Cancer Care - Common Symptoms in Cancer Patients

Question 1

Pain

Nociceptive Pain
Neuropathic Pain
Causes of Pain in Cancer Patients
Pain Assessment

Answer 1

1. ) Nociceptive Pain - direct activation of nociceptors in the peripheral somatosensory system
   - somatic: received from skin/bone/muscle, the sensation is a sharp, aching, or throbbing pain
   - visceral: received from internal structures such as the GI tract, the sensation is crampy
2. ) Neuropathic Pain - occurs with an abnormally functioning somatosensory nervous system
   - can be due to lesions: ischaemia, compression, infiltration, metabolic injury, transaction of a nerve
   - or can be due to dysfunction of the nervous system, abnormal signalling magnifies response to a stimulus
   - sensation: burning, tingling, shooting, stabbing, numbness, electric-like sensation
3. ) Causes of Pain in Cancer Patients
   - direct tumour involvement: bone or nerve infiltration
   - cancer therapy: post-surgical pain, post-chemo pain (e.g. peripheral neuropathy), post-radiotherapy pain
   - not related to cancer or cancer therapy
4. ) Pain Assessment - impact of the pain, concerns about pain treatment, subjective scale:
   - 0 = no pain
   - 1-3 = mild pain (little interference with ADLs)
   - 4-6 = moderate pain (interferes significantly w/ ADLs)
   - 7-10 = severe pain (disabling; cannot perform ADLs)

Question 2

Step 1 of the WHO Analgesic Ladder
(Simple Analgesics)

Paracetamol
NSAIDs
Adjuvants

Answer 2

1. ) Paracetamol - never really given on its own, often used as an adjunct for NSAIDs and opioids
   - unknown mechanism of action
   - maximum dose is 4g per day (2x500mg QDS)
   - risk of overdose/hepatotoxicity but needs 20-30 pills
2. ) NSAIDs - inhibits COX enzymes –> ↓production of prostaglandins –> ↓inflammation
   - often the first line as a simple analgesic
   - examples: ibuprofen, naproxen, aspirin, diclofenac
   - side effects: renal impairment, N+V, gastric ulcers or bleeding (if regular, should co-prescribe w/ a PPI)
   - COX-2 selective NSAIDs (celecoxib, etoricoxib) have reduced GI side effects but have increased CVS risk
3. ) Adjuvants - non-analgesics used w/ analgesics to help reduce pain, used in all stages (1, 2, and 3)
   - often used for neuropathic pain: amitriptyline (TCA) gabapentin and pregabalin (anticonvulsants)
   - amitriptyline is contraindicated in arrhythmias and post-MI (during the recovery period)
   - steroids: potentiates analgesia, good for pain caused by compression of nerves or spinal cord or ICP
   - dexamethasone: specifically good for liver mets
   - other adjuvants: anxiolytics, phenothiazines, amphetamines, topical local anaesthetics

Question 3

Opioids

Weak Opioids
Strong Opioids
Side Effects of Opioids
Special Considerations when Prescribing

Answer 3

1. ) Weak Opiates - step 2 of the WHO pain ladder
   - codeine, co-codamol, dihydrocodeine, tramadol
   - can be prescribed with a laxative or anti-emetic
   - opioids are often poor for neuropathic pain, consider early referral to a specialist for neuropathic pain
   - tramadol is a serotonin inducing drug so can lead to serotonin syndrome when used with other serotonin based drugs e.g. SSRIs
2. ) Strong Opiates - step 3 of the WHO pain ladder
   - morphine, diamorphine, oxycodone, fentanyl (TD only)
   - should stop all weak opioids if on strong opioids
   - mild-mod renal impairment (eGFR 10-50): oxycodone is used as it has a quicker onset of action however can still worsen renal failure
   - severe renal impairment (eGFR <10): fentanyl (SL fentanyl can be used in the acute pain setting)
   - should be co-prescribed with a laxative, can co-prescribe an antiemetic (if new to taking the opioid)
3. ) Side Effects
   - constipation: ↓in intestinal peristalsis and secretions, should always co-prescribe a laxative if regular
   - N+V: often transient on initiation, should co-prescribe an anti-emetic on first initiation of an opioid
   - drowsiness/sedation: transient for a few days on initiation, shouldn’t be persistent, advised not to drive on first 5 days or after an increase in dose
   - dry mouth: have cold drinks, avoid sugary drinks
   - opioid toxicity: resp depression, drowsiness, N+V, confusion, hallucinations, pinpoint pupils, jerking, treat with IV naloxone
4. ) Special Considerations
   - renal impairment: use lower doses than normal, stop routine dosing if urine output is minimal or none
   - liver failure: reduce dose or increase dosing interval
   - metabolism is often not affected by liver metastases

