Environmental/Toxicology Flashcards
What is the toxic dose for xylitol?
100mg/kg → hypoglycemia secondary to insulin stimulation (within 30-60 min)
500mg/kg → hepatotoxicity, acute hepatic necrosis (6-72 hours)
What is the MOA of anticoagulant rodenticide?
Inhibit Vitamin K epoxide reductase
What is the difference in terms of the treatment duration for 1st and 2nd generation anticoagulant rodenticide toxicity?
1st generation: 2 weeks
2nd generation: 4 weeks
For anticoagulant rodenticide intoxication, why do we measure PT instead of PTT?
PT is used to assess extrinsic pathway, and factor VII has the shortest half-life (6.2hr) → being able to detect the abnormalities earlier
For anticoagulant rodenticide intoxication, when should you check PT if vitamin K is not administered?
48 hours after exposure (this is when factor VII are all used up)
What is the onset of the clinical signs of cholecalciferol rodenticide toxicity?
4-36 hours
What is the lethal dose for cholecalciferol in dogs?
1.5 - 8 mg/kg
What is the general MOA of bromethalin?
Bromethalin and its more potent metabolite, desmethylbromethalin, cross the blood-brain barrier and uncouple mitochondrail oxidative phosphorylation by allowing H+ into the mitochondrial matrix –> no gradient to provide energy for ATP synthase –> no ATP –> failure of Na/K pumps –> cytotoxic oedema –> increased intracranial pressure.
What is the lethal dose of bromethalin for dogs and cats?
Dog: 4.7 mg/kg
Cat: 1.8 mg/kg
ER textbook: LD50 dog 2.4 mg/kg; cat 0.3 mg/kg
Main symptoms of bromethalin toxicity in dogs and cats
Dogs ingesting >LD50 present with acute convulsant syndrome vs CNS depression and paralysis with lower doses.
Cats have predominantly a depressive CNS form although seizures have also been reported.
Mortality is high in dogs but 100% in cats.
Does Strychnine cause a net inhibitory or excitatory effect of the CNS?
Net excitatory effect (because it inhibits the inhibitory pathway)
It blocks post-synaptic glycine receptor -> block the inhibitory effect of glycine on the spinal cord motor neuron -> exaggerated excitatory effect
What is the MOA of organophosphate toxicity?
Irreversibly binds to AChE → prevent breakdown of ACh → overstimulation of both the muscarinic and nicotinic receptors
True or False: Polyradiculoneuritis usually doesn’t cause autonomic dysfunction.
True
What is the MOA of metaldehyde toxicity?
In the stomach, metaldehyde undergoes partial hydrolysis in the stomach to produce acetaldehyde.
Metaldehyde decreases the concentration of GABA, serotonin and norepinephrine in the CNS → decrease the threshold for **seizures. **
**Monoamine oxidase **activity is increased following metaldehyde exposure.
Muscle tremors and the production of acidic metaldehyde metabolites cause severe electrolyte disturbances and metabolic acidosis.
What is the clinical triad for serotonin syndrome?
Altered mentation
Autonomic instability
Neuromuscular abnormalities
Where are most of the serotonin stored at?
Enterochromaffin cells and the myenteric plexus in the GI tract
List 5 effects of serotonin in peripheral nervous system.
Vasoconstriction
Bronchoconstriction
Urinary retention
Increased GI peristalsis
Platelet aggregration
Which amino acid is essential for serotonin formation?
Tryptophan
- Serotonin is formed in the body by hydroxylation and decarboxylation of the essential amino acid tryptophan by tryptophan hydroxylase
Can serotonin cross the BBB?
No
What are the two receptors mainly responsible for serotonin syndrome?
5-HT1
5-HT2A
What are the 5 mechanisms of serotonin toxicity?
1) Increased L-tryptophan → increased serotonin level in the neuron
2) Amphatamines → increased release of serotonin
3) MAO inhibitors → decreased serotonin metabolism → increased pre-synaptic level
4) Selective serotonin reuptake inhibitors (SSRI) → increased serotonin level at the synapse
5) Serotonin agonist → increased serotonin receptor activation
What type of drug is cyproheptadine?
