DAPSPOT 7.5%

Indications

• Multibacillary leprosy
• Paucibacillary leprosy
• Prophylaxis against Pneumocystis jirovecii pneumonia
• Treatment of mild to moderate Pneumocystis jirovecii pneumonia
• Dermatitis herpetiformis
• Lyme disease

Dosage

Adults: 100 mg three times a day for one month, subsequent dose

Mechanism of action

Dapsone acts by inhibiting the synthesis of dihydrofolic acid, competing with para-amino-benzoate for the active site of dihydropteroate synthetase. This action disrupts the folate pathway in bacteria and protozoa. Additionally, dapsone has anti-inflammatory properties, which are believed to be mediated through inhibition of neutrophil activity, including myeloperoxidase and lysosomal enzymes, and reducing tissue damage caused by neutrophils.

Pharmacodynamics

Dapsone has broad-spectrum activity, being effective against various bacteria and protozoa. It is particularly effective in treating leprosy as part of a multidrug regimen recommended by the World Health Organization. Its anti-inflammatory effects may help in conditions like dermatitis herpetiformis. Dapsone is rapidly absorbed, reaching peak plasma concentrations within hours, and is known to have a long duration of action due to its retention in tissues.

Pharmacokinetics

Dapsone is well absorbed from the gastrointestinal tract and is widely distributed in body tissues, with significant accumulation in the liver, kidney, skin, and muscle. The drug has a half-life of approximately 24 hours, allowing for once-daily dosing. It undergoes hepatic metabolism and is excreted primarily in urine, with traces remaining in the body for weeks after cessation of therapy.

Contra-indications

• Known hypersensitivity to dapsone or any of its components
• Severe glucose-6-phosphate dehydrogenase (G6PD) deficiency

Adverse effects

• Abdominal pain
• Anorexia
• Dry eye
• Fatigue
• Gastrointestinal disorders
• Headache
• Lymphadenopathy
• Nausea
• Photosensitivity reaction
• Skin discoloration
• Visual impairment
• Vomiting
• Weight loss
• Haemolytic anaemia
• Dapsone syndrome (rash with fever and eosinophilia)

Interactions

• Increased risk of methaemoglobinaemia with topical prilocaine
• Increased risk of methaemoglobinaemia with local anaesthetics
• Increased risk of methaemoglobinaemia with aminosalicylic acid
• Increased risk of methaemoglobinaemia with antiepileptics (fosphenytoin, phenobarbital, phenytoin, primidone)
• Increased risk of methaemoglobinaemia with nitrates
• Increased risk of methaemoglobinaemia with nitrofurantoin
• Increased risk of methaemoglobinaemia with nitroprusside
• Increased risk of methaemoglobinaemia with paracetamol
• Increased risk of methaemoglobinaemia with sulfonamides

Precautions

• Use with caution in hepatic impairment
• Use with caution in renal impairment
• Monitor blood disorders during long-term treatment
• Avoid use in patients with persistent abdominal pain and diarrhea

Pregnancy

Use with caution. Folic acid may be given to mother throughout pregnancy; higher doses recommended in third trimester due to risk of hemolysis and methaemoglobinaemia.

Breast-feeding

May alter color of milk; risk to infant very small unless infant is G6PD deficient.

Storage

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

Formulations

• Dapsone 50 mg

Indications

• Topical drug formulations
• Ophthalmic solutions
• Cosmetic products
• Transdermal drug delivery systems

Dosage

Children: Refer to specific product guidelines as carbomer is used as a formulation agent and does not have standard dosing.

Adults: Refer to specific product guidelines as carbomer is used as a formulation agent and does not have standard dosing.

Mechanism of action

Carbomer works by absorbing water and swelling to form a gel, which increases the viscosity of the formulation. This property is utilized in topical preparations to improve the delivery and stability of active ingredients, allowing for a more controlled release of the drug.

Pharmacodynamics

The pharmacodynamics of carbomer are primarily related to its physical properties as a gelling agent. It enhances the stability and viscosity of formulations, which can improve the bioavailability of drugs when used in topical applications. Carbomer itself has no systemic pharmacological effects since it is not absorbed into the bloodstream when applied topically.

Pharmacokinetics

Carbomer is not significantly absorbed through the skin or gastrointestinal tract, which means it does not have a traditional pharmacokinetic profile characterized by absorption, distribution, metabolism, and excretion. It primarily acts locally at the site of application.

