Cascabela thevetia · PhytoNexus

01 Identity and provenance

Accepted binomial: Cascabela thevetia
Common names: Yellow Oleander
Family (APG IV): Apocynaceae
Part used: Seed
Verification tier: Tier 2 · Verified Clinical columns reviewed and a source is on record.
Reviewer note (2026 audit): de Silva HA et al. Lancet 2003;361:1935-8 (MDAC RCT) | Rajapakse S. Clin Toxicol 2009. PubMed 19306191 | VERIFIED 2026 (batch 2) - synthetic analogue, application, interactions, side effects and references populated from retrieved primary/regulatory sources. Interactions labelled CLINICAL vs THEORETICAL. Marketed-formulation column intentionally blank. | DIAGNOSTIC

02 Constituent chemistry

Chemical class	Marker compound	Synthetic analogue in use
Cardiac glycosides	Thevetin A & B Seed	Digoxin, Digitoxin (TRUE STRUCTURAL analogue - thevetins and neriifolin are cardenolides inhibiting Na+/K+-ATPase).

The analogue column is what makes the interaction reasoning tractable: where a constituent has a marketed structural counterpart, the counterpart's interaction profile is the starting hypothesis for the plant.

Looking up structures and physicochemical properties from PubChem…

03 Stated application

Reported activity: No accepted therapeutic use. Toxicological reference only. Seed ingestion is a major method of self-harm in Sri Lanka and India, with tens of thousands of cases annually in South Asia.
Reported adverse effects: Nausea, vomiting, abdominal pain, diarrhoea; hyperkalaemia; brady- and tachyarrhythmias, sinus and AV nodal conduction block. Case-fatality about 10% in Sri Lanka. Typically affects young patients with no cardiac comorbidity - unlike digoxin toxicity.

04 Interaction matrix

Source column, verbatim: CLINICAL: additive with digitalis glycosides and hypokalaemia-inducing diuretics. LABORATORY: cross-reacts with digoxin immunoassays. TREATMENT EVIDENCE: anti-digoxin Fab reduces life-threatening arrhythmia and pacing need (RCT, Lancet 2000). NEGATIVE FINDING: multiple-dose activated charcoal showed NO mortality benefit in a 4632-patient RCT (6.3% vs 6.8% deaths, adjusted OR 0.96, 95% CI 0.70-1.33) - do not assume MDAC helps.
Normalised onto 2 canonical drug classes below.

Curated from the reviewed source

Drug class	Severity	Mechanism type	Provenance	Expected effect
Cardiac glycosides (digoxin, digitoxin) Cardiovascular	4Contraindicated	PD-additive + PK-transporter + assay interference	curated A	Nausea, xanthopsia, bradyarrhythmia, AV block, ventricular tachycardia an…	why ▾
Chemistry of this pair. Cardenolides and bufadienolides inhibit the sarcolemmal Na+/K+-ATPase directly, which is the same target as prescribed digitalis. Class mechanism. Cardenolide- and bufadienolide-bearing plants are themselves Na+/K+-ATPase inhibitors, so co-administration is pharmacological overdose. Several also inhibit intestinal P-glycoprotein, raising digoxin exposure, and cross-react with digoxin immunoassays so that serum levels become uninterpretable. Expected Nausea, xanthopsia, bradyarrhythmia, AV block, ventricular tachycardia and death; falsely reassuring or falsely high assay results. Management Treat as an absolute contraindication. If exposure has occurred, manage on ECG and clinical grounds, not on assay values, and consult toxicology about digoxin-specific Fab. Onset rapid Evidence A - human data with a cited source Matched on “digitalis glycosides” Find evidence for this pair Map this mechanism
Diuretics Renal	4Contraindicated	PD-additive + electrolyte-mediated	curated A	Hypokalaemia, hyponatraemia, dehydration, muscle weakness, cramps, arrhyt…	why ▾
Chemistry of this pair. Cardenolides and bufadienolides inhibit the sarcolemmal Na+/K+-ATPase directly, which is the same target as prescribed digitalis. Class mechanism. Aquaretic and saluretic botanicals add to renal potassium and sodium loss. Anthraquinone laxatives compound this through colonic potassium loss, and glycyrrhizin causes mineralocorticoid-like retention of sodium with kaliuresis. Expected Hypokalaemia, hyponatraemia, dehydration, muscle weakness, cramps, arrhythmia; potentiation of digoxin toxicity through low potassium. Management Check potassium, sodium and creatinine 1-2 weeks after starting. Avoid the combination entirely in patients also on digoxin. Onset rapid Evidence A - human data with a cited source Matched on “diuretics” Find evidence for this pair Map this mechanism

