INJECTA-FEM 150

Indications

• Contraception
• Secondary amenorrhea
• Dysfunctional uterine bleeding
• Menstrual cycle irregularities
• Management of hot flushes in men undergoing androgen suppression therapy

Dosage

Children: For contraception by deep intramuscular injection: 150 mg every 12 weeks, first dose to be administered within the first 5 days of the menstrual cycle or within the first

Adults: For contraception by deep intramuscular injection: 150 mg every 12 weeks, first dose to be administered within the first 5 days of the menstrual cycle or within the first 5 days postpartum (delay until 6 weeks postpartum if breastfeeding). For oral use: 20 mg once daily initially for 10 weeks, evaluate effect at the end of the treatment period.

Mechanism of action

Medroxyprogesterone acetate inhibits the production of gonadotropin, preventing follicular maturation and ovulation. This action also results in the thinning of the endometrium. Additionally, MPA reduces nuclear estrogen receptors and DNA synthesis in endometrial epithelial cells and can induce p53-dependent apoptosis in certain cancer cell lines while inhibiting GABA-A receptors.

Pharmacodynamics

MPA primarily acts by inhibiting gonadotropin production and reducing estrogen receptor activity in the endometrium. The drug has a wide therapeutic window, with effective doses ranging from 5 mg orally daily to 1000 mg weekly as a depo injection. However, long-term use is associated with reduced bone density, particularly in adolescents, potentially increasing the risk of osteoporosis and fractures.

Pharmacokinetics

The half-life of oral MPA ranges from 40 to 60 hours, whereas other formulations may exhibit considerably longer half-lives. This allows for extended duration of action, making MPA suitable for long-term use. MPA's pharmacokinetic profile necessitates careful monitoring, especially in long-term treatment scenarios.

Contra-indications

• Current breast cancer (unless progestogens are being used in the management of this condition)
• History of thromboembolism
• Undiagnosed vaginal bleeding
• Acute porphyrias

Adverse effects

• Menstrual cycle irregularities
• Nausea
• Weight changes
• Ovarian cyst pain
• Skin reactions
• Hot flushes
• Mild to moderate endometriosis
• Risk of breast cancer
• Decreased glucose tolerance
• Reduced bone density

Interactions

• Potential interactions with other hormonal contraceptives
• Caution advised with estrogen HRT in patients with a history of stroke
• Caution advised with estrogen HRT in patients with a history of venous thromboembolism

Precautions

• Careful monitoring in patients with systemic lupus erythematosus with positive or unknown antiphospholipid antibodies
• Seek specialist advice for patients with a history of ischemic heart disease
• Multiple risk factors for cardiovascular disease

Pregnancy

Not known to be harmful, remove implant if pregnancy occurs.

Breast-feeding

Progestogen-only contraceptives do not affect lactation.

Storage

Store at room temperature, away from light and moisture.

Formulations

• Deep intramuscular injection: 150 mg every 12 weeks
• Subcutaneous injection: 104 mg every 13 weeks
• Oral tablets: 20 mg once daily initially for 10 weeks

Dosage

Children: Refer to specific drug guidelines for paediatric dosing, as this varies widely.

Adults: Refer to specific drug guidelines for adult dosing, as this varies widely.

Mechanism of action

The mechanism of action will vary depending on the specific drug referred to as 'adjust'. Generally, medications designed to 'adjust' physiological parameters may work by modulating neurotransmitter systems, altering hormonal levels, or affecting enzyme activity to achieve therapeutic effects.

Pharmacodynamics

Pharmacodynamics will depend on the specific drug, but typically involves the interaction of the drug with its receptor sites, leading to a biological response. The efficacy and potency of the drug are influenced by its affinity for the target receptors and the subsequent signaling pathways activated.

Pharmacokinetics

Pharmacokinetics, including absorption, distribution, metabolism, and excretion, will vary by drug. Common factors influencing pharmacokinetics include bioavailability, half-life, and the presence of food or other drugs that may affect the drug's metabolism and elimination from the body.

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

• Adjustment of pH in pharmaceutical formulations
• Facilitation of drug absorption
• Used in sterile preparations

Dosage

Children: Refer to specific product guidelines for dosing information, as hydrochloric acid is typically used in a controlled setting based on formulation requirements.

Adults: Refer to specific product guidelines for dosing information, as hydrochloric acid is typically used in a controlled setting based on formulation requirements.

Mechanism of action

Hydrochloric acid dissociates in aqueous solution to release hydrogen ions (H+), leading to a decrease in pH. This acidic environment promotes the activation of pepsinogen to pepsin, an enzyme essential for protein digestion. Additionally, the acidity aids in the absorption of certain minerals and drugs that require an acidic environment for optimal bioavailability.

