Toxicology adverse drug effects and case management Flashcards
adverse drug reaction
Reactions occurring due to over-accumulation of the drug in the animal
“In-flow exceeds out-go”
ex: decreased ability to eliminate, altered metabolism, selective organ uptake
Any toxic or unintended response to a drug that occurs at appropriate therapeutic doses
Macrolide Endectocides adverse effects
TOXIC
Some collies are deficient in multi-drug resistance gene (MDR1)
act as GABA agonists when they bind receptor in MDR-1 deficient animals
Clinical Signs:
* Ataxia
* Behavioral changes
* Depressed, disoriented
* Bradycardia
* Hypersalivation
* Mydriasis
* Vomiting, diarrhea
* Tremors, seizures
Non toxic adverse reaction example
Corticosteroids given to dogs = PU/PD
* Others: THC, benzodiazepines, barbiturates
Partial inhibition of antidiuretic hormone (vasopressin) secretion
beneficial/therapeutic reaction example
Diphenhydramine
Antihistamine for allergy treatment
* Inverse agonist of histamine H1 receptor
* Binds same receptor as histamine
Sedative Effect (sleep aid, anxiolytic)
* Mild inhibitor of reuptake of serotonin
* Crosses blood-brain barrier antagonizing central H1 receptors
idiosynchratic adverse drug reactions
“Unique” or unusual – individual
Occurs in animals at therapeutic concentrations
Host-dependent, not dose-dependent
Rarely occur (< 0.1%) and are unpredictable
Dependent on chemical properties of drug, not pharmacological properties
Occurs within 1 to 2 months of drug therapy
Idiosyncratic hepatotoxicity more commonly reported
ex: carprofen hepatotoxicity 14-30 days during treatment
functional antagonism
An interaction between two or more drugs (or drugs + poison) that produce opposite effects on the same physiological function
Treating the clinical signs observed
ex: Strychnine
* inhibit glycine (inhibitory)
* causes: Excess sensory input & exaggerated responses, rigor, Sardonic “grin” – sustained facial muscle spasms, Seizures, convulsions
* treatment: calm NS (propofol)
chemical antagonism
A chemical interaction (reaction) that occurs between two drugs (or drug + poison) that produces a less toxic product
ex: Chelation therapy and heavy metal toxicity
ex: antivenom
chelation therapy
chemical antagonism
Chelation therapy and heavy metal toxicity
* 99% of lead is bound to hemoglobin (does not show up in serum)
* Goal: give a drug that chemically binds to the toxic metal in order to form a less toxic complex (chelation drug + toxic metal) for excretion
* levels in blood may go up first (pulls toxic metal out of bone, blood)
antivenom
chemical antagonism
Anti-venom – antibodies against venom
Given to counteract envenomation by poisonous snakes
Dispositional Antagonism:
Alteration of absorption, distribution or excretion of a poison or drug such that the concentration or duration of time the poison or drug is at the target organ is diminished
Absorption
* Administration of activated charcoal/cathartic
* Apomorphine
Activated charcol treatment
Dispositional Antagonism: Preventing Toxicant Absorption
“Activated” = petroleum or vegetable origin, not mineral/animal
Absorbs toxin/toxicant in GI tract > fecal excretion
Decreases systemic absorption
Implement immediately for maximal adsorption to poison
Receptor Antagonism
Two chemicals that bind the same receptor producing less toxicity than when given separately
ex: “blockers” = Naloxone competes with morphine-like drugs for same receptor
Stabilizing a poisoned patient
Airway/Breathing
* ex: tachypnea, bronchospasm
Circulation
* assess mucus membranes, BP, temp, HR
Disability/defects
* pupillary light reflex, mental statusm ambulation, GI
ABCD
Oral exposure decontamination
- Emesis
- Activated Charcoal
- Gastric Lavage
- Endoscopy/surgery
- Lipid Emulsion Therapy
ingestion of corrosive agents
dilute with milk or water
DO NOT INDUCE VOMITING
apomorphine
Emetic activity = stimulating dopamine receptors
Given parenterally (IM or IV) or topically in the conjunctival sac
Triggers CRTZ = vomiting
Preferred emetic drug for dogs
Side effects:
* CNS and respiratory depression, protracted vomiting
* Sedative side effects reversed with naloxone, does not stop vomiting
Clevor® (Ropinirole)
Ophthalmic solution for emesis in dogs
Dopamine agonist
Drops depend on body weight
5.1 – 10 kg = 3 drops in one eye
20.1 – 35 kg = 4 drops in one eye
Treatment for vomiting (protractive vomiting)
- Cerenia (Maropitant) – blocks neurotransmitter involved in emesis
- Reglan (Metoclopramide) – increases GI muscle contractions
Hydrogen Peroxide (3% H2O2)
** Dogs**
“Currently” recommended for at-home emesis induction in dogs…only 3% used. Higher concentrations = severe gastritis
Induces emesis by causing direct, gastric irritation (≈ 10 min)
1 to 5 mL/kg bwt (do not exceed 50 mL in dogs)
