15 – Stimulants

Question 1

Toxidromes

Answer 1

• 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

Question 2

• *Symptomatic and supportive care is generally the same
  Cholinergic toxidrome

Answer 2

• Consider OP/carbamate poisoning

Question 3

Anticholinergic toxidrome

Answer 3

• Atropine overdose

Question 4

Opioid/sedative toxidrome

Answer 4

• CNS depressants in general

Question 5

Sympathomimetic toxidrome

Answer 5

• Many stimulant drugs
• Mechanism: overstimulation of adrenergic, dopaminergic and/or serotonergic receptors
  o NE, DA, 5-HT = vasoconstriction, increased cardiac contractility, CNS excitation
• Ex. cocaine, amphetamines, MDMA, ecstasy, high dose serotonergic drugs, methylxanthines, ephedrine, bath salts

Question 6

**What are the clinical presentations you see with sympathomimetic toxidrome?

Answer 6

• Mydriasis
• Tachycardia, hypertension, arrythmias
• Tachypnea
• Altered mental state: hyperexcitable, agitated, anxious (maybe seizures)
• Sweating, hyperthermia
• Increased GI motility

Question 7

Antidepressants

Answer 7

• Widely used in human medicine
• Use in vet med: behaviour modification, anxiety, aggression
• Various categories

Question 8

Antidepressants: mechanism and target organs

Answer 8

• Overstimulation of serotonin, dopamine and/or NE receptors
• **CNS and CV
• Variable toxicity (ex. SSRI seems to be more common)

Question 9

Antidepressants: onset

Answer 9

• As early as 30 minutes post-exposure
  o Signs can be delayed up to 12-24 hrs

Question 10

Antidepressants: mild overdose clinical features

Answer 10

• Lethargy
• Ataxia

Question 11

Antidepressants: moderate to severe overdoses clinical features

Answer 11

• *SEROTONIN SYNDROME
• Hypersalivation, vomiting, diarrhea
• Hyperexcitability, ataxia, agitation, tremors, seizures, hyperthermia
• Tachycardia, hypertension, arrythmias
• (TCAs: ileus, urinary retention=anticholinergic toxidrome)

Question 12

What are other drugs that contribute to serotonin syndrome?

Answer 12

• Amphetamines
• 5HTP
• Tramadol
• Fentanyl, cocaine, bath salts
• CYP inhibitors

Question 13

Antidepressants: management

Answer 13

• Decontamination if not contraindicated
• **Antidote for serotonin syndrome: CYPROHEPTADINE
• Sedation: acepromazine
• Supportive care
• IVFT, methocarbamol
• Correction of acid-base abnormalities
• Frequent monitoring

Question 14

Antidepressants: diagnosis

Answer 14

• History of exposure, compatible clinical signs

Question 15

Antidepressants: prognosis

Answer 15

• Generally excellent with prompt medical care

Question 16

Beta-2 receptor agonists

Answer 16

• Blue rescue inhaler (contains salbutamol (albuterol))
• Vet med: relief of bronchoconstriction
  o Equine and feline asthma
• Difficult to establish toxicity

Question 17

Beta-2 receptor agonists: exposure scenario

Answer 17

• Chewed inhaler
  o Owners report hearing a ‘hiss’
  o Dogs
• Iatrogenic overdose is possible

Question 18

Beta-2 receptor agonists: mechanism

Answer 18

• Overstimulation of beta receptors
  o Loss of beta-2 selectivity = stimulation of beta 1 receptors

Question 19

Beta-2 receptor agonists: target organ

Answer 19

• CV
• CNS

Question 20

Beta-2 receptor agonists: onset

Answer 20

• Peracute

Question 21

Beta-2 receptor agonists: clinical features

Answer 21

• *cardiovascular/respiratory
  o Weakness, tachypnea, dyspnea
  o Vasodilation, hypotension=reflex tachycardia
  o Loss of beta-2 selectivity ( beta-1 effects: increased cardiac contractility, sinus tachycardia)
  o Severe: myocardial hypoxia
• *CNS: anxiety, restlessness, agitation, tachypnea, muscle tremors
• “burns” at back of mouth: pain control

Question 22

Beta-2 receptor agonists; clinical pathology

Answer 22

• *hypokalemia
  o Weakness, PU/PD, decreased urine concentrating ability, ECG abnormalities
  o Mechanism: stimulates intracellular K+ shifting

Question 23

Beta-2 receptor agonists: management

Answer 23

• Decontamination NOT possible
• *antidote: BETA-BLOCKERS
• *Correction of hypokalemia: potassium supplement
• Supportive care and monitoring

Question 24

Beta-2 receptor agonists: diagnosis

Answer 24

• Chewed inhaler
• Sympathomimetic toxidrome

Question 25

Beta-2 receptor agonists: prognosis

Answer 25

- Generally good with medical care o Guarded: severe tachycardia

Question 26

Cocaine

Answer 26

- Alkaloid from coca plant - Therapeutic use (humans): local anesthetic - Common drug abuse - Mechanism: blocks reuptake of NE, 5HT, DA=increased catecholamine released=**SYMPATHOMIMETIC - *target organs: *CNS, CV

Question 27

Amphetamines

Answer 27

- Medications that contain it: ADHD medications, narcolepsy medications, weight loss - Exposure scenarios: access to owner drugs/medications - Mechanism: increased 5HT, DA, NE

Question 28

Cocaine and Amphetamines: onset

Answer 28

- Within 30mins of ingestion

Question 29

Cocaine and Amphetamines: clinical features

Answer 29

- Sympathomimetic toxidrome - Severe cases: development of seizures, hyperthermia drives further progression o Arrythmias, DIC, coma

Question 30

Cocaine and Amphetamines: management

Answer 30

- No true antidote - Symptomatic and supportive care o Sedation: acepromazine o Tremors/seizures control o CV: beta-blockers, ECG, BP o Blood gas o IVLE

Question 31

Cocaine and Amphetamines: diagnosis

Answer 31

- History of exposure - Sympathomimetic toxidrome - Urine drug screen

Question 32

Cocaine and Amphetamines: prognosis

Answer 32

- Depends on severity of clinical signs and response to supportive care

Question 33

What are the toxic differentials for sympathomimetics?

Answer 33

- Ephedrine, pseudoephedrine - First generation antihistamines - PCP, LSD, bath salts - Methylxanthines (chocolate: caffeine, theobromine) - Tremorgenic mycotoxins - Strychnine, fluroacetate, metaldehyde - Nicotine - Water hemlock - Lead, salt - OP/carbamate insecticides, organochlorine insecticides