Analgesia Part 2 Flashcards
what do NSAIDs do
• Inhibit cyclo-oxygenases and so reduce prostaglandins (which sensitise the tissues to other inflammatory mediators resulting in pain)
• The NSAIDs (aspirin and ibuprofen) inhibit COX-1 and COX-2
○ Predominantly COX-1 inhibition
○ Aspirin is 150 times more effective at inhibiting COX-1 than COX-2
what is COX-1 / what does it do
COX-1 is the cyclo-oxygenase predominantly responsible for catalysing the reaction that produces prostaglandins associated with:
○ Platelet aggregation
○ Protection of the gastric mucosa
what is COX-2 / What does it do
COX-2 is the enzyme responsible for the generation of the inflammatory prostaglandins
Although in some situations COX-1 is also involved
the amount of aspirin needed to have sufficient anti-inflammatory effects by inhibition of COX-2 will cause what
Amount of aspirin needed to have sufficient anti-inflammatory effects by inhibition of COX-2 will cause gastric damage due to the amount of COX-1 inhibition
what does the action of the formed prostaglandins depend on
○ The pathological situation
○ Whether they are formed by COX-1 or COX-2
○Whether they are formed in excessive amounts
what is generated in low physiological amounts by COX-1 and what does this do
PGE2 is generated in low physiological amounts by COX-1 in gastric tissues and has a protective effect
when are prostaglandins generated in excessive amounts
Prostaglandins (especially PGE2) are generated in excessive amounts during inflammation via elevated COX-2 levels
what does PGE2 in large amounts produce
PGE2 in large amounts produces increased vasodilation, increased vascular permeability and sensitises pain fibre nerve endings to bradykinin, 5HT and other mediators
why does it make sense to have COX-2 selectives
Since the analgesic actions of NSAIDs appear to result from the inhibition of COX-2 (mainly, although COX-1 may be involved) it would make sense to have selective COX-2 inhibitors and spare COX-1
Therefore less gastric effect
are cox-2 inhibitors associated with a higher or lower risk of serious upper GIT side effects compared with non-selective NSAIDs
selective COX-2 Inhibitors are associated with a lower risk of serious upper GIT side effects compared with non-selective NSAIDs
what is celecoxib and what does it do
selective cox-2 inhibitor
Useful anti-inflammatory actions and fewer GIT damaging actions compared with non-selective NSAIDs
Note: this view may be too simplistic
Some data suggests that COX-2 generated prostaglandins may also contribute to gastric mucosal integrity and damage repair
what patients are all NSAIDs including COX-2 inhibitors contraindicated in
All NSAIDs (including selective COX-2 Inhibitors) are contraindicated in patients with active peptic ulceration Non-selective NSAIDs are contraindicated in patients with a history of peptic ulceration
what does the BNF recommend with regards to NSAIDs
do not use more than one oral NSAID at a time (including selective COX-2 inhibitors)
Regarding dental and orofacial pain - COX-2 selectives should be chosen to manage dental pain only in patients at high risk of gastric or duodenal ulceration (eg those with a history of peptic ulcer)
why are selective cox-2 inhibitors thought to be better tolerated by patients with clotting disorders
Highly selective COX-2 inhibitors do not have an effect on platelet aggregation and so many be better tolerated by patients with clotting disorders
what is another name for paracetamol
Acetaminophen
is paracetamol an NSAID
Paracetamol is traditionally included under the banner of NSAIDs although in reality it is a simple analgesic without anti-inflammatory activity
what are the properties of paracetamol
- Analgesic
- Antipyretic
- Little or no anti-inflammatory action
- No effects on bleeding time
- Does not interact significantly with warfarin
- Less irritant to GIT
- Suitable for children
- Relatively safe analgesics ~ very commonly used
explain the mode of action of paracetamol
