3. DEFINITION/OVERVIEW
Ivermectin and other macrolides, such as selamectin,
dormectin, moxidectin, and milbemycin, are antiparasitic
drugs that are effective against both external and
internalparasites.
In general, these drugs are commonly used, are very
effective, and have wide margins of safety.
Some collie-type breeds have a genetic mutation that
causes them to develop neurotoxicity at low doses.
In other breeds toxicity occurs only with severe overdose.
4. ETIOLOGY/PATHOPHYSIOLOGY
Ivermectin and other similarly acting drugs act as GABA
agonists at the neuromuscular junction in the peripheral nervous
system of nematode and arthropod parasites.
GABA is an inhibitory neurotransmitter.
In mammals, GABA - containing neurons are limited to the CNS
where the blood - brain barrier protects them from exposure to
many drugs, including ivermectin.
The multiple drug resistance gene, MDR1, encodes for P -
glycoprotein, a principal component of the blood - brain barrier.
The mutation, mmdr1 - 1 δ , results in loss of P - glycoprotein
function, and thereby allows access to the brain by ivermectin
and some other drugs that are also substrates of P -
glycoprotein. Dogs with this mutant allele are susceptible to
ivermectin toxicity at low doses.
Systems Affected :
The toxic effect is on the neurologic system; other organ
systems are affected indirectly.
5. SIGNALMENT/HISTORY
Genetic Basis :
oAnalysis of the history of the canine mutation shows that
dogs carrying the mutant allele mmdr1 - 1 δ are
descendants of a dog that lived in Great Britain before
1873
o7 Collie-type breeds and 2 Sighthound breeds were
identified as carrying this allele. These modern - day
breeds are: Collie, Shetland sheepdog, old English
sheepdog, McNab cattledog, Australian shepherd,
miniature Australian shepherd, and English shepherd. Two
other breeds of sighthound type but descended from the
common ancestor are silken windhound and longhaired
whippet.
oIvermectin sensitivity has been reported in border collie,
bearded collie, and Australian cattle dog.
6. Signs :
Toxicity is to the CNS with other systems affected
secondarily.
Ataxia
Tremors
Seizures
Coma
Death
7. Historical Findings :
• Ivermectin toxicity should be considered in a dog belonging to
a susceptible breed with a history of acute onset of neurologic
signs combined with recent exposure to drugs in this group.
• In dogs with the mutant allele, doses of ivermectin of 100 to
500 μ g/kg have caused toxicity.
• In other breeds, toxicity occurs only with severe overdoses ( >
2000 μ g/kg) usually caused by miscalculation using equine or
bovine preparations. The median lethal dose for experimental
beagle dogs was 80,000 μ g/kg.
• Exposure can also occur from dogs eating feces of treated
large animals because the drug is eliminated in the feces.
• Young animals are more susceptible to toxicity because their
blood - brain barrier is not fully developed.
• Toxicity has been reported in kittens at doses of 300 to 400 μ
g/kg.
8. CLINICAL FEATURES
Physical Examination :
Ataxia or recumbency and altered mental state (e.g., depression,
obtundation) are the primary neurologic signs with stupor, coma, and
even death occurring in severely affected dogs.
Those with depressed mentation may also have decreased gag reflex.
Muscle tremors, seizures, and loss of menace and pupillary light
response may occur.
Spinal cord reflexes may be normal or increased.
Other signs include bradycardia, mydriasis, miosis, hypersalivation and
vomiting.
Clinical signs in dogs can range in severity, even with
ingestion/exposure to similar doses.
Onset of signs can be within a few hours after administration of a single
dose.
Animals being treated daily may develop signs of toxicity only after
several days.
9. DIFFERENTIAL DIAGNOSIS
• Differentiation from other causes of acute onset
neurologic signs is based on a history of exposure to the
drug in a susceptible canine breed or severe overdose in
other animals.
10. DIAGNOSTICS
Laboratory :
• Ivermectin and other macrolides can be detected in serum,
gastrointestinal contents, liver, and fat but levels in tissues do
not correlate with toxicity because it is the concentration of the
drug in the brain that determines toxicity.
