Toxicology Flashcards
(210 cards)
1
Q
Common toxins for which IVLE is considered effective
A
Local anaesthetics, Pyrethrins, Baclofen, Metaldehyde, Beta-blockers, Psychotropics, Tramadol LMT BBPP
2
Q
Mode of action of holocyclotoxin
A
Inhibition of release of Acetylcholine from the NMJ. May block potassium channels in the ventricular myocardium.
3
Q
What is the MOA of Bisphosphonates
A
Lowers serum calcium levels by binding to hydroxyapatite crystals in the bone.
4
Q
What is the active constituent of Marajuana
A
Delta-9-tetrahydrocannabinol (THC)
5
Q
Half life of factor VII
A
6.2 hours
6
Q
Mode of action of Anatoxin-A and Homoanatoxin-A
A
Agonists at the nicotinic chonergic receptors in the CNS and neuromuscular junction. Continuous electrical stimulation results in eventual paralysis
7
Q
Clinical signs of cocaine toxicosis
A
Hyperactivity, ataxia, mydriasis, vomiting, hyper salivation, tremors, seizures, tachycardia, tachypnoea
8
Q
Nicotinic Signs
A
Tremors of the head and neck, progressing to full body tremors, weakness, paralysis
9
Q
Describe Mild, and Severe clinical signs associated with Pyrethrin toxicity.
A
Mild - Hypersalivation, paw flicking, ear twitching, hyperaesthesia
Severe - Hypersalivation, vomiting, diarrhoea, dermal hypersensitivity, Hyperthermia, hyperaesthesia, hyper excitability, ataxia, tremors, seizures, mydriasis
10
Q
Treatment of oxyuranus scutellatus envenomation
A
Specific Taipan antivenom only
11
Q
Toxins present in Tiger Snake Venom
A
Pre-and post-synaptic neurotoxins, myolysins, haemolysins, procoagulants. Primary toxin is notexin, which is a Phospholipase A2 that depletes acetylcholine, and is a potent mycotoxin causing muscle degeneration. Procoagulant has Factor Xa-like activity. Haemolysin is weak.
12
Q
Side effects of IVLE:
A
Hypersensitivity, pancreatitis, vomiting, nausea, fever, lipid emboli, ‘Fat overload syndrome’ - hyperlipidaemia, hepatomegaly, icterus, splenomegaly, thrombocytopenia, coagulopathy, haemolysis
13
Q
Clinical Signs of Elapid Antivenom reaction
A
Mild - Erythema, urticaria, periorbital oedema, angioedema
Moderate - Dyspnoea, stridor, wheezing, nausea, vomiting, abdominal pain
Severe - Cyanosis, hypoxia, hypotension, collapse, loss of consciousness
14
Q
MOA Vitamin D
A
Enhances calcium and phosphorus absorption from the gut, and plays a role in reabsorption of calcium from the kidney. At toxic doses, 25(OH)D3 takes over calcitriol for binding at receptor sites, causing a hypercalcaemia. Upregulation of receptors can occur, leading to hypercalcaemic effects until after toxin has cleared.
15
Q
Signs and Pnemonic for Atropine Overdose
A
‘Hot as a pistol, red as a beet, dry as a bone, mad as a hatter’ - Hyperthermia, erythema, belligerency, intestinal stasis, convulsions
16
Q
Clinical signs of THC toxicosis
A
Depression, ataxia, incoordination, urinary incontinence, vomiting, tremors, mydriasis, hypothermia, weakness, bradycardia
17
Q
Clinical signs of Taipan envenomation
A
Paralysis, coagulopathy, myolysis
18
Q
How do NSAIDs cause Nephrotoxic signs
A
Vasodilatory prostaglandins are required in the kidney to mediate vasoconstrictive stimulants that would otherwise impair renal blood flow.
19
Q
Toxins in Brown Snake Venom
A
Procoagulants and pre and post synaptic neurotoxins. Major components are texilotoxin and pseudonajatoxin. Texilotoxin is pre-synaptic, pseudonajatoxin is post-synaptic
20
Q
Clinical Signs of Death Adder envenomation
A
Paralytic signs predominate, weak coagulopathy
21
Q
Describe the haemolysins present in elapid snake venom
A
Cause haemolytic via Phospholipase A2 damage to the RBC membrane, resulting in direct lysis or indirect haemolytic via the formation of spherocytes and removal via the reticuloendothelial system.
22
Q
Describe the procoagulants present in elapid snake venom
A
Contain prothrombin activators C and D, which are serine proteases. Group C is present in the brown snake and taipan, and resembles the prothrombinase complex FXaVa which converts prothrombin to thrombin.
Group D is present in tiger snakes, contains a toxin similar to FXa without the FVa cofactor.
Both lead to a consumptive coagulopathy.
