SOFDERM CREAM

Indications

• Skin burns and wounds
• Sunburn
• Acne
• Psoriasis
• Digestive disorders
• Constipation

Dosage

Children: For topical use, apply Aloe vera gel as needed on the affected area. For oral formulations, consult product-specific dosing recommendations tailored to children's needs.

Adults: For topical use, apply Aloe vera gel directly to the affected area as needed. For oral consumption, refer to specific product guidelines, as formulations vary widely.

Mechanism of action

The primary mechanism of action of Aloe vera involves its anti-inflammatory and immunomodulatory properties. The polysaccharides, such as acemannan, enhance immune function and promote wound healing. Aloe also exhibits antimicrobial activity, which can help in preventing infections in wounds. In the gastrointestinal tract, Aloe may exert a laxative effect by stimulating intestinal peristalsis and enhancing mucosal secretions.

Pharmacodynamics

Aloe vera gel has demonstrable effects on skin hydration, wound healing, and anti-inflammatory responses. Its polysaccharide content is responsible for its ability to retain moisture and promote cell proliferation and migration, essential processes in tissue repair. Additionally, Aloe has shown potential in modulating inflammatory cytokines, which may contribute to its soothing effects when applied topically.

Pharmacokinetics

Aloe vera is typically administered topically or orally. When applied to the skin, it is absorbed locally, facilitating its effects on the epidermis and dermis. Oral consumption of Aloe products leads to absorption of its active compounds in the gastrointestinal tract, where they may exert systemic effects. The half-life and metabolism of Aloe components can vary depending on the formulation and route of administration, with the laxative effects usually occurring within a few hours after oral intake.

Adverse effects

• Abdominal cramps
• Diarrhea
• Electrolyte imbalance
• Dehydration
• Allergic reactions

Interactions

• May interact with diuretics, increasing the risk of electrolyte imbalance
• May affect the absorption of other medications due to its laxative effects

Precautions

• Use with caution in individuals with gastrointestinal disorders
• Not recommended for long-term use due to potential for dependence
• Avoid in cases of known allergy to aloe or its components

Pregnancy

Aloe is not recommended during pregnancy due to potential uterine stimulation and risks of miscarriage.

Breast-feeding

Aloe should be avoided during breastfeeding as safety has not been established.

Storage

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

Formulations

• Aloe vera gel
• Aloe vera juice
• Aloe extracts in capsules or tablets

Indications

• Hypertension
• Benign prostatic hyperplasia
• Urinary retention related to prostate enlargement

Dosage

Children: Refer to the BNF for Children for appropriate dosing guidelines in the paediatric population.

Adults: Refer to the BNF for specific dosing recommendations based on individual clinical scenarios.

Mechanism of action

Alpha acts by selectively blocking alpha-1 adrenergic receptors, which are responsible for mediating vasoconstriction in blood vessels. By inhibiting these receptors, alpha promotes vasodilation, leading to a decrease in peripheral vascular resistance and subsequently lowering blood pressure. Additionally, this action can help alleviate urinary symptoms associated with an enlarged prostate.

Pharmacodynamics

The pharmacodynamics of alpha involve its competitive antagonism at alpha-1 adrenergic receptors, resulting in decreased vasoconstriction and increased blood flow. This mechanism is beneficial in conditions characterized by high blood pressure and urinary retention due to prostatic enlargement. The onset of action typically occurs within hours, with peak effects observed within a few days of consistent dosing.

Pharmacokinetics

Alpha is absorbed well from the gastrointestinal tract, with peak plasma concentrations achieved within 1-3 hours post-administration. The drug undergoes hepatic metabolism, primarily via cytochrome P450 enzymes, resulting in active and inactive metabolites. The elimination half-life varies, but it generally is around 6-12 hours, allowing for once-daily dosing in many cases. Renal excretion is a significant route for its metabolites, necessitating caution in patients with renal impairment.

Interactions

• maois, irreversible + alpha blockers: Severe (increases effects)
• ribociclib + alpha blockers: Severe (increases exposure)
• cobicistat + alpha blockers: Moderate (increases exposure)
• idelalisib + alpha blockers: Moderate (increases exposure)
• dronedarone + alpha blockers: Unknown (increases exposure)
• antifungals, azoles + alpha blockers: Unknown (increases exposure)
• crizotinib + alpha blockers: Unknown (increases exposure)
• imatinib + alpha blockers: Unknown (increases exposure)
• letermovir + alpha blockers: Unknown (increases exposure)
• clarithromycin + alpha blockers: Unknown (increases exposure)

Indications

• Vitamin E deficiency
• Prevention of oxidative stress-related conditions
• Support for immune function
• Potential adjunctive therapy in chronic diseases such as coronary heart disease and cancer

Dosage

Adults: Refer to

Mechanism of action

The precise mechanisms of vitamin E's actions are not fully understood; however, it is known to act as an antioxidant by preventing free radical reactions with cell membranes. One key mechanism involves the termination of lipid peroxidation, where vitamin E interacts with unstable lipid radicals to produce stable lipids and a relatively stable vitamin E radical. This radical can be regenerated back to its active form through reactions with ascorbate or glutathione. Additionally, vitamin E may modulate inflammatory responses and is linked to cancer prevention through its effects on NF-kappaB signaling pathways.

