Strophanthin as a cardiac stimulant: Historical use and modern perspectives

Table of contents

1. Introduction. 1
2. Botanical origin. 1
3. Geographic distribution. 1
4. Strophanthus genus. 2
5. Physical characteristics of the Strophanthus plant. 2
6. Chemical nature of strophanthin. 2
7. Historical uses of strophanthin. 3
8. Traditional Medicine. 3
9. Cultural significance. 3
10. Early modern use and introduction to western medicine 4
11. Mechanism of action. 4
12. Mechanism of action as a cardiac stimulant. 4
13. Dosage and administration. 5
14. Therapeutic dosage. 5
15. Forms of administration 7
16. Narrow therapeutic window. 7
17. Preparation and formulation. 8
18. Traditional preparations. 8
19. Modern pharmaceutical formulas. 9
20. Challenges of preparation 10
21. Strophanthin in the treatment of cardiovascular diseases. 11
22. Historical use in heart failure. 11
23. Role as a heart stimulant. 11
24. Efficacy and clinical trials. 11
25. Comparison with modern drugs 12
26. Toxicity and safety concerns. 12
27. Cardiotoxicity. 12
28. Symptoms of poisoning. 13
29. Toxicity management. 13
30. Precautions and contraindications. 14
31. Conclusions 14
32. References. 14

 

 

Introduction

Strophanthin has been observed for years as an active ingredient in many herbal and allopathic medicinal products. It is also known as ouabain or g-strophanthin. The use of strophanthin dates back to the early 20th century. Its early use was discovered in Europe and Latin America due to its cardiotonic effects. In Africa, it was used as traditional medicine for several years, especially in areas where newer drugs were unavailable. Chemically, it is a glycoside with significant potential to increase cardiac contractility. It was also abundantly studied for other therapeutic actions before the discovery of better cardiac stimulants such as digoxin, which took its place. It was previously used in animal studies against hypovolemic shock. Later, its use was extended to cardiac pacing and resuscitation in humans [1].

Although largely superseded by more modern treatments, strophanthine continues to be studied for its pharmacological properties and toxicity, with research focusing on its potential use in alternative medicine. It continues to have value in toxicological and pharmacokinetic studies, and its impact on traditional remedies and early heart treatment is recognized in some regions. The following literature provides detailed information on the origin and history of strophanthin, its chemical nature and use in various preparations. Moreover, knowledge of its safety and efficacy profile is essential to understanding the value of its dosage in various cardiac stages, all of which are cited in the sections listed below [2].

Botanical origin

Strophanthin is a chemical ingredient extracted from the poisonous Strophanthus plant. It is both a medicinal and ornamental plant, known for its primitive use in the Apocynaceae family. There are more than 40 species, some of which are woody shrubs and small trees.

Geographical distribution

These plants are mainly native to regions of Africa, especially Southeast Asia, where they are abundant. Species Strophanthus thrive in warm, moist environments, including forests, savannas and riverbanks, where they are well adapted to a variety of habitats. These plants thrive in moderate to high humidity conditions, although they are hardy and can adapt to disturbed or less ideal environments. Although found mainly in their native regions, some species are successfully cultivated outside their natural habitats, with varying success depending on factors such as climate and soil type [3].

Genus Strophanthus

Some of the known Strophanthus species include Strophanthus amboensis, Strophanthus courmontii, Strophanthus gerrardii, Strophanthus hypoleucos and Strophanthus kombe. Strophanthus hispidus, Strophanthus gratus and Strophanthus kombe are species mainly used for the extraction of strophanthin and other active derivatives of this chemical component [4].

Physical characteristics of the Strophanthus plant

The physical characteristics of the Strophanthus plant vary from species to species, depending on its geographic location; like other plant species, Strophanthus is usually acclimated to the region in which it grows, making it suitable for survival. Key features of Strophanthus species include its woody vines and climbing nature, with small woody stems and sometimes resembling small trees. The height of the plants also varies greatly, ranging from 8 to 12 meters, with the tallest vines [5].

