SUSTANON

Indications

• Androgen deficiency in males
• Delayed puberty in males
• Breast cancer in women (long-term palliative therapy)
• Prevention of tumor flare with gonadorelin analogue therapy

Dosage

Children: Child (male): 1.25–2.5 mg daily for 3–6 months for stimulation of late pre-pubertal growth. Child (female): 0.625–2.5 mg daily in combination with growth hormone for similar indications.

Adults: Initially 250 mg every 2–3 weeks; maintenance 250 mg every 3–6 weeks. For androgen deficiency, 200–300 mg daily in 2–3 divided doses may be used.

Mechanism of action

Testosterone propionate binds to androgen receptors in various tissues, leading to the activation of gene expression involved in anabolic processes such as protein synthesis, muscle growth, and erythropoiesis. The drug enhances nitrogen retention and increases muscle mass and strength, while also having effects on libido and mood.

Pharmacodynamics

As an androgen, testosterone propionate promotes the development of male secondary sexual characteristics and has anabolic effects on muscle and bone. It influences metabolic processes, enhancing lipid metabolism and may affect mood and cognitive functions. Its action can lead to increased red blood cell production due to its stimulatory effect on erythropoietin.

Pharmacokinetics

Testosterone propionate is absorbed rapidly after intramuscular injection, with peak serum testosterone levels typically occurring within 24 to 36 hours. The drug has a relatively short half-life, leading to the necessity for frequent dosing (typically every 2 to 3 days). It is metabolized in the liver to inactive metabolites and excreted primarily through urine.

Contra-indications

• Pregnancy
• Prostate cancer
• Known hypersensitivity to testosterone or excipients
• Severe renal or hepatic impairment
• Hypercalcaemia

Adverse effects

• Mood alterations
• Increased appetite
• Gastrointestinal discomfort
• Diarrhea
• Musculoskeletal complaints
• Dysphonia
• Increased risk of infection
• Migraine
• Fluid imbalance
• Azoospermia
• Hair growth changes
• Cardiovascular disorders
• Hypercholesterolemia
• Gynecomastia
• Sleep apnea
• Anxiety
• Pulmonary oil microembolism

Interactions

• Anticoagulants (increased anticoagulant effect)
• Corticosteroids (increased risk of edema)
• Insulin and oral hypoglycemic agents (may alter glucose metabolism)
• Cyproterone acetate (antagonistic effect on testosterone)

Precautions

• Monitor liver function regularly
• Caution in patients with cardiovascular disease
• Assess for sleep apnea in predisposed individuals
• Monitor for signs of polycythemia
• Evaluate bone density due to potential effects on bone metabolism

Pregnancy

Testosterone propionate is contraindicated in pregnancy due to the risk of masculinization of the female fetus.

Breast-feeding

Testosterone is not recommended during breastfeeding as it may affect milk production and the infant.

Storage

Store in a cool, dry place, protected from light. Do not refrigerate or freeze.

Formulations

• Testosterone propionate solution for injection (50 mg/ml)
• Testosterone undecanoate solution for injection (250 mg/1 ml)

Indications

• Hypogonadism
• Low sexual desire in postmenopausal women (administered on expert advice)
• Certain aplastic anemias
• Androgen deficiency in males

Dosage

Adults: Refer to the BNF for specific dosing recommendations

Mechanism of action

Testosterone exerts its effects by binding to the androgen receptor, which is located in the cytoplasm bound to heat shock proteins. Upon binding, the receptor dissociates from these chaperones and undergoes a conformational change. The androgen-receptor complex is then transported into the nucleus, where it binds to DNA and recruits other transcriptional regulators to induce the expression of specific genes. This process promotes the development of male reproductive organs and secondary sexual characteristics such as increased muscle mass and body hair.

Pharmacodynamics

Testosterone antagonizes the androgen receptor to induce gene expression that leads to the growth and development of masculine sex organs and secondary sexual characteristics. The duration of action of testosterone varies among individuals, with a half-life ranging from 10 to 100 minutes. The therapeutic index is considered wide, as normal testosterone levels in adult men typically range from 300 to 1000 ng/dL. Caution is advised regarding the risk of secondary exposure to topical testosterone products, especially in children.

Pharmacokinetics

Testosterone is absorbed following administration and metabolized primarily by the liver. It has a variable half-life, and its plasma levels are influenced by factors such as the method of administration and individual patient characteristics. Testosterone undergoes conversion into dihydrotestosterone (DHT) and estradiol, which contribute to its physiological effects. Excretion occurs primarily through urine, with metabolites being eliminated from the body. Regular monitoring of testosterone levels and related parameters is recommended during therapy.

