Toxins and Venom Flashcards
(135 cards)
0
Q
What are the clinical sighs of aldicarb toxicity?
A
Muscarinic overstimulation
SLUDGE
Salivation, lacrimation, urination/urinary incontinence, defecation/diarrhea, gastric cramping, and emesis
Additional symptoms of the cholinergic toxidrome include miosis, bronchorrhea, bradycardia, and lethargy
Niconitic overstimulation: tachycardia, hypertension, muscle fasciculations, tremors, respiratory depression, respiratory failure
1
Q
What is the MOA of aldicarb?
A
Carbamate
Inhibits acetylcholinesterase leading to hyper excitability of cholinergic receptors
2
Q
Minimum lethal dosage of EG in dogs vs cats?
A
4.4-6.6 ml/kg dogs, 1.5 ml/kg cats
3
Q
List the pathway for ethylene glycol.
A
EG, glycoaldehyde, glycolate, glyoxylate, oxalate
(al-co-oxy-oxa)
ADH converts EG to glycoaldehyde AND glycoaldehyde to glycolate
4
Q
What is the rate limiting step in EG pathway?
A
glycolate to glyoxylate
5
Q
What are the most toxic metabolites of EG on a per weight basis?
A
glyoxylate and glycoaldehyde; HOWEVER, b/c of its longer half life and greater systemic accumulation, GLYCOLATE is thought to be the major mediator IN VIVOR
6
Q
The CNS effects that occur during the first 12 hours of exposure to EG thought to be due to…
A
- aldehyde metabolites
- hyperosmolality
- metabolic acidosis
7
Q
Clinical signs during 30 min to 12 h exposure to EG?
A
Depression, incoordination, ataxia, seizures, paresis, vomiting, coma, PU/PD, proprioception deficits, LMN signs, muscle fasciculations, hypothermia
Like me when drunk:)
8
Q
Clinical signs from 12 h to 24 h exposure to EG?
A
Sometimes resolution CNS signs (cats sometimes remain severely depressed), tachycardia, tachypnea, hypothermia, muscle fasciculations
9
Q
Clinical signs 24-72h post exposure to EG?
A
Severe GI signs, oliguria/anuria, seizures, death, anorexia, oral ulcerations, ptyalism
10
Q
Rise in osmolal gap ocurs as early as __ hr in cats and dogs and typically peaks by ___ hrs dogs.
A
1 hr, 6 hrs
11
Q
How long does the osmolal gap remain elevated after EG ingestion?
A
up to 18 h
12
Q
What is the normal osmolal gap?
A
10 mOsm/kg
13
Q
What method is best to determine the osmolal gap?
A
freezing point depression
14
Q
What normally develops in 3 hr of ingestion of EG?
A
high anion gap normochloremic metabolic acidosis
15
Q
Why does EG cause hypocalcemia?
A
chelation of calcium with oxalic acid to form calcium oxalate crystals
16
Q
Hyperglycemia is seen in over 70% of patients with EG toxicity. Proposed mechanims?
A
- aldehyde induced inhibition of glucose metabolism
- increased epinephrine
- increased endogenous cortisol
- uremia
17
Q
When are calcium oxalate crystals seen?
A
w/i 3 hr in cats, 4-6 hr dogs
18
Q
What can be done to the urine to help determine if EG toxicity?
A
Wood’s lamp the urine - will fluoresce up to 6 h after ingestion of toxin
19
Q
What can cause a false positive EG test?
A
- propylene glycol
- glycerol
- lactate dehydrogenas
- lactic acid
- less than 50 mg/dl EG
20
Q
What causes acidosis with EG toxicity?
A
- Metabolic products of EG (glycolic acid aka glycolate)
2. Increased lactic acid production caused by NAD depletion during EG metabolism
21
Q
Disadvantages to using ethanol to tx EG tox?