Other :
• Reversal of neurologic signs in response to the
anticholinesterase physostigmine supports but does not confirm
a diagnosis. Its use for this purpose is not recommended
because of adverse side effects.
• A DNA-based test for the mutant genotype is available and could
be used to confirm that a dog is at increased risk of toxicity.
Pathological Findings :
• No specific lesions are directly caused by these drugs.
11. THERAPEUTICS
Drug(s) of Choice :
• There is no specific antidote.
• If the drug has been ingested in the past 2 hours emesis should be
induced, provided that the patient is alert enough to protect its airway.
If the patient is not able to protect its airway, orogastric lavage under
general anesthesia with intubation should be performed.
• Orogastric lavage should be followed by activated charcoal and a
sorbital cathartic.
• Repeat doses of activated charcoal are indicated because of the
potential for enterohepatic recirculation.
• Anticholinesterase drugs have been administered as a diagnostic test
or for short - term improvement of clinical signs. Physostigmine may
result in partial improvement of signs but the effect lasts less than 1
hour. The potential toxicities of physostigmine are tremors, seizures,
ptyalism, lacrimation, urination, and defecation. It does not target
ivermectin toxicity directly and is not recommended.
12. • Picrotoxin, a GABA antagonist, has also been used to treat
ivermectin toxicity.
• Picrotoxin resulted in a rapid improvement in mental state
followed by a seizure.
• If treatment for seizures or tremors is required it may be
advisable to avoid the use of Benzodiazepines, such as
diazepam, because the binding sites for benzodiazepine,
GABA, and ivermectin are closely associated. It has been
proposed, but not proven that enhancement of the toxic
effects might occur. Barbiturates may be preferable
because their binding site in the brain is not as closely
associated with the ivermectin binding site.
13. Supportive Care :
• Patients should receive supportive care as
appropriate for their clinical signs and must be
closely monitored.
• Deterioration from the initial presenting signs for
approximately the next 6 days followed by gradual
improvement over the next 6 to 18 days is expected.
Longer courses have been reported.
• Special attention should be paid to the respiratory
and cardiovascular systems because hypoventilation
that requires mechanical ventilation and bradycardia
that requires treatment with an anticholinergic agent
such as glycopyrrolate have been reported.
14. • Aspiration pneumonia due to a combination of
recumbency and a decreased gag reflex can occur.
• Patients who are unable to eat and drink normally must
receive fluid and electrolyte therapy and nutritional
support. Oral intake of food or water should not be
attempted in patients with altered mental states because
they may have decreased gag reflexes and be unable to
properly protect their airway. In these patients,
nasogastric or gastric tube feeding is preferred but
intravenous nutrition may be preferred.
• Severely affected patients are recumbent and meticulous
care for the recumbent patient is needed.
Prognosis :
• The prognosis for recovery without long - term sequelae is
good even in severely affected patients provided that
aggressive intensive care support is administered.
16. DEFINITION/OVERVIEW
• Amitraz is applied topically to control ticks, mites, and lice.
• Flea and tick collars contain enough amitraz to cause
clinical signs of intoxication in a twenty-five - pound dog.
17. ETIOLOGY/PATHOPHYSIOLOGY
• Amitraz affects peripheral α1 - and α2 - adrenergic
receptor sites in the cardiovascular system and α 2 -
adrenergic receptor sites in the CNS, thus it is a α 2 -
adrenergic agonist.
• Toxic exposure can occur either through the oral or
dermal route.
• After high dose, oral ingestion peak plasma concentration
is reached at 6 hours and elimination half - life is as long
as 24 hours.
• The metabolites are excreted in the urine.
18. SIGNALMENT/HISTORY
• Toxicity in dogs is more commonly reported than in cats or
other species.
• Amitraz should never be used in cats.
Risk Factors/Causes :
• Increased predilection for toxicity in geriatric, sick, or toy
breed animals.
Historical Findings :
• Signs of sudden collapse, depression, vomiting, and
diarrhea.
