THUNDER-M TABLET

Indications

• Selenium deficiency
• Supportive therapy in conditions requiring antioxidant support
• Potential adjunct in cancer prevention strategies

Dosage

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

Adults: Initially 100–500 micrograms daily, adjusted according to response and serum levels.

Mechanism of action

Selenium is metabolized to selenophosphate and selenocysteine, which are essential for the synthesis of selenoproteins. This process involves the incorporation of selenium into proteins through a specialized tRNA that recognizes the RNA sequence UGA, which is facilitated by SECIS structures and SBP-2 proteins. Key selenoproteins, like glutathione peroxidases, help protect cells from oxidative damage, thus playing a significant role in reducing the risk of diseases such as atherosclerosis and certain cancers.

Pharmacodynamics

Selenium is incorporated into various selenoproteins that perform essential functions, including antioxidant activity, redox balance, and regulation of thyroid hormones. Its role in antioxidant defense mechanisms is particularly important for protecting cells against reactive oxygen species (ROS). Selenium supplementation has been linked to improved immune function and potential cancer prevention.

Pharmacokinetics

Selenium is absorbed through the gastrointestinal tract, and its bioavailability can vary based on the source and form of selenium. Once absorbed, it is distributed to various tissues, where it is incorporated into selenoproteins. Selenium is primarily excreted through urine, and its half-life can depend on dietary intake and individual metabolism. Selenium status can be assessed through blood levels of selenoproteins and selenium itself.

Adverse effects

• Nausea
• Anaemia
• Aplastic anaemia
• Skin reactions
• Gastrointestinal disorders

Precautions

• Selenium supplementation should not be given unless there is good evidence of deficiency.
• Use caution in patients with a history of hypersensitivity to selenium or its compounds.

Pregnancy

Limited information is available regarding selenium supplementation during pregnancy. Consult specialist sources for guidance.

Breast-feeding

Limited information is available; the effect of selenium on copper levels in milk is conflicting, and its impact on the infant is unknown.

Storage

After opening, store in a refrigerator (2–8°C).

Formulations

• Tablets (e.g., L-Selenomethionine 200 micrograms, SelenoPrecise 100 micrograms)
• Capsules (e.g., Trientine dihydrochloride 250 mg)
• Injection solutions (e.g., Sodium selenite 50 micrograms per 1 ml)

Indications

• Anxiety
• Depression
• Sexual dysfunction
• Fatigue

Dosage

Children: There is insufficient evidence to recommend a pediatric dosage; consult a healthcare professional.

Adults: Dosage for adults is not standardized; consult established herbal guidelines or a healthcare professional.

Mechanism of action

The exact mechanism of action of damiana is not well understood. It is thought to interact with the central nervous system, potentially influencing neurotransmitter systems. Some studies suggest that it may enhance mood and sexual function by modulating the levels of certain neurotransmitters like serotonin and dopamine.

Pharmacodynamics

Damiana exhibits mild stimulant and aphrodisiac effects. It is believed to enhance sexual function and improve mood, likely due to its influence on neurotransmitter activity. Its effects on anxiety and depression have been noted, but the clinical relevance and extent of these effects require further investigation.

Pharmacokinetics

Pharmacokinetic data specific to damiana is limited. Its active constituents, such as flavonoids and essential oils, may be absorbed through the gastrointestinal tract. The metabolism and excretion pathways remain largely uncharacterized, necessitating more research to fully understand its pharmacokinetic profile.

Adverse effects

• Nausea
• Vomiting
• Diarrhea
• Headaches
• Insomnia
• Allergic reactions

Interactions

• May interact with sedatives and antidepressants
• Potential interaction with blood sugar-lowering medications

Precautions

• Use with caution in patients with hormone-sensitive conditions
• Not recommended for individuals with liver or kidney disorders
• Should be avoided in pregnant and breastfeeding women

Pregnancy

There is insufficient evidence to determine the safety of damiana during pregnancy. It is generally advised to avoid its use.

Breast-feeding

Due to a lack of safety data, damiana should be used with caution during breastfeeding.