23
Q
What are the effects of serotonin in the peripheral nervous system
A
Vasoconstriction, platelet aggregation, uterine contraction, intestinal peristalsis, bronchoconstriction
24
Q
NSAID MOA
A
Produce reversible COX inhibition through competing with arachidonic acid for the active site on the enzyme
25
Toxins present in Cycads
Cycasin, Beta-methylamino-1-alanine (BMAA), and unidentified high molecular weight compound
26
Treatment of king brown envenomation
Polyvalent tiger brown antivenom, or black snake antivenom
27
Mode of action of lily toxicosis
Unknown. Involves direct damage to the renal tubular epithelium and subsequent renal failure.
28
Toxins present in RBBS venom
Neurotoxins, myotoxins, cytotoxins, haemolysins, weak anticoagulants. Major toxin is Pseudexin, causes haemolysis with Phospholipase A2 enzymes which may be direct (intravascular) or indirect (extravascular).
29
Why are cats more prone to paracetamol toxicity
They lack glucuronide, meaning they rely on cytochrome p450 for metabolism, which produces the toxic metabolite of paracetamol (NAPQI)
30
Pyrethrins MOA
Cause hyper excitability of cells by slowing the closure of sodium channels. This prolongs the period of sodium conductance, which increases length of depolarisation and causes repetitive firing
31
What is Phase I metabolism
Conversion of a xenobiotic into a polar, hydrophilic metabolite.
32
Treatment for pseudonaja texilitis
Monovalent brown snake or polyvalent tiger-brown antivenom
33
Secondary toxins identified in Ixodes holocyclus venom
Lethal non-paralysing toxin, cuticular toxin
34
MOA of acute Copper toxicosis
Unknown. Proposed that copper is directly cytotoxic to hepatocytes and RBCs when present in high enough concentrations, or due to copper-induced free radical formation.
35
Species of elapid snake where venom induced consumptive coagulopathy is seen
Tiger, Brown, Taipan
36
Clinical signs of blue-bellied black snake envenomation
Haemolysis, myolysis, mild paralysis
37
Scientific name RBBS
Pseudechis porphyriacus
38
Intravenous Lipid Emulsion dosing:
1.5mL/kg initial, then CRI of 0.25mL/kg/min for 30-60 min. Repeat in 4-6h if patient not lipaemic.
39
CNS signs seen with carbamate toxicity
Anxiety, restlessness, hyperactivity, depression, seizures, depressed respiration, coma
40
Clinical signs of 1080 toxicosis
CNS excitation progressing into convulsions, arrhythmias and respiratory failure.
41
Describe the anticoagulants present in elapid snake venom
Reversible with antivenom. Inhibit FX, FII, and platelets.
42
Source of Tetrodotoxin
Produced by commensal bacteria within the GIT of bony fish and crustacea, and is transferred into the liver, gonads, and skin of the fish. Puffer fish, Blue-ringed octopus, starfish, parrotfish
43
Scientific Name of the Tiger Snake
Notechis scutatus
44
MOA of amphetamines
Exact mechanism unknown. Has a stimulant effect on the cerebral cortex, RAS, and medullary respiratory centre. Cause a release of noradrenaline from adrenergic nerve terminals, having a direct stimulant effect on alpha and beta receptors. Inhibits monoamine oxidase.
45
Scientific name for Brown Snake
Pseudonaja texilitis
46
Treatment of 1080 toxicosis
Intubation, ventilation, and gastric lavage. Administration of sodium bicarbonate, while mechanically ventilating to ensure appropriate expulsion of carbon dioxide. Glyceryl monoacetate may be used to provide acetate ions to the TCA cycle, efficacy inconsistent.
47
Treatment of Tetrodotoxin toxicosis
No specific antidote - support paralysed patient with oxygen support, airway protection, mechanical ventilation.
48
Clinical signs of lily toxicosis
Vomiting, salivation, anorexia, depression, polyuria at 12-30 hours, anuria at 24 to 48 hours
49
Urine acidification achieved with:
100mg/kg Ammonium Chloride PO q12h
50
How to perform and interpret an atropine response test for carbamate and organophosphate toxicosis
Administer 0.02mg/kg Atropine IV, if none of the clinical signs improve, it is likely to be Carbamate or OP toxicosis
51
MOA of THC
Binding to CB1 and CB2 cannabinoid receptors. CB1 has effects on memory, perception, and control of movement.
52
Ddx Chocolate Toxicity
Caffeine exposure, Strychnine, Nicotine, Amphetamines, Tremorgens
53
Clinical Signs of Bromethalin Toxicosis
Muscle tremors, hyperthermia, extreme hyperexcitability, hyperaesthesia, seizures. Lower doses cause progressive signs over 1-2 weeks - ataxia, paresis, UMN paralysis
54
Treatment of serum sickness
Immunosuppressive doses of prednisolone with tapering after afew days.
55
Clinical signs of RBBS envenomation
Haemolysis, myolysis, +/- arryhthmias, weak paralysis, elevated clotting times.
56
Treatment for lead toxicosis
Calcium EDTA is the most effective chelating agent - 100mg/kg/d for 2-5d (split into 4 doses a day)
57
Specific treatment of ethylene glycol toxicosis
Ethanol for competitive inhibition of alcohol dehydrogenase.
