Carbon Monoxide, Cyanide, Pesticides

Question 1

How do you produce cyanide in the lab?

Answer 1

Add acid to NaCN or KCN

Question 2

What are some exposure routes to cyanide

Answer 2

natural: apple seeds, almonds
industrial: insecticides, fumigants, solvents
Smoke inhalation: cigarettes, combustion of polymeric nitrogen containing compounds (couches, carpets, etc)
Pharmaceutical: long term use of nitroprusside vasodilator

Question 3

How is the majority of cyanide metabolized?

Answer 3

80% of cyanide dose is metabolized to thiocyanate (SCN-) by the hepatic mitochondrial enzyme rhodanase

Question 4

What happens to the cyanide not metabolize in the main pathway?

Answer 4

breathed out as HCN
reaction to form a substitute of vit b12 (uses hydroxocobalamin)
oxidized to form formic acid
reacts with cystine

Question 5

How does cyanide cause toxicity?

Answer 5

Cyanide reacts with complex 4 (cytochrome c oxidase) in the ETC, preventing complex 4 from delivering electrons to reduce O2, and results in no aerobic ATP prod.

Question 6

Describe cyanide toxidrome (5)

Answer 6

Dizziness, headache, weakness, confusion
perceived shortness of breathe
tachypnea (fast breathing)
coma
pinkening of the skin

Question 7

Describe the treatment for cyanide poisoning

Answer 7

100% O2
volume control
bicarb for metabolic acidosis
Specific therapies:
- sodium thiosulfate (substrate for rhodanase)
- amyl nitrate (vasodilator by delivery of NO), also oxidizes Fe2+ to Fe3+ in Hb to form methemoglobin (higher affinity for CN than cytochrome C oxidase)
- hydroxocobalamin (substrate for production of vit b12 using cyanide)
- sodium nitrite –> oxidizes hb to methemoglobin

Question 8

When is thiocyanate determination used?

Answer 8

Used in cases of long term sodium nitroprusside use to measure CN exposure by SCN- levels. Not useful in acute cyanide poisoning

Question 9

What are the ways of cyanide analysis?

Answer 9

colorimetric
gc
lc
gcms

Question 10

Explain colorimetric analysis of CN

Answer 10

Take blood sample -> acidify, liberating CN from blood as HCN -> basic solution to trap CN -> react CN to form CNCl -> read the absorbance

Question 11

What are routes of exposure to CO

Answer 11

Incomplete combustion: housefires, improperly tuned furnace, indoor gas cooking, combustion engines
heme metabolism: some HbCO is found in urban smokers and non smokers (1-6%)

Question 12

Describe CO elimination and the half life in under different environments

Answer 12

in typical room air: CO is eliminated via lungs with half-life of 3-4 hrs
breathing 100% O2: CO half-life is 30-90min
hyperbaric O2: CO half-life is 15-25 min

Question 13

Describe CO Toxicity

Answer 13

CO has 250x binding affinity to Hb than O2, therefore O2 is replaced and there is no O2 to be delivered to peripheral tissues (in addition, binding of CO causes the other 3 O2 to bind more tightly to HB)

CO binds even more to cardiac myoglobin causing (hypotension, myocardial depression, and worsening tissue hypoxia)

likely some impairment of cellular respiration from binding to cytochrome C as well (indicated by symptoms)

Question 14

What are the physical findings of CO toxidrome? What are the specific findings at 5-10%. 15-25%. and 50-70%

Answer 14

Physical findings:
- tachypnea
- tachycardia
- hyper/hypotension
- hyperthermia
- cherry red skin in deceased
- memory disturbances
- coma, movement disorders
- decreased cognitive ability
- long term neuropsychiatric symptoms are seen for months

5-10%: aggravate pre-existing heart disease; headache
15-25%: nausea
50-70% hallucination, seizure, coma, death

Question 15

How is CO determined?

Answer 15

Use a co-oximeter to measure different forms of Hb including carboxyhemoglobin as a % by measuring different absorbance spectra of the various Hb

Question 16

How is CO toxicity treated?

Answer 16

100% O2
heart monitor for myocardial damage
manage metabolic disturbances as usual
hyperbaric O2 if symptoms persist after 4hrs at 100% O2
*remember to consider Cyanide exposure also

Question 17

What are the classes of insecticides?

Answer 17

Two classes of insect “nerve poison”
- organophosphates
- carbamates

Question 18

What is the mechanism of toxicity for organophosphates?

Answer 18

organophosphates irreversibly phosphorylates Serine residue on acetylcholine esterase enzyme in synaptic cleft of peripheral and central nerves, permanently inactivating it. No enzyme to metabolize released acetylcholine into choline and acetic acid anymore, so acetylcholine floods
1. parasympathetic synapses
2. neuromuscular junctions
3. sympathetic preganglionic synapses

Question 19

What is the mechanism of toxicity for carbamates?

Answer 19

Carbamates reversibly inactive acetylcholine esterase by alkylating the serine residue

Question 20

Describe the toxidrome of insecticide poisoning

Answer 20

Effects differ depending on which nerves are affected
1. Parasympathetic system: DUMBELS (diarrhea, urination, miosis, bronchospasm and bradycardia, emesis, lacrimation, salivation)
2. neuromuscular junction: cramping, weakness, fasciculation (twitching), paralysis of diaphragm
3. sympathetic system: Tachycardia, hypertension, dilated pupils, pallor

clinical presentation depends on relative amounts of stimulation, but typically the muscarinic symptoms dominate (DUMBELS)
- also nonspecific CNS neurotoxic effects: agitation, lethargy, confusion, seizure, coma

Question 21

How is insecticide poisoning treated?

Answer 21

First general steps:
Airway, breathing ,circulation
may need to paralyze patient
decontaminate with soap and water

Specific therapies
atropine: antimuscarinic anticholinergic
pralidoxime: dephosphorylates serine residue (only needed in organophosphate not carbamate toxicity)

Question 22

What are long term symptoms of insecticide poisoning

Answer 22

Organophosphate-induced delayed neuropathy (1-3 weeks after severe exposure)
weakness, ataxia (poor muscle control) , paralysis (no resp. symptoms)