- Hydroperoxides are generated from the metabolism of arachidonic acid by COX and exert a positive feedback to stimulate COX activity
- This feedback is blocked by paracetamol, thus indirectly inhibiting COX - especially in the brain
• Results in:
○ Analgesia
○ Antipyretic action
○ No reduction in peripheral inflammation
• A small component of the analgesic action of all NSAIDs is the reduction of prostaglandins in the pain pathways of the central nervous system, such as in the thalamus
○ This is the main site of action of paracetamol
- Alternative central mechanisms have also been proposed including reduced 5HT production or interference with the excitatory amino acid NMDA (N-Methyl-D-Aspartate) in spinal cord pathways
- Exact mode of action still unclear
why does paracetamol cause only little / no gastric mucosal irritation
Since it does not appear to have much effect on peripheral prostaglandins there is little / no gastric mucosal irritation
is paracetamol a safe analgesic
It is described as a ‘safe analgesic’ although it causes severe problems in overdose
when do you need to take caution when prescribing paracetamol
- Hepatic impairment
- Renal impairment
- Alcohol dependence
what are the side effects of paracetamol
these are rare
- rashes
- Blood disorders
- Hypotension reported on infusion ~Reduced blood pressure particularly if given IV
- Liver damage (and less frequently kidney damage) following overdose
what does paracetamol interact with
• Anticoagulants
○ Prolonged regular use of paracetamol possibly enhances the anticoagulant effects of the coumarins
○ Fairly minimal
- Cytotoxics
- Domperidone
- Lipid-regulating drugs
- Metoclopramide
how should you recommend odontogenic pain should be managed with paracetamol
For mild to moderate odontogenic or post-operative pain, an appropriate 5-day regime:
• Paracetamol tablets, 500mg
Send: 40 tablets
Label: 2 tablets 4x daily
what are the dosages recommended for children with paracetamol
For children: paracetamol tablets or soluble tablets, 500mg or oral suspension 120mg/5 ml or 250 mg/5 ml
○ 6months-2 years = 120mg 4x daily (max. 4 doses in 24 hours)
○ 2-4 years = 180mg 4x daily (max. 4 doses in 24 hours)
○ 4-6 years = 240mg 4x daily (max. 4 doses in 24 hours)
○ 6-8 years = 250mg 4x daily (max. 4 doses in 24 hours)
○ 8-10 years = 375mg 4x daily (max. 4 doses in 24 hours)
○ 10-18 years = 500mg 4x daily (max. 4 doses in 24 hours)
what advice should be given to patients regarding the dose of paracetamol
Advise patient that paracetamol can be taken at 4-hourly intervals but not to exceed the recommended daily dose
○ Maximum 4g for adults
• Overdose with paracetamol is dangerous because it can cause hepatic damage that is sometimes not apparent for 4-6 days
○ As little as 10-15g taken within 24 hours can cause severe hepatocellular necrosis
○ Transfer patients who have taken an overdose to hospital
what is the maximum dose of paracetamol for adults
Maximum dose = 4g daily (8 tablets
Always warn patient with regard to maximum dose and emphasise that they should not exceed this
what is the maximum dose of paracetamol for children
Depends on weight / age
See BNF
what are the side effects of overdose
As little as 10-15g (20-30 tablets) or 150mg/Kg of paracetamol taken with 24 hours may cause severe hepatocellular necrosis, and less frequently, renal tubular necrosis
• Anorexia, nausea, vomiting
○ Only early features of poisoning
○ Usually settle within 24 hours
- Persistence of these features beyond 24 hours is often associated with abdominal pain: right subcostal pain and tenderness, usually indicates development of hepatic necrosis
- Liver damage is maximal at 3-4 days after ingestion and may lead to jaundice, renal failure, haemorrhage, hypoglycaemia, encephalopathy, cerebral oedema and death
Therefore, despite a lack of significant early symptoms, patients who have taken an overdose of paracetamol should be transferred immediately to hospital
what is the name of teh opioid analgesia in the dental practitioners forumulary
