Nicotinic and Adrenergic Toxicants Flashcards
What are nicotinic receptors selectively blocked by?
hexamethonium
What are the most common early signs of nicotinic stimulation? What are some clinical signs?
CNS stimulation
- salivation, lacrimation
- emesis, diarrhea
- tachycardia, tachypnea
- shallow, slow respiration
- collapse, coma
- cyanosis
- bradycardia, weak pulse
- cardiac arrest
- excitation/depression
- muscle weakness, tremors, convulsions
- paralysis, loss of reflexes
What are the main sources of nicotine? What potent effect does it tend to have?
- plants
- tobacco products
- nicotine gum
- snuff
- nicotine sulfate (insecticides, immobilizing agent)
emetic effect —> limits absorption
What is the mechanism of toxicity of nicotine? How does it affect the adrenal medulla and CNS?
mimics ACh at sympathetic and parasympathetic ganglia, NMJ, and CNS causing immediate stimulation followed by a blockade
- causes the release of catecholamines
- stimulates chemoreceptor trigger zone to cause emesis
What is the major clinical sign of nicotine poisoning?
nicotinic stimulation followed by depression and paralysis
What is recommended for decontamination for nicotine poisoning? How can hyperthermia be resolved?
- emesis if orally exposed within past 1 hr
- gastric lavage, activated charcoal, catharsis, whole bowel irrigation
- wash animal with warm water and mild hand dishwashing soap with dermal exposure
external cooling with tepid running water and/or fanning
What drugs are recommended to control seizures associated with nicotine poisoning? With severe bradycardia?
- benzodiazepines: Diazepam, Lorazepam
- barbiturates
Atropine
What is a good way to hasten nicotine excretion?
acidification of the urine with ammonium chloride
Where is Tobacco (Nicotiana spp.) most commonly found? Why is risk of toxicity low?
all US, mostly in SW states
plant in unpalatable and animals will stay away if good quality forage is available
What are the 3 toxic principles of Tobacco (Nicotiana spp.)? What species are affected?
- pyridine alkaloids - nicotine
- teratogens - anabistine, anatabine
- polycyclic aromatic hydrocarbons (PAHs) - produced upon combustion (carcinogenic, mutagenic, teratogenic)
cattle, swine, sheep, horses, birds
What are some clinical signs of Tobacco (Nicotiana spp.)?
- dullness
- vomiting, salivation, diarrhea
- abdominal cramps
- bloat, colic
- frequent urination
- muscular weakness
- staggering, trembling, shivering, spasms, tremors
- 3rd eyelid protrusion, blindness
- prostration, opisthotonus
- irregular and weak pulse, heart palpitation
- elevated body temperature with colt extremities
- diaphragmatic spasms, respiratory paralysis, dyspnea, death
What is the main clinical signs of Tobacco (Nicotiana spp.) associated with swine?
TERATOGENESIS - pregnant sows may give birth to piglets with arthrogryposis if exposed within 35 days of gestation, causing prolongation of parturition and death of the piglet from neonatal asphyxiation
(sows do not show signs of toxicosis before giving birth to malformed piglets)
How can Tobacco (Nicotiana spp.) be diagnosed?
- history of exposure and clinical signs
- confirm by identifying nicotine or other nicotine-like alkaloids in blood, urine, GI contents, liver, or kidney
What are the main 2 options for decontamination of Tobacco (Nicotiana spp.) Which is most common?
- emesis or enterogastric lavage
- administer activated charcoal*
most cases are in livestock
What is recommended for treating the parasympathetic effects of Tobacco (Nicotiana spp.)?
Atropine
What is Conium maculatum (poison hemlock) known to contaminate? Where does it grow?
hay and grain
most of USA and southern Canada
What is the toxic principles of Conium maculatum (poison hemlock)? What 2 chemicals are present in each stage of the plant’s growth?
piperidine alkaloids
- LATE STAGES (seeds) = coniine
- EARLY STAGES = γ-coniceine (most toxic)
What species are most sensitive to Conium maculatum (poison hemlock)? What is the mechanism of toxicity? How does the toxic principle cause different effects?
cattle
nicotinic stimulation, then blockade of autonomic ganglia, NMJs, and adrenal medulla
- γ-coniceine = stimulatory
- coniine = mixed
- methyl coniine = inhibitory
What unique toxic effect do γ-coniceine and coniine in Conium maculatum (poison hemlock) have?
teratogenesis
What are the nicotinic clinical signs of Conium maculatum (poison hemlock) poisoning?