The leaves of plants usually have opposite phyllotaxy, meaning that the leaves are arranged on opposite sides and alternate at the nodes. The edges of the leaves are smooth, and the shape is elliptical or small oval. The leaves have a velvety and glossy texture, and the edges of the leaf veins are very distinct. Flowers occur in clusters or bunches and are very small. The color of the flowers varies depending on the species, and they are usually white, yellow, pink and red. The corolla consists of 4 to 5 petals, and the flower has a sweet, aromatic fragrance. The fruit of the Strophanthus plant is characterized by a long, slender capsule containing numerous flat, winged seeds. When ripe, the capsules naturally open, releasing the seeds, usually carried away by the wind. In some species, the fruits can grow up to 30 cm long. The stem and bark are usually woody, and the surface can be smooth or slightly striated. It is often brownish-green to grayish in color. In some species, the bark has a fibrous texture and was traditionally used to make rope [5].

Chemical nature of strophanthin

Strophantine is a cardiac glycoside that affects the cardiovascular system by inhibiting the Na+/K+ ATPase pump, increasing intracellular calcium levels in heart cells. This increase in calcium levels increases the strength of heart contractions, making strophanthine helpful in treating heart failure and arrhythmias. The chemical structure of strophanthin consists of two key components: an aglycone (the non-sugar part) called strophanthidin and a sugar molecule, usually glucose, which forms a glycoside through a glycosidic bond [6].

Strofantidine, a steroid-like molecule with a cardanolide structure, has a lactone ring that plays a key role in its ability to interact with the Na+/K+ ATPase pump. The sugar group improves the bioavailability and solubility of the compound, enabling efficient transport in the bloodstream. Structurally, strophanthidine shares similarities with other well-known cardiac glycosides, such as ouabain and digoxin. It increases cellular sodium concentration, raising calcium levels through the Na+/Ca2+ exchanger and enhancing cardiac contractions. Although strophanthine is effective in therapeutic applications, its potent effects also contribute to its toxicity. Excessive stimulation of the heart can cause dangerous side effects such as arrhythmias, underscoring the need for careful dosing [6].

Historical uses of strophanthin 

Traditional medicine

Cardiac Effects: Traditionally, Strophanthus seeds were extracted for use in congenital and later developed chronic heart disease in central parts of Asia and sub-Saharan Africa. Along with other herbal extracts such as chamomile, beet and ginseng, Strophanthus seeds have been used for their effectiveness in relieving symptoms associated with cardiovascular disease.

Dermal use: A particular active compound in these seeds, called Strophantine, was used orally and dermally in small amounts. External use of Strophantine involved crushing the seeds to form waste, which was then applied to the skin. This promoted wound healing and helped treat skin irritations, eczema, ulcers and sores.

Diuretic use: Strophanthin was also used in ancient times to exert a diuretic effect on the body. It was used in patients suffering from edema to induce a diuresis response in the body.

Other: Interestingly, Strophanthus seeds have a slightly bitter and unpleasant smell due to the toxic compounds they contain. This property has been used historically to repel insects and has been used along with other pungent ingredients [7].

Cultural significance

In some African spiritual beliefs, plants such as Strophanthus are seen as having more than just medicinal value; they possess spiritual power. These plants are often included in rituals to protect communities from harm, and can also play a role in divination, offering wisdom about health, mortality and other aspects of existence. The significance of Strophanthine and Strophanthus seeds is rooted in their dual use for both healing and fighting, symbolizing the interconnectedness of life and death. Deeply associated with traditional African healing practices, the plant embodies balance, respect for nature and spiritual understanding, reinforcing its importance in indigenous cultural traditions [7].

Early modern use and introduction to western medicine

Strophanthus has been used in African traditional medicine for centuries, particularly for its heart-stimulating effects. However, it was not until the 19th century that it came to the attention of medical researchers in Europe and the United States. African healers had long known that the seeds contained cardiac glycosides, which were used to treat heart failure and circulation problems, much like digitalis.

Western interest in the plant grew when scientists studied its medicinal potential in the 19th century. They succeeded in isolating strophanthin, which was soon recognized for its ability to strengthen heart contractions, making it beneficial in the treatment of heart disease. In the late 19th and early 20th centuries, strophanthine was widely used in the West to treat arrhythmias and congestive heart failure. However, due to its toxicity and the risks associated with its narrow therapeutic range, its use had to be carefully controlled. With the advent of safer alternatives such as digoxin, strophanthin's role in cardiac treatment began to decline. Nevertheless, it remains a significant example of how the traditional knowledge of indigenous cultures contributed to the development of Western pharmacology. Although strophanthine is no longer widely used in modern medicine, ongoing research into its potential therapeutic uses, particularly in neurology and antimicrobials, is helping to preserve its place in the broader conversation between traditional and modern scientific medicine [8].

