BASIC - PAIN & PALLIATIVE CARE Flashcards
1
Q
Name of strong opioids?
A
Morphine, diamorphine, Oxycodone
2
Q
4 indications for strong opioids?
A
- Acute pain relief – ACS, post-operative
- Chronic pain relief – Step 3 of ladder
- Relieve breathlessness in palliative care
- Acute pulmonary oedema (along with oxygen, furosemide, nitrates)
3
Q
Mechanism of action for strong opioids?
How is oxycodone different?
A
- Activation of opioid u (mu) receptors in CNS
- Reduces neuronal excitability and pain transmission
- In medulla – blunt response to hypoxia and hypercapnoea – reducing respiratory drive
- Reduce SNS activity
- Oxycodone is synthetic analogues of morphine
4
Q
Adverse effects of strong opioids?
A
o Nausea and vomiting o Constipation o Pupillary constriction o Skin – itching, vasodilation, sweating o Respiratory depression o Neurological depression
5
Q
Can you develop tolerance and dependence in strong opioids?
A
o Tolerance does develop and may need to higher the dose over time o Dependence apparent with cessation Anxiety, pain, breathlessness Dilated pupils, skin cool and dry o Not a problem in therapeutic doses
6
Q
Symptoms of toxicity in strong opioids?
A
o Persistent nausea and vomiting o Drowsiness o Confusion o Visual Hallucinations o Myoclonic jerks o Respiratory Depression o Pinpoint pupils (not always useful if on long term)
7
Q
When should dose reduction be done in strong opioids? What caution must you have?
A
- Dose reduction in hepatic failure and renal impairment and in elderly
- Do not give in respiratory failure except in palliative care
8
Q
Avoid strong opioids when? Why?
A
- Avoid in biliary colic – may cause spasm in sphincter of Oddi (use pethidine)
9
Q
What other drugs should you avoid ideally with strong opioids?
A
- Ideally avoid with other sedating drugs (antipsychotics, benzodiazepines, TCAs)
10
Q
Route of administration of strong opioids in acute and chronic setting?
A
o In acute setting – given IV
o Chronic pain – oral, IM, SC available
11
Q
What is oral morphine available as?
A
- Normal/Immediate release tablets and liquid – lasts 4 hours e.g. Oramorph
- Modified/Slow release tablets, granules, capsules – lasts 12 hours e.g. morphine sulphate tablets (MSTs), Zomorph capsules
12
Q
When would modified release morphine be used?
A
o Modified release morphine prescribed in regular treatment
13
Q
What is an appropriate dose of MR morphine? When would the dose be reduced?
How much % increase needed if not adequate?
A
Dose usually MST 20mg bd appropriate as Step 3
• Elderly, frail or renal impairment patients (fentanyl used in renal excretion) may need lower doses
• Titrate dose up by 30-50% increments to relieve pain
14
Q
For breakthrough pain, how much IR morphine given?
A
1/10-1/6 of the total daily regular dose in the PRN
15
Q
What names would you use in prescription?
A
Brand name prescribing for strong oral opioids
16
Q
What needs communicating to patient? (4)
A
o Explain that it is a highly effective painkiller and that ‘addiction’ is not an issue when it is used for pain control
o Warn patients that the dose may need to be increased over time as they become tolerant to its effects; this is normal and should not cause alarm
o Offer antiemetic (metoclopramide) and laxative (co-danthrusate or movicol)
o Do not operate heavy machinery or drive if feel drowsy or confused
17
Q
When would you review strong opioid prescription?
A
o Review in 1-2 weeks to assess effectiveness
18
Q
When given parenternally, what is the potency of MS and diamorphine?
What dose should be given of diamorphine then?
A
Parenteral diamorphine 3 times more potent than oral morphine
Parenteral MS is 2 times more potent
Total 24-hour SC continuous infusion diamorphine dose should be 1/3 of total 24-hour oral morphine dose
19
Q
Which strong opioids are given transdermally?
What do they look like?
A
o Fentanyl transdermal patches last 72 hours (can have buprenorphine patches)
Suitable for severe chronic pain already stabilised on other opioids
Buprenorphine looks like plaster and fentanyl is clear patch
20
Q
When oxycodone used, what are the MR and IR names?
A
• Immediate release (oxynorm) and slow release (oxycontin)
21
Q
Name of weak opioids?
A
Codeine, co-codamol, dihydrocodeine
22
Q
Indications of weak opioids?
A
- Step 2 on WHO analgesic ladder when simple analgesia (paracetamol) is insufficient
23
Q
Metabolism of weak opioids? Mechanism of weak opioids? Why is codeine sometimes not effective?
