clinical pathophysiology f toxic plants

clinical & pathological effects of toxic plants.

Presented to - Dr. Divakaran Nair.Prof. & HOD, Dept. of VPP. COVAS, Pookode.

Course no. VPP-609.Toxicopathology.

Presented bySindhu K.

M. V. Sc. Scholar,Dept. Of VPT.

Overview

• Introduction• Classification of toxic plants• Clinical & pathophysiology of toxic plants• Plants producing various poisoning• Treatment & management of poisoning plants

Toxic plant may be defined as “one which detrimentally affects the health of man or animal when eaten in such amount as would be taken normally or under special circumstances like restriction of choice of diet or extreme hunger”.

EtymologyTOXIN Toxon (Greek) for bow & arrow Toxicon poison dipped arrow

POISON Poi to drink & becoming potare in

Latin (potion) Venomous nature derived from wen to

win, & led to venus/venerate through “love potions” (venin)

Sec. plant Metabolites• The toxic (active) principles present in the

plants = PHYTOTOXINS.• Plant toxins may be referred as SPM.• SPM defense mechanism / survival

adaptations.Toxic plants are of 2 types• Plant containing toxic ingredients & are

known to be toxic to animals.• Plants which are normally not toxic to animals

but becomes so under unfavorable conditions.

Classification of toxic plants

I. Alkaloids II. Terpenes III. GlycosidesIV. Proteinaceous compoundsV. Organic acidsVI. Resins & Resinoids

Tropane/atropine like alkaloids

Atropine

Datura (jimsonweed)Erythroxylum (coca tree)Hyoscyamus (henbane)Mandragora (mandrake)

Pyrrolizidine alkaloids

Retronecine

Senecio (ragwort)Crotalaria sp.Heliotropium sp.Trichodesma sp.

Pyridine/Piperidine alkaloids

Conium (Hemlock)Lobelia (Indian tobacco)

Pyrrolidine-pyridine alkaloids

Nicotine

Nicotiana sp. (Tobacco)Equisetum sp. (Horse tail)

Purine alkaloids

caffeine

Coffea sp. (Coffee)Theobroma sp. (Cocoa)Camellia sp. (Tea)

Quinoline alkaloids

Quinine

Cinchona sp. (Quinine tree)Echninops sp. (Globe thistle)

Isoquinoline alkaloids

Morphine

Papaver somniferum (opium)Sanguinaria sp.Dicentra (Blood root)

Indole/indolizidine alkaloids

Strychnine

Strychnus (strychnine)Claviceps (Ergot)Psilocybe (Magic mushroom)Astragalus sp. (locoweed)Gelsemium sp.

Quinolizidine alkaloids

Anagyrine

Laburnum sp. (Golden chain)Baptisia sp. (False indigo)Cytisus sp. (Scotch broom)

Steroidal glycoalkaloids

Solanidine

Lycopersicum sp. (Tomato)Solanum sp. (Nightshades)

Steroidal alkaloids

Jervine

Veratrum sp.Zigadenus sp.

Diterpenoid alkaloids

Aconitine

Delphinium sp. (Larkspur)Aconitum sp. (Monkshood)

Phenylamine alkaloids

Ephedrine

Lophophora sp. (peyote)Ephedra sp.

Terpenes Biosynthesized by plants

Contains the branched 5-carbon skeleton of isoprene.

On the basis of number of isoprene units present in the

structure of the molecule, terpenes are categorized as

C-10 compounds monoterpenes

C-15 compounds sesquiterpenes

C-20 compounds diterpenes

C-30 compounds triterpenes

Monoterpenes• Cantharidine an animal

monoterpene from fly ash.• Picrotoxin from Anamirta

cocculus (Fish berries).

Sesquiterpenes• Coramyrtin from Coriaria

myrtifolia• Geigerin from Geigeria• Helenalin from Helenium

microcephalum

Diterpenes• Andromedotoxin• Mezerein • Aconitine from Aconitum

sp.

Triterpenes• Cicurbitacins (toxic principles of

bittergourd)• Lantadenes from Lantana sp.