Non-specific 5-HT1A and 5-HT2 receptor antagonist
What type of drug is chlorpromazine?
5-HT2 receptor antagonist; dopamine D2 receptor antagonist; phenothiazine derivative
* Side effect: hypotension
Similar to ACP but less potent
Does xylitol bind to activated charcoal? What about ethylene glycol?
Both toxins do not bind to activated charcoal
For NSAID intoxication, normally how long should the treatment be?
At least 3 half-lives
What are the 5 indications for extracorporeal therapies in AKI patients?
- Azotemia refractory to conventional medical management
- Anuria or severe oliguria
- Severe uremic signs
- Severe electrolyte or acid-base disturbances
- Life-threatening volume overload
What is the lethal dose of ethylene glycol in dogs and cats?
Dogs: 6.6 ml/kg
Cats: 1.5 ml/kg
What are the toxic metabolites of ethylene glycol?
In a retrospective study published in 2020 by Groover and colleague looking at extracorporeal blood purification in acutely intoxicated veterinary patients, what are the 4 most common complications? What is the survival rate and average time of hospitalization?
Complications (18.3%)
- Mild hypotension
- Thrombocytopenia
- Clotting of the extracorporeal circuit
- Hemorrhage
Survival rate: 83.3%
Average time of hospitalization: 49.2 ± 37.7 h
What is half-life of phenobarbital in dogs?
48 hours
What are half-life of diazepam and midazolam in dogs?
Diazepam: 2.5 hr
Midazolam: 1.9 hr
What is the dose of flumazenil for diazepam toxicity?
0.05 mg/kg IV
What is the MOA of Baclofen?
GABAb agonist
Why opioid can cause miosis in dogs?
Opioid stimulates the visceral nuclei of the oculomotor nuclear complex and the parasympathetic nerve that innervates the pupil.
True or False: Naloxone is a synthetic derivative of oxymorphone.
True
What is the dose of naloxone and what is the onset and duration?
Dose: 0.01-0.04 mg/kg
Onset: 1-2 minutes
Duration: 45-90 minutes
Why in 𝜷-blocker overdose/toxicity, mild hyperkalemia may be seen (2 reasons)
1) decreased cellular uptake of K+
2) lower aldosterone levels (β-blocker can suppress the catecholamine-induced renin release)
In a study published in 2004 by Vnuk and colleagues about high-rise syndrome in cats, falling from which floor or about which floor is associated with thoracic trauma?
7th floor or above
There are four degrees of burn wounds, what is their depth?
First-degree: only epidermis affected
Second-degree:
- Epidermis+ superficial part of dermis - Painful to touch, hair follicles preserved
- Epidermis + deep part of the dermis - hair follicle destroyed, decreased pain sensation
- Healing by contraction and epithelialization (may need surgery)
Third-degree: Epidermis + full thickness of dermis
- Insensitive to touch
Fourth-degree: full thickness burn with extension to muscles, bone and tendon
- In the JVECC review paper in 2012, they use superficial, superficial & partial thickness, deep partial thickeness, full thickness
In burn injury, how many percentage of the body surface area being involved can have severe metabolic derangement?
> 20%
- It is also classified as severe burn injury
In a study published in 2021 by Henriksson and colleagues about body surface area in dogs, what are the BSA of the follow body parts?
Head
Thorax
Abdomen
Thoracic limbs
Pelvic limbs
Head 14%
Thorax 18%
Abdomen 14%
Thoracic limbs 9%
Pelvic limbs 11%
In a study published in 2021 by Henriksson and colleagues about body surface area in cats, what are the BSA of the follow body parts?
Head
Thorax
Abdomen
Thoracic limbs
Pelvic limbs
Head 13%
Thorax 20%
Abdomen 15%
Thoracic limbs 7%
Pelvic limbs 12%
After severe burn injury, patients usually will experience two phases with very different hemodynamic status. What are these two phases and what are the timing?
