Desogest Film coated tablets

Indications

• Contraception
• Uterine fibroids

Dosage

Children: Refer to the BNF for Children for specific dosing information.

Adults: 75 micrograms daily, taken continuously at the same time each day starting on day 1 of the menstrual cycle. If the dose is delayed by more than 12 hours, the missed dose should not be taken, and the next dose should be taken at the normal time.

Mechanism of action

Desogestrel enters cells passively and selectively binds to progesterone receptors, producing an effect akin to a transcription factor, which modifies mRNA synthesis. Its active metabolite, etonogestrel, exhibits high progestational activity with minimal androgenicity. The primary contraceptive mechanism is the inhibition of ovulation, supplemented by changes in cervical mucus and endometrial alterations that reduce implantation likelihood.

Pharmacodynamics

Desogestrel affects reproductive hormones by modifying luteinizing hormone and follicle-stimulating hormone levels, leading to delayed menstruation and increased cervical mucus viscosity. It also influences metabolic processes, including insulin secretion and fat deposition. The primary therapeutic effect results from ovulation inhibition, confirmed by clinical trials showing a high efficacy rate compared to other progestogen-only contraceptives.

Pharmacokinetics

Following oral administration, desogestrel is rapidly absorbed and metabolized into etonogestrel, which is the active form. It has a half-life that allows for once-daily dosing. The pharmacokinetics might be altered by concomitant medications, particularly those affecting liver enzymes, leading to potential changes in efficacy.

Contra-indications

• Acute porphyrias
• Current breast cancer
• Hypersensitivity or allergy to peanuts or soya

Adverse effects

• Dizziness
• Breast tenderness
• Nausea
• Abdominal pain
• Changes in menstrual bleeding
• Headache
• Acne
• Weight gain

Interactions

• Antiepileptics (carbamazepine, eslicarbazepine, fosphenytoin, oxcarbazepine, perampanel, phenobarbital, phenytoin, primidone, rufinamide, topiramate) - may decrease efficacy
• Lamotrigine - may increase exposure
• Berotralstat - may decrease efficacy
• Lumacaftor - may decrease efficacy
• Modafinil - may decrease efficacy
• Rifamycins - may decrease efficacy
• St John's wort - may decrease efficacy
• Sugammadex - may decrease exposure

Precautions

• Caution in patients with cardiac dysfunction
• Monitor closely in patients with diabetes
• Consider risks in women with a history of venous thromboembolism

Pregnancy

Not known to be harmful.

Breast-feeding

Progestogen-only contraceptives do not affect lactation.

Storage

Store in a cool, dry place below 30°C, protect from light.

Formulations

• Desogestrel 75 micrograms tablet

Mechanism of action

Acetone acts as a solvent and is utilized in various biochemical pathways. It participates in the biosynthesis of isopropanol and is involved in the degradation pathways where it converts into other metabolites such as methylglyoxal and acetoacetate. It also plays a role in pyruvate fermentation and is integral to the fermentation processes in Clostridium acetobutylicum.

Pharmacodynamics

Acetone has a low molecular weight and is highly volatile, which allows it to penetrate biological membranes easily. Its pharmacological effects are primarily due to its role as a solvent and its ability to influence metabolic processes. Acetone can affect lipid metabolism and may impact energy homeostasis by influencing the balance between fat and carbohydrate utilization.

Pharmacokinetics

Acetone is rapidly absorbed through inhalation and dermal exposure. It is distributed throughout the body and can cross the blood-brain barrier. Metabolism occurs primarily in the liver where acetone is converted into acetoacetate and other metabolites. The elimination of acetone occurs mainly through renal excretion, with a half-life varying based on the route of exposure and individual metabolism.

Pregnancy

Acetone is classified as a pregnancy category C drug. Its effects during pregnancy are not well-studied, and caution should be exercised.

Breast-feeding

There is limited information on the excretion of acetone in breast milk. Caution is advised when using acetone during breastfeeding.