Contra-indications

• Pregnancy
• Breastfeeding
• Metastatic prostate cancer
• Known hypersensitivity to testosterone or any of its excipients
• Severe hepatic impairment
• Severe renal impairment

Adverse effects

• Acne
• Gynaecomastia
• Polycythaemia
• Mood changes
• Sleep apnoea
• Fluid retention
• Increased risk of thromboembolic events
• Increased prostate-specific antigen (PSA) levels

Interactions

• Somatrogon: Unknown (decreases concentration)
• Anticoagulants: Potential for enhanced anticoagulant effect
• Corticosteroids: Increased risk of fluid retention
• Insulin: May affect insulin sensitivity

Precautions

• Monitor haematocrit and haemoglobin before treatment
• Regular monitoring of prostate and PSA levels in men over 45 years
• Consider potential androgen toxicity in elderly patients
• Careful risk/benefit assessment in patients with cardiovascular conditions
• Caution in patients with a history of liver disease

Pregnancy

Avoid as it can cause masculinisation of the female fetus.

Breast-feeding

Avoid as testosterone may be excreted in breast milk.

Storage

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

Formulations

• Injectable solution
• Transdermal patch
• Topical gel
• Oral capsule

Indications

• Epilepsy
• Seizure disorders
• Focal seizures
• Generalized seizures

Dosage

Children: Refer to the relevant clinical guidelines or prescribing information for specific dosage recommendations.

Adults: Refer to the relevant clinical guidelines or prescribing information for specific dosage recommendations.

Mechanism of action

Isocarproate functions by modulating voltage-gated sodium channels, thereby inhibiting the excessive firing of neurons. Additionally, it enhances the inhibitory neurotransmitter GABA's action, leading to increased chloride influx into neurons, which contributes to hyperpolarization and decreased neuronal excitability.

Pharmacodynamics

The pharmacodynamic properties of isocarproate include its ability to reduce the frequency and intensity of seizures. It achieves this by altering neurotransmitter release and modulating synaptic transmission in the central nervous system. The drug is effective in suppressing both focal and generalized seizures.

Pharmacokinetics

Isocarproate is absorbed well after oral administration, with peak plasma concentrations occurring within 2 to 4 hours. It is metabolized in the liver, primarily via glucuronidation, and has a relatively short half-life, requiring multiple daily dosing to maintain therapeutic levels. The drug is excreted mainly through the urine, with a small percentage of unchanged drug present.

Adverse effects

• Drowsiness
• Dizziness
• Nausea
• Gastrointestinal disturbances
• Allergic reactions

Precautions

• Caution in patients with hepatic impairment
• Monitor for CNS depression when used with other CNS depressants
• Use with caution in the elderly

Pregnancy

Isocarproate should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus. Consult a healthcare professional before use.

Breast-feeding

It is not known whether isocarproate is excreted in human milk. Caution should be exercised when administering to breastfeeding women.

Storage

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

Indications

• Pain relief
• Inflammation reduction
• Fever reduction
• Various therapeutic applications depending on specific phenyl-containing compounds

Dosage

Children: Refer to BNF for Children for dosage recommendations.

Adults: Refer to specific phenyl-containing compound for dosage recommendations.

Mechanism of action

Compounds containing the phenyl group often act by modulating neurotransmitter pathways, inhibiting cyclooxygenase enzymes, or interacting with various receptor sites, depending on the specific drug structure. For example, phenyl-containing analgesics may work by blocking the synthesis of prostaglandins, thus reducing pain and inflammation.

Pharmacodynamics

The pharmacodynamics of phenyl-containing compounds vary widely based on the specific drug, but many exhibit effects such as analgesia, anti-inflammatory activity, or antipyretic properties. The phenyl group can enhance lipophilicity, allowing for better absorption and distribution in the body.

Pharmacokinetics

The pharmacokinetics of phenyl-containing compounds are dependent on their chemical structure. Generally, these compounds have varied absorption rates, metabolism predominantly through hepatic pathways, and excretion primarily via renal mechanisms. The presence of the phenyl group can influence the half-life and bioavailability of the drug.

Pregnancy

Safety during pregnancy is not established. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

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

Storage

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

Indications

• Nutritional supplementation
• Metabolic disorders
• Potential use in energy metabolism enhancement

Dosage

Children: Refer to the BNF for Children for appropriate dosing information as it may vary based on indication and formulation.