Question 4

Morphine Prescribing

General Priniciples
Regular Doses
PRN Doses
Other Drugs/Routes
Controlled Drug Prescription

Answer 4

1. ) General Principles
   - total daily doses (TDD): sum of the number of regular doses and the number of PRN doses over 24hrs
   - round down when calculating PRN dose
2. ) Regular Doses - zomorph (SR morphine sulphate)
   - always taken 2x a day (BD), 12 hours apart
   - SR dose = TDD/2, zomorph only comes in capsules of 10, 30, 60, 100, 200mg, need MST tablets for more flexible doses (5, 10, 15, 30, 60, 100, 200mg)
   - all patients on regular (SR) opioids should have IR opioid (oramorph) for breakthrough pain
3. ) PRN Doses - oramorph (IR morphine sulphate)
   - PRN dose = TDD/6, generally round down
   - can request another PRN dose after just 1 hour
   - consider increasing the routine doses if the patient is using the PRN oramorph 3+ more times a day
   - oramorph comes in liquid form and is 10mg/5ml
   - bottles of oramorph come in 100, 300, 500ml
   - oramorph is also used as PRN in TD fentanyl
   - SC morphine is used as PRN for syringe drivers
4. ) Other Drugs/Routes
   - syringe drivers: are used when PO is not feasible, they deliver SC morphine over 24hrs (not BD)
   - PO morphine (2):(1) SC morphine
   - PO codeine (10):(1) PO morphine
   - TD fentanyl –> PO morphine: the smallest patch is 12mcg/hr which equates to 45mg of morphine in 24hrs
5. ) Controlled Drug Prescription - supply of 2 weeks of opioids on discharge until the GP reviews
   - instructions for patient: take morphine SR (zomorph) 60mg BD for 14 days, take morphine IR (oramorph) 10mg PRN up to 1 hourly for breakthrough pain
   - instructions for pharmacist: supply 28 (twenty-eight) morphine SR (zomorph) 60mg capsules, supply 1 300ml bottle of morphine IR (oramorph)
   - assume oramorph is taken BD for 14 days

Question 5

Nausea and Vomiting

Control of Nausea and Vomiting
Causes of Nausea and Vomiting
Chemotherapy Induced Nausea and Vomiting

Answer 5

1. ) Control of Nausea and Vomiting
   - vomiting centre: receptors (H1, 5HT2, NK1, ACh) triggered by the CTZ, CN VIII nucleus, higher and autonomic centres
   - CTZ: receptors (D2, 5HT3, NK1), triggered by toxins in blood and the CN VIII nucleus
   - vestibulocochlear nucleus: receptors (H1, ACh)
2. ) Causes of Nausea and Vomiting
   - gastric stasis: opioids, ascites, hepatomegaly, post-op
   - chemical/metabolic: due to toxins or electrolyte disturbances e.g. sepsis, renal/liver failure, ↓Na, ↑Ca
   - bowel obstruction: mechanical or functional
   - raised ICP/intracerebral: affects CN VIII nucleus
   - movement disorders: e.g. vertigo, ataxia
   - constipation, post-op, CINV, anxiety
3. ) Chemotherapy-Induced Nausea and Vomiting
   - risk factors: <50yrs, female, past hx of N+V, specific chemo agents, (smoking is a protective factor)
   - Mx: ondansetron (5HT3), aprepitant (NK1) and dexamethasone, metoclopramide (often backup)

