Lecture 21 Cardiovascular Toxicology-II Flashcards
- What plant is pictured below?
- What does this plant do?
- Where can this be sourced from?
- Where is the toxin concentrated/located in the plant?
- Gossypol (Bi-naphthyl-aldehyde)
- Makes the cotton plant more insect-resistant
- cotton plants (Gossypium spp.); Cotton seed, cottonseed meal, cottonseed cake
- Toxin is concentrated in glands within the seeds
What plant is pictured below?
Gossypol (Bi-naphthyl-aldehyde)
Cottonseed is widely used in what industry?
Livestock Feed Industry
Cottonseed is high in what?
How much does it cost to use?
What is cottonseed deficient in?
- High protein (26-40%)
- High fiber (17-20%)
- High fat (23%)
- High energy content (91% total digestible
nutrients [TDN]) - Economical
- BUT it is deficient in essential amino acids
(lysine & tryptophan), vitamins (A & D)
and minerals (calcium)
What species are susceptible to Gossypol (Bi-naphthyl-aldehyde)?
- Monogastrics (but horses are relatively
resistant) - Ruminants are resistant (young cattle are not)
* Gossypol binds to soluble protein components in rumen liquor –> reduced toxicity - Sheep and poultry are of intermediate
sensitivity - Maximum gossypol allowed in swine and
poultry feed is 100 ppm –> Gossypol regulation in feed followed massive deaths of swine and poultry in 1900s
What is the ADME of Gossypol (Bi-naphthyl-aldehyde)?
◦ Gossypol occurs in _____ and _____ forms
◦ The _____ form is more bioavailable and toxic
◦ Exposure is always ____
◦ Gossypol accumulates in ? but not in ____
◦ Gossypol occurs in free and bound forms
◦ The free form is more bioavailable and toxic
◦ Exposure is always oral
◦ Gossypol accumulates in plasma, heart, liver,
muscle and testis but not in milk
What is the MOT of Gossypol (Bi-naphthyl-aldehyde)?
______ myocardial _______
- Destroys cardiac muscle and interferes with ________ by affecting ___ movement
Has anti-________ effects in males (Damages ________ epith., decreased sperm _______) and females (Suppresses ______ and _________)
Chelates _____ and causes lysis of RBCs –> ____
Binds ______ _____ in GI tract making them
unavailable for absorption
Inhibits ________ synthesis
Induces nutritional deficiencies:?
Focal myocardial necrosis
- Destroys cardiac muscle and interferes with conduction by affecting K+ movement
Has anti-fertility effects in males (Damages spermatogenic epith., sperm motility) and females (Suppresses estradiol and progesterone)
Chelates iron and causes lysis of RBCs anemia
Binds amino acids in GI tract making them
unavailable for absorption
Inhibits protein synthesis
Induces nutritional deficiencies: vit. A & E, Ca, and amino acids
What are the clinical signs of Gossypol (Bi-naphthyl-aldehyde) toxicosis?
May present as ________ death or ______ _______ breathing (‘_______’ in pig) unresponsive to _________ therapy
Gradual heart ______ (edema, _____ vein
distension, congestion)
Anorexia, weakness, rough hair-coat/poor-doer
and death
Cattle may display decreased heat tolerance and hemoglobinuria
Reproductive problems: decreased male & female fertility
May present as sudden death or chronic labored breathing (‘thumping’ in pig) unresponsive to antibiotic therapy
Gradual heart failure (edema, jugular vein
distension, congestion)
Anorexia, weakness, rough hair-coat/poor-doer
and death
Cattle may display decreased heat tolerance and hemoglobinuria
Reproductive problems: decreased male & female fertility
Sudden death in Gossypol toxicosis is misdiagnosed in what species?
Mis-Dx in lambs: over-eating
Chronic labored breathing in Gossypol toxicosis is misdiagnosed as what?
Mis-Dx: pneumonia
How do you Dx Gossypol (Bi-naphthyl-aldehyde) toxicosis?
