Section VII Toxicology Flashcards
(Complete) Neurotoxicoses, hepatotoxicoses, Renal, GI, Cardiorespiratory and Haemtologic toxicosis (406 cards)
1
Q
What are the two main goals of decontamination?
A
- Prevention of systemic absorption
- Enhancing elimination
2
Q
What are the methods of decontamination?
A
- Oral decontamination
- Enemas
- Ocular decontamination
- Dermal decontamination
- Inhalant decontamination
- Advanced elimination
3
Q
What are the methods of oral decontamination?
A
- Dilution
- Emesis
- Activated charcol
- Cholestramine
4
Q
What are the methods of dermal decontamination?
A
Bathing and clipping
5
Q
What are the methods of advanced elimination?
A
- Intravenous lipid emulsion
- Therapeutic plasma exchange
- Haemodialysis and charcoal haemoperfusion
6
Q
How is oral decontamination used in the management of toxicosis?
A
It is used to:
1. Prevent systemic absorption of orally ingested toxicants
2. To make a toxin less irritating or corrosive
3. To enhance elimination of toxicants
7
Q
When should oral decontamination be avoided in case of toxin exposure?
A
When a patient is unable to protects its airways.
8
Q
What is the purpose of dilution in cases of toxin exposure?
A
Used to decrease oral and gastric irritation
9
Q
What is the dose rate of dilution?
A
2ml/kg PO milk or water in a bowl or via syringe
10
Q
When is dilution indicated in toxin exposure?
A
In cases of ingestion or petrol, corrosive or caustic agents and plants containing insoluble calcium oxaletes
The calcium in milk may also be of benefit in decreasing absorption of some toxicants including fluroquinalones, fluroide, tetracyclines and bisphosphonate.
11
Q
What is the purpose of emesis in cases of toxin exposure?
A
To remove ingested toxins from the stomach
12
Q
What percentage of stomach contents are expected to be recovered following emesis?
A
40-60%
13
Q
What time frame is emesis recovery most likely to be successful?
A
30-90 minutes following ingestion
14
Q
When is emesis contraindicated?
A
In cases of ingestion or caustic substances or petrol or if the patient is at high risk of aspiration.
15
Q
What are the common medications used to induced emesis in dogs?
A
- Apomorphine at 0.03-0.04mg/kg IV , SC or in the conjunctival sac - centrally acting
- Ropinirole eye drops which act by stimulating the dopamine receptors in the CRTZ
- 3% hydrogen peroxide at 0.5ml/kg PO up to 50ml total dose, can be repeated after 10mins if no vomiting has occured
16
Q
What are the common medications used to induced emesis in cats?
A
- Dexmedetomidine 7mcg/kg IV
- Xylazine 0.44 mg/kg IM
Additional motion can also be used in combination
17
Q
Why can’t hydrogen peroxide not be used in cats?
A
Can induce necroulcerative haemorrhage gastritis
18
Q
What is the purpose of activated charcoal?
A
To prevent absorption of toxins in the gastrointestinal tract
19
Q
When should activated charcoal be used in cases of intoxication?
A
Should be considered in pets with recent toxin exposure that are still in the gastrointestinal tract or toxins that undergo enterohepatic recirculation
20
Q
What should the first dose of activated charcoal be given with?
A
A cathartic such as sorbitol
21
Q
In which cases should multiple dose of activated charcoal be given?
A
In some cases (not all) of toxins that undergo enterohepatic recirculation, these follow up dose should be given at half the initial dose and without a cathartic.
22
Q
Which toxins is activated charcoal ineffective?
A
- heavy metal
- corrosive materials
- hydrocarbons
- fluroide
- xylitol
- ethanol
- petrol
23
Q
What is the main risk of administering activated charcoal?
A
Life threating hypernatraemia
24
Q
What are the risk factors of developement of hypernatraemia in causes of intoxication?
A
- Small animals
- Dehydration
- Ingestion of osmotically active substances e.g. chocolate, paintballs or soft chew medications/supplements
25
How should a patient be handled/monitored after activated charcoal administration?
1. Monitoring or serum sodium
2. IVFT
3. FA to water
26
How does activated charcoal, paintballs, chocolate and soft chew medications cause hypernatraemia?
Because of the osmotic effects of activated charcoal, the cathartic present in activated charcoal, or both it draw free water out and into the GI tract resulting in hypernatraemic dehydration.
27
What are the signs of hypernatraemia?
Neurological signs e.g. tremors, seizures secondary to cerebral odema. GI signs. Lethargy.
28
How is activated charcoal induced hypernatraemia treated?
Since it is an acute onset this can be correctly quickly.
1. Resuscitating or hydration with LRS
2. Then IVFT 0.45% saline solution with 2.5% dextrose at a rate of 40 ml/hour (92 ml/kg/day).
3. Diazepam (0.5-1 mg/kg intravenously) and/or methocarbamol (75 mg/kg intravenously) to control the tremors.
4. Warm water enemas
29
Why is a 0.45% saline solution combined 2.5% dextrose used to treat acute hypernatraemia?
when we are administering 0.45% NaCL + 2.5% dextrose, that extra 2.5% dextrose is mixed in to the 500 ml bag to make the fluid isosmolar. Giving 0.45% NaCL ALONE is contraindicated, as it’s not an isotonic fluid (it’s osmolality is only 154 mEq/L) Our normal body’s osmolality is approximately 300 mosml/L, so we should always give a fluid that is approximately 300 mosm/L (any balanced, isotonic fluid is usually 300 mosm/L). That extra dextrose increases the osmolality of a bag of 0.45%NaCL to approximately 300 mosm/L, making it a safe fluid to give. That dextrose is also metabolized by cells and provides free water to the patient, helping to lower the sodium in the body.
30
What is the action of cholestyramine?
Binds to bile acids in the intestines forming an insoluble complex and is excreted in the faeces.
31
When is cholestyramine indicated?
It is used off-label is cases of cholecalciferol, sago palm, blue green algae and NSAIDs.
32
What is the dose of cholestyramine?
0.3-1g/kg PO q8
33
What is the amount used for warm water enema?
5-10ml/kg
34
How is ocular decontamination performed?
Large quantities of flush (eye wash or artificial tears) for 20-30mins.
35
What is intravenous lipid emulsion?
It is a sterile emulsion of soybean, oil, egg phospholipids and glycerins.
36
When is intravenous lipid emulsion therapy indicated?
It is used in the treatment of severe lipophilic intoxications e.g.
- bupivicaine and other local anaethetics
- moxidectin
- ivermectin
- calcium channel blockers
- baclofen
- permethrin
- THC
- ibuprofen
37
What is the dose regime for intravenous lipid emulsion therapy?
Use a 20% lipid solution with an initial bolus of 1.5ml/kg IV followed by 0.25ml/kg/min for 30-60 minutes. Doses can be repeated q4-6hrs if the patient is still showing clinical signs and the patient is no longer lipaemic (lipaemia occurs as a side effect of ILE therapy).
38
What are the side effects of intravenous lipid emulsion therapy?
1. Hypertriglyceridaemia
2. Volume overload
3. Persistent and gross lipaemia
4. Corneal lipidosis
39
What is therapeutic plasma exchange?
it has been used on veterminary medicine to remove toxicants with high protein binding and low volume of distribution. It removed a patients plasma and associated protein bound toxin and replaces it with new plasma.
40
In what cases can therapeutic plasma exchange be used?
Been suggested for NSAIDs
41
What are the potential sides effects of therapeutic plasma exchange?
- hypotension
- bleeding
- clot formation
- sepsis
- allergic reaction
42
What are the indications for acepromazine in cases of toxicosis?
Agitation and hypertension
43
What is the dose of acepromazine?
0.05-0.1mg/kg IV
44
What is atipamezole used for in cases of toxicosis? What are the indications?
Toxicosis with amitraz, xylazine, dexmedetomidine, brimonidine, clonidine and tizanidine
Sedation, bradycardia, hypotension
45
What is the dose of atipamezole?
50 mcg/kg IM
46
What is atropine used for in cases of toxicosis? What are the indications?
Organophosphates and carbomates, solanum spp, clitocybe and inocyte mushrooms.
Indications: Bradycardia, AV block, SLUDGE - M signs.
47
What are SLUDGE-M signs?
Salivation
Lacrimation
Urination
Defecation / Diarrhea
Gastrointestinal upset
Emesis
Miosis and muscle spasms
48
What are the indications for cyproheptadine in causes of toxicosis?
Serotonin syndrome
49
What are the indications for levetiracetam in causes of toxicosis?
seizures
50
What are the indications of methocarbamol in cases of toxicosis?
Generalised muscle tremors
51
What is the dose of methocarbamol?
55-220 mg/kg slow IV titrated to effect
52
When is propanolol indicated?
It's a beta blocker used in cases of albuterol intoxication resulting in sinus tachycardia
53
When is pyridoxine indicated?
Isoniazid and gyromitra mushroom intoxication when causing seizures. Also an adjustive therapy for etheylene glycol intoxication
54
When is vitamin K indicated?
Known or suspected exposure to an anticoagulant or prolonged coagulation values
55
What is the dose of vitmain K?