58
Clinical signs of eastern small-eyed snake envenomation
Profound myopathy and myoglobinuria
59
Treatment of Carbamate Toxicosis
Atropine @ 0.1-0.5mg/kg will relieve muscarinic and CNS but not nicotinic signs. Anticonvulsants for Nicotinic signs
60
Toxins present in Rhinella marina venom
Bufogenins & bufotoxins, Bufotenins, Catecholamines, Indoalkylamines
61
Mode of action of Penitrem A and Roquefortin
Uncertain if they act independently or synergistically. Proposed that Penitrem A can inhibit CNS glycine production
62
Factors that can reduce Vd
Binding to plasma proteins, being unable to cross the capillary layer
63
Clinical signs of PAPP toxicosis
Hypoxia, collapse, coma, blue to brown MM
64
Clinical signs and stages of iron toxicosis
Stage 1: first 0-6 hours. GI signs predominate (vomiting, haematemesis, diarrhoea, abdominal pain)
Stage 2: Hours 6-24. Apparent recovery
Stage 3: Hours 12 to 96. Return of GI signs, metabolic acidosis, shock, hepatic failure, cardiovascular collapse, coagulopathy
Stage 4: Weeks 2-6. GI obstruction after fibrosis repair of tissue (doesn't always happen)
65
Why are cats thought to be more sensitive to the toxic effects of pyrethrins?
Deficiency of hepatic glucuronosyltransferase. As pyrethrins undergo hepatic hydroxylation and conjugation into glucuronides or sulphates.
66
What is serum sickness
A type III hypersensitivity reaction seen after administration of antivenom. An immune response to antibody complexes being deposited on endothelial surfaces
67
MOA Zinc Phosphide Toxicosis
Phosphide becomes unstable in the acid environment of the stomach to release phosphine gas. Causes corrosion to the mucosa of the GI, respiratory tract, and oxidative injury to the parenchyma. It can freely diffuse into intracellular compartments and initiate neutrophilic attack. Increases ROS and causes oxidative damage. Can inhibit cholinesterase.
68
MOA of anticoagulant rodenticides
Blocks the action of vitamin K epoxide reductase, leading to a progressive depletion in clotting factors.
69
How do NSAIDs cause GI toxic signs
GI defence mechanisms are mediated by prostaglandins: bicarbonate and mucus secretion, blood flow, epithelial cell turnover, mucosal immunocyte function. Prostaglandins are also responsible for the inhibition of gastrin and Hal release. Also topically irritant.
70
Clinical signs of xylitol toxicosis
Vomiting, lethargy, ataxia, seizures, hypoglycaemia, coagulopathy
71
What is the MOA of Pralidoxime
Attaches to cholinesterase inhibitors and removes them from the enzyme, thereby inactivating it
72
Clinical signs and phases of ethylene glycol toxicosis
Stage I (Inebriation) - Vomiting, nausea, depression, disorientation, seizures, anorexia. 30 min to 12h
Stage II (Metabolic Acidosis) - Tachypnoea, tachycardia. 12-24h
Phase III (Oligura/Anuria) - Clinical signs of renal disease. 72-96h
73
What determines the ability of a drug to be treated by IVLE?
Lipophilicity of the drug, determined by Log P value. A product with a value >1.0 is considered to be affected by IVLE. The higher the lipophilicity of a drug, the more likely IVLE is to be effective
74
Treatment of Copperhead envenomation
Polyvalent tiger-brown antivenom
75
Mode of action of Bufotenins
Pressor agents similar in structure to oxytocin, thought to be hallucinogenic
76
Treatment of Iron Toxicosis
Decontamination with emesis or lavage in first few hours. May perform gastronomy if tablets have formed a bezoar.
Fluid support, GI protectants, Desferroxamine @ 15mg/kg/h if Serum iron >300mcg/dL or if signs severe . Little benefit from desferroxamine >12h post-ingestion
77
MOA of Cocaine
Blockage of norepinephrine and serotonin uptake, leading to excess of neurotransmitters at receptor sites. Also sensitises sympathetic effector cells to the effects of catecholamines
78
What are the effects of serotonin in the central nervous system
Effects on mood, aggression, thermoregulation, sleep, vomiting, and pain perception
79
Dose ranges and expected signs for Methylxanthines
>15mg/kg - Mild GI upset and hyperactivity
20mg/kg - Mild Toxicity
33-50mg/kg - Increased HR
40-50mg/kg - Severe toxicity
60mg/kg - Seizures
Onset of signs for caffeine in 1-2h, theobromine in 6-12h
80
Describe the mechanism of the cardiotoxin in taipan venom
Aka taicatoxin. Inhibits calcium channels in the myocardium, leading to prolonged repolarisation and arrhythmias. Negative inotrope, chronotrope, and positive lusitrope.
81
Ddx for carbamate toxicosis
OPs, tremorgenic mycotoxins, pyrethrins, garbage intoxication, blue-green algae, muscarinic mushrooms
82
Describe the metabolism of Ethylene Glycol once absorbed
Alcohol dehydrogenase converts ethylene glycol to glycoaldehyde --> glycolic acid --> glyoxylic acid. Glyoxylic acid is the toxic metabolite.