Storage

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

Indications

• Vitamin E deficiency
• Antioxidant supplementation
• Support for skin health
• Support for eye health
• Support for immune function

Dosage

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

Adults: Refer to the BNF for specific dosing information based on indication.

Mechanism of action

Allracalphatocopherol acts as a lipid-soluble antioxidant, scavenging free radicals and preventing the oxidation of polyunsaturated fatty acids in cell membranes. This action helps to maintain the structural integrity of cells and protects them from oxidative stress.

Pharmacodynamics

The pharmacodynamic effects of allracalphatocopherol include its ability to inhibit lipid peroxidation, enhance immune response, and modulate gene expression related to inflammation and cell signaling. It plays a vital role in preventing cellular damage and may have implications in chronic disease prevention.

Pharmacokinetics

Allracalphatocopherol is well absorbed from the gastrointestinal tract when taken orally, with peak plasma concentrations occurring within 4 to 8 hours. It is distributed throughout body tissues, with a high affinity for adipose tissue. The elimination half-life ranges from 13 to 48 hours, and it is primarily excreted in bile and urine as metabolites.

Pregnancy

There are no adequate and well-controlled studies in pregnant women. Allracalphatocopherol should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is not known whether allracalphatocopherol is excreted in human milk. Caution should be exercised when administered to a nursing woman.

Storage

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

Indications

• Hypovolemic shock
• Severe burns
• Postoperative fluid replacement
• Sepsis
• Trauma management

Dosage

Children: Refer to established guidelines for specific dosing, as it varies based on the type of colloidal solution used and the clinical condition being treated.

Adults: Refer to established guidelines for specific dosing, as it varies based on the type of colloidal solution used and the clinical condition being treated.

Mechanism of action

Colloidal solutions work by maintaining oncotic pressure in the blood, thus helping to retain fluid within the vascular system. This is primarily due to the large molecular weight of the colloidal particles, which cannot easily pass through capillary walls. The presence of colloids in the blood helps to draw water into the circulation, increasing blood volume and improving tissue perfusion.

Pharmacodynamics

The pharmacodynamics of colloidal solutions are centered on their ability to exert osmotic pressure, which helps maintain blood volume and pressure. This effect is particularly important in conditions such as hypovolemia and shock, where fluid replacement is necessary to restore hemodynamic stability. The efficacy of colloidal solutions can vary depending on the type of colloid used, as well as the underlying clinical condition being treated.

Pharmacokinetics

Colloidal solutions are typically administered intravenously and their pharmacokinetics can vary based on the specific formulation. Generally, colloids are distributed throughout the vascular compartment and have a longer duration of action compared to crystalloids, as they remain in circulation longer. The elimination of colloids is primarily through the reticuloendothelial system, where they are metabolized or eliminated by the liver and spleen. Factors such as particle size and composition can influence their distribution and clearance.

Adverse effects

• Allergic reactions
• Injection site reactions
• Nausea
• Vomiting
• Headache
• Fever

Precautions

• Use with caution in patients with known allergies to any component of the formulation
• Monitor for signs of hypersensitivity during administration
• Consider volume overload in patients with cardiac or renal impairment

Pregnancy

The safety of colloidal solutions during pregnancy has not been established. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is not known whether colloidal solutions are excreted in human milk. Caution should be exercised when administering to breastfeeding mothers.

Storage

Store at room temperature, protect from light, and do not freeze. Keep out of reach of children.

Formulations

• Colloidal silver
• Colloidal gold
• Colloidal iron
• Other metal colloids

Indications

• Lactose intolerance
• As a filler or excipient in pharmaceutical formulations

Dosage

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

Adults: Refer to the BNF for specific dosing information based on clinical context.

Mechanism of action

Lactose is metabolized in the intestine by the enzyme lactase into its constituent monosaccharides, glucose and galactose. In individuals with lactase deficiency, unabsorbed lactose passes into the colon, where it is fermented by bacteria, leading to gas production and osmotic effects that contribute to diarrhea.