Tramadol is what?
A
- Metabolised in liver to produce small amounts of morphine (from codeine) or dihydromorphine (dihydrocodeine)
- Agonists of opioid u (mu) receptors
- 10% of Caucasians has less active form of key metabolising enzyme (CYP450 2D6) so may be ineffective
- Tramadol is synthetic analogue of codeine, also a 5-HT and NA reuptake inhibitor – not a great drug
24
Q
Side effects of weak opioids?
A
- Nausea
- Constipation
- Dizziness
- Drowsiness
- Neurological and respiratory depression
25
Interactions of weak opioids? When should tramadol not be used?
- Ideally do not combine opioids and other sedating drugs (antipsychotics, benzodiazepines, TCAs)
- Tramadol should not be used with drugs that lower seizure threshold (SSRIs, TCAs)
26
Contraindications of weak opioids?
- NEVER GIVE CODEINE OR DIHYDROCODEINE IV – histamine anaphylaxis
- Acute respiratory depression, comatose patients
27
When are weak opioids used in caution and dose reduction necessary?
- Both renal and hepatic impairment – dose reduction
| - Tramadol lowers seizure threshold – caution in epilepsy
28
Prescription of weak opioids? Typical codeine starting dose?
| Any other considerations?
- Can be prescribed orally, IM
- Starting dose – codeine 30mg orally 4-hourly
- Consider prescribing laxative (Senna) for regular administration
- Should be withdrawn gradually to avoid symptoms
29
Communication to patient about weak opioids?
- Advise patients to avoid driving or operating heavy machinery if they become drowsy or confused while taking the new painkiller
- Mention that painkillers should always be stored out of reach of children
30
Review of weak opioids?
- Review after 1-2 weeks and assess need to move up and down ladder
31
What strengths does co-codamol come in? Typical starting dose of Step 2 on WHO ladder?
- Co-codamol comes in 3 strengths:
o 8mg codeine and 500mg paracetamol
o 15mg codeine and 500mg paracetamol
o 30mg codeine and 500mg paracetamol
- Prescribe codeine 30mg when progressing from ‘Step 1’
- Paracetamol can be given with opioids too
32
Indications of paracetamol?
- 1st line analgesic for acute and chronic pain
| - Antipyretic
33
Mechanism of paracetamol?
- Weak cyclooxygenase (COX) inhibitor, involved in prostaglandin metabolism
- Increase pain threshold and reduce (PGE2) concentrations in thermoregulatory region, controlling fever
- Specifically, COX-2 isoform (inflammation) rather than COX-1 isoform (protecting gastric mucosa, regulating renal blood flow and clotting)
34
Adverse effects of paracetamol?
Few
35
Normal metabolism of paracetamol? What happens in overdose of paracetamol? Treated with?
- Overdose – liver failure
o Metabolised by CYP450 enzymes to toxic N-acetyl-p-benzoquinone imine (NAPQI) which is conjugated with glutathione before elimination
o NAPQI accumulation causes hepatocellular necrosis
o Treated with acetylcysteine (depending on plasma paracetamol level, <12 hours and not vomiting) and activated charcoal (if <4 hours)
36
Dose reduction in paracetamol?
- Dose reduced in liver toxicity
37
Cautions about use of paracetamol?
o Chronic excessive alcohol use
o Malnutrition
o Low body weight
o Hepatic impairment
38
Which drugs increase rate of NAPQI production in overdose?
- CYP450 inducers
39
Prescription of paracetamol?
- Oral paracetamol can be purchased in retail outlets
- Regular administration or PRN
- Available as tablets, caplets, capsules, soluble tablets or oral suspensions
- IV is possible
40
Communication to patient about paracetamol?
| When should effects be felt?
- Effects should be felt around half an hour after taking it
- Warn them not to exceed the recommended maximum daily dose because of the potential risk of liver poisoning
- Advise them that many medicines purchased from the chemist (e.g. cold and flu preparations) contain paracetamol
- Warn them to check the label
41
Typical paracetamol dose?
0.5-1g every 4-6 hours, maximum 4g per day
42
Name of NSAIDs
Ibuprofen, diclofenac, etoricoxib
43
Indications of NSAIDs?
- PRN for mild-to-moderate pain
| - Regular treatment of pain related inflammation
44
Mechanism of NSAIDs?
| How is etoricoxib different?
