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Flashcards in Environmental/Toxic Deck (180):
1

2 possible causes of acute hepatic necrosis with xylitol toxicity?

ATP depletion
Increased generation of ROS

2

Cocaine MOA

Inhibits presynaptic neuronal uptake of dopamine, NE, and serotonin = enhanced sympathetic transmission (tachycardia, arrhythmias, hypertension) & CNS (excitement & euphoria)

Blocks fast sodium channels = local anesthetic activity

3

Toxin in mountain laurel (rhododendron) and MOA

grayanotoxins: bind 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

4

N-acetylcysteine MOA?

Increased synthesis and availability of glutathione (NAC --> cysteine)

For acetaminophen:
Substrate for sulfation (less toxic metabolites)
Direct binding and detoxification of NAPQI

5

MOA of anticoagulant rodenticide

Inhibits vitamin K epoxide reductase which is needed to convert inactive vitamin K to active vitamin K

6

What is the difference between first and second generation anticoagulant rodenticides?

Second generation products are longer acting so vitamin K therapy should be continued for at least 4 weeks

7

MOA of bromethalin rodenticide

Uncoupling of oxidative phosphorylation with a resultant decrease in ATP production. Decrease in cellular energy leads to inability of the Na/K-ATPase pump to function. This leads to a buildup of intracellular sodium followed by water movement into the cells and resultant cerebral edema and elevated intracranial pressure.

8

MOA of zinc phosphide rodenticide

Once it comes into contact with gastric acid it is hydrolyzed to phosphine gas and free radicals. When it is ingested with food there is enhanced susceptibility to zinc phosphide due to increased gastric acid.

Phosphine gas disrupts mitochondrial respiration as well as produces free radicals such as reactive oxygen species

9

Describe the pathophysiology of carbon monoxide poisoning

Carbon monoxide competitively and reversibly binds to hemoglobin at the same sites as oxygen but with an affinity that is 230-270 times greater, resulting in marked anemic, hypoxia.

Carboxyhemoglobin shifts the oxygen-hemoglobin dissociation curve to the left, resulting in less offloading at the tissue level.

10

How does hydrogen cyanide cause toxicity?

It interferes with utilization of oxygen by cellular cytochrome-oxidase and thereby causes histotoxic hypoxia.

11

Describe some of the changes to the respiratory tract that can be seen with smoke inhalation

Direct thermal injury can cause mucosal edema, of which laryngeal edema is of greatest concern.

Noxious gases can be inhaled (or gases are converted to acids within the respiratory tract).

Decreased lung compliance due to alveolar atelectasis due to impaired pulmonary surfactant activity as well as pulmonary edema.

Progressive mucosal edema can cause mucosal sloughing.

Smoke inhalation can cause a reflex bronchoconstriction which may worsen airway obstruction.

12

How does smoke inhalation increase the likelihood of bacterial pneumonia?

It may impair alveolar macrophage function. There are also stagnant luminal contents which create a favorable environment for bacteria.

13

What are the three possible outcomes in pure, uncomplicated carbon monoxide poisoning?

1. complete recovery with possible transient hearing loss but no permanent effects.

2. recovery with permanent central nervous system abnormalities

3. death

14

Hyperemia of the mucous membranes in a case of smoke inhalation can be caused by what?

carboxyhemoglobinemia

cyanide toxicosis

systemic vasodilation

local vasodilation due to mucosal irritation

15

Why is oxygen supplementation beneficial in carbon monoxide poisoning?

the half-life of CO is 250 minutes i patients with normal respiratory exchange breathing room air, but is reduced to 26-148 minutes at an FiO2 of 100%.

16

How is cyanide toxicity treated?

IV sodium nitrite followed by IV sodium thiosulfate.

