Exam 3- Ethylene Glycol-OTC medications Flashcards
Do all antifreeze products contain toxic levels of Ethylene Glycol?
NO!
Propylene glycol does not have nay EG in it
Where is ethylene glycol metabolized?
Liver and kidneys
Oxalic acid binds calcium and deposits in the kidneys
Cats have a high baseline production of oxalic acid.
(lower lethal dose)
Excreted in the urine
Mechanism of action for Ethylene Glycol
Ethylene glycol is absorbed in the GI tract. In the liver it is metabolized by Alcohol Dehydrogenase. Glycolic Acid metabolized by Lactic dehydrogenase.
Acidosis occurs: Increased Osmolar gap, renal edema, and ulceration
Oxalic acid binds Ca. CaOxalate crystal deposition
Renal necrosis & Death
Clinical signs associated with Ethylene glycol
Initially- Drunken animal: vomiting, depression, PU/PD, ataxia
12-72hrs- Severe acidosis: Tachypnea, V, Dpression/Comatose, Bradycardia, Miosis, Seizures
>72hrs- Renal Failure: Oliguria ->Anuria, Oral ulcerations, Convulsions, Death
what samples are to be collected for ethylene glycol?
Ante mortem: Urine or serum
Post mortem: Kidney, Rumen contents
If you are not able to collect urine in a live patient with Ethylene glycol toxicity, what is the prognosis?
Poor!
What clinical pathology findings are consistent with Ethylene glycol?
Calcium oxalate crystalluria, Acidic urine, Azotemia, stress leukogram
What gross lesions and observations are associated with Ethylene glycol Intoxication?
Kidneys are pale, firm/congested +/- Pale streaks
Histopath is very telling: Block the light with a piece of paper (substitute to polarized lens)
On microscopic evaluation of the brain, what do you find with Ethylene Glycol toxicities
Deposition of crystals in vasculature.
What are the treatments associated with Ethylene Glycol?
Prevention of metabolsm is the goal
Diluted ethanol IV! (cheap, but side effects are possible)
Antidote: 4-metylprazole (extremely expensive)
Inhibits Alcohol dehydrogenase preventing the conversion of ethylene glycol to Glycoaldehyde
where do you find Methylxanthines
Coffee (caffeine), Theobromine (chocolate), Theophylline
What is a source for Theophylline?
Tea, human asthma medication, various foods and beverages
What toxicity is of concern with chocolate consumption?
Caffeine, AND Theobromine
How are Methylxanthines excreted?
Urine, Bile, and milk
Methylxanthines MOA
Competative antagonist of adenosine (Bronchodilation, Tachycardia, Vasoconstriction, CNS stimulation)
Increased intracellular calcium
Inhibiton of phosphodiesterase (increased cAMP -» Increased release of catecholamines
Stimulation of sympathetic Nervous system
Clinical Signs associated with Methylxanthine Toxicity
CNS (hyperactivity, Agitation, Seizures) Cardiac (tachycardia, arrhythmias) Increased motor activity- Hyperexcitable, tremors Polyuria GI irritation- vomiting and diarrhea
What is the ideal sample for diagnostic testing associated with Methylxanthine toxicity?
GI content, serum, plasma, urine, milk
Lesions- no specific lesions, Evaluate oral cavity for the presence/odor of chocolate
what treatment is indicated for Methylxanthine Toxicity
Artificial respiration
Control seizures- Diazepam
Control arrhythmias: Lidocaine (dogs), Propranolol (Cats)
Decreased Blood Pressure- Metoprolol, Propranolol
Decontamination- Emesis, Gastric Lavage, Activated Charcoal
What is the drug in Tylenol?
Acetaminophen
can Acetaminophen be used in Cats?
Absolutely not. NO dose is safe
Why can’t cats have Acetaminophen?
Cats lack the enzyme glucluron L transferase. This prevents - not able to metabolize Acetaminophen to NAPQI
How is Acetaminophen broken down in dogs
Acetaminophen is broken down to NAPQI. It then binds to proteins and causes lipid peroxidation. RBC lysis & hepatic necrosis -> Death
Clincial Signs associated with Acetaminophen in CATS?
Hematological effects-> myoglobinemia, hemolytic anemia, hematuria
Metabolic effects - Facial edema and swollen paws
Hepatic complications at high doses- encephalopathy, coagulopathy
Clinical Signs associated with Acetaminophen in DOGS?
Gastrointestinal: anorexia, nausea, vomiting, diarrhea
Hepatic associated complications: hemolysis, icterus
Hematological effects at high doses
What samples need to be collected for diagnosis of Acetaminophen
Serum and whole blood -> clin path- hepatic damage, anemia (heinz bodies in cats)
Liver and kidney -> histopathology
what liver lesions are associated with Acetaminophen?
Centrilobular to diffuse hepatic necrosis
What treatment is recommended for Acetaminophen?