1.5 - 2.5 mg/kg PO q12 for 7-30 days
56
How do we known when to discontinue vit K therapy?
check pt 60-72 hours after last dose of vit K to ensure continued treatment is not required.
57
What are the side effects of vit K?
Can cause anaphylaxis
58
What are the indications for yohimbine?
Same as atipamezole.
59
What is the mechanism of action of aminopyridine (avitrol)?
Blocks potassium channels and increased acetylcholine release
60
What are the clinical signs of aminopyridine intoxication?
Weakness, hypersalivation, vomiting, dyspnoea, tachycardia, tremors and seizures.
61
How do you treat aminopyridine intoxication?
Supportive care.
62
What is the mechanism of action of 5-fluorouracil?
Chemo drug - neuro signs possibly due to disruption of the krebs cycle or inhibition of gaba production.
63
What are the signs of 5-fluorouracil intoxication?
vomiting, altered mentation, ataxia, tremors or seizures. BM suppression in 2-4 weeks.
64
How is 5-fluorouracil treated?
Supportive. Levetiracetam for seizures.
65
What is the mechanism of neurotoxicosis of 5-hydroxytryptophan?
Increased production of serotonin.
66
What are the clinical signs of 5-hydroxytryptophan?
Serotonin syndrome
67
What do products with 5-hydroxytryptophan commonly contain?
xylitol
68
What are the signs of serotonin syndrome?
CNS stimulation, vomiting, tremoring, seizures, hyperthermia (secondary to tremoring and seizuring), diarrhea, abdominal pain, and mydriasis
69
What is the mechanism of neurotoxicosis of acetylcholinesterase insecticides e.g. organophosphates and carbamol?
Inhibits acetylcholinesterase
70
What are the signs of organophophate or carbamol intoxication?
SLUDGE signs
71
What is the mechanism of neurotoxicosis of alcohols?
Enhances inhibitor effects of gaba and inhibits glycine binding
72
What is the treatment of alcohol intoxication?
Naloxone, atipamezole or yohimbine may reverse CNS depression; haemodialysis.
73
What is the mechanism of neurotoxicosis of a2 agonist intoxication?
Potentiates a2 adrenergic receptors to inhibit the release of noradrenaline
74
What is the treatment of a2 agonist intoxication?
atipamezole or yohimbine
75
What is the mechanism of neurotoxicosis of amphetamines/MDMA intoxicosis?
Sympathomimetic result in adrenaline release and serotonin release resulting in hypertension, tachycardia, CNS excitation, seizure, hyperthermia etc.
76
What is the treatment of amphetamines/MDMA intoxicosis?
- Acepromazine for agitation
- Propanolol for inappropriate and persistent sinus tachycardia
77
Why should benzos be avoided in causes of amphetamine and MDMA intoxication?
As it can cause paradoxical excitation
78
What is the mechanism of neurotoxicosis of MAO inhibitors (selegiline)?
Inhibits serotonin breakdown by inhibiting MAO resulting in serotonin syndrome
79
What is the mechanism of neurotoxicosis of SSRI intoxication?
Inhibits serotonin reuptake and some also inhibit noradrenaline results in serotonin syndrome
80
What is the treatment for anti-depressant intoxication include MAO inhibitor and SSRIS?
cyproheptadoine and acepromazine for their anti-serotonin effects
Propanolol for persistent sinus tachycardia
ILE may be effective
81
What is the treatment of TCA intoxication?
Titrate pH to 7.55 with IV sodium bicarbonate
82
What is the mechanism of neurotoxicosis of baclofen iontoxication?
It is a centrally acting muscle relaxant, it is a gaba b agonist that binds to both the pre and post synaptic receptors results in CNS and respiratory depression, paralysis of muscles arrhythmias hyotension and seizures
83
How is baclofen intoxication treated?
ventilatory support and haeodialysis
84
What is the mechanism of neurotoxicosis of barbiturate intoxication?
Activated gaba a receptors, inhibits glutamate receptors and inhibits the release of noradrenaline and acetylocholine
85
What is the treatment of action of barbiturate intoxication?
supportive/ILE
86
What is the mechanism of neurotoxicosis of benzodiazepines?
activates gaba a receptors
87
What is the treatment of benzodiazepine intoxication?
Flumazenil
88
What is the mechanism of neurotoxicosis of bromethalin (type of rat poision)?
uncouple oxidative phosphorylation in neurol and glial cell mitochondria resulting in fluid accummulatgion within myelin results in neuro signs
89
What is the treatment of bromethalin (type of rat poison) intoxication?
Decontamination is most important
90
What is the mechanism of neurotoxicosis of bupropion (anti-depressant)?
Inhibits reuptake of dopamine and noradrenaline and antagonises nicotine acetylcholine receptors
91
What is the treatment of bupropion (anti-depressant) intoxication?
supportive, ILE
92
What is the treatment of cannibis intoxication?
supportive, ILE
93
What is the mechanim of neurotoxicosis of carbon monoxide intoxication?
Binds to haemohglobin reducing oxygen carrying capacity
94
What is the mechanism of neurotoxicosis of cocaine intoxication?
CNS stimulant, block reuptake of noradrenaline and serotonin
95
What the treatment for cocaine intoxication?
Supportive ILE
96
What are the clinical signs of ethylene glycol in toxication?
Neuro - ataxia and seizures
Renal failure
Vomiting
97
What is the mechanism of neurotoxicosis of ethylene glycol intoxication?
Alcohol effects of parent compound, metabolites causes a severe acidosis
98
What is the mechanism of neurotoxicosis of grayanotoxins (Kalmia, Rhododendron, pieris spp.)?
Inhibits sodium channels
99
What are the clinical signs of grayanotoxins intoxication?
Vomiting, cardiac arrhythmias, ataxia, seizures
100
What is the mechanism of neurotoxicosis of Isoxazole mushrooms Amanita muscaria, A. pantherina) toxicosis?
Ibotenic acid, a glutamate and glycine receptor agonist, and muscimol, a GABAA agonist
101
What are the clinical signs of Isoxazole mushrooms Amanita muscaria, A. pantherina) toxicosis?
GI upset, CNS depression, disorientation, paresis, opisthotonos, seizures, respiratory depression, or coma
102
What should be avoided in Isoxazole mushrooms toxicosis?
Benzodiazepines
103
What is the mechanism of neurotoxicosis of isoxazoline toxicosis?
Inhibits GABA and glutamate receptors in insects
104
What are the clinical signs of isoxazoline insecticide toxicosis?
GI upset, lethargy, ataxia, rare tremors and seizures (often singular)
105
What is the treatment for isoxazoline toxicosis?
Supportive, if topical, dermal decontamination
106
What is the mechanism of action of lead toxicosis that leads to neurological signs?
Competes with zinc ions which disrupts GABA production and activity; alters synaptic transmission at smooth muscle neuromuscular junctions
107
What are the clinical signs of lead toxicosis?
Acute: GI upset, ataxia, tremors, agitation, seizures
Chronic: GI upset, lethargy, behavior changes, intermittent seizures, anemia, megaesophagus
108
How do you treat lead toxicosis?
Blood lead level; chelation with succimer (DMSA), calcium EDTA, BAL, or penicillamine
109
What is the mechanism of neurotoxicosis of local anaesthetic toxicosis?
Inhibits recovery of sodium channels
110
What are the clinical signs of local anaesthetic toxicosis?
GI upset, methemoglobinemia, cardiac arrhythmias, seizures
111
How do you treat local anaesthetic toxicosis?
Supportive care
112
What is the mechanism of neurotoxicosis of LSD toxicosis?
Increases serotonin
113
What are the clinical signs of LSD toxicosis?
Ataxia, mydriasis, depression or excitation, vocalization
114
What is the treatment for LSD toxicosis?
Supportive care
115
What is the mechanism of action of macadamia toxicosis?
Unknown
116
What are the clinical signs of macadamia toxicosis?
Weakness, CNS depression, GI upset, ataxia, tremors, nonfebrile hyperthermia
117
What is the treatment for macadamia toxicosis?
Supportive; most resolve in 24 hours
118
What is the mechanism of neurotoxicosis of macrocyclic lactone intoxication?
At low doses, inhibits GABA; at high doses, potentiates GABA
119
What are the clinical signs of macrocyclic lactone intoxicosis?
CNS depression, ataxia, weakness, blindness, respiratory depression, bradycardia, hypothermia, coma
120
What is the treatment of macrocyclic lactone toxicosis?
Supportive care; ILE
121
What is the mechanism of neurotoxicosis of metaldehyde toxicosis?
Exact mechanism unknown; decreases serotonin, norepinephrine, monoamine oxidase and GABA
122
What are the clinical signs of metaldehyde toxicosis?
Rapid onset of tremors, seizures, nonfebrile hyperthermia, tachycardia
123
How is metaldehyde toxicosis treated?
Methocarbamol for tremors
124
What is the mechanism of neurotoxicosis of methylxanthine (Caffeine, theobromine, theophylle) toxicosis?
Inhibit cyclic nucleotide phosphodiesterases and antagonize the effects of adenosine a1 and a2 receptors
125
What are the clinical signs of methylxanthine toxicosis?