Adverse effects

• Local irritation
• Allergic reactions
• Redness
• Swelling

Precautions

• Avoid contact with eyes
• Use caution in individuals with known allergies to carbomers
• If irritation occurs, discontinue use

Pregnancy

Carbomer is generally considered safe for use during pregnancy, but it is always advisable to consult a healthcare provider before use.

Breast-feeding

Carbomer is not known to be absorbed systemically, making it likely safe for use while breastfeeding, but consulting a healthcare provider is recommended.

Storage

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

Formulations

• Gel
• Cream
• Ointment
• Powder

Indications

• General anesthesia
• Induction of anesthesia
• Sedation in surgical procedures

Dosage

Children: Refer to the BNF for Children for specific dosing information based on age and weight.

Adults: Dosage varies depending on the procedure and patient characteristics; refer to specific clinical guidelines.

Mechanism of action

The exact mechanism of action of diethyl ether is not completely understood. It is believed to produce reversible loss of consciousness through interactions with membrane lipids and hydrophobic regions of membrane-bound proteins. The drug may alter the function of ion channel proteins, potentially affecting the GABA receptor, which is implicated in the modulation of neuronal excitability. Additionally, ether has been shown to increase plasma levels of adrenaline and noradrenaline, suggesting stimulation of neurosympathetic and adrenomedullary functions.

Pharmacodynamics

Ether induces general anesthesia characterized by a reversible loss of sensation and consciousness. Its anesthetic properties are thought to be the result of its effects on neuronal signaling and neurotransmitter systems, primarily by enhancing inhibitory neurotransmission through GABAergic pathways, leading to decreased neuronal excitability and a sedative effect.

Pharmacokinetics

Diethyl ether is rapidly absorbed through the lungs and is distributed widely in body tissues due to its lipophilicity. It is metabolized primarily in the liver, and elimination occurs through exhalation and minor metabolic pathways. The onset of action is swift, with effects seen within minutes of inhalation, and recovery is equally rapid upon cessation of exposure.

Adverse effects

• Nausea
• Vomiting
• Respiratory depression
• Cardiovascular instability
• Hypotension
• Delayed recovery from anesthesia

Interactions

• May potentiate the effects of other central nervous system depressants
• Increased risk of respiratory depression when used with opioids
• Potential interaction with alcohol, leading to enhanced sedation

Precautions

• Use with caution in patients with respiratory or cardiovascular diseases
• Monitor for signs of respiratory depression
• Ensure appropriate equipment and personnel are available for anesthesia

Pregnancy

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

Breast-feeding

Use with caution; limited data available on excretion in breast milk.

Storage

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

Formulations

• Inhalation solution
• Liquid for inhalation

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

Dosage

Children: Dosing for pediatric patients should be determined based on specific clinical guidelines and the formulation used, as general dosing information for homopolymers is not established.

Adults: Dosage is dependent on the specific application and formulation of the homopolymer. Refer to specific product guidelines for dosing recommendations.

Mechanism of action

The mechanism of action of homopolymers varies depending on their chemical composition and structure. Generally, they can interact with biological systems through various pathways, including adhesion to cell surfaces, encapsulation of drugs, and modification of drug release profiles. Their inert nature and ability to form hydrogels can aid in controlled drug delivery.

Pharmacodynamics

Homopolymers exhibit pharmacodynamic properties that are influenced by their molecular weight, degree of crystallinity, and functional groups. These properties can impact drug solubility, release rates, and bioavailability. The interactions with biological tissues are primarily physical rather than chemical, affecting factors such as drug absorption and distribution.

Pharmacokinetics

The pharmacokinetics of homopolymers are not defined in the traditional sense as they do not typically undergo metabolism like small molecule drugs. Instead, their behavior in the body is determined by their degradation rate, which can depend on factors such as the polymer's structure and the presence of enzymes. Excretion usually occurs through the kidneys or via biodegradation into smaller, non-toxic components.

Pregnancy

The safety of homopolymers during pregnancy has not been established. Consultation with a healthcare provider is recommended before use.

Breast-feeding

Data on the excretion of homopolymers in human milk are not available. Caution is advised when administering to nursing mothers.

Storage

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

Dosage

Children: Refer to specific guidelines for pediatric dosing; consult the BNF for Children for accurate dosage information.

Adults: Refer to specific guidelines for use; dosage may vary based on the context of use.

