Analgesics in MOS 2 Flashcards
What is the most common cause of acute liver injury in Europe and North America?
Paracitamol poisoning
What are the main properties of paracetamol?
- antipyretic
- analgesic
What type of pain should paracetamol be used for following oral surgery ?
mild to moderate
What is the maximum therapeutic dose of paracetamol ?
4g/24h
What are PROMs ?
patient reported outcome measures
What does the oral surgery guidance for commissioners of service recommend following oral surgery?
it recommends that all patients be contacted by telephone 24 hours after their surgery to enquire about unmanaged pain, haemorrhage and nerve injury
What is the most commonly used opioid analgesic?
Paracetamol
The US approved name for paracetamol is …
acetaminophen
Paracetamol causes euphoria and alters the mood. True or false
False
Paracetamol is the _______ name
International non-properietary name
British Approved Name
Acetaminophen was sold under the name ____ in the USA (1955)
Tylenol
In 1956, 500 mg tablets of paracetamol went on sale in the UK under the brand name ______.
panadol
The childrens formulation of paracetamol was released in 1958 and called…
Panadol Elixer
What is the MOA of paracetamol?
- inhibition of COX-3 isoenzyme
- inhibition of COX-1 variant and subsequent reduced release of prostanoid release in the CNS
(is effective in COX-1 variant present in CNS; reduces prostaglandins that have a role in causing fevers)
What is the primary mechanism by which paracetamol is able to reduce fever
central inhibition
When are weak plasma concentrations of paracetamol present following ingestion ?
30-60 minutes
Briefly describe how paracetamol is inactivated
it is inactivated by conjugation to glucoronide and sulphate (to a lesser extent)
How is paracetamol excreted?
via the kidneys
What is the NNT for 1g of paracetamol in oral surgery ? What does this mean
1.87
This means that for every 2 (1.87 rounded up) patients who receive 1g of paracetamol, one will get greater than 50% pain relief and would not have done so if they received the placebo
Why has paracetamol been described as a weak analgesic?
this because it has affected by the ceiling effect meaning that increasing the dose will not confer any further analgesic benefit
What is the benefit of using paracetamol with other analgesics ?
- superior pain relief
- permits reduction in opioid drug doses
What are the indications for paracetamol use ?
- headache
- fever
- period pain
- toothache, other dental pain
- back pain
- muscular and joint pain
- neuralgia
- pain associated with colds/flus
Why is paracetamol the analgesic of choice for children?
this is because it is not associated with Reyes syndrome
Why is paracetamol sometimes preferred for use in the elderly?
because it lacks the gastric erosive properties
How can you guard patients from accidental overdoses?
- advise them to follow dosing regime on the label
- avoid prolonged and excessived doses
Patients and their escorts must always be informed if paracetamol has been used intra/post operatively. True or false
True
this will prevent further overdose as patient is made aware that they have received it during their treatment
-allows pt to monitor futher dose
Why should patients be warned about combination analgesics ?
this is because they may also contain paracetamol
Allows patient to monitor dose and prevent overdose
Recent evidence has shown that high dose levels of paracetamol may be associated with …
the same GI and cardiovascular adverse events as non-selective NSAIDs
What dose of paracetamol is recognised as toxic?
- 150mg/kg
- 12 g
or less if they are a high risk patient then the dose required for hepatotoxicity may be less
State some patients that may be at increased risk of hepatotoxicity from paracetamol
- adolescents with eating disorder
- adolescents with gluthathione depletion
- patients taking enzyme inducing drugs such as phenytoin or rifampicin (this has not been definitely shown)
What is reported to reduce the ceiling of toxicity of paracetamol?
(causing a lower dose to be hepatotoxic)
chronic alcohol ingestion
Many individuals have no symptoms 24h after a paracetamol overdose. True or false
True
What are some symptoms that may be experienced in the first 24 hours of a paracetamol overdose?
- vague abdominal pain
- nausea
What are the signs of a paracetamol overdose after the first 24 hours?
- signs of liver failure
- encephalopathy
- hypoglcaemia
- coagulopathy
It is not important to establish the exact timing and amount of paracetamol injected in an overdose. True or false
False
an attempt should be made, it is prudent to do so
What treatment can be provided for hepatotoxic overdose that has occurred within the last hour?
gastric decontamination with activated charcoal
What is the mainstay treatment paracetamol poisoning?
N-acetylcysteine
The decision to start N-acetylcysteine treatment depends on…
- time of presentation after the overdose
- serum levels of paracetamol
- liver enzymes
What is the effect of prolonged and short term use of paracetamol on coumarins?
Prolonged use:
* enhace anticoagulant effect of coumarins (e.g. warfarin)
short term use (i.e. post operative analgesic)
* unlikely to have an effect
What is the effect of concomitant use of paracetamol and antiepileptic drugs?
