drugs Flashcards
NSAIDS toxicosis mechanism + toxicity. target organs_
Target organs: gastrointestinal tract, kidneys, CNS
* Exacerbated with dehydration
* Hepatotoxicity possible
- Mechanism: inhibition of COX expression (COX 1, COX 2) → decreased prostaglandin production
- ↓ GI mucosal + renal blood flow
- ↓ Mucosal barrier repair and cell turnover
- ↓ GI immune function
- ↓ GI mucosal protection: bicarbonate, mucus secretion
- Relevant toxicokinetics: many are highly protein bound + undergo enterohepatic recirculation
NSAIDS species differences
- Consider cats twice as sensitive as dogs → deficient hepatic glucuronide conjugation
- Differences in clinical presentation: renal failure in cats vs. GI ulcers in dogs
- Ferrets are very sensitive to ibuprofen
horses: narrow margin of safety
uncommon in cattle/ small ruminants
NSAID clinical features
- Onset: within hours to days (dose-dependent) first you see is GI.
Gastrointestinal:
* Anorexia, abdominal pain
* Vomiting, diarrhea
* Dehydration, hypovolemia
* Underlying pathology: ulcers (esp. stomach, duodenum)
* Risk of GI perforation and septic peritonitis
* Pale MM
* Tachypnea, tachycardia
* Horses: colic, diarrhea, fever, anorexia
Renal:
-painful abdomen, PU/PD
-renal insufficiency 2nd to hypoperfuction.
-PM LESION: renal papillary necrosis or in horses right dorsal colitis **
CNS: depression, ataxia, stupor, seizers.
NSAIDS tox causes of death
- GI perforation secondary to ulceration
- Acute kidney injury and renal failure
- CNS toxicosis
NSAID carprofen
-idiosyncratic hepatopathy (not dose dependent)
* Acute hepatic necrosis
* Case reports: good prognosis with D/C
drug and prompt medical treatment
NSAID tox management
- No specific antidote
- Decontamination if not contraindicated
- Aggressive symptomatic and supportive care
- Gastroprotectants: sucralfate, misoprostol, -prazole drugs, famotidine
- Renal support: IVFT to maintain → 2X maintenance for 24 hours, 72 hours (naproxen)
- CNS: anticonvulsants
- Frequent monitoring
- Horses: low stress, reduced work/exercise, low bulk diet
NSAID diagnosis
-history of exposure (access to owner medication, overdose in clinic or at home)
* Quantification in blood, urine
* Imaging: loss of serosal detail if peritonitis
- DDx:
- Bleeding: anticoagulant rodenticides
- GI ulcers/erosions: corrosive products (bleach)
- Prognosis: companion animals - generally excellent with prompt medical attention
- Perforation: grave prognosis
Acetaminophen mechanism + toxicity
- Mechanism: bioactivation reaction** - production of reactive metabolite (NAPQI) → depletion of cellular glutathione + oxidative injury
- Damage to proteins and cell membranes
- Target organs: blood (cats), liver (dogs, cats**
species differences: cats, ferrets» dogs. because no glucuronidation.
- Dose-response:
- One 500 mg tablet can kill a cat → no safe dose for cats**
- Dogs: >50 mg/kg warrants decontamination and monitoring
- > 200 mg/kg: methemoglobinemia
Acetaminophen clinical features
Onset: within 4-12 hours of ingestion
*Gi signs first Vomiting, anorexia, diarrhea
* Depression, lethargy
* Tachypnea, tachycardia
* Chemosis, facial edema, paw swelling (cats** characteristic finding)
- Within 24-36 hours: progression to hepatic necrosis, methemoglobinemia, oxidative damage hemolytic anemia
- Yellow, brown, and/or cyanotic MM
- Jaundice, abdominal pain
- CNS involvement: tremors, seizures, coma
- Can be fatal
acetaminophen lab findings
- Clinical pathology:
- Regenerative anemia
- Blood smear: Heinz bodies due to oxidative damage.