Client-based measurement = 5 mL = 1 teaspoon
Ineffective in cats – hemorrhagic gastritis
Froth and foam at mouth and sometimes don’t vomit
Burns usually noted on arrival at clinic
emetic agents in cats
Xylazine (Rompun®, Anased®)
Dexmedetomidine (Precedex™)
Emetic activity = stimulates α2-adrenergic receptors and vomiting center
Cats: Considered emetics of choice; 0.44 mg/kg IM
Dogs: 1.1 mg/kg SC or IM
Side effects: CNS and respiratory depression, bradycardia, hypotension
Side effects reversed with yohimbine
When to induce vomiting
Usually induce <1hr after ingestion
asymptomatic patient
Can induce ≤ 6 hours
* Grapes, raisins
* Xylitol
* Massive ingestions
* Chocolate
* Bezoars
Drugs that decrease gastric emptying (longer window):
* Opioids
* Anticholinergics
* Tricyclic antidepressants
* Salicylates
Contraindications for Emesis Induction
Patient is symptomatic
Laryngeal paralysis
Megaesophagus
Risk of aspiration pneumonia
* Brachycephalic breeds (Bulldogs, Boston Terriers)
* Ingestion of hydrocarbons (Petroleum products, Gasoline, Kerosene, Motor oil)
* < 3 months old
Ingestion of corrosive agents (Batteries, Toilet bowl or drain cleaners, Oven cleaners)
Patient is seizing
Rodents, horses, ruminants, rabbits
activated charcol
“Activated” = petroleum or vegetable origin, not mineral/animal
Adsorbs toxin/toxicant in GI tract > fecal excretion
* Decreases systemic absorption
Effective for toxicants that undergo enterohepatic recirculation
may contain cathartics
Cathartics
Sorbitol
* Poorly absorbable salts that osmotically draw water into the gut lumen > stimulate movement enhancing elimination of activated charcoal
Large Animals:
* Magnesium sulfate and sodium sulfate are used as cathartics
* Sorbitol can also be used as a laxative/cathartic
What does NOT bind charcol?
Alcohols
* Ethylene glycol
* Ethanol
Xylitol
Heavy metals
Nitrates, nitrites, chlorates
contraindications for activated charcol
Late-stage presentation
Hypernatremia
Hypovolemic shock
Compromised airway
GI obstruction
Risk of aspiration pneumonia
* Caustic substance
* Hydrocarbon
Vomiting animal
Lack of borborygmi
gastric lavage
May be more effective than emesis at removing gastric contents
Requires prep, IV catheter, sedation, intubation, endotracheal insufflation, flush with 5-10 mL/kg warm water, agitate stomach, aspirate contents, pump stomach
When?
* Ingestion of deadly medications/life-threatening situations
* Beta-blockers, metaldehyde, calcium-channel blockers
* Unsuccessful emesis
* Species that cannot vomit
* Symptomatic patients with large ingestion
gastric lavage contraindications and risks
Contraindications
* Ingestion of hydrocarbons or corrosives
* Recent surgery
* Patient unstable
Risks
* Aspiration pneumonia
* Esophageal/gastric rupture
* Electrolyte imbalances
lipid emulsion therapy
Typically soybean oil
Creates a lipid “sink” in the blood > lipid binds highly lipid soluble toxicants
Given IV as a bolus dose at 1.5 mL/kg (20% lipid emulsion)
* Followed by infusion at 0.25 mL/kg/minute for 30-60 minutes)
* Repeat if blood not lipid-filled in PCV tube
* See lipid layer at about 1-2% of volume
Monitor vitals
Case reports:
* Macrolide endectocide overdose
* Baclofen
* NSAIDs
* Marijuana
* Tremorigenic mycotoxins
What samples to collect antemortem?
- Vomitus (all available)
- Urine (all available)
- Whole blood (5 mL in red top clot tube)
- Whole blood (5 mL in purple top EDTA tube)
- Serum
- Source material – water, food, suspect foodstuff, bait
- Hair or fur (if dermal exposure)
What samples to collect antemortem?
- Vomitus (all available)
- Urine (all available)
- Whole blood (5 mL in red top clot tube)
- Whole blood (5 mL in purple top EDTA tube)
- Serum
- Source material – water, food, suspect foodstuff, bait
- Hair or fur (if dermal exposure)
What samples to collect postmortem?
- Liver
- Stomach contents
- Brain (1/2)
- Kidney (1/2)
- Urine
- Eyeball or ocular fluid
- Any source material (Water, food, suspect foodstuff, bait)
Fix representative tissues in 10% formalin
Save samples for bacteriology and virology
What samples to collect postmortem?
- Liver
- Stomach contents
- Brain (1/2)
- Kidney (1/2)
- Urine
- Eyeball or ocular fluid
- Any source material (Water, food, suspect foodstuff, bait)
Fix representative tissues in 10% formalin
Save samples for bacteriology and virology
Qualitative test
Positive or Negative
* No concentrations given
* Ethylene glycol
* Cyanide
* Colorimetric tests
quantitative test
Concentrations of drug, toxin, or toxicant are calculated (quantitated)
Usually report in units of:
* ppb = parts per billion
* ppm = parts per million
ppb vs ppm
1,000 ppb = 1 ppm
1 ppm =
* 1 mg/L
* 1 µg/g
* 1,000 ppb
* 10,000%
1 ppb =
* 1 µg/L
* 1 ng/g
* 0.001 ppm
* 0.0000001%