In the case of smoke inhalation, sodium thiosulfate should be used alone as sodium nitrite results in the formation of methemoglobin which could further compromise oxygen carrying ability

17

Describe some of the treatments for airway management following smoke inhalation

Tracheostomy if laryngeal obstruction

Empiric bronchodilators

Supplemental humidified oxygen which regular saline nebulization and coupage

Gentle activity is encouraged

Mucolytics may be used

18

True or false, mycoplasma species lack a cell wall

True, all members of the class lack a cell wall, thus they are damaged easily outside the host, and are difficult to identify with most staining techniques

19

In what locations are nonhemotropic mycoplasma infections found?

Respiratory tract, ocular, urogenital, nervous system, and systemically

20

True or false, mycoplasma are considered normal flora of the UPPER respiratory tract in dogs and cats

True

For the lower respiratory tract, they have been isolated from the lungs of healthy dogs buts not healthy cats

21

Why are ureaplasmas (a form of mycoplasma) found more commonly in the urogenital tract?

They require urea for a carbon source

22

True or false, mycoplasma has been found to cause disease in the lower urinary tract in cats

False, because of the lack of a cell wall, mycoplasma is at a high risk for osmotic damage from highly concentrated feline urine

23

What is the gold standard for diagnosis of a nonhemotropic mycoplasma infection?

Cultures

As the organism is slow growing it may be difficult to culture, it may require special growth media and transport

24

What are the benefits of PCR over culture for diagnosis of nonhemotropic mycoplasma infection?

Has improved sensitivity over culture, able to identify nonviable organisms, faster results

25

Which bacteria (actinomyces or nocardia) are part of the normal flora of the oropharynx, gastrointestinal tract, and urogenital tract?

Actinomyces

Nocardia is found in the environment and is inoculated via penetrating wound or from inhalation

26

Describe the staining and morphology of actinomyces and nocardia

Gram positive, rod shaped

Actinomyces is non-acid fast, nocardia is partially acid-fast

27

What is the empiric antibiotic treatment of choice for actinomycosis? for nocardiosis?

Actinomycosis - penicillins

Nocardiosis - TMS

28

Which has a better prognosis, actinomycosis or nocardiosis?

Actinomycosis, reported cure rates of 90% in the dog

Vs. nocardia which has 50% mortality rate and 38.5% euthanasia rate from lack of clinical response

29

How do the biologic requirements of actinomyces and nocardia differ?

Actinomyces is facultative or an obligate anaerobe

Nocardia is aerobic

30

How low should actinomycosis be treated?

How long should nocardiosis be treated?

Actinomycosis should be treated for 6-12 months

Nocardiosis should be treated for 1-3 months for simple cutaneous infections, up to 1 year for severe systemic infections

31

What are the clinical sighs of aldicarb toxicity?

Muscarinic overstimulationSLUDGESalivation, lacrimation, urination/urinary incontinence, defecation/diarrhea, gastric cramping, and emesisAdditional symptoms of the cholinergic toxidrome include miosis, bronchorrhea, bradycardia, and lethargyNiconitic overstimulation: tachycardia, hypertension, muscle fasciculations, tremors, respiratory depression, respiratory failure

32

Minimum lethal dosage of EG in dogs vs cats?

4.4-6.6 ml/kg dogs, 1.5 ml/kg cats

33

List the pathway for ethylene glycol.

EG, glycoaldehyde, glycolate, glyoxylate, oxalate(al-co-oxy-oxa)ADH converts EG to glycoaldehyde AND glycoaldehyde to glycolate

34

What is the rate limiting step in EG pathway?

glycolate to glyoxylate

35

What are the most toxic metabolites of EG on a per weight basis?

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

36

The CNS effects that occur during the first 12 hours of exposure to EG thought to be due to...

1. aldehyde metabolites2. hyperosmolality3. metabolic acidosis

37

Clinical signs during 30 min to 12 h exposure to EG?

Depression, incoordination, ataxia, seizures, paresis, vomiting, coma, PU/PD, proprioception deficits, LMN signs, muscle fasciculations, hypothermiaLike me when drunk:)

38

Clinical signs from 12 h to 24 h exposure to EG?