History of extended feeding of _________ meal
or ___________ products
Clinical signs, especially _____ death or chronic _____
Lack of response to _________ therapy
Postmortem lesions: signs of _________
are the most important
Analytical detection of significant concentrations of ____ gossypol in feed
◦ Must be correlated with history, clinical signs, and PM findings
History of extended feeding of cottonseed meal
or cottonseed products
Clinical signs, especially sudden death or chronic
dyspnea
Lack of response to antibiotic therapy
Postmortem lesions: signs of cardiomyopathy
are the most important
Analytical detection of significant
concentrations of free gossypol in feed
◦ Must be correlated with history, clinical signs, and PM findings
How do you Tx Gossypol (Bi-naphthyl-aldehyde) toxicosis?
There is no effective Tx
Remove source (withdraw cottonseed
products from diet)
Activated charcoal and saline cathartics are
of little value
◦ Gossypol toxicosis entails chronic exposure and is cumulative in nature
Treat heart failure and pulmonary edema
Give nutritional supplements (vitamin A, Fe,
lysine and protein)
All toads produce _______, but venom potency
varies with ________ and __________ _________.
venom, species, geographic, locations
The most toxic toads in North America are?
◦ Rhinella marina formerly Bufo marinus (cane or
marine toad)
◦ Bufo alvarius (Colorado River toad)
Toxic toads are primarily found in ?
FL, TX, CO, AZ, HI
Which species are susceptible to toxic toads?
Dogs and sometimes cats and ferrets
Avoid “toad-licking” and “smoking toad”!
Sacrament for Church of the Toad of Light
What are the toxic principles of Toxic toad toxicosis?
Christine Sucks Balls In Bed
Bufadienolides (bufagenins and bufotoxins)
◦ Structurally similar to cardiac glycosides
Bufotenine
Catecholamines (dopamine, epinephrine,
norepinephrine)
Serotonin
Indolealkylamines
Toxicity of toxic toads is variable, based on?
Variable depending on size of toad and dog
◦ Severe toxicoses result when small dogs
encounter large toads (larger parotid glands
= more secretions = more toxins)
◦ 1mg secretion per kg bw results in clinical
signs of intoxication
Describe the ADME of toxic toad toxicosis.
Exposure is usually in the summer and during
periods of high humidity
Toxins are produced and stored in the parotid
glands which are along the neck and
parascapular region of the toad
When mouthed/bitten by a dog/cat, toads
release toxins in a thick milky-white substance
via pores on the parotid glands
The toxins are rapidly absorbed via the buccal
mucous membranes. They can be absorbed via
GI tract mucosa, broken skin and conjunctiva
Elimination is via urine
What are the main exposure periods of toxic toads?
Main exposure periods
* Summer
* Late summer/fall
* Periods of high humidity
What is the MOT of toxic toad toxicosis?
Bufadienolides are ________ ________-like
substances that inhibit ____/____/______
◦ Also affect voltage-gated ____, _____, and _____ channels → disruption of excitable cells
Bufotoxins cause ___________
Bufotenine has systemic ______ activity and
is a __________
Indolealkylamines are ______________
Catecholamines are ____________
__________ and ___________ act
synergistically to produce greater cardio-
respiratory effects
Bufadienolides are cardiac glycosides-like
substances that inhibit Na+,K+-ATPase
◦ Also affect voltage-gated Na+, K+, and Ca2+
channels → disruption of excitable cells
Bufotoxins cause vasoconstriction
Bufotenine has systemic pressor activity and
is a hallucinogen
Indolealkylamines are hallucinogenic
Catecholamines are arrhythmogenic
Catecholamines and bufadienolides act
synergistically to produce greater cardio-
respiratory effects
What are the clinical signs of toxic toad toxicosis?
Rapid onset, death can occur in 15 min
Brick-red buccal cavity mucous membranes,
hypersalivation, vomiting, vocalization, pawing
at the mouth, and foaming at the mouth
Anxiety, disorientation, ataxia, falling, blank
stare, mydriasis, nystagmus, hyperactivity,
hyperesthesia, opisthotonus, convulsions/
seizures, recumbency, coma
Tachypnea, hyperthermia, acidosis (metabolic
and/or respiratory) and hyperkalemia
Cardiac glycoside-like effects
◦ Arrhythmias (bradycardia, sinus tachycardia,
atrioventricular block, supraventricular and
ventricular tachycardia, ventricular fibrillation)
◦ Sudden death
How do you Dx toxic toad toxicosis?
History of witnessed exposure and clinical
signs