Analgesia Flashcards
(51 cards)
1
Q
What is the definition of pain?
A
An unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage.
2
Q
Describe (P)RAT.
A
- Prevent - it is important to prepare a patient for any pain you will inflict as their doctor.
- Recognise
- Assess
- Treat
3
Q
Which questions must you ask yourself before you inflict pain on a patient?
A
- Do I need to do this?
- Can I do it skillfully and quickly?
- Can I minimise the pain?
- Pre-emptive analgesia (anticipate pain).
4
Q
List non-pharmacological techniques of pain management.
A
- Treat the underlying cause (eg. reduce / immobilise the fracture).
- RICE (cold pack for first 72 hours post minor MSK injury).
- Explanation / education / reassurance.
- Change of focus away from pain (distraction).
- TENS
- Hypnosis
- Acupuncture
5
Q
What is step 1 on the reverse WHO ladder?
A
- Mild pain
- Continue simple analgesics
6
Q
What is step 2 on the reverse WHO ladder?
A
- Moderate pain
- Use mild opioid eg. codeine, tramadol.
- Continue simple analgesics.
7
Q
What is step 3 on the reverse WHO ladder?
A
- Severe pain
- Use strong opioid eg. morphine.
- Also continue to use simple analgesics.
- Start at this level for acute nociceptive pain. Go down the ladder as the patient gets better and the pain decreases.
8
Q
Which questions must you ask yourself before pescribing?
A
- Which drug am I going to give this patient for this problem?
- Which route am I going to give it by?
- What dose? (What weight is the patient, is there a reason to reduce the dose?)
- How often? (Are the kidneys working? Increase length of dose if you are worried about renal function) Regularly or as required?
- Any adjuvant prescribing required?
- When prescribing opioids, remember a laxative and possibly an antiemetic.
9
Q
What are the possible routes of administration for pain medication?
A
- Topical
- Oral
- IM injection
- IV infusion
- Lolipops
- Directly into the CNS (dose is much smaller)
- Transcutaneous
- Per rectum
10
Q
What are the properties of paracetamol?
A
- Reduces pain (analgesic agent) and has anti-pyretic ability.
- Can be administered orally or per rectum.
- Effective within 40-60 minutes.
- Variable bioavailability.
11
Q
What are the properties of Falgan?
A
- IV paracetamol
- Onset within 5 minutes, peak effect at 40-60 minutes.
- Lasts 4-6 hours.
12
Q
Describe how paracetamol works.
A
- Paracetamol acts centrally in the brain, as opposed to the actual site of tissue damage.
- It acts on the peroxidase site, then have an effect on the cox enzymes.
- The end result is that is diminishes the amount of prostaglandins produced.
- It stimulates serotinergic pathway involved in descending inhibition.
- Pain is modulated in the dorsal horn. There is a descending inhibitory pathway which comes from the periaqueductal gray matter through the medulla and acts on the dorsal horn.
- It stimulates this inhibitory descending pathway.
- Third mechanism of action is the anti-pyretic effect.
13
Q
What are the positives of using paracetamol?
A
- SAFE AND EFFECTIVE
- Cheap
- Number needed to treat (compared to placebo) ~4 to achieve a >50% reduction in moderate pain over 4-6 hours.
- Safe in theraputic dosage.
- Synergistic effect with NSAIDs and opioids (allows less use of these).
- Antipyretic action but poor anti-inflamatory action.
14
Q
Describe the pharmacokinetics of paracetamol.
A
- Absorbed from the small bowel.
- High, but variable bioavailablilty.
- Metabolised in the liver.
15
Q
Describe the effects of paracetamol toxicity.
A
- Foremost cause of acute hepatic failure in the UK.
- Symptoms:
- <8 hours of nausea / vomiting
- 12-36 hours - usually no symptoms
- 24-72 hours - hepatic failure
16
Q
What is the treatment for acute hepatic failure secondary to paracetamol toxicity?
A
N-acetyl cysteine
17
Q
Describe the properties of NSAIDs.
A
- Anti-inflammatory
- Analgesic
- Anti-pyretic
- All of these actions are related to the primary action of these drugs:
- Inhibit prostaglandin biosynthesis by direct action on cyclo-oxygenase enzymes.
- Paracetamol has an indirect mechanism of action, NSAIDs are DIRECT.
18
Q
What is the mechanism of action of NSAIDs?
A
- All inhibit cyclo-oxygenase (COX) but do so by two main mechanisms:
- (1) - an irreversible, time-dependent inhibition of the enzyme (aspirin).
