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Question 1

risk factors for CINV

Answer 1

• younger age < 50 yo
• female
• low prior chronic alcohol intake (< 1 glass/day)
• history of motion sickness
• history of emesis during previous pregnancy
• anxiety

Question 2

CINV combinations

Answer 2

1) high emetogenic risk
- acute: NK1 + 5HT3 + DEXA +/- OLA
- delayed: DEXA d2-4 or ola if used

2) moderate emetogenic risk
- acute: 5HT3 + DEXA
- delayed: DEXA d2-3

3) low emetogenic risk
- acute: 5HT3 or DEXA or DOPA
- no delayed

Question 3

NK1 antagonist

Answer 3

1) types
- Aprepitant (day 1 PO 125mg OD, day 2, 3 PO 80mg OD)

2) MOA
- act on NK-1 receptor, prevent substance P from binding
- attenuate vagal afferent signals and exert antiemetic effect

3) AE
- low frequency fatigue, weakness, N, hiccups

4) DI
- CYP3A4 inhibitor (steroids, warfarin, benzodiazepine, some chemo like ifosfamide)

Question 4

5HT3 antagonist

Answer 4

1) types
- IV/PO ondansetron (day 1 8-16mg, day 2 onwards 8mg BD, max 18mg/dose)
- IV/PO ganisetron (day 1 1mg OD, day 2 onwards 1mg OM)
- IV/PO palonosetron (combine with NK-1 detupitant on d1)

2) AE
- headache and constipation
- black box warning for constipation

Question 5

NK1 + 5HT3 antagonist combination

Answer 5

1) Akynzeo
- netupitant 300mg + palonosetron 0.5mg
- day 1 PO 1 caps OD
- single-dose convenience, superior delayed CINV prevention, fewer drug interactions

2) apreptiant + 5HT3 antagonist
- aprepitant 3d (125mg d1, 80mg d2-3) + 5HT3 on d1
- more flexible choices
- lower cost

Question 6

dexamethasone

Answer 6

1) MOA
- unknown, partially due to activity in central nervous system

2) dose
- d1: IV/PO 12mg OD
- d2 onwards: 8mg for highly emetogenic

3) AE
- transient elevation in glucose, insomnia, anxiety, gastric upset (w/after food)
- less common: psychosis, ulcer reactivation

Question 7

dopamine antagonist

Answer 7

1) MOA
- block DA receptor in chemoreceptor trigger zone
- stimulate anticholinergic activity in gut
- increase gut motility
- antagonism of peripheral serotonin receptors in intestine

2) dose
- IV/PO metoclopramide 10mg TDS PRN

3) AE
- mild sedation and diarrhoea, EPSE
- avoid prescribing with olanzapine

4) others
- more for breakthrough CINV
- domperidone block peripheral, metoclopramide block central

Question 8

olanzapine

Answer 8

1) MOA
- antagonist of multiple receptors involved in CINV (DA, 5HT, hist, cholinergic)

2) dose
- 5-10mg OD
- lower dose (2.5mg OD) for elderly

3) AE
- fatigue, sedation, postural hypotension, anticholinergic SE

Question 9

benzodiazepine

Answer 9

1) MOA
- bind to benzodiazepine receptors in postsynaptic GABA neuron to enhance inhibitory effect of GABA
- leads to sedation, reduce anxiety, depression of vomiting centre

2) dose
- alprazolam 0.5-1mg
- lorazepam 0.5-2mg
- night before treatment, 1-2 hrs before chemotherapy begins

3) AE
- drowsiness, dizziness, hypotension, anterograde amnesia, paradoxical reactions (hyperactive, aggressive behaviour)
- caution falls in elderly

4) others
- used for anticipatory CINV

Question 10

adjunctive for CINV

Answer 10

for refractory CINV

1) haloperidol
- block DA receptor in chemoreceptor trigger zone
- PO/IV 0.5-2mg q4-6h

2) phenothiazine (prochlorperazine, chlorpromazine, promethazine)
- block DA receptor in chemoreceptor trigger zone
- prochlorperazine PO 10mg TDS/QDS PRN
- AE: drowsiness, hypotension, akathisia, dystonia, EPSE

Question 11

breakthrough CINV

Answer 11

• additional agent from different class, ideally different MOA
• hydration and fluid replacement for losses

