Toxicology Exam I

Front 1

What is the difference between toxicity and toxicosis?

Back 1

Toxicity is the relative potency of a toxicant - usually compared on a mg/kg basis. Toxicosis is a pathologic condition that results from exposure to a toxicant.

Front 2

What is the difference between dose and dosage?

Back 2

Dose is the total amount of toxican received by and animal dosage is the amount of toxicant per unit of animal weight.

Front 3

What is the difference between quantal response and graded response?

Back 3

A quantal response (population response) is a binary response, the effect happens or it does not happen. A graded response (individual response) is where the toxic effects become more severe as the dose increases.

Front 4

What is the difference between LD50 and therapeutic ratio?

Back 4

LD50 is the dose likely to cause death in 50% of a given species/age/sex group under specified conditions. The therapeutic ratio is the ratio of LD50 to ED50 (units are %).

Front 5

Name five toxicity factors associated with the toxicant.

Back 5

1. Solubility 2. Polarity
3. Vehicle and formulation effects 4. Chemical interactions

Front 6

What type of biotransformation happens in Phase I?

Back 6

oxidation , reduction, hydrolysis

Front 7

What type of biotransformation happens in Phase II?

Back 7

conjugation with endogenous molecules

Front 8

Name five things that influence biotransformation?

Back 8

1. Parenchymal organ disease 2. Toxicant localization in tissues with little PI/PII activity 3. Age and metabolic activity
4. Species-specific variation and individual variation 5. Gender and hormone differences

Front 9

Name eight factors asociated with the envioronment that affect toxicity.

Back 9

1. season 2. temperature
3. light facotrs 4. housing
5. constructions 6. heating systems 7. air circulation
8. bedding

Front 10

Compare the different routes of toxicant exposure and their toxicant concentration.

Back 10

IV has the highest concentration, followed by inhalation, then oral and dermal, which have similar concentrations.

Front 11

What are the timeframes associated with acute, sub-chronic and chronic exposures?

Back 11

Acute: assess toxicity after single or multiple doses up to 24 hours following exposure
Sub-Chronic: After 30-90 days of repeated or continuous exposure
Chronic: prolonged exposure 3 or more years in the dog

Front 12

Describe first-order elimination.

Back 12

First order reactions are the most common. Rate is directly proportional to [A]. Rate=k[A]^m. t1/2=0.693
10 half lives will virtually eliminate all the toxicant from the body.

Front 13

Describe zero-order elimination.

Back 13

A saturated process proceeding at maximum amount the body can handle per unit time. Reaction rate is independent of [A]. Kinetics may change to first order after process is no longer saturated.

Front 14

What information should be obtained as part of a history?

Back 14

Breed, sex, age, weight, previous health history, identity of agent and route, concentration and amount of agent, time of exposure, type of clinical signs, tx administered and response to tx., animal's environment

Front 15

Name three methods of evacuating the gut.

Back 15

Emesis, gastric lavage, enterogastric lavage

Front 16

Name three emetics, the route of administration, and any side effects.

Back 16

Hydrogen peroxide (3%) - oral, works within 20 minutes.
Apomorphine hydrochloride - via conjunctival sac, IV, IM, SQ. CNS depression possible.
Xylazine hydrochloride - good in cats, IM, sedation.

Front 17

When is gastric lavage contraindicated?

Back 17

The substance is caustic, corrosive or a volatile hydrocarbon. Large, chunky material may not be adequately retrieved by gastric lavage.

Front 18

What is meant by "activated" charcoal?

Back 18

Carbonaceous compounds are treated with steam and acid to produce a highly porous material capable of trapping a wide range of organic substances.

Front 19

List some compounds which do not adsorb well with activated charcoal.

Back 19

Alcohols (including ethylene glycol), hydrocarbons, metals, inorganic minerals and corrosive agents.

Front 20

When is AC contraindicated?

Back 20

When there is a significant danger of aspiration. Esophageal or GI perforation is suspected. The animal is experiencing severe vomiting.

Front 21

When are cathartics contraindicated?

Back 21

When diarrhea or dehydration are already present, or in the case of ileus or obstruction. If animal has renal insufficiency or slowed gut transit, hypermagnesemia may result from magnesium sulfate administration.

Front 22

What are the two classes of cathartics?

Back 22

Osmotic cathartics and bulk cathartics.