-Metabolic acidosis - (Met)Hemoglobinuria
- PM: hepatomegaly with enhanced reticular pattern
- Jaundice
acetaminophen management
- Decontamination if not contraindicated
- Antidote: N-acetylcysteine***
Mechanism of N-acetyl cysteine - Increases hepatic glutathione synthesis
- Enhances sulfation
- Symptomatic and supportive care
- Fluids, oxygen
- Hemolytic anemia: blood transfusion
- Hepatoprotectants: SAMe, silymarin, vitamin E
- MetHb: methylene blue
acetaminophen diagnosis. DDx and prognosis.
- History of exposure, compatible C/S.
facial and paw swelling, heinz bodies on blood smear are characteristic. - DDx for MetHb: oxidizing agents (mothballs, phenolic compounds, chlorate herbicides, garlic/onion)
- Heinz bodies: zinc, skunk musk, mothballs, phenolics (cats), garlic/onion
Prognosis: variable
* Any cat with any exposure: at least guarded
* Severe liver damage with no response to treatment: grave
metronidazole use, dose. clinical signs, management.
- Therapeutic use: antibacterial (Clostridium spp.), antiprotozoal (Giardia spp.)
-toxic dose is higher than label dose for several days. - Hallmark: vestibular signs**
- Head tilt, circling, nystagmus
- Central vestibular disease
- Management: D/C metronidazole → symptoms should resolve rapidly
- Diazepam reportedly speeds recovery (0.5 mg/kg PO q8 for min. 5 days)
-good prognosis
ivermectin mech and toxicity
Macrocyclic lactone – broad spectrum antiparasitic drug
* Heartworm preventative, anthelminthic
* Pastes, liquids, tablet
-more toxic in ABCB1 mutation dogs (border collie, shepards)
CNS target organ
mechanism: Potentiation of glutamate and GABA-gated chloride channels-> CNS depression
ABCB1 have defective PGP pumps
- Toxicity
- ABCB1-1 polymorphism minimum toxic dose: 0.1 mg/kg BW
- Normal dogs: >2 mg/kg B
I V E R M E C T I N –
C L I N I C A L F E A T U R E S
- Onset: several hours or days (dose-dependent)
- Lethargy, depressed/dull mentation
- Disorientation, ataxia
- Vomiting, hypersalivation
- Mydriasis
- Blindness
- Severe intoxications: seizures, obtundation, respiratory depression,
death - Nonspecific bloodwork findings
ivermectin induced blindness
- Underlying pathology: retinal edema ± folds and separation
- Exact mechanism unknown – GABA mediated?
- Absent menace, sluggish-to-absent PLRs
- In any acutely blind animal:
- Fundic exam
- ± Electroretinography (ERG): decreased b-wave amplitude
- Cannot be detected postmortem
I V E R M E C T I N – M A N A G E M E N T
- No specific antidote
- Decontamination if not contraindicated: Dermal
- Symptomatic and supportive care: IVFT, intubation and ventilation if indicated, seizure and tremor control, temperature management
- Monitoring of blood gas parameters to assess ventilation, checking for gag reflex
- Prolonged monitoring and treatment may be required
- Animals generally regain their sight slowly
- Reports of successful treatment with IVLE
ivermectin diagnosis/ DDX/ prognosis
Diagnosis: history of exposure, compatible clinical signs
* Analysis of liver or serum for ivermectin
- DDx: CNS depressants barbiturates, opiates, tremorgenic mycotoxins
- Prognosis: generally good with appropriate supportive care
- Severely affected patients: prolonged care often required
P Y R E T H R O I D S – M E C H A N I S M + T O X I C I T Y
- Target organ: CNS
- Mechanism: prolonged Na+ channel opening in nerves → repetitive action potential firing
- CNS excitation
- Toxicity: generally low in mammals
- Exceptions: cats, animals with liver damage**