Sometimes resolution CNS signs (cats sometimes remain severely depressed), tachycardia, tachypnea, hypothermia, muscle fasciculations

39

Clinical signs 24-72h post exposure to EG?

Severe GI signs, oliguria/anuria, seizures, death, anorexia, oral ulcerations, ptyalism

40

Rise in osmolal gap ocurs as early as __ hr in cats and dogs and typically peaks by ___ hrs dogs.

1 hr, 6 hrs

41

How long does the osmolal gap remain elevated after EG ingestion?

up to 18 h

42

What is the normal osmolal gap?

10 mOsm/kg

43

What method is best to determine the osmolal gap?

freezing point depression

44

What normally develops in 3 hr of ingestion of EG?

high anion gap normochloremic metabolic acidosis

45

Why does EG cause hypocalcemia?

chelation of calcium with oxalic acid to form calcium oxalate crystals

46

Hyperglycemia is seen in over 70% of patients with EG toxicity. Proposed mechanims?

1. aldehyde induced inhibition of glucose metabolism2. increased epinephrine3. increased endogenous cortisol4. uremia

47

When are calcium oxalate crystals seen?

w/i 3 hr in cats, 4-6 hr dogs

48

What can be done to the urine to help determine if EG toxicity?

Wood's lamp the urine - will fluoresce up to 6 h after ingestion of toxin

49

What can cause a false positive EG test?

1. propylene glycol2. glycerol3. lactate dehydrogenas4. lactic acid5. less than 50 mg/dl EG

50

What causes acidosis with EG toxicity?

1. Metabolic products of EG (glycolic acid aka glycolate)2. Increased lactic acid production caused by NAD depletion during EG metabolism

51

Disadvantages to using ethanol to tx EG tox?

1. exacerbates hyperosmolality2. exacerbates osmotic diuresis3. worsens metabolic acidosis by enhancing formation of lactate from pyruvate

52

How does ethanol cause hypoglycemia?

Metabolized to acetaldehyde which impairs gluconeogenesis

53

Advantages of 4MP?

1. Greater affinity for ADH than ethanol2. Not associated with CNS depression, hyperosmolality, or osmotic diuresis

54

What's different b/t cats and dogs regarding use of 4MP?

Cats require much higher doses, up to 6 times higher

55

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)

56

Signs of muscarinic overstimulation?

PNS: vomiting, diarrhea ptyalism, urination, bradycardia, miosis, bronchorrhea, tenesmus

57

Signs of nictotinic overstimulation?

SNS: tachycardia, hypertension, mydriasisCNS: agitation, coma, respiratory depression/failureNM jxn: muscle fasciculation, weakness, paralysis

58

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)

59

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)

60

What is methiocarb?

molluscicide and insecticide, carbamate, less toxic than aldicarb

61

How do you make a definitive diagnosis of aldicarb toxicity?

gas chromatography or mass spectrometry on tissue, urine, vomit, stomach contents

62

How is measuring AChE activity helpful with aldicarb tox?

<25% diagnostic if C/S fitNot reliable in cats b/c of presence of pseudocholinesterase in feline erythrocytes

63

What was most common lab abnormalities with aldicarb tox?

1. lactic acidosis2. hyperglycemia

64

How does atropine help with aldicarb tox?

parasympatholytic - helps with muscarinic sings (not nicotinic)

65

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

66

How is aldicarb excreted?

kidneys

67

What about aldicarb causes respiratory failure?

peripheral - profound NM weakness d/t nictonic overstimcentral - depression of medullary resp centerothers: aspiration pneumonia, bronchorrhea, bronchoconstriction

68

How could diphenhydramine be helpful with aldicarb tox?

blocks nicotinic receptor overstimulation (only been shown effective due to OP tox, not carbamate tox)

69

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

70

What was survival in aldicarb tox paper?

91%

71

What 6 systems are evaluated on the SSS?

pulmonarycardiovascularlocal woundGI systemhematologic systemCNS

72

In humans, SSS > ___ is considered severe?

8

73

Immediate adverse effects of antivenom.