Pharmacodynamics

The pharmacodynamics of lactose are primarily related to its effects on gastrointestinal function. In healthy individuals, lactose is effectively broken down into glucose and galactose, which are absorbed and utilized for energy. In individuals with lactose intolerance, the unabsorbed lactose can cause osmotic diarrhea and colonic fermentation, leading to discomfort and symptoms associated with lactose intolerance.

Pharmacokinetics

Lactose is not absorbed in the gastrointestinal tract until it is hydrolyzed into glucose and galactose by lactase. The absorption of glucose and galactose occurs in the small intestine. The half-life is not applicable as lactose is not typically administered as a medication but is rather ingested as a natural component of food. Its metabolism primarily occurs in the intestine.

Adverse effects

• Bloating
• Diarrhea
• Abdominal pain
• Flatulence

Precautions

• Use with caution in patients with lactose intolerance.
• Consider potential for gastrointestinal upset in sensitive individuals.

Pregnancy

Lactose is generally considered safe for use during pregnancy. However, consult a healthcare professional for individual advice.

Breast-feeding

Lactose is safe to use while breastfeeding, as it is a natural sugar present in breast milk.

Storage

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

Formulations

• Powder
• Granules
• Tablets
• Syrup

Indications

• Nutritional support
• Source of carbohydrates
• Dietary fiber source
• Animal feed

Dosage

Children: As with adults, there are no specific dosing recommendations for maize for children. It can be introduced into the diet in age-appropriate forms and quantities, keeping in mind the overall dietary balance.

Adults: There are no specific dosing recommendations for maize as it is typically consumed as part of a balanced diet. It can be included in daily meals in various forms such as whole kernels, flour, or as part of dishes.

Mechanism of action

Maize primarily acts as a source of energy due to its high carbohydrate content. The complex carbohydrates in maize are broken down into glucose, which is then utilized by the body for energy production. It also contributes to dietary fiber intake, which can aid in digestive health and regulation of blood sugar levels.

Pharmacodynamics

The consumption of maize influences blood glucose and insulin levels due to its carbohydrate content. It has a relatively low glycemic index when consumed in whole form, which can help in managing blood sugar levels. The dietary fiber present in maize can also promote satiety and aid in weight management.

Pharmacokinetics

The digestion of maize begins in the mouth with salivary amylase breaking down starches into simpler sugars. In the stomach and small intestine, enzymes further break down these carbohydrates. The resultant glucose is absorbed into the bloodstream, where it is transported to cells for energy production. The absorption rate can vary based on the form of maize consumed (e.g., whole kernels versus processed forms).

Pregnancy

Maize is generally considered safe for consumption during pregnancy as it is a staple food and provides essential nutrients.

Breast-feeding

Maize is safe to consume while breastfeeding and can provide important nutrients to both the mother and the infant.

Storage

Store in a cool, dry place, away from moisture and pests. Properly sealed containers can help prolong shelf life.

Formulations

• Whole maize grains
• Maize flour (cornmeal)
• Maize starch
• Maize oil

Indications

• Topical antiseptic for skin disinfection
• Surgical scrubs and hand sanitizers
• Wound care management
• Pharmaceutical excipient in solid and liquid formulations

Dosage

Children: Refer to specific product guidelines for pediatric dosing recommendations, as doses can vary based on formulation and intended use.

Adults: Refer to specific product guidelines for dosing recommendations, as doses can vary based on the formulation and intended use.

Mechanism of action

Povidone acts by forming a complex with iodine when used as an antiseptic, which releases iodine slowly to exert its antimicrobial effect. The iodine disrupts microbial cell walls and interferes with protein synthesis, leading to cell death. Additionally, as a polymer, povidone can enhance drug solubility and stability by forming a hydrophilic matrix.

Pharmacodynamics

Povidone has a broad spectrum of antimicrobial activity against bacteria, viruses, and fungi. Its antiseptic properties are primarily due to the release of iodine, which is effective in reducing microbial load and preventing infection. The polymer's ability to bind to various substances allows it to be utilized in formulations that require improved stability and solubility.