- (2) - A rapid, reversible competitive inhibition of the enzyme (the rest).
- Eg. ibuprofen, naproxen.
- Binds reversibly to the enzyme.
- Competes with natural substrate, arachidonic acid.
- Clinically, aspirin is most commonly used as an anti-platelet drug.
19
Q
What is Reye’s syndrome?
A
- A rare, but life-threatening disorder of children or young adults.
- Children under 16 should not take products containing aspirin.
- Usually occurs following a viral illness (+ingestion of aspirin).
- Persistent uncontrolled vomiting and altered consciousness.
- Still GCS15 but working really hard to orientate themselves.
- Derangement of liver enzymes.
20
Q
Describe prostaglandins.
A
- Inflammation is always accompanied by the release of prostaglandins.
- Predominantly PGE2 but also PG12.
- PGD2 from mast cells.
- PGE2, PG12 and PGD2 act as potent vasodilators.
- Also synergise with other inflammatory mediators (eg. histamine and bradykinin).
- Potentiate histamine and bradykinin actions on postcapillary venule permeability and pain sensory nerves.
21
Q
Describe COX-1
A
- Constitutive
- Important in maintaining GIT integrity.
- Important in maintaining the gut mucosa. If you inhibit them you are more likely to cause GI bleed and peptic ulceration.
22
Q
Describe COX-2
A
- Inducible
- Involved in inflammatory response.
- Implicated in cancer development.
- COX2 isn’t always around but it comes forqward in cancer and is heavily involved in pain.
- There is an increase in thrombotic action - people having strokes and MIs because they were on these drugs.
- So, it is mostly COX1 inhibitors which are prescribed.
23
Q
Describe the anti-pyretic effect of NSAIDs.
A
- Body temperature is regulated by the hypothalamus.
- Fever occurs when the hypothalamic thermostat ‘set-point’ is raised.
- Bacterial endotoxins cause release of factors (eg. interleukin 1) from macrophages.
- Interleukin 1 causes generation of prostaglandins in the hypothalamus (PGEs).
- Prostaglandins increase the thermostat ‘set-point’.
- Therefore, NSAIDs act by preventing the formation of prostaglanding and prevent the rise in temperature.
- No effect on normal body temperature.
24
Q
What are the properties of non-selective NSAIDs?
Give examples.
A
-
Propionic acids
- Eg. ibuprofen, naproxen
- Not prodrugs
- Well absorbed
- Last for 4-6 hours
-
Fenamates
- Eg. mefenamic acid
- If a patient is at risk of a GI bleed, you should also prescribe a proton pump inhibitor when you prescribe a COX1 inhibitor.
25
What are the clinically important side effects of NSAIDs?
* GI complications
* Chronic kidney disease
* NSAID related hypersensitivity (can provoke wheeze in certain patients).
* Cardiovascular disease (reduced efficacy of ACEI) - it can minimise the decrease in BP resulting from the ACE-inhibitor - it minimises the effect of the ACEI.
* Thrombotic sequelae
* Bone healing - good for bone pain but have a negative impact on bone healing.
26
What are the interactions of NSAIDs which cause renal impairment?
ACE inhibitor + NSAIDs + diuretic = renal impairment.
27
Give examples of strong opioids.
* Morphone
* Oxycodone
* Diamorphine
* Fentanyl
* Pethidine
* Remifentanil
* Methadone
28
Give examples of weak opioids.
* Codeine
* Dihydrocodeine
* Loperamide
29
What are the antagonists used or opioids?
* Naloxone
* Naltrexone
30
What is loperamide?
* An opioid which is not an analgesic.
* Works on the myenteric plexus in the gut.
* Trade name = immodium.
31
What are the sites of action of opioids?
* MU opioid receptors (MOP)
* Kappa (KOP)
* Delta (DOP)
* Nociception (NOP)
32
What is the most powerful analgesic site?
MU opioid receptor
33
Describe the effects of opioids at a cellular level.
* When an opioid attaches to a receptor it has 2 effects:
* It opens potassium channels - high concentration inside cell, low concentration outside the cell, so potassium goes out.
* Closes calcium channel so calcium doesn't enter the cell.
* Minimised the conversion of ATP to cAMP.
* Ultimate effect is reduced neurotransmitter release. So, it *dampens* the nervous system.
34
What is the effect of opioids on the cardiovascular system?
* Bradycardia
* Direct action on the SA node
* Direct action on the sympathetic drive
* Decreased sympathetic drive
* Morphine releases histamine
* Causes peripheral vasodilation
* **Overall effect is that patient experiences drop in blood pressure.**
35
What are the actions of opioids on the central nervous system?