Pharmacodynamics

The primary pharmacodynamic action of hydrochloric acid is the maintenance of gastric acidity, which is essential for normal digestive processes. The acidic environment helps in denaturing proteins, activating digestive enzymes, and providing a barrier against pathogenic microorganisms. Its effects can influence the absorption and efficacy of various medications, particularly those that are pH-dependent.

Pharmacokinetics

Hydrochloric acid does not undergo significant systemic absorption when used in its normal contexts, as it acts locally within the gastrointestinal tract. The amount of hydrochloric acid produced by the stomach varies with food intake and physiological needs. It is secreted by parietal cells in the gastric mucosa, and its secretion is regulated by neural, hormonal, and local factors. The half-life of hydrochloric acid is not applicable as it is continuously produced and neutralized within the gastrointestinal tract.

Contra-indications

• Hypersensitivity to hydrochloric acid or any of its components
• Severe renal impairment
• Active gastrointestinal bleeding

Adverse effects

• Abdominal pain
• Diarrhea
• Nausea
• Vomiting
• Esophageal irritation
• Gastric mucosal irritation
• Electrolyte imbalances

Interactions

• May interact with alkaline substances, potentially neutralizing hydrochloric acid
• Caution with antacids as they may affect the efficacy of hydrochloric acid

Precautions

• Use with caution in patients with a history of gastritis or gastric ulcers
• Monitor electrolytes in prolonged use
• Use cautiously in patients with respiratory conditions due to potential aspiration risks

Pregnancy

Hydrochloric acid is classified as a category C drug. Use during pregnancy only if clearly needed and the potential benefits justify the risks to the fetus.

Breast-feeding

There is limited data on the excretion of hydrochloric acid in human milk. Use with caution during breastfeeding.

Storage

Store in a cool, dry place away from direct sunlight and heat. Ensure the container is tightly closed.

Formulations

• Oral solutions
• Injectable forms
• Tablets

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

• Contraception
• Management of abnormal uterine bleeding
• Endometriosis
• Dysmenorrhea
• Hormonal replacement therapy

Dosage

Children: For paediatric dosing, refer to the BNF for Children

Adults: For contraception, the usual dosage is 150 mg administered intramuscularly every 3 months. For other indications, refer to the BNF for specific dosing guidance.

Mechanism of action

Medroxyprogesterone acts as a progestin, transforming the proliferative endometrium into a secretory one in women with adequate endogenous estrogen. It inhibits the secretion of pituitary gonadotropins, leading to prevention of follicular maturation and ovulation, and results in endometrial thinning, thereby exerting contraceptive effects. It is suggested that the drug acts at the hypothalamus, as it does not suppress the release of luteinizing hormone and follicle-stimulating hormone following administration of gonadotropin-releasing hormone.

Pharmacodynamics

Medroxyprogesterone exhibits progestational effects, inducing changes in the endometrial lining, thereby preparing it for potential implantation of an embryo. It also has mild androgenic properties and some anabolic effects, though it lacks significant estrogenic activity in humans. The drug also influences the hypothalamic-pituitary-gonadal axis by inhibiting gonadotropin release, affecting ovarian function and menstrual cycle regulation.

Pharmacokinetics

Medroxyprogesterone is absorbed following intramuscular or subcutaneous administration, with peak plasma concentrations occurring within a few days. The drug undergoes hepatic metabolism and is primarily excreted in urine. The pharmacokinetics may vary based on the route of administration, with intramuscular injections providing a longer duration of action compared to oral dosages.

Interactions

• sugammadex+medroxyprogesterone: Unknown (decreases exposure)

Pregnancy

Medroxyprogesterone is used during pregnancy for specific indications, such as to prevent premature labor or for other clinical reasons as determined by a healthcare provider. It is classified under Category X for contraceptive use, indicating that it should not be used during pregnancy due to potential risks.

Breast-feeding

Medroxyprogesterone is excreted in breast milk. Caution is advised when administering to nursing mothers, as the effects on the infant are not well established.

Storage

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

Indications

• Preservative in cosmetics
• Preservative in pharmaceutical formulations
• Antimicrobial agent in food products

Dosage

Children: Refer to specific product guidelines for dosing information, as methylparaben is primarily used as a preservative rather than a therapeutic agent.

Adults: Refer to specific product guidelines for dosing information, as methylparaben is primarily used as a preservative rather than a therapeutic agent.