Question 6

Anti-Emetics

Metoclopramide 
Haloperidol 
Cyclizine 
Ondansetron 
Levomepromazine 
Dexamethasone

Answer 6

1. ) Metoclopramide - D2 (++), 5HT3 (+), PO/SC/IV
   - prokinetic: increases gastric emptying by ↑tone at LOS and ↓tone at pyloric sphincter
   - usage: gastric stasis, partial/functional obstruction, constipation (alongside laxatives) and chemical N+V
   - dose: PO/SC 10mg TDS + PRN
   - contraindicated in Parkinson’s due to EPSE
2. ) Haloperidol - D2 (+++), PO/SC/IM
   - best used to treat chemically/metabolically induced vomiting as it acts on D2 receptors in the CTZ (toxins)
   - dose: 0.5-1.5mg nocte + PRN
   - contraindicated in Parkinson’s due to EPSE
   - D2 antagonists: prochlorperazine, domperidone (safe in Parkinson’s as it doesn’t cross the BBB)
3. ) Cyclizine - H1 (+++), ACh (+), PO/SC/IV
   - acts on H1 receptors in the vomiting centre and the CNVIII nucleus as well as vagally-mediated N+V
   - mechanical bowel obstruction: vagally mediated
   - raised ICP/intracerebral: CN VIII affected in raised ICP
   - movement disorders: CN VIII
   - used 2nd line for post-op N+V (unable to use ondansetron)
   - dose: PO 50mg BD-TDS, syringe driver in obstruction
   - side effects: drowsiness and anti-muscarinic SEs
4. ) Ondansetron - 5HT3 (+++), PO/IV
   - prevents serotonin exciting enteric neurones which ↓GI motility/peristalsis and ↓GI secretions
   - usage: post-op, chemo/radiotherapy-induced N+V
   - side effects: constipation, headache, ↑LFTs, QT prolongation, extra-pyramidal effects
   - avoid in migraines as triptans use HT3 receptors
5. ) Levomepromazine - 5HT2 (+++), (D2+, ACh+, H1+)
   - can be used orally or SC as an infusion
   - best used in end of life care as it is sedating
6. ) Dexamethasone - reduces inflammation/swelling
   - mainly oral but can also be given in a SC infusion
   - used alongside cyclizine for raised ICP N+V as well as N+V due to bowel obstruction
   - can affect circadian rhythm so avoid past 6pm

Question 7

Constipation

Causes
Clinical Features
Management

Answer 7

1. ) Causes
   - drugs: opioids, antimuscarinics, antacids
   - secondary effects of disease: dehydration, inactivity, ↓fibre, delirium, MSCC, lack of privacy
   - direct effects of malignant tumours: nerve damage, bowel obstruction, hypercalcaemia
2. ) Clinical Features
   - unsatisfactory defecation due to infrequent stools, difficult stool passage or tenesmus
   - stools are often dry and hard, may be abnormal size
   - associated sx: abdominal pain and distension, N+V, flatulence, overflow diarrhoea, anorexia, malaise, and distress or worsening confusion
   - must exclude: faecal impaction, bowel obstruction, anal fissures, painful haemorrhoids, local tumours
3. ) Management
   - alleviate contributing factors: impaction, poor diet, dehydration, having to use a bedpan, lack of privacy, anal fissure, painful haemorrhoids, or local tumour
   - prevention: stimulant laxative (Senna) should be prescribed alongside constipating agents (opioids)
   - 1°: stimulant laxative e.g. Senna
   - 2°: add an osmotic (Macrogol/Lactulose) OR stool softener (docusate sodium)
   - 3°: rectal treatment via suppository or enema

