Analgesics in MOS 3 Flashcards
What is the NNT for 60 mg of codeine?
16.7
What is the NNT of 60mg codeine in combination with 1g of paracetamol?
2.2 (1.8-2.9)
hence it has a higher efficacy
based on data from 197 patients
Opioids are effective for what kinds of pain following oral surgery?
moderate to severe pain
What are some side effects of opioids?
- nausea
- vomiting
- constipation
The WHO pain ladder was originally applied to the management of ____ pain. However, it is now applied to the management of all types of pain
cancer
Give examples of mild opioid drugs
codeine phosphate dihydrocodeine
tramadol
Give an example of a stronger opioid drug
morphine
What is an opioid?
this is a compound that has pharamacologucal activity at an opioid receptor. It may be endogenous or administered, naturally occuring or synthetic
What is an opiate?
this term is strictly reserved to describe alkaloids that are derived naturally from the opiate poppy (papaver somniferum)
What is the UK definition of a narcotic?
an addictive drug affecting mood or behaviour
What is the USA definition of a narcotic?
narcotic refers to opioids for medicinal use as well as illegally used opium derivatives
What is opium?
an extract of the juice of the poppy which has been used for social and medicinal purposes for thousands of years as an agent to produce analgesia, euphoria and sleep
What is the most abundant opiate found in opium?
morphine
Give examples of synthetic compounds that have been produced by chemical modification of morphine
- codeine
- diamorphine
- pethidine
How do opioids differ from one another?
- relative efficacy
- pharmakokinetics (body does to the drug)
- other actions
How can the effects of opioids be reversed ?
opioid antagonist such as naloxone
How have opioids been traditionally classified?
- weak
- intermediate
- strong
What adverse side effect does high dose codeine cause?
respiratory depression
What are the 3 principal classes of opioid receptors?
- u- mu
- kappa
- delta
Opioids produce majority of their therapeutic and adverse effects by acting as agonists at ____ receptors
- u- mu receptors
Endogenous opioids do not cause any side effects. True or false
true
Opioids also exhibit a ceiling effect similar to non-opioid analgesics. True or false
False
the analgesic response to the opioids acting on the u-receptors continues to increase with increasing dose
What is the recommended analgesic regime for mild pain following a forceps extraction?
paracetamol 1g every 6 hours regularly (maximum fo 4g/24 hours)
What is the recommended analgesic regime for moderate pain following surgical removal of a tooth?
ibuprofen 400mg every 6 hours
(maximum 2.4g/24 h) and paracetamol 1g every 6 hours as necessary
What is the recommended analgesic regime for severe pain following surgical removal of a tooth involving bone removal ?
ibuprofen 400mg every 6 hours regularly (maximum 2.4g/24hours) and paracetamol 1g/codeine 60 mg combination every 6hours regularly
Opioids are often localised in high concentrations in highly perfused tissues. Give examples of such tissues
- lungs
- liver
- kidneys
- spleen
What is the most common route of administration of opioid analgesics ?
orally
________ preparations of opioids are more rapdily absorbed than solid preparations
liquid
Why might the oral dose of opioids required to provide sufficient analgesic relief be higher than the dose required if it were administered parenterally?
this is due to significant first pass metabolism by glucoronidation in the liver
IM injections of opioids can be administered. Give examples of muscles most often used
- deltoids
- vastus lateralis muscles
Why are IM opioid injections not ideal?
- painful
- not acceptable to some patients
- variable absorption
*
Why must IV administration of opioids be done slowly?
to minimise adverse effects
What are the key requirements for IV administration of opioids?
- skilled nursing
- pharmacy support
- infusion pump for continuous or patient controlled administration
What opioid is available via a transdermal drug delivery system ?
fentanyl
Why are transdermal opioids contraindicated for use in acute post-operative pain?
this is because they are slow release
high incidene of side effects
What drug is the gold standard for acute pain management?
morphine
What does PCA refer to?
patient controlled analgesia
- use of a device (programmable pump) for self administration of small doses of opioids intravenously
What side effect of opioids is most commonly observed in PCA when compared to other conventional routes of administration?
itching
What is the NNT of a single oral dose of 30mg of dihydrocodeine? What is the consequence of this?
8.1
does not provide effective analgesia for acute post operative pain
What is the NNT of 400mg of ibuprofen?
2.5 (2.4-2.7)
(this data is based on a cochrane systematic review involving only 3 trials)
A single dose of tramadol is equivalent to …
1000 mg of paracetamol
What is the NNT of 100mg dose of tramadol ?
4.6 (3.6-6.4)
What adverse side effects have been reported following use of tramadol in dental extraction trials?
- vomiting
- nausea
- dizziness
What is the postulated mechanism for opioid induced side effects such as nausea and vomiting?
stimulation of opioid receptors within the chemoreceptor trigger zone in the postrema of the medulla
What is the effect of opioids on the GI system?