Mechanism of action

Strophantine is a cardiac glycoside that acts primarily by inhibiting the Na+/K+-ATPase pump, a key enzyme that regulates the gradient of sodium and potassium ions across the cell membrane. By binding to the α subunit of this pump, strophanthine blocks its action, leading to the accumulation of sodium inside the cell. This sodium imbalance indirectly induces an increase in calcium levels via the sodium-calcium exchanger, which under these conditions acts in reverse. Calcium influx increases myocardial contractility, which is a key driver of cardiac function [9].

The Na+/K+-ATPase pump pumps three sodium ions out of the cell and brings two potassium ions into the cell, which requires ATP energy. When strophanthin inhibits this pump, sodium ions accumulate in the cell. The sodium imbalance causes the sodium-calcium exchanger, which normally exchanges intracellular calcium for sodium, to reverse its function. This leads to an influx of calcium into the cell, interacting with proteins such as troponin, which increases myocardial contractility (positive inotropic effect) [9].

Mechanism of action as a cardiac stimulant

Strofantin increases the heart's ability to contract, which is particularly beneficial in conditions such as heart failure, in which the heart's ability to pump is reduced. Increased calcium strengthens the contraction of heart muscle fibers, improving the heart's minute capacity and helping to restore normal blood circulation. This effect is particularly valuable in patients with impaired heart function or acute heart failure.

In addition, strophanthine can mildly affect the electrical activity of the heart, slowing the heart rate (negative chronotropic effect) by increasing the vagal voltage. Controlling heart rate can help treat arrhythmias such as atrial fibrillation. The combination of improved contractility and regulated heart rate leads to better oxygen delivery to tissues, alleviating symptoms of heart failure. However, the use of strophanthine is limited due to its narrow therapeutic window. Toxicity can occur at high doses, leading to arrhythmias, gastrointestinal problems and even life-threatening complications. Therefore, careful monitoring is necessary when using this drug [10].

Dosage and administration

The dosage of Strophantine depends on the specific condition being treated, the patient's age and general health. The drug is administered intravenously under controlled clinical conditions, and the dose is adjusted based on the patient's response and monitoring for potential toxicity. It is crucial to start with a lower dose and gradually increase it to avoid side effects, with close monitoring to ensure safe and effective use. More details on the dosage and administration of this pacemaker are given below:

Therapeutic dosage

The therapeutic dose of Strophantine may vary depending on the patient's condition, age and response to treatment. However, typical doses of Strophantine, used as a cardiac stimulant, are as follows:

1. Initial dose (saturating dose)

   • For acute heart failure, Strophantine can be administered intravenously, usually in doses of 0.5 to 1 mg.
   • If necessary, this dose can be repeated after 12-24 hours, depending on the patient's response.

2. Maintenance dose

   • After the initial saturating dose, the maintenance dose is usually 0.25 to 0.5 mg per day, depending on clinical status and individual response.

It is important to note that the healthcare professional should always determine the exact dose based on the patient's specific needs and adjust it carefully to avoid toxicity. Close monitoring for symptoms of overdose, such as cardiac arrhythmias, is essential, as strophanthine has a narrow therapeutic index.

Strofantin, a potent cardiac glycoside, requires careful dose adjustment in patients with hepatic or renal impairment. These conditions can affect the metabolism and excretion of the drug, increasing the risk of toxicity. Depending on the patient's condition, it may also be necessary to adjust the dose based on body weight [11].

Regulation of renal function:

• Renal dysfunction:

  Because Strophantine is eliminated mainly by the kidneys, patients with renal impairment may experience delayed clearance of the drug, increasing the risk of toxicity. In these patients, the dose should be reduced or the interval between doses lengthened.

  • Depending on the severity of mild to moderate renal impairment, a dose reduction of about 25-50% may be necessary.
  • Severe renal impairment may require more significant dose reductions, and in some cases strophanthine may be contraindicated, especially if renal function is significantly impaired.

Liver regulation:

• Liver dysfunction:

  Although the liver does not primarily metabolize strophanthine, hepatic dysfunction can still indirectly affect the pharmacokinetics of the drug, especially when it leads to changes in binding proteins or overall metabolic status. However, hepatic adjustments are generally less critical compared to renal adjustments.

