Calotropis gigantea · PhytoNexus

01 Identity and provenance

Accepted binomial: Calotropis gigantea
Common names: Safed Aak
Family (APG IV): Apocynaceae
Part used: Latex, Root bark
Verification tier: Tier 2 · Verified Clinical columns reviewed and a source is on record.
Reviewer note (2026 audit): Al-Mezaine HS et al. Am J Ophthalmol 2005;139:199-202 | PMC8544100 (South India cohort) | 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. | ROUTE

02 Constituent chemistry

Chemical class	Marker compound	Synthetic analogue in use
Cardenolides	Calotropin, Uscharin Latex, Root bark	Digoxin (FUNCTIONAL/STRUCTURAL - calotropin and uscharin are cardenolides). Latex anti-inflammatory action is histamine- and prostaglandin-mediated.

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: Traditional use in Ayurveda, Siddha and Unani for skin, respiratory and GI complaints. The margin between therapeutic and toxic dose is very narrow. Latex has documented analgesic activity, which masks injury.
Reported adverse effects: OCULAR - the dominant presentation in India. Accidental latex inoculation while plucking flowers (temple offerings to Lord Shiva; flower vendors were 55% of one series) causes SUDDEN PAINLESS blurring with photophobia - pain is often absent because the latex is analgesic, so patients present late. In 29 eyes: 86% presented below 20/60; corneal oedema with Descemet folds in all; iridocyclitis 31%; secondary glaucoma 24%. 93% recovered in 3-14 days with topical steroid, but 74% had persistently reduced endothelial cell count at 3 months - PERMANENT endothelial loss. Also contact dermatitis, vesication; systemic ingestion causes ECG changes and cardiotoxicity.

04 Interaction matrix

Source column, verbatim: CLINICAL: additive with cardiac glycosides and with hypokalaemia-inducing drugs. Topical corticosteroids are the mainstay for ocular exposure.
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 “cardiac glycosides” Find evidence for this pair Map this mechanism
Corticosteroids Endocrine	4Contraindicated	PD-additive + PK-CYP3A4	curated A	Pseudohyperaldosteronism: hypertension, hypokalaemia, oedema, myopathy; C…	why ▾
Class mechanism. Glycyrrhizin inhibits 11-beta-hydroxysteroid dehydrogenase type 2 and prolongs cortisol half-life, potentiating mineralocorticoid effect. Anthraquinone laxatives compound steroid-driven potassium loss, and CYP3A4 inhibition raises systemic corticosteroid exposure. Expected Pseudohyperaldosteronism: hypertension, hypokalaemia, oedema, myopathy; Cushingoid features at unchanged steroid dose. Management Restrict licorice-containing products. Check potassium and blood pressure. Reduce steroid dose if features of excess appear. Onset rapid Evidence A - human data with a cited source Matched on “corticosteroids” 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
Diuretics Renal	4Contraindicated	PD-additive + electrolyte-mediated	predicted D	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 D - in silico rule prediction only Find evidence for this pair Map this mechanism

05 Hazard register

exposure route - ocular inoculation from latex; injury is painle

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.

Calotropis procera Aak	Apocynaceae	Same genus (Calotropis)
Chlorophytum borivilianum Safed Musli	Asparagaceae	Shares the common name "safed"

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
Calotropis procera Aak	Apocynaceae	4	1.00
Senna alexandrina Senna	Fabaceae	4	0.33
Digitalis purpurea Foxglove	Plantaginaceae	3	0.75
Digitalis lanata Woolly Foxglove (Grecian Foxglove)	Plantaginaceae	3	0.75
Nerium oleander Kaner (Oleander)	Apocynaceae	3	0.75
Cascabela thevetia Yellow Oleander	Apocynaceae	3	0.75

10 References and notes

Source column: Basak SK et al. Indian J Ophthalmol 2009;57:232-4. doi:10.4103/0301-4738.49402

Basak SK et al. Indian J Ophthalmol 2009

Basak SK et al. Indian J Ophthalmol 2009 manual

57:232-4. doi:10.4103/0301-4738.49402

doi:10.4103/0301-4738.49402 manual

BibTeX for all 2 records

@article{BasakSKet2009,
  title = {Basak SK et al. Indian J Ophthalmol 2009},
  author = {Basak SK et al.},
  journal = {Indian J Ophthalmol},
  year = {2009},
}

@article{anon,
  title = {57:232-4. doi:10.4103/0301-4738.49402},
  doi = {10.4103/0301-4738.49402},
}

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