Dihydrocodeine
where does opioid analgesics act
Act in the spinal cord
Especially in the dorsal horn pathways associated with paleo-spinothalamic pathway
Ie act centrally on opioid receptors
opioid analgesia causes central regulation of pain in what
○ Periaqueductal grey matter
○ Nucleus reticularis paragigantocellularis
○ Raphe magnus nucleus
how do opioid receptors produce their effects
They produce their effects via specific receptors which are closely associated with the neuronal pathways that transmit pain to the CNS
what is opioid a term used for
Opioid is a term used for both naturally occurring and synthetic molecules that produce their effects by combining with opioid receptors
are opioid analgesics useful for dental pain
Opioid analgesics are relatively ineffective in dental pain
what are the problems with opioid analgesics
• Dependence
○ Psychological and physical
○ Withdrawal of the drug will lead to psychological cravings and the patient will also be physically ill
• Tolerance - only to depressant effects
○ As the body becomes more tolerant to the drug the patient is going to require more and more to get the same effect
○ To achieve the same therapeutic effects the dose of the drug needs to be progressively increased
• Effects on smooth muscle:
○ Constipation
§ Can occur after few doses of dihydrocodeine
○ Urinary and bile retentiob
○ Long term can make patients uncomfortable
what effect does opioid analgesics have on the CNS
• Depresses ○ Pain centre ~ Alters awareness / perception of pain ○ Higher centres ○ Respiratory centre ○ Cough centre ~Cough suppression ○ Vasomotor
• Stimulate
○ Vomiting centre ~ Dihydrocodeine often causes nausea and vomiting which limits it value in dental pain [If they cannot ingest the drug then they are not going to absorb very much of the drug]
○ Salivary centre
○ Pupillary constriction
What are the common side effects of opioids
○ Nausea
○ Vomiting
○ Drowsiness
○ Larger doses produce respiratory depression and hypotension
what are the other side effects of opioids
○ Difficulty with micturition ○ Ureteric or biliary spasm ○ Dry mouth ○ Sweating ○ Facial flushing ○ Headache ○ Vertigo ○ Bradycardia ○ Tachycardia ○ Palpitations ○ Postural hypotension ○ Hypothermia ○ Hallucinations ○ Dysphoria ○ Mood changes ○ Dependence ○ Miosis ○ Decreased libido or potency ○ Rashes / urticaria / pruritis
what enhances the effects of opioids
effects of opioids enhanced by alcohol
what are the cautions with opioid use
• Hypotension • Hypothyroidism • Asthma • Decreased respiratory reserve • Prostatic hyperplasia • Pregnancy / breast-feeding • May precipitate coma in hepatic impairment ○ Reduce dose or avoid • Renal impairment ○ Reduce dose or avoid ○ Cannot excrete the drug fully • Elderly and debilitated ○ Reduce dose ○ Considerable reduction in dose if it is needed • Convulsive disorders • Dependence
what are the contraindications to opioid use
- Acute respiratory depression
- Acute alcoholism
• Raised intracranial pressure / head injury
○ Interferes with respiration
○ Affects pupillary responses vital for neurological assessment
what is codeine
A natural alkaloid found in opium poppy
1/12th the potency of morphine
what are the properties of codeine
- Effective orally
- Low dependence
• Usually in combination with NSAIDs or paracetamol
○ Eg co-codamol ~ this is over the counter
§ 8mg codeine
§ 500mg paracetamol
○ 30mg codeine and 500mg paracetamol is prescription only formula but we cannot prescribe as dentists
- Effective cough suppressant
- Available over the counter
what is a common side effect of codeine
Common side effect = constipation
is codiene availalble on teh dental list
Codeine phosphate not on dental list
The only codeine combination on the dental list is dihydrocodeine
what is dihydrocodeine known as
Dihydrocodeine Tartrate DF118 Forte (trade name)
what is the potency of dihydrocodeine
Potency similar to codeine
what routes can dihydrocodeine be taken
SC (subcutaneous) or IM (intra-muscular) = controlled drug