  • In patients with mild to moderate hepatic impairment, no significant dose modification is necessary, but close monitoring is recommended.
  • Strophantine prescription should be carefully considered in cases of severe hepatic impairment, as any toxicity of the drug may be increased due to altered pharmacodynamics.

Weight-based adjustments:

• Dosage based on body weight: Although strophanthine dosing is usually not highly dependent on body weight, some cases may require consideration of body weight, especially in pediatric or very young adult patients. In such cases, an individualized approach should be taken, starting at a lower dose and titrating based on clinical response and toxicity monitoring.
  • A lower starting dose (e.g., 0.02 mg/kg) is generally recommended for pediatric patients and then gradually adjusted based on clinical response.
  • For obese patients, while body weight may not significantly affect dosage, dosage adjustments based on lean body mass can sometimes be considered to avoid excessive drug accumulation.

General guidelines for dose adjustments:

• Monitoring:

  Regular monitoring of serum electrolytes (especially potassium and calcium) and renal function is crucial for dose adjustments. Electrolyte imbalances can exacerbate the toxic effects of strophanthin.

• Clinical response:

  Dose adjustments should always be based on clinical response to achieve optimal therapeutic effects while minimizing the risk of toxicity.

Ultimately, Strophantine dosage should be individualized based on careful assessment of the patient's renal and hepatic function, body weight and response to treatment. Monitoring for signs of toxicity, including arrhythmias, gastrointestinal disturbances, and effects on the central nervous system, is essential to ensure the safe use of the [12].

Forms of administration

Strophantine is usually available by injection and is administered under close medical supervision. The two routes of Strophantine administration are as follows:

1. Intravenous (IV) injection

   • Strofantin is most often administered intravenously in hospital or clinic settings. Intravenous injection allows for rapid absorption and onset of action, making it particularly useful in acute situations such as heart failure or arrhythmias.

2.  intramuscular (IM):

   • Strofantin, although less frequently, can also be administered intramuscularly in some cases, especially when intravenous access is not possible. Intramuscular injection leads to slower absorption compared to the intravenous route.

Strofantin is available in only one dosage form: solution for injection. The solution can be administered intravenously or intramuscularly. The concentration of the solution usually varies, but it is often supplied as a 0.25 mg/mL or 0.5 mg/mL solution. Strofantin in oral form was available on the market several years ago in tablet form, but it has been withdrawn.

Narrow therapeutic window

A narrow therapeutic index is the small margin between the minimum effective and minimum toxic doses of a drug. Small changes in drug dose or blood levels can lead to serious side effects or reduced effectiveness. Given the risks associated with the use of Strophantine (due to its narrow therapeutic index and potential toxicity), it is usually only available in hospitals or health care facilities where health care professionals can closely monitor a patient's response to the drug. Oral or other non-injectable forms are not usually available for Strophantine drug [13].

Preparation and formulation

Traditional preparations

Strophanthin extracts and tinctures are traditionally prepared by extracting the active compounds from the seeds or leaves of the Strophanthus plant, which contains potent cardiac glycosides.

Preparation of strophanthin extracts:

To prepare the extract, the plant's seeds are first harvested and dried in a shaded, cool place to prevent degradation of the active compounds. After drying, the seeds are ground into a fine powder. The powdered material is soaked in a solvent, usually alcohol (ethanol) or a mixture of water and alcohol, to extract the active ingredients, including the seed glycosides. The soaking process, known as maceration, usually lasts from several days to weeks, depending on the desired concentration of the extract. After maceration, the mixture is filtered to separate the liquid extract from plant residues. The resulting liquid is concentrated by evaporation of the solvent, yielding a more potent extract containing the therapeutic components of Strophantine

Preparation of tinctures from strophanthin:

The process is similar to that used for tinctures, but involves soaking the plant material in ethanol or other suitable alcohol. The typical ratio of plant material to alcohol is about 1:5 or 1:10, with the alcohol acting as a solvent to extract the bioactive compounds. The mixture is left to steep for 1-2 weeks, shaking occasionally to improve the extraction process. After steeping, the liquid is strained to remove plant matter, leaving a tincture that contains concentrated active ingredients.

Due to the potency of strophanthin, these traditional preparation methods require careful handling and precise dosing. Its cardiac glycosides can be toxic if not used properly. In modern medicine, strophanthin is often administered in more controlled pharmaceutical forms rather than in crude herbal preparations.