Question 12

non pharm for CINV

Answer 12

• small frequent meals, avoid heavy meals
• avoid greasy, spicy, very sweet or salty food, food with strong flavor/smells
• sip small amount of fluids and not chug
• avoid caffeinated beverages
• avoid lying flat for 2 hrs after eating
• anticipatory CINV: behavioural therapy (relaxation, systemic desensitisation, music therapy), acupuncture/acupressure

Question 13

risk factors for chemotherapy induced diarrhoea

Answer 13

• > 65 yo
• female
• eastern cooperative oncology (ECOG) performance status (PS) at least 2
• bowel inflammation/malabsorption
• bowel malignancy
• biliary obstruction
• first cycle of chemo, cycle duration > 3 wks, concomitant neutropenia, mucositis, vomiting, anorexia, anaemia

Question 14

chemotherapy induced diarrhoea pathophysiology

Answer 14

direct damage and inflammation to mucosa intestine -> imbalance between absorption and secretion

Question 15

severity of chemotherapy induced diarrhoea

Answer 15

1) Grade 1
- increase of < 4 stools per day above baseline

2) grade 2
- increase of 4-6 stools per day above baseline
- limit activities of daily living

3) grade 3
- increase of > 7 stools per day above baseline
- hospitalisation
- limiting self care

4) grade 4
- life threatening, surgent, intervention needed

5) grade 5
- death

Question 16

octreotide (sandostatin)

Answer 16

1) MOA
- decreased hormone secretion = increased transit time within intestine, decrease secretion of fluid, increase absorption of fluid and electrolytes

2) AE
- bradycardia, arrhythmia, constipation, abdominal pain, enlarged thyroid, N/V, headache, dizziness

3) dose
- 100-150mcg SC TDS
- may increase by 50mcg increment after 24h

Question 17

uncomplicated chemotherapy induced diarrhoea

Answer 17

• grade 1 or 2, no complicating signs or symptoms
• withhold chemotherapy for grade 2, resume when symptoms resolve + reduce duration
• diet modifications
• loperamide (usual guardian dose), continue until 12h no diarrhoea
• if diarrhoea improve then continue diet modification
• if diarrhoea don’t improve then

** schedule loperamide 2mg every 2 hr
** start oral Abx
** treat accordingly if progress to severe/complicated
** if still diarrhoea after loepramide then octreotide/other second line agent

Question 18

complicated chemotherapy induced diarrhoea

Answer 18

• grade 3 or 4
• grade 1 or 2 with at least one of: cramping, > grade 2 N/V, decreased performance status, fever, sepsis, neutropenia, frank bleeding, dehydration
• withhold chemotherapy, resume when all symptoms resolve at lower dose
• octreotide 100-150mcg SC TDS with dose escalation to 500mcg TDS
• IV fluid hydration
• IV Abx (cipro 7 days)

Question 19

non pharm for chemotherapy induced diarrhoea

Answer 19

• probiotics with lactobacillus
• avoid caffeine, alcohol, fruit juice, food that are spicy or high in fat or fibre, dietary supplements
• avoid lactose at least 1 wk after CID resolved
• small frequent meals
• BRAT diet (banana, rice, applesauce, toast)
• more than 3L of clear fluids containing salt and sugar (electrolyte containing fluids)

Question 20

irinotecan-associated diarrhoea

Answer 20

MOA
- irinotecan converted in liver to SN38
- SN38 cause diarrhoea by: damage epithelial cells, increase motility and transit time, bile acid reabsorption, alter gut microbiome (which produces beta glucuronidases and promotes reactivation of SN-38-G)
- SN-38 deactivated by UDP-GT-1A1 to SN-38
(homozygous for UDPGT1A1*28 -> decreased expression)

early
- develop within 24h
- dose dependent, occur during infusion
- also cause cholinergic response
- last 30 mins
- treatment
** atropine IV/SC 0.25-1mg, max 1.2mg

late
- after 24h from administration
- occur at any dose/frequency
- treat with loperamide 4mg after first loose stool, 2mg every 2 hrs (or 4mg every 4 hrs at night) until 12 hrs passed without bowel movement

