plant toxins and the heart

toxin types

aconite alkaloids

taxus alkaloids

cardiac glycosides

sodium-potassium pump

high sodium out and low potassium out

pump causes opp for balance using ATP hydrolysis

action potential is in

excitabel cells

neurosn and muscles

electrical conduction system of human heart

modified cardiac cells: SA node, AV node, His bundle, Purkinje fibers

certain sequence is key

aconite alkaloids

family Ranunculaceae

aconitine in aconitum spp.

aconitum spp

monkshood/wolfsbane

known as arrow poison

aconitine

From buttercups, causes Na channels to open early and stay open longer

agonist of voltage gated sodium channels

causes of aconitine

contamination, adulteration, inadequate processing of roots, large doses, mistakenly consumed

warning: wear gloves and not lotion

aconitine symptoms

weakness, numbeness, vomiting, dizziness, arrythmia, coma, death

acotinine structure

has a piperidine with ring with NH at top

aconitum spp plant

spirea japonica

rosacaea

toxin from veatchine group, least toxic

traditional chinese medicine

aconite alklaoids

aconite alkaloids types

aconitine

atisine

veatchinine

taxus alkaloids

taxaceae

taxus spp. (yew)

Taxus spp.

yew

ornamental shrub/tree

red aril is only nontoxic

often highly manicured and trimmed

non flowering confier

aril

acessory covering of certain seeds that commonly develops from seed talk, found in both angisperms and gymnosperms

juniper berry

Cupressaceae fam

juniperus L.

female seed cone of junipers

only spice known from conifers

for flavor gin

taxus baccata L

yew

taxine B

taxine B

in plant parts

red aril edible

antagonist Ca and Na channels

hypotension, cardiac arrest, death

drugs and taxus

some useful anti-cancer drgs

semisynthetic approaches

6 trees per patient

paclitaxel

Taxus spp toxin

binds tubulin to prevent breakdown and induce apoptosis

often used in combo with other drugs

docetaxel

taxus toxin

semi-synthetic analogue

Cardiac Glycosides types

from many families

cardinolide and bufadieaolides

cardiac glycosides structure

sugar: carbon rings with many hydroxyl groups

and nonsugar (aglycone)

glycosdic bond between

cardenolide

bufienolide

cardiac glycosides mechanism and effects

binds and disables cardiac Na/K pump

cellular sodium increases causign calcium increase

intracellular Ca causes muscle contraction (troponin)- irregular, intense contractions, death

cardiac glycosides treatment

atropine

stimulates heart

Apocynaceae (Dogbane Family)- Cardiac glycosides

most toxic

some produce cardioactive steroids and otehrs produce monoterpene indole alkaloids with nerbous system effects

monarch butterfly and milkweed plant

apocynace fam

cardiac glycoside relation

Asclepias spp

store toxins in adult stages

nerine oleander butterfly

nerum oleander

apocynace fam

cardiac glycoside relation

oleandrin

whole plant is toxic, fresh, or dried- smoke and sticks/stirring

oleandrin

strophanthus kombe

apocynacaea fam

cardiac glycoside

g-Straophanthin (onabain)

arrow poisons kill elephants

onobain

increased cardiac output

less readily absorbed by GI tract

rapidly eliminated

plantaginaceae family-cardiac lgycosides

foxglove fam

digitalis lanata

digitalis lanata

digoxin

digoxin

used in systematic heart failure (weak LV, doesnt pump properly), increased cardiac output and decreased hospitalizations

digoxin vs digitoxin?

Ranunculaceae fam- cardiac glycosides

adonis spp (pheasants eyes): can kill horses if eaten

families in cardiac glycosides

apo, plant, ran, aspa

Asparagaceae fam- cardiac glycosides

convullaria majalis (lily of valley), convallotoxin

convallotoxin

other cardiac plant toxins

khat-catha edalis (celastraceae): chewed for centuries, used where alcohol prohibited, moved around world by expatriates

mistletoe