Shelf life of strophanthin extracts and tinctures:

The shelf life of Strophantine extract and tincture is usually 1 to 3 years, depending on storage conditions and the type of solvent used. Both should be stored in a cool, dry place away from direct sunlight, heat and air to preserve their potency. Extracts and tinctures should be stored in airtight, preferably dark glass containers to prevent degradation. The alcohol in tinctures helps preserve the active ingredients, but prolonged exposure to light or air can reduce their effectiveness. It is important to observe any expiration dates listed by the manufacturer and regularly check the preparation for any changes in appearance, color or odor that may indicate a loss of potency or potential degradation. Proper storage ensures the stability and safety of formulations [14].

Modern pharmaceutical formulas

Modern pharmaceutical preparations of Strophantine are typically manufactured in controlled environments to ensure precise dosage and consistency, minimizing the risk of toxicity. Unlike traditional herbal extracts or tinctures, which are prepared with less control, modern pharmaceutical preparations standardize active ingredients, ensuring both safety and efficacy.

Extraction and purification

The process begins with the extraction of strophanthin from the seeds of the Strophanthus plant using advanced solvent extraction techniques. Ethanol or a mixture of ethanol and water is commonly used as the solvent. The plant material is finely ground and then macerated with the solvent to extract the cardiac glycosides. After extraction, the solvent is removed by evaporation, leaving a concentrated extract containing strophanthin. This extract undergoes further purification processes, such as chromatography, to isolate and purify the active glycosides, ensuring a precise concentration of the active compound.

Formula:

The purified Strophantine extract is then formulated into specific pharmaceutical dosage forms, most commonly solutions for injection or suspensions for injection. These are prepared to meet strict concentration standards, with exact amounts of the active ingredient measured and standardized to ensure therapeutic efficacy. Solutions for injection are usually mixed with stabilizing agents, preservatives and solvents to maintain stability and prevent microbial contamination.

Quality control and standardization:

Strophantine's modern pharmaceutical preparations undergo rigorous quality control tests. These include potency, purity and sterility tests. Each batch of Strophantine is analyzed to ensure that it contains the right amount of active glycosides and is free of impurities. In addition, stability tests are conducted to ensure that the drug retains its efficacy and safety throughout its shelf life.

Stability and durability:

Modern Strophantine formulations, particularly solutions for injection, are designed to be stable over time. Several factors affect stability, including the type of solvents used, the composition of preservatives and packaging. To increase stability, manufacturers use stabilizing and preservative agents to prevent degradation and microbial contamination. The active compound, Strophantine, is sensitive to factors such as light, temperature and exposure to air, which can cause degradation and loss of potency. Therefore, these formulations are usually packaged in airtight, light-resistant containers and stored under controlled conditions [15].

The shelf life of modern pharmaceutical preparations of Strophantine is usually 2 to 3 years if stored properly. Strophantine should be stored in a cool, dry place away from direct sunlight and temperature extremes to preserve potency. Freezing or exposure to high temperatures can compromise the stability of the drug, so manufacturers recommend storage at controlled room temperature, typically 59°F to 77°F (15°C to 25°C). Be sure to check the expiration date on the package before use. Once opened or diluted, shelf life may be shortened, and proper storage instructions should be strictly followed to avoid loss of effectiveness. Regular quality control tests ensure that the drug remains effective and safe throughout its shelf life, confirming that it meets specifications for potency and sterility [14].

Challenges of preparation

Preparing pure and effective forms of strophanthin for clinical use presents several challenges, mainly due to the potency of the plant and the need for precise dosing. Purity and standardization are difficult to achieve because the concentration of active glycosides can vary naturally depending on the plant species, environmental factors and the age of the plant. Advanced extraction methods such as chromatography are required to isolate strophanthin, but they are time-consuming and expensive. In addition, the extraction process must protect the glycosides from degradation caused by light, heat or oxygen.

Formulating stable, safe and effective pharmaceutical formulations is also a challenge. Strophanthin's toxicity and narrow therapeutic index mean that even small changes in dosage can have serious consequences. Stability is critical, requiring careful packaging in light-resistant, airtight containers to prevent degradation. Complex regulatory and manufacturing requirements also add to the cost and difficulty of producing strophanthin. These challenges underscore the need for rigorous quality control, safe formulation practices and careful patient monitoring [16].