Question 21

constipation risk factors

Answer 21

• lowered fluid intake and dehydration
• loss of appetite (anorexia)
• lack of fibre/bulk-forming foods in diet
• overuse of laxatives
• low level of physical activity
• thyroid problem
• depression
• high levels of Ca/K in blood
• cancer growing into large intestine or pressing on spinal cord
• AE of drugs for cancer treatment
  ** pain reliever (opioid)
  ** chemotherapy (vinca alkaloids e.g. vincritstine, vinblastine, vinorelbine)
  ** antinaseua drugs (ondansetron, ganisetron, anticonvulsant)

Question 22

mucositits pathophysiology

Answer 22

• damage to mucosa due to cancer therapy
• direct damage to epithelial cells
  ** tissue response varies by seasonal/circadian changes
  ** targeted therapies (cetuximab, bevacizumab, rituximab, other small molecule inhibitors) cause GI toxicities
  ** EGFRi cuz EGF maintain mucosal integrity

Question 23

mucositis process

Answer 23

1) initiation
- direct toxicity, oxidative stress, increased vascular permeability -> local accumulation of drugs

2) upregulation
- 4-5 days after treatment
- ROS damage DNA -> epithelial cell death
- extent of damage based on rate of oral epithelium proliferation
- nuclear factor-kB activated by chemo/radio -> production of pro-inflammatory cytokines and expression of adhesion molecules -> tissue damage, activate COX-2, angiogenesis, apoptosis

3) signalling and amplification
- pro-inflammatory cytokines released (TNF-alpha, IL-1beta, IL-6) -> positive feedback loop -> increased/extend damage to mucosa

4) ulceration
- 7 days after treatment
- prior injury to basal epithelial cells -> Atrophy and mucosal breakdown
- oxidative stress -> inflammatory infiltrates
- macrophages activated by colonising bacteria
- further increased production of pro-inflammatory cytokines

5) healing
- day 12-16
- epithelial cell proliferation and differentiation -> return of local flora
- continued angiogenesis -> increased risk of future mucositis

Question 24

risk factors for mucositis

Answer 24

patient related factors
- autoimmune disorders, DM, female, caucasians, genetic predisposition for tissue damage, folic/vit b12 deficiencty

treatment related factors
- chemotherapy
** varies by agent and regimen
** s-phase agent highest risk
** prolonged/repetitive long doses -> higher risk than bolus doses
** more cycles = higher risk
** renal/hepatic impairment = reduce clearance = higher risk
** previous therapies toxic to mucosa
** previous episodes of mucositis

• radiation
  ** increase risk when added on to chemotherapy
  ** dependent on radiation source, dosage, dose intensity, volume of mucosa irritated
  ** smoking/alcohol increase risk
  ** higher risk in presence of xerostomia and infection

Question 25

symptoms of mucostiis

Answer 25

1) day 0-5 - asymptomatic - redness, swelling, burning, increased sensitivity 2) Day 0-7 - desquamation, white patches 3) day 6-12 - contiguous pseudo membranes 4) day 7-16 - painful erosions, ulceration

Question 26

grading

Answer 26

1) WHO - grade 0: no evidence - grade 1: erythema and soreness - grade 2: ulcer, eating solid - grade 3: ulcer, require liquid diet - grade 4: ulcer, not able to take PO - grade 5: NA 2) NCI-CTCAE - grade 0: NA - grade 1: asymptomatic or mild, no itnervention - grade 2: moderate pain, modified diet - grade 3: severe pain, interfere with PO intake - grade 4: life threatening - grade 5; death

Question 27

MASCC prevention for mucositis

Answer 27

1) palifermin - kertinocyte growth factor, fking expensive - reduce duration and severity for haem cancers - IV 60 mcg/kg/day for 3 consecutive days before and within 24-48 hrs after myelotoxic therapy (total 6 doses) 2) oral cryotherapy - suck ice chips -> vasoconstrict -> hope chemo don't reach oral mucosa - prevention after bolus 5-FU

Question 28

opioid definitions

Answer 28

1) opioid tolerance - person using opioids with reduced response to medication -> need more opioid for same effect - at least 60mg PO morphine, 25mcg transdermal fentanyl, 30mg PO oxycodone, 8mg PO hydromorphone, 25mg PO oxymorphone, equinalagesic dose of another opioid 1 wk or longer 2) opioid dependence - body adjust normal functioning around opioid, physical symptoms when stopped 3) opioid addiction - unsuccessful attempt to cut down/control use -> social problems/failure to fulfil obligations - usually comes after both opioid tolerance and dependence