- GI upset (dogs, cats: 20 mg/kg); agitation, tachycardia (>40 mg/kg)
- tremors, seizures (>60 mg/kg).
Signs begin within minutes (caffeine-only products) to 6-12 hours (chocolate).
126
How do you treat methylxanthine toxicosis?
Supportive, as appropriate: emesis if not showing any clinical signs; IV fluids; beta-blockers if cardiac tachyarrhythmias; seizures respond to barbiturates (e.g., phenobarbital); activated charcoal is rarely given due to risk of hypernatremia (fluid shifts)
127
What is the mechanism of action of metronidazole toxicosis?
unknown
128
What are the clinical signs of metronidazole toxicosis?
GI upset, ataxia, hypermetria, tremors, vertical nystagmus, seizures
129
What is the treatment of metronidazole toxicosis?
Discontinue metronidazole; diazepam to hasten recovery
- Oral diazepam (at approximately 0.43 mg/kg orally every 8 hours for three days)
130
What is the mechanism of neurotoxicosis of nicotine toxicosis?
Low dose: stimulates nicotinic acetylcholine receptors
High dose: blocks nicotinic receptors due to persistent depolarization
131
What are the clinical signs of nicotine toxicosis?
Vomiting. Low dose: agitation, tachycardia, tremors. High dose: bradycardia, respiratory depression, weakness, paresis
132
What should be avoided in cases of nicotine toxicosis?
Antacids as they enhance absorption
133
What are the clinical signs of opioid toxicosis?
Lethargy, ataxia, GI upset, bradycardia, hypothermia, hypotension, nonfebrile hyperthermia (cats), CNS depression, coma
134
What is the treatment of opioid toxicosis?
Naloxone to reverse
135
What is the mechanism of action of phenylpropanolamine toxicosis?
Vasoconstriction
136
What are the clinical signs of phenylpropanolamine?
Agitation, tachycardia (followed by bradycardia), hypertension, tremors, piloerection
137
What is the mechanism of action of pyrethrin toxicosis?
Prolongs sodium influx and reduces potassium efflux, which enhances the action potential and results in repetitive nerve discharge
138
What are the clinical signs of pyrethrin toxicosis?
Tremors, dermal paresthesia, agitation, seizures, GI upset with oral exposure
139
Which animal is more sensitive to pyrethrin toxicosis?
cats
140
What is the treatment of pyrethrin toxicosis?
Bathe if dermal, methocarbamol for tremors; ILE
141
What is the mechanism of action of zinc toxicosis?
Direct irritant to GI tract; releases phosphine gas, which interrupts cellular aerobic respiration in mitochondria, leading to decreased energy production, free radical formation, and damaged cellular membranes, proteins, and nucleic acids
142
What are the clinical signs of zinc toxicosis?
Vomiting, lethargy, CNS depression, tremors, agitation, seizures, coma, ataxia, rigidity, nystagmus, tachypnea, dyspnea, pulmonary edema, AKI - increased renal values and liver enzyme activities, acidosis and haemolysis
143
What is the treatment for zinc toxicosis?
Supportive; antacids to raise stomach pH;
Chelation with succimer or CaEDTA or d-penicillamine
public health concern with humans inhaling phosphine gas from ingesta (move patient to well-ventilated area)
144
How can you diagnose neurotoxicoses?
1. Mostly history and clinical signs
2. Radiographs for suspect metal toxicosis
3. A serum ethylene glycol test for suspected toxicosis
4. Over the counter urine drug screen test
5. Electrolytes/blood gas
145
What toxins can causes acute blindness?
- Hypernatremia (activated charcoal, ice melts, play dough, salt)
- Ivermectin
- Lead
- Metaldehyde
- Paintballs
146
What toxins can cause tremors?
- Hypernatremia (activated charcoal, ice melts, play dough, salt)
- Metaldehyde
- Pyrethrin/pyrethroids (bifenthrin, permethrin)
- Strychnine
- Tremorgenic mycotoxins (penitrem A, roquefortine)
147
What toxins can cause muscle weakness, paresis, paralysis?
- Black widow spider (Lactrodectus spp.)
- Bromethalin
- Coral snake (Elapidae spp.)
- Fertilizers (especially manure-based)
- Ionophores (lasalocid, monensin)
- Macadamia nut
- Metronidazole
- Tea tree oil (Melaleuca spp.)
- 2,4-D and phenoxy herbicides
148
Which toxins can causes nervous system depression?
- Alcohols
- Alpha-2 agonists
- Antidepressants
- Antihistamines—low doses
- Baclofen
- Barbiturates
- Benzodiazepines (alprazolam, clonazepam, diazepam, lorazepam)
- Diethylene glycol
- Ethylene glycol
- Hypernatremia
- Imidazoline decongestants
- Ivermectin (abamectin, moxidectin, etc.)
- Lead
- Marijuana
- Muscle relaxants (cyclobenzaprine, methocarbamol)
- Mushrooms
- Nicotine
- Non-steroidal anti-inflammatory drugs—high doses
- Opioids
- Phenothiazines
- Piperazine
- Propylene glycol
149
What toxins can cause Nervous system excitation +/- seizures?
Amphetamines
Antidepressants (TCA, SSRI, atypical)—high doses
Antihistamines (diphenhydramine, loratadine)—high doses
Baclofen
Bromethalin
Brunfelsia spp.
Cicuta spp. (water hemlock)
Cocaine
Cold medications (pseudoephedrine, ephedrine, phenylephrine)
Cyanobacteria
5-Fluorouracil
5-Hydroxytryptophan
Hypernatremia (activated charcoal, ice melts, play dough, salt)
Isoniazid
Isoxazoline insecticides (afoxolaner, fluralaner, sarolaner)
Lead
LSD
Metaldehyde
Methylxanthines (caffeine, chocolate, theophylline)
Metronidazole
Mushrooms (isoxazole, Psilocybe spp.)
Nicotine
Organophosphate or carbamate insecticides (aldicarb, methomyl, disulfoton)
Phenylpropanolamine
Pyrethrin/pyrethroid insecticides
Toads (Rhinella marina, Incilius alvarius)
Tremorgenic mycotoxins (penitrem A, roquefortine)
Yohimbine
Zinc phosphide/aluminum phosphide
150
What is the minimum diagnostic database for suspected neurotoxicosis?
- Thorough history
- CBC
- Biochemistry with lytes
- Blood pressure
- Blood gas
151
What are the medications used for chelation of lead? What are the doses?
Chelators effective for lead elimination include:
- succimer (10 mg/kg PO q8h for 10 days)
- edetate calcium disodium (CaEDTA, 25 mg/kg SQ q6h for 5 days or 75 mg/kg IV q6h for 2-5 days, diluted to 10 mg/mL for administration)
- d-penicillamine (30-110 mg/kg/day PO divided q6h for 7 days), or dimercaprol (British anti-Lewsite [BAL], 3-6 mg/kg IM q6-8h
152
What medications can be used for stimulatory signs/seizures?
- acepromazine
- Diazepam in some case but can worsen certain toxins
- Seizure can be controlled with diazepam, levetiracetam, midazolan or phenobarbital or inhalant anaesthesia
153
How is serotonin syndrome treated?
A serotonin antagonist such as cyproheptadine. Propranolol may also antagonize serotonin activity
154
How are tremors treated in toxicosis?
Methocarbamol
155
What are the hepatotoxicants of veterinary importances?
1. Drugs/supplements:
2. Plants e.g. cycads
3. Mushrooms/fungi: Amatoxins, aflatoxins, blue green algae (Cyanobacteria)
4. Heavy metals: iron
156
What are the hepatotoxic drugs of veterinary importance?
Acetaminophen
Anabolic steroids (e.g., stanozolol)
Aspirin
Azathioprine
Azole antifungals
CCNU (lomustine)
Corticosteroids
Diazepam
Diethylcarbamazine
Halothane
Ketoconazole
Mebendazole
Megestrol acetate
Methimazole
NSAID (e.g., carprofen)
Phenobarbital
Phenytoin
Primidone
Tetracycline
Trimethoprim-sulfa
Zonisamide
157
What are some common supplements that can result in hepatotoxicity?
- alpha-lipoic acid
- joint supplements
158
How long does it take paracetamol to reach peak plasma levels after oral dosing?
10-60min
159
What is the toxic dose of paracetamol in dogs?
≥75-100 mg/kg
160
What is the toxic dose of paracetamol in cats?
>10mg/kg
161
What is the toxic metabolite in paracetamol?
N-acetyl-para-benzoquinone imine (NAPQI)
162
Describe the mechanism of action of liver injury of acetominophen toxicosis?
N-acetyl-para-benzoquinone imine (NAPQI) is generated by cytochrome P450 oxidation in the liver and kidney when the normal glucuronidation and sulfation pathways are saturated. Intrinsic antioxidants such as glutathione or cysteine bind NAPQI, preventing cellular injury, but when these antioxidant systems are depleted, NAPQI binds to cellular macromolecules, resulting in hepatocellular injury and death. Ultimately results in methemoglobinemia and liver necrosis.