• The variability of plant material makes it difficult to maintain purity and standardization.
• Advanced extraction techniques are required, but they are costly and time-consuming.
• Strophanthin is sensitive to degradation, requiring careful formulation and storage.
• The narrow therapeutic index makes accurate dosing crucial to avoid toxicity.
• Strict regulatory guidelines and manufacturing processes increase production costs.

Environmental and ethical issues

Sustainable harvesting and ethical considerations in the use of Strophanthus plants are key to ensuring that the species remains viable for future use, while minimizing environmental impacts. Over-harvesting, especially of wild populations, can threaten the plant's natural habitat and reduce biodiversity. Responsible harvesting practices are essential to promote sustainability, such as growing Strophanthus plants in controlled environments or through sustainable cultivation methods. In addition, ethical considerations include ensuring fair trade practices and the welfare of local communities involved in harvesting, ensuring fair compensation and promoting environmental protection. Ensuring that the harvesting and use of the plants is done with both environmental sustainability and social justice in mind is critical to the long-term viability of strophanthin-based products

Strophantine in the treatment of cardiovascular diseases

Historical use in heart failure

Strophanthin, extracted from the seeds of the Strophanthus plant, has a rich history of treating heart failure, arrhythmias and other cardiovascular conditions. In the past, the plant was used by indigenous African and Asian peoples to treat heart disease, and its potent cardiac glycosides were considered key to improving heart function. In the late 19th century, Strophanthus gained recognition in Western medicine as a treatment for heart failure and congestive heart failure, mainly due to its ability to increase the strength of heart contractions. A potent cardiac stimulant, strophanthin was often used when other treatments, such as digitalis, failed or caused side effects. Despite its effectiveness, it was gradually replaced in the 20th century by more reliable, modern drugs.

Role as a heart stimulant

Strophantine acts as a cardiac stimulant through its active compound, ouabain, a type of cardiac glycoside. It increases the force of heart muscle contractions by inhibiting the Na+/K+-ATPase pump, which maintains the ionic balance in the membranes of heart cells. This inhibition raises intracellular sodium levels, increasing the concentration of calcium in heart cells. Higher calcium levels increase myocardial contractility, improving heart function, especially in heart failure. The positive inotropic effect of strophanthin also helps stabilize abnormal heart rhythms, making it valuable in treating irregular heart rhythms. It is particularly beneficial in severe heart failure, in which the heart has difficulty pumping blood efficiently [17].

Efficacy and clinical trials

Clinical studies of strophanthine have shown its effectiveness in increasing cardiac output and alleviating heart failure symptoms, although its use has declined in favor of modern drugs. Early studies showed that strophanthine could increase myocardial contractility, improve circulation and reduce fluid retention, which is common in patients with heart failure. However, contemporary studies show limited use of strophanthine, mainly due to the availability of safer alternatives. For example, it is sometimes compared to digoxin, another cardiac glycoside. Some studies indicate that strophanthine may have a more favorable side effect profile than digoxin, with a shorter half-life and potentially lower risk of toxicity. However, the clinical use of strophanthine remains limited due to better established drugs such as digoxin [18].

Comparison with modern drugs

Compared to modern drugs such as digoxin and beta-blockers, strophanthine is now less commonly used. Digoxin, like strophanthine, works by inhibiting the Na+/K+-ATPase pump to increase cardiac contractility. However, digoxin has been more extensively studied, with established dosing protocols and a long half-life, making it more predictable for treatment. Beta-blockers are now preferred for the treatment of heart failure because they reduce heart rate, lower myocardial oxygen demand and improve survival rates, with proven mortality benefits. While Strophantine was once the drug of choice for treating heart failure and arrhythmias, modern drugs such as digoxin and beta blockers offer more reliable, safer and effective therapeutic options [19].

Toxicity and safety concerns

Cardiotoxicity

Strophantin, a potent cardiac glycoside derived from the seeds of the Strophanthus plant, carries a significant risk of cardiotoxicity when used inappropriately or in excessive amounts. Strophanthin's therapeutic index is narrow, meaning that the margin between an effective dose and a toxic dose is very small. Overdose of strophanthine can result in serious cardiovascular effects due to its effects on the electrolyte balance of the heart. The drug works by inhibiting the Na+/K+-ATPase pump, which is required to regulate the concentration of sodium and potassium ions in cardiac cells. This inhibition leads to an increase in intracellular sodium levels, which in turn increases the concentration of calcium ions in heart cells. Increased calcium levels increase myocardial contractility, but also interfere with the heart's normal electrical conduction, which can cause arrhythmias (irregular heart rhythms).