Pharmacokinetics

Povidone is not absorbed systemically when applied topically, as it remains localized at the site of application. Its pharmacokinetics are largely dependent on the formulation and route of administration, with the polymer being metabolized by hydrolysis and excreted in urine as low-molecular-weight compounds. The release and activity of iodine are influenced by the concentration of povidone and the presence of organic matter.

Adverse effects

• Local irritation
• Allergic reactions
• Skin rashes
• Hypersensitivity reactions

Precautions

• Use with caution in patients with known allergies to iodine or povidone-iodine
• Avoid use in deep puncture wounds or serious burns

Pregnancy

Povidone is generally considered safe for use during pregnancy, but it is advisable to consult a healthcare professional before use.

Breast-feeding

Povidone is considered safe during breastfeeding, but it is recommended to consult a healthcare professional.

Storage

Store at room temperature, away from moisture and heat. Keep the container tightly closed.

Formulations

• Topical solution
• Ointment
• Surgical scrub
• Gauze impregnated with povidone-iodine

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.

Indications

• Silicosis
• Chronic obstructive pulmonary disease (COPD)
• Lung cancer associated with silica exposure

Dosage

Adults: Silica is not administered as a drug, but rather

Mechanism of action

Silica, particularly crystalline forms like quartz and cristobalite, can induce cytotoxicity and morphological transformation in cells. The cytotoxic effects are attributed to the presence of silanol groups and trace iron on the silica surface, which can generate reactive oxygen species. These interactions lead to cellular damage and transformation, suggesting multiple molecular mechanisms underlying silica's biological effects. The activity is sensitive to the silica's surface structure and composition, indicating that the biological response is a phenomenon originating from the silica's surface characteristics.

Pharmacodynamics

Silica's pharmacodynamic effects are largely related to its cytotoxic and transforming properties, particularly in lung tissue. The inhalation of crystalline silica can lead to the activation of inflammatory pathways, oxidative stress, and apoptosis in alveolar macrophages and epithelial cells. This can result in chronic inflammation, fibrosis, and ultimately, diseases such as silicosis and lung cancer. The degree of these effects varies based on the type of silica, its crystalline structure, and the presence of surface modifications.

Pharmacokinetics

The pharmacokinetics of silica is complex as it is not absorbed systemically when inhaled or ingested. Instead, inhaled silica particles can deposit in the alveolar region of the lungs, where they may persist for long periods. The body responds to silica exposure through inflammatory processes, and macrophages attempt to phagocytize silica particles. However, the persistence of these particles can lead to chronic lung conditions. Clearance mechanisms are inefficient, leading to prolonged retention in lung tissue.

Adverse effects

• Cytotoxicity
• Morphological transformation of cells
• Respiratory issues
• Silicosis
• Lung cancer

Precautions

• Use caution in occupational settings with silica dust exposure
• Regular monitoring of lung function in exposed individuals

Pregnancy

There is insufficient data on the effects of silica on pregnancy. It is advised to minimize exposure.

Breast-feeding

Limited data available; caution is advised due to potential respiratory effects.

Storage

Store in a cool, dry place, away from moisture and incompatible materials.

Formulations

• Crystalline silica
• Amorphous silica (diatomaceous earth)
• Silica gel

Indications

• Nutritional supplementation
• Energy source in enteral nutrition
• Excipient in pharmaceutical formulations

Dosage

Children: Refer to specific guidelines or product inserts for dosing information, as it can vary based on the context of use.

Adults: Refer to specific guidelines or product inserts for dosing information, as it can vary based on the context of use.

Mechanism of action

Starch is broken down into glucose units by enzymes such as amylase during digestion. The glucose is then absorbed in the intestines and utilized for energy production in the body's cells. This pathway involves hydrolysis of the glycosidic bonds, converting starch into simpler sugars.

Pharmacodynamics

Starch primarily serves as an energy source. Its digestion and absorption lead to an increase in blood glucose levels, which provides energy for metabolic processes. In this context, it plays a crucial role in maintaining energy homeostasis in the body.