Question 29

initiation for opioid

Answer 29

- immediate release first - lowest effective dose - avoid increasing dose above level less likely to yield diminishing returns in benefits

Question 30

initiating PO morphine dose

Answer 30

1) acute pain, opioid naive - PO 10mg every 4 hrs, up to 30mg every 4 hrs for severe pain + low risk respiratory depression 2) acute pain, chronic opioid - 5-20% daily MME as IR 3) chronic pain, include cancer pain - 5-15mg PO every 4 hrs - non cancer pain titrate no more than 25-50% total dose - cancer pain titrate 30-100% total dose in prior 24 hr period

Question 31

renal dose adjust morphine

Answer 31

1) CrCl > 60: none 2) CrCl 30-60: alternative or 50-70% usual initial dose, consider extend dose interval 3) CrCl 15-30: avoid, if need then 25-50% usual initial dose, extend dose interaval 4) CrCl < 15: avoid 5) HD 3x/wk: avoid, if need then 25-50% 6) PD: avoid, use alternative

Question 32

hepatic dose adjust morphine

Answer 32

1) A - none, extend dose interval 2) B - 50% usual dose, extend 3) C - avoid, if need reduce > 50% usual dose, extend interval

Question 33

short to long acting opioids

Answer 33

- chronic pain: scheduled doses superior to PRN doses - add 50-100% of PRN usage to around the clock schedule dose, institute plan to taper down - rescue PRN dose 10-20% daily opioid requirements

Question 34

morphine conversion

Answer 34

1) morphine 30mg 2) hydromorphone 7.5mg 3) oxycodone 15-20mg 4) hydrocodone 30-45mg 5) oxymorphone 10mg 6) codeine 200mg 7) tramadol 300mg 8) tapentadol 75-100mg

Question 35

fentanyl

Answer 35

1) 90-134 mg/day morphine = 25 mcg/h 2) 135-224 mg/day morphine = 50mcg/h 3) 225-314 mg/day morphine = 75mcg/h 4) 314-404 mg/day morphine = 100mcg/h give syrup/other morphine for PRN dose, fentanyl for regular regimen patch got black box warning, only can use for opioid tolerant patients

Question 36

methadone

Answer 36

1) PO morphine < 60mg = 2 - 7.5 mg methadone per day 2) PO morphine 60-199mg = 10 : 1 ratio (< 65 yo), 20 : 1 (> 65 yo) 3) PO morphine > 200mg = caution, don't exceed initial dose 25mg/day

Question 37

ketamine

Answer 37

- anesthetic in hospital - effect on NMDA receptors -> reverse opioid tolerance -> useful in patient with opioid hyperalgesia - orally in small dose

Question 38

adjuvants for cancer pain

Answer 38

1) gaba acting anticonvulsants - gabapentin, pregabalin - neuropathic pain - can cause sedation 2) SNRI - duloxetine but not common 3) tramadol (2 for 1) - serotonin effect + opioid effect 4) lidocaine patches - not common

Question 39

monitoring for opioid related pain

Answer 39

- pain control, respiratory and mental status - blood pressure - signs of misuse, abuse, substance use disorder - signs and symptoms of hypogonadism and hypoadrenalism

Question 40

end of life syndrome

Answer 40

1) dyspnoea - common in lung cancer - consider non pharmaco - O2 therapy helpful in some cases, consider if previous bleomycin chemo - can use opioid for respiratory depression patient to reduce respiratory rate and make them feel more comfortable 2) Secretions - glycopyrrolate, anticholinergic 3) agitation/delirium - both patient and caregivers - look for meds related causes 4) anorexia/cachexia 5) persistent nausea 6) chronic diarrhoea/constipation 7) insomnia/over-sedation 8) wound care/pressure ulcer

Question 41

effect on disease state on nutrition

Answer 41

1) reduced volitional intake 2) N/V, D 3) change in appetite/early satiety 4) malabsorption 5) nutrient loss (dialysis) 6) impaired metabolism, increased energy expenditure, protein catabolism

Question 42

associated complications

Answer 42

1) increased complications 2) poor wound healing 3) compromised immune status 4) impairment of organ functions 5) increased use of healthcare resources 6) increased mortality