If excessive amounts of strophanthine are taken, the positive inotropic effect becomes excessive, causing an irregular or excessively strong heartbeat. This can result in ventricular fibrillation, atrial arrhythmia and even cardiac arrest. Bradycardia (slow heart rate) is another common symptom of strophanthine toxicity, as the drug can interfere with normal cardiac stimulation. Untreated arrhythmias and electrical disturbances can lead to cardiogenic shock and heart failure. The risk of toxicity is extremely high in patients who are also receiving other drugs that affect heart rate or electrolyte balance, such as diuretics, which can lead to hypokalemia (low potassium levels). This condition exacerbates the toxic effects of cardiac glycosides [20].

Symptoms of poisoning

Symptoms of strophanthine poisoning can vary depending on the severity of the overdose, but usually start with gastrointestinal symptoms, which are common with glycoside toxicity. These include nausea, vomiting and diarrhea, which often occur soon after an overdose. As toxicity progresses, more severe symptoms develop, mainly involving the cardiovascular and nervous systems. Patients may experience bradycardia, palpitations or irregular heart rhythms such as premature ventricular contractions or atrial fibrillation. Visual disturbances, such as blurred vision or seeing yellow halos around lights, are also typical of glycoside toxicity and are considered a hallmark symptom.

In more severe cases of poisoning, patients may show symptoms of heart failure, including pulmonary edema (accumulation of fluid in the lungs) and circulatory collapse. Hypotension (low blood pressure) is a common feature of severe poisoning, especially in patients with prolonged cardiac arrhythmias or shock. Electrolyte imbalances, especially low potassium levels, low magnesium levels or high calcium levels, can worsen the situation, making it crucial to closely monitor these levels in patients receiving Strophantine. Because these symptoms can escalate quickly, it is extremely important to recognize the signs of poisoning quickly to prevent fatal outcomes.

Toxicity management

Treatment of strophanthine toxicity begins with immediate discontinuation of the drug. If a patient has life-threatening cardiac arrhythmias or severe symptoms, treatment will depend on the nature and severity of the toxicity. In mild cases, careful monitoring and supportive care may be sufficient, but more aggressive interventions are needed in more severe cases.

Suppose a patient is experiencing arrhythmias, particularly ventricular fibrillation or other life-threatening rhythms. In such a case, antiarrhythmic drugs such as lidocaine or phenytoin may be warranted to stabilize the heart's electrical activity. Potassium supplementation is often necessary to correct hypokalemia, since low potassium levels increase the risk of arrhythmias while taking Strophantine. In some cases, magnesium supplementation may also be given to prevent torsades de pointes, a specific form of arrhythmia associated with glycoside toxicity.

Digoxin-specific antibodies may be considered to reverse the effects of severe toxicity, although they are more commonly used for digoxin toxicity than strophanthine. Atropine can be used to treat bradycardia (slowing of the heart rate), while electrical cardioversion or defibrillation may be necessary if the arrhythmia is refractory to drug therapy. Close monitoring of the patient's electrolyte levels, heart rhythm and vital signs is crucial during treatment. In some cases, hospitalization in an intensive care unit for continuous observation and intervention may be required.

Precautions and contraindications

Several precautions should be observed when using Strophantine, mainly due to the risk of toxicity and potential side effects. Renal insufficiency is a significant risk factor for Strophantine toxicity, as the drug is eliminated mainly by the kidneys. Patients with renal failure may have impaired clearance of Strophantine, leading to accumulation and increased toxicity. Similarly, patients with liver disease may have altered metabolism of the drug, requiring dose adjustments.

Strofantin should be used with extreme caution in patients with electrolyte imbalances, especially hypokalemia, hypomagnesemia or hypercalcemia, as these conditions increase the likelihood of dangerous cardiac arrhythmias during treatment with cardiac glycosides. The drug is contraindicated in patients with known hypersensitivity to strophanthine or other glycosides, as severe allergic reactions may occur. Patients with ventricular arrhythmias, severe heart failure or heart block should avoid Strophantine, as its use may exacerbate these conditions [21].