19. CLINICAL FEATURES
• Neurological signs as depression, ataxia, and weakness
• Cardiovascular collapse with bradycardia, recumbency,
and hypotension
• Gastrointestinal signs of vomiting, diarrhea, and
abdominal pain
20. DIFFERENTIAL DIAGNOSIS
• Recreational and prescription drugs such as marijuana,
opioids, barbiturates, benzodiazepines, phenothiazines,
antihypertensive drugs, skeletal muscle relaxants, and
other depressive drugs
• Ivermectin or milbemycin in very high doses to sensitive
breeds
• Alcohols such as ethanol, ethylene glycol (antifreeze),
methanol (wind shield washer fluid), isopropyl alcohol
(rubbing alcohol)
• Tick paralysis, botulism
• Head trauma
• Cardiovascular collapse
21. DIAGNOSTICS
Complete Blood Count/Biochemistry :
• Hyperglycemia is common.
• Liver enzymes may rarely be elevated.
Imaging :
• Abdominal radiology may reveal a collar buckle in the
gastrointestinal tract.
Pathological Findings :
• High - dose and prolonged exposure shows increased
liver weight; slight enlargement of hepatocytes; thinning of
the zonae fasciculata and reticularis; slight hyperplasia of
the zona glomerulosa of the adrenal glands
22. THERAPEUTICS
Drug(s) of Choice :
• Treatment of amitraz poisoning is best accomplished by
gastric decontamination and administration of antidotes
(yohimbine or atipamezole).
Precautions/Interactions :
• Do not administer atropine, even if bradycardia occurs.
Atropine may relieve some clinical signs, however may
cause other clinical signs to worsen, and may contribute
to hypertension.
• Do not induce emesis if the toxic substance was Mitaban
® dip, due to risk of aspiration pneumonia.
23. Ingestion of Collar; Asymptomatic Patient :
• Emetic as 3% USP hydrogen peroxide (2.2 m/kg PO
maximum 45 ml after feeding a moist meal);
apomorphine, and especially xylazine, not recommended
• Endoscopic retrieval of collar if large segments within the
stomach; usually numerous small pieces are located
throughout the gastrointestinal tract, making endoscopic
removal difficult or unrealistic.
• Surgical removal of collar from gastrointestinal tract
• Activated charcoal (2 g/kg PO) containing sorbitol
24. Marked Depression :
• May require pharmacologic reversal of the α 2 - adrenergic
effects
• Yohimbine (Yobine) — 0.11 mg/kg IV, administered slowly;
reverses depression and bradycardia within minutes; objective
is to keep the patient in a state of low – level depression with
normal heart rate, blood pressure, body temperature, and
blood glucose concentrations
• Collar ingestions — monitor for recurrence of clinical signs;
may need additional yohimbine until collar segments appear in
the stool
• Atipamezole (Antisedan) — 0.05 mg/kg IM; reported to reverse
poisoning within 10 minutes; repeated as needed; can be used
an alternative when yohimbine is unavailable
• Yohimbine and atipamezole may require initial repeated
administration every 4 to 8 hours because half - life in dogs is
short and elimination half - life of amitraz is longer.
26. DEFINITION/OVERVIEW
• Ingestion of chocolate (methylxanthine alkaloids) in sufficient
quantity to cause gastrointestinal, neurologic, and cardiac
abnormalities
27. ETIOLOGY/PATHOPHYSIOLOGY
• Methylxanthine alkaloids – theobromine and caffeine from
the cocoa bean
• Methylxanthines – adenosine receptor antagonist in the
CNS; causing stimulation and cerebral vasoconstriction;
direct myocardial stimulator — tachycardia; increased
calcium entry into the sarcoplasmic reticulum —
increased skeletal and myocardial contractility
• Caffeine — phosphodiesterase inhibitor; increased cAMP
and the release of catecholamines
• Theobrominine — undergoes enterohepatic recirculation
• Theobromine and caffeine LD50 = 100 to 200 mg/kg,
however, clinical signs can be seen as low as 20 mg/kg
28. Incidence/Prevalence :
• More common during the holiday season due to increased
availability
• Cocoa shell mulch; increasing in popularity for
landscaping
Systems Affected :
• Gastrointestinal — vomiting and diarrhea
• Urologic — polyuria, polydipsia
• Nervous — hyperactivity, CNS stimulation, seizures
• Musculoskeletal — tremors, hyperreflexia
• Cardiovascular — tachycardia, increased myocardial
contractility
29.