- muscular weakness and trembling
- ataxia
- rapid pulse
- mydriasis
- salivation
- abdominal pain
- frequent urination and defecation
- lacrimation
- depression
- paresis, respiratory paralysis
What 2 non-nicotinic clinical signs are associated with Conium maculatum (poison hemlock) poisoning?
- musty, mousy smell in breath and urine
- teratogenic syndrome - joint deformities, crooked legs, kinked tails, cleft palate depending on gestation stage of exposure
- CATTLE: day 40-50 = cleft palate
- CATTLE: day 40-100 = contractures and cleft palate
Where is it most common to find Lupinus (Lupine/Bluebonnet)?
Rocky Mountains westward (cause the most deaths in Montana, Idaho, and Utah)
What are the 2 toxic principles of Lupinus (Lupine/Bluebonnet)? Where are they most concentrated in the plant?
- quinolizidine and piperidine alkaloids
- anagyrine
pods and seeds
What is the mechanism of toxicity of Lupinus (Lupine/Bluebonnet)? What species is most affected?
- alkaloids = nicotinic
- anagyrine = teratogenic
sheep
What 2 species rarely develop Lupinus (Lupine/Bluebonnet) toxicity? Why?
- cattle
- horses
do not usually eat pods
How do clinical signs of Lupinus (Lupine/Bluebonnet) compare in sheep and cattle?
SHEEP = labored breathing, depression, salivation, ataxia, clonic spasms, seizures, butting other animals and pressing against the fence, respiratory failure, coma, death (most susceptible)
CATTLE = excessive salivation, teeth-grinding, muscular weakness, ataxia, recumbency, respiratory paralysis, death (rare)
What causes teratogenic syndrome in Lupinus (Lupine/Bluebonnet) toxicity? How are calves affected? In what 2 states has this been reported?
anagyrine
crooked calf disease affecting front limbs, neck, and spine due to impairment of fetal movement during gestation (+/- cleft palate)
SD, NE
How can poison hemlock and Lupinus toxicity be diagnosed?
- history of plant ingestion
- clinical signs
- chemical analysis of blood, stomach contents, liver, and kidney
What makes Lobelia cardinalis (Cardinal flower) toxic?
contains nicotinic alkaloids - lobeline, lobelidine and others
What makes Laburnum anagyroides (Golden chain) toxic?
nicotinic quinolizidine alkaloid - cytisine
What is the main source of Imidazothiazoles, like Levamisole? What is the mechanism of toxicity?
antiparasitics (antinematode, microfilaricide) and immunostimulants
acts as a nicotine-like ganglionic stimulant with both nicotinic and muscarinic effects to cause stimulation, then a blockade of ganglionic and skeletal muscle transmission
What are the main clinical signs of Imidazothiazole toxicity?
- DUMBELS
- anxiety, irritability
- head shaking, lip licking
- muscle tremors and seizures
- ataxia
- hyperesthesia
- clonic convulsions with CNS depression
- behavioral changes
- tachypnea
- collapse and death due to respiratory failure
What species are susceptible to Imidazothiazole toxicity?
- sheep
- swine
- cattle
- dogs
- horses
No antidote is available for Imidazothiazole toxicity. What symptomatic therapy is used?
Atropine - controls cholinergic signs
Adrenergic receptors locations and responses:
What are some non-specific, α1 selective, and α2 selective adrenergic agonists? What are they used to treat?
Epinephrine, Norepinephrine - anaphylaxis, cardiac arrest
Phenylephrine, Methozamine - decongestants
Clonidine - hypertension, anxiety
What are some non-specific, β1 selective, and β2 selective adrenergic agonists? What are they used to treat?
