Lecture 9- toxicants affecting the cardiac and respiratory systems

arrhthmias

Bradycardia - Tachycardia

AV blockade

QT Prolongation

what will happen when a arrhythmia occurs

decrease cardiac function

chronic heart toxicity will cause

hypertrophy

malignant arrhythmia

xenobiotics can cause

etal gene expression causing heart hypertrophy

cell death causing heart failure

anti- arrhythmics

Na channel block, β blocker, K channel block, Ca channel block

inotropics

glycosides, Ca sensitizing, sympathomimetics

CNS drugs

phenothiazines, tricyclic antidepressants – postural hypotension

local anesthetics

cocaine, lidocaine, bupivacaine – Na channel block

anthracyclines

doxorubicin – ROS induced cardiomyopathy

antineoplastics drugs

5-fluorouracil (ECG), cyclophosphamide (hemorrhagic necrosis)

antibiotics

Aminoglycocides – reduce Ca channel, Ca binding

Macrolides - erythromycin

Flouroquinolones - moxifloxicin

antihistamines

terfenedine, astemizole

prokinetic drug

cisapride

methylxanthines

theophylline, caffeine

sildenafil

PDE 3 inhibitors

Ionophores – carboxylic polyether antibiotics, isolated from Streptomyces cinnamonensis

given as feed additive, coccidiostat

what does monensin do to horses

prolong depolarization, repolarization, V-tach, AV block

what does monensin do to cattle

QT, QRS prolongation, 1 degree AV block, muscle damage

ionophore toxicity often the result of

mixing error at feed mill

 tri-aza-pentadiene compound used in flea collars of dogs.

amitraz

amitraz exerts toxicity by

inhibiting the enzyme monoamine oxidase and works as an a2- adrenergic receptor agonist

cardiac effect of a2 adrenergic agonists

bradycardia, first and second degree atriventricular and diminished cardiac output

good example of meloidae consumption

blister beetle

where can blister beetle be found

alfalfa fields where large swarms tend to congregate

when the fields are harvested the blister beetles are crushed and incorporated into the bales of hay

blister beetles contain what

cantharidin that is an inhibitor of the serine- threonine protein phosphatase

cantharidin blocks

the adenosine A1 receptors which regulate myocardial oxygen consumption, yielding anti adrenergic effect in ventricular cardiac myocytes

cardiac symptoms of cantharidin

increased heart rate and myocardial dysfunction and often colic in horses

thumps- diaphragmatic contraction due to hypocalcemia

signs of bufo toad poisoning

profuse, sometimes frothy salivation,

accompanied by vigorous head shaking,

pawing at the mouth, and retching

Cardiac and CNS involvement can be life-

threatening

how do bufo toads poison

parotoid glands secrete a milky- white fluid known as bufotoxin a mix of steroid lactone sthat include glycosides (bufadienolides) as well as epinephrine, norepinephrine, and serotonin

where are foxglove found

roadsides and meadows

foxglove

toxic principles of fox glove

Several digitalis glycosides.

All parts of the plant contain the toxic components; both fresh and dry material are

toxic.

toxicokinetics of foxglove

Absorbed from the GI tract and Half-life in dogs is 16 to 40 hours.

GI involvement eliminated by hepatic metabolism and in the urine.

including anorexia, colic and diarrhea often precede CV signs.

mechanism of toxicity of foxglove

inhibition of Na K pump resulting primarily in intracellular calcium imbalance and cardiac rhythm disturbances

toxic dose foxglove

has not been determine for plant material but blood level > 3 ng/ml are toxic in dogs

what causes during digitalis cardiac toxicity

Sinus bradycardia and arrest

A/V block (usually 2nd degree)

Atrial tachycardia with A/V Block

Development of junctional rhythm PVC’s, VT/ V fib (bi-directional VT)

milkweed

toxic priniple of milkweed

cardenolides

galitoxin

toxicokinetics of milkweed

depending on the animal and plant symptoms usually appear within hours

mechanism of toxicity for milkweed

Several digitalis glycosides.

All parts of the plant contain the toxic components; both fresh and dry material are

toxic.

clinical signs of milkweed

begin with ataxia, depression, and weakness, labored breathing and in severe cases cardiac arrhythmias and seizures

oleander nerium

toxic principles of oleander nerium

cardiac glycosides, oleandrin and neriine being the principle toxic agents

what is the most toxic part of oleander nerium

red flowers

toxicokinetics of oleander nerium

readily absorbed from the GI tract; large dose can be fatal within an hour

lilly of the valley

toxic principle of lilly of the valley

cardiac glycosides, convallotoxin

azalea

toxic principle of azalea

grayanotoxins

mechanism of toxicity of azalea

bind to voltage gated sodium channel producing a state of depolarization

diagnosis of azalea

depression, excess salivation, vomiting, bradycardia, arrhythmias, and seizures

mountain laurel

what part of mountain laurel is the most poisonous

green part, flowers, twigs, and pollen

toxic principle of mountain laurel

grayanotoxins

mechanism of toxicity of mountain laurel

bind to voltage gated sodium channel producing a state of depolarization

clinical signs of mountain laurel

initial symptoms are excessive salivation, perspiration, vomiting, dizziness, weakness and paresthesia in the extremities and around the mouth, low blood pressure and sinus bradycardia

avocado toxic principle

persin

most poisonous part of avocado

leaves, bark, skin or pit

what does persin cause

myocardial necrosis

what can persin do to lactating animals

hemorrhage of mammary gland

kalanchoe

toxic principle of kalanchoe

bufadienolides

when do clincial signs show for kalanchoe

after consuming 7 mg/ kg

dogbane

what does dogbane contain

a resin, apocynin, and cardiac glycoside similar to foxglove digitalis

what animal is most affected by dogbane

sheep

cottonseed

what is the major toxic ingredient in cottonseed

gossypol

prolonged exposure to cottonseed can cause

acute heart failure resulting from cardiac necrosis; hepatic, renal, reproductive, or other systems may also be affected

what type of animals are most affected by cottonseed

monogastrics

Yew Taxus

toxic principle of yew taxus

taxine alkaloids

mechanism of toxicity of yew taxus

taxine alkaloids produce direct effects on cardiac ion channels resulting primarily in conduction disturbances