83
Complications of Metaldehyde Toxicosis
Metabolic acidosis, hyperthermia, DIC, hepatic injury, respiratory failure, transient blindness
84
Tests to Confirm Vitamin D Toxicosis
Serum PTH (will be suppressed), Serum calcitriol, ionised calcium, serum 25(OH)D3 (increased up to 15x)
85
MOA of Baclofen
Stimulation of GABA and inhibition of substance P and glutamate, resulting in flaccidity, respiratory depression, hypotension
86
Name the 4 Mycotoxins
Aflatoxin, Vomitoxin, Penitrem A, Roquefortin
87
Treatment of Pseudechis porphyriacus envenomation
Polyvalent tiger-brown antivenom or black snake antivenom
88
Signs seen with chronic carbamate exposure
Downregulation of acetylcholine receptors at muscarinic sites, leading to nicotinic syndrome
89
Clinical signs of Aflatoxicosis
Weakness, lethargy, GI upset, Icterus, coagulopathy, hypoglycaemia
90
Confirmation of carbamate toxicosis
History of ingestion, found in vomitus or faeces, assessment of cholinesterase activity of whole blood, atropine response test
91
Mode of action of Bufogenins and Bufotoxins
Inhibition of Na/K ATPase pump, resulting in intracellular sodium and calcium accumulation and potassium depletion. Results in increased excitability of neurons and cardiac purkinje fibres
92
Clinical Signs of Brown Snake Envenomation
Paralysis, consumptive coagulopathy, +/- haemolytic. Generally no myolysis. Pre-paralytic signs demonstrated with a lethal dose - vomiting, haematemesis, haemoptysis, trembling, salivation
93
Organophosphate Toxicosis antidote and MOA
2-PAM aka pralidoxime. Not available in Australia. Binds the OP-inactivated acetylcholinesterase and causes unbinding of the organophosphate which reactivates the enzyme. However, after some time organophosphate binding is irreversible.
94
Treatment of Vitamin D Toxicosis
Emesis if ingestion in past 6 hours, activated charcoal and cathartic if not contraindicated. Repeated activated charcoal recommended. Bisphosphonates - Pamidronate at 1.3-2mg/kg over 2-4h q4d for 2 infusions. IVFT @ 2-3x maintenance to enhance calcium excretion. Antiemetics and GI protectants.
95
Treatment of Zinc Phosphide Toxicosis
Keep in well ventilated area (can pose risk to other animals and human staff). Emesis contraindicated. Alter gastric pH to be greater than 4.0 with magnesium or aluminium hydroxide (gaviscon, mylanta), IVFT, antiemetics, +/- pressors, +/- anticonvulsants, +/- magnesium for life threatening arrhythmias, N-AC for ROS scavenging.
96
How do NSAIDs cause coagulopathic signs
COX is essential for the formation of thromboxane, which is both a vasoconstrictor and platelet activator.
97
Two forms of vitamin D in mammals
Vitamin D2 (ergocalciferol) derived from plants, Vitamin D3 (cholecalciferol) derived from animals
98
Contraindications for use of activated charcoal
Patients at risk of aspiration, toxins that don't reliably bind to activated charcoal, patients that have ingested caustic material, patients that have ingested osmotically active agents
99
Treatment of PAPP toxicosis
Slow administration of methylene blue, no more than 10mg/kg over 12h. ASAP
100
Toxic doses of xylitol
>0.1g/kg for hypoglycaemia, >0.5g/kg for hepatic toxicity
101
Treatment of blue-bellied black snake envenomation
Polyvalent tiger-brown antivenom or black snake antivenom
102
Mode of action of Anatoxin-A(s)
A naturally occurring acetylcholinesterase inhibitor that leads to persistent stimulation and neuromuscular shock. Causes muscarinic and nicotinic overstimulation. Death in minutes.
103
Mode of action of Brunfelsia toxicosis
Unknown, compounds thought to be similar to strychnine toxicosis - blocking inhibitory effects of glycine in anterior horn.
104
Clinical signs of Brunfelsia toxicosis
Agitation, excitement, nervousness, tremors, paddling, seizures
105
King brown snake envenomation clinical signs
Myolysis, haemolysis, paralysis, coagulopathy
106
Black whip snake envenomation clinical signs
Bite site pain, local tissue destruction
107
Decontamination and Treatment for Organophosphate Toxicosis
Emesis not recommended if symptomatic or product in a petroleum-base. Administration of activated charcoal and sorbitol. Atropine to control bronchial secretions and bradycardia - mild toxicity dose 0.1-0.5mg/kg q1-2h, severe toxicity 1-2mg/kg q1-2h. Quarter dose IV and remainder SC or IM. Support with IVFT, gastroprotectants, antiemetics, anticonvulsants
108
Confirmation of Zinc toxicosis
Presence of radiopaque metallic FBs on radiography, Heinz bodies in RBCs, serum zinc levels
109
Acid diuresis is used for:
Amphetamines and Phencyclidine
110
What is the difference between a toxin and a toxicant
A toxin is a poison originating from biological processes, whereas a toxicant is a broad term for all poisons
111
Clinical signs of chronic lead poisoning
Abdominal discomfort, vomiting, diarrhoea, lethargy, weight loss, anaemia, intermittent seizures, mega-O
112
Mode of action of Cycasin in Cycad toxicosis
Metabolised to Methylazoxymethanol (MAM) in the GIT, which is absorbed by the portal vein, and oxidised by cytochrome p450, undergoes glucuronidation and is excreted in the bile. Metabolism of MAM yield alkylating agents that are directly toxic to hepatocytes. Causes centrilobular and midzonal necrosis.