A
- exacerbates hyperosmolality
- exacerbates osmotic diuresis
- worsens metabolic acidosis by enhancing formation of lactate from pyruvate
22
Q
How does ethanol cause hypoglycemia?
A
Metabolized to acetaldehyde which impairs gluconeogenesis
23
Q
Advantages of 4MP?
A
- Greater affinity for ADH than ethanol
2. Not associated with CNS depression, hyperosmolality, or osmotic diuresis
24
What's different b/t cats and dogs regarding use of 4MP?
Cats require much higher doses, up to 6 times higher
25
What therapies are used to prevent metabolism of glycoxylic acid (glyoxalate) to toxic end products?
Thiamine (converts it to alpha hydroxy and beta ketoadipate) and pyridoxine (converts it to glycine then hippurate, needs benzoate)
26
Signs of muscarinic overstimulation?
PNS: vomiting, diarrhea ptyalism, urination, bradycardia, miosis, bronchorrhea, tenesmus
27
Signs of nictotinic overstimulation?
SNS: tachycardia, hypertension, mydriasis
CNS: agitation, coma, respiratory depression/failure
NM jxn: muscle fasciculation, weakness, paralysis
28
Anastasio, JVECC, 2011. What were the most common clinical signs of acute aldicarb toxicity?
vomiting (M 93%), ptyalism (M 86%), diarrhea (M 80%), tremors (N 73%)
others: dull mentation, bradycardia (M), increased resp effort, miosis (M), ataxia (N), hyperthermia, tachycardia (N), mydriasis (N), tenesmus (M), resp failure (N)
29
DDx for acute aldicarb toxicity?
1. intoxication (other carbamate, OPs, nicotine, phenothiazines,
mushrooms with muscarine)
2. envenomation (spider, scorpion, neurotoxic snake)
3. Infectious dz (botulism, lepto, encephalitis, meningitis)
4. Neuro dz (epilepsy, cerebral vasculitis, subarachnoid or subdural hemorrhage or hematoma)
5. metabolic dz (uremia, hypo or hyper glu, myxedema coma, thyrotoxicosis)
30
What is methiocarb?
molluscicide and insecticide, carbamate, less toxic than aldicarb
31
How do you make a definitive diagnosis of aldicarb toxicity?
gas chromatography or mass spectrometry on tissue, urine, vomit, stomach contents
32
How is measuring AChE activity helpful with aldicarb tox?
<25% diagnostic if C/S fit
| Not reliable in cats b/c of presence of pseudocholinesterase in feline erythrocytes
33
What was most common lab abnormalities with aldicarb tox?
1. lactic acidosis
| 2. hyperglycemia
34
How does atropine help with aldicarb tox?
parasympatholytic - helps with muscarinic sings (not nicotinic)
35
What are side effects of atropine?
GI stasis, constipation and prolonged retention of toxin, dry mouth, thirst, mydriasis, tachycardia, dysphagia, if severe then dyspnea, ataxia, muscle tremors, resp failure, death
36
How is aldicarb excreted?
kidneys
37
What about aldicarb causes respiratory failure?
peripheral - profound NM weakness d/t nictonic overstim
central - depression of medullary resp center
others: aspiration pneumonia, bronchorrhea, bronchoconstriction
38
How could diphenhydramine be helpful with aldicarb tox?
blocks nicotinic receptor overstimulation (only been shown effective due to OP tox, not carbamate tox)
39
How is 2-PAM helpful?
oximes decrease toxicity of cholinesterase inhibitors by reactivating cholinesterases (used for OP tox, not really needed for carbamate b/c spontaneous hydrolysis occurs that rapidly reactivates AChE); HOWEVER, may be synergistic with atropine with carbamate toxicity from human studies
40
What was survival in aldicarb tox paper?
91%
41
What 6 systems are evaluated on the SSS?
```
pulmonary
cardiovascular
local wound
GI system
hematologic system
CNS
```
42
In humans, SSS > ___ is considered severe?
8
43
Immediate adverse effects of antivenom.
