BASIC - PAIN & PALLIATIVE CARE Flashcards
Name of strong opioids?
Morphine, diamorphine, Oxycodone
4 indications for strong opioids?
- 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)
Mechanism of action for strong opioids?
How is oxycodone different?
- 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
Adverse effects of strong opioids?
o Nausea and vomiting o Constipation o Pupillary constriction o Skin – itching, vasodilation, sweating o Respiratory depression o Neurological depression
Can you develop tolerance and dependence in strong opioids?
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
Symptoms of toxicity in strong opioids?
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)
When should dose reduction be done in strong opioids? What caution must you have?
- Dose reduction in hepatic failure and renal impairment and in elderly
- Do not give in respiratory failure except in palliative care
Avoid strong opioids when? Why?
- Avoid in biliary colic – may cause spasm in sphincter of Oddi (use pethidine)
What other drugs should you avoid ideally with strong opioids?
- Ideally avoid with other sedating drugs (antipsychotics, benzodiazepines, TCAs)
Route of administration of strong opioids in acute and chronic setting?
o In acute setting – given IV
o Chronic pain – oral, IM, SC available
What is oral morphine available as?
- 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
When would modified release morphine be used?
o Modified release morphine prescribed in regular treatment
What is an appropriate dose of MR morphine? When would the dose be reduced?
How much % increase needed if not adequate?
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
For breakthrough pain, how much IR morphine given?
1/10-1/6 of the total daily regular dose in the PRN
What names would you use in prescription?
Brand name prescribing for strong oral opioids
What needs communicating to patient? (4)
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
When would you review strong opioid prescription?
o Review in 1-2 weeks to assess effectiveness
When given parenternally, what is the potency of MS and diamorphine?
What dose should be given of diamorphine then?
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
Which strong opioids are given transdermally?
What do they look like?
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
When oxycodone used, what are the MR and IR names?
• Immediate release (oxynorm) and slow release (oxycontin)
Name of weak opioids?
Codeine, co-codamol, dihydrocodeine
Indications of weak opioids?
- Step 2 on WHO analgesic ladder when simple analgesia (paracetamol) is insufficient
Metabolism of weak opioids? Mechanism of weak opioids? Why is codeine sometimes not effective?
Tramadol is what?
- 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
Side effects of weak opioids?
- Nausea
- Constipation
- Dizziness
- Drowsiness
- Neurological and respiratory depression
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)
Contraindications of weak opioids?
- NEVER GIVE CODEINE OR DIHYDROCODEINE IV – histamine anaphylaxis
- Acute respiratory depression, comatose patients
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
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
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
Review of weak opioids?
- Review after 1-2 weeks and assess need to move up and down ladder
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
Indications of paracetamol?
- 1st line analgesic for acute and chronic pain
- Antipyretic
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)
Adverse effects of paracetamol?
Few
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)
Dose reduction in paracetamol?
- Dose reduced in liver toxicity
Cautions about use of paracetamol?
o Chronic excessive alcohol use
o Malnutrition
o Low body weight
o Hepatic impairment
Which drugs increase rate of NAPQI production in overdose?
- CYP450 inducers
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
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
Typical paracetamol dose?
0.5-1g every 4-6 hours, maximum 4g per day
Name of NSAIDs
Ibuprofen, diclofenac, etoricoxib
Indications of NSAIDs?
- PRN for mild-to-moderate pain
- Regular treatment of pain related inflammation
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
SE of NSAIDs?
- GI toxicity
- Renal impairment
- Increased risk of MI/CVA
- Fluid retention
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
Contraindications of NSAIDs
o Severe renal impairment
o Heart Failure
o Liver failure
Cautions of NSAIDs in prior history of?
o Peptic ulcer disease
o GI bleeds
o CVD
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
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
Names of antimuscarinics? (antispasmodics)
Hyoscine butylbromide (Buscopan)
Indications of antimuscarinics?
- IBS
- Colicky pain in cancer
- Palliative care - Reduce copious respiratory secretions (death rattle)
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
SE of antimuscarinics?
- Tachycardia
- Dry mouth
- Constipation
- Urinary retention
- Blurred vision
Contraindications of antimuscarinics?
Avoid
- GI obstruction
- Urinary retention
- Arrhythmias
Cautions in antimuscarinics?
Caution
- Angle-closure glaucoma
Interactions of antimuscarinics?