Applications

Strophanthin, derived from the Strophanthus plant, has historically been important in the treatment of heart failure and arrhythmias due to its ability to increase myocardial contraction. It works by inhibiting the Na+/K+-ATPase pump, increasing intracellular calcium levels and improving cardiac function. Despite its early success, strophanthine's narrow therapeutic index and risk of toxicity, along with the emergence of safer and more effective alternatives such as digoxin and beta-blockers, have led to its decline in modern medical use. Although its use has declined, it remains a significant example of natural agents contributing to advances in medicine[16]

Disclaimer

This article was written for educational purposes and is intended to raise awareness of the substance under discussion. It is important to note that the article is about the substance in general - it is not a description of a specific product (chemical reagent). We do not suggest the use of chemical reagents on humans - this is prohibited by law, for a product to be used for treatment it must be registered as a drug. The information contained in the text is based on available scientific research and is not intended to serve as medical advice or promote self-medication. The reader should consult any health and treatment decisions with a qualified health professional.

 

References

1. Doepp, M.J.A.J.o.M., C. Research, and Reviews, May Strophanthin be a valuable cardiac drug? 2023. 2 (9): s. 1-6.
2. Doepp, M.J.R.B., Strophanthin, an excellent cardiac drug. 2023. 3 (03): s. 356-359.
3. Kombe, S.K.-S., Strophanthus seed. Strophantus Kombe (Strophantus Kombe) - a plant of the cuticular family.
4. Condy, G., Strophanthus amboensis Apocynaceae: Apocynoideae.
5. Fraser, T.R.J.E. and E.S.T.o.T.R.S.o. Edinburgh, XXI.-Strophanthus hispidus: its Natural History, Chemistry, and Pharmacology. 1890. 35 (4): p. 955-1027.
6. Grosa, G., et al, LC-ESI-MS/MS characterization of strophanthin-K. 2005. 38 (1): s. 79-86.
7. Bonah, C.J.H. and technology, "The Strophanthin question: Early scientific marketing of cardiac drugs in two national markets (France and Germany, 1900-1930). 2013. 29 (2): s. 135-152.
8. Bhalla, A., et al, Native medicines and cardiovascular toxicity, w Heart and toxins. 2015, Elsevier. p. 175-202.
9. Pogorelova, V., A. Panait, and A.J.B. Pogorelov, Nonspecific effect of Na+/K+-ATPase inhibition with strophanthin or under hypothermia in rat heart. 2014. 59 : p. 768-771.
10. Fuerstenwerth, H.J.A.J.o.T., Ouabain-The key to cardioprotection? 2014. 21 (5): s. 395-402.
11. Bonah, C., "We need for digitalis preparations what the state has established for serumtherapy...'From Collecting Plants to International Standardization: The Case of Strophanthin, 1900-38., w Evaluating and Standardizing Therapeutic Agents, 1890-1950.. 2010, Springer. s. 202-228.
12. Anderson, K.-E., et al, Cardiac Glycosides: Part II: Pharmacokinetics and Clinical Pharmacology. 2012: Springer Science & Business Media.
13. Fürstenwerth, H.J.I.j.o.c.p., Ouabain-the insulin of the heart. 2010. 64 (12): s. 1591.
14. POULTON, P.-E., DISCUSSION ON THE NEW PHARMACOP (EIA.
15. Ganatra Tejas, H., et al, A SYSTEMIC REVIEW ON CHALLENGES WITH CURRENTLY AVAILABLE CARDIOTONICS AND THEIR SAFER HERBAL ALTERNATIVES USED IN INDIA. 2012. 2 (1): p. 11-23.
16. McKenzie, A. The rise and fall of Strophanthin. w International Congress Series. 2002 Elsevier.
17. Hambarchian, N., et al, Ouabain increases myofibrils' Ca2+ sensitivity, but does not affect Ca2+ release in human skin fibers. 2004. 492 (2-3): p. 225-231.
18. Mohammadi, K., et al, Positive inotropic effect of ouabain on isolated heart is accompanied by activation of signal pathways that link Na+/K+-ATPase to ERK1/2. 2003. 41 (4): p. 609-614.
19. Zulian, A., et al, Activation of c-SRC underlies differential effects of ouabain and digoxin on Ca2+ signaling in arterial smooth muscle cells. 2013. 304 (4): p. C324-C333.
20. Botelho, A.F., et al, Comparative cardiotoxicity of low doses of digoxin, ouabain, and oleandrin. 2020. 20 : p. 539-547.
21. Reynolds, A., M.L.J.C.J.o.P. Horne, and Pharmacology, Studies on the cardiotoxicity of ouabain. 1969. 47 (2): s. 165-170.