Bradycardia, 2nd degree AV block, agitation, injection of pinnae and sclera, vomiting, fever, nausea, tachycardia, trembling, anaphylaxis

74

OPCA is ___ times as otent as ACP

5.2

75

Size of ACP vs OPCA

150 kDa vs 50 kDa

76

Intralipid is from what fat?

soybeal oil based emulsion of long chain triglycerides

77

Fat overload syndrome can cause...

fat embolism, hyperlipidemia, hepatomegaly, icterus, splenomegaly, thrombocytopenia, increased clotting times, hemolysis

78

Adverse effects on pulmonary system from ILE.

increased PAP, increased venous admixture, decreased PaO2/FiO2, increased A-a, intrapulmonary shunting

79

ILE improvement theories

1. Improved myocardial performance by providing energy substrate2. Drug sequestration or lipid sink theory

80

The higher the log P value, the more lipophilic a drug or chemical becomes. T/F

TP>1

81

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

82

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)

83

What is a cholinergic crisis?

result of cholinergic overload at NM jxn secondary to inhibition of cholinesterase

84

Atropine MOA in cholinergic crisis.

competes with acetylcholine for the postsynaptic muscarinic receptor (does nothing for nicotinic receptors but helps with bronchospasm and bronchorrhea)

85

Neurotoxin from Clostridium tetani

tetanospasm - prevents release of inhibitory neurotransmitters and results in unopposed muscle excitation and dysautonomia

86

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

87

What is the earliest sign of Mg toxicity?

deep tendon hyporeflexia

88

Effects of venom A?

Irreversible, pre-synaptic acting neurotoxin composed of acidic peptide and basic protein. Acidic: noncompetitive CCB blocks ACh releaseBasic: acts like PLA2 to hydrolyze acetyl bond on phospholipids

89

Effects of venom B?

edema, tissue necrosisproteolytic enzymes and cytotoxinshyaluronidase and collagenase spread venom, protease cause coagulopathy

90

Most common signs of cats vs dogs with essential oil products. Genovesse, JVECC, 2012

Cats - behavioral changes, seizures, tremorsDogs - lethargy92% clinical signs, 50% resolved with bath, 50% needed more care

91

What are terpenes?

essential oils that are rapidly orally and dermally absorbed d/t lipophilic nature

92

Salbutamol (albuterol) inhaler toxicity dogs...

tachycardia, hypokalemia, oral burns!! (pressurized hydrocarbons cause frostbite)

93

Incidence of neurotoxicity from rattlesnake envenomation?Julius, JVECC, 2012

5.4%

94

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 survivial3. 11.8% PPV, half survived4. Overall mortality 18%5. Cats * longer LOH6. Cats overrepresented with neuro signs7. Diphenhydramine and colloids assc'd with survival

95

Crotalidae polyvalent immune Fab (ovine) antivenom made from...

Eastern and Western diamondbacks, Mojave rattlesnake, cottonmouth

96

ACP antivenom made from....

horses inoculated with Eastern and Western diamondback, Central and South American rattlesnakes, Fer-de-Lance

97

What is myokymia?

muscle fasciculation associated with envenomationMOA: interaction of venom components with calcium or calcium binding sites on the nerve membrane

98

MOA of Mojave toxin?

inhibits ACh release at PRESYNAPTIC terminal of the NM jxn, causing inhibition of NM transmission and eventually complete NM blockade

99

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

100

Toxic dose 5FU

5 mg/kg, lethal at 40 mg/kg

101

Signs os 5FU toxicity

CNS (seizures, depression, ataxia, tremors), respiratory (cyanosis, distress), GI (diarrhea, vomiting, salivation), cardiac arrhythmias, death, severe myelosuppression, ocular signs

102

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

103

How do you treat seizures from 5-FU?

phenobarb, meperidine, anesthesia - diazepam not effective

104

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

105

Coral snake venom inhibits....plt aggregation.

ADP

106

What lab parameters were elevated in all coral snake dogs?