Bradycardia, 2nd degree AV block, agitation, injection of pinnae and sclera, vomiting, fever, nausea, tachycardia, trembling, anaphylaxis
44
OPCA is ___ times as otent as ACP
5.2
45
Size of ACP vs OPCA
150 kDa vs 50 kDa
46
Intralipid is from what fat?
soybeal oil based emulsion of long chain triglycerides
47
Fat overload syndrome can cause...
fat embolism, hyperlipidemia, hepatomegaly, icterus, splenomegaly, thrombocytopenia, increased clotting times, hemolysis
48
Adverse effects on pulmonary system from ILE.
increased PAP, increased venous admixture, decreased PaO2/FiO2, increased A-a, intrapulmonary shunting
49
ILE improvement theories
1. Improved myocardial performance by providing energy substrate
2. Drug sequestration or lipid sink theory
50
The higher the log P value, the more lipophilic a drug or chemical becomes. T/F
T
P>1
51
How does heparin treat complications of ILE?
Heparin causes the release of LPL and hepatic lipase from endothelium, an can potentially act as the rate limiting step in metabolism of triglycerides
52
Side effects of cholinesterse inhibitors.
Pharnygeal and bronchial secretions, increased pharyngeal and bronchial secretions, diarrhea and enhanced GI peristalsis, increased urination, resp depression, arrest if desensitization blockade (abundance Ach at synapse)
53
What is a cholinergic crisis?
result of cholinergic overload at NM jxn secondary to inhibition of cholinesterase
54
Atropine MOA in cholinergic crisis.
competes with acetylcholine for the postsynaptic muscarinic receptor (does nothing for nicotinic receptors but helps with bronchospasm and bronchorrhea)
55
Neurotoxin from Clostridium tetani
tetanospasm - prevents release of inhibitory neurotransmitters and results in unopposed muscle excitation and dysautonomia
56
Beneficial effects of Mg for tetanus?
Nonspecific calcium channel blocker (decreases calcium entry into presynaptic terminals and decreases release of ACh)
Decreases sensitivity of postsynaptic motor endplates to ACh - relaxation
57
What is the earliest sign of Mg toxicity?
deep tendon hyporeflexia
58
Effects of venom A?
Irreversible, pre-synaptic acting neurotoxin composed of acidic peptide and basic protein.
Acidic: noncompetitive CCB blocks ACh release
Basic: acts like PLA2 to hydrolyze acetyl bond on phospholipids
59
Effects of venom B?
edema, tissue necrosis
proteolytic enzymes and cytotoxins
hyaluronidase and collagenase spread venom, protease cause coagulopathy
60
Most common signs of cats vs dogs with essential oil products. Genovesse, JVECC, 2012
Cats - behavioral changes, seizures, tremors
Dogs - lethargy
92% clinical signs, 50% resolved with bath, 50% needed more care
61
What are terpenes?
essential oils that are rapidly orally and dermally absorbed d/t lipophilic nature
62
Salbutamol (albuterol) inhaler toxicity dogs...
tachycardia, hypokalemia, oral burns!! (pressurized hydrocarbons cause frostbite)
63
Incidence of neurotoxicity from rattlesnake envenomation?Julius, JVECC, 2012
5.4%
64
Findings from Julius, JVECC, 2012, Neurotoxicity in cats/dogs from rattlesnake envenomation.
1. incidence 5.4%
2. No diff b/t type of antivenom or #vials and neurotox, LOH, or survivial
3. 11.8% PPV, half survived
4. Overall mortality 18%
5. Cats * longer LOH
6. Cats overrepresented with neuro signs
7. Diphenhydramine and colloids assc'd with survival
65
Crotalidae polyvalent immune Fab (ovine) antivenom made from...