Glycosides Complex organic compounds having glycone attached to

aglycone/genin moiety by ether linkage

Neutral in reaction

Soluble in alcohol, less soluble in water & insoluble in

ether

They don’t combine with acids to form salts

Names ends with suffix –in.

Eg: digitoxin, ouabin, scillarin, glycyrrhizin, senegin.

Cyanogenic glycosides

Amygdalin

Amygdalin (Almond seed)HCN in Hydrangea, Linum (Linseed)Prunus (Wild cherry)Sorghum vulgare (Jowar) Sorghum sudanese (Sudan grass)Gossypol (cotton seed)

Steroidal (cardionilides/

cardiac glycosides) Digitoxin

Digoxin from Digitalis sp.Oubain from Strophanthus Convallarin from ConvallariaAscleipas (Milk weed)Nerium oleander

Steroidal (saponigenic glycosides)

Argostemme (Corn cockle)Phytolacca (Poke weed)Hedera (English ivy)

Coumarin glycosides

Esculin

Ausculus glabraMoldy Meliolotus sp. (White sweet clover)Ipomoea sp. (Sweet potato)

Anthraquinone glycosides

Cassia fistula (Senna)Aloe sp.

Mustard glycosides

Sinigrin

Thiocyanates/isothiocyanates of mustard oil.(Brasssica nigra)

Proteinaceous compounds Plant proteins = harmless + beneficial agents.

Plant protein + seed reserve proteins important source of

food.

Ingestion protein hydrolysis enzymatic reactions in GIT

absorption of amino acids protein biosynthesis in the body.

However; there are no. of proteins, peptides/amines which

are of toxicological importance.

Eg: toxalbumins, polypeptides, amines.

Toxalbumins (proteins)

• Abrin from Abrus precatorius

• Ricin from Ricinus communis

Polypeptides • Amatoxins, phallotoxins & phalloidin from Amanita sp.

Amines• Aminotryptaline from seeds of Sativus

odoratus• Phoradendron sp. (Berries of mistle

toe)• Mimosine from Mimosa pudica• Canavanine from Canavalia ensiformis

(Jack beans)• Leucaena leucocephala (Subabul)

Organic acidsAcids accumulated in plants, particularly in their fruits

but are non-toxic.1. Malic acid2. Tartaric acid3. Citric acid4. Ascorbic acidBut other plant acids possess significant toxic property

solely due to their acidityEg: plant oxalic acid & its soluble Na, K or NH4 salts.

Oxalic acid & soluble salts• Oxalic acid• Potassium oxalate• Sodium oxalate

Resins & resinoidsToxic plant resins = phenolic compounds Important naturally occurring phenolic resin in plants Exists as amorphous & brittle solids Insoluble in water, soluble in organic solvents (alcohol,

chloroform & ether)I. TetrahydrocannabinolII. HypericinIII. Urushiol

Tetrahydrocannabinol

• Cannabis sativa (marijuana or hemp)

Hypericin • Hypericum perforatum

Urushiol• Poison ivy• Poison oak• Rhus sp.

CLINICAL & PATHOLOGICAL EFFECTS

• Specific action of toxicantsReceptor mediated, ionic channels, enzyme mediated, carrier molecules mediated events.• Non specific action of toxicantsPhysical toxicants, direct chemical injury, interference with body metabolism, impairment of O2 transport, injury to vascular system, altered Ca++ homeostasis, immunomodulations, carcinogenesis, non-specific action on enzymes & proteins, tissue residual effects.

General Clinical signs affecting systems

1. CNS: ConvulsionCyanide, nitrate, strychnine, OP, Carbamates, Picrotoxin. Coma Bromide, CO, Nicotine, Morphine, ZnP. Ataxia OP, carbamates, Thallium.2. Digestive system:Nausea, vomiting & diarrhoea heavy metals, fluoride, paraffin, muscarine, OP. Constipation Opioids, Oxalate producing plants. Hypersalivation OP &

Carbamates.Dry mouth Atropine, Opioids & Phenothiazines.