- Adverse effects enhanced with other antimuscarinics e.g. TCAs
How are antimuscarinics given?
- Usually given SC, either by injection or syringe driver
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
Name of 5-HT antagonist antiemetics?
Ondansetron, granisetron
Indications of 5-HT antagonists?
- Nausea and vomiting – prophylaxis and treatment
- Particularly chemotherapy
Mechanism of 5-HT antagonists?
- 5-HT3 antagonists in the CTZ and gut
- Particularly good at stopping emetogenic substances in blood causing nausea
SE of 5-HT antagonists?
- Constipation, diarrhoea, headaches
Contraindications of 5-HT antagonists?
- Prolonged QT interval
Which drugs should be avoided and why?
Avoid in drugs that prolong QT interval:
- Antipsychotics, amiodarone, ciprofloxacin, macrolides, quinine, SSRIs
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
Names of phenothiazine antiemetics?
Levomepromazine, prochlorperazine
Indications of phenothiazine antiemetics?
- Nausea and vomiting treatment and prophylaxis
- First generation antipsychotic
Mechanisms of phenothiazine antiemetics?
- Blockage of D2 receptors in CTZ and gut, H1 and Ach in vomiting centre and vestibular system
SE of phenothiazine antiemetics?
- Drowsiness
- Postural hypotension
- Extrapyramidal syndromes – acute dystonic reaction and tardive dyskinesia
- Prolong QT interval
Contraindications of phenothiazine antiemetics?
o Severe liver disease
o Prostatic hypertrophy
Which drugs should be avoided and why?
- Drugs that prolong QT interval
o Antipsychotics, amiodarone, ciprofloxacin, macrolides, quinine, SSRIs
When is this prescribed? What monitoring is needed?
Prescribing - Specialist advice usually needed Monitoring - Prolactin baseline and 6 months, then yearly - EPSE
Typical dose of levomepromzine?
Oral - 6mg OD at bed
Syringe Driver - 5-25mg/24 hours
Names of H receptor antagonists antiemetics?
Cyclizine, promethazine
Indications of H antagonists?
- Prophylaxis and treatment of nausea and vomiting
o Palliative care – cerebral and cerebellar problems
o Motion sickness and vertigo
Mechanism of H antagonists?
- Blockage of the Histamine-1 and acetylcholine receptors predominate in vomiting centre and communication with vestibular system
SE of H antagonists?
- Drowsiness (cyclizine least drowsy)
- Anticholinergic – dry mouth, throat, blurred vision, constipation
- IV - tachycardia
Contraindications of H antagonists?
- Hepatic encephalopathy
- Prostatic hypertrophy (develop urinary retention)
Interactions with H antagonists?
- Sedation – benzodiazepines, opioids
- Anticholinergics increased with ipratropium or tiotropium
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
Name of dopamine antagonists antiemetics?
Metoclopramide, domperidone
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
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
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
Contraindications of dopamine antagonist antiemetics?
- Children and young adults
- Parkinson’s (Metoclopramide)
- Gastrointestinal obstruction/perforation, 3-4 days after GI surgery
Caution in dopamine antagonist antiemetics?
- Reduce dose in renal and hepatic impairment
Interactions of dopamine antagonists antiemetics?
- Risk of EPSE increased with antipsychotics
- Do not combine with dopaminergic agents for Parkinson’s - antagonise
Prescription of dopamine antagonist antiemetics?
o Short term use – 5 days
o Dose 10mg up to TDS
o Metoclopramide available IV/IM and orally
What monitoring should be done in dopamine antagonists antiemetics?
o Monitor extrapyramidal symptoms if prolonged use
Name of neuropathic agents?
Gabapentin, pregabalin
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)
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
SE of gabapentin/pregabalin?
- Drowsiness
- Dizziness
- Ataxia
- Usually improve over first few weeks
When is dose reduction needed in gabapentin/pregabalin?
- Dose reduced in renal impairment
Interactions of gabapentin/pregabalin?
- Sedative effects enhanced when combined with sedating drugs (benzos)
Prescription of gabapentin/pregabalin?
- Oral, start at low dose and increase over weeks
- Appropriate escalating-dose regimens are listed in the BNF
What to avoid when on gabapentin/pregabalin?
- Avoid driving or operating machinery until confident side effects have settled