113
Strychnine MOA
Rapid absorption from GIT and MM. Rapid metabolism by hepatic microsomal enzymes to strychnine-N-oxide. Block the inhibitory action of glycine on the anterior horn of cells of the spinal cord, leading to excessive neuronal activity and exaggerated reflex arcs.
114
4 other proposed mechanisms of IVLE
1. Restoration of myocyte function through increasing intracellular calcium, with the resultant inotropy defeating depressive effects of intoxication. (Local anaesthetics)
2. Supplementation of cardiac energy supplies, overwhelming the blockade of fatty acid transport by local anaesthetics.
3. Interference with the binding of local anaesthetics to sodium channels
4. Accelerated shunting
115
Lethal Dose of Vitamin D
0.1-2mg/kg
116
Mode of action of nodularins
Inhibition of serine-threonine protein phosphatases, resulting in disruption of cytoskeletal components. Acute liver necrosis, intrahepatic haemorrhage, and shock.
117
What is Phase II metabolism
Conjugation of the xenobiotic or metabolite with a functional group that results in a multi-fold increase in water solubility
118
MOA Xylitol
Strong stimulator of insulin release, causing severe hypoglycaemia. Two proposed mechanisms of hepatic necrosis - either depletes hepatic cellular ADP, ATP and inorganic phosphorus, or metabolism of xylitol produces ROS.
119
MOA of Lysergic Acid Diethylamide
LSD. True mechanism undefined. Common site of action at 5-HT receptors, with the 5-HT2a receptor thought to modulate hallucinogens. Clinical course is difficult to predict due to variable effect
120
Define Chemical Antidote
An antidote that works directly on the toxicant to make it less toxic or more readily excreted
121
What is COX-2
An inducible enzyme, responsible for the production of pro-inflammatory prostaglandins
122
Treatment of mild Rhinella marina envenomation
Wiping of gums for 10-15 minutes with a moist cloth, administration of an anticonvulsant
123
When is emesis induction contraindicated?
Ingestion of corrosive substances or hydrocarbons, if the patient is already vomiting, a patient demonstrating clinical signs of toxicosis, predisposing disease creating risk for aspiration.
124
When is gastric lavage indicated?
When emesis is contraindicated or unsuccessful, and the toxin has a high risk of mortality. Considered most effective within 10-30 minutes, and declining efficacy at 60-120 minutes
125
What is the fate of serotonin after synaptic release?
Active reuptake and inactivation by monoamine oxidase
126
Describe the two types of neurotoxin present in elapid snake venom.
Pre-synaptic: Blocking release of acetylcholine into the NMJ through binding and hydrolysing of the motor nerve terminal, causing degeneration and preventing recycling of acetylcholine after exocytosis. (Phospholipase A2 is the active 'ingredient')
Post-Synaptic: Block acetylcholine receptors. May be reversible with antivenom, slower onset of paralysis.
127
Define Pharmacological Antidote
An antidote that binds to the toxin or binds to the target of the toxin. Can antagonise toxic agents at the receptor site and oppose clinical signs of toxicosis.
128
Treatment of Strychnine Toxicosis
Emesis if not contraindicated. Gastric lavage under GA if severe signs. Pentobarbital, Diazepam, or Methocarbamol to control tremors. Pentobarbital abolishes the spontaneous activity of spinal cord neurons. Oxygen support as required.
129
Muscarinic Signs
SLUDGE - Salivation, Lacrimation, Urination, Defecation, Gastroenteritis
130
What are the toxic components in chocolate
Methylxanthines - Theobromine & Caffeine
131
Mode of action of Tetrodotoxin
Blockage of sodium channels, preventing the generation of action potentials. Peripheral nerve fibres affected the most. Results in LMN paralysis and hypoventilation
132
Treatment of death adder envenomation
Death Adder specific antivenom required.
133
Clinical signs of Copperhead envenomation
Weak coagulopathy, haemolysis, paralysis
134
Lethal dose of methylxanthines
100-150mg/kg
135
When is ion trapping indicated?
When products are a weak acid or base, and are excreted unchanged through the kidneys. Ideally compounds aren't protein bound and are primarily distributed to the ECF
136
Define Ion Trapping (as a decontamination method)
Alteration of urine pH to inhibit reabsorption of toxins across the renal tubular membranes. Toxins are trapped in their ionised form to be excreted in the urine.