163
What is the onset of action of acetominophen toxicosis?
2-4 hours for methemoglobinemia and 24-48 hours for liver injury
164
What laboratory abnormalities do you see for liver injury?
AST, ALT and TBIL elevations
165
How do you manage paracetamol toxicosis?
1. Supportive care, management of clinical signs
2. IVFT
3. GI decontamination
4. Administration of glutathione precursors such as n-acetylcysteine at 140mg/kg IV loading dose, followed by 70 mg/kg IV q6 for 6 doses and s-adenosylmethionine at 20mg/kg PO q24 or can divide into q8-12 doses
5. Ascorbic acid (30 mg/kg PO, SQ, IV q6h) helps reduce methemoglobin to hemoglobin
166
What is the mechanism of liver injury of Alpha lipoic acid toxicosis?
Oxidative injury, binding of cellular thiol groups
167
What is the toxic dose of alpha lipoic acid in cats?
Cats are 10× more sensitive than dogs; dosages >13 mg/kg = hepatocellular damage
168
What is the toxic dose of alpha lipoic acid in dogs?
>126 mg/kg = hepatocellular injury
169
What is the mechanism of liver injury of diazepam toxicosis?
immune-mediate response in suspected
170
What is the onset of action of diazepam toxicosis?
Onset after 3-7 days of oral dosing
171
What is the mechanism of liver injury or iron toxicosis?
Free radical production causing oxidative injury
172
What chelation therapy is recommended for iron toxicosis?
chelate with deferoxamine (15 mg/kg/h or 40 mg/kg slow IV q4-8h) when serum iron >300 mcg/dL
173
What is the dose of iron toxicosis in dogs?
20 mg/kg, gastrointestinal injury; ≥60 mg/kg, hepatic injury
174
What is the mechanism of liver injury of joint supplement toxicosis?
Suspected manganese toxicosis. Reported only in dogs.
175
What is the dose of joint supplement toxicosis in dogs?
Reported in dogs only; oral manganese dosage of 86 mg/kg from joint chews was lethal.
176
What is the mechanism of liver injury of NSAID toxicosis?
Unknown, theories include mitochondrial injury, oxidative injury, neoantigen formation
177
What does NSAID toxicosis do to the liver?
Causes an idiosyncratic hepatopathy in dogs generally occurs after 2-3 weeks or more of therapy; usually reversible; hepatopathy not reported in cats
178
When is methimazole toxicity seen? How is it treated?
Usually in first month of therapy; usually reversible
179
What is the mechanism of liver injury of sulfonamide toxicosis?
Neoantigen formation triggers immune response
180
Which fungi is most commonly associated with aflatoxins?
Aspergillus
181
What are the common sources of aflatoxins?
corn and other grains, peanuts, soybeans, tree nuts, and cottonseed
182
Describe the mechanism of liver injury of aflatoxins.
The toxicity of AFB1 is due to its biotransformation into toxic epoxides that bind cellular proteins and nucleic acid, resulting in altered protein synthesis, energy production, cellular metabolism, enzyme activity, and nucleic acid transcription and translation. These processes lead to hepatocellular degeneration, necrosis and apoptosis. The low levels of toxic metabolites generated under normal circumstances are dealt with by endogenous antioxidant molecules such as glutathione, and it is only in the face of excessive exposure that significant cell injury occurs. Aflatoxin-induced DNA damage can result in genetic and epigenetic alterations that can persist and lead to chronic liver injury and carcinogenesis.
183
Why are dogs and cats more sensitive to aflatoxins?
Compared to most other mammalian species, dogs and cats have inherently low hepatic glutathione concentrations and low glutathione-s-transferase activity, making them more sensitive to aflatoxin-induced liver injury.
184
How soon do clinical signs develop in cases of alfaxatoin exposure?
Clinical signs of aflatoxicosis may develop within 1-2 days of ingestion of feeds contaminated with very high levels of aflatoxin but may be delayed for weeks to months in cases of chronic exposure to more moderately elevated aflatoxin concentrations.
185
How is aflatoxin toxicosis treated?
Non-specific
- Anti-emetic
- GI protectants
- IVFT
- Vit K for coagulopathies
- N-acetycysteine or s-AME or silymarin for glutothionine precursors and hepatoprotection
186
Describe the mechanism of liver injury of blue-green algae (Cyanobacteria) toxicosis?
Hepatocyanotoxins are absorbed from the ileum and are taken up by hepatocytes via a bile acid transporter. Within the hepatocyte, these peptides bind and disable cytoskeletal proteins, initiate lipid peroxidation, and bind to and fragment DNA. The overall cellular effect of HCs is loss of membrane integrity, decreased protein synthesis, necrosis, and apoptosis leading to rounding and detachment of hepatocytes from the basement membrane and intrahepatic “hemorrhage” into areas devoid of hepatocytes. In severe intoxications, massive loss of hepatocytes results in pooling of large volumes of blood within the liver, resulting in hepatomegaly and rapid death due to hypovolemia. Surviving patients experience acute hepatic insufficiency that can lead to hepatic failure
187
What laboratory finding are often seen with cyanobacteria toxicosis?
Serum liver enzyme activities, bile acid concentrations, and bilirubin concentrations are abnormal; hypoglycemia, hypokalemia and hyperammonemia may occur. Depending on the degree of hepatic injury, coagulopathy or encephalopathy may develop
188
How is cyanobacteria toxicosis treated?
- supportive care
- symptomatic therapy
- Cholestyramine (300-1000 mg/kg PO q8h) should be considered if the patient’s condition is amenable to oral administration
- Hepatoprotection with N-acetylcysteine, s-AME or silymarin should be considered
189
Describe the mechanism of liver injury of cycad toxicosis?
Cycasin, the primary hepatotoxin, is biotransformed in the intestine to methylazoxymethanol (MAM), a metabolite that is hepatotoxic, neurotoxic, mutagenic, teratogenic, and carcinogenic. MAM alkylates nucleic acids, impairing cellular protein synthesis and resulting in cell death.
190
What are the clinicopathological findings is cases of cycad toxicosis?
Clinicopathologic alterations consistent with liver failure (elevated bilirubin concentrations, liver enzyme activities, and bile acid concentrations; elevated coagulation times; hypoglycemia) may take up to 24-48 hours to develop. Azotemia, bilirubinuria, hematuria, and cylindruria may occur.
191
How do you treat cycad intoxication?
1. Decontamination with emesis and activated charcoal
2. IVFT
3. Anti-emetics
4. GI protectants
5. Vit K
6. Hepatoprotectants
192
Where is xylitol found?
Gum, lollies, toothpastes, cosmetics and oral medications
193
Describe the mechanism of action of xylitol toxicosis.
Dogs have a unique physiologic response to xylitol that results in a rapid, sustained, and dose-dependent rise in insulin release, which in turn triggers a precipitous drop in blood glucose levels. Some dog also develop elevated liver enzymes and some progress to severe hepatic necrosis.
194
How do you treat xylitol toxicosis?
Decontamination and supportive care. If concerned for hepatic necrosis/ coagulopathy vit K and hepatoprotectants.
195
What are the common renal toxicants in dogs and cats?
1. Allium spp
2. Aminoglycosides
3. Amphotericin B
4. Cholecalciferol and Vit D analogues
5. Cisplatin
6. Ethylene glycol
7. Lilium and hemerocallis spp.
8. Pit vipers
9. NSAIDS
10. Sulfonamides
11. Tetracyclines
12. Vitis spp. e.g. grapes and raisins
13. Zinc
196
How does cholecalciferol/vit D analogues causes an AKI?
It has the potential to cause an AKI secondary to hypercalcaemia and renal mineralisation.
197
What are the most common sources of cholecalciferol/vit D analogues?
Rodenticides and human medications
198
How do you managecholecalcifierol/vit D toxicosis?
1. Decontamination e.g. emesis and activated charcoal
2. Cholestyramine resin
3. Ca+, Phosp, BUN and creat should be monitored daily until 96 hours after exposure
4. Once hypercalcaemia develops treatment is focused on returning calcium and phosp to normal
Once serum Ca++ levels normalize, the patient should be weaned off saline diuresis and discharged on oral medications. Following discharge Ca++ should be monitored at least 2-3 times per weeks for 2-3 weeks
Treatment may be required for weeks due to the long half-life of calcidio
199
What is the prognosis of vit D toxicosis?
The prognosis is good if the exposure is treated promptly. The prognosis is guarded to poor once hypercalcemia develops and grave once soft-tissue mineralization develops.
200
Where is ethylene glycol found?
automotive antifreeze, de-icers, home solar units, inks, brake fluids, and snow globe-type decorations.
201
How do you diagnose ethylene glycol toxicosis?
While the gold standard is gas chromatography-mass spectroscopy quantitative analysis of serum EG levels, cage-side EG tests are available. They have good sensitivity but are lacking in specificity. False positives can be seen from the presence of alcohols, propylene glycol, glycerol, and sorbitol.7-9 Osmolal gap and acid-base testing can be used in conjunction with a cage-side EG test to best determine the need for treatment. An increased serum osmolal gap (>20 mOsm/kg) within 1-2 hours of the exposure is indicative of the presence of an exogenous solute like EG.
