BRAVIFO 100

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

• Adjuvant treatment of operable node-positive and node-negative breast cancer
• Treatment of hormone-refractory metastatic prostate cancer
• Initial chemotherapy for metastatic breast cancer
• Treatment of advanced ovarian cancer in combination with cisplatin
• Initial chemotherapy of non-small cell lung cancer with cisplatin
• Treatment of metastatic gastric adenocarcinoma
• Treatment of locally advanced squamous cell carcinoma of the head and neck

Dosage

Children: Refer to the BNF for Children for detailed paediatric dosing guidelines.

Adults: Refer to product literature or local protocols for specific dosing information.

Mechanism of action

Paclitaxel interferes with the normal function of microtubule growth by hyper-stabilizing their structure. It binds to the beta subunit of tubulin, locking the microtubule structure in place and preventing disassembly. This disrupts the dynamic instability necessary for essential cellular functions, including mitosis, and promotes apoptosis in cancer cells by inhibiting the function of the apoptosis regulator Bcl-2.

Pharmacodynamics

Paclitaxel acts as an antineoplastic agent by promoting the assembly of microtubules and preventing their depolymerization. This results in the formation of abnormal microtubule structures and inhibits cellular processes essential for cell division and function. It is indicated for first-line and subsequent therapy in advanced ovarian carcinoma and other malignancies, demonstrating a significant ability to induce programmed cell death in cancer cells.

Pharmacokinetics

Paclitaxel is administered intravenously and exhibits a multi-compartment pharmacokinetic profile. It is extensively metabolized by the liver, primarily through cytochrome P450 enzymes. Its half-life can vary widely due to extensive protein binding and distribution in tissues. The drug's clearance is affected by hepatic function, necessitating monitoring in patients with liver impairment.

Contra-indications

• Severe hypersensitivity to paclitaxel or any excipients
• Severe hepatic impairment
• Pregnancy

Adverse effects

• Abdominal pain
• Alopecia
• Anaemia
• Appetite decreased
• Arrhythmia
• Arthralgia
• Asthenia
• Constipation
• Diarrhoea
• Dyspnoea
• Fluid imbalance
• Haemorrhage
• Hypersensitivity
• Hypertension
• Hypotension
• Increased risk of infection
• Myalgia
• Nausea
• Neutropenia
• Pain
• Peripheral neuropathy
• Sepsis
• Skin reactions
• Stomatitis
• Taste altered
• Thrombocytopenia
• Vomiting

Interactions

• Dabrafenib (severe - decreases exposure)
• Bosentan (severe - decreases exposure)
• Mitotane (severe - decreases exposure)
• Rifampicin (severe - decreases exposure)
• Selpercatinib (severe - increases exposure)
• St John's Wort (severe - decreases exposure)
• Berotralstat (moderate - increases concentration)
• Eliglustat (moderate - increases exposure)
• Sotorasib (moderate - increases exposure)
• Tucatinib (moderate - increases exposure)

Precautions

• Monitor liver function in hepatic impairment
• Caution in patients with acute porphyrias
• Caution in patients with pre-existing heart conditions

Pregnancy

Paclitaxel is contraindicated in pregnancy due to potential harm to the fetus.

Breast-feeding

Breastfeeding is not recommended during treatment with paclitaxel due to potential adverse effects on the infant.

Storage

Store in a refrigerator (2°C to 8°C). Protect from light. Do not freeze.

Formulations

• Paclitaxel 80mg/8ml concentrate for solution for infusion

Indications

• Constipation
• Labor induction
• Topical treatment for skin conditions

Dosage

Children: Refer to the BNF for Children for appropriate pediatric dosing guidelines, as no specific doses are provided.

Adults: Refer to specific guidelines for adult dosing based on the formulation used and the condition being treated, as no standardized dose is provided.

Mechanism of action

Ricinoleic acid, the main active component of castor oil, acts as a stimulant laxative. It works by increasing the peristaltic movement of the intestines, which aids in the evacuation of stool. Additionally, it may inhibit the absorption of water in the intestines, resulting in softer stools. The oil is also believed to have anti-inflammatory properties, which can be beneficial in treating certain skin conditions.

Pharmacodynamics

The pharmacodynamic properties of castor oil include its ability to stimulate intestinal motility and increase the secretion of intestinal fluids. This leads to a faster transit time for stool through the bowel. In topical applications, castor oil exhibits emollient and moisturizing effects, promoting healing and soothing irritated skin. Its anti-inflammatory effects may also contribute to the reduction of swelling and pain in inflamed tissues.