Front 23

List three osmostic cathartics and describe how they work.

Back 23

Magnesium sulfate and sodium sulfate are saline cathartics that act by increasing fluid retention in the gut. Sorbitol is a non-absorbable sugar. Sorbitol can be added directly to the AC solution.

Front 24

Describe how ocular exposures occur and how they should be treated.

Back 24

Oular exposures usually only involve the superficial layers of the cornea or conjunctiva. Immediate irrigation should be performed with body-temperature tap water LRS or normal saline for 20-30 minutes.

Front 25

How should dermal exposures be managed and what are some considerations for treating dermally exposed patients?

Back 25

Bathing is standard method of decontamination. First, animals should be stabilized and assessed prior to bathing. Liquid hand dish detergents are the best soaps to use. Repeated bathing and rinsing may be required. If sticky or viscous material present, Goop or Go Jo hand cleaners may be needed followed by hand dish soap. Clipping or shaving the hair may also be required.

Front 26

What is meant by the term "ion trapping?"

Back 26

The principle behind ion trapping is that charged molecules cannot cross biological membranes and are thus trapped in a particular space. Most often applied to toxins that are predominantly excreted through the kidney, where they are "trapped" in urine in their ionized form.

Front 27

Under what conditions is ion trapping likely to be successful?

Back 27

Successful ion trapping:
1. compound is excreted predominantly unchanged through the kidneys
2. compound is a weak electrolyte with a suitable pKa
3. toxicant is primarily distributed to the extracellular space and is not protein bound

Front 28

When is ion trapping contraindicated?

Back 28

1. toxicant has a large volume of distribution
2. strongly protein bound
3. highly lipid soluble
4. is cleared primarily by tissue or hepatic metabolism

Front 29

How can acid or alkaline diuresis be performed?

Back 29

Acid diuresis is useful for weak bases such as amphetamines. Should administer ammonium chloride PO (but recognize that most patients already have a pre-existing metabolic acidosis)

Alkaline diuresis is useful for weak acids such as phenobarbital. Should administer sodium bicarbonate in IV fluids. complications include volume overload, hypernatremia, decreased serum ionized calcium, dec oxygen delivery to tissues, paradoxical CNS acidosis, hypokalemia. Contraindications include existing metabolic alkalosis, hypokalemia, hypocalcemia

Front 30

What samples should be collected antemortem?

Back 30

Blood (whole or serum), urine, stomach contents, suspect bait, hair

Front 31

What samples should be collected postmortem?

Back 31

Always: liver, kidney, stomach contents, fat, urine, globe of eye, brain.
Sometimes: hair, bile, heart clot blood

Front 32

What general clinical considerations for the seizuring patient are important in regards to acid/base status of the patient?

Back 32

Acid-base disturbances can result from physical exertion (acidosis from excess lactic acid during extreme muscle activity). It is also important to know (and be able to control) the acid base status for certain treatments such as ion trapping.

Front 33

What general clinical considerations for the seizuring patient are important in regards to rhabdomyolysis and myoglobinuria?

Back 33

Myoglobin is toxic to renal tubule cells and can cause secondary renal failure.

Front 34

What general clinical considerations for the seizuring patient are important in regards to patient temperature?

Back 34

Hyperthermia is often seen with seizures - probably from excess muscle activity, but maybe also from damage to temp reg center hypothalamus??)?

Front 35

What treatment options are available to control the seizure in a seizuring patient?

Back 35

1. Benzodiazepines (Diazepam=valium) (may not be strong enough
2. Barbituates (phenobarbital, pentobarbital
3. Skeletal muscle relaxants (Methocarbamol=Robaxin-V)
4. Short acting hypnotics (Propofol) - not labeled for use in seizures, but a good option when other therapies not effective
5. Inhalation anesthetics (Isoflurane)
Also, ascess airway and cardiac function, maintain hydration to keep kidney well-perfused, monitor and correct acid/base disturbances, monitory and correct hyperthermia (wet down, use fan), avoid stimulation

Front 36

What considerations are necessary in regards to using an emetic on a patient that may seizure?

Back 36

Inducing emesis may actually cause a seizure. Seizuring patients are in danger of aspirating vomitus.

Front 37

What is the mechanism of strychnine?