Epinephrine, Isoproterenol
Xamoterol, Dobutamine, Prenalterol - cardiogenic shock
Albuterol, Formoterol, Terbutaline, Clenbuterol - bronchodilators
What is the mechanism of toxicity of bronchodilators? What are the main clinical signs of toxicity?
stimulation of β-adrenergic receptors
peripheral vasodilation causing…
- hypotension
- bronchodilation and pulmonary edema
- muscle tremors and weakness
- increased HR and arrhythmias
- tachypnea
- vomiting, hypokalemia
Why is decontamination not possible or advisable in the case of bronchodilator toxicity?
rapid absorption and onset of clinical signs
- can induce emesis if within 15-30 min of ingestion
- activated charcoal can be used with large ingestions of syrup
What are the main 3 clinical signs of bronchodilator toxicity that can be treated?
- hypotension - IV fluids
- hyperactivity - Diazepam
- tachycardia - IV propanolol
What are 4 examples of decongestants? What is the mechanism of toxicity?
- Pseudoephedrine
- Phenylephrine
- Phenylpropanolamine
- Ephedrine
sympathomimetic stimulation of α and β adrenergic receptors
What are the 3 syndromes associated with decongestant toxicity?
- α-adrenergic syndrome - hypertension, tachycardia, pale MM, mydriasis, reduced GI motility, hyperactivity (α1/α2)
- β-adrenergic syndrome - weakness, tachycardia, vasodilation (hypotension), bronchodilation, hypokalemia, hyperactivity, tachypnea, depression, muscle tremors, death (β1/β2)
- mixed syndrome - hypertension, tachycardia, mydriasis, dry MM
What 2 drugs are recommended to control seizures with decongestant toxicity? What is usually avoided? Why?
- Phenothiazines - Acepromazine, Chlorpromaine
- Barbiturates
Benzodiazepeines (Diazepam) - dogs become more agitated
What are the main sources of Amitraz? In what 2 animals should they be used carefully? In what species is it contraindicated?
- products for demodectic mange, mite, tick, and lice control (dips, collars, shampoos, pour-ons)
- agricultural pesticides (esp. on fruit trees)
cats and puppies
horses - causes ileus
How does absorption compare with ingestion and dermal exposure?
INGESTION = rapid absorption
DERMAL = relatively slow absorption after dipping
What are the 3 mechanisms of toxicity of Amitraz?
- α2-adrenergic receptor agonist in the CNS to decrease NE release —> sedation
- α1 and α2 adrenergic agonism in PNS
- inhibits monoamine oxidase (MAO) to cause behavioral and neurotoxic effects (MAO catabolizes catecholamine neurotransmitters)
What are the 2 most common central α2 clinical signs upon Amitraz toxicity? What does chronic exposure cause?
- CNS depression/sedation —> coma
- bradycardia
endocrine disruption and developmental/reproductive toxicity
How does Amitraz cause ileus in horses?
α-adrenergic agonism causes GI hypomotility —> ileus —> severe colic
What are the 2 antidotes for Amitraz toxicity?
α-adrenergic antagonists to reverse bradycardia, hyperglycemia, and CNS depression)
- Atipamezole
- Yohimbine
What are some non-specific, α1 selective, and α2 selective adrenergic antagonists? What are they used to treat?
Phentolanine, Phenoxybenzamine - hypertension
Prazosin, Doxazocin, Tamsulosin - hypertension, urinary flow
Yohimbine, Idazoxan
What are some non-specific, β1 selective, and β2 selective adrenergic antagonists? What are they used to treat?
Propanolol, Timolol, Nadolol, Pindolol
Metoprolol, Acebutolol, Atenolol, Esmolol - angina, hypertension, dysrhythmias
Butoxamine
What clinical signs are suggestive of sympatholytic syndrome?
(anti-adrenergic —> α and β antagonists)
- vomiting
- hyperventilation
- convulsions
- hypotension, bradycardia/tachycardia
- heart block, arrhythmias
- miosis
- depression
- bronchoconstriction
- lethargy
- decreased/absent bowel sounds