Pharmacodynamics

Vitamin E functions primarily as an antioxidant, protecting cells against oxidative stress and inflammatory processes. It helps to mitigate the damaging effects of reactive oxygen species (ROS) and is vital in maintaining the integrity of cell membranes. Vitamin E deficiency can lead to various health issues, including impaired immune function and increased susceptibility to chronic diseases such as coronary heart disease and certain cancers. It also plays a role in safeguarding other fat-soluble vitamins from oxidative degradation.

Pharmacokinetics

Tocopheryl is absorbed through the intestinal tract and is typically transported in the bloodstream by lipoproteins. The bioavailability of vitamin E can be influenced by dietary fat intake, as it is fat-soluble. Once absorbed, tocopheryl is stored in the liver and adipose tissues. The metabolism of vitamin E involves conversion to various metabolites, which can be excreted in urine and bile. The half-life of alpha-tocopherol in the body can vary, but it is generally several hours to days, depending on individual factors and dietary intake.

Adverse effects

• Nausea
• Diarrhea
• Abdominal cramps
• Fatigue
• Headache

Interactions

• May enhance the effects of anticoagulants, increasing the risk of bleeding
• May interact with statins, potentially increasing risk of muscle disorders
• May reduce the effectiveness of certain chemotherapy agents

Precautions

• Use with caution in individuals with a history of bleeding disorders
• Monitor prothrombin time in patients on anticoagulants
• Consult healthcare provider before use in pregnant or breastfeeding women

Pregnancy

Vitamin E is generally considered safe during pregnancy when used in recommended amounts, but high doses should be avoided as they may pose risks.

Breast-feeding

Vitamin E is excreted in breast milk; consult a healthcare provider before supplementation while breastfeeding.

Storage

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

Formulations

• Capsules
• Soft gels
• Liquid formulations
• Tablets

Indications

• Hypertension
• Angina pectoris
• Supraventricular tachycardia
• Atrial fibrillation
• Atrial flutter

Dosage

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

Adults: Refer to the BNF for specific dosing guidelines based on the condition being treated and patient characteristics.

Mechanism of action

Verapamil works by selectively blocking L-type calcium channels, which are essential for the influx of calcium ions during depolarization in cardiac and vascular smooth muscle cells. This blockade decreases intracellular calcium levels, resulting in reduced cardiac contractility (negative inotropic effect), decreased heart rate (negative chronotropic effect), and vasodilation, which collectively help in managing conditions like hypertension and angina.

Pharmacodynamics

Verapamil exhibits dose-dependent effects on cardiac conduction and vascular tone. It slows conduction through the atrioventricular (AV) node, which is beneficial in treating certain types of supraventricular tachycardias. Its vasodilatory effects lead to a reduction in peripheral vascular resistance, contributing to its antihypertensive properties. The onset of action occurs within 1 hour after oral administration, with effects lasting for several hours.

Pharmacokinetics

Verapamil is well absorbed from the gastrointestinal tract but undergoes extensive first-pass metabolism in the liver, leading to variable bioavailability (usually 20-35%). It is highly protein-bound (90-95%), primarily to albumin. The elimination half-life ranges from 3 to 7 hours, with metabolites also exhibiting pharmacological activity. Renal excretion accounts for the elimination of both unchanged drug and metabolites, necessitating caution in patients with renal impairment.

Contra-indications

• Severe hypotension
• Cardiogenic shock
• Severe left ventricular dysfunction
• Second- or third-degree AV block (unless a functioning pacemaker is present)

Adverse effects

• Hypotension
• Bradycardia
• Heart block
• Peripheral edema
• Constipation
• Headache
• Dizziness
• Fatigue

Interactions

• amiodarone+verapamil: Severe (increases risk of cardiodepression)
• verapamil+betablockers, non-selective: Severe (increases risk of cardiovascular adverse effects)
• intravenous dantrolene+verapamil: Severe (increases risk of acute hyperkalaemia and cardiovascular collapse)
• grapefruit juice+verapamil: Severe (increases exposure)
• miconazole+verapamil: Moderate (increases exposure)
• verapamil+bictegravir: Moderate (increases exposure)
• verapamil+panobinostat: Moderate (increases exposure)
• verapamil+thrombin inhibitors: Moderate (increases exposure)
• verapamil+dabigatran: Moderate (increases exposure)
• enzalutamide+verapamil: Unknown (decreases exposure)

Precautions

• Use with caution in patients with hepatic impairment
• Monitor heart rate and blood pressure regularly
• Caution in patients with a history of heart failure

Pregnancy

Use in pregnancy only if the potential benefit justifies the potential risk to the fetus. Consult local guidelines.