Predicted from constituent chemistry

These edges are not clinical findings. Each one is a rule inference: a constituent class in this plant is known to act on a target that the drug class also acts on. They are shown because a blank cell reads as “safe”, and for a Tier 1 entry a blank cell only means “not yet looked at”. Treat them as a literature-search agenda, not as a warning.

Drug class	Severity	Mechanism type	Provenance	Expected effect
Antiarrhythmics Cardiovascular	4Contraindicated	PD-additive + electrolyte-mediated	predicted D	Proarrhythmia, QT prolongation, torsade de pointes, ventricular arrhythmi…	why ▾
Chemistry of this pair. Cardenolides and bufadienolides inhibit the sarcolemmal Na+/K+-ATPase directly, which is the same target as prescribed digitalis. Class mechanism. Botanicals that shift potassium or magnesium, block sodium or potassium channels, or prolong repolarisation add to class I and class III antiarrhythmic effects on an already unstable myocardium. Expected Proarrhythmia, QT prolongation, torsade de pointes, ventricular arrhythmia. Management Avoid. If unavoidable, baseline and follow-up ECG with QTc measurement plus potassium and magnesium correction. Onset rapid Evidence D - in silico rule prediction only Find evidence for this pair Map this mechanism

05 Hazard register

assay interference - cross-reacts with digoxin immunoassays. Ant

06 Confusable material

These entries could be mistaken for this one in trade, in the herbarium, or in a prescription. Powdered material is often indistinguishable, so the check is macroscopic, microscopic and chromatographic rather than nominal.

Nerium oleander

Kaner (Oleander)

Apocynaceae

Shares the common name "oleander"

07 Mechanism map

Chemistry sorts to the left, pharmacology to the right. Dashed edges are predicted. Drag nodes, scroll to zoom, export at 3× for a figure.

species

chemical class

marker compound

drug class

expected effect

hazard

08 Open literature

Abstract-scoped query built from this binomial, its common names and its marker compounds, run live against Europe PMC, PubMed and OpenAlex, then ranked locally against an evidence hierarchy.

Checking openFDA spontaneous reports…

09 Isomechanistic neighbours

Species whose interaction profile overlaps this one, ranked by shared severity weight rather than by count — a shared contraindication counts for more than a shared minor signal. Practical use: these are the plants you should not stack with this one, because the mechanisms summate.

Species	Family	Shared classes	Jaccard
Digitalis purpurea Foxglove	Plantaginaceae	3	1.00
Digitalis lanata Woolly Foxglove (Grecian Foxglove)	Plantaginaceae	3	1.00
Nerium oleander Kaner (Oleander)	Apocynaceae	3	1.00
Urginea indica Indian Squill	Asparagaceae	3	1.00
Drimia maritima European Squill	Asparagaceae	3	1.00
Convallaria majalis Lily of the Valley	Asparagaceae	3	1.00

10 References and notes

Source column: Eddleston M et al. Lancet 2000;355:967-72 (anti-digoxin Fab RCT)

355:967-72 (anti-digoxin Fab RCT)

Randomised controlled trial manual

Eddleston M et al. Lancet 2000

Eddleston M et al. Lancet 2000 manual

BibTeX for all 2 records

@article{anon,
  title = {355:967-72 (anti-digoxin Fab RCT)},
}

@article{EddlestonM2000,
  title = {Eddleston M et al. Lancet 2000},
  author = {Eddleston M et al.},
  journal = {Lancet},
  year = {2000},
}

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