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FOS 2 > Use Only As Directed > Flashcards

Use Only As Directed Flashcards

1
Q

Dosing of Acetaminophen

  • What is the recommended dosing for regular strength acetaminophen in adults?
  • What about extra strength?
  • IV?
A
  • Not to exceed 3g /day, 2 tabs (each 325mg) every 4 - 6 hours
  • 1000mg (2 tablets) every 6 hours
  • 1000mg IV every 6 hours
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2
Q

What are the adverse affects of acetaminophen?

A

Nausea

Vomiting

Pruritus (itching)

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3
Q

What constitutes an acute toxic dose of acetaminophen?

What constitutes a chornic toxic dose of acetaminophen?

A

> 7.5g in single dose (adult)

> 150mg/kg (pediatric)

Same parameters but taken over longer period of time

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4
Q

Describe the absorption of tylenol.

A

It is absorbed in the small intestine and its absorption is dependent on gastic emptying. Absorption is also dependent on the form that was administered. It undergoes first pass metabolism in the liver and has about 85 - 95% Bioavailability.

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5
Q

Describe the distribution of acetaminophen?

A

Vd = 1L / kg

About 10 - 25% binds to protein, more binds to protein at toxic doses

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6
Q

Briefly describe the metabolism of acetaminophen.

A

Acetaminophen that is administered orally undergoes first pass metabolism. Approximately 5% is excreted unchanged in the urine, 20-45% is excreted undergoes sulfation, 40 - 65% undergoes glucuronidation, and the remaining 5 - 15% undergoes oxidation via CYP2E1 where it is converted to NAPQI which is highly toxic. Glutathione is used to detoxify this compound to make it inert and excretable.

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7
Q

How is metabolism of acetaminophen different in children?

A

They can tolerate higher levels of the durg without becoming toxic b/c they shunt the drug into glucuronidation and sulfonation more than adults. They also are triggered to vomit more often with overdose.

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8
Q

Describe the changes in metabolism that occur with toxic overdose?

A

The sulfation and glucuronidation pathways are saturated so more of the drug is shunted to the oxidative pathway where it is converted into toxic NAPQI. The body’s glutathione stores are depleted, leading to inability to detoxify acetaminophen and build up of the toxic compound.

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9
Q

What factors influence acetaminophen toxicity?

A

Dose ingested

Time between ingestion and treatment

Age

Excessive CYP2E1 activity due to induction by chronic alcohol or drug use

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10
Q

How does chronic alcohol use contribute to acetaminophen toxicity?

A

Alcohol induces cytochrome P450s, which depletes glutathione stores, makes a person more susceptible to OD of tylenol

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11
Q

How can other drugs impact acetaminophen toxicity?

A

Decreased glucuronidation or sulfation metabolism due to simultaneous use of drugs that compete with acetaminophen for use of these pathways.

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12
Q

What are the 4 stages of acetaminophen poisoning?

A
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13
Q

What is the time window for stage 1 poisoning?

What are the symptoms?

A

0 - 24 hours

Commonly asymptomatic, but can experience nausea, malaise, vomiting

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14
Q

Stage II Poisoning

  • What is the time frame?
  • What enzymes are elevated?
  • Where do patients experience pain?
  • What liver proteins are elevated?
  • What kidney symptoms may present?
A
  • 24 - 72 hours
  • AST, ALT
  • Right upper quadrant
  • Prothrombin time, total bilirubin
  • Oliguria (decreased urine output)
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15
Q

Stage III Poisoning

  • Time frame?
  • Symptoms
A
  • 72 - 96 hours
  • Jaundice, confusion, elevation liver enzymes, hyperammonemia, hypoglycemia, lactic acidosis, renal failure
  • death
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16
Q

Stage IV Poisoning

  • Time frame
A

If survive, stage III this is recovery phase, begins day 4 and lasts up to 2 weeks but usually resolves by day 7

17
Q

How do you manage acetaminophen overdose?

A

Determine if ingestion occurred

Determine if ingestion requires treatment

Initiate appropriate treatment

18
Q

If you suspect a person has OD’d on acetaminophen, what is the first thing you should do?