30. SIGNALMENT/HISTORY
• Dogs — puppies and young dogs more commonly affected
• Cats — rarely
Historical Findings :
• Recent chocolate ingestion reported
• Gastrointestinal signs; vomiting and diarrhea (2 – 4 hours)
• Polyuria/polydipsia
• Hyperactivity and anxiety
• Neurologic signs — tremors, seizures
33. DIAGNOSTICS
• CBC and serum biochemistry: hypokalemia
• Urine specifi c gravity: low
• Stomach content analysis: presence of chocolate and
methylxanthine
• Plasma, serum, and urine: theobromine levels
34. THERAPEUTICS
• The objective is to eliminate the methylxanthine toxin by
decontamination and support of clinical signs.
• Induce emesis if alert
• Orogastric lavage
• Activated charcoal
• Intravenous fluid diuresis: intravenous crystalloid fluids;
high rates as tolerated by the patient
• Urinary catheter; theobromine is reabsorbed in the
bladder
35. Drug(s) of Choice :
Emetics :
• Apomorphine: Dogs 0.02 to 0.04 mg/kg IV; 0.1 mg/kg SQ; 0.25 mg/kg
conjunctival sac; Cats 0.04 mg/kg IV; 0.08 mg/kg IM or SQ
• Hydrogen peroxide: 1 to 5 ml/kg PO
• Xylazine : Dogs 0.2 mg/kg IV; 0.5 to 1 mg/kg IM or SQ; Cats 0.44
mg/kg IM
Toxin Binding :
• Activated charcoal: 2 to 8 g/kg PO every 6 to 8 hours
Seizures :
• Diazepam: Dogs 0.5 to 2 mg/kg IV; Cats 0.5 to 1 mg/kg IV
36. Ventricular Tachycardia :
• Lidocaine: 1 to 2 mg/kg IV bolus over 30 seconds; 25 to 80 μ g/kg per
min CRI
Muscle Tremors :
• Methocarbamol: 44 mg/kg IV; administer half slowly until relaxation
and continue to effect
Precautions/Interactions :
• Do not induce vomiting if obtunded, having seizures, or otherwise
unable to protect airway
• Cats: Lidocaine use caution; apomorphine is controversial; diazepam
may induce liver failure
• Avoid corticosteroids and erythromycin; reduced methylxanthine
excretion
• Methylxanthines are excreted in milk and cross the placenta
38. DEFINITION/OVERVIEW
• Acetaminophen (paracetamol) is a common over-the
counter pain medication.
• Acetaminophen possesses antipyretic and analgesic
properties similar to NSAIDs, although it does not have
any anti-infl ammatory properties.
• Acetaminophen is found in over two hundred over-the-
counter and prescription medications.
39.
40. ETIOLOGY/PATHOPHYSIOLOGY
• Metabolized by the liver via two pathways:
• The major pathway converts acetaminophen to inactive
metabolites through conjugation to inactive glucuronide
and sulfate metabolites.
• The minor pathway metabolizes acetaminophen by the p -
450 mixed function oxidase to a highly reactive toxic
metabolite, NAPQI. (N - acetyl - para – benzoquinoneimine)
• Under normal circumstances this minor route produces
little NAPQI, but in the event of acetaminophen toxicity,
the glucuronidation pathway becomes saturated and
metabolism shifts to the production of NAPQI
41. • Under nontoxic conditions, glutathione is conjugated to NAPQI,
which effectively detoxifies it. In toxic conditions, glutathione
stores quickly become depleted, leaving NAPQI free to bind to
lipid in the hepatocyte membrane and causing hepatocellular
necrosis.
• NAPQI also causes severe oxidative damage to red blood cells
by causing the oxidation of hemoglobin to metHb, a compound
that does not carry oxygen. Oxidation of hemoglobin also causes
the formation of Heinz bodies.
• Cats lack glucuronyl transferase, which decreases the amount of
metabolism through the major pathway.