137
Methiocarb MOA
Cholinesterase inhibition, causing continued neuronal depolarisation by acetylcholine. Muscarinic, Nicotinic, and CNS signs develop. Ongoing depolarisation causes paralysis, because repolarisation of the membranes is inadequate
138
Clinical Signs of Organophosphate Toxicosis
Rapid onset of signs. Muscarinic signs appear first - SLUDGE (Salivation, Lacrimation, urination, Defecation, Gastroenteritis). Nicotinic (tremors of head and neck, generalised tetany & stiffness, weakness, paralysis) and CNS (anxiety, restlessness, hyperactivity, obtundation, tonic-clonic seizures, coma) follows.
139
List some pharmacologic antidotes
N-Acetylcysteine, Pralidoxime, Vitamin K, Fomepizole, Ethanol, Atipamezole, Atropine, Flumazenil, Naloxone
140
Two hepatotoxins produced by cyanobacteria
Microcystins and Nodularins
141
How is serotonin produced?
Produced and stored in enterochromaffin cells of the GIT, or in serotonin-producing neurons in the CNS. Serotonin is produced using tryptophan as a precursor
142
Treatment of eastern small-eyed snake envenomation
Polyvalent tiger-brown antivenom
143
Clinical Signs of Vitamin D Toxicosis
May not appear for 36-48h. Depression, weakness, anorexia, vomiting, PU/PD, constipation, dehydration +/- GI bleeding (due to mineralisation of stomach wall). Metastatic mineralisation of organs in severe cases.
144
Treatment of VICC
Antivenom to neutralise procoagulant toxins, support for following 12-48h while clots factors re-synthesise. FFP use controversial, and shouldn't be done until after antivenom administration.
145
When is surgical decontamination of toxins indicated?
If an item is unable to be removed by emesis or endoscopy,
146
What drugs have a high serotonergic potential
5-hydroxytryptophan, amitriptyline, dextromethorphan, fluoxetine, paroxetine, meperidine, selegiline, sertraline, venlafaxine
147
Treatment of severe Rhinella marina envenomation
Gastric lavage or endoscopy to remove toad if swallowed, oxygen therapy, judicious frusemide use, atropine if bradycardic, pressors for vasodilatory shock, antiarrhythmics if ventricular tachyarrhythmias present, TIVA to control tremors, Mannitol with prolonged seizure activity, +/- digoxin-specific antibody fragments
148
Treatment of Serotonin Syndrome
Induce emesis and administer activated charcoal if not indicated. Repeated doses may be required for sustained release drugs. Airway control and MV may be required. Sedate with chlorpromazine, which has 5-HT2a blocking properties. Provide Cyproheptadine at 1.1mg/kg PO q6h.
149
MOA of arsenic toxicosis
Trivalent arsenicals interact with sulfhydryl groups of biologic compounds, thus interfering with the action of enzymes, coenzymes, and substrates.
Pentavalent arsenicals either become trivalent arsenicals, or prevent ATP formation through substitution for phosphorus, creating adenosine diphosphate arsenate
150
Methods of confirmation of elapid snake envenomation.
History/visualised bite, CK & Coags, Consistent clinical signs, SVDK on urine/bite site/serum
151
Clinical signs of Methylxanthine Toxicosis
Nausea, Vomiting, Diarrhoea, Tachycardia, Tachyarrhythmias, Bradycardia, Hypertension, PU/PD, Tachypnoea, Respiratory failure, Hypokalaemia, Hyperexcitability, Seizures
152
What is the proposed MOA of metaldehydes
Increase of excitatory neurotransmitters , decrease of inhibitory neurotransmitters, or lowering of seizure threshold. Reduction of GABA considered to be main culprit.
153
List some functional antidotes
Bisphosphonates, Cyroheptadine, Acepromazine, Misoprostol
154
MOA and Metabolism of Elemental Iron
Iron enters the circulation and binds to transferrin. When iron binding is saturated, iron is free to interact intracellularly. Produces free radicals intracellularly and causes oxidative tissue damage.
155
Describe the myotoxins present in elapid snake venom
Bind to muscle fibres and cause progressive degradation of muscle cells with release of breakdown products.
156
Dose ranges and severity of toxicity for iron ingestion
<20mg/kg: Gastric upset
20-60mg/kg: Mild to moderate intoxication
>60mg/kg: Serious threat for severe intoxication
>100mg/kg: Can be fatal
157
Clinical signs of arsenic toxicosis
Haemorrhage, pulmonary oedema/visceral congestion, abdominal pain, salivation, collapse, vomiting, diarrhoea
158
List some chemical antidotes
Antivenom, chelating agents, Digoxin immune Fab Fragments
159
Describe the metabolism of Vitamin D3 after ingestion
Transported in plasma to the liver by vitamin-D binding protein. In the liver, it is metabolised to 25(OH)D3, which is the main circulating metabolite of Vitamin D. This is not well regulated. 25(OH)D3 is further metabolised to Calcitriol and 24,25(OH)D3 in the PCT. This is tightly regulated.
160
Treatment for Notechis scutatus envenomation
Polyvalent Tiger-Brown antivenom
161
Which receptors are considered responsible for serotonin syndrome?