Mechanism of action

Hydroxide ions act primarily as bases, neutralizing acids to form water and salts. They participate in various biochemical pathways, including selenium metabolism and the degradation of reactive oxygen species. Hydroxide can influence enzyme activity and stability by altering the pH of the environment, thereby affecting metabolic reactions.

Pharmacodynamics

Hydroxide ions can impact biological processes by changing the local pH, which influences enzyme activity, ion transport, and the solubility of other compounds. Their ability to neutralize acids can help regulate physiological pH, contributing to homeostasis in living organisms.

Pharmacokinetics

As an inorganic ion, hydroxide does not undergo traditional pharmacokinetic processes like absorption, distribution, metabolism, or excretion. Instead, it is rapidly equilibrated in biological fluids and participates in acid-base reactions, having immediate effects on the local environment.

Pregnancy

There is limited information regarding the use of hydroxide during pregnancy. Consult a healthcare professional for advice.

Breast-feeding

Limited data is available on the excretion of hydroxide in breast milk. Consult a healthcare professional before use.

Storage

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

Indications

• Allergic conditions
• Autoimmune diseases
• Asthma and chronic obstructive pulmonary disease (COPD)
• Certain cancers (e.g., leukemia, lymphoma)
• Skin conditions (e.g., dermatitis)
• Inflammatory bowel disease
• Multiple sclerosis exacerbations
• Severe infections requiring immunosuppression

Dosage

Children: Refer to BNF for Children for specific dosing; doses vary significantly based on the child's age, weight, and condition being treated.

Adults: Refer to BNF for specific dosing; typically, initial doses range from 4 to 48 mg depending on the severity of the condition.

Mechanism of action

Methylprednisolone exerts its effects by binding to glucocorticoid receptors, leading to the modulation of gene expression. This interaction influences the transcription of anti-inflammatory proteins while suppressing the expression of pro-inflammatory genes, ultimately resulting in reduced inflammation and immune response.

Pharmacodynamics

The pharmacodynamic effects of methylprednisolone are characterized by its ability to decrease inflammation, suppress the immune response, and affect carbohydrate metabolism. Therapeutic doses lead to various systemic effects, including modification of leukocyte distribution and inhibition of cytokine production.

Pharmacokinetics

Methylprednisolone is well absorbed after oral administration, with a bioavailability of approximately 50%. It has a volume of distribution that reflects extensive tissue binding. The drug is metabolized primarily in the liver through conjugation and reduction, and its metabolites are excreted in urine. The half-life varies based on the route of administration but is generally around 18 to 36 hours.

Adverse effects

• Increased blood pressure
• Hyperglycemia
• Weight gain
• Mood changes
• Insomnia
• Gastrointestinal disturbances
• Increased susceptibility to infections

Interactions

• methylphenidate+apraclonidine: Severe (decreases effects)
• methylthioninium chloride+bupropion: Severe (increases risk of severe hypertension)
• methylphenidate+linezolid: Severe (increases risk of elevated blood pressure)
• rasagiline+methylphenidate: Severe (increases risk of a hypertensive crisis)
• mao-inhibitors+methylphenidate: Severe (increases risk of a hypertensive crisis)
• dronedarone+methylprednisolone: Moderate (increases exposure)
• miconazole+methylprednisolone: Moderate (increases concentration)
• antifungals, azoles+methylprednisolone: Moderate (increases exposure)
• crizotinib+methylprednisolone: Moderate (increases exposure)

Precautions

• Use with caution in patients with hypertension
• Monitor blood glucose levels in diabetic patients
• Consider potential for infection risk due to immunosuppression
• Evaluate for psychiatric effects in susceptible individuals

Pregnancy

Corticosteroids may be used during pregnancy if the potential benefit justifies the risk to the fetus. Careful monitoring is advised.

Breast-feeding

Corticosteroids are excreted in breast milk; caution is advised. Monitor the infant for potential effects.

Storage

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

Formulations

• Tablets
• Injectable solutions
• Topical preparations

Mechanism of action

Methylsulphate functions as a methylating agent, transferring a methyl group to nucleophiles. This process involves the formation of a sulfonium ion, which is highly reactive and can readily react with nucleophilic sites on various substrates, leading to methylation reactions.

