water-attracting) and hydrophobic (water-repelling) properties, which allows them to stabilize the emulsion by forming a protective barrier around the droplets of one liquid phase, preventing coalescence. This mechanism is crucial for maintaining the stability and homogeneity of the emulsified mixture.

Pharmacodynamics

The pharmacodynamic properties of emulsifying agents are largely related to their ability to stabilize emulsions and enhance the delivery of active pharmaceutical ingredients. By improving the solubility of hydrophobic compounds in aqueous environments, emulsifiers can enhance the bioavailability of certain drugs. Their action can also modify the release profiles of drugs from emulsified formulations.

Pharmacokinetics

The pharmacokinetics of emulsifying agents depend on their chemical structure, molecular weight, and the formulation in which they are used. Generally, emulsifiers are not absorbed systemically when used in pharmaceutical preparations; rather, they act locally at the site of application or in the gastrointestinal tract. The metabolism and excretion of emulsifying agents can vary, but many are excreted unchanged in the feces.

Adverse effects

• Gastrointestinal discomfort
• Nausea
• Diarrhea

Precautions

• Use with caution in patients with known allergies to emulsifiers or similar compounds
• Monitor for gastrointestinal symptoms in patients with pre-existing gastrointestinal disorders

Pregnancy

Emulsifiers are generally considered safe for use during pregnancy, but caution is advised. Consult healthcare professionals for individual assessment.

Breast-feeding

Emulsifiers are typically regarded as safe during breastfeeding, yet it is recommended to consult healthcare professionals for personalized advice.

Storage

Store in a cool, dry place away from direct sunlight. Ensure the container is tightly closed to prevent moisture absorption.

Formulations

• Liquid emulsions
• Creams and lotions
• Powdered emulsifiers

Indications

• Angina pectoris
• Heart failure
• Hypertensive emergencies
• Myocardial infarction

Dosage

Children: Dosing in children is not well established; refer to

Adults: For acute angina, 0.3 to 0.6 mg sublingually. For transdermal patches, doses vary based on the specific product; consult guidelines for individualized dosing.

Mechanism of action

Nitroglycerin is converted by mitochondrial aldehyde dehydrogenase in vascular smooth muscle cells to nitric oxide (NO). NO activates guanylate cyclase, leading to the conversion of guanosine triphosphate (GTP) to cyclic guanosine 3',5'-monophosphate (cGMP). cGMP induces relaxation of vascular smooth muscle, which results in vasodilation and increased blood flow, particularly to the heart. This mechanism reduces myocardial oxygen requirements and alleviates angina symptoms.

Pharmacodynamics

Nitroglycerin causes relaxation of vascular smooth muscles, leading to both arteriolar and venous dilation. This results in increased myocardial blood flow, reduced cardiac preload and afterload, and lowered myocardial wall stress. Additionally, it alleviates coronary artery spasms and decreases systemic vascular resistance and blood pressure. Tolerance may develop with prolonged use, reducing efficacy due to desensitization of smooth muscle and potential inhibition of mitochondrial aldehyde dehydrogenase.

Pharmacokinetics

Nitroglycerin is rapidly absorbed and undergoes significant first-pass metabolism when administered orally. It has a half-life of about 1-4 minutes when given intravenously. The onset of action varies depending on the route of administration, with sublingual forms acting within minutes and transdermal patches providing sustained release. The drug is metabolized primarily in the liver and excreted in urine as metabolites.

Contra-indications

• Hypersensitivity to nitroglycerin or any of its components
• Severe anemia
• Increased intracranial pressure
• Hypotension
• Cardiomyopathy with obstructive lesions
• Severe aortic stenosis

Adverse effects

• Headache
• Dizziness
• Hypotension
• Tachycardia
• Nausea
• Flushing
• Methemoglobinemia

Interactions

• Concurrent use with phosphodiesterase type 5 inhibitors (e.g., sildenafil, tadalafil) may lead to severe hypotension
• Antihypertensives may enhance the hypotensive effect of nitroglycerin
• Alcohol may increase the risk of hypotension
• Other vasodilators may have additive effects

Precautions

• Use with caution in patients with renal or hepatic impairment
• Monitor blood pressure regularly
• Consider potential for tolerance with prolonged use
• Should not be abruptly discontinued after long-term use

Pregnancy

Nitroglycerin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Limited data available.