Mechanism of action

The mechanism of cytotoxic action of parabens, including methylparaben, may be linked to mitochondrial failure. This is dependent on the induction of membrane permeability transition, which is accompanied by mitochondrial depolarization and depletion of cellular ATP through the uncoupling of oxidative phosphorylation.

Pharmacodynamics

Methylparaben exhibits antimicrobial activity against a range of bacteria and fungi. Its effectiveness as a preservative is attributed to its ability to disrupt microbial cell membranes and inhibit essential metabolic processes, ensuring the stability and safety of various formulations.

Pharmacokinetics

Methylparaben is absorbed following topical application and is metabolized by hydrolysis to p-hydroxybenzoic acid, which is then excreted in urine. The pharmacokinetics may vary based on the route of administration and formulation. Studies suggest a relatively low systemic absorption when used in topical applications.

Pregnancy

There is limited data on the use of methylparaben in pregnancy. It should be used only if clearly needed and the benefits outweigh any potential risks.

Breast-feeding

Methylparaben is excreted in breast milk. Caution is advised when using products containing methylparaben while breastfeeding.

Storage

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

Indications

• Cryotherapy for the destruction of abnormal tissue
• Treatment of warts, moles, and other skin lesions
• Nitrogen narcosis in diving

Dosage

Children: Refer to the BNF for Children for appropriate dosing recommendations in paediatric patients.

Adults: For cryotherapy, the dosage and duration depend on the specific condition being treated and should be determined by the healthcare provider. Refer to specific guidelines for each condition.

Mechanism of action

In cryotherapy, the mechanism of action involves three stages: heat transfer, cell injury, and inflammation. The boiling point of liquid nitrogen is -196°C, which initiates heat transfer, leading to cell injury during the thawing process. The inflammation stage follows, characterized by edema and erythema, resulting from cellular death and contributing to local cell destruction. Additionally, nitrogen can cause direct toxic effects on brain functions, leading to nitrogen narcosis, which impairs cognitive abilities and motor functions due to its impact on nerve conduction.

Pharmacodynamics

Nitrogen's pharmacodynamics relate to its behavior in cryotherapy and asphyxiation. In cryotherapy, it induces tissue destruction through rapid cooling, leading to apoptosis of abnormal cells. In high-pressure environments, nitrogen narcosis affects the central nervous system, producing symptoms similar to alcohol intoxication, ultimately decreasing reasoning, decision-making abilities, and manual dexterity.

Pharmacokinetics

Nitrogen does not undergo metabolism in the traditional sense, as it is an inert gas at physiological conditions. Its pharmacokinetics involve physical principles of gas exchange and partial pressures. In the case of nitrogen narcosis, the effects are influenced by the partial pressure of nitrogen in the bloodstream, which increases with depth during diving. Nitrogen is primarily eliminated from the body through respiration.

Adverse effects

• Narcotic effect at high pressures
• Stupor or euphoria
• Decreased motor function and manual dexterity
• Asphyxiation due to oxygen displacement

Precautions

• Careful monitoring in environments with high nitrogen pressures
• Avoidance of rapid ascents in diving to prevent nitrogen narcosis
• Use in controlled settings to prevent asphyxiation risks

Pregnancy

Nitrogen is generally considered safe in terms of direct effects during pregnancy; however, the safety of exposure in high-pressure environments should be assessed.

Breast-feeding

Nitrogen is not known to affect breastfeeding; however, caution is recommended in environments where nitrogen levels may displace oxygen.

Storage

Store in a cool, dry place away from heat sources; liquid nitrogen should be handled with care due to extreme cold.

Formulations

• Liquid nitrogen
• Nitrogen gas (compressed)

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

• Emulsifying agent in drug formulations
• Stabilizer for parenteral preparations
• Solubilizer for hydrophobic drug compounds
• Ingredient in topical formulations

Dosage

Children: Refer to specific product guidelines, as dosing varies based on formulation and intended use.

Adults: Refer to specific product guidelines, as dosing varies based on formulation and intended use.

Mechanism of action

Polysorbate functions primarily as an emulsifying agent. It reduces the surface tension between immiscible liquids, allowing them to mix more easily. This property is particularly useful in stabilizing emulsions and suspensions, facilitating the delivery of active pharmaceutical ingredients in various formulations.

Pharmacodynamics

Polysorbate does not exert pharmacological effects in the traditional sense, as it does not bind to specific receptors to elicit a physiological response. Instead, it plays a crucial role in modifying the physical properties of drug formulations, thereby enhancing drug delivery and absorption. Its ability to solubilize drugs enhances their bioavailability, particularly for poorly soluble compounds.