202
How do you calculate osmolal gap?
measured serum osmolality minus the calculated serum osmolality.
Serum osmolality is calculated using the following formula: 1.86 × (Na+ + K+ + glucose/18 + BUN/2.8),
assuming Na+ and K+ are in mEq/L and glucose and BUN are in mg/dL; with metric units (all mmol/L), the formula is 1.86 × (Na+ + K+ + glucose + BUN).
203
How do you treat ethylene glycol toxicity?
Fomepizole (4-methylpyrazole) is the preferred ADeH inhibitor.
Or Ethanol
204
How does fomepizole work?
It directly inhibits the enzyme and causes less central nervous system (CNS) depression, diuresis, and acidosis than ethanol does.
205
How long should fomepizole be used for in the treatment of ethylene glycol toxicity?
Fomepizole should be continued until at least 36 hours post-exposure or until an EG test is negative.
206
How does ethanol work in treating ethylene glycol toxicity?
Ethanol does not directly inhibit Alcool dehydrogenase, but rather serves as a competitive substrate for the enzyme.
207
How long should ethanol be used for in the treatment of ethylene glycol toxicity?
Ethanol should be continued for at least 24 hours beyond the point where renal and acid-base values are normal
208
What is the mechanism of renal toxicity of allium spp?
Secondary to hemolysis
209
What is the mechanism of renal toxicity of aminoglycosides?
Interfere with phospholipid metabolism in the lysosome of proximal renal tubular cells
210
What is the mechanism of renal toxicity of amphotericin B?
Renal vasoconstriction
211
What is the mechanism of renal toxicity of cholecalciferol?
Hypercalcemia from enhanced GI Ca++ absorption, mobilization of osteoclasts, enhanced renal Ca++ resorption
212
What is the mechanism of renal toxicity of cisplatin?
Activates signaling pathways causing tubular cell injury and death
213
What is the mechanism of renal toxicity of ethylene glycol?
EG metabolites are cytotoxic to renal tubular cells. Accumulation of CaOx crystals in renal tubules, renal tubular acidosis.
214
What is the mechanism of renal toxicity of lilium and hemerocallis spp.?
Cats only. Unknown. Renal injury occurs due to necrosis of the proximal renal tubular epithelium. The toxin has also caused degeneration of pancreatic acinar cell.
215
What is the mechanism of renal toxicity of Pit vipers?
Venom causes hemolysis and thrombotic microangiopathy
216
What is the mechanism of renal toxicity of NSAIDs?
Inhibition of prostaglandin synthesis via COX enzyme inhibition, leading to renal vasoconstriction, decreased GFR, anoxia.
217
What is the mechanism of renal toxicity of sulfonamides?
Crystalluria
218
What is the mechanism of renal toxicity of tetracyclines?
Decreased utilization of amino acids
219
What is the mechanism of renal toxicity of vitis spp?
Unknown (tartaric acid suspected)
220
What is the mechanism of renal and GI toxicity of zinc?
Secondary to hemolysis and is a GI irritation
221
What are the clinical signs of renal toxicants?
1. Vomiting
2. AKI
3. Haemolysis in some cases
4. PU/PD, anuria
222
How do you manage actue hypercalcaemia secondary to Vit D toxicosis?
1. IVFT 0.9% NaCL 100-180ml/kg/day initially then adjusted to maintain hydration
2. Low calcium diet
3. Bisphosphonates: Pamidronate or zoledronate
4. Predniosolone
5. Furosemide
6. Phosphate binders
223
What is the function of 0.9% NaCL in managing acute hypercalcaemia?
Na+ competes with Ca++ for resorption in renal tubules
224
Why should LRS be avoided in hypercalcaemi patients?
It contains calcium
225
What is the function of a low calcium diet in managing acute hypercalcaemia?
Reduce exogenous Ca++, upregulation of metabolizing enzymes, lowering calcidiol levels
226
What are the options for a low calcium diet?
Macaroni and lean ground beef, many prescription renal and urinary tract diets
227
What is the function of bisphosphonates in managing acute hypercalcaemia?
Inhibits osteoclastic bone resorption
228
What is the function of prednisolone in managing acute hypercalcaemia?
Reduce bone resorption, decrease intestinal absorption and increase renal elimination of Ca++
229
What is the function of furosemide in managing acute hypercalcaemia?
Promote calciuresis
230
What is the function of phospahte binders in managing acute hypercalcaemia?
Reduces intestinal absorption of phosphorus
231
How is lily toxicosis managed?
1. Decontamination e.g. bathing, emesis and activated charcoal
2. Intravenous diuresis: continuing diuresis for at least 48 hours is recommended to prevent anuric renal failure
232
How is NSAID intoxication managed?
1. Decontamination e.g. emesis and activated charcoal if alert and within 1 hour of ingestion. If the NSAID undergoes enterohepatic recirculation, a second dose of AC can be given 6-8 hours after the first dose
2. Cholestyramine has been shown to bind many NSAIDs and can be used in the first 24-48 h after an exposure
3. Base line UA, and biochem performed and rechecked daily
4. IVT at 2 x maintenance
5. PPI e.g. omeprazole or pantropazole
6. Sulcralfate or misoprostal
7. TPE - more evidence if need however before it can be recommended
233
What is the toxic component of grapes and raisins?
Tartaric acid
234
What are the clinicopathologic finding in grape and raisin intoxication?
Clinicopathologic findings can include azotemia, hypercalcemia, hyperphosphatemia, increased alanine aminotransferase (ALT) activity, hyperglycemia, hyperkalemia, hypokalemia, isosthenuria, hyposthenuria, proteinuria, glucosuria, pyuria, crystalluria, and cylindruria
235
How is grape intoxication managed?
1. Decontamination: induction of emesis, activated charcoal should only be given in patients with large exposure and poor emesis results.
2. If emesis is successful risk of AKI is considered low and patients can be monitored at home
Monitoring at home - these patients should not be given an antiemetic prior to discharge so as not to mask the development of any vomiting. Patients should have a renal chemistry profile and urinalysis rechecked at 24-48 hours post exposure or sooner if any clinical signs develop at home.
If decontamination is unsuccessful should be admitted to the hospital for isotonic crystalloid fluid diuresis for 48 hours. Renal profiles and urinalyses should still be monitored. Most patients that are promptly treated with fluid diuresis do not develop AKI
236
Chapter 136: Gastrointestinal toxicoses
237
What classifies an acidic substance?
Substances that have a pH <7
238
At what pH can certain substances cause tissue damage and coagulative necrosis?
pH 2
239
What are the common gastrointestinal Toxicants of Dogs and Cats?
1. Medications/drugs: e.g. 5-Fluorouracil, Colchicine, Methotrexate, NSAIDs, Methyxanthines (Caffeine, theobromine).
2. Household Chemicals: e.g. Bleach, Detergents, Petrol, Phenol.
3. Heavy Metals and Elements e.g. Metals such as iron, lead, zinc, arsenic
4. Batteries
5. Pesticides and Herbicides e.g. Boric acid
6. Plant-Derived Toxins: e.g. Chinaberry tree, Cycad palms, Diterpene esters, Essential oils, Grayanotoxins, Lectins/toxalbumins, Protoanemonin, Triterpenoid,
240
What is the mechanism of action of arsenic toxicosis?
Binds to sulfhydryl groups and interferes with cellular metabolism
241
What are the clinical signs of arsensic toxicosis?
Hemorrhagic gastroenteritis, hypotension, hypovolemia
242
What is mechanism of action of battery ingestion/toxicosis?
Liquefactive necrosis
243
What are the clinical signs of battery ingestion?
Vomiting, ptyalism, ulcers
244
What is the mechanism of action of bleach toxicosis?
Mucosal irritant; corrosive
245
What are the clinical signs of bleach ingestion/toxicosis?
Vomiting, ptyalism, diarrhea, oral irritation, ulcers
246
What is the mechanisms of action of boric acid toxicosis?
Irritant
247
What are the clinical signs of boric acid toxicosis?
Vomiting
248
What is the mechanism of acid of chinaberry tree toxicosis?
Tetranortriterpenes (cytotoxic)
249
What are the clinical signs of chinaberry toxicosis?
Vomiting, lethargy, diarrhea, neurologic signs are rare
250
What is the mechanism of action of colchine?
Anti-metabolite, inhibits spindle formation in cell division and destruction of RBC-producing cells in bone marrow
251
What are the clinical signs of colchine toxicosis?
Vomiting, bloody diarrhea, bone marrow suppression and anaemia
252
What is the mechanism of action of detergent ingestion?
Locally corrosive
253
What are the clinical signs of detergent ingestion?
Vomiting, ulcers.
254
What is the mechanism of action of diterpene esters?
Blistering compounds
255
What are the clinical signs of diterpene esters?
Vomiting, oral inflammation
256
What is the mechanism of action of essential oils?
unknown
257
What are the clinical signs of essential oils ingestion?
Vomiting, potential for CNS or liver damage
258
What is the mechanism of action of fertilizer ingestion?
GI irritation
259
What are the clinical signs of fertilizer ingestion?