Back 37

Blocks inhibitory actions fo glycine (an inhibitory neurotransmitter) in the spinal cord. Especially important is the action of glycine on Renshaw cells. Renshaw cells normally inhibit motor neurons after they fire, preventing a positive feedback loop. After strychnine poisoning, sensory input causes muscle contractions which cause more sensory input which cause harder contractions, etc. until muscle is in tetanus.

Front 38

What clinical signs are expected with strychnine toxicosis?

Back 38

Clinical signs have a rapid onset and progression. Initially nervousness, apprehension, anxiety, increased respiratory rate, excessive salivation, but no vomiting. Followed by ataxia, muscle spasms and stiffness. No paddling or running usually, just rigidity with few periods of relaxation btw seizure episodes. Death usually due to inhibition of respiration or physical exhaustion.

Front 39

How should strychnine exposures be managed?

Back 39

Do not induce emesis because of rapid onset of signs. Gastric lavage or enterogastric lavage followed by AC and saline cathartic is better. Control seizures with drugs - diazepam not usually effective. Keep animal in dark, quiet environment.

Front 40

What clinical signs are expected after ingestion of water hemlock?

Back 40

Rapid onset and progression of signs: signs by 1 hour and death by 1-3 hours. Will see excessive salivation, vigorous chewing movements, teeth grinding and frequent urination and defication seen early. Followed by ataxia, tremors, violent seizures. Death usually due to respiratory paralysis and asphyxia.

Front 41

What is the name of the toxin in water hemlock? Where is it found?

Back 41

Circutoxin is an unsaturated long-chain alcohol present in pungent yellow fluid in base of hollow stems and roots.

Front 42

How should water hemlock exposures be managed?

Back 42

Animals usually are found dead, but can try to control seizures with a barbituate. To prevent further problems with herd, dig up or burn plants or use an herbicide.

Front 43

What is the mechanism of action of tetanus toxin?

Back 43

Tetanospasm (the clinically important endotoxin)is formed under anaerobic conditions and prevents release of glycine presynaptically. The toxin enters neurons and travels retroaxonally to the CNS. Tetanolysin induces pore formation in cells to aid in replication of tetanus organism at the wound site.

Front 44

What clinical signs are seen with tetanus toxin?

Back 44

Generalized musculoskeletal stiffness, abnormal blinking from fine motor tremors of eyelid/elevated third eyelid. Sardonic grin - contraction of muscles of lips. Progresses to severe muscular rigidity, "sawhorse stance," fixed stare, erect ears, reluctance to eat or drink due to "lockjaw," elevated tail "pump-handle tail," flared nostrils. Recumbancy due to muscle rigidity and convulsions possible. Death due to contraction of muscles of respiration (asphyxia).

Front 45

How should exposures to tetanus toxin be treated?

Back 45

Antibiotics to eliminate bacterial replications. Antitoxin therapy to neutralize unbound circulating toxin - short duration and will not reverse clinical signs. Clean and debride wound. Place animal in dark, quiet environment and provide nutritional support. Tranqs and muscle relaxers may be required. Give tetanus toxoid (vaccine).

Front 46

What conditions surround devlopment of tetanus toxicosis?

Back 46

Dirty wound contaminated with Clostridium tetani which produces toxin under anaerobic conditions. Prevent with tetanus vaccination program, give pre-surgical doses of antitoxin, and practice good husbandry practice (clean needles and blades.

Front 47

What is the general mechanism of action of sodium fluoroacetate (compound 1080)?

Back 47

Fluoroacetate is metabolized to fluorocitrate (the ultimate toxic metabolite) which inhibits aconitase in the Krebs cycle. Blocking of the Krebs cycle causes energy depletion, citrate and lactate accumulation and acidosis. Interference with cellular respiration and metabolism of carbs, fats and proteins.

Front 48

What clinical signs are expected with sodium fluoroacetate (compound 1080) toxicosis?

Back 48

Onset is in 30 minutes to 3 hours. Dogs show anxiety, frenzied behavior, running, howling, hyperesthesia, vomiting, salivation, U/D, tenesmus, hyperthermia. Convulsions with near normal periods in between with anoxia during convulsions. Non-responsive to external stimuli. As cellular energy is depleted, animals become weaker, comotose and die. Cats, sheep and pigs also show cardiac arrhythmia with episodes of bradycardia. Herbivores and monkeys show primarily cardiac signs.

Front 49

What is sodium fluoroacetate/compound 1080 used for?