Eastern and Western diamondbacks, Mojave rattlesnake, cottonmouth
66
ACP antivenom made from....
horses inoculated with Eastern and Western diamondback, Central and South American rattlesnakes, Fer-de-Lance
67
What is myokymia?
muscle fasciculation associated with envenomation
| MOA: interaction of venom components with calcium or calcium binding sites on the nerve membrane
68
MOA of Mojave toxin?
inhibits ACh release at PRESYNAPTIC terminal of the NM jxn, causing inhibition of NM transmission and eventually complete NM blockade
69
MOA for hypokalemia from snake envenomation?
release of endogenous epinephrine that stimulates beta receptors on the cell surface, thereby stimulating Na-K-ATPase pumps, leasing to intracellular shift of potassium
70
Toxic dose 5FU
5 mg/kg, lethal at 40 mg/kg
71
Signs os 5FU toxicity
CNS (seizures, depression, ataxia, tremors), respiratory (cyanosis, distress), GI (diarrhea, vomiting, salivation), cardiac arrhythmias, death, severe myelosuppression, ocular signs
72
5-FU MOA
metabolism of 5FU into fluorouridine triphosphate that then interferes with RNA synthesis and fxn; inhibits thymidylate synthase via FdUMP which leads to depletion of thymidine 5' monophopshate and thymidine 5' triphosphate thus accumulating deoxyuridine mono- and tri- phosphate - goes into new DNA and doesn't work well leading to cell death
73
How do you treat seizures from 5-FU?
phenobarb, meperidine, anesthesia - diazepam not effective
74
What is the neurotoxin MOA coral snakes?
postsynaptic alpha-neurotoxins; block the nicotinic acetylcholine receptors of NM jxns and cause a curare-like effect characterized by vasomotor instability, CNS depression, and muscle paralysis
75
Coral snake venom inhibits....plt aggregation.
ADP
76
What lab parameters were elevated in all coral snake dogs?
AST and CK
77
T/F - Both dogs and cats show hemolysis after coral snake envenomation.
F - only dogs
78
Clinical signs of marijuana toxicity
CNS depression, ataxia, mydriasis, increased sensitivity to motion or sound, hyperesthesia, ptyalism, tremors, acute onset urinary incontinence
79
Toxic compound marijuanan.
delta-tetrahydrocannabinol (delta-THC)
80
MOA permethrins
modulate sodium ion channels, causing them to say open for a longer period of time, resulting in repetitive discharging of excitable cells
81
How do you know of a drug is lipid soluble?
partition coefficient, log P reported to indicate lipophilicity, higher values = greater lipophilicity
82
MOA for lipids
1. Lipid sink
| 2. Cardioprotective by provision of FAs which are major substrate of cardiac ATP production, + cardiac inotropic effects
83
Potential adverse effects of lipids
acute allegic rxns, anaphylactoid reactions, fat overload syndrome (liver, fat embolism, thrombocytopenic, coagulopathy), sepsis, neuro signs, thrombophlebitis
84
Osmolality of 20% lipids
350 mOsm/kg
85
Lipid antidote
heparin
86
Most common clinical sign from SSRI intoxication
CNS depression (JVECC, 2012)
neuro and GI most common overall signs
87
How is serotonin made?
from tryptophan via enzymes tryptophan hydroxylase and tryptophan decarboxylase
88
Where is serotonin made?
most in CNS and enterochromaffin cells, some platelets
95% stored in GI enterochromaffin cells and plts
89
Where is serotonin stored in CNS?
presynaptic vesicles of serotonergic neurons, pineal gland, and catechoalminergic neurons
metabolized by monoamine oxidase (MAO)
90
What SSRI was associated with dose effect on clinical signs?
fluoxetine (JVECC, 2012)
91
What is the toxin in mountain laurel (rhododendron) and MOA.
