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Module 6 - Therapeutics > Paracetamol > Flashcards

Paracetamol Flashcards

1
Q

What is another term for paracetamol?

A

Acetaminophen

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2
Q

Name 3 analine derivatives?

A
  • Phenacetin.
  • Acetanalid.
  • Acetaminophen.
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3
Q

What are 3 trairs of analine derivatives?

A

Analgesic:
- Mild-moderate pain (similar to aspirin).
- Anti-pyretic (similar to aspirin).
- Anti-inflammatory

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4
Q

Which analine derivative was withdrawn and why?

A
  • Phenacetin
  • Due to renal toxicity.
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5
Q

What is the mode of action of paracetamol (3)?

A
  • more of a PERIPHERAL anti inflammatory effect.
  • Limited inhibition of COX1/2 activited.
  • Stronger inhibition of COX-3 activity?
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6
Q

What are 3 less robust potential modes of action of paracetamol?

A
  • Selective Inhibitor neuronal PG synth.
  • Activation serotonergic pathways spine.
  • Inhibition Nitric Oxide synthase.
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7
Q

On what point of the analgesic ladder is paracetamol located according to the WHO?

A

FIRST LINE.

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8
Q

How strong is paracetamol considered as an analgesic?

A

Mild to moderate.

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9
Q

Can paracetamol treat acute pain? Chronic pain?

A

BOTH ACUTE AND CHRONIC.

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10
Q

6 Effects of paracetamol?

A
  • No effects on platelet aggregation.
  • Little effect respiratory.
  • Little effect cardiovascular.
  • Reportedly fewer ADR’s (cf NSAIDs).
  • Little or no gastric irritation.
  • No relevant impact on uric acid excretion.
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11
Q

Can paracetamol be used for inflammatory conditions?

A

Yes, although less effective than aspirin and NSAIDs.

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12
Q

2 cases where NSAIDs are contraindicated. What can be used instead?

A

Where NSAID’s are CI (ex. asthmatics, ulcerative gut conditions).

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13
Q

Is paracetamol useful as a pre-emptive drug?

A

Less useful as pre-emptive because it does not block the sensitization pain pathways.

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14
Q

What are the 5 different forms paracetamol is available in?

A
  1. Tablet
  2. Capsule.
  3. Elixir.
  4. Suppository.
  5. IV.
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15
Q

Which part of the body is paracetamol most absorbed?

A

GI - particularly SMALL INSTESINE.
- 1st pass metabolism limited.

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16
Q

When is the peak plasma concentration reached? What is the % bioavailability?

A
  • 30 to 60 mins.
  • Bioavailability 70%.
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17
Q

What is the half life of paracetamol? What if it is present in toxic concentrations?

A
  • Half life 2-4 hours.
  • Toxic concetrations 4-8 hours.
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18
Q

Where does biotransformation of paracetamol occur?

A

liver

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19
Q

What does paracetamol react with when it is deactivated?

A

Conjugation with cysteine, glucuronic and sulphuric acid.

(98% of the biotransformation).

20
Q

What is a potential toxic metabolite of paracetamol biotransformation?

A

N-acetyl-p-benzoquinone imine NAPQI

21
Q

How is paracetamol eliminated?

A

Renal aka KIDNEYS.

22
Q
A

be careful with warfarin

23
Q
A

ince

24
Q

Name 2 potential skin side effects of paracetamol.

A

RARE
- Steven johnson syndrome.
- Toxic epidermal necrolisis.

25
Q

Name a rare physiological side effect that may arise from paracetamol use?

A

BLOOD DYSCRASIAS (thrombocyto, neutro, leucopenia).

26
Q

2 rare side effects that may arise from paracetamol use?

A
  • Skin reactions.
  • Blood dyscrasias.
27
Q

What drug does paracetamol interact with? What is the effect?

A

Interaction with WARFARIN.
- Alterations in INR + bleeding.

28
Q

What is an important consideration for patients with RENAL INSUFFICIENCY when prescribing paracetamol? Why?