AST and CK

107

T/F - Both dogs and cats show hemolysis after coral snake envenomation.

F - only dogs

108

Clinical signs of marijuana toxicity

CNS depression, ataxia, mydriasis, increased sensitivity to motion or sound, hyperesthesia, ptyalism, tremors, acute onset urinary incontinence

109

Toxic compound marijuanan.

delta-tetrahydrocannabinol (delta-THC)

110

MOA permethrins

modulate sodium ion channels, causing them to say open for a longer period of time, resulting in repetitive discharging of excitable cells

111

How do you know of a drug is lipid soluble?

partition coefficient, log P reported to indicate lipophilicity, higher values = greater lipophilicity

112

MOA for lipids

1. Lipid sink2. Cardioprotective by provision of FAs which are major substrate of cardiac ATP production, + cardiac inotropic effects

113

Potential adverse effects of lipids

acute allegic rxns, anaphylactoid reactions, fat overload syndrome (liver, fat embolism, thrombocytopenic, coagulopathy), sepsis, neuro signs, thrombophlebitis

114

Osmolality of 20% lipids

350 mOsm/kg

115

Lipid antidote

heparin

116

Most common clinical sign from SSRI intoxication

CNS depression (JVECC, 2012)neuro and GI most common overall signs

117

How is serotonin made?

from tryptophan via enzymes tryptophan hydroxylase and tryptophan decarboxylase

118

Where is serotonin made?

most in CNS and enterochromaffin cells, some platelets95% stored in GI enterochromaffin cells and plts

119

Where is serotonin stored in CNS?

presynaptic vesicles of serotonergic neurons, pineal gland, and catechoalminergic neuronsmetabolized by monoamine oxidase (MAO)

120

What SSRI was associated with dose effect on clinical signs?

fluoxetine (JVECC, 2012)

121

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

122

Salicylate toxicity MOA

uncouples oxidative phosphorylation and disturbs Krebs

123

Antidote for salicylate toxicity

none

124

Principle tx of salicylate toxicity

1. urinary alkalinization to increase rate of excretion2. hemodialysis effective

125

Mechanism of GI signs in salicylate toxicity

Direct antagonism of prostaglandins which normally serve to increase epithelial cell turnover and mucus/bicarb secretion

126

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)

127

What type of metabolic acidosis seen with salicylate tox?

increased AG metabolic acidosis (lactate and ketoacids accumulate d/t uncoupling of oxidative phosphorylation)

128

What lung problem can occur with salicylate toxicity?

noncardiogenic pulmonary edema

129

Goals of urinary alkalinization with salicylate toxicity?

NaHCO3 to keep urine pH 7.5-8 and blood pH 7.35-7.5Increases renal excretion 10-20X

130

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)

131

What is the rational for empirically supplementing glucose with salicylate toxicity

neuroglycopenia can occur despite a normal blood glucose

132

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

133

Cocaine MOA

inhibits presynaptic neuronal uptake of dopamine, NE, and serotonin, and causes blockade of fast sodium channels = neuro and cardio signs

134

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

135

What 2 drugs may antagonize the effects of amphetamines and cocaine by antagonizing or blocking catecholamines

chlorpromazine, haloperidol

136

Why do dogs become PU/PD after ingestion of cholecalciferol?

inhibition of ADH

137

MOA of cardiac arrhythmias after cholecalciferol ingestion?

1. mineralization of heart2. changes in ratio of IC to EX ion concentratione3. increase in depolarization threshold

138

Tx cholecalciferol ingestion?

