Which medications fall into the macrocyclic lactones?
-avermectins
-milbemycins
What are the clinical effects of macrocyclic lactone toxicity?
neuro:
-ataxia
-weakness
-disorientation
-paddling
-head pressing
-tremors
-seizures
-coma
ophthalmic:
-mydriasis
-central blindness*
-retinal edema
GI:
-hypersalivation
-vomiting
Resp:
-hypoventilation
-poor chest excursions
CV:
-hyperthermia
-hypothermia
-bradycardia
-hypotension
What is the treatment for macrocyclic lactone toxicity?
-emesis or gastric lavage
-multi-dose AC; at least 3
-seizure control
-IV lipids (less effective in ABCB1-mutation dogs)
-mechanical ventilation
What is the prognosis for macrocyclic lactone toxicity?
-good prognosis with early intervention/IV lipids
-blindness may resolve
What are the characteristics of nicotine?
-found in chewing tobacco, cigarettes, e-liquid, cigars, and gum/patches
-slowly absorbed in acidic gastric environment
-e-liquid readily absorbed through skin and mucus membranes
What are the mechanisms of toxicity with nicotine?
-stimulates CRTZ to cause vomiting
-low doses and high doses in the early stage cause excitement
-high doses in the later stage cause depression
What are the clinical signs of nicotine toxicity?
general:
-salivation
-vomiting
-diarrhea
-low heart rate followed by high heart rate
-high resp. rate
-high BP
low dose/early high dose:
-hyperexcitability
-tremors
-ataxia
-seizures
high dose progression:
-CNS depression
-descending paralysis
-resp. failure
What is the management for nicotine toxicosis?
-emesis or gastric lavage
-AC
-IV fluid diuresis
-sedation for agitation
-antiemetics
-avoid antacids (hasten absorption)
-possible beta blockers
-mechanical ventilation
What are the characteristics of 5-fluorouracil toxicity?
-injectable and topical chemotherapeutic
-targets GI and bone marrow
-neurotoxic; mechanisms not well understood
What are the clinical signs of 5-FU toxicity?
-vomiting
-diarrhea
-tremors
-ataxia
-disorientation
-hyperthermia
-agitation
-hyperesthesia
-seizures
-resp. distress
-coma
-severe myelosuppression
What is the progression of clinical signs with 5-FU toxicity?
-GI signs after 10 minutes to 5 hrs
-seizures after 30 minutes to 26 hrs
-death after 6 to 24 hrs
-severe myelosuppression after 2 to 14 days
What is the mortality rate of 5-FU toxicity?
60-65%
What are the lab work findings in 5-FU toxicity?
CBC:
-leukopenia
-neutropenia
-thrombocytopenia
-anemia
*run baseline, 12h, 24h, then q24-72 hrs for 2 weeks to look for bone marrow suppression
CHEM:
-mild liver enzyme increases
BLOOD GAS:
-metabolic acidosis
What is the management for 5-FU toxicity?
-bathing
-NO EMESIS
-AC if asymptomatic
-hospitalize for 24 hours
-aggressive seizure control (gas anesthesia)
-mannitol (cerebral edema)
-hypertonic saline (cerebral edema)
-GI protectants
-antibiotics if leukopenic
-mechanical ventilation
-extracorporeal therapy
What are the characteristics of calcium channel blockers?
-used to treat hypertension and tachyarrhythmias
-affect cardiac muscle, vascular smooth muscle, and beta cells of pancreas
What are the clinical effects of Ca2+ blockade?
-decreased SA node firing and delayed AV conduction
-decreased excitation-contraction coupling/decreased contractility
-decreased vascular smooth muscle contraction; allows vasodilation
-impaired beta cell function leading to hypoinsulinemia and hyperglycemia
-dilation of capillaries to increase capillary permeability
What are the clinical signs of Ca2+ blocker toxicosis?
-bradycardia
-AV dissociation
-AV blockade
-hypotension
-hypokalemia
-hyperglycemia
-vomiting
-diarrhea
-ileus
-diffuse weakness/lethargy
-pulmonary edema
What is the management for Ca2+ blocker toxicosis?
-emesis
-gastric lavage with large ingestion
-AC
-judicious fluid therapy (must be careful due to inability to regulate HR)
-frequent ECG and BP monitoring
-calcium gluconate
-IV lipids
-vasopressors for hypotension
-temporary transvenous pacing
-glucagon, insulin, and/or dextrose as needed-
-atropine usually INEFFECTIVE
What are the characteristics of beta blockers?
-B1 affects SA and AV nodes, myocardium, and kidney
-B2 affects multiple sites
What are the clinical effects of beta-blockade?
-occurs within 8 hrs
-decreased HR
-decreased BP
-shock
-depressed mentation
-seizures
-non-cardiogenic pulmonary edema
-mild hyperkalemia
What are the management steps for beta-blocker toxicosis?
-similar to Ca2+ channel blockers
-hemodialysis
-airway protection/ventilatory support
What are the characteristics of beta 2-receptor agonists?
-treat asthma and COPD
-can have tablet ingestion or inhaler punctures
-effects within 30 minutes
-can have beta-1 activation at high doses
What are the clinical effects of beta-receptor agonists?
-vasodilation
-hypotension
-reflex tachycardia
-hyperglycemia
-hypokalemia (can be severe)
What are the clinical signs of beta-receptor agonist toxicity?
-agitation
-increased HR and RR
-tremors
-hyperthermia
-scleral injection
-conjunctivitis
-vomiting
-salivation
-BP changes
-hypoventilation w/ severe hypokalemia
-rhabdomyolysis
-oral mucosal injury
-upper airway obstruction