• In cats, relatively smaller amounts of acetaminophen will produce
more toxic metabolite and therefore cause more severe toxicity
compared to dogs.
• Feline hemoglobin is also unique and contains eight sulfhydryl
groups. Because of this unique property, feline hemoglobin is
more sensitive to oxidation and can form metHb more rapidly
with smaller amounts of acetaminophen.
• In cats, methemoglobinemia may happen rapidly and become
fatal before they show signs of hepatotoxicosis.
42. Systems Affected :
• Hepatobiliary: liver necrosis
• Cardiovascular: facial and
paw edema
• Hemic/lymphatic/immune:
Depletion of glutathione
causes oxidative damage
to red blood cells and
converts hemoglobin to
metHb
Facial edema may be seen in dogs, but it
is more commonly seen in cats with
acetaminophen
toxicity.
43. Genetics :
• Toxicity is observed in cats more frequently seen
than dogs due to their smaller body size and
decreased ability to glucoronidate and eliminate
acetaminophen.
Incidence/Prevalence :
• Most common drug toxicity in cats
• Less common in dogs
44. SIGNALMENT/HISTORY
Species :
• Most frequently cats, less commonly dogs
• No known breed predilections
History :
• Administration of acetaminophen or history of ingestion of
acetaminophen. Owners may not be aware that
acetaminophen has potentially life - threatening effects in
dogs and cats.
• Owners may notice clinical signs within 1 to 4 hours after
ingestion or signs may be delayed until after metHb or
hepatotoxicity occurs.
45. Physical Examination Findings :
• Anorexia, salivation, vomiting, abdominal pain
• Hypothermia
• Depression, weakness, coma in severe cases
• Methemoglobinemia
• Brown or cyanotic mucous membranes
• Tachypnea
• Respiratory difficulty/distress
• Dark, chocolate - colored blood and urine
• Edema of the face and paws (most commonly in cats,
observed more rarely in dogs)
• Death
Risk Factors/Causes :
• Acetaminophen overdose
46. DIFFERENTIAL DIAGNOSIS
Other drugs/toxicities causing methemoglobinemia:
• Nitrites
• Phenacetin
• Nitrobenzene
• Phenol and cresol compounds
• Sulfites
• Naphthalene
• Resorcinol in cats
• Pyridium
• Local anesthetics
• Garlic or onions
47. DIAGNOSTICS
Complete Blood Count/Biochemistry/Urinalysis :
• Heinz bodies, especially in cats
• Possibly anemia due to lysis of affected red blood cells
• Elevated ALT, Alk Phos
• Liver values may increase 24 to 36 hours post - ingestion.
• Elevated total and direct bilirubin
• Serum may be icteric
• Large doses may be nephrotoxic; may see increases in
BUN and creatinine
• May see orange or dark colored urine with hemoglobinuria
or methemoglobinuria
48. Toxic Dose :
Dogs
• 100 mg/kg is hepatotoxicity
• 200 mg/kg and methemoglobinemia may be seen
Cats
• No safe dose for cats; 10 mg/kg has produced toxic signs,
although generally not seen until 30 to 40 mg/kg. Cats
generally show severe signs of methemoglobinemia
rather than hepatotoxicosis.
49. THERAPEUTICS
Drug(s) of Choice :
Induction of emesis
• Apomorphine: 0.03 mg/kg to
0.04mg/kg IV, IM, or 1.5 to 6
mg dissolved in the
conjunctival sac
Vomitus containing Tylenol PM that
contains acetaminophen.
50. • Xylazine: 0.44 to 1.1 mg/kg IM or SQ
• Hydrogen peroxide: 1 to 2 ml/kg PO (max dose of 30 ml). If not
successful in 10 minutes give another dose once.
Gastric lavage
• If emesis is unsuccessful or contraindicated (if animal is neurologically
inappropriate or has decreased gag reflex)
Activated charcoal
• Repeat every 3 to 4 hours; acetaminophen undergoes enterohepatic
recirculation
• 2 to 5 g/kg
N - acetylcysteine (Mucomyst)
• 140 mg/kg PO or IV loading dose
• 70 mg/kg PO or IV every 6 hours for seven treatments
• Consider giving 240 mg/kg PO or IV as a loading dose in severe cases
• Activated charcoal inactivates N - acetylcysteine if it is given PO. Wait
at least 30 to 60 minutes between treatments
• Provides sulfhydryl source to bind NAPQI, and thus protects
hepatocytes and red blood cells.
