Environment and toxicity

Question 1

What are the 3 proposed MoA for intralipid?

Answer 1

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

Question 2

What is bupivicaine’s mechanism of toxicity on the heart?

Answer 2

Blocks carnitine acylcarnitine translocase which inhibits mitochondrial use of FFA

Question 3

Antidote for amphetamines and serotonin syndrome:

Answer 3

Cyproheptadine (serotonin antagonist)

Question 4

Antidote for benzodiazepine

Answer 4

Flumazenil

Question 5

Antidote for digoxin

Answer 5

Digoxin immune Fab fragments (dose dependent, expensive, not always available)

Question 6

Antidote for ethylene glycol:

Answer 6

Ethanol
Fomepizole (4-methyl prazole)

Question 7

Antidote for iron

Answer 7

desferrioxamine chelation

Question 8

Antidote for lead

Answer 8

succimer (2,3 DMA) chelation

Question 9

Antidote for lead and zinc:

Answer 9

Ca EDTA (contraindicated if lead still in GIT)

Pencillamine chelation (contraindicated if lead still in GIT)

Question 10

Antidote for organophosphates and carbamates (muscarinic signs)

Answer 10

Atropine

Question 11

Antidote for organophosphates (nicotinic signs)

Answer 11

2-PAM (paralidoxime) - reactivates phosphorylated cholinesterases z

Question 12

Antidote for paracetamol

Answer 12

N-acetylcysteine

Question 13

Antidote for PAPP (foxecute predator bait)

Answer 13

Methylene blue

Question 14

Antidote for vitamin K

Answer 14

Phytonadione

Question 15

what is the toxic metabolite of paracetamol?

Answer 15

NAPQI (N-acetyl-p-benzoquinoneimine)
PAP (para-aminophenol)

Question 16

mechanism of toxicity for strychnine

Answer 16

uptake of glycine (inhibitory NT) at the inhibitory synapses of Renshaw cells in CNS

Question 17

Toxic MoA of chocolate:

Answer 17

Theobromine and caffeine:
- PDEi -> increase cAMP and intracellular Ca => NM excitation, gastric secretion and increased chrontropy and inotropy
- Adenosine antagonist => increase CNS excitation

Question 18

Cardiovascular effects of hypothermia:

Answer 18

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

Question 19

Respiratory effects of hypothermia:

Answer 19

• 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

Question 20

Acid-base abnormality caused by hypothermia:

Answer 20

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.

Question 21

Neuromuscular effects of hypothermia:

Answer 21

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

Question 22

Coagulation effects of hypothermia:

Answer 22

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)

Question 23

Renal effects of hypothermia:

Answer 23

• 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

Question 24

Pathophysiologic sequence of heat stroke:

Answer 24

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

Question 25

Diving reflex:

Answer 25

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.

Question 26

Severity of electrocution depends on which 3 factors:

Answer 26

• 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

Question 27

Why does eletrocution cause NCPE?

Answer 27

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

Question 28

Name an elapid snake in America?

Answer 28

Coral snake

Question 29

Were do coral snakes hang out?

Answer 29

Arizona, Texas, South-Eastern (Florida etc.)

Question 30

Main venom components in coral snakes?

Answer 30

Post-synpatic alpha neurotoxin - blocks nicotinic ACh receptors at the NMJ, cholinesterase
Phosphlipase (minimal) - hemolysin (inhibit PLT aggregation), myotoxin, cardiotoxin

Question 31

The most predominant venomous snake in the US?

Answer 31

Pit vipers (crotalids)

Question 32

Name 3 pit vipers and where they are found in the US:

Answer 32

Eastern diamond back rattlesnack (Southeast, Florida)

Cottonmouth/Water moccasin (watersnake, Southeast but extends a bit wider in region)

Copperhead (eastern USA) - rarely require antivenin

Question 33

Components of crotalinae venom:

Answer 33

Snake venom metalloproteinases: tissue destruction, coagulation, PLT dysfunction

Hyaluronidase - conective tissue breakdown

Phospholipidase A - cytotoxin-hemolysis (ecchinocytes, spherocytes), anti-Xa, some neurotoxin

Phosphodiesterase - hypotension

Question 34

Main toxin in black widow spider envenomation:

Answer 34

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

Question 35

Main toxin in brown recluse spider:

Answer 35

Sphingomyelinase D - secondary dermonecrotic factor, prolongs aPTT

Question 36

Main toxin of Bufo toads:

Answer 36

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)