Pharmacodynamics

The pharmacodynamics of methylsulphate is primarily related to its role as a methylating agent in biochemical reactions. It can alter the structure and function of biological molecules, potentially affecting cellular processes and signaling pathways. However, detailed pharmacodynamic studies specific to therapeutic use are limited.

Pharmacokinetics

There is limited information on the pharmacokinetics of methylsulphate, given its typical use as a reagent in laboratory settings rather than a clinical drug. When used in chemical reactions, its reactivity and transformation into other compounds would dictate its pharmacokinetic profile, which could vary significantly based on the specific context of use.

Pregnancy

There is limited data on the use of methylsulphate in pregnancy. Consult relevant guidelines.

Breast-feeding

Data on the excretion of methylsulphate in human milk is not available. Caution is advised.

Storage

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

Indications

• Preservative in cosmetics
• Preservative in pharmaceuticals
• Preservative in food products

Dosage

Children: Refer to specific product guidelines as dosing varies based on formulation and concentration used.

Adults: Refer to specific product guidelines as dosing varies based on formulation and concentration used.

Mechanism of action

Parabens work by inhibiting the growth of microorganisms through their ability to disrupt the cellular processes of bacteria and fungi. They penetrate the microbial cell membrane and disrupt enzyme and protein functions, leading to cell death. Parabens are known to have low toxicity and are metabolized by the body, subsequently being excreted in urine.

Pharmacodynamics

Parabens demonstrate broad-spectrum antimicrobial activity, making them effective preservatives in various formulations. Their efficacy is influenced by factors such as concentration, pH, and the presence of other ingredients in the formulation. Due to their structural similarity to estrogen, there has been concern regarding their potential endocrine-disrupting effects, although the clinical significance of this is still debated.

Pharmacokinetics

Parabens are readily absorbed through the skin and gastrointestinal tract. Once absorbed, they are rapidly metabolized primarily in the liver. They undergo hydrolysis to form para-hydroxybenzoic acid, which is then conjugated with glucuronic acid and excreted in urine. The half-life of parabens in the human body is relatively short, and they are eliminated rapidly.

Adverse effects

• Allergic reactions, such as skin rashes
• Irritation at the site of application
• Endocrine disruption (in high concentrations)

Precautions

• Use with caution in individuals with known sensitivities or allergies to parabens
• Consider potential endocrine effects with prolonged exposure

Pregnancy

Parabens are generally considered safe in cosmetics and personal care products during pregnancy, although caution is advised due to potential endocrine disruption.

Breast-feeding

Parabens are considered safe in breastfeeding, but it is recommended to use products with minimal or no parabens when possible.

Storage

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

Formulations

• Topical creams
• Lotions
• Shampoos
• Conditioners
• Makeup products
• Pharmaceutical preparations

Dosage

Children: Refer to specific drug formulations and product labels as purified substances can vary widely in their use and dosing.

Adults: Refer to specific drug formulations and product labels as purified substances can vary widely in their use and dosing.

Mechanism of action

The mechanism of action for purified compounds varies widely depending on the specific substance. Generally, purified drugs exert their effects by interacting with specific biological targets, such as receptors, enzymes, or ion channels, leading to a desired therapeutic effect. This interaction can involve binding to receptors to activate or inhibit signaling pathways, modulating enzymatic activity, or altering physiological processes.

Pharmacodynamics

Pharmacodynamics describes the effects of a drug on the body and the relationship between drug concentration and effect. For purified drugs, this can involve dose-response relationships and the time course of their action. The purified form often enhances potency and reduces variability in response among patients, which can lead to more predictable therapeutic outcomes. The overall effect is determined by the drug's affinity for its target, the efficacy of the drug-receptor interaction, and the downstream signaling pathways activated as a result of this interaction.

Pharmacokinetics

Pharmacokinetics involves the absorption, distribution, metabolism, and excretion (ADME) of a drug. For purified substances, absorption can be more efficient due to the absence of impurities that may affect solubility or stability. Distribution may also be enhanced, leading to higher bioavailability. Metabolism can be influenced by the structure of the purified compound, as it may be metabolized more readily by liver enzymes. Excretion typically occurs through the kidneys or liver, depending on the molecular characteristics of the purified drug.

Pregnancy

Consult with a healthcare professional, as the safety of purified forms of medications during pregnancy may vary depending on the specific substance.

Breast-feeding

Consult with a healthcare professional, as the safety of purified forms of medications during breastfeeding may vary depending on the specific substance.