51. Metabolism of acetaminophen to both toxic and non - toxic by - products. In acetaminophen
toxicity, the conjugation pathways become saturated and lead to increased p450
metabolism to N - acetyl - parabenzoquinoneimine (NAPQI), the toxic metabolite. Toxicity
also leads to glutathione depletion which perpetuates hepatic damage and also contributes
to oxidative damage of red blood cells. N - acetylcysteine helps get rid of NAPQI through
conjugation to nontoxic by - product.
52. Vitamin C (ascorbic acid)
• 30 mg/kg PO or SQ every 6 hours
• Questionable efficacy
• May cause gastrointestinal upset
Cimetidine
• 5 to 10mg/kg every 6 to 8 hours IV, IM
• Reduces metabolism of acetaminophen by the cytochrome p - 450
oxidative system in the liver
• Use as adjunct to N - acetylcysteine
Supportive therapy
• Intravenous fluids
• ± O2 therapy
• ± Packed red blood cells or whole blood if necessary
• Feed cats kitten food due to increased sulfhydryl group substrates
S - adenosyl methionine (sAMe; denosyl)
• 18 mg/kg PO every 24 hours on an empty stomach
• Chronic treatment until liver enzymes are within normal limits
53. Contraindications :
• Drugs that may perpetuate clinical signs
Precautions/Interactions :
• Drugs that are metabolized by the liver may have prolonged
half - lives; drugs that are biotransformed by the liver may be
less effective.
Activity :
• Activity should be restricted.
Appropriate Health Care :
• Evaluate immediately when presented with brown or cyanotic
mucous membranes,
Nursing Care :
• Gentle handling is imperative for clinically affected animals. It is
important to minimize stress as much as possible, especially in
cats.
• Animals presenting in respiratory distress may require
immediate oxygen supplementation.
55. DEFINITION/OVERVIEW
• Ingestion of anticoagulant rodenticide compounds results
in a depletion of vitamin K and functional vitamin K -
dependent coagulation factors and causes an acquired
coagulopathy.
56. ETIOLOGY/PATHOPHYSIOLOGY
• Vitamin K, a fat-soluble vitamin, is a crucial cofactor for
hepatic posttranslational carboxylation of coagulation
factors II, VII, IX, and X (and protein C and protein S)
• Anticoagulant rodenticide ingestion inhibits the hepatic
enzyme, vitamin K epoxide reductase, and prevents the
recycling of the vitamin K metabolite, vitamin K epoxide,
back to its functional form
• Once hepatic vitamin K stores are depleted, production of
functional vitamin K-dependent coagulation proteins ceases
and causes the formation of PIVKAs (proteins induced by
vitamin K antagonists or absence)
• PIVKAs are incapable of chelating calcium and therefore
are unable to successfully partake in secondary
hemostasis.
59. SIGNALMENT/HISTORY
No specific signalment, although intact animals may be more likely
to roam and be accidentally or maliciously exposed to toxins.
Risk Factors/Causes :
• The presence of vitamin K antagonist rodenticides in the
immediate environment.
Historical Findings :
• May reveal possible exposure to or ingestion of anticoagulant
rodenticides
• Ingestion of an animal that consumed anticoagulant rodenticide
(relay toxicosis)
• Vomit or feces with green - or turquoise - colored granules in it
• Respiratory difficulty or hemorrhage
60. CLINICAL FEATURES
• Clinical features are similar for dogs and cats.
• Clinically asymptomatic if ingestion occurred < 48 hours
previously.
• Clinical signs associated with deep tissue hemorrhage
(hemoptysis, hemothorax, hemoabdomen, hemarthrosis,
intracranial, pericardial, sublingual or subcutaneous
hemorrhage) most frequently develop between 2 and 6
days following consumption.