(antiepileptic drugs like carbamazapine, phenobarbital and phenytoin)
metabolism of paracetamol is accelarated thus reducing its analgesic efficacy
Briefly describe the drug interaction that occurs between paracetamol and busulfan
- metabolism of cytotoxic drug busulfan is inhibited in the presence of paracetamol
- thus caution is advised within 72 hours of paracetamol use
1g dose of paracetamol provides analgesia for…
4 hours
What is the maximum dose of safety for paracetamol?
4g
[[hence 1g dose of paracetamol cannot be taken every 4 hours despite the analgesic effect wearing off after 4 hours]]
What formulation of paracetamol can improve patient compliance with regards to appropriate dosing?
controlled release formulation
Why should control release formulations of paracetamol be taken regularly and not “as required”?
they may take as long as 4 hours to reach peak analgesic effect
Outline the composition of the modified release paracetamol preparation Panadol Extend
- bilayer tablet contaning paracetamol 665mg
- one layer containng immediate release paracetamol (31% 0ff 665mg)
- second layer containing sustained release paracetamol (69% of 665mg)
What is the recommended dose of Panadol Extend?
2 665mg (1.33g) tablets 3x daily
maximum daily dose of 6 tablets (3.99g)
Panadol extend can provide analgesic relief for up to __ hours
8
What route of administration for paracetamol has a predictable onset and duration of action?
parenteral
1g of IV paracetamol has a similar analgesic efficacy to …
2 g of the prodrug of paracetamol, proparacetamol
What is second port of call (after paracetamol) for analgesia in children?
ibuprofen
What is the first choice OTC for analgesia and antipyresis in children?
paracetamol
Children seem to be less susceptible to acute toxicity with paracetamol compared to adults. True or false
True
What is the global paediatric dose for paracetamol ?
varies between 10-15mg/kg
What is the paediatric dose of paracetamol in the UK?
10mg/kg every 4-6 hours up to a maximum of 4 doses a day
What is the recommended paediatric dose of paracetamol in the USA?
10-15mg/kg up to 5x daily
total dose of 50-75mg/kg
What is the recommended paediatric dose of paracetamol in Australia?
15mg/kg every 4 hours
total dose of 60mg/kg/day
Oral elixirs of paracetamol cannot be used to substitute purpose made suppositories. Why is this?
this is because they are not absorbed rectally
What is the analgesic of choice in pregnancy?
paracetamol
Why is the use of paracetamol not contraindicated in breastfeeding despite it being excreted in breast milk?
it is not excreted in clinically significant amounts
Codeine alone is a poor analgesic for acute pain. What can improve its analgesic strength?
combination with paracetamol
What is the NNT of paracetamol (600/650mg) with 60mg of codeine ?
3.6
What is the NNT of 1g of paracetamol with 60mg of codeine?
2.2
(lower NNT- higher analgesic efficacy)
What compound analgesic containing paracetamol was withdrawn from the UK market by the MHRA? Why?
Co-proximol
325mg paracetamol + 32.5 mg dextroproxyphene
due to fatal toxiciy with often as little as 15-20 tablets particularly when taken with alcohol
What paracetamol /NSAID combination has shown signs of superiority compared to others according to cochrane systematic reviews?
paracetamol and ibuprofen
What does the choice of analgesia depend on?
- the anticipated severity of post operative pain
- age
- patient health
Paracetamol has grown in its use for intravenous day case GA for oral surgery. True or false
True
What is the oral dose of paracetamol for adults?
1g every 4-6 hours
Maximum 4g for 24 hours
What is the oral dose of paracetamol for children aged 2-4 years old?
180mg
What is the oral dose of paracetamol for children aged 4-6 years old?
240 mg
What is the oral dose of paracetamol for children aged 6-8 years old ?
240-250mg
What is the oral dose of paracetamol for children aged 8-10 years old?
360-375mg
What is the oral dose of paracetamol for children aged 10-12 years old?
480-500mg
What is the oral dose of paracetamol for children aged 12-16 years old?
480-750mg
What is the IV infusion dose over 15 minutes for paracetamol for children 10-15kg in weight?
15mg/kg every 4-6h
maximum 60mg/kg/24h
What is the IV infusion dose over 15 minutes for paracetamol for adults and children over 50kg?
1g every 4-6 hours
max 4g/24 hours
What is the dose of paracetamol by rectum for adults and children over 12 years?
1g ever 4-6 hours
max 4g/24hours
What is the dose of paracetamol by rectum for children 1-5 years old?
125-250mg
What is the dose of paracetamol by rectum for children 5-12 years old ?
250-500mg
max 4g/24hours