Storage

Store in a cool, dry place, away from light and moisture, and keep out of reach of children.

Mechanism of action

Dapsone acts against bacteria and protozoa in the same way as sulphonamides, that is by inhibiting the synthesis of dihydrofolic acid through competition with para-amino-benzoate for the active site of dihydropteroate synthetase. The anti-inflammatory action of the drug is unrelated to its antibacterial action and is still not fully understood. Dapsone is a structural analog of para-aminobenzoic acid (PABA) and a competitive inhibitor of dihydropteroate synthase (folP1P2) in the folate pathway ... The effect on this evolutionarily conserved pathway also explains why dapsone is a broad-spectrum agent with antibacterial, anti-protozoal, and antifungal effects. The anti-inflammatory effects of dapsone occur via inhibition of tissue damage by neutrophils. First, dapsone inhibits neutrophil myeloperoxidase activity and respiratory burst. Second, it inhibits activity of neutrophil lysosomal enzymes. Third, it may also act as a free radical scavenger, counteracting the effect of free radicals generated by neutrophils. Fourth, dapsone may also inhibit migration of neutrophils to inflammatory lesions. 1-30 Ug/mL dapsone interfered with myeloperoxidase-H2O2-halide-mediated cytotoxic system in polymorphonuclear leukocytes. Kinetic studies revealed competitive inhibition of myeloperoxidase. Its action in dermatitis herpetiformis may be explained by effect on this system.

Pharmacodynamics

Dapsone is a sulfone with anti-inflammatory immunosuppressive properties as well as antibacterial and antibiotic properties. Dapsone is the principal drug in a multidrug regimen recommended by the World Health Organization for the treatment of leprosy. As an anti-infective agent, it is also used for treating malaria and, recently, for Pneumocystic carinii pneumonia in AIDS patients. Dapsone is absorbed rapidly and nearly completely from the gastrointestinal tract. Dapsone is distributed throughout total body water and is present in all tissues. However, it tends to be retained in skin and muscle and especially in the liver and kidney: traces of the drug are present in these organs up to 3 weeks after therapy cessation.

Mechanism of action

The mechanism of action by which .... ethyl ether produce/s/ reversible loss of consciousness is still unclear. Anesthesia can be produced by a wide variety of chemical agents, ranging from inert rare gases to steriodal molecules. This apparent lack of specificity, together with the observation that general anesthesia can be reversed by high pressure, poses a unique pharmacological problem. Most theories concern interaction of anesthetics with either membrane lipids or hydrophobic regions of specificic membrane-bound proteins. One hypothesis is that the anesthetic changes the function of an ion channel protein by modifying the conformation of the protein. Some investigators suggest that the GABA receptor may be the ion channel protein that is affected by inhalation of anesthetic agents... The most appropriate concept for the mechanism of general anesthesia /may be/ a the heterogenous site of anesthetic action, including both lipid and protein membrane components linked with neuronal function. In chronically catheterized rats, diethyl ether increased plasma adrenaline and noradrenaline concentrations indicating that this drug stimulates both neurosympathetic and adrenomedullary functions. These effects appear to be centrally mediated, since ganglionic blockade or spinal transection completely counteracted the diethyl ether induced increases in plasma calcium levels. Hippocampal EEG signals derived from chronically implanted electrodes in the freely moving rat were recorded before and after administration of centrally acting drugs, and analyzed by power and coherence spectra. Diethyl ether induced a low frequency (3-6 c/s) theta power and coherence peak in the immobile rat, which was sensitive to atropine or scopolamine. The residue spectrum, defined as the EEG spectrum with the theta harmonics removed, was sensitive to centrally acting drugs. Diethyl ether suppressed fast waves of 50-100 c/s, and some conditions, enhanced 15-50 c/s waves. The plasma beta-endorphin responses to ether and handling stress were examined in animals of various ages. At each age studied there was a significant, stress-induced elevation of plasma beta-endorphin-like immunoreactivity levels were higher in animals 3,7, and 14 days of age than in adults. Cortical action potential activity is suppressed by ether anesthesia and is not affected when sensory fibers in the sciatic nerve are stimulated. Consequently, ether blocks sensory pathways to the cortex; the blockade occurs even before cortical activity is entirely suspended. In contrast, pentobarbital suppresses activity in the cortex without blocking the sensory path to it during sciatic nerve stimulation.

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.