* **Analgesia**
* Sedation - might be a good thing, but a problem in prescribing opioids for chronic pain.
* Euphoria - post major trauma this is a good thing but it makes the drug one of misuse and dependence.
* Acts on CN3 and causes pinpoint pupils.
36
What are the actions of opioids on the respiratory system?
* Depresses respiration
* Decrease respiratory rate
* Decrease tidal volume
* This decreases minute volume (blood gas = increased pCo2).
* The effector is the respiratory system but actually the effect of the opioid is on the CNS (it acts on the MOP receptors in the brainstem).
* Anti-tussive action (stops patient coughing) - can be very useful in palliative care (tumour pressing on the lung, or endotracheal tube toleration).
* Morphine releases histamine and can cause wheeze (bronchoconstriction) in vulnerable patients.
37
What are the actions of opioids on the GI tract?
* Delayed motility in the gut.
* Direct action on the chemoreceptor trigger zone.
* Action on the vestibular apparatus.
* **All of these are likely to cause nausea.**
* ****If a patient is on opioids for a prolonged period, they develop tolerance to the nausea, but when starting an opioid you MUST prescribe an antiemetic.
* Constipation
* Continuous laxative
38
What are the other, non-specific effects of opioids?
* Urticaria
* Itch
* Urinary retention
* Immunosuppression - thought to be via natural killer cells.
* Effect on pituitary and hypothalamus hormones (these are the origins of the naturally occuring endogenous opioids)
* Decreased prolactin
* Increased ADH
* Changes to these hormones is likely to be a feedback mechanism.
39
Describe the effect of pharmacogenetics on codeine.
* Codeine is a prodrug - it has no effect until it is metabolised.
* In slow metabolisers you can give them codeine and it is useless. It has no analgesic effect.
* In faster metabolisers, the same dose would equal an overdose.
* **Contraindicated in children because of the pharmacogenetics.**
40
Where are the majority of drugs metabolised?
The liver
41
The majority of drugs are metabolised to the liver.
Give an example of an exception to this.
* **Remifentanil**
* Metabolised by plasma esterases
* So, it has a very short action
* Usually given by infusion
* Usually given as an anaesthetic
42
Describe how morphine is metabolised?
* Metabolised to the liver, but is metabolised to active metabolites which are excreted by the kidney.
* So, if you give morphine to a patient with chronic kidney disease, its effect will be prolonged.
43
What are the markers of opioid toxicity?
* If the patient has:
* Drowsiness
* Pinpoint pupils
* Decreased respiratory rate
* Think about whether the patient is being overdosed with opioids.
44
Describe the effect of an opioid antagonist.
Give an example.
* An antagonist is a drug with a high affinity for the receptor but no intrinsic activity.
* Naloxone will reverse effects of an opioid overdose.
* Naltrexone is an opioid antagonist but is used to maintain people who have got clean from opioids.
* Shorter acting than opioids
* May have to repeat the dose or start a naloxone infusion.
45
What is methadone?
A long-acting opioid
46
Define tolerance.
A physiological state characterised by a decrease in the effects of a drug with chronic administration.
**You need to give increasing dose to get the same effect.**
47
Define dependence.
The drug induces a rewarding experience. Drug takin becomes compulsive.
48
Define withdrawl.
A group of symptoms which occur on cessation of a psychoactive substance that has been taken over a prolonged period. There may be physiological disturbance. Withdrawl indicated dependence.
49
What are the 2 mainstays of treatment for neuropathic pain?
* Tricyclic antidepressants
* Gabapentin / pregabalin
50
Describe the properties of tricyclic antiepressants.
* Primary mechanism of action is pe-synaptic inhibition of NA and 5-HT reuptake.
* Enhances descending inhibition ('damping') of pain in the dorsal horn.
* Analgesic effect is separate from anti-depressant effect.
* Analgesic effects in a few days to a week.
* Anti-depressant effects take 2-4 weeks.
* Small dose (25-75mg) at night.
* Side effects (which often limit use):
* Sedation
* Dry mouth
* Constipation
* Urinary retention
* Contraindicated post MI
51
Describe the properties of gabapentin / pregabalin.
* Primary mechanism of action is via voltage gated calcium channels.
* Thought as a result to disrupt NMDA receptor pain.
* Significant euphoric effects.
* Excreted unchanged in urine so take note if patient has chronic kidney disease.
* Minimal side effects other than drowsiness.
