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58 Cards in this Set
- Front
- Back
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what are the two main processes of acetaminophen metabolism that create nontoxic metabolites?
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i. Most of the drug is metabolized in the liver by glucuronidation or sulfation. The end products are non-toxic metabolites.
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what is the less common metabolic pathway for acetomeniphen that produces a toxic metabolite/
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ii. A small percentage is metabolized by CYP450 to N-acetyl-p-benzoquinone-imine (NAPQI), which is an active intermediate. Under normal circumstances (normal doses) NAPQI is detoxified by glutathione.
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what is the toxic intermediate in CYP450 metabolism of acetomenophen
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N-acetyle-p-benzoquinone-imine(NAPQI)
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what is responsible for detoxifiying NAPQI
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glutathione
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when does acetamenophin overdose occurs?
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i. Glutathione is saturated and can’t detoxify all of the NAPQI.
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what happens when acetamenophin overdose happens
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ii. Excess NAPQI binds to hepatocytes, causing necrosis. The liver is the primary organ of toxicity.
iii. Renal damage may also occur. iv. Myocardial damage and pancreatitis have been reported. |
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what is the normal half-life of acetominophen?
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2-3 hours
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what occurs with half life during overdose?
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absorbtion is delayed and half-life is increased
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what is the duration of decline in acetomenophen overdose?
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96 hours at which point patient usually begins to recover, gets a transplant, or dies.
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what is the time frame of phase 1 acetomenophen overdose?
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0--24h
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what is appearance of phase 1 acetomenophen overdose?
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b. Phase 1 (0-24 hours)
i. Symptoms are often absent. ii. Anorexia, nausea, pallor, vomiting, diaphoresis, lethargy may be present. iii. Very rarely – coma and metabolic acidosis. |
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what is time frame for acetomenophen overdose phase 2
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c. Phase 2 ( 24-72 hours)
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what is appeance of phase 2 overdose
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c. Phase 2 ( 24-72 hours)
i. Initial symptoms, when present, become less pronounced. ii. Right upper quadrant pain. iii. Chemical evidence of hepatic dysfunction develops. |
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what is time frameof phase 3 overdose?
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72-96
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what occurs in phase 3 overdose
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d. Phase 3 (72-96 hours)
i. Frank hepatic failure develops – encephalopathy and coagulopathy. ii. The patient either recovers, dies, or undergoes transplant. |
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what is time frame of phase 4 overdose?
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4days - 2 weeks
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what is the appearance of phase 4 overdose?
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e. Phase 4 (4 days – 2 weeks)
i. Recovery phase ii. Long-term hepatic sequelae are unlikely. |
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who is less likely to develop acetomenophen toxicity?
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children less likely than adults
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when should serum level of acetaminophen be drawn in overdose?
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a. Absorption of acetaminophen is usually rapid. However, it may be delayed in overdose so serum levels should not be drawn before 4 hours because the peak serum concentration may not have been reached yet.
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when does the nomogram start in acetomenophen overdose?
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at 4 hours after ingestion
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why is it important to suspect acetaminophen OD in patient with overdose but uncertain type?
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bc acetaminophen tox may provide no specfic symptoms until its too late
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for what is a nomogram used?
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the nomogram provided in our notes to decide if you should initiate therapy or not.
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what does the upper line in the nomogram indicate?
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The upper line denotes the levels at which there is potential for toxicity.
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when is treatment reccomended by the nomogram
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The upper line denotes the levels at which there is potential for toxicity. However, treatment is still recommended even if the levels fall below this line, but above the lower line
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why is there a lower line in the nomogram?
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This lower line allows for a margin of error in case the estimate of the time of ingestion is faulty.
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what is used to treat acetomenophen OD?
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activated charcoal can be used to treat
N-acetylcysteine is the antidote |
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what is the MOA of N-acytlcystiene(NAC)
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i. The mechanism is unclear, it may enhance glutathione stores or have an anti-oxidant effect.
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when can NAC be used?
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ii. NAC is most effective when given within 8 hours of ingestion, but it may be beneficial up to 24 hours post-ingestion. In selected cases you may use it even after 24 hours. An example of this would be a patient present 2 days after ingestion, with low serum levels but clinically evident signs of liver failure.
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how is usually prepared?
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f. IV NAC is the typically used preparation. It has several benefits over oral NAC, including a one-day course rather than a three day course, and avoidance of the foul taste and smell of the po NAC.
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what are the typical amounts of taken acetomenophen that would be counted as overdose?
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10g in adults
150mg/kg in younger people 200mg/kg in kids younger than 6(due to fact that this age group is less prone to toxicity) |
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do you need to do serial repeats of acetomenophen levels when doing treatment?
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no, 1 check 4 hours after ingestion, is enough only repeat if first labs drawn prior to this.
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what type of overdose is a nomogram useful for treating?
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acute ingestion only
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what does activated Charcoal do?
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binds many different types of poisons in the GI tract and prevents them from being absorbed into the blood. this is frontline treatment in any case of suspected overdose of an unsure substance.
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when should charcoal be given?
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in any overdose case where type is not known for sure and should be only given the first day.
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how is chronic ingestion type overdose assessed to see if it should be treated?
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APAP level, Liver funtion test, GI symptoms, usually air on side of treatment if at all unsure
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what are the 3 types of toxic gases?
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simple asphyxiants
chemical asphyxiants irritants |
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what are examples of simple asphyxiants?
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helium
methane ethane |
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what ist he MOA of simple asphyxiants?
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displace oxygen
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what are clinical manifestations of simple asphyxiants?
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brain/heart stuff
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what is treatment for simple asphyxiants?
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nothing really just get them out of the gas maybe treat symptoms
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what is the main example of chemical asphyxiant?
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carbon monoxide
cyanide hydrogen sulfide |
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how does carbon monoxide work?
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prevent O2 binding in the body
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what do you check to see if someone has been exposed to carbon monoxide?
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carboxyhemoglobin
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how do you treat carbon monoxide poisening?
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hyperbaric oxygen chambers
normal oxygen pressors intubation |
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what is MOA of cyanide?
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binds cytochrome oxidase and affects oxidative phosphorilation, impairs oxygen release in tissues
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what is an odd source of cyanide poisen?
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chewing on certain seeds
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what is the treatment for cyanide?
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hydroxycobalamine-
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where does hydrogensulfide come from
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bacterial decomposition of proteins
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what are the antidotes to hydrogensulfide?
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analnitrite/sodium nitrite
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how are irritant gases broken down?
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high water solubility
intermediate water solubility low water solubility |
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where do high water solubility usually affect people
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upper respiratory
eyes noes throat |
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where can high water solubitily gases affect people if the exposure is large enough?
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all the way down airway
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where can low water solubitly gases affect people?
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only in the lower airway
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what are some examples of high water solubility gases
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ammonia
choramine hydrogenchloride |
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what is an example of a low water solubitily gas
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phosgene(seen several hours after exposure)
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what is an example of intermediate water solubility gas
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chlorine gas
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what is treatment for irritant gases
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treat with oxygen
bronchodilator neutralize acids |
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what are the end results of the nontoxic metabolic pathways
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a-glucuronid
a-sulfate |