• In the acutely bleeding patient, hypoproteinemia will
generally develop prior to the anemia; anemia may
develop simultaneously or before hypoproteinemia in the
face of slow and sustained hemorrhage.
61. DIFFERENTIAL DIAGNOSIS
• Similar between dogs and cats, with the exception of
variations in inherited coagulation factor deficiencies
• Hepatic failure
• Disseminated intravascular coagulation
• Dilutional coagulopathy
• Congenital factor deficiency
• Massive heparin overdose
• Absolute vitamin K deficiency (malnourished patients
receiving broad – spectrum antibiotic therapy, posthepatic
biliary obstruction, or exocrine pancreatic insufficiency or
intestinal malabsorption)
62. DIAGNOSTICS
• Diagnosis is often made with a history, clinical
presentation, or coagulation profile that supports the
diagnosis, all in the face of a rapid response to vitamin K
1 therapy.
Pathological Findings :
• Presence of nonclotting blood found on aspiration of body
cavity or swelling.
• Hemorrhage in the airways; uncommonly hemorrhage
from mucosal surfaces
63. THERAPEUTICS
Treatment depends on timing of ingestion and the urgency of the
clinical presentation.
Drug(s) of Choice :
• Emesis is induced if ingestion occurred within previous 2 hours.
• Activated charcoal administration is ideal if ingestion occurred
within previous 2 hours; this however may delay efficacy of
orally administered vitamin K 1.
• Vitamin K 1 : 2.5 to 5 mg/kg per day PO for up to 6 weeks
(dependent on agent ingested) is indicated for all patients with
confirmed or even suspected ingestion; oral administration is
generally more rapidly effective ( < 12 hours) than SQ (12 – 24
hours) and safer than intravenous dosing (risk of anaphylaxis).
64. • Vitamin K 1 therapy alone is usually sufficient to reverse
the anticoagulant effect in patients with prolonged PT
without hemorrhage.
• In more urgent cases (i.e., presence of hemorrhage)
plasma (fresh frozen or frozen) 10 to 15 ml/kg or whole
blood (fresh or stored) up to 20 ml/kg are administered,
concurrently with oral or SQ vitamin K 1 to promptly
(although temporarily) reverse anticoagulation.
• Cautious intravenous fluid administration to reverse
shock, while minimizing exacerbation of further
hemorrhage with unnecessary or excessive increases in
blood pressure.
• Oxygen therapy if hypoxemia is present or in an attempt
to ease respiratory distress; avoid nasal oxygen
cannulation due to risk of inducing hemorrhage/epistaxis.
65. Precautions/Interactions :
• Orally administered vitamin K may be insufficiently absorbed if
concomitant intestinal malabsorption or extrahepatic biliary
obstruction is present; hepatic dysfunction tempers the
response to vitamin K 1 therapy.
• Allergic reactions (i.e., urticaria, angioneurotic edema) may
occur with SQ vitamin K 1 therapy, whereas anaphylaxis is a
concern with intravenous administration.
• Vitamin K 1 administered IM may result in hematoma formation
and therefore is contraindicated.
• Small - gauge needles should be used for SQ administration of
vitamin K 1 (or any other parenteral medications) in several
different sites to expedite absorption.
• Gastroenteric lavage is not indicated due to rapidly reversible
nature of toxicity.
Alternative Drugs :
• Oxyglobin ® may be utilized to temporarily improve oxygen -
carrying capacity if blood products are not readily available,
providing time for vitamin K1 therapy to become effective.
66. Diet :
• Administration of vitamin K 1 with a high fat meal (i.e.,
canned food) improves bioavailability.
Activity :
• With complicated toxicity, activity should be limited to
avoid exacerbation of hemorrhage.
Surgical Considerations :
• Thoracocentesis may be indicated if the development of a
hemothorax sufficiently compromises respiration.
• Preferably avoid unnecessary procedures until
coagulation ability has normalized.
67. REFERENCES
• Small Animal Emergency and Critical Care by Elisa M.
Mazzaferro, MS, DVM, PhD, DACVECC (Blackwell’s Five-
Minute Veterinary Consult)