Back 49

Used as a rodenticide and predacide since 1940's. Use as a predicide cancelled in 1972 and as a rodenticide in 1990. Limited use of livestock protection collars still allowed.

Front 50

How should sodium fluoroacetate/compound 1080 exposures be managed?

Back 50

Treatment is generally not rewarding. Enterogastric lavage and AC can be tried. Give pentobarbitol for seizure control. Slow infusion of IV fluids with bicarbonate may increase survival - monitor calcium and potassium. Acetamide has been used in New Zealand.

Front 51

What is metaldehyde used for?

Back 51

Slug bait, snail bait, molluscicide.

Front 52

What clinical signs are present with metaldehyde poisoning?

Back 52

Signs begin almost immediately to 3 hours after ingestion. Salivation, restlessness, anxiety, panting, vomiting and ataxia early. Progression to tremors, hyperthermia, convulsions. Signs usually resolve by 12 to 72 hours with treatment, but liver enzymes can become elevated after 48-72 hours and should be monitored.

Front 53

What is the general mechanism of 5-Fluorouracil (5-FU)?

Back 53

5-FU is a pyrimidine antimetabolite or "false pyrimidine" that interferes with DNA synthesis and RNA function once metabolized by actively dividing cells. Inhibition of tymidylate synthetase which prevents formation of thymidine which is necessary for DNA synthesis (hence, no cell division). Also incorporated into RNA which leads to inhibition of protein synthesis. A third mechanism involves the production of fluorocitrate which inhibits energy production (similar to compound 1080).

Front 54

How should exposures to 5-FU be managed?

Back 54

Decontamination: emesis if less than 30 minutes or gastric/enterogastric lavage and AC/C. Seizure control may require days of treatment - diazepam not usually effective. Give GI protectants for GI mucosal sloughing - sucralfate, misoprostol, omeprazole. Analgesics - butorphanol, Antibiotics (broad spectrum), monitor and treat leukopenia (appears 5-20 days post exposure) with Filgrastim (Neupogen), a granulocyte colony stimulating factor.

Front 55

Inhibits glycine, Renshaw cells, rapid onset, apprehension, severe seizures, respiration impaired, very sensitive to external stimuli, usually no vomiting, control seizures, decontaminate, supportive care, poor prognosis

Back 55

Strychnine

Front 56

Yellow resin in stem and chambered root, cicutoxin, rapid, rapid onset and progression, tremors, violent seizures, usually found dead, poor prognosis

Back 56

Water Hemlock

Front 57

Prevention of glycine release, retroaxonal transport, anaerobic conditions, spores environmentally stable, tremors, rigidity, sardonic grin, pump-handle tail, asphyxia, antibiotics, antitoxin, tranquilizers/muscle relaxants, poor prognosis

Back 57

Tetanus, Clostridium tetani, tetanospasm

Front 58

Slug and snail baits, mechanism may include inhibiting GABA, signs can be rapid or take up to 3 hours to develop, salivation, restlessness, anxiety, tremors, seizures, aggressive decontamination, tremor/seizure control, supportive care, good prognosis in most cases

Back 58

Metaldehyde

Front 59

Old rodenticide/ predacide, metabolized to fluorocitrate, inhibition of aconitase and therefore Krebs cycle, energy depletion, rapid, rapid onset, vomiting, salivation, tenesmus, vocalization, violent convulsions, coma, death, treatment usually not effective, sodium bicarbonate, decontamination, acetamide, prognosis very poor

Back 59

Sodium flouroacetate, Compound 1080

Front 60

Antimetabolite chemotherapeutic, interferes with DNA and RNA synthesis, ingestion of owner’s medication, bone marrow suppression, decontamination, seizure control, GI protectants, analgesics, antibiotics, filgrastim, prognosis guarded to poor

Back 60

5-fluorouricil, 5-FU

Front 61

What factors account for the environmental persistence of organochlorines?

Back 61

Organochlorides are highly lipophilic and tend tend to reside in fat. They're persistant in the environment and have residue concerns in food animals. May need to test fat, or lean out before slaughter. Lidane is still available as a prescription for lice and scabies - animal preps taken off market, but may still be available.

Front 62

What clinical signs can be expected with organochloride exposure?

Back 62

Salivation, vomiting, tremors, ataxia, Tonic-clonic seizures, paddling, clamping of jaw.
May last for 2-3 days

Front 63

What animals are particularly sensitive to organochlorides?

