Hemoglobin Pharm

Question 1

Hb is a ____ ___ with ___ pairs of _____ chains where there are ____ heme molecules attached

Answer 1

conjugated protein; two; polypeptide; 4

Question 2

What does heme contain at the center of its ____ ring?

Answer 2

iron (Fe2+); protoporphyrin

Question 3

How does one get CO produced? What could be causes of this?

Answer 3

Incomplete combustion of carbon-containing material;
methane (house fuel; burns clean), coal (unclean burner), gasoline (somewhere in between the other two burning-wise), also INTERNAL PRODUCTION (minimal)

Question 4

How does CO gain entry and exit? What normally happens when you remove someone from the source of CO to the CO levels? When is one case where this doesn’t happen?

Answer 4

Direct respiration (increased respiration = increased dose and increased rate of elimination); eventually you will have increased rate of elimination; 
METHYLENE CHLORIDE (converted to CO in vivo) and the CO levels INCREASE after removal from CO source

Question 5

Give four parts of CO “pharmacology”

Answer 5

1. CO binds Hb (200-250 x the affinity of O2: shifts O2 dissociation curve, decrease in erythrocyte 2,3-diphosphoglycerate)
2. binds myoglobulin (direct myocardial toxicity)
3. binds to mito cytochrome oxidase (inhibits cellular respiration: effect increased with hypoxia and hypotension)
4. displaces NO from platelets (forms peroxynitrites, leading to free read damage contributing to CNS long term toxicity)

Question 6

CO Acute Clinical Effects include

Answer 6

mild: HA, N/V, dizziness
moderate: chest pain, blurred vision, dyspnea on exertion, tachycardia, tachypnea, cognitive deficits, myonecrosis, ataxia
severe: seizures, coma, dysrhythmias, hypotension, MI/ischemia, skin bullae

Question 7

Potential CO “late/chronic effects” include

Answer 7

cognitive dysfunction;
dementia, psychosis, amnesia;
parkinsonism, paralysis chorea, cortical blindness, apraxia, agnosias, peripheral neuropathy, incontinence;
lucent period 2-40 days prior to sequelae

Question 8

Mech of late effects includes what?

Answer 8

Reperfusion injury;

1. during recovery, WBC’s attracted and adhere to brain microvasculature (cyclooxygenase dysfunction)
2. WBC’s release proteases, converts xanthine DH to XO, promoting free rad formation –> dealyed lipid peroxidation

Question 9

Risk of delayed neurologic effects typically include

Answer 9

1. adults (>30) appear to be at greater risk

2. loss of consciousness

Question 10

During evaluation of someone with CO poisoning, what are you looking for?

Answer 10

1. End organ manifestations of toxicity: CNS, cardiac, perfusion
2. CO level (of relative importance since it can be high and person’s fine, or be low and person’s sick)

Question 11

For O2 sat, what is used to evaluate someone with CO poisoining?

Answer 11

1. Pulse oximetry (falsely normal since carboxyhemoglobin is read as oxyhemoglobin)
2. arterial blood gas (co-oximeter is appropriate; calculation falsely normal since pressure of dissolved O2 in the blood is not affected)

Question 12

Treatment of CO poisoning?

Answer 12

1. ABC’s, O2 (shortens half life of CO)
2. consider hyperbaric oxygen (shortens CO half life and increases O2; maybe prevents lipid peroxidation and later NEUROLOGICAL SEQUELAE?)

Question 13

Some indications for HBO?

Answer 13

1. LOC (syncope, coma, seizures)
2. GCS < 15 on presentation
3. CO level: >25%
4. myocardial ischemia, ventricular dysrhythmias
5. Neurologic signs

Question 14

What might be rarely seen with CO poisoining in the brain?

Answer 14

bilateral low density areas of the globus pallidus, putamen, and caudate nuclei seldom seen

Question 15

How can you pick cyanide out?

Answer 15

1. Lactate > 10 mmol/L (significant cyanide levels)

2. Patient not responding to supportive care (if CO alone, oxygen should make it go away)

Question 16

Form of cyanide? Where does CN bind?

Answer 16

1. gas (chem warfare/industrial accidents)
2. cyrstal (mucous membrane or po exposure, like with JEWELERS, electroplating, house fires);
   binds to cytochrome A3 on the ETC (no ATP –> onset of multi-system organ failure)

Question 17

Treatment of CN?

Answer 17

1. ABC’s, supportive care, advanced cardiac life support, largely not successful
2. “cyanide antidote kit/package”
3. Hydroxocobalamin (binds CN to make cyanocobalamin)

Question 18

What is the mech behind the cyanide antidote kit/package?

Answer 18

1. Use e.g. sodium nitrite (also amyl) to attract CN (or even H2S from sewer gas) from the Fe3+ on cytochromes to the Fe3+ in the Hb (bad if there’s CONCURRENT CO POISONING)
2. Sodium thiosulfate: enhances normal metabolism of CN through rhodanase enzyme
3. Hydroxocobalamin (Vit B12a): binds CN to make cyanocobalamin

Question 19

When is hydroxocobalamin useful for CN?

Answer 19

1. smoke-inhalation victim NOT improving despite supportive care including O2
2. Intentional CN exposure (give concurrently with sodium thiosulfate)

Question 20

Methemoglobin is

Answer 20

heme iron oxidized to ferric form; rate of heme oxidation increased, and there is limited reduction of heme

Question 21

Causes of methemoglobinemia; symptoms of it

Answer 21

1. congenital
2. infantile disposition
3. external causes;
4. 0-10% meth: asymptomatic
5. 10-20%: apparent cyanosis
6. 20-50%: dizziness, fatigue, HA, exertional dyspnea
7. > 50%: lethargy/stupor
8. > 70% coma and death

Question 22

O2 sat methemoglobin measures

Answer 22

1. pulse oximetry: falsely and aberrantly lowered (measured as BOTH oxy and deoxyHb will fall rapidly into high 80s)
2. arterial blood gas (co-oximeter appropriate; calculation falsely normal because pO2 not affected)

Question 23

What could lead to acquired methemoglobinemia?

Answer 23

1. Drugs (nitrites, nitrates in infants, sulfas, dapsone, local anesthetics)
2. Toxins (nitrites, nitrates in infants, ninline dyes, diarrheal illness in infants)

Question 24

Treatment of methemoglobinemia?

Answer 24

1. ABC’s
2. Decontamination
3. Methylene blue (NADPH reductase cofactor that gains electron and donates to methemoglobin)

Question 25

When is methylene blue indicated?

Answer 25

Methemoglobin level >20-30% or symptoms; cautions: 1. hemolytic anemia from weak oxidizing capability 2. painful at injection site (dysuria) 3. higher doses can cause dyspnea, restlessness, tremor, precordial pain, apprehension

Question 26

Non-responders to methylene blue

Answer 26

1. hemoglobin M disease 2. G6PD deficiency 3. CL salts INACTIVATED G6PD 4. sulfhemoglobinemia (similar symptoms to methemoglobinemia, with methemoglobin levels elevated; treatment is SUPPORTIVE!!)