Question 43

nutritional screening and assessment

Answer 43

1) nutritional screening - identify patient at nutrition risk - based on unintentional weight loss, nutritional intake, muscle wastage - > 3: nutritional risk - 3-4: risk of moderate malnutrition - 5-9: risk of severe malnutrition 2) refer to dietician/nutritional specialist 3) nutritional assessment - anthropometric measurement - biochemical assessment - clinical assessment - dietary assessment 4) formulation of nutritional regimen

Question 44

estimated EER

Answer 44

25-35 kcal/kg body weight

Question 45

total energy expenditure (TEE)

Answer 45

TEE = resting energy expenditure (REE) x activity factor x stress factor (activity factor) - sedentary 1.2 - somewhat active 1.3 - average 1.4 - above average 1hr per day 1.5 - very active 2 hrs per day 1.6 more than 2 hrs per day 1.7 - professional 1.8 (stress factor) - undernourished 0.85 - surgery 1.05-1.15 - sepsis 1.2-1.4 - multiple trauma 1.4 - burns 2 - IBD 1 - systemic inflammation 1.5 - cancer 1.1-1.5

Question 46

modes of measurement

Answer 46

1) indirect calorimetry (gold standard) - measure gas exchange during consumption of substrates - tedious and costly - not suitable for mechanical ventilation 2) predictive equations - lower accuracy

Question 47

protein requirements

Answer 47

1) healthy adult 0.8g/kg/day 2) trauma/surgery/burn 1.5-2g/kg/day 3) sepsis/critical illness 1.5-2, up to 2.5g/kg/day 4) CKD no dialysis 0.6 - 0.8 g/kg/day 5) CKD HD/PD 1.2g/kg/day 6) CKD CRRT up to 2g/kg/day

Question 48

non pharm for malnutrition

Answer 48

1) small frequent meals with snacks in between 2) consume more protein/caloric dense food 3) soft, low fibre food easier on stomach 4) various oral nutritional supplements

Question 49

enteral nutrition indication

Answer 49

cannot receive/toelrate adequate nutrition by oral intake

Question 50

types of enteral access

Answer 50

1) pre-pyloric - nasogastric (NG), percutaneous endoscopic gastrotomy (PEG) - higher tolerance to bolus and wide range of products - may be used for feeding - not for delayed gastric emptying - may be used for venting (aspriate/withdraw stuff) 2) post-pyloric - nasojejunal (NJ), percutaneous endoscopic jejunostomy (PEJ) - smaller bore, less discomfort - higher risk for tube clogging - used in conditions that result in dysfunctionality in proximal GIT - lesser aspiration risk - long term use PEJ

Question 51

types of enteric formula

Answer 51

1) modular - single nutrient - fortifier to enhance specific nutritional component/augment oral diet 2) (Semi) elemental - partially/completed hydrolysed nutrients - impaired GI function, impaired tolerance to standard feeds 3) polymeric - intact macronutrients - sufficiently functional GIT 4) immune-modulating/disease specific - all the guardian feeds - if unable to tolerate volume then consider EN feeds with higher caloric density/add myotein to increase protein content

Question 52

drug nutrient interactions for enteric feed

Answer 52

- not a problem for bolus/intermittent if adequate flushing - inappropriate administration lead to meds binding to tube, med-feed interaction, alter dosage form -> stop feed, flush before and after drug administration, other alternatives in appropriate dosage form

Question 53

enteral feed complications

Answer 53

1) refeeding syndrome 2) occlusion of feeding tube - jejunal > gastric tube - medication administration - concentrated, high protein, fibre-enriched 3) tube displacement 4) aspiration 5) infections secondary to microbial contamination 6) N/V/C/D

Question 54

enteral feed monitoring

Answer 54

1) intolerance 2) Gastric residual volume - assess 30-60 mins after feeding to see if pt has ability to process food normally - high GRV = GI dysfunction - pH, consistency, color 3) blood glucose level, electrolytes, fluid balance 4) long term weight gain for nutritional improvement

Question 55

strategies to maximise EN

Answer 55

1) continuous instead of bolus 2) prokinetic agents (metoclopramide, domperidone, IV erythromycin) 3) post-pyloric feeding if intolerant to gastric feeding 4) semi-elemental/elemental for malabsorption issue 5) if functional gut then use to maintain function

