Mucomyst
(Acetylcysteine, Acedote)
Indicated for acetaminophen (APAP)
overdose and management of thick,
viscid secretions. For our purposes
of transport, APAP overdose is our
most likely scenario.
Acetylcysteine classification
• Therapeutic classifications:
– Antidote for Tylenol (APAP) overdose. Acts as a
binding agent for metabolized APAP.
– Mucolytic.
Oral versus IV
• Oral administration is much cheaper.
• Oral administration is the preferred route for therapy
unless contraindications exist (e.g aspiration,
persistent vomiting).
• Both oral and intravenous are well tolerated. Nausea
and vomiting are common with oral administration.
Intravenous use has been associated with the
development of anaphylactoid reactions.
• Typical therapies are the 72 hour oral or 20 hour IV
regimen.
Oral versus IV
• Intravenous indications:
– Refractory emesis despite antiemetics.
– Concomitant ingestion that requires continuous
gastrointestinal decontamination that would interfere with
oral administration.
– Gastrointestinal bleeding/obstruction or caustic ingestion.
– Altered mental status/high aspiration risk.
– Patient refusal to take orally, NG tube not an option.
– Neonatal APAP toxicity from maternal overdose.
– In utero exposure from maternal OD (i.e., pregnant
patient).
Interactions and contraindications
• Activated charcoal may absorb orally administered
Acetylcysteine and decrease therapeutic effect.
Interaction Rating = Moderate
• Nitroglycerin can dilate blood vessels and increase
blood flow. Taking Acetylcysteine seems to increase
the effects of nitroglycerin. This could cause
increased chance of side effects including headache,
dizziness, and lightheadedness. Interaction Rating =
Major. Also included is Viagra, Cialis and Levitra.
Adverse effects / side effects
• For both oral and IV administration
– Drowsiness, vasodilation (hypotension),
bronchospasm, nausea, vomiting, rash, pruritis
(itching).
• For IV only administration
– Anaphylaxis, angioedema, chills and fever.
• Most reactions will occur during the loading dose.
• Asthmatics are more likely than non-asthmatics to
experience side effects.
Pregnancy category B
• Pregnancy Category B
• It is not known whether this drug is excreted in
human milk. Because many drugs are excreted in
human milk, caution should be exercised when
Acetylcysteine is administered to a nursing woman.
Acetylcysteine indications
as a mucolytic
• Acetylcysteine is indicated for abnormal, viscid, or
thick mucous secretions in such conditions as:
– Chronic bronchopulmonary disease
– Acute bronchopulmonary disease
– Pulmonary complications of cystic fibrosis
– Tracheostomy care
– Atelectasis due to mucous obstruction
Mucolytic doseage
• Typically given as inhalation nebulizer.
– Inform patient of “rotten egg” smell prior to
administration.
– 3 to 5 ml of 20% solution or 6 to 10 ml of 10%
solution 3-4 times daily until secretions
decreased.
• Oral administration. Take medication as ordered.
Acetylcysteine as mucolytic
• WARNINGS
• After proper administration of Acetylcysteine, an
increased volume of liquified bronchial secretions may
occur. When cough is inadequate, the airway must be
maintained open by mechanical suction if necessary.
Where there is a mechanical block due to foreign body or
local accumulation, the airway should be cleared by
endotracheal aspiration, with or without bronchoscopy.
Asthmatics under treatment with Acetylcysteine should
be watched carefully. Most patients with bronchospasm
are quickly relieved by the use of a bronchodilator given
by nebulization. If bronchospasm progresses, the
medication should be discontinued immediately.
APAP overdose pathophysiology
• Acetaminophen is a common pharmaceutical that is
available to patients as a solitary agent and in
combination with many other drugs. Patients may
present with intentional, accidental, acute, and
chronic ingestions
• Regardless of formulation, the time from ingestion to
peak acetaminophen level is approximately 4 hours.
Liquid formulations peak somewhat quicker, and
even extended-release preparations are almost
completely absorbed by 4 hours.
APAP overdose pathophysiology
• Acetaminophen is metabolized primarily through the
liver. The oxidative step is responsible for production of
N-acetyl-p-benzoquinoneimine (NAPQI). In therapeutic
doses of acetaminophen, NAPQI is detoxified via hepatic
clearance. With supratherapeutic ingestions of
acetaminophen, the binding protein (glutathione)
becomes depleted, and NAPQI binds to hepatocellular
proteins, causing liver toxicity.
• Acetylcysteine serves as a binding agent substitute. In
critically ill patients Acetylcysteine may stop multi-organ
failure and improve cerebral edema.
Acute ingestion of APAP
• Acute ingestions are single ingestions occurring within a
4-hour period. When this history is clear, the appropriate
treatment protocol is straightforward. Serious sequelae
are avoidable as long as therapy is begun within 8 hours
of ingestion. A 4-hour acetaminophen level is obtained.
• Acetylcysteine therapy is initiated if the acetaminophen
concentration is on or above the nomogram treatment
line, the AST is elevated, or the acetaminophen
concentration is greater than 10 mcg/mL and the time of
a suspected toxic ingestion is unknown.
Chronic ingestion of APAP
• By definition, chronic ingestions are multiple,
occurring over more than 4 hours.
• Risk factors may place patients at higher risk for
hepatotoxicity. These include malnutrition, chronic
alcohol use, in children, an associated febrile illness,
and use of drugs that induce the CYP2E1 system
(Most drugs undergo deactivation and/or
metabolism by CYP2E1, either directly or by
facilitated excretion from the body).
Acetylcysteine
As An Antidote for APAP Overdose
• There are no contraindications to oral
administration of Acetylcysteine in the
treatment of acetaminophen overdose.
• Oral administration of Acetylcysteine,
especially in the large doses needed to treat
acetaminophen overdose, may result in
nausea, vomiting and other gastrointestinal
symptoms. Rash with or without mild fever
has been observed rarely.
Acetylcysteine oral dosing
for APAP overdose
• Adult and children, 140 mg/kg loading dose
followed by 70 mg/kg every 4 hours x 17
doses.
• Oral Acetylcysteine tastes horrible and may
effect patient compliance.
Acetylcysteine (for APAP overdose)
IV administration
• Watch for breathing complications. Asthmatic
patients are more likely than nonasthmatic patients
to experience side effects.
• The most significant may result in flushing, urticaria,
pruritus, bronchospasm, angioedema, hypotension,
and tachycardia.
• Although approximately 1% of these reactions are
severe, the majority are mild. They should be treated
symptomatically, and the infusion should be held.
Medical direction should be contacted.
Acetylcysteine (for APAP overdose)
IV therapy for adult and children
• Loading dose: 150mg/kg in 200ml D5W over 1 hour.
(200cc per hour)
• 1st maintenance dose: 50mg/kg in 500ml D5W over 4
hours. (125cc per hour).
• 2nd maintenance dose: 100mg/kg in 1000ml D5W
over 16 hours. (65cc per hour).
• Dosages typically are calculated the same for
pediatrics versus adults.
• Note: These are typical doses. Physician orders may
change.
Supportive APAP overdose treatment
Maintain fluid and electrolyte balance based
on clinical evaluation of state of hydration and
serum electrolytes.
• Treat as necessary for hypoglycemia.
• Administer vitamin K1 if prothrombin time
ratio exceeds 1.5 or fresh frozen plasma if the
prothrombin time ratio exceeds 3.0.
• Diuretics and forced diuresis should be
avoided.