Breast-feeding

Nitroglycerin is excreted in breast milk, caution is advised when administering to nursing mothers.

Storage

Store in a tightly closed container at room temperature, away from moisture and heat.

Formulations

• Sublingual tablets
• Transdermal patches
• Oral extended-release capsules
• Intravenous infusion
• Topical ointment

Dosage

Children: Refer to the BNF for Children for appropriate dosing information in paediatric cases, especially in instances of overdose.

Adults: Refer to the BNF for specific dosing information based on clinical circumstances, particularly in cases of overdose.

Mechanism of action

Ethylene glycol is metabolized by alcohol dehydrogenase to glycoaldehyde, which is subsequently converted to glycolic, glyoxylic, and oxalic acids. These metabolites contribute to anion gap metabolic acidosis and are responsible for tissue injury through the formation of insoluble calcium oxalate crystals.

Pharmacodynamics

The toxicity of ethylene glycol arises from its metabolites, particularly glycolic and oxalic acids. These compounds induce metabolic acidosis, lead to renal failure through calcium oxalate crystal deposition in the kidneys, and can cause neurological impairment. The anion gap increases due to the accumulation of these acids, leading to complications such as cardiovascular instability and potential multi-organ failure.

Pharmacokinetics

Ethylene glycol is rapidly absorbed after oral ingestion. It undergoes first-pass metabolism primarily in the liver, where it is converted into its toxic metabolites. The elimination half-life of ethylene glycol varies but is generally prolonged in cases of renal impairment. Renal excretion of metabolites contributes to the duration of toxicity, necessitating prompt medical intervention in cases of overdose.

Adverse effects

• Metabolic acidosis
• Renal failure
• CNS depression
• Hypocalcemia
• Cardiovascular collapse
• Pulmonary edema

Precautions

• Use with caution in patients with renal impairment
• Monitor for signs of metabolic acidosis
• Evaluate electrolyte levels, particularly calcium

Pregnancy

There is limited data on the safety of ethylene glycol in pregnancy. It should only be used if clearly needed.

Breast-feeding

It is unknown if ethylene glycol is excreted in human milk. Caution is advised.

Storage

Store in a tightly closed container at room temperature, away from heat and moisture.

Formulations

• Liquid

Indications

• Used as an emulsifying agent in pharmaceutical formulations
• Used in food products for texture and stability
• May be indicated in topical preparations to enhance drug absorption

Dosage

Children: Refer to specific product guidelines as doses can vary widely based on formulation and intended use.

Adults: Refer to specific product guidelines as doses can vary widely based on formulation and intended use.

Mechanism of action

Monostearate functions primarily as a surfactant. It reduces the surface tension between components in a mixture, allowing for better emulsification of oils and water. This action enhances the dispersion of active ingredients and improves their absorption in the gastrointestinal tract.

Pharmacodynamics

As an emulsifier, monostearate facilitates the formation of stable emulsions, which can lead to improved drug delivery and absorption. Its ability to enhance solubility of lipophilic compounds can result in increased bioavailability of certain drugs, making them more effective.

Pharmacokinetics

Monostearate is generally considered non-toxic and is metabolized by the body through hydrolysis into glycerol and stearic acid. It is poorly absorbed in the gastrointestinal tract due to its large molecular structure, and any absorbed amounts may be further metabolized or excreted. The onset and duration of action depend on the formulation in which it is used.

Pregnancy

Monostearate is generally considered safe for use during pregnancy, but it is important to consult with a healthcare provider for personalized advice.

Breast-feeding

Monostearate is typically regarded as safe during breastfeeding, but a healthcare provider should be consulted to ensure no adverse effects on the infant.

Storage

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

Formulations

• Monostearate powder
• Monostearate capsules
• Monostearate ointment

Indications

• Constipation
• Bowel preparation prior to surgical procedures or diagnostic tests

Dosage

Children: Refer to specific guidelines or BNF for Children for dosing information.

Adults: Refer to specific guidelines or BNF for detailed dosing information.

Mechanism of action

Polyethylene glycol works by osmotically retaining water in the intestinal lumen, which increases the water content of the stool. This enhances the passage of stool through the intestines and promotes bowel movements. The high molecular weight of polyethylene glycol prevents its absorption in the gastrointestinal tract, ensuring that it remains in the lumen to exert its effects.