Decontamination (induce emesis if necessary), Activated charcoal
Antidote: N-Acetylcysteine
Supportive treatment: antioxidant, RBCs (treatment of methemaglobin and anemia), Blood transfusion (coagulopathy)
What is the antedote for Acetaminophen?
N-Acetylcysteine
What is the active ingredient in Aspirin
Acetylsalicylic Acid
Can Aspirin be used in cats?
Yes! therapeutic levels are 10-25mg/kg/day
Toxic is much higher
MOA for Aspiring (Acetylsalicylic Acid)
Aspirin metabolized in the liver to metabolites
Salicylate inhibits COX, decreased Prostacyclin, decreased Thromboxane. Uncoupling of oxidative Phosphorylation
GI and Renal necrosis +/- Bleeding
Clinical Signs associated with Acetylsalicylic Acid
Predominately GI complications (anorexia, Vomiting, diarrhea and melena), Anuria, Muscle weakness, respiratory depression, CNS Depression
What samples and diagnostics are associated with Acetylsalicylic acid?
Whole blood (Metabolic acidosis, hepatic damage, decreased PCT increased PT/PTT, azotemia) Serum, urine, and whole blood- detection of aspirin Liver, kidney, stomach and intestines (histopath)
What lesions are associated with Aspirin
Gastric ulceration and perforation (GI bleeding), hepatic and renal necrosis
What treatments are associated with Aspirin
Decontaminate- emesis, AC, cathartics
Supportive: IV fluids, assisted ventilation, transfusions, Gastro protectants (Misoprostol, sucralfate, H2 blockers)
MOA for Ibuprofen
Metabolized in the liver and undergoes enterohepatic recirculation.
Inhibition of COX
Decreased prostaglandin (decreased blood flow, decreased epithelial function)
GI and Renal Necrosis
Clinical Signs associated with Ibuprofen
GI (1-2hrs)
Anorexia, nausea, vomiting, abdominal pain
Renal (12hrs-5 days)
Oliguria/anuria, painful renal palpation, uremic breath
Acute renal failure can occur in as little as 12 hours
What samples should you collect for Ibuprofen
Whole Blood, Serum, Urine,
Kidney for histopathology
Clinical Pathology: Metabolic acidosis, hepatic damage, secondary anemia due to blood loss, azotemia
What lesions are seen with Ibuprofen
GI: erosions, ulcerations, perforations, mucosal edema
Renal necrosis: papillary, cortical, coagulative with tubule dilation
treatment for Ibuprofen intoxication
No antidote
Decontamination: Emesis, activated charcoal (repeated doses), cathartics
Supportive care: IV fluids, Blood transfusions, Gastro protectants
what is
5-Fluorouracil
Topical used for skin tumors in humans.
What is the toxic level of 5-Fluorouracil in canines
> 43mg/kg is fatal.
One dog punctured the tube without ingestion, and died
Cats are more sensitive than dogs.
MOA of 5-Fluouracil
Inhibits RNA function, Tissue with high metabolic turnover affected
Clinical signs of 5-Fluouracil
Rapid onset of signs
GI: bloody vomiting, diarrhea
CNS: Depression, tremors, seizures
Bone marrow suppression, anemia and decreased immune function
DEATH in 7 hours
Treatment of 5-Fluouracil
Aggressive and heroic treatment required
Decontamination ASAP, limited capability due to rapid onset of clinical signs
Seizure control- Phenobarbital (4-16mg/kg IV)
IV fluids- maintain perfusion & hydration.
GI protectants- H2 blockers (Famotidine, Ranitidine, Omeprazole)
Broad spectrum antibiotics
Bone marrow suppression: Neupogen SQ every 3-5 days
can you use Diazepam in cases of 5-FU intoxication?
No, it will be of little use
What is the MOA of tricyclic Antidepressents?
5-HT Reuptake inhibited
NE reuptake inhibited- Hypotension
Muscarinic binding of ACh inhibited. Anticholinergic effects
Histamine Blocked- causing SEDATION
Clinical signs associated with TCAs
Small overdoses: Mild sedation, anorexia
Large overdose: Profound sedation, Cardiovascular collapse- leading cause of death
Treatment for TCA consumption
Decontamination- emesis, AC
EKG– monitor for widening of QRS, IVF 2x maintenance
Control seizures: Diazepam/Benzodiazepines
Physostigmine- Cholinesterase inhibitor
Serotonin Re-Uptake inhibitors MOA
5-HT reuptake inhibited
Increase of 5-HT in synapse
Development of SErotonin syndrome
Clinical Signs associated with SSRI’s
CNS stimulation- excitation, tremors, seizures, Hyperthermia
GI: vomiting, Colic, Diarrhea
What samples should you collect for SSRI ingestion
Blood- detection of SSRI by GC/MS, Little help in interpreting degree of treatment necessary
No lesion
Treatment of SSRI ingestion
Decontination: Emesis, AC Supportive: Phenobarbital- Seizures Cyproheptadine- 5-HT antagonist Cool IV fluids: Rehydrate and treat hyperthermia Antiemetics as needed
What is serotonin syndrome
Drug induced synrome due to elevated serotonin levels in the CNS- dogs are more susceptible than other species.