- 1 mL of 45% permethrin applied to a 4.5 kg cat can be lethal
P Y R E T H R O I D S – clinical features
- Onset: within a few minutes to days
- Prominent clinical signs:
- Vomiting, diarrhea
- Depressed mentation or hyperexcitable
- Tremors**, twitching, muscle fasciculation
-Mydriasis - Hypersalivation
- Ataxia
- Severe cases: seizures, coma
- Can be fatal if seizures cannot be controlled
pythethroid management
- No specific antidote
- Decontamination if not contraindicated – dermal or GI
- Ensure cat cannot groom itself
- Tremors: do not GI decontaminate**
- Tremor control: methocarbamol
- Supportive care:
- IVFT
- Thermoregulatio
pyrethroids diagnosis, DDx, prognosis
- Diagnosis: history of application of OTC flea products meant for dogs, dog recently treated with topical
product in a house with a cat - DDx: CNS excitation → strychnine, fluoroacetate, metaldehyde, OP/carbamate insecticides
- Prognosis: good with early and aggressive treatment
- Status epilepticus: poor
toxidromes
- TOXic SynDROMES
- Cluster of clinical signs characteristic of a group of agents
- Recognition of the toxidrome important even when exact agent is unknown
- Symptomatic and supportive care is generally the same
- Examples of toxidromes:
- Cholinergic – consider OP/carbamate poisoning
- Anticholinergic – atropine overdose
- Opioid/sedative – CNS depressants in general
- Sympathomimetic – many stimulant drugs
sympathomimetic toxidrome
- Mechanism: overstimulation of adrenergic, dopaminergic, and/or serotonergic receptors
- NE, DA, 5HT → vasoconstriction, increased cardiac contractility, CNS excitation
*causes: Cocaine, amphetamines, MDMA, ecstasy, high dose serotonergic drugs, methylxanthines, ephedrine, bath salts
clinical: mydrasis, tachycardia, hypertension, arrythmias, altered mental state, anxious, sweating, hyperthermia, increased GI motility.
antidepressants mechanism and toxicity
- Mechanism: overstimulation of serotonin, dopamine, and/or norepinephrine receptors
- Target organs: CNS, CV
- Toxicity: variable
antidepressant medications clinical features
Onset: as early as 30 minutes post-exposure
* Signs can be delayed up to 12-24 hours
* Mild overdose: lethargy, ataxia
* Moderate to severe overdoses: serotonin syndrome
GI: hypersalivation, vomiting, diarrhea
* CNS: hyperexcitability, agitation, ataxia, mydriasis,
tremors, seizures, hyperthermia
* CV: tachycardia, hypertension, arrhythmias
* TCAs - additional anticholinergic effect: ileus, urinary retention
* Anticholinergic toxidrome
drugs that contribute to serotonin syndrome
-antidepressants
* Amphetamines (MDMA, ADHD meds)
* 5HTP
* Tramadol
* Fentanyl, cocaine, bath salts
* CYP inhibitors
antidepressant medication management
- Decontamination if not contraindicated
- Antidote for serotonin syndrome: cyproheptadine***
- Serotonin receptor antagonist
- Sedation: acepromazine
- Supportive care:
- IVFT, methocarbamol, antiemetic therapy, seizure control
- Correction of acid/base abnormalities, thermoregulation
-frequent monitoring
B E T A - 2 R E C E P T O R A G O N I S T S mech and toxicity
-blue inhalor, salbutamol. dogs chew or it leaks
- Mechanism: overstimulation of receptors
- Loss of B2 selectivity → stimulation of B1 receptors
- Target organ: CV, CNS
- Toxicity: difficult to establish
B2 receptor agonists clinical features
Onset: peracute
- Cardiovascular/respiratory:
- Weakness, tachypnea, dyspnea
- Vasodilation, hypotension → reflex tachycardia
- Loss of B2 selectivity
- B1 effects:↑ cardiac contractility, sinus tachycardia
