drugs Flashcards
(60 cards)
1
Q
NSAIDS toxicosis mechanism + toxicity. target organs_
A
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
2
Q
NSAIDS species differences
A
- 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
3
Q
NSAID clinical features
A
- 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.
4
Q
NSAIDS tox causes of death
A
- GI perforation secondary to ulceration
- Acute kidney injury and renal failure
- CNS toxicosis
5
Q
NSAID carprofen
A
-idiosyncratic hepatopathy (not dose dependent)
* Acute hepatic necrosis
* Case reports: good prognosis with D/C
drug and prompt medical treatment
6
Q
NSAID tox management
A
- 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
7
Q
NSAID diagnosis
A
-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
8
Q
Acetaminophen mechanism + toxicity
A
- 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
9
Q
Acetaminophen clinical features
A
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
10
Q
acetaminophen lab findings
A
- Clinical pathology:
- Regenerative anemia
- Blood smear: Heinz bodies due to oxidative damage.
-Metabolic acidosis - (Met)Hemoglobinuria
- PM: hepatomegaly with enhanced reticular pattern
- Jaundice
11
Q
acetaminophen management
A
- 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
12
Q
acetaminophen diagnosis. DDx and prognosis.
A
- 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
13
Q
metronidazole use, dose. clinical signs, management.
A
- 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
14
Q
ivermectin mech and toxicity
A
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
15
Q
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
A
- 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
16
Q
ivermectin induced blindness
A
- 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
17
Q
I V E R M E C T I N – M A N A G E M E N T
A
- 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
18
Q
ivermectin diagnosis/ DDX/ prognosis
A
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
19
Q
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
A
- 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
20
Q
P Y R E T H R O I D S – clinical features
A
- 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
21
Q
pythethroid management
A
- 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
22
Q
pyrethroids diagnosis, DDx, prognosis
A
- 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
23
Q
toxidromes
A
- 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
24
Q
sympathomimetic toxidrome
A
- 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.
25
antidepressants mechanism and toxicity
* Mechanism: overstimulation of serotonin, dopamine, and/or norepinephrine receptors
* Target organs: CNS, CV
* Toxicity: variable
26
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
27
drugs that contribute to serotonin syndrome
-antidepressants
* Amphetamines (MDMA, ADHD meds)
* 5HTP
* Tramadol
* Fentanyl, cocaine, bath salts
* CYP inhibitors
28
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
29
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
30
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
31
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
32
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
33
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
34
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
35
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
36
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
37
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
38
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
39
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
40
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
41
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.
42
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
43
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)
44
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
45
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
46
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
47
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
48
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
49
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
50
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
51
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
52
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
53
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
54
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
55
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
56
xylazine management
* Antidote: atipamezole (antisedan)
* Supportive care: blood pressure support, oxygen, ventilation support
* Frequent monitoring of CV and respiratory systems
-decontamination if not contraindicated
57
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
58
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)
59
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
60
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