Contributing factors : Decreased re-uptake of 5-HT, increased synthesis, decreased breakdown of 5-HT.
LSD is a 5-HT antagonist
Clinical Signs associated with Serotonin Synrome
CNS: Agitation, Vocalization GI: Vomiting Neuromuscular: Tremoring, Ataxia Hyperthermia Blindness
Toxicokinetics associated with Amphetamines
Rapid GI absorption
Lipid soluble -> wide distribution: Brain
Very little metabolism
Excreted in the urine.
MOA for Amphetamines
Increased Catecholamine release
Decreased reuptake: NE, serotonin, Dopamine
Clinical signs of Amphetamines
Sympathomimetic: Mydriasis, CArdiac stimulant, CNS stimulant
What samples should be collected for Amphetamines?
Urine and stomach contects- detect the parent compound
What are recommended treatment methods for Amphetamines
No Antidote
Decontaminate
Supportive: Sedatives, IV fluids, Tachycardia, Tremors, Acidify Urine
What sample should you collect for Cocaine?
excreted in the urine
Plasma, stomach contents
Heart, and lung for Histopathology
MOA for Cocaine
Blocks Na+ channels -> conductance distrubances
Increased catecholamine release: increased vasoconstriction
Increased calcium in cardiac tissues
increased contractility, increased O2 demand
Clinical Signs associated with Cocaine
Sympathomimetic- mydriasis
Powerful CNS stimulant: Hyperesthesia, hyperactivity, erratic behavior, seizures
Cardiotoxic** Tachycardia, Arrhythmias, Hypertension -> Death
What are lesions associated with Cocaine
Pulmonary and cardiac hemorrhage
Pericardial edema
Treatment associated with Cocaine
No antidote
Decontamination- Emesis and AC
Control caradiac arrhythmias (B blocker - Propranolol)
Control Seizures- Diazepam/Phenobarbital
Respiratory support, control hyperthermia
Marijuana toxicokinetics
Rapid absorption (oral, inhalation)
Metabolized in the liver
Lipophilic- distributes to brain and fat
Excreted in the bile
MOA of Marijuana
Acts on CBD receptors in the body- higher affinity than endogenous cannabinoids
GABA release inhibited-
Norepinephrine & serotonin release also affected
What samples should be collected for cases of Marijuana
SErum, urine, Stomach contents, Liver, kidney
Source product
Clinical Signs associated with THC
CNS depressant Vomiting Euphoria -> Depression -> Coma Mydriasis Urinary incontinence (dribbling urine)
CBD clinical signs
Variable Asymptomatic in some cases Vomiting Depression: lethargy, ataxia Agitated
Clinical Signs associated with synthetic cannabinoids
Severe effect CNS stimulation Seizures/convulsions Ataxia Vomiting
Treatment for Marijuana cases
No antidote associated with it
Slow recovery- clinical effects may last for days
Decontamination: emesis, AC
Supportive
**Respiratory support and stimulation-Doxapram
Agitation and seizure control: butorphanol, diazepam, barbiturates
Where are opioids metabolized and excreted?
Metabolized in the liver, excreted in the urine
Clincial signs in DOGS and Opioids
Early excitation progressing to: respiratory depression, Death within 12 hours
Clinical signs in Cats and horses with Opioids
Excitation, aggression, seizures, mydriasis
What samples are needed to detect opioids
serum or urine
What are treatment methods associated with Opioids
Naloxone -> reverse respiratory and CNS depression
Reversal agent- full antagonist
Butorphanol- PArtial antagonist
Decontamination- emesis, AC, fluids
Diazepam- control seizures if necessary
supportive Care- artificial respiration.MOA of ethanol
Acts as an anesthetic agent by reversibly binding action potentials of neurons
Clinical Signs associated with Ethanol
Drowsiness/Depression
Unconsciousness
Respiratory and cardiac depression
coma and even death
what samples are you evaluating to detect Ethanol?
Blood- BAC
Diagnosis is typically based on history of exposure
Treatment associated with Ethanol
early decontamination: emesis, gastric lavage, activated charcocal
Supportive Care: respiratory support- maintain ventilation, respiratory stimulants, O2
MOA associated with Xylitol
Stimulates pancreatic secretion of insulin (dogs)
unknown: causes hepatic necrosis
Clinical Signs associated with Xylitol
Hypoglycemia (10-60min)
secondary to hepatic necrosis: DIC, icterus, hemorrhage, melena, Diarrhea
Loss of coordination and seizures
treatment associated with Xylitol
No antidote
Decontamination: Emesis (contraindicated if hypoglycemic signs are present)
IV crystalloid fluids (with dextrose even if initial BG is normal)
Supportive hepatic care
will Activated charcoal be effective in Xylitol cases
no- it has poor binding and little effect.
