Plant Blog Entry: Oleander

Introduction:

Nerium Oleander, most commonly known as Oleander or Nerium, is a toxic shrub in the Apocynaceae family and is commonly cultivated as a landscaping plant in more temperate climates (1). Figure 1: Picture of Oleander Plant (2)

Oleander has both toxicological and pharmacological properties (1). The main mechanism through which Oleander exhibits toxic effects is through the presence of cardiac glycosides, which inhibit cardiac Na+/K+-ATPase (1).

 

Biotransformation:

Oleander contains many different toxic phytochemicals, but the main cardenolide present in Oleander is Oleandrin (1).

Figure 2: Chemical structures of cytotoxic phytochemicals and cardiac glycosides present in Oleander (1)

 

Oleandrin is similar in structure to digoxin, which is a cardiac glycoside that can be used therapeutically. The gut microbiome is responsible for  metabolizing cardiac glycosides, and since Oleandrin is similar in structure to digoxin, there is evidence that shows the gut microbiome is likely to dictate the pharmaco-toxicological effects of oleander (1).

Figure 3: Biotransformation of oleander that shows the role of the gut microbiome in the metabolism of cardiac glycosides (1).

 

Toxicokinetics and Mechanism of Action:

Oleander’s toxicity comes from the presence of cardiac glycosides in all parts of the plant (1). However, the roots and seeds contain the highest amount of these cardiac glycosides (1). These cardenolides inhibit the Na+/K+-ATPase pump on cardiomyocytes, which leads to a buildup of Na+ in those cells (1).

 Figure 4: Oleandrin is a cardiac glycoside that inhibits the Na+/K+-ATPase pump, which leads to an increase in intracellular Na+. The increase of sodium increases the amount of calcium in the cell, which causes cardiac muscle contraction and vasoconstriction (1).

At therapeutic doses, cardiac glycosides can be effective in treating cardiac arrhythmias and congestive heart failure because they can cause an increase in the force of cardiac contractions while also reducing heart rate (3).  However, cardiac glycosides have a narrow therapeutic range, and because Oleandrin is highly lipotoxic, and has rapid gastrointestinal absorption, and slow urinary excretion, it can result in a fatal poisoning (1).

Toxicity:

  • Carcinogenicity
    • There is no evidence suggesting that oleander is carcinogenic
  • Mutagenicity
    • No evidence to suggest that oleander is mutagenic
  • Teratogenicity
    • No evidence to suggest oleander is teratogenic
  • Hepatotoxicity
    • Clinical evidence does show some hepatotoxicity (1)
  • Cardiac toxicity
    • Oleander primarily effects the heart as oleandrin acts as a cardiac glycoside

Target Organs and Signs and Symptoms of Toxicity:

Oleandrin effects the following organ systems(4):

  • Cardiovascular System
  • Gastrointestinal System
  • Nervous System
  • Skin (in cases of contact with Oleander sap)

Signs and Symptoms of Toxicity (4):

  • Nausea, vomiting, and/or diarrhea
  • Fever and headache
  • Decrease in heart rate (bradycardia) or blood pressure (hypotension)
  • Pain in stomach or abdomen
  • Confusion, disorientation
  • Numbness and loss of sensation
  • Vision Abnormalities, i.e. blurred vision
  • Skin rashes or hives from allergic reaction
  • Feeling dizzy or faint
  • In severe cases:
    • Depression and appearance of halo around objects may be seen

Treatment:

In addition to supportive treatment, the following treatments are used in cardiac glycoside poisonings:

Figure 5: Table of treatments for general cardiac glycoside poisoning. Note that dosing may need to be higher in cases of yellow oleander poisoning because of the inability to adequately quantify the body burden based on blood tests (5).

 

If appropriate treatment is received, oleander poisonings, even intentional, do not have to be fatal. However, it should be noted that children are particularly susceptible to poisoning, and as little as the ingestion of one leaf could be fatal to a child (6), whereas an adult could live through the ingestion of a handful of leaves (6).

 

Summary:

  • Oleander is a toxic plant that contains oleandrin, a toxic phytochemical that is similar in structure to digoxin, another cardiac glycoside
    • Oleandrin affects the Na+/K+-ATPase pump, which can affect how the heart contracts and heart rate
    • Oleander also affects the gastrointestinal system and nervous system, in addition to the cardiovascular system
  • Symptoms of a poisoning include:
    • Gastrointestinal symptoms
      • Nausea, vomiting, and diarrhea
    • Cardiovascular symptoms
      • Heart arrhythmias
      • Bradycardia
      • Hypotension
    • Nervous system symptoms
      • Dizziness
      • Fainting
      • Blurred vision or seeing a halo around objects
  • Treatments include:
    • Airway stabilization and supportive treatments
    • Activated charcoal if close to time of ingestion
    • Anti-Digoxin FAB
    • Atropine
    • Insulin/Dextrose
  • If treated in time, the prognosis for oleander poisoning is good, with few fatalities
    • However, children are more susceptible to smaller doses
    • If treatment is not sought, either in time or at all, oleander poisoning can be fatal

 

 

Resources:

  1. Dey, Priyankar. “The Pharmaco-Toxicological Conundrum of Oleander: Potential Role of Gut Microbiome.” Biomedicine & Pharmacotherapy, Elsevier Masson, 18 June 2020.
  2. [Photo of Oleander Plant] 2020. Retrieved from https://hgic.clemson.edu/factsheet/oleander
  3. Ambrosy, Andrew P. et al. “The Use of Digoxin in Patients With Worsening Chronic Heart Failure: Reconsidering an Old Drug to Reduce Hospital Admissions”,
    Journal of the American College of Cardiology, Volume 63, Issue 18, 2014 1823-1832.
  4. Tangella, Krish. “First Aid for Oleander Poisoning”, DoveMed, 28 February 2018.
  5. Roberts, Darren M., et al. “Pharmacological Treatment of Cardiac Glycoside Poisoning.” Br J Clin Pharmacol. 81:3. 488-495
  6. “Nerium Oleander L.” Nerium Oleander L. IPCS INCHEM. Accessed 28 July 2020.