grayanotoxins - bind to sodium channels in excitable cell membranes of nerve, heart, skeletal muscle which increases membrane permeability of sodium ions in the excitable membranes, thus maintaining the cells in the state of depolarization
92
Salicylate toxicity MOA
uncouples oxidative phosphorylation and disturbs Krebs
93
Antidote for salicylate toxicity
none
94
Principle tx of salicylate toxicity
1. urinary alkalinization to increase rate of excretion
| 2. hemodialysis effective
95
Mechanism of GI signs in salicylate toxicity
Direct antagonism of prostaglandins which normally serve to increase epithelial cell turnover and mucus/bicarb secretion
96
What acid base disturbance seen with severe salicylate toxicity?
respiratory alkalosis or mixed (metabolic acidosis with respiratory alkalosis)
Toxin directly stimulates respiratory center causing tachypnea and respiratory alkalosis --> kidneys get rid of bicarb which makes it worse for impending metabolic acidosis (lactate and ketoacids)
97
What type of metabolic acidosis seen with salicylate tox?
increased AG metabolic acidosis (lactate and ketoacids accumulate d/t uncoupling of oxidative phosphorylation)
98
What lung problem can occur with salicylate toxicity?
noncardiogenic pulmonary edema
99
Goals of urinary alkalinization with salicylate toxicity?
NaHCO3 to keep urine pH 7.5-8 and blood pH 7.35-7.5
Increases renal excretion 10-20X
100
Why is it important to prevent hypokalemia with salicylate toxicity?
Potassium reabsorption prevents excretion of an alkaline urine b/c of the exchange of potassium for hydrogen in the distal tubule (intercalated type A cell)
101
What is the rational for empirically supplementing glucose with salicylate toxicity
neuroglycopenia can occur despite a normal blood glucose
102
Amphetamine toxicity MOA
indirect-acting sympathomimetic amines and clinical signs d/t enhanced adrenergic stimulation and serotonin syndrome. Hyperdynamic sage can cause severe hyperthermia with rhabdomyoloysis, CNS signs, AKI, metabolic abnormalities
103
Cocaine MOA
inhibits presynaptic neuronal uptake of dopamine, NE, and serotonin, and causes blockade of fast sodium channels = neuro and cardio signs
104
Phencyclidine MOA
dissociative that antagonizes NMDA operated calcium channels; causes marked CNS depression or stimulation; increased ICP, also acts on delta-receptors causing dysphoria and hallucinations
105
What 2 drugs may antagonize the effects of amphetamines and cocaine by antagonizing or blocking catecholamines
chlorpromazine, haloperidol
106
Why do dogs become PU/PD after ingestion of cholecalciferol?
inhibition of ADH
107
MOA of cardiac arrhythmias after cholecalciferol ingestion?
1. mineralization of heart
2. changes in ratio of IC to EX ion concentratione
3. increase in depolarization threshold
108
Tx cholecalciferol ingestion?
Tx hypercalcemia - saline diuresis to induce calciuresis, furosemide, glucocorticoids, salmon calcitonin (can cause anaphylaxis), pamidronate
calcitonin and pamidrongate inhibit osteoclastic activity
109
LD50 bromethalin dogs vs cats
dogs 4.7 mg/kg, cats 1.8 mg/kg
110
MOA bromethalin
uncouples oxidative phosphorylation, Na, K ATPase pumps fail, in goes water -- cerebral edema and neuro predominate as clinical signs
Enterohepatic recirculation, lots of charcoal
111
Histopathologic evidence of bromethalin toxicity?
diffuse white matter vacuolation (spongy degeneration) with microgliosis
112
What enhances zinc phosphide toxicity?
food b/c gastric acid secretion; once ingested and in acidic environment zinc phosphide hydrolyzed to phosphine gas and free radicals
113
Strychnine MOA
prevents uptake of glycine at inhibitory synapses of Renshaw cells in CNS; inhibition of an inhibitory pathway called disinhibition, results in net excitatory effect from excessive afferent input and efferent response
114
Risks of gastric lavage
hypoxia, dysrhytmias, laryngospasm, perforation of GI tract or pharynx, fluid and electrolyte abnormalities, aspiration pneumonia, aspiration pneumonitis
115
Contraindications to gastric lavage
loss of protective airway reflexes (unless patient indubated), ingestion of a strong acid or alkali, ingestion of a hydrocarbon with a high risk of aspiration potential, risk of GI hemorrhage due to an underlying medical or surgical condition, hyponatremia if lavage with water
116
If gastric lavage performed at 60 minutes post ingestion, mean recovery of markers?