Vomiting, rarely hind limb weakness/stiffness
260
What is the mechanism of action of herbicide ingestion?
Irritation from the surfactants
261
What are the clinical signs of herbicide ingestion?
Vomiting, oral ulcers with concentrates
262
What is the mechanism of action of insoluble calcium oxalate plants?
Mechanical irritation
263
What are the clinical signs of insoluble calcium oxalate plants?
Vomiting, ptyalism, gagging
264
What is the mechanism of action of lectins/toxalbumins?
Stops protein synthesis
265
What are the clinical signs of lectins/toxalbumins?
Vomiting, multiorgan failure
266
What is the mechanism of action of Methotrexate?
Chemotherapeutic
267
What are the clinical signs of methotrexate ingestion?
Vomiting, anorexia, bone marrow suppression
268
What is the GI mechanism of NSAIDs intoxication?
Inhibition of prostaglandin synthesis via COX inhibition, causes vasoconstriction of gastric mucosa, increased gastrin secretion
269
What are the clinical signs of NSAID intoxication in relation to the GI system?
Vomiting, GI ulcers, AKI
270
What is the mechanism of action of petrol ingestion?
Destruction of surfactant if inhaled/aspirated
271
What are the clinical signs of petrol ingestion?
Vomiting, aspiration pneumonia, pneumonitis
272
What is the mechanism of action of phenol ingestion?
Denatures proteins
273
What are the clinical signs of phenol intoxication?
Oral ulcers, vomiting; neurologic signs rare
274
What is the mechanism of action of protoanemonin?
Vesicant
275
What are the clinical signs of protoanemonin ingestion?
Oral ulcers, vomiting, ptyalism
276
What is the mechanism of action of Triterpenoid saponins?
Direct irritation
277
What are the clinical signs of triterpenoids?
Vomiting and diarrhoea
278
What is considered an alkaline substance?
pH > 7
279
What are some common alkaline substances?
- Alkaline battery fluid
- Calcium carbide
- Calcium hydroxide
- Washing soda
- Sodium hydroxide
- Trisodium phosphate
- Potassium hydroxide
280
What do fertilisers normally contain?
Nitrogen, phosphorus and potassium.
281
How is fertiliser intoxication treated?
1. Decontamination e.g. emesis
2. Anti-emetics
3. IVFT in cases of dehydration and ongoing losses
Note activated charcoal does not bind effectively to fertilizer.
282
What are some common ingredients in fertilizer?
1. Cocoa bean mulch
2. Manures
3. Meals e.g. bone, bloods, fish, feather, crab and kelp
4. Seaweed Extract
5. Sewage Sludge
283
What toxicosis can occur with ingestion of cocoa bean mulch?
Potential from methylxanthine toxicosis
284
What are some common names of plants that contain insoluble calcium oxalates?
Chinese evergreen, Alocasia; elephant’s ear, Flamingo plant, Jack-in-the-pulpit, Cuckoo-pint, Caladium; elephant’s ear, Wild calla; wild arum, Dumb cane varieties, Devil’s ivy; pothos varieties, variegated philodendron, taro vine, Monstera spp, Philodendron varieties, Peace lily, Skunk cabbage, Nephthytis, Malanga, caladium, elephant’s ears, Calla lily, arum lily, Umbrella tree (Australian or Queensland), schefflera
285
How is insoluble calcium oxalate toxicosis treated?
- Induction of emesis and administration of activated charcoal are not indicated in IO ingestions.
- Diluting with a dairy product (milk, yogurt, cottage cheese), and rinsing the mouth to remove crystals are appropriate.
- If severe vomiting and diarrhea are present, an antiemetic and fluids can be given.
- If needed, sucralfate slurries (0.25-1 g PO) may be used.
Calcium oxalate crystals do not reach the kidneys and kidney injury is not part of this type of intoxication. Therefore, systemic signs aren’t anticipated, and the prognosis is good
286
What are polyurethane adhesives?
Polyurethane adhesives are used as glues, tile adhesives, spray foams, and surface coatings.
287
What occurs when polyurethane adhesives are ingested?
Polyurethane adhesives that contain isocyanates can expand. When animals ingest the adhesive, the glue expands and polymerizes into a large, friable foreign body in the stomach. The adhesives are hygroscopic (water-absorbing), and the reaction proceeds even faster at body temperature. One study documented an 8-fold increase in volume over 2 hours. This can results in FB obstruction. The expanded glue is also rough and it damages the stomach mucosa, leading to gastric hyperemia, ulceration, and risk of perforation.
288
What is the treatment of polyurethane adhesives?
Usually surgery to remove the FB. GI protectants.
289
Cardiorespiratory Toxicosis
Chapter 137
290
What makes the heart and lungs more susceptible to toxin damage?
The heart receives all the systemic circulation and needs a steady supply of nutrients (adenosine triphosphate [ATP], oxygen, etc.). Any toxin that affects these processes can be detrimental. The myocardium does not have the ability to regenerate to any meaningful degree. The lungs receive almost all inhaled toxins.
291
What are the common cardiorespiratory toxicants of dogs and cats?
1. Medications/food: ACE inhibitors, albuterol, beta blockers, calcium channel blockers, digoxin, phenopropanolamine, tricyclic antidepressant, Methylxanthines (caffeine, theobromine, theophylline) and Imidazoline decongestants
2. Insecticides and herbicides e.g. anticholingeric insecticides (organophosphate, carbamates), paraquat
3. Plants e.g. milkweed, lily-of-the-valley, foxglove, Kalanchoe, laurel, apple, crabapple, oleander, firefly, pieris, stonefruit, rhododendron, azalea, taxus species
4. Bufo toad
5. Gases e.g. carbon monoxide, carbon dioxide, methane, natural gas, sulfuryl fluoride, smoke, hydrogen sulfide
6. Cyanide
7. Petrol
292
What are the common ACE inhibitors?
1. Enalapril
2. Benazepril
3. Lisinopril
4. Captopril
293
What are the common beta blockers?
1. Atenolol
2. Metoprolol
3. Labetalol
4. Esmolol
294
What are the common calcium channel blockers?
1. Diltiazem
2. Verapamil
3. Nifedipine
295
What are the common imidazoline decongestants?
1. Oxymetazoline
2. Xylometazoline
3. Tetrahydrozoline
4. Naphazoline
296
What is albuterol?
Bronchodilator used for treating bronchospasm in asthma
297
What is the mechanism of action of albuterol when given therapeutic doses?
It is a selective beta-2 agonist. Stimulation of beta-2 receptors activates adenyl cyclase in cellular membranes, leading to increases in cyclic adenosine monophosphate (AMP). This causes bronchodilation, peripheral vasodilation, and an intracellular shift of potassium.
298
What is the mechanism of action of albuterol in cases of an overdose?
Beta-1 receptors are primarily located in the myocardium and stimulation increases both force (inotropy) and rate (chronotropy) of myocardial contractions. Hypokalaemia due to the shift of potassium.
299
What is the most common way pets become exposed to albuterol?
Biting into inhalers, it is well absorbed both orally and by inhalation.
300
What are the clinical signs of albuterol overdose?
1. Initial agitation followed by depression is common
2. Sinus tachycardia (200-300 bpm): The longer sinus tachycardia continues, the more pathological arrhythmias are seen and the higher the risk of myocardial necrosis
3. Tachypnea
4. Weakness
5. Death
301
How is albuterol toxicosis treated?
1. Emesis and activated charcoal administration are only effective if done quickly after ingestion
2. IVFT
3. Heart rate and rhythm should be monitored for 12 to 24 hours.
4. If tachycardic a non-selective beta blockers e.g. propanolol 0.02-0.06mg/kg IV; titrated up as needed to achieve a more appropriate HR <200/min. Not only will it decrease the heart rate, but it will also help normalize the serum potassium concentration.
5. If the serum potassium is still <2.5 mEq/L after beta blocker administration, potassium should be supplemented because hypokalemia further predisposes to ventricular arrhythmias
Signs usually resolve by 12 hours but can persist up to 48 hours
302
What is the mechanism of action of organophosphates and carbamates?
These are anticholinergic insecticides which inhibits acetylcholinesterase resulting in excessive neurotransmitted activity.
303
What are the clinical signs of organophosphate and carbamate toxicosis?
1. SLUGE-M signs
2. Harsh lung sounds due to increase respiratory secretions
3. Bradycardia
304
What is the mainstay of treatment of organophosphates or carbamates?
Atropine (0.1-0.2 mg/kg one-fourth IV, rest IM or SQ)
305
What is the mechanism of action of milkweed toxicosis?
Cardiac glycoside
306
What is the mechanism of action of beta blockers overdose?
Inhibit catecholamine binding to beta receptors resulting in hypotension and bradycardia
307
What is the mechanism of action of bufo toad toxicosis?
Cardiac glycoside
308
What is the mechanism of action of carbon dioxide inhalation?
Simple asphyxiant
309
What is the main clinical sign of carbon dioxide inhalation?
Hypoxaemia
310
What is the mechanism of action of carbon monoxide inhalation?
Binds to hemoglobin (carboxyhemoglobin) and reduces oxygen carrying capacity
311
What is the main clinical signs of carbon monoxide inhalation?