Tx hypercalcemia - saline diuresis to induce calciuresis, furosemide, glucocorticoids, salmon calcitonin (can cause anaphylaxis), pamidronatecalcitonin and pamidrongate inhibit osteoclastic activity

139

LD50 bromethalin dogs vs cats

dogs 4.7 mg/kg, cats 1.8 mg/kg

140

MOA bromethalin

uncouples oxidative phosphorylation, Na, K ATPase pumps fail, in goes water -- cerebral edema and neuro predominate as clinical signsEnterohepatic recirculation, lots of charcoal

141

Histopathologic evidence of bromethalin toxicity?

diffuse white matter vacuolation (spongy degeneration) with microgliosis

142

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

143

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

144

Risks of gastric lavage

hypoxia, dysrhytmias, laryngospasm, perforation of GI tract or pharynx, fluid and electrolyte abnormalities, aspiration pneumonia, aspiration pneumonitis

145

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

146

If gastric lavage performed at 60 minutes post ingestion, mean recovery of markers?

8.6-13%

147

Theories for ILE

1. Lipid sink - sequestration of lipophilic compounds in the newly created lipid compartment2. Myocardial energy substrate improving cardiac performance3. Increasing cardiac calcium to restore myocardial fxn4. Increasing the overall fatty acid pool, which overcomes inhibition of mitochondrial fatty acid metabolism (eg, bupivicaine toxicity)

148

List drugs/toxins that are not absorbed by activated charcoal.

1. Hydrocarbons2. Lithium3. Ferrous sulfate (conflicting reports)4. Potassium5. Ethanol

149

Urinary alkalinization is useful for what toxins?

SALICYLATES, PHENOBARBITAL, methotrexate, chlorpropamide, 2.4-dichlorophenoxyacetic acid, diflunasil

150

Contraindications to urinary alkalinization?

Renal failure, heart failure (sodium load) - relative

151

Complications of urinary alkalization?

Hypokalemia most common, hypocalcemia, coronary vasoconstriction (alkalemia shifts curve to left), cerebral vascoconstriction

152

When should whole bowel irrigation be considered?

Sustained release or enteric coated drugs in patient presenting 2 hours after ingestion

153

Contraindications for WBI?

bowel obstruction, perforation, ileus, recent surgery, hemodynamic instability, vomiting, GI hemorrhage

154

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

155

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 peroxidationFood increases absorption b/c dec gastric acidity

156

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

157

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

158

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)

159

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

160

What's used in humans to treat frostbite?

aspirin and prostacyclin

161

SSRI toxicosis cats, JVECC, 2013, findings.

1. 24% clinical signs2. Sedation > GI > CNS stimulation = CV = hyperthermia3. No deaths4. venlafaxaine had most clinical signs5. No assc'n b/t dose ingested and clinical signs

162

Where is serotonin made normally?

raphe nuclei

163

Systemic effects of serotonin?

vasoconstriction, plt aggregation, intestinal peristalsis, bronchoconstriction

164

SSRI MOA

block reuptake of serotonin in presynapse, increasing serotonin at synaptic cleft

165

What is the MOA of aldicarb?

CarbamateInhibits acetylcholinesterase leading to hyper excitability of cholinergic receptors

166

What are the three types of calcium channels and which is the most sensitive to beta blockers?

Neuronal (N) type
Transient (T) type
Long-lasting (L) type - most sensitive

167

Where are L type calcium channels found in the highest concentrations?

Atria
Vascular smooth muscle
Skeletal muscle

168

What are the three major types of calcium channel blockers and what are their primary effects?

Phenylalkylamines (verapamil) - primarily chronotropic and dromotropic effects

Benzothiazepines (diltiazem) - Chronotropic and dromotropic effects

Dihydropyridines (amlodipine) - systemic vascular resistance and coronary resistance

169

Describe the cardiac effects of calcium channel blockers

They inhibit the inward flow of calcium needed to initiate depolarization of the SA and AV node. This leads to slowed SA node activity, decreased conduction of impulses through the AV node, and resultant bradycardia

A negative inotropic effect is seen due to decreased calcium released from the sarcoplasmic reticulum and a decreased force of contraction

170

Describe the vascular effects of calcium channel blockers

Calcium channels are in the vascular smooth muscle cells and are needed for vasoconstriction. Calcium channel blocks result in dilatation in systemic and coronary arteries and arterioles. Less of an effect is seen on veins as they have less smooth muscle in their walls.