Question 8

Malignant Bowel Obstruction

Pathophysiology
Operable Bowel Obstruction
Inoperable Bowel Obstruction

Answer 8

1. ) Pathophysiology - often a gradual onset and a combination of mechanical and functional obstruction
   - mechanical: tumour w/in lumen or outside bowel wall
   - functional: infiltration of myenteric plexus
   - more common in bowel and ovarian cancer
2. ) Operable Bowel Obstruction
   - surgical intervention: has high morbidity/mortality
   - endoscopic stenting, venting gastrostomy
   - cautious use of pro-kinetic may help partial or functional obstruction
3. ) Inoperable Bowel Obstruction
   - rest bowel initially to see if it will resolve: limit oral fluids, give IV hydration, NG tube for large vomiting
   - correct electrolyte imbalances (↓K, ↓Mg)
   - analgesics, anti-emetics, anti-secretory drugs (octreotide - somatostatin analogue)
   - hyoscine butylbromide can be used for bowel colic caused by bowel obstruction
   - trial of dexamethasone
   - not resolving: syringe driver, prognosis will be weeks to months

Question 9

Intractable Breathlessness

Pathophysiology
General Management
Medical Management

Answer 9

1. ) Pathophysiology - breathlessness is an objective sign, whereas dyspnoea is a subjective symptom
   - direct causes: primary lung cancer or lung mets
   - indirect effects of cancer: anaemia, pleural effusion, PE, SVCO, surgery
   - non-malignant causes: pneumonia, COPD, heart failure, and anxiety (major part of dyspnoea)
2. ) General Management
   - simple measures: relaxation and breathing techniques, keep the room cool (fan, open window)
   - encourage exercise within the person’s capabilities
   - adaptations of ADLs and lifestyle expectations
3. ) Medical Management - these can be considered
   - low dose IR morphine e.g. oramorph 1-2mg PRN
   - short term benzo: SL lorazepam or SC midazolam
   - bronchodilator if wheeze is thought to be caused by partial airway obstruction from a tumour
   - oxygen therapy: if at risk of symptomatic hypoxia

Question 10

Signs of Impending Death

Cardiac and Circulatory Changes
Respiratory Changes
GI/GU Changes
General Changes

Answer 10

1. ) Cardiac and Circulatory Changes
   - skin mottling/discolouration: ↓blood perfusion
   - ↓consciousness/delirium: ↓cerebral perfusion
   - ↓CO: ↓ BP, ↑HR, central/peripheral cyanosis
2. ) Respiratory Changes
   - noisy respirations: due to retention of secretions in the pharynx and the upper respiratory tract
   - Cheyne-Stokes respirations: notable changes in breathing, reassure families that this is normal
3. ) GI/GU Changes
   - ↓appetite: weight loss, dehydration, do not need to force food or fluids, provide good mouth care
   - swallowing difficulties: stop feeding if choking
   - ↓urine output: may have urinary incontinence
4. ) General Changes
   - prolonged drowsiness, sleeping more due to profound weakness and fatigue, this is normal
   - become more withdrawn and detached from surroundings due to disorientation
   - hallucinations: may see or speak to things, normal
   - pressure ulcers from being bedbound

Question 11

Anticipatory Medicines for End of Life Care

General Information
Pain and/or Breathlessness
Anxiety, Agitation, and Seizures
Nausea+Vomiting, Hallucinations
Respiratory Secretions

Answer 11

General Information
- involve patients and relatives in discussions early
- stop any medications that have no benefit
- switch essential medications to non-oral routes
- most drugs given through a syringe driver
- always use the lowest effective dose

1. ) Pain and/or Breathlessness
   - SC infusion of morphine for regular pain
   - SC PRN (1hrly) morphine 2.5-5mg 1hrly
2. ) Anxiety, Agitation, and Seizures
   - SC PRN (1hrly) midazolam 2.5-5mg
   - can give SC infusion of an anti-epileptic if suffering from seizures already
3. ) Nausea+Vomiting, Hallucinations
   - SC PRN (4hrly) Levomepromazine 2.5-5mg
4. ) Respiratory Secretions
   - SC PRN (4hrly) glycopyyronium 200-400mcg
   - can be aided by sitting the patient up
   - alternative is hyoscine butylbromide (hyoscine hydrobromide causes sedative effects)
   - hyoscine butylbromide is also used in bowel colic which may occur from bowel obstruction

Intractable Hiccups - 1°chlorpromazine OR haloperidol, gabapentin, dexamethasone is also used particularly if there are hepatic lesions