Pharmacokinetics

Polysorbate is generally considered to be non-toxic and is not absorbed to a significant extent when administered orally. It is metabolized by the liver and excreted primarily through the gastrointestinal tract. The pharmacokinetic profile may vary depending on the route of administration and the specific formulation in which it is used.

Adverse effects

• Allergic reactions
• Skin irritation
• Gastrointestinal disturbances

Precautions

• Use cautiously in patients with known allergies to polysorbates or related compounds
• Monitor for allergic reactions in susceptible individuals

Pregnancy

Polysorbate is generally considered safe for use during pregnancy, but consult with a healthcare provider for specific cases.

Breast-feeding

Polysorbate is considered safe during breastfeeding, but consult with a healthcare provider for individual advice.

Storage

Store at room temperature, away from direct sunlight and moisture.

Formulations

• Polysorbate 20
• Polysorbate 80

Indications

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

Dosage

Children: Refer to the specific product guidelines, as dosages may vary based on formulation and intended use.

Adults: Refer to the specific product guidelines, as dosages may vary based on formulation and intended use.

Mechanism of action

The mechanism of propyl paraben may be linked to mitochondrial failure dependent on induction of membrane permeability transition accompanied by the mitochondrial depolarization and depletion of cellular ATP through uncoupling of oxidative phosphorylation.

Pharmacodynamics

Propylparaben acts primarily as an antimicrobial agent, inhibiting the growth of bacteria and fungi. Its effectiveness is attributed to its ability to disrupt microbial cell membranes and interfere with metabolic processes, particularly in energy production within the mitochondria.

Pharmacokinetics

Propylparaben is absorbed through the skin and gastrointestinal tract. It undergoes rapid metabolism, primarily in the liver, where it is conjugated to glucuronic acid and excreted in urine. Its half-life is relatively short, resulting in quick clearance from the body. The compound exhibits low systemic toxicity at typical exposure levels.

Pregnancy

Propylparaben is generally considered safe for use in pregnant women, but caution is advised due to limited human data.

Breast-feeding

Propylparaben is considered safe during breastfeeding, but it is advisable to consult a healthcare provider.

Storage

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

Formulations

• Topical creams
• Lotions
• Cosmetic products

Mechanism of action

Medroxyprogesterone acetate (MPA) inhibits the production of gonadotropin, preventing follicular maturation and ovulation, which is responsible for it’s ability to prevent pregnancy. This action also thins the endometrium. MPA reduces nuclear estrogen receptors and DNA synthesis in epithelial cells of the endometrium. MPA can also induce p53 dependant apoptosis in certain cancer cell lines, and inhibit GABA-A receptors.

Pharmacodynamics

Medroxyprogesterone acetate (MPA) inhibits gonadotropin production, reduces nuclear estrogen receptors and DNA synthesis in epithelial cells of the endometrium, and induces p53 dependant apoptosis in cancer cell lines. MPA oral tablets have a half life of 40-60 hours and other formulations can have half lives that are considerably longer, so the duration of action is long. The therapeutic window is wide as patients may take doses ranging from 5mg orally daily to 1000mg as a depo injection weekly. Long term use of MPA is associated with a reduction in bone density and patients who taking MPA during adolescence may have lower peak bone mass than untreated patients, which can also increase the risk of osteoporosis and fractures in the future.