Pharmacokinetics

Starch is not absorbed in its polymeric form; it must first be enzymatically hydrolyzed into simpler sugars such as maltose and glucose. The digestion and absorption of starch occur predominantly in the small intestine, with glucose being readily absorbed into the bloodstream. The rate of absorption can vary depending on the type of starch and its physical form.

Adverse effects

• Allergic reactions
• Gastrointestinal discomfort
• Diarrhea
• Constipation

Precautions

• Use with caution in individuals with known allergies to starch or starch derivatives
• Monitor for gastrointestinal symptoms in patients with a history of digestive disorders

Pregnancy

Starch is generally considered safe for use during pregnancy. However, it should be consumed in moderation as part of a balanced diet.

Breast-feeding

Starch is deemed safe for nursing mothers when used in moderation as part of a balanced diet.

Storage

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

Formulations

• Powder
• Granules
• Tablets
• Suspensions

Dosage

Children: Refer to established dietary guidelines for children, as specific dosing for stearic acid is not typically defined.

Adults: Refer to established dietary guidelines and clinical recommendations for fatty acid intake, as specific dosing for stearic acid is not typically defined.

Mechanism of action

Stearic acid is metabolized in the liver and can be converted to oleic acid through a process called desaturation. It does not significantly affect cholesterol levels compared to other saturated fatty acids, as it can be converted into monounsaturated fatty acids. Stearic acid may also modulate signaling pathways involved in inflammation and metabolism.

Pharmacodynamics

Stearic acid exhibits various physiological effects, including modulation of lipid metabolism. It has been shown to influence the composition of cell membranes and can affect the fluidity and function of membranes due to its saturated structure. Stearic acid may also play a role in the regulation of gene expression related to lipid metabolism and inflammation.

Pharmacokinetics

Stearic acid is absorbed from the gastrointestinal tract and is incorporated into chylomicrons for transport in the bloodstream. It is metabolized primarily in the liver, where it undergoes beta-oxidation to produce energy. The elimination half-life and specific metabolic pathways may vary based on dietary intake and individual metabolic differences.

Pregnancy

There are no established guidelines regarding the use of stearic acid during pregnancy. Consultation with a healthcare provider is recommended.

Breast-feeding

There is limited information available on the use of stearic acid during breastfeeding. Caution is advised.

Storage

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

Formulations

• Capsules
• Tablets
• Powder
• Topical ointments

Dosage

Children: Refer to the specific product information for dosing guidance. Doses are determined by the active ingredients and clinical indications.

Adults: Refer to the specific product information for dosing guidance. Doses are determined by the active ingredients and clinical indications.

Mechanism of action

The mechanism of action of Tabcoat involves the formation of a polymeric layer around the tablet, which can dissolve at specific pH levels in the gastrointestinal tract. This allows for targeted drug release, enhancing bioavailability and improving the therapeutic effect of the encapsulated drug.

Pharmacodynamics

The pharmacodynamics of Tabcoat is largely dependent on the active pharmaceutical ingredient (API) it coats. The coating itself does not exert pharmacological effects but plays a critical role in the drug's release profile. The rate of dissolution can be influenced by factors such as gastrointestinal pH, presence of food, and the specific formulation of the coating material.

Pharmacokinetics

The pharmacokinetics of a drug coated with Tabcoat will vary based on the API. Generally, the coated tablets are designed to dissolve in the intestines, leading to absorption into the systemic circulation. Factors such as absorption rate, distribution, metabolism, and excretion are influenced by the characteristics of both the coating and the drug itself.

Pregnancy

Consult with a healthcare provider as safety in pregnancy has not been established.

Breast-feeding

Consult with a healthcare provider as safety during breastfeeding has not been established.

Storage

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

Dosage

Children: Refer to the BNF for Children for appropriate paediatric dosing information.

Adults: Refer to the specific BNF guidelines for dosing information as it may vary based on the condition being treated.