Pharmacodynamics

The pharmacodynamic profile of polyethylene glycol involves its ability to increase stool water content, thereby reducing stool consistency and facilitating easier passage. It does not stimulate intestinal motility directly but rather relies on the osmotic effect to promote bowel evacuation. The onset of action typically occurs within 24 to 96 hours after ingestion.

Pharmacokinetics

Polyethylene glycol is not absorbed systemically, and its pharmacokinetics are characterized by its presence solely in the gastrointestinal tract. It is excreted unchanged in the stool. The volume of polyethylene glycol administered can influence the effectiveness and timing of its action, but its absorption is negligible, making systemic side effects rare.

Adverse effects

• Abdominal cramping
• Diarrhea
• Nausea
• Vomiting
• Bloating
• Flatulence

Precautions

• Use with caution in patients with gastrointestinal disorders or bowel obstruction.
• Ensure adequate hydration during use to prevent dehydration.

Pregnancy

Polyethylene glycol is generally considered safe during pregnancy, but should be used under medical supervision.

Breast-feeding

Polyethylene glycol is excreted in breast milk in very small amounts and is generally regarded as safe during breastfeeding.

Storage

Store at room temperature, away from moisture and heat.

Formulations

• Powder for oral solution
• Liquid formulation

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.

Indications

• Pain relief
• Cold and flu symptoms
• Digestive issues
• Allergy symptoms
• Stress management
• General wellness

Dosage

Children: Refer to specific product guidelines and consult a healthcare professional for appropriate dosing.

Adults: Refer to specific product guidelines and consult a healthcare professional for appropriate dosing.

Mechanism of action

The mechanism of action for self-care treatments varies widely depending on the substance or therapy being used. For example, over-the-counter medications may work by blocking pain signals in the nervous system or reducing inflammation. Herbal supplements may exert their effects through various pathways such as antioxidant activity or modulation of immune responses. Overall, self-care approaches aim to restore balance and promote well-being through various biological and physiological mechanisms.

Pharmacodynamics

Pharmacodynamics for self-care medications can include a range of effects depending on the specific treatment. Common effects might include analgesia from non-steroidal anti-inflammatory drugs (NSAIDs), sedation from antihistamines, or improved gastrointestinal function from antacids. The efficacy and safety of self-care treatments largely depend on the correct identification of the condition being treated, appropriate dosing, and individual patient factors such as age, weight, and comorbid conditions.

Pharmacokinetics

Pharmacokinetics of self-care treatments also varies by the specific substance. Generally, the pharmacokinetic profile includes absorption, distribution, metabolism, and excretion (ADME) characteristics. For example, oral medications are typically absorbed in the gastrointestinal tract and may undergo first-pass metabolism in the liver before reaching systemic circulation. The half-life of a drug determines its duration of action and frequency of dosing, which is crucial for effective self-management.

Mechanism of action

Mupirocin specifically and reversibly binds to bacterial isoleucyl transfer-RNA (tRNA) synthetase, which is an enzyme that promotes the conversion of isoleucine and tRNA to isoleucyl-tRNA. Inhibition of this enzyme subsequently leads to the inhibition of the bacterial protein and RNA synthesis. Mupirocin is bacteriostatic at lower concentrations but it exerts bactericidal effects with prolonged exposure, killing 90-99% of susceptible bacteria over a 24 hour period.

Pharmacodynamics

Mupirocin is reported to be active against susceptible aerobic gram-positive cocci, such as _Staphylococcus aureus_, _Staphylococcus epidermidis_, and other beta-hemolytic streptococci_Streptococcus pyogenes_. It mediates its antibacterial activity by inhibiting the bacterial protein synthesis and formation of bacterial proteins essential for survival. The minimum bactericidal concentration (MBC) against relevant pathogens is generally eight-fold to thirty-fold higher than the minimum inhibitory concentration (MIC). In one clinical study investigating the therapeutic effectiveness of topical mupirocin in impetigo, the therapeutic response rate was about 94 to 98% after one week following the end of therapy. In clinical studies of patients with primary and secondary skin infections, both elimination of the bacterial pathogen and clinical cure or improvement hav been demonstrated in over 90% of patients receiving topical mupirocin. Mupirocin resistance as high as 81% has been reported previously. Resistance to mupirocin, which occurs more frequently in methicillin-resistant than methicillin-susceptible staphylococci, may occur with the production of a modified isoleucyl-tRNA synthetase, or the acquisition of, by genetic transfer, a plasmid mediating a new isoleucyl-tRNA synthetase.