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

Medroxyprogesterone shares the pharmacologic actions of the progestins. In women with adequate endogenous estrogen, medroxyprogesterone transforms a proliferative endometrium into a secretory one. Medroxyprogesterone has been shown to have slight androgenic activity in animals. Anabolic effects have also been reported, but the drug apparently lacks appreciable estrogenic activity in humans. In animals, the drug exhibits pronounced adrenocorticoid activity, but a clinically important effect has not been observed in humans. Medroxyprogesterone inhibits the secretion of pituitary gonadotropins following usual IM or subcutaneous dosages (eg, 150 or 104 mg every 3 months), thus preventing follicular maturation and ovulation and resulting in endometrial thinning; these effects result in contraceptive activity. Available evidence indicates that these effects do not occur following oral administration of usual dosages (ie, 5-10 mg daily as single daily doses) of the drug. High doses of medroxyprogesterone inhibit pituitary secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and will prevent cyclic gonadotropin surges that occur during the normal menstrual cycle. It has been suggested that the drug acts at the hypothalamus since it does not suppress the release of LH and FSH following administration of gonadotropin-releasing hormone and since basal concentrations of LH and FSH remain within the low normal range when the drug is used as a contraceptive. Although the mechanism of action has not been determined, medroxyprogesterone has antineoplastic activity against some cancers (eg, endometrial carcinoma, renal carcinoma). Progestins elicit, to varying degrees, all the pharmacologic responses usually produced by progesterone: induction of secretory changes in the endometrium, increase in basal body temperature (thermogenic action), production of histologic changes in vaginal epithelium, relaxation of uterine smooth muscle, stimulation of mammary alveolar tissue growth, pituitary inhibition, and production of withdrawal bleeding in the presence of estrogen. /Progestins/ Following binding to cytoplasmic receptor protein, steroid is transported to nucleus, and complex is bound there in reactions analogous to those described... for estrogens. However, there is no apparent need for receptor alteration, as with estrogen receptor. /Progesterone/ Although medroxyprogesterone acetate (MPA) is used as an injectable contraceptive, in hormone replacement therapy (HRT) and in treatment of certain cancers, the steroid receptors and their target genes involved in the actions of MPA are not well understood. /Investigators/ show that MPA, like dexamethasone (dex), significantly represses tumour necrosis factor (TNF)-stimulated interleukin-6 (IL-6) protein production in mouse fibroblast (L929sA) cells. In addition, MPA repressed IL-6 and IL-8 promoter-reporter constructs at the transcriptional level, via interference with nuclear factor kappaB (NFkappaB) and activator protein-1 (AP-1). Furthermore, like dex, MPA does not affect NFkappaB DNA-binding activity. /The authors/ also observed significant transactivation by MPA of a glucocorticoid response element (GRE)-driven promoter-reporter construct in both L929sA and COS-1 cells. The MPA-induced nuclear translocation of the glucocorticoid receptor (GR), as well as the antagonistic effects of RU486, strongly suggest that the actions of MPA in these cells are mediated at least in part via the GR. /Investigators/ assessed the transcriptional effects of MPA as compared with those of progesterone and dihydrotestosterone (DHT) in human breast cancer cells. A new progesterone receptor-negative, androgen receptor-positive human breast cancer cell line, designated Y-AR, was engineered and characterized. Transcription assays using a synthetic promoter/reporter construct, as well as endogenous gene expression profiling comparing progesterone, MPA and DHT, were performed in cells either lacki

Mechanism of action

...The mechanism of cytotoxic action of parabens may be linked to mitochondrial failure dependent on induction of membrane permeability transition accompanied by the mitochondrial depolarization and depletion of cellular ATP through uncoupling of oxidative phosphorylation.

Mechanism of action

In cryotherapy, mechanism of action could be classified into three stages: 1. heat transfer, 2. cell injury and 3. inflammation. Boiling point of liquid nitrogen is -196°C, which is the responsible for creating the initial stage which is heat transfer. The second stage is cell injury which is induced during thawing conditions of the cells. The last step in the cryotherapy is the inflammation stage which is characterized by edema and erythema. Inflammation occurs as a result of cellular death and it helps in local cell destruction. ... Nitrogen also has a direct toxic action of its own, affecting brain functions and inducing a stupor or euphoria. Nitrogen narcosis ("rapture of the deep" or "the martini effect") results from a direct toxic effect of high nitrogen pressure on nerve conduction and produces effects similar to alcohol intoxication. Complex reasoning, decision-making ability, motor function, and manual dexerity decrease. Individuals vary in this response widely, but it typically can be noticed among divers at depths exceeding 100 ft (30 m). For example, certain individuals experience no effect at depths of < or = 130 ft, whereas others feel some effect at around 80 ft. Nonetheless, the narcotic effect increases with increasing depth so that each additional 50 ft incrementally produces the effect of "another martini". A simple asphyxiant, nitrogen's main toxicty arises from its ability to displace O2 and generate an atmosphere that does not support the chemical reactions needed for maintenance of life. The displacement of O2 can be complete or incomplete, leading to varying degrees of hypoxia. Nitrogen is an inert substance and does not exert a direct toxicological effect. Nitrogen acts by the physiological effect of simple asphyxia on the target species within a Controlled Atmosphere Treatment (CAT) bubble. The biocide action of nitrogen is due to its displacement of oxygen from an atmospheric oxygen level of 20.8% to levels < 0.2% v/v in the CAT bubble. The level of oxygen is the critical factor. Victims exposed to atmospheres deficient in oxygen, i.e. < 19%, will begin to display signs and symptoms of oxygen-deficient exposure of air due to an increase in nitrogen.

Mechanism of action

...The mechanism of propyl paraben may be linked to mitochondrial failure dependent on induction of membrane permeability transition accompanied by the mitochondrial depolarization and depletion of cellular ATP through uncoupling of oxidative phosphorylation...