5-HT1a and 5-HT2a
162
What is GI Dialysis
Multiple doses of activated charcoal for toxins that undergo enterohepatic recirculation
163
Apomorphine Mode of Action
Synthetic opiate that stimulates dopamine receptors in the CRTZ
164
Clinical signs of Tetrodotoxin toxicosis
Vomiting first, progressive LMN paralysis
165
What is the proposed toxicant present in raisins and grapes?
Tartaric acid
166
What are the five mechanisms that can lead to serotonin syndrome
1. Increase in serotonin synthesis (provision of precursors)
2. Increase in serotonin release from pre-synaptic neurons (amphetamines, cocaine)
3. Blockade of serotonin uptake from the synapse (TCAs, SSRIs, opioids)
4. Decreased serotonin metabolism (MAOIs)
5. Stimulation of serotonergic receptors by serotonin agonists (psilocybin, LSD)
167
Define the Volume of Distribution (Vd)
A proportion between the amount of a chemical found in the blood, to the total amount present in the body at any one time. High Vd implies a well distributed chemical
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Symptoms of Rhinella marina envenomation
Tachycardia, hypertension, arrhythmias, seizures, tremors, hyperaesthesia, ptyalism, ataxia
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MOA of Para-Aminopropiophenone toxicosis
PHAPP metabolite formed within the liver causes development of methaemoglobinaemia.
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How is the therapeutic index of a drug determined?
LD50/ED50
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Mode of action of microcystins
Free radical production, mitochondrial alteration, and oxidative stress resulting in hepatotoxicity
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Alkaline diuresis achieved with:
1-2mEq/kg Sodium Bicarbonate IV over 6h
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Clinical signs of serum sickness
Urticaria, oedema, lymphadenopathy, polyarthropathy, proteinuria
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Mode of action of Aflatoxin
Absorbed from the intestine and transported to the liver, there metabolically activated to 8,9 epoxide by cytochrome p450. 8.9 epoxide binds to macromolecules within cells and causes necrosis of metabolically active cells - hepatic and renal to lesser extent
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Treatment of eastern small-eyed snake envenomation
Polyvalent tiger-brown antivenom
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Clinical Signs of Tiger Snake Envenomation
Paralysis, rhabdomyolysis, haemolytic, consumptive coagulopathy. Pre-paralytic signs may occur (CV collapse due to hypotension, vomiting, salivation, defecation, trembling)
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Species of lily causing toxicosis
Lilium spp and Hemerocallis spp
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Clinical signs of acute lead poisoning
Anorexia, vomiting, abdominal pain, behaviour changes, ataxia, tremors, hyperexcitability, seizures
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How do NSAIDs cause hepatotoxicity
Unknown. Possibly due to individual genetic polymorphisms in detoxification enzymes
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Treatment of amphetamine toxicosis
Sedation with phenothiazines (dopamine antagonists), may also use benzodiazepines, but they can serve to exacerbate the effects of amphetamines, Control of tachyarrhythmias with antiarrhythmics. Can trial urinary acidification in severe cases.
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Mode of action of Vomitoxin
Direct CRTZ stimulation, causes acute profuse vomiting
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Three Neurotoxins produced by cyanobacteria
Anatoxin-A, Homoanatoxin-A, Anatoxin-A(s)
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Treatment of arsenic toxicosis
Correct systemic shock. Chelation therapy with Dimercaprol.
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MOA of Ethylene Glycol toxicosis
Glyoxylic acid is oxidised to oxalic acid, which binds to serum calcium to form calcium oxalate crystals, which causes GIT irritation, and renal tubular damage. Metabolites inhibit oxidative phosphorylation, glucose metabolism, protein synthesis, and DNA replication. Glycolic acid causes metabolic acidosis.
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Toxins likely to respond to forced diuresis
Toxins with a high rate of renal excretion - Amphetamines, Bromides, Lithium
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Differentials for signs seen with Metaldehyde Toxicosis
Amphetamines, Blue-Green Algae, Bromethalin, Chocolate, Ivermectin, Methionine, Pyrethrins, 1080, Strychnine, Xylitol
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Describe the normal pathway of Vitamin K in producing Vitamin K-dependent clotting factors
Vitamin K Hydroquinone is oxidised with the gamma-carboxylase enzyme to Vitamin K Epoxide, which assists in the transformation of a non-functional factor to a functional factor. Vitamin K Epoxide is reduced with the epoxide-reductase enzyme to Vitamin K quinone, which is then reduced with Vitamin K reductase to Vitamin K hydroquinone.
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What is the difference between first order kinetics, and zero order kinetics, as they pertain to drug metabolism?
First order kinetics describes metabolism of a xenobiotic at a rate proportional to the amount of product in the body at any time. Zero order kinetics describes metabolism in a saturable pathway, meaning that only a finite amount of chemical may be removed at any time.
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MOA of Bromethalin
Uncoupling of oxidative phosphorylation, resulting in reduced tissue ATP and reduced activity of ATP-dependent Na/K pumps. Impaired activity of ion pumps leads to cellular swelling and movement of fluid into myelinated regions of the brain.