Pharmacokinetics

Castor oil is absorbed in the gastrointestinal tract, where it is metabolized to ricinoleic acid. The onset of action for its laxative effect typically occurs within 2 to 6 hours after oral administration. The duration of action varies, but effects usually last for several hours. When applied topically, castor oil penetrates the skin and may provide localized effects without significant systemic absorption.

Adverse effects

• Abdominal cramps
• Diarrhea
• Nausea
• Vomiting
• Dehydration

Precautions

• Use with caution in patients with gastrointestinal disorders
• Not recommended for prolonged use
• Monitor for signs of dehydration

Pregnancy

Castor oil is generally not recommended during pregnancy due to potential uterine contractions and risk of premature labor.

Breast-feeding

Castor oil should be used with caution during breastfeeding as it may cause gastrointestinal discomfort in nursing infants.

Storage

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

Formulations

• Liquid
• Capsules

Indications

• Acidulant in food and beverages
• Preservative in pharmaceutical formulations
• pH adjuster in various chemical preparations

Dosage

Children: Refer to product-specific guidelines for appropriate dosing based on formulation and indication.

Adults: Refer to product-specific guidelines for appropriate dosing based on formulation and indication.

Mechanism of action

Citric acid acts by chelating metal ions, which can enhance the solubility of certain compounds and improve their bioavailability. It also contributes to the acidity of the environment, which can influence enzymatic activity and metabolic pathways, particularly in the degradation of citronellol.

Pharmacodynamics

Citric acid exhibits mild pharmacological effects primarily attributed to its role in metabolic processes. It aids in the regulation of pH levels, which can impact enzymatic reactions and biochemical pathways. The acid's chelating properties may help to reduce the toxicity of certain metal ions in biological systems.

Pharmacokinetics

Citric acid is rapidly absorbed after oral administration and is metabolized in the liver. It undergoes conversion to various metabolites in the citric acid cycle, contributing to energy production. The elimination primarily occurs through urine, with minimal accumulation in the body.

Pregnancy

Citric acid is generally regarded as safe during pregnancy when used in food amounts. However, consult a healthcare provider for advice on medicinal use.

Breast-feeding

Citric acid is considered safe during breastfeeding when consumed in food amounts. For medicinal use, consult a healthcare provider.

Storage

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

Indications

• Mild to moderate dehydration
• Severe dehydration
• Electrolyte imbalances
• Diarrhea and vomiting
• Heat-related illnesses

Dosage

Children: Pediatric doses for rehydration should be guided by the severity of dehydration and the specific recommendations found in the BNF for Children. Generally, oral rehydration solutions are recommended, with adjustments based on age and weight.

Adults: The dosage for adults typically involves oral rehydration solutions containing specific electrolyte concentrations. For severe cases, intravenous fluids may be administered under medical supervision, with the type and rate depending on clinical evaluation.

Mechanism of action

Rehydration therapies work primarily by restoring fluid balance and supplying necessary electrolytes, such as sodium and potassium, to the body. Oral rehydration solutions contain specific concentrations of salts and sugars that enhance water absorption in the intestines, promoting faster recovery from dehydration.

Pharmacodynamics

The pharmacodynamic effects of rehydration solutions are primarily to correct fluid and electrolyte imbalances. By providing an appropriate osmotic gradient, these solutions facilitate the absorption of water and electrolytes from the gastrointestinal tract into the bloodstream, thus replenishing lost fluids and restoring normal physiological function.

Pharmacokinetics

The pharmacokinetics of rehydration solutions depend on their composition. Oral rehydration solutions are rapidly absorbed in the intestines, with peak plasma concentrations of electrolytes generally achieved within 1 to 2 hours after administration. Intravenous fluids can have immediate effects, restoring intravascular volume and improving circulation almost instantly, depending on the type and rate of infusion.

Pregnancy

Dehydration can pose risks during pregnancy, including reduced amniotic fluid and impaired fetal development. Proper hydration is essential.

Breast-feeding

Maintaining hydration is crucial for breastfeeding mothers, as dehydration can affect milk production.

Storage

Dehydrated substances should be stored in a cool, dry place, away from moisture to prevent rehydration.

Indications

• Constipation
• Bowel preparation before colonoscopy or surgery

Dosage

Children: Refer to specific product guidelines for dosing instructions.

Adults: Refer to specific product guidelines for dosing instructions.

Mechanism of action

Polyoxyl works by retaining water in the stool, increasing its bulk and consistency. This osmotic effect stimulates bowel movements by softening the stool and promoting peristalsis. The water-retaining properties are attributed to its high molecular weight and hydrophilicity, which allow it to attract and hold water within the gastrointestinal tract.