A

Call poison control

19
Q

How do you diagnose acetaminophen overdose?

A

Patient history

  • Intent of use (intentional or unintentional)
  • Pattern (accute vs. chronic)
  • Co-ingested drugs
  • Co-morbind conditions (alcohol use, drugs, etc.)

Labs

  • acetaminophen levels in blood
  • AST/ALT and bilirubin
  • metabolic panel
  • Urine toxicity panel
20
Q

What are therapeutic levels of acetaminophen in the blood?

What is a toxic level in the blood?

A

10 - 25 mcg/ml

> 200mcg/ml

21
Q

What are 2 treatments for acetaminophen overdose?

A
  • If time since ingestion is < 4hours, activated charcoal can be used. It coats the lining of the stomach and absorbs the acetaminophen that hasn’t yet been absorbed. This is administered with sorbitol, which is a laxative to promote excretion.
  • N-acetylcysteine - this is a glutatione precursor so it promotes production of glutathione to combat the NAPQI that is produced.
22
Q

What does the Rumack Matthew graph tell you?

A

The rumack matthew graph can be used to assess a person’s risk for hepatic toxicity depending on the time since ingestion and the blood concentration of acetaminophen. The different areas of the graph help you assess how to treat a patient depending on where they fall on the graph.

23
Q

The rumack matthew graph is not applicable to those who display toxicity due to _______ use of acetaminophen.

A

Chronic

24
Q

How is chronic acetaminophen toxicity diagnosed and treated?

A

Presents with serum levels that appear therapeutic, but signs and symptoms of hepatotoxicity and lab findings of liver injury.

Thorough history, treat as acute overdose with unknown ingestion time –> administer NAC

25
Q

N-acetylcysteine is used for 2 things. What are they?

A

Acetaminophen toxicity - restores hepatic glutathione enhancing non-toxic conjugation to glutathione of NPAQI

Mucolytic therapy - its free -SH group opens up disulfide bonds in mucoproteins, lowering mucous viscosity

26
Q

What are side effects of NAC?

A
  • Unpleasant smell and taste and vomiting is common
  • Can lead to hypotension and tachycardia
  • Can lead to angioedema, itching and hives
  • Can lead to broncospasm
27
Q

When a person is assessed and is identified as needing NAC treatment, when would you give oral vs. IV therapy?

A

Oral - alert, awake, oriented, suspected to be compliant with treatment as oral schedule is longer

IV - shorter treatment schedule, used if there are reasons to suspect oral schedule will not or cannot be followed. Side effects are more pronounced with IV so it’s not exclusively used.

28
Q

Who bears the burden of safety for an OTC drug?

A

The patient

29
Q

How does a drug become an OTC drug?

A

The drug must first be made as a prescription only drug and go through additional rounds of testing and provide a more robust burden of proof that the drug is safe to use by patients from different backgrounds (education, language, etc).

30
Q

What does an OTC monograph inform manufacturers and consumers of?

A

Manufacturer

  • “Recipe Book” telling acceptable ingredients, doses, formulations and labeling
  • Manufacturers follow conditions to market drug
  • No FDA pre-approval for manufacturers, assume that manufacturers are following monograph but they don’t actually check unless it is brought to their attention by someone else. Can impose penalities for non-adherence.

Consumers

  • Describes conditions for use determined to be generally recognized as safe and effective (GRASE)
31
Q

What must be in the OTC monograph?

A
  • Active ingredients
  • Dosage strength
  • Dosage form
  • Indications for use
  • Warnings
  • DIrections for use
  • Must ensure customers can diagnose underlying condition, determine if drug is appropriate, self administer safely, avoid serious side effects, and recognize when to see a physician
32
Q

What are some limitations of FDA authority?

A

The FDA does not regulate the practice of medicine, so advisory boards can make recommendations but ultimately it is congress that passes the laws regulating drugs. Adverse events are reported yearly but reporting is voluntary.

FOS 2 (44 decks)

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