- Inhibit synthesis of prostaglandins from arachidonic acid by inhibiting cyclooxygenase (COX
- COX-1 stimulates prostaglandin synthesis essential to preserve gastric mucosa, maintain renal perfusion (by dilating afferent glomerular arterioles) and inhibit thrombus formation at the vascular endothelium
- COX-2 expressed in response to inflammatory stimuli stimulates production of prostaglandins that cause inflammation and pain
- Therapeutic benefits of NSAIDs are principally COX-2 inhibition and adverse effects by COX-1 inhibition
- Selective COX-2 inhibitors (e.g. etoricoxib) developed to reduce the adverse effects
45
SE of NSAIDs?
- GI toxicity
- Renal impairment
- Increased risk of MI/CVA
- Fluid retention
46
Interactions of NSAIDs in:
GI ulceration
GI bleed
Renal impairment
```
- GI Ulceration
o Aspirin, corticosteroid
- GI bleeding
o Anticoagulants, SSRIs, venlafaxine
- Renal Impairments
o ACEi, diuretics
```
47
Contraindications of NSAIDs
o Severe renal impairment
o Heart Failure
o Liver failure
48
Cautions of NSAIDs in prior history of?
o Peptic ulcer disease
o GI bleeds
o CVD
49
Prescription of NSAIDs?
- Available as tablets, suspensions, gels, suppositories, injectable
- Acute pain treatment should be stopped when resolved
- Taken with food to minimise GI upset
50
Communication to patients about NSAIDs?
Any time you should stop NSAIDs?
What other meds could be prescribed?
- Warn patients that the most common side effect is indigestion and advise them to stop treatment and seek medical advice if this occurs
- For patients with acute pain, explain that long-term use, e.g. beyond 10 days, is not recommended due to the risk of side effects
- Advise patients requiring long-term treatment (particularly if they have renal impairment) to stop NSAIDs if they become acutely unwell or dehydrated to reduce the risk of damage to the kidneys
- Can use gastroprotection for patients at increased risk
51
Names of antimuscarinics? (antispasmodics)
Hyoscine butylbromide (Buscopan)
52
Indications of antimuscarinics?
- IBS
- Colicky pain in cancer
- Palliative care - Reduce copious respiratory secretions (death rattle)
53
Mechanism of antimuscarinics?
| What are the effects?
- Competitive inhibitor of Ach
- Blocks the parasympathetic ‘rest and digest’ effects so:
o Increase HR and conduction
o Reduces smooth muscle tone
o Reduces peristaltic contraction
o Relax pupillary constrictor and ciliary muscles preventing accommodation
54
SE of antimuscarinics?
- Tachycardia
- Dry mouth
- Constipation
- Urinary retention
- Blurred vision
55
Contraindications of antimuscarinics?
Avoid
- GI obstruction
- Urinary retention
- Arrhythmias
56
Cautions in antimuscarinics?
Caution
| - Angle-closure glaucoma
57
Interactions of antimuscarinics?
- Adverse effects enhanced with other antimuscarinics e.g. TCAs
58
How are antimuscarinics given?
- Usually given SC, either by injection or syringe driver
59
Typical hyoscine dose in palliative care?
SC 20mg every 4 hours PRN, can be adjusted up to 20mg every hour
Syringe driver - 20-120mg/24 hours
60
Name of 5-HT antagonist antiemetics?
Ondansetron, granisetron
61
Indications of 5-HT antagonists?
- Nausea and vomiting – prophylaxis and treatment
| - Particularly chemotherapy
62
Mechanism of 5-HT antagonists?
- 5-HT3 antagonists in the CTZ and gut
| - Particularly good at stopping emetogenic substances in blood causing nausea
63
SE of 5-HT antagonists?
- Constipation, diarrhoea, headaches
64
Contraindications of 5-HT antagonists?
- Prolonged QT interval
65
Which drugs should be avoided and why?
Avoid in drugs that prolong QT interval:
| - Antipsychotics, amiodarone, ciprofloxacin, macrolides, quinine, SSRIs
66
Prescription of 5-HT antagonists?
- Oral, rectal or IV administration - 8mg BDS for 5 days starting before chemotherapy
- Dose to be taken an hour before symptoms anticipated if oral (IV immediately)
- Expensive so only used for chemotherapy N&V
67
Names of phenothiazine antiemetics?
Levomepromazine, prochlorperazine
68
Indications of phenothiazine antiemetics?
- Nausea and vomiting treatment and prophylaxis
| - First generation antipsychotic
69
Mechanisms of phenothiazine antiemetics?
- Blockage of D2 receptors in CTZ and gut, H1 and Ach in vomiting centre and vestibular system
70
SE of phenothiazine antiemetics?
- Drowsiness
- Postural hypotension
- Extrapyramidal syndromes – acute dystonic reaction and tardive dyskinesia
- Prolong QT interval
71
Contraindications of phenothiazine antiemetics?
o Severe liver disease
| o Prostatic hypertrophy
72
Which drugs should be avoided and why?