- delayed gastric emptying
- altered intestinal tone (increased)
- altered intestinal motility - propulsive contractions reduced
This results in constipation
How can the GI effects of opioids be managed in patients on short term therapy?
- pts counselled to take water and fibre
- laxative can also be prescribed
Why is morphine contraindicated for patients having day-case surgery?
potential for nausea and vomiting
________ can be used to counteract itching side effect of opioid use.
antihistamines
non-sedating antihistamines are preferable here to avoid increasing opioid induced drowsiness
Certain opioids, such as ____, can be more sedative than others.
morphine
What is the effect of morphine and other mu/kappa agonists on the eyes?
pupil constriction
due to excitatory action in parasympatheric nerve innervations
What is the result of opioid inhibition of brainstem respiratory centres?
- reduced respiratory rate
- reduced tidal volume
Briefly state what respiratory depression is
this is where there is a reduced response to carbondioxide
________ hypotension is an adverse effect of opioid use.
postural
How can opioid overdoses be managed
naloxone
What is naloxone ?
u-opioid receptor competitive antagonist
blocks u-receptors and produces rapid reversal of symptoms
Diamorphine is commonly medically used in the USA and other European countries. True or false
False
never used in USA and some other European countries
Briefly describe the affinity of codeine with opioid receptors
codeine has low affinity for opioid receptors
State another name for morphine
3 methyl morphine
What is responsible for the analgesic effects of codeine ?
10% of codeine is coverted following demethylation with the CYP2D6 enzyme. This produces morphine which is responsible fot the analgesic effect.
What is the bioavailability of codeine?
50%
What is the bioavailability of morphine?
25%
What is the bioavailability of tramadol?
75%
Give examples of medications that are able to block the demethylation of codeine into morphine
- SSRI- selective serotonin reuptake inhibitors
- some antihistamines e.g. diphenhydramine
What are the available codeine/paracetamol combinations available in the UK?
- 30/500 (30mg of codeine phosphate, 500mg of paracetamol) - high strength
lower stregth combinations
* 8/500
* 12.8/500
Aside from pain management, what are some other uses of codeine?
- anti-tussive (stop coughing)
- anti-diarrhoeal
What is the adult dose of orally administred codeine?
30-60mg every 4 hours for a maximum of 240mg daily
What is the IM dose of codeine?
30-60 mg every 4 hours
What is the half life of dihydrocodeine?
4 hours
What is the oral dose of dihydrocodeine?
30 mg every 4-6 hours
What is the oral dose of dihydrocodeine for children >4years old?
0.5-1mg/kg evert 4-6 hours
What is the subcutaneous/IM dose of dihydrocodeine for adults?
50mg every 4-6 hours
What is the subcutaneous/IM dose of dihydrocodeine for children >4 years old ?
0.5-1mg/kg every 4-6 hours
What is the MOA of tramadol?
- selective u-receptor agonist
- weak inhibitor of the reuptake of noradrenaline and serotonin (resembles the action of TCAs)
Tramadol potentiates descending inhibitory pathways. What is the benefit of this?
this action has been shown to have efficacy in the management of chronic pain
Why is tramadol not a controlled drug in many countries?
this is because is has low potential for abuse and addiction
What is the half life of tramadol?
7 hours
What is the oral dose of tramadol for adults and children >12 years ?
50-100mg not more often than every 4 hours
What is the IM/IV dose of tramadol for adults and children over 12 years old?
50-100mg every 4-6 hours
Why is morphine most commonly give via IV or IM injection?
absorption of morphine by mouth is variable
What is the half life of morphine?
2-3 hours
What is the main mode of inactivation of morphine ?
hepatic metabolism
metabolites are then excreted in the urine
(this is the same for most other opioids)
PCA is most commonly used for ________ .
morphine
What is the IM/subcutaneous dose of morphine?
10mg initially every 4 hours
(5mg in elderly/frail)
What is another name for diamorphine?
heroin
What is diamorphine?
semi-synthetic opioid with no activity at the u(mu) receptor
Diamorphine is used medically in …
the UK
The use of tramadol is not recommended for children under 12 years old. True or false
True
What is the recommended dose of morphine for 12-18 year olds ?
2.5-10mg every 4 hours
Opioids should be avoided in…
Pregnant patients or those who are breastfeeding
Opioids should be used with caution in …
- patients with impaired respiratory function
- avoided in COPD patients
- avoided in parients presenting with head injury before full neurological investigation
- hypotension
- urethral stenosis
- myasthenia gravia
- prostatic hypertrophy
- obstructive and inflammatory bowel disorders
- disease of biliary tract
- convulsive disorders
When is a reduced opioid dose recommended?
- elderly patients
- hypothyroidism
- adrenocortical insufficiency
What clinical scenarios require a reduction in opioid doses?
patients with hepatic or renal impairements
they should be reduced or avoided entirely