Breast-feeding

Verapamil is excreted in breast milk, caution is advised when used during breastfeeding.

Storage

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

Formulations

• Tablets
• Sustained-release tablets
• Injection

Mechanism of action

The mechanism of action for most of vitamin E's effects are still unknown. Vitamin E is an antioxidant, preventing free radical reactions with cell membranes. Though in some cases vitamin E has been shown to have pro-oxidant activity. One mechanism of vitamin E's antioxidant effect is in the termination of lipid peroxidation. Vitamin E reacts with unstable lipid radicals, producing stable lipids and a relatively stable vitamin E radical. The vitamin E radical is then reduced back to stable vitamin E by reaction with ascorbate or glutathione. Cancer development and progression are closely associated with inflammation. NF-kappaB (nuclear factor kappaB) provides a mechanistic link between inflammation and cancer, and is a major factor controlling the ability of malignant cells to resist tumor surveillance mechanisms. NF-kappaB might also regulate tumor angiogenesis and invasiveness and the signalling pathways that mediate its activation provide attractive targets for new chemopreventive and chemotherapeutic approaches. ROS (reactive oxygen species) initiate inflammation by up-regulation of pro-inflammatory cytokines and therefore antioxidants provide a major defence against inflammation. alpha-Tocopherol is a lipid-soluble antioxidant. In addition to decreasing lipid peroxidation, alpha-tocopherol may exert intracellular effects. Hence, the aim of this study was to test the effect of alpha-tocopherol supplementation in cancer prevention via suppression of NF-kappaB-mediated pro-inflammatory cytokines. alpha-Tocopherol treatment significantly down-regulates expression, synthesis as well as secretion of pro-inflammatory cytokine IL-6 (interleukin-6) in cancerous mice. It also suppresses NF-kappaB binding to IL-6 promoter in liver leading to decreased secretion of IL-6 in serum. The regulation of the signalling pathway by alpha-tocopherol is found apart from its antioxidant capacity to reduce lipid peroxidation. Thus, the present study provides evidence for the hypothesis that besides the powerful free radical scavenging effects, alpha-tocopherol has genomic effects in down-regulation of pro-inflammatory cytokine and cancer prevention via the NF-kappaB-dependent pathway. Mitocans are drugs selectively killing cancer cells by destabilizing mitochondria and many induce apoptosis via generation of reactive oxygen species (ROS). However, the molecular events by which ROS production leads to apoptosis has not been clearly defined. In this study with the mitocan alpha-tocopheryl succinate (alpha-TOS) the role of the Bcl-2 family proteins in the mechanism of malignant cell apoptosis has been determined. Exposure of several different cancer cell lines to alpha-TOS increased expression of the Noxa protein, but none of the other proteins of the Bcl-2 family, an event that was independent of the cellular p53 status. alpha-TOS caused a profound conformational change in the pro-apoptotic protein, Bak, involving oligomerization in all cell types, and this also applied to the Bax protein, but only in non-small cell lung cancer cells. Immunoprecipitation studies indicated that alpha-TOS activates the two BH1-3 proteins, Bak or Bax, to form high molecular weight complexes in the mitochondria. RNAi knockdown revealed that Noxa and Bak are required for alpha-TOS-induced apoptosis, and the role of Bak was confirmed using Bak- and/or Bax-deficient cells. We conclude that the major events induced by alpha-TOS in cancer cells downstream of ROS production leading to mitochondrial apoptosis involve the Noxa-Bak axis. It is proposed that this represents a common mechanism for mitochondrial destabilization activated by a variety of mitocans that induce accumulation of ROS in the early phases of apoptosis. /alpha-Tocopheryl succinate/

Pharmacodynamics

Vitamin E is a collective term used to describe 8 separate fat soluble antioxidants, most commonly alpha-tocopherol. Vitamin E acts to protect cells against the effects of free radicals, which are potentially damaging by-products of the body's metabolism. Vitamin E deficiency is seen in persons with abetalipoproteinemia, premature, very low birth weight infants (birth weights less than 1500 grams, or 3½ pounds), cystic fibrosis, and cholestasis and severe liver disease. Preliminary research suggests vitamin E may help prevent or delay coronary heart disease and protect against the damaging effects of free radicals, which may contribute to the development of chronic diseases such as cancer. It also protects other fat-soluble vitamins (A and B group vitamins) from destruction by oxygen. Low levels of vitamin E have been linked to increased incidence of breast and colon cancer.