Question 56

parenteral nutrition indication

Answer 56

cannot receive/tolerate enteral route

Question 57

parenteral access devices

Answer 57

1) peripheral - outside central vessels (arms, feet) - frequent re-site - nutrient delivery limited by osmolarity and concentration - not for long term 2) central - large bore blood vessels (distal superior vena cava, inferior vena cava, right atrium) - types a) non-tunneled central venous catheter (large vessels, straight out from chest, shorter tube shorter duration to prevent infection 2 wks) b) tunneled central venous catheter - under skin = lesser risk of infection c) peripherally inserted central catheter (PICC) d) implanted port

Question 58

types of nutriens

Answer 58

1) macronutrients - AA (4kcal/g) - dextrose (3.4 kcal/g, given regardless of high glucose levels to avoid excessive ketone production, high infusion rate > max glucose oxidation leads to hyperglycaemia and hepatic steatosis) - lipids (10kcal/g, linoleic and alpha-linoleic acid, 20-30% total calories) - usually protein : non protein about 50-80% carbs 50-20% lipids 2) micronutrients - electrolytes (usuals + acetate, chloride for acid-base balance) - multivitamins - trace elements (copper manganese need liver/gall bladder function)

Question 59

drug nutrient interaction for PN

Answer 59

1) not a problem if administered via separate lumen in same access device 2) Y site vs admixture 3) TPN vs total nutrition admixture - TPN no lipids, TNA got lipids 4) administration of incompatible drug can cause precipitation, loss of activity, phase separation of lipid emulsion, toxicity - separate peripheral IV cannula - if needed, pause, flush before and after drug then resume PN

Question 60

device related complication

Answer 60

1) occlusion (thrombosis, clotting, inadequate flush, precipitate cuz drug incompatability/crystalisation) 2) malpositioning 3) catheter related bloodstream infection

Question 61

metabolic complications

Answer 61

1) refeeding syndrome 2) hyper/hypo glycaemia 3) fluid overload 4) intestinal failure associated liver disease - lack of gut stimulation by cholecystokinin (CCK) -> biliary stasis, fat malabsorption, cholestasis 5) metabolic bone disease - aluminum common contaminant in TPN - originate in glass bottle, manufacture, additives - prolonged use = accumulate in bone = low bone turnover = predisposed to osteoporosis/osteomalacia/insufficient vit D

Question 62

monitoring parameters

Answer 62

blood glucos elevels, electrolyte, fluid balance, weight, renal function test, liver function test, triglycerides, signs of infection

Question 63

refeeding patho

Answer 63

1) prolonged starvation -> catabolic state -> break down glycogen store, muscle, fats 2) insulin level go down, glucagon levels go up 3) body draw electrolytes from other stores (intracellular: magnesium, potassium, phosphate ; extracellular: sodium, chloride) so blood test show borderline deficit but not total deficit 4) when reintroduced feeds body go into anabolic state -> increase insulin -> drive glucose uptake into cell and shift electrolytes into cell (potassium, magnesium, phosphate) -> drop in serum levels of electrolytes 5) final results - exert osmotic pressure -> shift in fluids -> fluid retention/oedema - hypoK, hypoMg, hypophosphate - potentially fatal: arrhythmia, cardiac failure, neuromuscular complications

Question 64

risk factor for refeeding

Answer 64

(either one of) 1) BMI < 16 2) unintentional weight loss > 15% in past 3-6 months 3) little/no nutritional intake > 10 day s 4) low levels of K, Mg, phosphate before feeding (either 2 of) 1) BMI < 18.5 2) unintentional weight loss > 10% in past 3-6 months 3) little or no nutritional intake > 5 days 4) history of alcohol misuse or drugs, including insulin, chemotherapy, antacids, diuretics

Question 65

refeeding management

Answer 65

1) identify high risk pt 2) check serum electrolyte at baseline 3) correct deficiencies before feeding, defer feeding if electrolytes too low 4) administer thiamine (vit b1) 100-200mg 7-10 days 5) start low go slow, if high risk then reduce kcal by 50%, if no signs of refeeding then replenish further till 100% 6) continue monitor electrolyte as feeding progress, adjust accordingly