Adults: Refer to specific clinical guidelines or consult the BNF for appropriate dosing information as it may vary based on indication and formulation.

Mechanism of action

Phenylpropionate is primarily involved in metabolic processes. It may exert its effects through modulation of fatty acid metabolism and energy homeostasis. Specific pathways include the involvement in β-oxidation and potential interactions with peroxisome proliferator-activated receptors (PPARs), which regulate gene expression related to lipid metabolism.

Pharmacodynamics

Phenylpropionate exhibits properties that can influence lipid metabolism and energy utilization within the body. Its effects on fatty acid oxidation can lead to alterations in energy expenditure. The pharmacodynamic profile is characterized by its ability to impact metabolic pathways, although detailed receptor interactions remain less defined.

Pharmacokinetics

The pharmacokinetic properties of phenylpropionate, including absorption, distribution, metabolism, and excretion, have not been extensively documented in the available literature. As a carboxylic acid derivative, it is likely absorbed through the gastrointestinal tract, metabolized primarily in the liver, and excreted via the kidneys. Further studies would be needed to define specific parameters such as half-life and bioavailability.

Pregnancy

There is insufficient data on the safety of phenylpropionate in pregnancy. It should only be used if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Caution should be exercised when phenylpropionate is administered to a nursing mother. The effects on the breastfeeding infant are not well studied.

Storage

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

Mechanism of action

The androgen receptor exists in the cytoplasm bound to the heat shock proteins HSP90, HSP70, and other chaperones. After binding to an androgen, the androgen receptor dissociates from HSP90 and undergoes a conformational change to slow the rate of dissociation from the androgen receptor. The androgen-receptor complex is transported into the nucleus where it binds to DNA and recruits other transcriptional regulators to form a pre-initiation complex and eventually induce expression of specific genes. Testosterone and its active metabolite dihydrotestosterone (DHT) act as an agonist of the androgen receptor to activate the receptor and upregulate the expression of androgen receptors, promoting the development of masculine sex organs including the prostate, seminal vesicles, penis, and scrotum. Agonism of the androgen receptor is also responsible for the development of secondary sexual characteristics including facial and body hair, enlargement of the larynx, thickening of the vocal cords, and changes in muscle and fat distribution. Low-grade chronic inflammation is commonly found in patients with polycystic ovary syndrome (PCOS) who exhibit hyperandrogenism or hyperandrogenemia. Clinical studies have shown that hyperandrogenemia is closely correlated with low-grade chronic inflammation. However, the mechanism underlying this correlation remains unclear. Recent studies have suggested that adipocytes increase the production of proinflammatory mediators such as interleukin-6 (IL-6) and macrophage chemotactic protein-1 (MCP-1) when the inflammatory signal transduction cascade system is activated by external stimuli. The present study aimed to evaluate the effects of testosterone on the innate signalling and expression of proinflammatory mediators in 3T3-L1 adipocytes, which were or were not induced by lipopolysaccharide (LPS). The effects of testosterone on the expression of proinflammatory mediators, nuclear factor-kappaB (NF-kappaB), and extracellular signal-regulated kinase 1/2 (ERK1/2) signalling pathways were investigated using an enzyme-linked immunosorbent assay, reverse transcriptase-polymerase chain reaction, western blot analysis and an electrophoresis mobility shift assay. Testosterone induces IL-6 and MCP-1, and enhances LPS-induction of IL-6 and MCP-1. However, the effects are not simply additive, testosterone significantly enhanced the effects of LPS-induced inflammation factors. Testosterone induces the phosphorylation of ERK1/2 and NF-kappaB. The effect of testosterone on the expression of IL-6 and MCP-1 is inhibited by PD98059, an ERK1/2 inhibitor, and PDTC, an NF-kappaB inhibitor. The results indicate that testosterone enhances LPS-induced IL-6 and MCP-1 expression by activating the ERK1/2/NF-kappaB signalling pathways in 3T3-L1 adipocytes. Androgens reportedly stimulate the production of erythrocytes, apparently by enhancing the production of erythropoietic stimulating factor.

Pharmacodynamics

Testosterone antagonizes the androgen receptor to induce gene expression that causes the growth and development of masculine sex organs and secondary sexual characteristics. The duration of action of testosterone is variable from patient to patient with a half life of 10-100 minutes. The therapeutic index is wide considering the normal testosterone levels in an adult man range from 300-1000ng/dL. Counsel patients regarding the risk of secondary exposure of testosterone topical products to children.