Mechanism of action

The mechanism of action for White involves its interaction with specific biological pathways, leading to the desired pharmacological effects. The precise pathways may include modulation of receptor activity or alteration of enzyme function, although specific details are not provided.

Pharmacodynamics

Pharmacodynamics of White includes its effects on the body, including therapeutic effects and potential side effects. As a compound, it may exert its influence on multiple physiological systems, which can lead to changes in symptoms or disease progression.

Pharmacokinetics

Pharmacokinetics of White involves its absorption, distribution, metabolism, and excretion. Understanding these parameters can help predict how the drug behaves in the body, including onset of action and duration of effect. Detailed pharmacokinetic data is not specified.

Mechanism of action

Desogestrel enters the cell passively and acts by binding selectively to the progesterone receptor and generating low androgenic activity. Its binding produces an effect like a transcription factor and thus, it produces modifications in the mRNA synthesis. The active metabolite of desogestrel, [etonogestrel], presents a combination of high progestational activity with minimal intrinsic androgenicity. Combination oral contraceptives act by suppression of gonadotropins. Although the primary mechanism of this action is inhibition of ovulation, other alterations include changes in the cervical mucus, which increase the difficulty of sperm entry into the uterus, and changes in the endometrium which reduce the likelihood of implantation. Receptor binding studies, as well as studies in animals, have shown that 3-keto-desogestrel, the biologically active metabolite of desogestrel, combines high progestational activity with minimal intrinsic androgenicity. The relevance of this latter finding in humans is unknown. In contrast to traditional progestogen-only pills, the contraceptive effect of Cerazette is achieved primarily by inhibition of ovulation. Other effects include increased viscosity of the cervical mucus. Recent studies have demonstrated that desogestrel activates the estrogen receptor-alpha at an activity of about 50% of that of 17beta-estradiol but activates the estrogen receptor-beta at an activity of only 20%. Desogestrel and/or its metabolite 3-keto-desogestrel (etonogestrel) were strongly progestogenic (approximately twofold over progesterone), weakly or not androgenic in animal studies in vivo and in-vitro binding assays and weakly or not active on the glucocorticoid receptor. The active metabolite of desogestrel, 3-ketodesogestrel, strongly bound to and activated progesterone receptor-A and, to a slightly lesser extent, progesterone receptor-B Improvement in oral contraceptive formulations was originally achieved through dose reduction of the estrogen and progestogen components. Recently, further improvement was achieved by increasing the selectivity of contraceptive progestins. The ratio between the affinity for the progesterone receptor and the affinity for the androgen receptor is an indicator of progesterone (or androgen) selectivity of a progestin. This ratio (selectivity index) reflects the relative amount of androgenic or progestational effect at a given dose. Relative selectivity can be characterized with in vitro receptor-binding studies and animal pharmacologic experiments. In comparison with levonorgestrel, desogestrel displays markedly lower androgenicity and slightly increased relative progestational activity. In receptor-binding experiments and animal pharmacologic studies, 3-keto-desogestrel, the active metabolite of desogestrel, shows the highest selectivity index. The favorable effect of desogestrel-containing oral contraceptives on lipoprotein metabolism and preexisting androgen-dependent skin disorders and the absence of adverse effects on blood pressure and body weight are attributed to the increased progestin selectivity of desogestrel. For more Mechanism of Action (Complete) data for DESOGESTREL (6 total), please visit the HSDB record page.

Pharmacodynamics

The effects of desogestrel are divided on reproductive including modification of luteinizing hormone and follicle stimulating hormone, declines on the onset of menstruation, and increases the viscosity of the vaginal fluid; and on metabolic that includes increase insulin secretion and resistance, increased lipase activity, and increased fat deposition. The effect of desogestrel on the lipids has been studied extensively and the results are contradictory. Desogestrel main therapeutic effect due to its mechanism of action is known to be related to the inhibition of the ovulation in 97% of the cycles. This effect was proven in clinical trials in non-breastfeeding women from which the Pearl failure rate was reported to be of 0.17 per 100 women-years. This result indicated that desogestrel is more efficient when compared to other progestogen-only pills. All the therapeutic effect is produced by a transformation of the endometrium followed by an inhibition of the ovulation due to the suppression of other hormones. Desogestrel has been widely confirmed to be related to an increase in the risk of venous thromboembolism due to the driven increased in blood coagulation factors, leading to a pronounced prothrombotic state. However, the effects of desogestrel are known to not impact significantly the level of total cholesterol remaining in the range of change of 10% which allows it to be a molecule that presents a favorable lipid profile.