Hypoxaemia
312
What is the mainstay of treatment of carbon monoxide inhalation?
Oxygen; hyperbaric chamber (reduces carboxyhemoglobin levels faster)
313
What is the mechanism of action of the lily-of-the-valley?
Cardiac glycoside
314
What is the mechanism of action of cyanide toxicosis?
Inhibits oxidative phosphorylation, leading to cellular hypoxia
315
How is cyanide toxicosis treatment?
Hydroxocobalamin (75-150 mg/kg IV over 7.5 min) or sodium nitrite plus sodium thiosulfate
Dogs: sodium nitrite: 16 mg/kg IV of a 3% solution, followed by sodium thiosulfate 150-500 mg/kg IV bolus
316
What is the mechanism of action of foxglove toxicosis?
Cardiac glycoside
317
What is the mechanism of action of digoxin overdose?
Cardiac glycoside
318
What is the mechanism of action of hydrogen sulfide toxicosis?
Depressed respiratory center of brain resulting in anoxia.
319
What is the mechanism of action of kalanochoe toxicosis?
Cardiac glycoside
320
What is the mechanism of action of laurel toxicosis?
Grayanotoxin
321
What is the mechanism of action of apple and crabapple toxicosis?
Cyanogenic glycoside - would need to eat a very large amount of the seeds for toxicosis
322
What is the mechanism of action of methane inhalation?
Simple asphyxiant resulting in hypoxaemia
323
What is the mechanism of action of natural gas inhalation?
Simple asphyxiant resulting in hypoxaemia
324
What is the mechanism of action of oleander toxicosis?
Cardiac glycoside
325
What is the mechanism of action of paraquat toxicosis?
Free radical production in lungs
326
What is a long term consequence of paraquat toxicosis?
Pulmonary fibrosis
327
What is the mechanism of action of firefly toxicosis?
Lucibufagins (related to cardiac glycosides)
328
What is the mechanism of action of pieris?
Grayanotoxin
329
What is the mechanism of action of stone fruit toxicosis?
Cyanogenic glycosides
330
What is the mechanism of action of rhododendron, azalea?
Grayanotoxin
331
What is the mechanism of action of sulfuryl fluoride inhalation?
Fluoride binds calcium resulting in hypocalcaemia
332
What are the clinical signs of sulfuryl fluoride inhalation?
Hypocalcaemia and secondary arrhythmias, tetany, seizures and death.
333
What is the mainstay of treatment of sulfuryl fluoride?
Correction of hypocalcaemia
334
What is the mechanism of action of smoke inhalation?
Irritation of airways, particulates
335
What are the consequences of smoke inhalation?
Pulmonary edema, hypoxemia. Important to monitor for 24 hours
336
What is the mechanism of action of TCA overdose?
Blocks sodium channels. Results in arrhythmias and serotonin syndrome
337
What is the mainstay of treatment of TCA overdose?
Titrate pH to 7.55 with IV sodium bicarbonate
338
What is the mechanism of action of calcium channel blockers?
Calcium channel blockers (CCBs) are used for treating tachyarrhythmias by slowing conduction through the atrioventricular (AV) node via frequency-dependent channel blockade at the AV node (nondihydropyridine-type CCBs, e.g., diltiazem, verapamil), and for treating systemic hypertension via direct action on calcium channels in smooth muscle (dihydropyridine-type CCBs, e.g., amlodipine, nifedipine).
339
What occurs in overdose of a calcium channel blocker?
Leads to:
- Bradycardia
- Severe hypotension
- Hyperglycemia
- Hyperkalemia
- Hypokalemia
- Hypocalcemia
Noncardiogenic pulmonary edema has been reported in cases of massive overdose
340
How is an overdose of a calcium channel blocker treated?
1. Decontamination e.g. emesis, activated charcoal
2. Monitoring HR, rhythm and electrolytes
3. IVFT and calcium if hypotrensive and hypocalcaemic
4. IV lipid emulsion therapy can be attempted if there is no change in cardiovascular parameters.
5. Other therapeutics that can be tried include atropine and isoproterenol for bradyarrhythmias and norepinephrine, phenylephrine, dopamine, or dobutamine for hypotension.
6. Insulin/dextrose has improved survival in a canine model by improving cardiac inotropy
341
What is the mechanism of action of cardiac glycosides?
Cardiac glycosides inhibit the myocardial cell Na+/K+ ATPase pump. This results in increased intracellular sodium. The sodium is eliminated by an exchange with calcium. The sarcoplasmic reticulum binds the excess intracellular calcium and uses it to increase contractility, leading to more forceful contractions.7 A similar mechanism in the central nervous system (medulla) increases vagal tone, lowering heart rate.
342
What are the effects of cardiogenic glycosides?
Cardiac effects may include:
- first-, second-, or third-degree AV block
- premature atrial or ventricular complexes
- atrial or ventricular tachycardia, and ST segment changes being the most common.
Other effect include:
- vomiting
- lethargy
- inappetence
- anorexia.
343
What is the treatment for cardiac glycoside toxicosis?
1. Decontamination e.g. emesis, activated charcoal binds to cardiac glycosides and decreases digoxin absorption by 96%.
2. Cholestyramine and IV lipid emulsion (ch. 132) have also been shown to be beneficial in decontamination
3. Antiarrhythmic treatment should be instituted as appropriate
4. Choose a non-calcium containing fluid to avoid increasing the risk of arrhythmias. Potassium levels should be monitored, and insulin/dextrose administered if hyperkalemia is noted
5. There is a digoxin-specific immune fragment antigen-binding (Fab) product available for humans that has been used off label in dogs and cats
344
How long can clinical signs last for in cases of cardiac glycoside intoxication?
Clinical signs can last for days due to the long half-life of cardiac glycosides
345
What are the signs of toad intoxication?
Signs begin almost immediately and include hypersalivation, vomiting, weakness, lethargy, vocalization, arrhythmias (brady- and tachyarrhythmias), tachypnea, ataxia, tremors, collapse, seizures, and death.
346
What is the treatment for toad intoxication?
1. Decontamination - If the toad was swallowed and the patient is not showing clinical signs, emesis should be induced or endoscopic or surgical removal should be considered.
2. Digoxin immune Fab may provide antidotal treatment.
347
What is the toxic dose of fireflies?
Based on experimental studies, approximately 1 firefly per kilogram could be enough to cause significant cardiovascular abnormalities.
348
What is the mechanism of action of grayanotoxins?
They bind to sodium channels in the excitable cell membranes of nerves and cardiac and skeletal muscle. This increases the membrane permeability of sodium ions and maintains the cells in a state of prolonged depolarization. When severe, this negative chronotropic action decreases sinoatrial node activity, causing arrhythmias and potentially sinus arrest.
349
How is grayanotoxins toxicosis treated?
- Emesis can be induced, and activated charcoal can be administered in pets that are not showing clinical signs.
- Monitoring heart rate and rhythm is important. Cardiac arrhythmias may require antiarrhythmic treatment. Signs can last for 1-2 days.
350
What is the mechanism of action of imidazoline decongestants?
They are sympathomimetic agents with primary effects on alpha-adrenergic receptors.
351
What are the clinical signs of imidazoline decongestant intoxication?
vomiting, weakness, lethargy, bradycardia, respiratory depression, and coma.
352
How soon after ingestion of imidazoline decongestants do we see signs?
30 minutes to 4 hours of exposure
353
How is imidazoline decongestant toxicosis treated?
Reversal of clinical signs can be achieved with atipamezole (50 mcg/kg, one-fourth IV, rest IM) or yohimbine (0.1 mg/kg IV).
These medications may need to be repeated in 1-2 hours
354
How is paraquat toxicosis treated?
Paraquat is poorly absorbed from the GI tract, so induction of emesis and administration of activated charcoal can be given even to patients who are showing clinical signs. Paraquat levels peak in the lungs 4-5 days after exposure. Hemodialysis gives the best prognosis. Oxygen increases oxidative injury in the lungs. The prognosis is guarded to poor.
355
What are the signs of phenylopropanolamine overdose?
Agitated and tachycardic, but as the blood pressure increases (vasoconstriction), they may become lethargic and bradycardic.21 Piloerection, tremors, and seizures can also occur.
356
How soon after phenylpropanolamine overdose do signs occur and how long can they last for?
Within 30-90 minutes and may continue up to 48 hour
357
What is the treatment of phenylpropanolamine overdose?
1. Emesis if non-clinical
2. Management of hypotension with nitroprusside or other vasodilators
3. Atropine is contraindicated in bradycardia as it can worsen hypertension
4. IVFT
5. As with intoxications with other stimulants, cyproheptadine may be given if signs of serotonin syndrome develop.
358
When do animal typically get expose to sulfuryl fluoride?
It is a fumigant gas used to kill termites
359
What is the treatment of sulfuryl fluoride toxicosis?
maintaining ventilation, oxygenation, and correcting the hypocalcemia.
Other electrolytes, such as potassium and magnesium, can also be affected.
Lidocaine can be used appropriately for ventricular dysrhythmias.
Fluids should be used judiciously as pulmonary edema can occur. The prognosis is poor.