8.6-13%
117
Theories for ILE
1. Lipid sink - sequestration of lipophilic compounds in the newly created lipid compartment
2. Myocardial energy substrate improving cardiac performance
3. Increasing cardiac calcium to restore myocardial fxn
4. Increasing the overall fatty acid pool, which overcomes inhibition of mitochondrial fatty acid metabolism (eg, bupivicaine toxicity)
118
List drugs/toxins that are not absorbed by activated charcoal.
1. Hydrocarbons
2. Lithium
3. Ferrous sulfate (conflicting reports)
4. Potassium
5. Ethanol
119
Urinary alkalinization is useful for what toxins?
SALICYLATES, PHENOBARBITAL, methotrexate, chlorpropamide, 2.4-dichlorophenoxyacetic acid, diflunasil
120
Contraindications to urinary alkalinization?
Renal failure, heart failure (sodium load) - relative
121
Complications of urinary alkalization?
Hypokalemia most common, hypocalcemia, coronary vasoconstriction (alkalemia shifts curve to left), cerebral vascoconstriction
122
When should whole bowel irrigation be considered?
Sustained release or enteric coated drugs in patient presenting 2 hours after ingestion
123
Contraindications for WBI?
bowel obstruction, perforation, ileus, recent surgery, hemodynamic instability, vomiting, GI hemorrhage
124
How do you perform WBI?
Enteral administration (NG tube) of large amounts of polyethylene glycol electrolyte solution, osmotically active, liquid stool, no net absorption or secretion so no significant changes in water or electrolytes occur
125
MOA zinc phospide rodenticides
After ingestion, phosphine gas produced by hydrolysis of zinc phospide in acidic moist stomach; phosphine gas rapidly absorbed across gastric mucosa then who knows...possible inhibition cytochrome C oxidase, inhibition serum acetyl cholinesterase activity, formation of reactive hydroxyl radicals, inhibition of catalase and peroxidase resulting in lipid peroxidation
Food increases absorption b/c dec gastric acidity
126
Tx zinc phosphide tox?
increase stomach pH (aluminum hydroxide, calcium carbonate, magnesium) then make vomit or do gastric lavage, charcoal probably not helpful, but give anyway
127
What kind of drug is PPA
sympathomimetic amine, acts as an alpha-adrenergic receptor agonist and indirectly through increased release of stored norepi by alpha- and beta-adrenergic receptors
128
PPA toxicity (JAVMA, 2011, findings)
Dose dependent side effects, 61% dogs showed signs including agitation, vomiting, mydriasis, lethargy, tremor/twitching, panting, bradycardia, tachycardia, hypertension, erythema, one dog died that ate 145 mg/kg (therapeutic dose 1-1.5 mg/kg)
129
What is the toxin in bath salts?
methylene-dioxypyrovalerone (MDPV) - inhibit NE and dopamine reuptake and act as central system stimulants, clinical signs extreme sympathetic stimulation
130
What's used in humans to treat frostbite?
aspirin and prostacyclin
131
SSRI toxicosis cats, JVECC, 2013, findings.
1. 24% clinical signs
2. Sedation > GI > CNS stimulation = CV = hyperthermia
3. No deaths
4. venlafaxaine had most clinical signs
5. No assc'n b/t dose ingested and clinical signs
132
Where is serotonin made normally?
raphe nuclei
133
Systemic effects of serotonin?
vasoconstriction, plt aggregation, intestinal peristalsis, bronchoconstriction
134
SSRI MOA
block reuptake of serotonin in presynapse, increasing serotonin at synaptic cleft