- Severe: myocardial hypoxia → arrhythmias
- CNS: anxiety, restlessness, agitation, tachypnea, muscle tremors
- Clin path:
- Hypokalemia: weakness, PU/PD, decreased urine concentrating ability, ECG abnormalities
B2 receptor agonisnts management and diagnosis
- Decontamination not possible
- Antidote: beta-blockers (propranolol)**
- Correction of hypokalemia: potassium supplementation**
- Supportive care and monitoring: ECG, blood pressure, IVFT, sedation, methocarbamol
- Diagnosis: chewed inhaler, sympathomimetic toxidrome
- Prognosis: generally good with medical care
- Guarded: severe tachycardia
NAVALE K+ toxic dose: 0,5 mEq/kg/hr
cocaine
- Alkaloid from the coca plant (Erythroxylum coca)
- Therapeutic use (human medicine): local anesthetic
Toxicity
* Estimated oral LD50: 6-12 mg/kg (dogs)
* Mechanism: blocks reuptake of NE, 5HT, DA → increased
catecholamine release → sympathomimetic
- Target organs: CNS, CV
A M P H E T A M I N E S
- Exposure scenario: access to owner drugs/medications
- Mechanism: ↑ 5HT, DA, NE
- Amphetamine
- Symptoms at >1 mg/kg
- Severe poisoning >10 mg/kg
cocaine + amphetamines clinical feautures
-Onset: within 30 minutes of ingestion
- Sympathomimetic toxidrome:
- CNS: restlessness, excitability/agitation, circling, mydriasis, anxiety, tremors
- CR: tachycardia, hypertension, tachypnea, hypertension
- Hyperthermia, panting
- Hypersalivation
- MDMA: may develop serotonin syndrome
- Severe cases: development of seizures; hyperthermia drives further progression
- Arrythmias, DIC, coma
cocaine + amphetamines management and diagnosis
- No true antidote
- Symptomatic and supportive care
- Sedation: acepromazine
- Tremors/seizure control, thermoregulation, IVFT
- CV: beta-blockers, ECG, blood pressure
Diagnosis: history of exposure (owner
medications/drugs), sympathomimetic toxidrome, urine drug screen
- Prognosis: depends on severity of clinical signs and response to supportive car
opioids mechanism + toxicity
Mechanism: interaction with opioid receptors in spinal cord, limbic system, and brain
- Target organs: CNS, CV, respiratory, GI
- Toxicity - minimum lethal dose varies by drug
- Morphine lethal dose
opioids clinical features
- Onset: within minutes of injection, within 30 minutes of ingestion
- GI: vomiting, constipation or defecation, salivation
- CNS: depression/sedation (dogs), excitation (cats)
- CV: bradycardia, arrythmias
- Miosis (dogs), mydriasis (cats)
- Hypothermia (dogs), hyperthermia (cats)
- Severe: respiratory depression**, cyanosis, constipation, seizures, coma
- Cause of death: hypoxia, respiratory failure
opioids management
- Antidote: naloxone** (0.04 mg/kg IV or IM) – pure opioid antagonist
- Monitor for CNS and respiratory depression
- May need to intubate and ventilate
- Blood gas: ventilation; pulse oximeter (SpO2)
- CV monitoring: ECG, blood pressure
- Thermoregulation
- Serotonin syndrome: cyproheptadine
Ensure you are wearing proper PPE**
* If you give IN Narcan: don’t stand in front of the dog
opioids management + diagnosis
- Diagnosis: working dog ADR after completing a search, overdose in clinic, access to owner drugs
- Urine drug test
- Prognosis
- Good with rapid recognition of toxicity, naloxone, and appropriate supportive care
- Guarded with delayed intervention or hypoxemia
- Positive response to therapy is a good prognostic indicator
benzodiazepines mech and toxicity
- Diazepam, midazolam
-used for seizure control
-exposure scenarios: ingestion of human prescription medication, overdose in clinical settings.