360
What is the mechanism of action of yew toxicosis?
They inhibit the normal exchange of sodium and calcium across myocardial cells. This depresses cardiac depolarization and leads to arrhythmias (potentially fatal).
361
What is the treatment of yew toxicosis?
Activated charcoal will bind taxine alkaloids, but the stress of administration could potentially worsen clinical signs. Treatment consists of supportive care. Patients that survive 12 hours are likely to survive the intoxication.
362
Haematologic toxicoses
Chapter 138
363
What are the common haematological toxicants in dogs and cats?
1. Medications e.g. acetaminophen, apixaban, rivaroxaban, aspirin, chemotherapeutics, clopidogrel, chloramphenicol, colchine, estrogens, local anaesthetics, phenazopyridine, phenylbutazone, polysulfated glycoaminoglycan, sulfonamides
2. Plants e.g. allium spp (e.g. onion, garlic, leeks and shallots)
3. Anticoagulant rodenticides
4. Heavy metals e.g. Lead, zinc
5. Recluse spiders, pit viper
6. Naphthalene
7. Propylene glycol
364
What is the mechanism of action of anticoagulant rodenticide ingestion?
They work by blocking the recycling of vitamin K, by inhibiting the enzyme vitamin K 1,2,3-epoxide reductase. Vitamin K is needed to carboxylate clotting factors II, VII, IX, and X results in depletion of these factors.
365
How soon after ingestion does spontaneous bleeding occur?
3-7 days after ingestion
366
What are the most common sites of bleeding in causes of anticoagulant rodenticide ingestion?
Sites of hemorrhage include the thorax (most commonly), abdomen, joints (especially in large-breed dogs), subcutis, or central nervous system (CNS).
367
How is anticoagulant rodenticide ingestion treated?
- Decontamination can be attempted within 4 hours of ingestion
- Vitamin K1 (1.25-2.5 mg/kg/day), The duration of treatment depends on the agent ingested. For warfarin (Coumadin), 14 days; for all other ARs, treatment should continue for 30 days except for bromadiolone, which is for 21 days.
- Fresh frozen plasma in severe cases
- Whole blood transfusion
368
Which monitoring tool can we use to assess anticoagulant rodenticide intoxication?
PT and APTT. Since factor VII has the shortest half-life in dogs and cats, the PT can become prolonged first, within 48-72 hours of exposure. Therefore, a single PT assessed between these hours should be sufficient to determine if treatment is needed.
369
Describe the metabolism of acetaminophen.
- Quickly absorbed and peak plasma levels are seen at 10-60 minutes (60-120 min for extended release).
- It is distributed into most body tissues, with the highest concentrations in the periportal zone of the liver and the renal medulla.
- The metabolism of acetaminophen occurs primarily in the liver
370
What is the mechanism of action of acetaminophen toxicosis?
A byproduct of acetaminophen metabolism, via phase 1 deacetylation, is para-aminophenol (PAP). It is implicated in the hematotoxic effects seen in cats and dogs. While PAP is rapidly conjugated to glutathione (GSH) or acetate in laboratory rodents, cats have a reduced capacity for n-acetylation and dogs lack the hepatic n-acetyltransferase enzyme. GSH becomes depleted in the RBCs, and hemoglobin is oxidized to MetHgb. MetHgb values increase within 2-4 hours, followed by Heinz body formation.
371
What is the benefits of N-acetylcysteine in cases of acetominophen toxicosis?
Decreases the half-life of methemoglobin in cats from 10 to 5 hours
372
What is the toxic dose of naphthalene mothballs?
Naphthalene mothballs are very toxic, and 1-2 mothballs can cause methemoglobinemia and hemolysis
373
How are agents that cause bone marrow suppression treated?
1. Decontamination if in the earliest stages (subclinical), specific antidotes if available (e.g., leucovorin for methotrexate)
2. Filgrastim (1-5 mcg/kg SQ daily) can be administered if severe neutropenia develops
3. RBC transfusions may be used for treating anaemias
4. Darbepoetin (0.45 mcg/kg)
374
What can cause hyperoestogenism?
1. Estrogen producing tumours e.g. sertoli cell tumour
2. Medications e.g. bill control
3. Supplements
375
How long does it take for estrogens to cause bone marrow suppression?
signs can take up to 14 days to manifest
376
What is the mechanism of action of toxins that cause methemoglobinemia?
Methemoglobin (MetHgb) occurs when the iron in hemoglobin is oxidized from the ferrous form (Fe2+) to the ferric form (Fe3+); the ferric form of iron is incapable of carrying oxygen (ch. 27). This change reduces the blood’s oxygen carrying capacity; in animals with MetHgb, the blood appears dark brown and the mucous membranes take on a “chocolate” or muddy cast.
377
How is methemoglobinaemia treated?
1. Decontamination
2. Activated charcoal
3. N-acetylcysteine can be administered with a loading dose of 140 mg/kg PO or IV followed by 70 mg/kg PO q6h for 5-7 additional doses.
4. Ascorbic acid (20-30 mg/kg PO, IM, IV q8h × 3 days) can be given, as it reduces MetHgb back to hemoglobin
5. Oxygen should be administered as needed
6. Methylene blue (1-1.5 mg/kg slow IV) can be used for accelerating the reduction of MetHgb back to hemoglobin.
378
Why is the use of methylene blue controversial in cats?
The use of methylene blue is considered controversial in cats as it can cause Heinz bodies and MetHg
379
What are the allium spp.?
- Onion
- Garlic
- Leeks
- Chives
380
What is the toxic dose of onions in dogs?
15-30 g/kg of raw onions
381
How soon after allium spp intoxication are signs seen?
Changes in hematocrit may be seen in as little as 12 hours but typically are seen in 2-5 days.
382
What is the mechanism of action of zinc toxicosis?
Results in haemolysis
383
How is zinc toxicosis treated?
1. Decontamination e.g. emesis. Activated charcoal in ineffective against heavy metals
2.PPIs
Note chelation and rarely required as zinc level will drop rapidly following removal of the metal.
384
How can you diagnosis zinc toxicosis?
1. Radiographs may be helpful but absence on radiographs does not completely rule it out
2. Blood zinc levels may be measured
385
How are toxins that causes haemolysis treated?
1. Decontamination e.g. emesis, activated charcoal if appropriate
2. Id hemolysis has already begun, IV fluid diuresis should be administered to protect the kidneys from hemoglobinuric nephropathy
3. Sodium bicarbonate (2-3 mEq/kg given over several hours in IV fluids) may help to minimize hemoglobin precipitation in the renal tubules.
4. If the anemia is severe, transfusions of whole blood or packed RBCs can be used for supplying enough oxygen carrying capacity to make the patient comfortable
386
How do we monitor patients that have ingested a toxin that can cause haemolysis?
Serial hematocrits and blood smears looking for Heinz bodies can be monitored for about 5 days after exposure, as peak effects can be delayed for several days. Owners should be instructed to monitor for pale mucous membranes, weakness, and hemoglobinuria
387
What is the mechanism of action of allium spp.?
Oxidative damage to RBC from propyl disulfides
388
What are the clinical signs of allium spp.?
Anaemia
389
What is the mechanism of action of rivaroxaban?
Inhibits Xa
390
What is the mechanism of action of aspirin toxicosis?
Acetylation of platelet cyclooxygenase results in a thrombocytopathy
391
What is the mechanism of action of chemotherapeutics agent in the case of toxicosis?
Destruction of RBC-producing cells in bone marrow
392
What is the mechanism of action of chloramphenicol toxicosis?
Bone marrow suppression
393
What is the mechanism of action of clopidogrel?
Inhibits platelet aggregation
394
What is the mechanism of action of estrogens?
Bone marrow suppression
395
What is the mechanism of action of lead toxicosis?
Decreased heme synthesis, increased RBC fragility
396
What CBC changes are seen in lead toxicosis?
Anemia (microcytic, hypochromic), basophilic stippling, nRBCs
397
What is the mechanism of action of local anaesthetic toxicosis?
Oxidation of iron in RBC resulting in methemoglobinemia
398
What is the mechanism of action of recluse spider evenomation?
Depletion of factors VII, IX, XI, XII and thrombocytopenia
399
What is the mechanism of action of methimazole toxicosis?
Bone marrow suppression
400
What is the mechanism of action of phenazopyridine toxicosis>?
Metabolized to acetaminophen resulting in methemoglobinemia
401
What is the mechanism of action of phenylbutazone toxicosis?
Bone marrow aplasia resulting in anaemia and pancytopaenia
402
What is the mechanism of action of pit viper envenomation?
Increased vascular permeability, consumptive coagulopathies, hypercoagulation results in haemorrhage, hypovolaemia and AKI
403
What is the mechanism of action of polysulfated glycoaminoglycan?
Antithrombin activity
404
What is the mechanism of action of propylene glycol?
Oxidative damage to RBC
405
What is PAPP?
PAPP is para-aminopropiophenone bait and it is used for controlling wild dogs and foxes, is highly toxic to dogs, including domestic and working dogs.
406
What can PAPP bait toxicosis cause?
Methemoglobinemia