Pharmacodynamics

The pharmacodynamic profile of polyoxyl includes its ability to enhance stool water content, thereby improving fecal passage through the intestines. This results in increased stool frequency and decreased transit time. Polyoxyl does not significantly affect electrolyte balance, making it a safe option for chronic constipation management.

Pharmacokinetics

Polyoxyl is not absorbed systemically; it remains in the gastrointestinal tract where it exerts its effects. The onset of action can vary but typically occurs within 24 to 72 hours after administration. The elimination of polyoxyl occurs through fecal excretion, with no significant metabolism or renal clearance involved.

Adverse effects

• Nausea
• Vomiting
• Diarrhea
• Abdominal cramps
• Allergic reactions

Precautions

• Use with caution in patients with gastrointestinal disorders.
• Monitor for allergic reactions in patients with a history of hypersensitivity.

Pregnancy

Polyoxyl is generally regarded as safe for use during pregnancy, but specific clinical guidance should be consulted.

Breast-feeding

Polyoxyl is considered safe during breastfeeding, though maternal factors should be assessed.

Storage

Store at room temperature, away from moisture and heat. Keep out of reach of children.

Formulations

• Oral solution
• Tablet
• Topical cream

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

Paclitaxel interferes with the normal function of microtubule growth. Whereas drugs like colchicine cause the depolymerization of microtubules in vivo, paclitaxel arrests their function by having the opposite effect; it hyper-stabilizes their structure. This destroys the cell's ability to use its cytoskeleton in a flexible manner. Specifically, paclitaxel binds to the β subunit of tubulin. Tubulin is the "building block" of mictotubules, and the binding of paclitaxel locks these building blocks in place. The resulting microtubule/paclitaxel complex does not have the ability to disassemble. This adversely affects cell function because the shortening and lengthening of microtubules (termed dynamic instability) is necessary for their function as a transportation highway for the cell. Chromosomes, for example, rely upon this property of microtubules during mitosis. Further research has indicated that paclitaxel induces programmed cell death (apoptosis) in cancer cells by binding to an apoptosis stopping protein called Bcl-2 (B-cell leukemia 2) and thus arresting its function. Evidence suggests that paclitaxel also may induce cell death by triggering apoptosis. In addition, paclitaxel and docetaxel enhance the effects of ionizing radiation, possibly by blocking cells in the G2 phase, the phase of the cell cycle in which cells are most radiosensitive. Paclitaxel is an antimicrotubule antineoplastic agent. Unlike some other common antimicrotubule agents (e.g., vinca alkaloids, colchicine, podophyllotoxin), which inhibit microtubule assembly, paclitaxel and docetaxel (a semisynthetic taxoid) promote microtubule assembly. Microtubules are organelles that exist in a state of dynamic equilibrium with their components, tubulin dimers. They are an essential part of the mitotic spindle and also are involved in maintenance of cell shape and motility, and transport between organelles within the cell. By binding in a reversible, concentration-dependent manner to the beta-subunit of tubulin at the N-terminal domain, paclitaxel enhances the polymerization of tubulin, the protein subunit of the spindle microtubules, even in the absence of factors that are normally required for microtubule assembly (e.g., guanosine triphosphate [GTP]), and induces the formation of stable, nonfunctional microtubules. Paclitaxel promotes microtubule stability even under conditions that typically cause depolymerization in vitro (e.g., cold temperature, the addition of calcium, the presence of antimitotic drugs). While the precise mechanism of action of the drug is not understood fully, paclitaxel disrupts the dynamic equilibrium within the microtubule system and blocks cells in the late G2 phase and M phase of the cell cycle, inhibiting cell replication. ... Taxol induces tubulin polymerization and forms extremely stable and nonfunctional microtubules. Taxol has demonstrated broad activity in preclinical screening studies, and antineoplastic activity has been observed in several classically refractory tumors. These tumors include cisplatin resistant ovarian carcinoma in phase II trials and malignant melanoma and non-small cell lung carcinoma in phase I studies.

Pharmacodynamics

Paclitaxel is a taxoid antineoplastic agent indicated as first-line and subsequent therapy for the treatment of advanced carcinoma of the ovary, and other various cancers including breast cancer. Paclitaxel is a novel antimicrotubule agent that promotes the assembly of microtubules from tubulin dimers and stabilizes microtubules by preventing depolymerization. This stability results in the inhibition of the normal dynamic reorganization of the microtubule network that is essential for vital interphase and mitotic cellular functions. In addition, paclitaxel induces abnormal arrays or "bundles" of microtubules throughout the cell cycle and multiple asters of microtubules during mitosis.