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Treatment for elapid antivenom reaction
If mild - administer chlorpheniramine and continue at slower rate.
More severe reactions - Stop infusion, supply with oxygen/adrenaline/fluid boluses as required.
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MOA of Lead Toxicosis
Once absorbed, >90% of lead is bound to RBCs. Unbound lead is distributed to bone, teeth, liver, kidney, lungs, and brain. Lead precipitates as an insoluble salt in bone and forms long-term storage there.
Lead competes with calcium ions, resulting for substitution of calcium in biological processes - cerebral oedema, glutamate-induced oxidative stress within the brain. Can also inhibit cytochrome p450, leading to increased levels of tryptophan, and thus serotonin. Competes with other cations to interfere with GABA production and activity in the CNS. Affects the mitochondrial permeability transition pores, starting to cascade apoptosis pathway. Interferes with sulfhydryl groups causing anaemia.
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Clinical signs of Zinc toxicosis
Severe intravascular haemolysis (clinical signs of anaemia, hyperbilirubinaemia), initially develops severe GI signs.
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Clinical signs seen with metaldehydes
Tachycardia, anxiety, hyperaesthesia, nystagmus, salivation, ataxia, vomiting, muscle tremors presenting to tonic-clonic seizures
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Most popular proposed mechanism of IVLE
Lipid Sink theory - ILE forms fat droplets that provide a lipid chamber separate from the aqueous chamber, in which lipophilic compounds can dissolve, leaving less available to the tissues
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Clinical signs of serotonin syndrome
Autonomic - diarrhoea, mydriasis, tachycardia, tachypnoea, hypertension, fever
Neuromuscular - Hyperreflexia, myoclonus, seizures, rigidity, hyperthermia, respiratory muscle compromise
Altered Mentation - Agitation, confusion, disorientation, excitement
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What are the 3 pathways of paracetamol metabolism, and which is the toxic pathway.
Oxidation, Sulphation, and Glucuronidation. Oxidation results in the formation of NAPQI which causes oxidative damage to hepatocytes and haemoglobin
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Treatment of Bromethalin Toxicosis
Emesis after ingestion and provision of activated charcoal and sorbitol as long as not contraindicated. Activated charcoal administration can continue for up to 2-4 days. Maintain hydration, seizures control, and cerebral oedema .
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Treatment of Pyrethrin toxicosis
Emesis performed if indicated, or endoscopic retrieval of flea/tick collar. Bathing and oral lavage, clipping of fur. Methocarbamol to control tremors, IVLE if severe
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Clinical Signs of Salbutamol Toxicosis
Hypokalaemia (weakness), tachycardia, arrhythmias, hyperglycaemia
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MOA ethanol toxicosis
Suspected to inhibit NMDA glutamate receptors in brain cells
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Clinical Signs of Zinc Phosphide Toxicosis
Most dogs vomit within 15-60 minutes of ingestion, but clinical signs can be delayed up to 4 hours. Cellular hypoxia develops as it is absorbed - apprehension, anxiety, discomfort, pacing, weakness, cardiovascular collapse, seizures, ventricular arrhythmias
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Clinical Signs of Strychnine Toxicosis
Within 10-120 minutes of ingestion. Nervousness, apprehension, anxiety, tachypnoea, muscle spasms, stiffness, tonic-extensor convulsions. Death as a result of respiratory paralysis
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Define Functional Antidote
An antidote that works to lessen clinical signs associated with intoxication, but has no chemical or physical interaction with toxicants
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MOA of Methylxanthines
Antagonism of adenosine (an inhibitory neuromodulator), and inhibition of phosphodiesterase that breakdown cAMP. An increase in intracellular cAMP leads to beta-adrenergic stimulation in cardiac cells, and increased stimulation of neurons.
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Treatment of Zinc Toxicosis
Supportive, chelation therapy controversial. Support with IVFT, blood products, gastroprotectants, continuous monitoring of CBC and chemistry
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MOA Organophosphates
Acts as a competitive inhibitor of cholinesterase enzymes and allows excess accumulation of acetylcholine at the NMJ. Causes excessive stimulation of muscarinic, nicotinic, and CNS receptors. Both acetylcholinesterase and pseudocholinesterase are inhibited.
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Initial Diagnostics for a patient presenting with Zinc Phosphide toxicosis
ECG, BP, radiographs, Co-oximetry, CBC, UA, Blood cholinesterase.
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MOA of 1080 toxicosis
Lethal synthesis effect on the TCA cycle. Binds with Acetyl-CoA to form Fluoroacetyl-CoA, which then combines with oxaloacetate to form fluorocitrate. Fluorocitrate blocks aconitase and stops the TCA cycle, leading to cellular energy depletion. Accumulation of cellular citrate also leads to hypocalcaemia and hypomagnesaemia
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Clinical signs of macadamia nut toxicosis
Weakness, depression ,vomiting, ataxia, tremors, hyperthermia, joint & muscle pain
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What is COX-1
A constitutive enzyme, responsible for physiologic functions. Synthesises prostaglandins that regulate normal cellular activity.