Mechanism of action

Nitroglycerin is converted by mitochondrial aldehyde dehydrogenase in smooth muscle cells to nitric oxide (NO), a potent vasodilator. NO activates the enzyme guanylate cyclase, which converts guanosine triphosphate (GTP) to cyclic guanosine 3',5'-monophosphate (cGMP) in vascular smooth muscle and other tissues. cGMP is an endogenous vasodilator of vascular smooth muscle: it causes protein kinase-dependent phosphorylation and activates downstream cascades that promote relaxation and increased blood flow in veins, arteries and cardiac tissue. An _in vitro_ study using mouse aorta suggests that nitric oxide, an active metabolite of nitroglycerin, targets the natriuretic peptide receptors. The drugs used to treat angina alleviate symptoms by increasing blood flow to the ischemic myocardium and/or by reducing myocardial oxygen requirements. ... /Nitrates/ reduce myocardial oxygen requirements through their effects on the systemic circulation. Their major systemic action is a reduction in venous tone, which leads to pooling of blood in peripheral veins, decreased venous return, and reduced ventricular volume and myocardial tension (preload). /Org nitrates/ Although it predominately affects vascular smooth muscle /nitroglycerin/, the bronchioles, gastrointestinal tract (including biliary system), ureters, and uterus are affected. Free radicals of nitric oxide may activate guanylate cyclase, resulting in increased synthesis of cyclic GMP. Nitric oxide may combine with sulfhydryl groups in the endothelium and produce S-nitrosothiols, which stimulate guanylate cyclase production. N-acetyl-cycteine may enhance this process by providing a source of sulfhydryl groups. Cyclic GMP appears to reduce stored calcium and interfere with calcium-activated smooth muscle contractions. Organic nitrates... lead to the formation of the reactive free radical nitric oxide, which can activate guanylyl cyclase and increase the synthesis of cyclic GMP in smooth muscle and other tissues... A cyclic GMP-dependent protein kinase catalyzes the phosphorylation of various proteins in smooth muscle. Eventually, the light chain of myosin is dephosphorylated. Phosphorylation of the myosin chain regulates the maintenance of the contractile state in smooth muscle. Nitrates also may alter the prostaglandin system by inhibiting thromboxane synthetase and permitting preferential formation of prostacyclin over thromboxane A2. Both of these two short-acting vasoactive substances are formed from prostaglandin precursors. Prostacyclin is a potent vasodilator which causes smooth muscle relaxation through phosphorylation of the myosin light chain kinase. This reduces its ability to to be activated by calciun and calmodulin.

Pharmacodynamics

Nitroglycerin causes the relaxation of vascular smooth muscles, causing arteriolar and venous dilatation. It increases blood flow to the myocardium and reduces cardiac preload and afterload, decreasing myocardial wall stress and ameliorating anginal symptoms. Nitroglycerin also reduces coronary artery spasm, decreasing systemic vascular resistance as well as systolic and diastolic blood pressure. Like other organic nitrates, repeated and prolonged administration of nitroglycerin can lead to the development of tolerance or desensitization of vascular smooth muscle to further nitroglycerin-induced vasorelaxation. This loss of efficacy may be associated with the inhibition of mitochondrial aldehyde dehydrogenase, which is an important enzyme involved in the bioactivation of nitroglycerin. Nitroglycerin tolerance may be accompanied by pro-oxidant effects, endothelial dysfunction, and increased sensitivity to vasoconstrictors.

Mechanism of action

Ethylene glycol is metabolized by alcohol dehydrogenase to glycoaldehyde, which is then metabolized to glycolic, glyoxylic, and oxalic acids. These acids, along with excess lactic acid are responsible for the anion gap metabolic acidosis. Oxalic acid readily precipitates with calcium to form insoluble calcium oxalate crystals. Tissue injury is caused by widespread deposition of oxalate crystals and the toxic effects of glycolic and glyoxylic acids.

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.