3. Respiratory system:Dyspnoea Opioids, OP, cyanide, nitrate & nitrite producing plants, strychnineHyperpnoea aspirin, isoniazid, atropine, nicotine, apomorphine.Slow respiration atropine late stage

4. Skin. Hair & nails:Cyanosis (metHb.) nitrite producing plantsPhotosensitisation Lantana camara, Alopecia alkali sulphide, X-radiation

5. Urogenital tractsUrinary retention atropine, opioids

Micturation & incontenance OP & CarbamatesCrystalluria oxalates, amaranthus.

Poisonous plants • Cyanogenetic plants• Plants producing lathyrism• Plants producing thiamine deficiency• Plants producing Photosensitization• Datura & related plants• Oleander & Cardiotoxic plants.• Plants containing toxic lectins/ castor bean

poisoning.• Ipomoea poisoning• Cotton seed/gossypol poisoning• Nux vomica poisoning.

Cyanogenetic plants• Eucalyptus, kappa/ tapioca, sorgum/corn, linseed cake,

bitter almond.• MOA: HCN + trivalent iron of cytochrome oxidase

inhibits ETC

• Tissue anoxia in brain • Peracute & acute toxicity, chronic toxicity.• restless, laboured & quick breathing, stumbling gait,

tachycardia, salivation, lachrymation, mydriasis, cyanotic mucus membrane & bitter almond smell.

• Sodium nitrite & Sodium thiosulphate.

Cattle & sheep @ 20 mg/kg slow IV followed

by sod. Thiosulphate @ 500 mg/kg slow IV

as 25% soln.

Dogs & cats @ 25 mg/kg slow IV as 1 %

soln. followed by sod. Thiosulphate @ 1.25

g/kg slow IV as 25% soln.

Horses @ 16 mg/kg slow IV as 1 % soln.

followed by sod. Thiosulphate @ 30-40

mg/kg slow IV as 20 % soln.

Plants producing lathyrism

• Legume lathyrus / wildpea / Khesari dal• Osteolathyrism – BAPN (irreversible inhibition

of lysyl oxidae)• Neurolathyrism – ODAP (symmetrical axonal

degeneration)

Osteolathyrism & Neurolathyrism

Plant producing thiamine deficiency• Braken fern/ pteridium aquilinum

• Toxic principles – Thiaminase, aplastic anaemia factor, Ptaquiloside, haematuria factor, Quercetin.

• Cattle: bleeding from body orifices Urogenital, Nostrils, GIT, severe BM depression, thrombocytopenia, HYPHEMA, enzootic haematuria, death due to anaemia.

• Horses: emaciation, lethargy, wt. loss, recumbancy followed by muscular tremors, clonic spasms & Opisthotonus, colic, braken staggers, haemolytic crisis.

Oxalate accumulated plants• Sarcobatus, rheum, beet.• Ruminants/ Cattle • Soluble potassium &

sodium oxalates.• MOA- form complex with

serum Ca++ hypocalcemia muscular weakness, CNS depression, CVS collapse.

Plant producing

photosensitisation• Primary Hypericin, fagopyrin

• Secondary senecio sp. Lantana sp.

Plants producing

allergic stomatitis • Lantana

• Acacia• Dracula stromonium• Jatropa leaves/ cake• Abrus spp

Strychnos nux vomica poisoning• Alkaloid – strychnine & brucine

Treatment of poisoning

• Preventing continuous absorption of toxicant

• Preventing distribution of toxicant to target site

• Increasing threshold level of toxicity• Hastening elimination of absorbed toxicant• Enhancing metabolic conversion of

absorbed toxicant.

Preventing continuous absorption of toxicant

• Gastric lavage• Adsorption theraphy• Purgation/ cathartics• Enema• Cleansing of eyes/ skin/ hairs• Gastrotomy/ rumenotomy• Dilution• Complex formation

Preventing distribution of toxicant to target site

• Ion-trapping• Alternate binding site• Complex formation

Increasing threshold level of toxicity

• Rx for resp. depression• Monitoring cardiac disturbances• Control of shock• Control of acidbase disturbances• Maintenance of uresis• Rx of Hypo/Hyper thermia

Hastening elimination of absorbed toxicant

• Ion-trapping• Dialysis• Diuresis• Specific treatment