Oral (tablet form) = not controlled
what is the dose of dihydrocodeine
Oral: 30mg every 4-6 hours as necessary
(40, 60, 120mg tablets are not available on the Dental List)
Oral is the only route on the dental list
what are the side effects of opioids
The same as general opioids side effects:
• Nausea / vomiting
• Constipation
• Drowsiness
Larger doses: • Respiratory depression • Hypotension • Ureteric spasm • Biliary spasm • Many more
what are dihydrocodeine interactions
many ~ see BNF
serious interactions =
• Antidepressants MAOIs
• Dopaminergics (Parkinsonism)
what are the cautions of dihydrocodiene
Same as general opioid cautions: • Hypotension • Asthma • Pregnancy / lactation • Renal / hepatic disease • Elderly / children Never prescribe in raised intracranial pressure / suspected head injury
when is dihydrocodeine used
○ Moderate to severe pain
○ However BNF states that due to the side effects of nausea and vomiting it is of little value for dental pain
○ Not very effective for post-operative dental pain
what can overdose of opiods cause
- Opioids cause varying degrees of coma, respiratory depression, & pinpoint pupils
- The specific antidote Naloxone is indicated if there is coma or bradypnoea
• Naloxane has a shorter duration of action than many opioids
○ Therefore close monitoring and repeated injections / infusion may be necessary according to respiratory rate and depth of coma
what are the different types of neuropathic and functional pain in dental treatment
○ Trigeminal neuralgia
○ Post-herpetic neuralgia
○ Functional: TMJ or atypical facial pain
what drug on the dental list can treat neuropathic and functional pain
• At present the only drug on the dental list is carbamazepine
○ Proprietary band eg Tegretol
○ Anti-convulsant [Emergency drug for epilepsy]
○ Can also be used to control trigeminal neuralgia
what drugs can treat trigeminal neuralgia
• Carbamazepine on dental prescribers’ formulary
• Other drugs used for trigeminal neuralgia include:
○ Gabapentin
○ Phenytoin
At present these are not included on the dental list
what are the clinical features of trigeminal neuralgia
○ Severe spasms of pain
§ ‘electric shock’
§ Lasts seconds
○ Usually unilateral
○ Older age group
○ Trigger spot identified
§ Triggers could be washing face or cold wind hitting face
§ Recurrence of symptoms usually means greater severity
○ Females more than males
○ Periods of remission
○ Recurrences often greater severity
○ Tends to only affect one branch of the trigeminal nerve but can affect more
how would you prescribe carbamaxepine to treat trigeminal neuralgia
○ 100 or 200mg tablets
○ Starting dose 100mg once or twice daily
§ But some patients may require higher initial dose
○ Increase gradually according to response of patient
§ Step ladder increasing dose
○ Usual dose: 200mg 3-4x daily
§ Up to 1.6g daily in some patients
○ Maintenance dose = 200mg 3-4x daily
○ Maximum dose = 1.6g daily
what are the side effects of carbamazepine
Extensive list - see BNF • Dizziness • Ataxia • Drowsiness ○ As it is usually prescribed to older patients want to be wary of this as it might mean an increased risk of falls • Leucopenia and other blood disorders
how is needed if a patient is on carbamzepine
Patient blood monitoring needed
- Blood count
- Liver function tests
- As a minimum these tests should be asked for to get a baseline to see if there are any pre-existing issues before the patient starts this drug
what are contrainidcations of carbamazepine
• AV conduction abnormalities
○ Unless paced
• History of bone marrow depression
• Porphyria
what are the cautions of prescribing carbamazepine
- Hepatic / renal / cardiac disease
- Skin reactions
- History of haematological reactions to other drugs
- Glaucoma
- Pregnancy / breast-feeding
- Avoid abrupt withdrawal
what are the 6 analgesic drugs to be familiar with in the dental practitioners formulary
- Aspirin (NSAID)
- Ibuprofen (NSAID)
- Diclofenac (NSAID)
- Paracetamol
- Dihydrocodeine (opioid)
- Carbamazepine