171

Describe the pancreatic effects of calcium channel blockers

Beta cells of the pancreatic islets which produce insulin also contain L type calcium channels. Calcium channel blockers may induce decreased insulin release leading to increased glucose levels in the blood and decreased glucose in the cells

Lack of intracellular glucose may impair cardiovascular function (the heart has to switch to fatty acid metabolism)

172

Describe the two types of beta receptors - where are they found, and what do they do

Beta 1 receptors: located primarily in the heart, kidney, and adipose tissue. Stimulation of these receptors results in increases in heart rate, myocardial contractility, AV conduction velocity, and automaticity of subsidiary pacemakers

Beta 2 receptors: located primarily in the smooth muscle of the bronchial and vascular walls where they produce relaxation. They are also located in the pancreas, GI, and reproductive tracts

173

What beta receptors do the following drugs affect?
propranolol, atenolol, esmolol, sotalol

Propanolol - Beta 1 and 2
Atenolol - Beta 1
Esmolol - Beta 1
Sotalol - Beta 1 and 2

174

Describe the cardiac effects of beta blockers

Decreases transmembrane calcium flow by decreasing cyclic AMP synthesis, thereby decreasing atrial and ventricular contractility, slowing of the heart rate, and slowing the spread of excitation through the AV node and ventricles

175

Describe the pulmonary, pancreatic, GI, vascular, and renal effects of beta blockers

Pulmonary - bronchoconstriction or bronchospasm
Pancreatic - inhibition of insulin release leading to decreased glycogenolyis, lipolysis, and gluconeogenesis
GI - contraction of the smooth muscle
Vascular - contraction of the smooth muscle
Renal - suppression of catecholamine-induced renin release resulting in decreased aldosterone synthesis

176

Describe the pharmacokinetics of calcium channel blockers

Rapidly and almost completely absorbed via the GI tract
Have extensive first pass metabolism
Reach peak serum concentration in 20-45 minutes (or 4-12 hours for sustained release products)
80% protein bound
Metabolized the liver (cytochrome P450 CYP3A)
Certain classes are strong inhibitors of hepatic microsomal enzymes
Elimination half life varies, 2 to 30 hours
Excretion is primarily through urine

177

Describe the pharmacokinetics of beta blockers

More lipid soluble ones (propranolol) require haptic biotransformation before excretion
Lipid soluble compounds have large volume of distribution and CNS faster and more extensively
Water soluble ones (atenolol) are excreted by the kidney
Esmolol is water soluble but does not accumulate as it is metabolized by erythrocytes

178

What clinical signs /physiologic derangements are seen with beta blocker or calcium channel blocker overdose?

Bradycardia
Negative inotropy and chronotropy leading to decreased cardiac output
Hypotension
Tissue hypoperfusion
Cardiovascular shock

179

How do the following drugs work in treatment of beta blocker and calcium channel blocker overdose?

Atropine
Adrenergic agents (dopamine, epic, norepi, etc)
Vasopressin
Glucagon
Intravenous lipid emulsion

Atropine - vagolytic that can be given to reverse bradycardia and AV blockade

Adrenergic agents (dopamine, epic, norepi, etc) - used to counter hypotension, can pick alpha and beta activity based on what effects are being seen clinically

Vasopressin - used for refractory hypotension, stimulates V1 receptors

Glucagon - binds to receptor that are distinct from L type calcium channels and adrenergic receptors, stimulates adenyl cyclase which results in cAMP formation, and promotes release of Ca from sarcoplasmic reticulum, it also stimulates the AV and SA node so it has inotropic, dromotropic, and chronotropic properties

Intravenous lipid emulsion - they are variable fat soluble so may be contained in the "lipid compartment" and may also increase cardiac performance

180

How does a calcium channel blocker overdose contribute to metabolic acidosis?

Calcium channel blockers inhibit mitochondrial calcium entry at the sarcolemma and mitochondrial membrane, which decreases pyruvate dehydrogenase activity. Pyruvate can't enter the Krebs cycle and lactate accumulates