Storage

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

Formulations

• Dried leaves
• Capsules
• Tinctures
• Extracts

Indications

• Fatigue
• Stress management
• Cognitive enhancement
• Immune support
• General well-being

Dosage

Children: Refer to specific product guidelines, as dosing in children should be determined by a healthcare professional.

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

Mechanism of action

Ginseng is thought to exert its effects through several mechanisms, including modulation of the hypothalamic-pituitary-adrenal (HPA) axis, enhancement of antioxidant activity, and regulation of neurotransmitter levels. Ginsenosides, the active compounds in ginseng, may influence cellular signaling pathways, promote neuroprotection, and enhance immune responses.

Pharmacodynamics

The pharmacodynamic effects of ginseng are attributed primarily to its active constituents, ginsenosides, which interact with various receptors and enzymes in the body. These interactions can lead to increased energy metabolism, improved cognitive function, enhanced physical performance, and modulation of the immune system. Ginseng may also exhibit adaptogenic properties, helping the body to maintain homeostasis under stress.

Pharmacokinetics

Ginsenosides undergo extensive metabolism in the body, primarily by the liver. Bioavailability can vary significantly based on the specific ginsenoside and the method of administration. Ginseng is usually administered orally, with effects typically observed within several hours after ingestion. The elimination half-life of ginsenosides can vary based on the specific compound and individual metabolism, with some studies suggesting that effects may persist for several hours to days.

Adverse effects

• Insomnia
• Headache
• Gastrointestinal disturbances
• Nervousness
• Hypertension
• Allergic reactions

Interactions

• May interact with anticoagulants (e.g., warfarin)
• May enhance the effects of caffeine
• May affect insulin levels and blood sugar control
• Potential interaction with immunosuppressants

Precautions

• Use with caution in patients with hypertension
• May cause sleep disturbances; avoid use before bedtime
• Should be used cautiously in patients with diabetes
• Consult a healthcare provider before use in individuals with autoimmune conditions

Pregnancy

Limited data available. Generally not recommended due to potential hormonal effects.

Breast-feeding

Limited data available. Consult a healthcare provider before use.

Storage

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

Formulations

• Dried root
• Powdered extract
• Capsules
• Tinctures
• Teas

Indications

• Erectile dysfunction
• Pulmonary hypertension
• Heart failure
• Chronic obstructive pulmonary disease (COPD)

Dosage

Children: Refer to the BNF for Children for appropriate dosing guidelines, as paediatric dosing can differ significantly from adult dosing.

Adults: Refer to the BNF for specific dosing information, as it varies depending on the particular phosphodiesterase type inhibitor and the condition being treated.

Mechanism of action

Phosphodiesterase type inhibitors work by blocking the degradation of cAMP and cGMP, which results in increased levels of these second messengers within cells. Elevated cAMP levels lead to smooth muscle relaxation, vasodilation, and increased myocardial contractility. Additionally, cGMP plays a critical role in vascular smooth muscle relaxation and platelet aggregation inhibition.

Pharmacodynamics

The pharmacodynamic effects of phosphodiesterase type inhibitors include enhanced vasodilation, improvement in myocardial oxygen supply, and reduced myocardial oxygen demand. This results in beneficial effects for patients with conditions such as heart failure, pulmonary hypertension, and certain forms of erectile dysfunction. The time to onset of action and duration of effect can vary depending on the specific agent within this class.

Pharmacokinetics

Phosphodiesterase type inhibitors are generally well absorbed after oral administration, with peak plasma concentrations typically achieved within 1 to 2 hours. The metabolism of these drugs primarily occurs in the liver via cytochrome P450 enzymes, leading to various metabolites. The elimination half-life varies between agents but is generally in the range of 4 to 12 hours, with renal excretion being a significant route of elimination for some compounds.