Mechanism: enhance binding of GABA to receptors in CNS → CNS depression
* Specific GABA binding site for benzodiazepines: GABAA
- Toxicity: in general, toxicity is considered low
- Wide margin of safety
- Exception: oral diazepam in cat
benzodiazepines clinical features
- Onset: within 30-60 minutes after ingestion/exposure
- CNS depression → confusion, ataxia/incoordination, lethargy
- CV: bradycardia, hypotension
- Vomiting
- Tremors, hypothermia, weakness
- Paradoxical excitation and hyperactivity possible
- Severe overdose: respiratory depression, coma, seizures
CATS: fulminant liver failure with repeated oral diazepam. related to glucocornidation. liver failure enzymes.
benzodiazepines management
Decontamination: if oral ingestion – emesis induction and A/C
* Antidote: flumazenil**- benzodiazepine receptor antagonist
* Short half-life: ~1 hr (dogs)
* Diazepam and nordiazepam half-life: 2.4 and 2.9 hrs (dogs), 5.5 and 21 hrs (cats
-supportive care
-Diagnosis: history of ingestion of human prescription, overdose in a clinical setting, analysis in blood and urine (human OTC urine test)
* Prognosis: good with antidote and adequate supportive care
* Oral diazepam in cats: guarded to poor
barbiturates mech and toxicity
Mechanism: activation of GABA receptors, inhibition of glutamine receptors, inhibition of NE
and ACh release
* CNS depression
* Suppression of hypoxic drive + chemoreceptor drive
- Toxicity:
- Phenobarbital
- Dog oral LD50: 150 mg/kg BW
- Cat minimum lethal dose 125 mg/kg BW
- Euthanasia dose (Euthasol - pentobarbital): 1 mL per 10 lbs BW (1 mL per 4.5 kg)
- Pentobarbital oral LD50: 85 mg/kg BW (dog)
barbiturates clinical features
- Onset: within minutes to several hours post exposure
- Weakness
- CNS: depression, ataxia, incoordination, disorientation, mydriasis, recumbency, coma
- Hypothermia
- Hypoventilation
- CV: tachycardia or bradycardia
- High doses: myocardial depression
- Death due to respiratory depression**
- Hepatotoxicosis in patients on long-term PB treatment for idiopathic epilepsy (associated
with PB >35 mcg/mL (hepatic cirrhosis)
PB therapeutic range: 25-35 mcg/mL
barbiturates management
- No specific antidote
- Recent ingestion: emesis with A/C
- Severe depression: gastric lavage, A/C
- Respiratory monitoring and support: intubation, oxygen, MV
- CV monitoring and support: ECG, BP, cardiac drugs
-long acting prolonged treatment required
barbiturates diagnosis
- Diagnosis: accidental administration of euthanasia solution, ingestion of euthanized animal,
overdose of prescribed medication - Human OTC urine drug test, analysis in stomach contents and blood
- Prognosis: good with early medical management
veterinarians + pentobarbital
- Responsibility to inform clients about proper disposal of animals euthanized with pentobarbital
(or other euthanasia drugs) according to local bylaws - Must be documented in the medical record or on a signed consent form
- A veterinarian may be liable if the client was not informed of the risks
local anethestics mechanism + toxicity
- Target organs: CNS, CV
- Mechanism: block voltage-gated Na+ channels in nerves and myocardium
- CNS depression, myocardial depression
- Lidocaine (20 mg/mL) – more neurotoxic
- Bupivacaine (0.5 mg/mL) – more cardiotoxic
local anesthetics clinical signs
- Clinical features – Local Anesthetic System Toxicity (LAST)
- CNS: first to appear*
- Sedation, weakness, ataxia
- Initial CNS excitation: muscle twitching that can progress to seizures
- Higher concentrations: profound CNS depression and coma, respiratory arrest
- CV: bradycardia, decreased contractility, vasodilation
- Can progress to cardiac arrest