- Drugs that prolong QT interval
| o Antipsychotics, amiodarone, ciprofloxacin, macrolides, quinine, SSRIs
73
When is this prescribed? What monitoring is needed?
```
Prescribing
- Specialist advice usually needed
Monitoring
- Prolactin baseline and 6 months, then yearly
- EPSE
```
74
Typical dose of levomepromzine?
Oral - 6mg OD at bed
| Syringe Driver - 5-25mg/24 hours
75
Names of H receptor antagonists antiemetics?
Cyclizine, promethazine
76
Indications of H antagonists?
- Prophylaxis and treatment of nausea and vomiting
o Palliative care – cerebral and cerebellar problems
o Motion sickness and vertigo
77
Mechanism of H antagonists?
- Blockage of the Histamine-1 and acetylcholine receptors predominate in vomiting centre and communication with vestibular system
78
SE of H antagonists?
- Drowsiness (cyclizine least drowsy)
- Anticholinergic – dry mouth, throat, blurred vision, constipation
- IV - tachycardia
79
Contraindications of H antagonists?
- Hepatic encephalopathy
| - Prostatic hypertrophy (develop urinary retention)
80
Interactions with H antagonists?
- Sedation – benzodiazepines, opioids
| - Anticholinergics increased with ipratropium or tiotropium
81
Prescription of H antagonists? Typical dose?
| What communication is needed?
- Given orally, IV, IM
- Typical prescription 50mg 8-hourly PRN (syringe driver 150mg/24 hours)
- Communication
o May affect driving and skills tasks
82
Name of dopamine antagonists antiemetics?
Metoclopramide, domperidone
83
Indications of dopamine antagonist antiemetics?
- Prophylaxis and treatment of nausea and vomiting in reduced gut motility
- Palliative care – Nausea and vomiting due to gastric stasis and irritation, hiccups
84
Mechanism of dopamine antagonist antiemetics?
- D2 receptor is main receptor in chemoreceptor trigger zone (CTZ)
- Dopamine promotes relaxation of stomach and LOS and inhibits gastroduodenal coordination
- Blocking D2 has prokinetic effect
85
SE of dopamine antagonist antiemetics?
| Why does domperidone not have some of these effects?
- Diarrhoea
- Metoclopramide
o Extrapyramidal syndromes – acute dystonic reaction (facial and skeletal muscle spasms)
o Galactorrhoea, gynaecomastic
- Domperidone does not cross BBB
86
Contraindications of dopamine antagonist antiemetics?
- Children and young adults
- Parkinson’s (Metoclopramide)
- Gastrointestinal obstruction/perforation, 3-4 days after GI surgery
87
Caution in dopamine antagonist antiemetics?
- Reduce dose in renal and hepatic impairment
88
Interactions of dopamine antagonists antiemetics?
- Risk of EPSE increased with antipsychotics
| - Do not combine with dopaminergic agents for Parkinson’s - antagonise
89
Prescription of dopamine antagonist antiemetics?
o Short term use – 5 days
o Dose 10mg up to TDS
o Metoclopramide available IV/IM and orally
90
What monitoring should be done in dopamine antagonists antiemetics?
o Monitor extrapyramidal symptoms if prolonged use
91
Name of neuropathic agents?
Gabapentin, pregabalin
92
Indications of gabapentin/pregabalin?
- Focal epilepsies (if carbamazepine and other antiepileptics not adequate)
- Neuropathic pain (diabetic nephropathy, palliative/cancer neuropathic pain)
- Migraine prophylaxis (Gabapentin)
- GAD (pregabalin)
93
Mechanism of gabapentin/pregabalin?
- Gabapentin is closely related to GABA neurotransmitter
- Binds to voltage-sensitive calcium (Ca2+) channels, preventing inflow of Ca and neurotransmitter release
- Reduces neuronal excitability
- Pregabalin is structural analogue of gabapentin
94
SE of gabapentin/pregabalin?
- Drowsiness
- Dizziness
- Ataxia
- Usually improve over first few weeks
95
When is dose reduction needed in gabapentin/pregabalin?
- Dose reduced in renal impairment
96
Interactions of gabapentin/pregabalin?
- Sedative effects enhanced when combined with sedating drugs (benzos)
97
Prescription of gabapentin/pregabalin?
- Oral, start at low dose and increase over weeks
| - Appropriate escalating-dose regimens are listed in the BNF
98
What to avoid when on gabapentin/pregabalin?
- Avoid driving or operating machinery until confident side effects have settled
