Hemoglobin Pharm Flashcards
Hb is a ____ ___ with ___ pairs of _____ chains where there are ____ heme molecules attached
conjugated protein; two; polypeptide; 4
What does heme contain at the center of its ____ ring?
iron (Fe2+); protoporphyrin
How does one get CO produced? What could be causes of this?
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)
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?
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
Give four parts of CO “pharmacology”
- CO binds Hb (200-250 x the affinity of O2: shifts O2 dissociation curve, decrease in erythrocyte 2,3-diphosphoglycerate)
- binds myoglobulin (direct myocardial toxicity)
- binds to mito cytochrome oxidase (inhibits cellular respiration: effect increased with hypoxia and hypotension)
- displaces NO from platelets (forms peroxynitrites, leading to free read damage contributing to CNS long term toxicity)
CO Acute Clinical Effects include
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
Potential CO “late/chronic effects” include
cognitive dysfunction;
dementia, psychosis, amnesia;
parkinsonism, paralysis chorea, cortical blindness, apraxia, agnosias, peripheral neuropathy, incontinence;
lucent period 2-40 days prior to sequelae
Mech of late effects includes what?
Reperfusion injury;
- during recovery, WBC’s attracted and adhere to brain microvasculature (cyclooxygenase dysfunction)
- WBC’s release proteases, converts xanthine DH to XO, promoting free rad formation –> dealyed lipid peroxidation
Risk of delayed neurologic effects typically include
- adults (>30) appear to be at greater risk
2. loss of consciousness
During evaluation of someone with CO poisoning, what are you looking for?
- End organ manifestations of toxicity: CNS, cardiac, perfusion
- CO level (of relative importance since it can be high and person’s fine, or be low and person’s sick)
For O2 sat, what is used to evaluate someone with CO poisoining?
- Pulse oximetry (falsely normal since carboxyhemoglobin is read as oxyhemoglobin)
- arterial blood gas (co-oximeter is appropriate; calculation falsely normal since pressure of dissolved O2 in the blood is not affected)
Treatment of CO poisoning?
- ABC’s, O2 (shortens half life of CO)
- consider hyperbaric oxygen (shortens CO half life and increases O2; maybe prevents lipid peroxidation and later NEUROLOGICAL SEQUELAE?)
Some indications for HBO?
- LOC (syncope, coma, seizures)
- GCS < 15 on presentation
- CO level: >25%
- myocardial ischemia, ventricular dysrhythmias
- Neurologic signs
What might be rarely seen with CO poisoining in the brain?
bilateral low density areas of the globus pallidus, putamen, and caudate nuclei seldom seen
How can you pick cyanide out?
- Lactate > 10 mmol/L (significant cyanide levels)
2. Patient not responding to supportive care (if CO alone, oxygen should make it go away)
Form of cyanide? Where does CN bind?
- gas (chem warfare/industrial accidents)
- 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)
Treatment of CN?
- ABC’s, supportive care, advanced cardiac life support, largely not successful
- “cyanide antidote kit/package”
- Hydroxocobalamin (binds CN to make cyanocobalamin)
What is the mech behind the cyanide antidote kit/package?
- 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)
- Sodium thiosulfate: enhances normal metabolism of CN through rhodanase enzyme
- Hydroxocobalamin (Vit B12a): binds CN to make cyanocobalamin
When is hydroxocobalamin useful for CN?
- smoke-inhalation victim NOT improving despite supportive care including O2
- Intentional CN exposure (give concurrently with sodium thiosulfate)
Methemoglobin is
heme iron oxidized to ferric form; rate of heme oxidation increased, and there is limited reduction of heme
Causes of methemoglobinemia; symptoms of it
- congenital
- infantile disposition
- external causes;
- 0-10% meth: asymptomatic
- 10-20%: apparent cyanosis
- 20-50%: dizziness, fatigue, HA, exertional dyspnea
- > 50%: lethargy/stupor
- > 70% coma and death
O2 sat methemoglobin measures
- pulse oximetry: falsely and aberrantly lowered (measured as BOTH oxy and deoxyHb will fall rapidly into high 80s)
- arterial blood gas (co-oximeter appropriate; calculation falsely normal because pO2 not affected)
What could lead to acquired methemoglobinemia?
- Drugs (nitrites, nitrates in infants, sulfas, dapsone, local anesthetics)
- Toxins (nitrites, nitrates in infants, ninline dyes, diarrheal illness in infants)
Treatment of methemoglobinemia?
- ABC’s
- Decontamination
- Methylene blue (NADPH reductase cofactor that gains electron and donates to methemoglobin)
When is methylene blue indicated?
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
Non-responders to methylene blue
- hemoglobin M disease
- G6PD deficiency
- CL salts INACTIVATED G6PD
- sulfhemoglobinemia (similar symptoms to methemoglobinemia, with methemoglobin levels elevated; treatment is SUPPORTIVE!!)