- Bupivacaine: more cardiotoxic
- CNS and CV signs occur concurrently
- Hypotension, cardiovascular collaps
local anesthetics antidote
-IVLE
-* Supportive care: anticonvulsant drugs, IVFT, oxygen (intubation and ventilation if necessary), positive inotropes, CV monitoring (ECG, BP)
* Diagnosis: recent administration of local anesthetic, inadvertent IV administration, chewed ointment tube
* Prognosis: dictated by severity of clinical signs and response to medical management
* Good with lidocaine, guarded with bupivacaine
marijuana mechanism + toxicity
- Mechanism: binds to CB1 and CB2 receptors in the CNS
- CB1: psychoactive → affects memory, perception, and movement control
- CNS, especially the cerebellum
- CB2: analgesia, anti-inflammatory
- PNS, immune system
- Toxicity: minimum lethal oral dose >3 g/kg (dogs)
- Not acutely toxic
- Behavioural effects occur at 1000x less (3 mg/kg)
- Relevant toxicokinetics
- Lipophilic
- Different hepatic metabolism between dogs and humans
marijuana clinical features
- Onset: within 30 minutes of ingestion
- GI: vomiting possible
- CV: tachycardia or bradycardia
- CNS: dullness/depression, ataxia, weakness, hyperesthesia**
- Severe cases: seizures, coma
- Some dogs: CNS stimulation
- Other: mydriasis, “blood shot” eyes, urinary incontinence, vocalization, ptyalism, hypo or hyperthermia
marijuana management and diagnosis
- No specific antidote
- Decontamination if not contraindicated
- Symptomatic and supportive care
- Diagnosis: history of exposure, clinical signs
- Human OTC urine test: THC-COOH → false negatives
- Some labs offer quantitative testing (LC/MS)
- Prognosis: good to excellent
xylazine mech and toxicty
- Emerging public health issue: adulterant in street drugs
- Mechanism: alpha-2 adrenergic receptor agonist
- Target organs: CNS, CV
- Therapeutic: sedation, muscle relaxation, analgesia
- Overdose: profound sedation
xylazine clinical features
- Similar presentation to opioid overdose + lack of response to naloxone
- CV: bradycardia, vasodilation, hypotension
- CNS: progressive CNS depression, can proceed to respiratory depression
- Hypoventilation, cyanosis, apnea
- Muscle twitching, miosis, hypothermia, vomiting, salivation
- Intracarotid administration: convulsions
xylazine management
- Antidote: atipamezole (antisedan)
- Supportive care: blood pressure support, oxygen, ventilation support
- Frequent monitoring of CV and respiratory systems
-decontamination if not contraindicated
CNS depressants - toxic differentials
- Drugs discussed in lecture: opioids, benzodiazepines, barbiturates, alpha-2 agonists, 9-THC
- Alcohol, methanol, ethylene glycol
- Antipsychotics (acepromazine, quetiapine, others)
- Sleep medications: zolpidem (Ambien), zopiclone
- Ketamine, GHB
- Baclofen
- Hepatic encephalopathy – consider causes of hepatotoxicosis
- Uremic encephalopathy – consider causes of nephrotoxicosis
Nsaid key points
- NSAIDs: poisonings are common with human OTC forms (ibuprofen, naproxen)
- Target organs: GI, kidney, CNS
- Cats and ferrets > dogs
- Characteristic lesions: papillary necrosis (small animals), right dorsal colitis (horses)
Acetaminophen key points
- Bioactivated to toxic metabolite in the liver
- Target organ: RBCs (cats), liver (dogs)
- No safe dose for cats – poor glucuronidators, more readily saturated sulfation pathway
- Heinz body oxidative damage hemolytic anemia
- Antidote: NAC
CNS stimulants cause of death
sympathomimetic toxidrome – cause death through uncontrolled seizures or
cardiac arrhythmias
* Target CNS ± CV systems
* Management generally the same → sedation, beta-blockers, other support care
* Asthma inhalers: hypokalemia