Back 63

Cats and small dogs.

Front 64

What clinical signs can be expected from 4-aminopyridine and how should exposures be treated?

Back 64

Rapidly absorbed from gut and signs in 10-15 minutes. Birds: Disorientation, seizures, vocalization, fly abnormally, death
Mammals: Hyperexcitability, salivation, tachycardia, tremors, seizures
Death due to cardiac and respiratory arrest
Signs within 10 – 15 minutes, death by 4 hours
Tx: avoid emesis, do lavage and AC/SC. control siezures, use propanolol for tachyarrhythmias.

Front 65

What is 4-aminopyridine used for? What's the commercial name?

Back 65

Bird control - Avitrol

Front 66

What are the proposed mechanisms of action of methylxanthines?

Back 66

1. Competitive antagonism of adenosine receptors
2. Affects intracellular calcium (inc amount of Ca++ entering cells and inhibit uptake and sequestration of calcium by sarcoplasmic reticulum of striated muscle)
3. Inhibition of cellular phosphodiesterase (inc cAMP and inc signaling)
4. Stimulation of sympathetic NS - inc levels of circulating catecholamines epi and norepi.

Front 67

What clinical signs are expected with methylxanthines?

Back 67

Within 6-12 hours: polydipsia, vomiting, diarrhea, restlessness. Progression to hyperactivity, polyuria, ataxia, tremors, seizures. May also see tachycardia, premature ventricular contractions, tachypnea, hypertension, hyperthermia, coma. Death due to cardiac arrhythmias or respiratory failure.

Front 68

What toxicokinetic factors account for chocolate’s long half-life in dogs?

Back 68

a)Readily absorbed orally
b)Some extended release products (caffeine)
c)Well distributed to all tissues; cross placenta barrier & into milk
d)EH recirculation
e)Reabsorbed from bladder wall
f)Theobromine has T ½ = 17.5 hrs

Front 69

How should exposures to methylxanthines be managed?

Back 69

a)Decon – induce emesis if no CI exist, administer AC/cathartic
•Chocolate may melt in stomach; emesis can be successful even after several hrs if no clinical signs
•Multiple doses of AC to interrupt EH recirculation
b)Tremor/seizure control
c)Propranolol for tachyarrhythmias
d)Atropine for bradycardia
e)Lidocaine for PVC
f)Catheterize bladder to avoid reabsorption of methylxanthine thru bladder wall; walk freq if possible
g)Supportive tx

Front 70

What is the general mechanism by which imidazoles are produced, resulting in “bovine bonkers?”

Back 70

1. Treatment of higher quality forages
2. High temperatures
3. Too much ammonia
4. Amt of grain left in straw can ↑ sugar content  more rxn w/ amino group  prod of imidizoles
5. Alfalfa, Bermuda grass, forage sorghums, orchard grass, brome, & fescue have all been assoc w/ BB

Front 71

chlorinated, lipophilic, biaccumulate, affect sodium channels and GABA, nausea, vomiting, agitation, tremors, seizures, bathe, anti-seizure medications, supportive

Back 71

Organochlorine insecticides

Front 72

avicide, rapid, rapid, rapid, blocks K+ channels, increased release of ACh, tremors, seizures, cardiac arrhythmias, death, seizure control, AC/SC, propranolol

Back 72

4-aminopyridine

Front 73

caffeine, theobromine, theophylline, rapid absorption, enterhepatic recirculation, reabsorption through bladder wall, adenosine antagonists, modulate intracellular calcium, inhibit phosphodiesterase, sympathomimetic, pu/pd, vomiting, hyperactivity, tremors, seizures, tachycardia, emesis, AC/SC, anti-seizure medications, propranolol, fluids

Back 73

Methylxanthines

Front 74

bovine bonkers, treatment of low quality feeds, interaction of amino group with reducing sugar to produce imidazole, rapid onset, nervousness, ear twitching, tremors, seizures, nursing calves at risk, remove feed, keep quiet

Back 74

Ammoniated feed

Front 75

excess sodium, water deprivation, crosses into CSF, inhibits glycolysis, osmotic gradient, cerebral edema, neurological signs, serum/CSF/brain sodium elevated, eosinophilic perivascular cuffing, rehydrate slowly

Back 75

Hypernatremia, sodium ion toxicosis