Interactions

• aminophylline+phosphodiesterasetype-: Severe (increases exposure)
• cobicistat+phosphodiesterasetype-: Severe (increases exposure)
• idelalisib+phosphodiesterasetype-: Severe (increases exposure)
• clarithromycin+phosphodiesterasetype-: Severe (increases exposure)
• mitotane+phosphodiesterasetype-: Severe (decreases exposure)
• nicorandil+phosphodiesterasetype-: Severe (increases risk of hypotension)
• tucatinib+phosphodiesterasetype-: Severe (increases exposure)
• ribociclib+phosphodiesterasetype-: Severe (increases exposure)
• rifampicin+phosphodiesterasetype-: Severe (decreases exposure)
• theophylline+phosphodiesterasetype-: Severe (increases exposure)

Indications

• Erectile dysfunction
• Impotence
• Sexual dysfunction

Dosage

Children: null

Adults: The usual starting dose for erectile dysfunction is 5.4 mg taken three times daily, which may be increased as needed, but should not exceed 6-10 mg daily.

Mechanism of action

Yohimbine is a pre-synaptic alpha-2 adrenergic blocking agent. It is thought to enhance erectile ability through blockade of central alpha-2 adrenergic receptors, leading to increased sympathetic nervous system activity, norepinephrine release, and altered neurotransmitter dynamics.

Pharmacodynamics

Yohimbine is structurally similar to reserpine and acts as a weak blocker of presynaptic alpha-2 adrenergic receptors. It increases parasympathetic (cholinergic) activity and decreases sympathetic (adrenergic) activity, which may enhance penile blood flow and erection. At higher doses, yohimbine can stimulate mood but may also increase anxiety. Yohimbine has a mild anti-diuretic action and is not known to significantly influence cardiac stimulation or beta-adrenergic mediated effects.

Pharmacokinetics

Yohimbine is absorbed rapidly after oral administration, with peak plasma concentrations occurring within 1-2 hours. It is extensively metabolized in the liver, and its metabolites are primarily excreted via the kidneys. The half-life of yohimbine varies, but it generally ranges from 0.5 to 2 hours, depending on individual factors such as metabolic rate and health status.

Contra-indications

• Hypersensitivity to yohimbine or any of its components
• Patients with a history of severe anxiety or panic disorders
• Patients with significant cardiovascular disorders
• Renal impairment

Adverse effects

• Anxiety
• Hypertension
• Tachycardia
• Dizziness
• Nausea
• Headache
• Insomnia
• Gastrointestinal disturbances

Interactions

• Caution with other medications that affect blood pressure or the central nervous system
• Potential interactions with monoamine oxidase inhibitors (MAOIs)
• May interact with other adrenergic agents

Precautions

• Use with caution in patients with a history of psychiatric disorders
• Monitoring of blood pressure is advised during treatment
• Not recommended for use in combination with other medications that may amplify its effects

Pregnancy

Yohimbine is not recommended during pregnancy due to insufficient safety data.

Breast-feeding

The safety of yohimbine during breastfeeding has not been established, caution is advised.