Mechanism of action

...Some quartz and cristobalite dusts (crystalline) as well as the diatomaceous earths (amorphous), but not the pyrogenic amorphous silica, were cytotoxic and induced morphological transformation of SHE cells in a concentration-dependent manner. The ranking in cytotoxicity was different from that in transforming potency, suggesting two separate molecular mechanisms for the two effects. The cytotoxic and transforming potencies were different from one dust to another, even among the same structural silicas. The type of crystalline structure (quartz vs cristobalite) and the crystalline vs biogenic amorphous form did not correlate with cytotoxic or transforming potency of silica dusts. Comparison of cellular effects induced by original and surface modified samples revealed that several surface functionalities modulate cytotoxic and transforming potencies. The cytotoxic effects appeared to be related to the distribution and abundance of silanol groups and to the presence of trace amounts of iron on the silica surface. Silica particles with fractured surfaces and/or iron-active sites, able to generate reactive oxygen species, induced SHE cell transformation. The results show that the activity of silica at the cellular level is sensitive to the composition and structure of surface functionalities and confirm that the biological response to silica is a surface originated phenomenon. In vivo exposure of rat lungs to crystalline silica either by intratracheal instillation or by inhalation results in an increase in mRNA levels for inducible nitric oxide synthase (iNOS) in bronchoalveolar lavage cells (BALC), elevated nitric oxide (.NO) production by BALC, and an increase in .NO-dependent chemiluminescence (CL) from alveolar macrophages (AM). Induction of iNOS message occurs in both AM and polymorphonuclear leukocytes (PMN) harvested from silica-exposed lungs but is not significantly elevated in lavaged lung tissue. This review presents characteristics of simple and complicated coal workers' pneumoconiosis (CWP) as well as pathologic indices of acute and chronic silicosis by summarizing results of in vitro, animal, and human investigations. These results support four basic mechanisms in the etiology of CWP and silicosis: a) direct cytotoxicity of coal dust or silica, resulting in lung cell damage, release of lipases and proteases, and eventual lung scarring; b) activation of oxidant production by pulmonary phagocytes, which overwhelms the antioxidant defenses and leads to lipid peroxidation, protein nitrosation, cell injury, and lung scarring; c) activation of mediator release from alveolar macrophages and epithelial cells, which leads to recruitment of polymorphonuclear leukocytes and macrophages, resulting in the production of proinflammatory cytokines and reactive species and in further lung injury and scarring; d) secretion of growth factors from alveolar macrophages and epithelial cells, stimulating fibroblast proliferation and eventual scarring. Results of in vitro and animal studies provide a basis for proposing these mechanisms for the initiation and progression of pneumoconiosis. Data obtained from exposed workers lend support to these mechanisms. /The authors/ reported previously that freshly fractured silica (FFSi) induces activator protein-1 (AP-1) activation through extracellular signal-regulated protein kinases (ERKs) and p38 kinase pathways. In the present study, the biologic activities of FFSi and aged silica (ASi) were compared by measuring their effects on the AP-1 activation and phosphorylation of ERKs and p38 kinase. The roles of reactive oxygen species (ROS) in this silica-induced AP-1 activation were also investigated. FFSi-induced AP-1 activation was four times higher than that of ASi in JB6 cells. FFSi also caused greater phosphorylation of ERKs and p38 kinase than ASi. FFSi generated more ROS than ASi when incubated with the cells as measured by electron spin resonance (ESR). Studies using ROS-sensitive dyes and