Environment and toxicity Flashcards
What are the 3 proposed MoA for intralipid?
1) Lipid sink
2) increase FFA transport helping heart in bupivicaine toxicity to overcome inhibition of FFA by mitochondria of cardiomyocytes
3) increase intracellular Ca -> increasing contractility
What is bupivicaine’s mechanism of toxicity on the heart?
Blocks carnitine acylcarnitine translocase which inhibits mitochondrial use of FFA
Antidote for amphetamines and serotonin syndrome:
Cyproheptadine (serotonin antagonist)
Antidote for benzodiazepine
Flumazenil
Antidote for digoxin
Digoxin immune Fab fragments (dose dependent, expensive, not always available)
Antidote for ethylene glycol:
Ethanol
Fomepizole (4-methyl prazole)
Antidote for iron
desferrioxamine chelation
Antidote for lead
succimer (2,3 DMA) chelation
Antidote for lead and zinc:
Ca EDTA (contraindicated if lead still in GIT)
Pencillamine chelation (contraindicated if lead still in GIT)
Antidote for organophosphates and carbamates (muscarinic signs)
Atropine
Antidote for organophosphates (nicotinic signs)
2-PAM (paralidoxime) - reactivates phosphorylated cholinesterases z
Antidote for paracetamol
N-acetylcysteine
Antidote for PAPP (foxecute predator bait)
Methylene blue
Antidote for vitamin K
Phytonadione
what is the toxic metabolite of paracetamol?
NAPQI (N-acetyl-p-benzoquinoneimine)
PAP (para-aminophenol)
mechanism of toxicity for strychnine
uptake of glycine (inhibitory NT) at the inhibitory synapses of Renshaw cells in CNS
Toxic MoA of chocolate:
Theobromine and caffeine:
- PDEi -> increase cAMP and intracellular Ca => NM excitation, gastric secretion and increased chrontropy and inotropy
- Adenosine antagonist => increase CNS excitation
Cardiovascular effects of hypothermia:
Initially: catecholamine release => tachycardia and inceased BP
As hypothermia progresses, alpha-1 receptor sensivity to norepi decreases => vasodilation, decrease BP
Sinus bradycardia due to decreased diastolic repolarisation
Initially decease in CO offest by decrease in metabolic O2 consumption rate
As hypothermia worsens: decrease CO predisposes patients to dysrrhythmia: a.fib -> ventricular fibrillation
Respiratory effects of hypothermia:
- bronchospasm, bronchorrhea
- decrease cellular metabolism, decrease CO2, therefore decrease stimulus for respiratory => lower RR and depth when CBT < 28C
- impaired airway protective mechanism + compromised mucociliary defences predisposes to asp pneumonia
- most severe: apnoea, NCPE in severe cases
Acid-base abnormality caused by hypothermia:
Acidaemia - mixed resp-metabolic acidosis
Resp: decreased ventilation, increased solubility of CO2 in blood
Metabolic: decreased hepatic metabolism and renal tubular excretion. Lactic acidosis from shivering and hypoperfusion. Decreased buffering activity of cold blood.
Neuromuscular effects of hypothermia:
progressive decrease in cerebral blood flow: ataxia, decreased conscious, hyporeflexia and pupillary sluggishness -> progress to pupillary dilation, areflexia -> less than 25C cerebrovascular autoregulation is lost and there is marked decrease in metabolic rate -> 20C EEG flatline
Coagulation effects of hypothermia:
Hypocoagulability
Primary haemostasis: increased PLT sequestration in liver & spleen, decreased aggregation due to decreased thromboxane B2, granule release and vWF expression
Secondary haemostasis: decreased function of clotting factors
TEG: prolonged formation time with no effect on clot strength (elevated K time and decreased alpha angle)
Renal effects of hypothermia:
- cold diuresis: vasoconstriction interpreted as relative hypervolemia
- decreased responsiveness to ADH
- decreased CO -> RBF -> GFR in moderate hypothermia
- tubular dysfunction: decreased glucose, H+ excretion and increased electrolyte excretion
Pathophysiologic sequence of heat stroke:
Initial production of IL1, 6 from muscles released into circulation + ↑ systemic levels of endotoxin (GIT)
Mediate excessive activation of leucocytes and endothelial cells
Proinflammatory and antinflammatory cytokines released: activation of coagulation & inhibition of fibrinolysis
Direct endothelial cell injury due to heat + initial hypercoagulable state = microthrombosis & progressive tissue injury => MODS
Diving reflex:
Occurs within seconds of face contacting cold water (before unconsciousness): trigeminal nerve sends signal to CNS to cause bradycardia, hypertension and preferential shunting of blood to the cerebral and coronary circulation, protecting brain and heart from hypoxic injury.
Severity of electrocution depends on which 3 factors:
- electrical resistance: dry skin higher resistance, less severe
- intensity of current: current = voltage/resistance. Higher voltage worse if resistance same
- nature of current: alternating worse, longer duration due to muscular contractions preventing victim from releasing powercord
Why does eletrocution cause NCPE?
CNS insult -> massive sympathetic outflow => severe vasoconstriction and systemic hypertension => increased ventricular afterload, decreased left ventricular stroke volume and blood accumulates in pulmonary vasculature => increased hydrostatic pressure results in pulmonary oedema
Name an elapid snake in America?
Coral snake
Were do coral snakes hang out?
Arizona, Texas, South-Eastern (Florida etc.)
Main venom components in coral snakes?
Post-synpatic alpha neurotoxin - blocks nicotinic ACh receptors at the NMJ, cholinesterase
Phosphlipase (minimal) - hemolysin (inhibit PLT aggregation), myotoxin, cardiotoxin
The most predominant venomous snake in the US?
Pit vipers (crotalids)
Name 3 pit vipers and where they are found in the US:
Eastern diamond back rattlesnack (Southeast, Florida)
Cottonmouth/Water moccasin (watersnake, Southeast but extends a bit wider in region)
Copperhead (eastern USA) - rarely require antivenin
Components of crotalinae venom:
Snake venom metalloproteinases: tissue destruction, coagulation, PLT dysfunction
Hyaluronidase - conective tissue breakdown
Phospholipidase A - cytotoxin-hemolysis (ecchinocytes, spherocytes), anti-Xa, some neurotoxin
Phosphodiesterase - hypotension
Main toxin in black widow spider envenomation:
Neurotoxin - alpha-Latrotoxin: ACh release at nerve terminals, depolarisation and inhibit their uptake
Late on: blocks neurotransmission due to depletion of synaptic vesicle at NMJ
Main toxin in brown recluse spider:
Sphingomyelinase D - secondary dermonecrotic factor, prolongs aPTT
Main toxin of Bufo toads:
Bufogenins and bufotoxins: digoxin like cardioactive steroids, inhibit Na-K-ATPase in myocytes -> increase intracellular Na and Ca, predisposing to SVTs or ventricular arrhythmias. Can cause bradycardia.
Bufotenins: catecholamines (CNS, CVS effects) and serotonin (seizures, tremors, ptyalism, hallucinations)