1) Resuscitation phase (hypodynamic or ebb phase)
- immediately after injury till 24-72 hours later
- Hypovolemic, decreased cardiac output, increased vascular permeability, vasoconstriction, decreased peripheral blood flow
2) Hyperdynamic hypermetabolic phase (flow phase)
- 3-5 days after injury
- decreased vascular permeability, increased heart rate, and decreased peripheral vascular resistance resulting in an increase in CO
- Release of counter-regulatory hormones, cortisol, glucagon, and catecholamines are the drive
When do the exfoliation of tracheal epithelial lining of the trachea and main-stem bronchi occur after smoke inhalation?
3-5 days later
- High risk of bronchial obstruction
What is the definition of primary and secondary hypothermia?
Hypothermia: core body temperature **< 37 C **(98.6 F)
Primary: caused by excessive exposure to low environmental temperatures.
Secondary: a result of disease, trauma, surgery, or drug-induced alteration in heat production and thermoregulation
Where is the thermoregulatory center in the body?
Hypothalamus
What are the 4 primary mechanisms of heat loss?
Convection - body surface to air
Conduction -body surface to object
Radiation
Evaporation
Why hypotension develops in hypothermic patients?
Vascular responsiveness to norepinephrine at the α1-receptor decreases
Does hypothermia-induced bradycardia atropine responsive?
No
Why during severe hypothermia patient’s respiratory rate and tidal volume usually reduce?
Decrease CO2 production from the tissue → decreased respiratory drive
What is the most commonly seen acid-base imbalance during marked hypothermia?
Respiratory acidosis & metabolic acidosis
- Metabolic acidosis - decreased blood buffering capacity, decreased hepatic metabolism, decreased acid excretion from the urine, increased lactate due to shivering and decreased tissue perfusion
List 3 coagulation changes during hypothermia.
1) Thrombocytopenia (sequestration by the liver and spleen)
2) Decreased platelet aggregation (secondary to decreased production of thromboxane B2, decreased platelet granule secretion, attenuation of P selectin expression, and diminished expression of the von Willebrand factor receptor )
3) Prolonged aPTT/PT
For every 1C decrease in the temperature, how will the HCT change?
Increase by 2%
Explain the pathophysiology of cold diuresis.
Vasoconstriction (before core temperature drops) → relatively increased blood volume → diuresis
Core temperature drops → decreased response to vasopressin → unable to reabsorb water at collecting tubule
In moderate hypothermia, GFR decreases due to decreased cardiac output and renal blood flow
Explain the cause of hyperglycemia during moderate hypothermia.
1) Decreased cardiac output and renal blood flow → reduced renal clearance of glucose
2) Decreased insulin sensitivity
3) Decreased insulin secretion from the pancreas
What is the pathophysiology of rewarming shock?
Active external rewarming can cause peripheral vasodilation → relative hypovolemia and hypotension
What is core temperature afterdrop during the rewarming process?
- Usually happens at the beginning of the rewarming
- The cold peripheral blood returns to the core → decrease core body temperature even more
- These complications are most likely to occur when the extremities are warmed before the core; therefore application of external heat should be focused on the truncal regions of the body, not the extrem- ities.
What is the pathophysiology of rewarming acidosis.
The return of the peripheral blood is colder and has higher level of lactate → causes acidosis
- These complications are most likely to occur when the extremities are warmed before the core; therefore application of external heat should be focused on the truncal regions of the body, not the extrem- ities.
What is the recommended rewarming rate?
0.5 - 2 C/hr
When the environmental temperature increases, which two of the heat dissipation mechanisms are responsible for 70% of the thermoregulation?
Convection
Radiation
What are the three protective mechanisms of the body during increased heat?
1) thermoregulation
2) acute-phase response
- leukocytosis
- synthesis of acute-phase proteins ↑
- stimulate the hypothalamic-pituitary-adrenal axis, - activate endothelial cells and WBCs
3) intracellular heat shock proteins
- protect against denaturation of intracellular proteins - help to regulate the baroreceptor response during heat stress → preventing hypotension