A
  • INCREASE THE MINIMUM DOSING INTERVAL
  • GREATER THAN 6 HOURS.
  • Elimination time will be prolonged.
29
Q

Can regular therapeutic doses of paracetamol cause any harm?

A

Can lead to HEPATOTOXICITY (liver).

30
Q

4 condition where prescription of paracetamol must be considered carefully?

A
  1. Liver disease.
  2. Alcoholism.
  3. Malnutrition.
  4. Dehydration.
31
Q

What is the STANDARD ADULT DOSE OF PARACETAMOL.

A

10-15mg/kg every 4-6 hours for a DAILY MAXIMUM of 4g.

32
Q

How is the majority of the therapeutic dose of paracetamol metabolized?

A
  • Majority of the absorbed dose is metabolized by the GLUCORONIDATION and SULPHATION pathways to form NON TOXIC METABOLITES which are then EXCRETED in the URINE.
33
Q

What is the remainder of the therapeutic dose metabolized by? What is the pathway called?

A
  • Remainder is metabolized by CYP450.
  • Cytokrine pathway.
34
Q

What are the drugs that induce the CYP450 enzyme? Why is this important?

A

SCRAPPP

  • St John’s Wort.
  • Carbemazepine.
  • Rifampicin.
  • Alcohol.
  • Phenobarbitol.
  • Phenytoin.
  • Primidone.
  • Inducing this enzyme means paracetamol can be metabolized to NAPQI more quickly, increasing the likelihood of TOXICITY.
35
Q

6 potential side effects of paracetamol according to a SYSTEMATIC REVIEW?

A
  1. Increased mortality.
  2. Cardiovascular adverse events (MI, stroke, fatal CHD).
  3. GI adverse events (ulcers, upper GI bleeding).
  4. Renal impairement.
  5. 2x rate acute liver failure than NSAIDs.
  6. 4x more likely to have abnormal LFTs.
36
Q

What is considered a HIGHLY TOXIC DOSE of paracetamol? (both in grams and tablets). What can this lead to?

A

10-15 grams.
- 20-30 tablets.
- Severe and irreversible HEPATOCELLULAR NECROSIS aka ACUTE LIVER DAMAGE.

37
Q

When the patient has other existing risk factors (name them), how low can the HIGHLY TOXIC DOSE BE?

A
  • Enzyme inducing drugs.
  • Malnutrition.

8g!!!!

38
Q

What is generally considered a fatal amount of paracetamol (in g)?

A

25g

39
Q

When does maximal liver damage occur?

A

3-4 days post ingestion.

40
Q

3 early symptoms of paracetamol overdose?

A

Early symptoms:
- Mild GI upset (if any).
- Vague abdominal discomfort (subcostal tenderness).
- Nausea and vomiting.

41
Q

What is the treatment for paracetamol overdose?

A
  1. Acetylcysteine IV ideally in 13 HOURS- UP TO 32 HOURS MAY BE EFFECTIVE.
  2. Activated charcoal - only if 1 is not available.
42
Q

8 symptoms of LATE paracetamol overdose?

A

3-4 days:
- Jaundice.
- Bleeding.
- CNS impairment.
- Onset hepatic failure - must have LIVER TRANSPLANT.
- Renal tubular necrosis.
- Encephalopathies.
- Hypoglycemia.
- Cerebral edema.

43
Q

What is the COMPENSATING PATHWAY to compensate for over NAPQI production following overdose?

A

Following overdose, NAPQI is conjugated with intrahepatic glutathione.

44
Q

What is the % fatality of paracetamol?

A

5% DEATH.

45
Q

What happens when the intrahepatic glutathione stores deplete?

A

NAPQI COVALENTLY BINDS to hepatic cells, causing hepatocellular necrosis.

46
Q

7 preparations/ brand names that contain paracetamol?

A
  • Panadol.
  • Lemsip.
  • beechams cold and flu .
  • Calpol.
  • Alvedon.
  • Sopadol.
  • Co-codamol.

Module 6 - Therapeutics (2 decks)

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