Storage

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

Formulations

• Tablets
• Capsules
• Oral solutions

Mechanism of action

Selenium is first metabolized to selenophosphate and selenocysteine. Selenium incorporation is genetically encoded through the RNA sequence UGA. This sequence is recognized by RNA ste loop structures called selenocysteine inserting sequences (SECIS). These structures require the binding of SECIS binding proteins (SBP-2) to recognize selenocystiene. The specialized tRNA is first bound to a serine residue which is then enzymatically processed to a selylcysteyl-tRNA by selenocystiene sythase using selenophosphate as a selenium donor. Other unidentified proteins are required as part of the binding of this tRNA to the ribosome. Selenoproteins appear to be necessary for life as mice with the specialized tRNA gene knocked out exhibited early embryonic lethality. The most important selenoproteins seem to be the glutathione peroxidases and thioredoxin reductases which are part of the body's defenses againts reactive oxygen species (ROS). The importance of selenium in these anti-oxidant proteins has been implicated in the reduction of atherosclerosis by preventing the oxidation of low density lipoprotein. Selenium supplementation is also being investigated in the prevention of cancer and has been suggested to be beneficial to immune function. Converging data from epidemiological, ecological, and clinical studies have shown that selenium (Se) can decrease the risk for some types of human cancers. Induction of apoptosis is considered an important cellular event that can account for the cancer preventive effects of Se. Prior to occurrence of apoptosis, Se compounds alter the expression and/or activities of signaling molecules, mitochondria-associated factors, transcriptional factors, tumor suppressor genes, and cellular reduced glutathione. Mechanistic studies have demonstrated that the methylselenol metabolite pool has many desirable attributes of chemoprevention, whereas the hydrogen selenide pool with excess of selenoprotein synthesis can lead to DNA single-strand breaks. To elucidate the effects of Se on cytotoxic events, it should be remembered that the chemical forms and the dose of Se, and the experimental system used, are determinants of its biological activities. This mini-review focuses on elucidation of the molecular mechanisms of cancer prevention by Se with the apoptotic approach. /Selenium/ Selenium status can also influence thyroid hormone function via the deiodinase enzymes. Selenium is a critical component of the deiodinase enzymes, including iodothyronine 5'-deiodinases, which convert the prohormone thyroxine (T4) to the active circulating form, triiodothyronine (T3). Selenium is also a component of GPX, the main enzyme responsible for protecting thyroid cells against oxidative damage. GPX is involved in the detoxification of hydrogen peroxide, which is produced in the thyroid during the conversion of T4 to T3. /Selenium/ Selenium readily substitutes for sulfur in biomolecules and in many biochemical reactions, especially when the concentration of selenium is high and the concentration of sulfur is low in the organism. Inactivation of the sulfhydryl enzymes necessary for oxidative reactions in cellular respiration, through effects on mitochondrial and microsomal electron transport, might contribute to acute selenium toxicity. Selenium may have a role in hepatic heme metabolism that is related to GPX or lipid peroxidation. Selenocysteine is specifically found in some proteins (e.g., glutathione peroxidase); selenomethionine appears to randomly substitute for methionine in protein synthesis. This appears to be an additional mechanism for intermediate- or chronic-duration toxicity. Skin, hair, and nail damage are significant indicators of chronic selenium overexposure. The mechanism causing these integumentary effects is unclear, but could be related to the high selenium concentrations in these tissues as a consequence of the substitution of selenium for sulfur in certain amino acids, including the disulfide bridges that pr

Pharmacodynamics

Selenium is incorporated into many different selenoproteins which serve various functions throughout the body.

Mechanism of action

Yohimbine is a pre-synaptic alpha 2-adrenergic blocking agent. The exact mechanism for its use in impotence has not been fully elucidated. However, yohimbine may exert its beneficial effect on erectile ability through blockade of central alpha 2-adrenergic receptors producing an increase in sympathetic drive secondary to an increase in norepinephrine release and in firing rate of cells in the brain noradrenergic nuclei. Yohimbine-mediated norepinephrine release at the level of the corporeal tissues may also be involved. In addition, beneficial effects may involve other neurotransmitters such as dopamine and serotonin and cholinergic receptors.

Pharmacodynamics

Yohimbine is an indolalkylamine alkaloid with chemical similarity to reserpine. Yohimbine blocks presynaptic alpha-2 adrenergic receptors. Its action on peripheral blood vessels resembles that of reserpine, though it is weaker and of short duration. Yohimbine's peripheral autonomic nervous system effect is to increase parasympathetic (cholinergic) and decrease sympathetic (adrenergic) activity. It is to be noted that in male sexual performance, erection is linked to cholinergic activity and to alpha-2 adrenergic blockade which may theoretically result in increased penile inflow, decreased penile outflow or both. Yohimbine exerts a stimulating action on the mood and may increase anxiety. Such actions have not been adequately studied or related to dosage although they appear to require high doses of the drug. Yohimbine has a mild anti-diuretic action, probably via stimulation of hypothalmic center and release of posterior pituitary hormone. Reportedly Yohimbine exerts no significant influence on cardiac stimulation and other effects mediated by (beta)-adrenergic receptors. Its effect on blood pressure, if any, would be to lower it; however, no adequate studies are at hand to quantitate this effect in terms of Yohimbine dosage.