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Multi-morbid > Chemotherapy-Induced Diarrhoea, Constipation, Mucositis > Flashcards

Chemotherapy-Induced Diarrhoea, Constipation, Mucositis Flashcards

1
Q

Other predictive factors of CID

A
  1. First cycle of chemotherapy
  2. Cycle duration greater than 3 weeks
  3. Concomitant neutropenia
  4. Other symptoms such as mucositis, vomiting, anorexia, or anaemia
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2
Q

Risk factors for CID

A
  1. Age greater than 65 years
  2. Female
  3. ECOG performance status of at least 2
  4. Bowel inflammation or malabsorption
  5. Bowel malignancy
  6. Biliary obstruction
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3
Q

Potential Causative Agents for Chemotherapy-Induced Diarrhoea

A

a. Cisplatin/Oxaliplatin
b. Cyclophosphamide
c. Cytarabine
d. 5-FU/Capecitabine
e. Gemcitabine
f. Methotrexate
g. Doxorubicin/Daunorubicin
h. Taxanes
i. Irinotecan/Topotecan
j. Oral Targeted Therapy

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4
Q

MOA of CID

A

Direct damage and inflammation to mucosa of intestine, which leads to imbalance between absorption and secretion

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5
Q

Severity grading for CID

A

CTCAE Version 5.0

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6
Q

Grade 1

A

Increase of <4 stools per day above baseline

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7
Q

Grade 2

A

Increase of 4-5 stools per day above baseline
Limiting ADL

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8
Q

Grade 3

A

Increase of ≥7 stools per day above baseline
Hospitalisation needed
Limiting self-care

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9
Q

Grade 4

A

Life threatening
Urgent intervention needed

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10
Q

Grade 5

A

Death

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11
Q

Criteria for complicated CID

A

● Grade 3 or 4
● Grading 1 or 2 with at least one of the following
○ Cramping
○ >Grade 2 N/V
○ Decreased performance status
○ Fever
○ Sepsis
○ Neutropenia
○ Frank bleeding
○ Dehydration

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12
Q

Criteria for uncomplicated CID

A

Grade 1 or 2
No complicating signs or symptoms

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13
Q

CID goals of therapy

A
  1. Decrease morbidity and mortality from CID
  2. Improve QOL and ADL
  3. Improve recovery of intestinal mucosa
  4. Decrease hospitalisation
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14
Q

Management of uncomplicated CID

A
  1. Withhold chemotherapy for Grade 2
  2. Diet modifications
  3. If diarrhoea persists after 12-24 hours…
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15
Q

When to resume chemotherapy for Grade 2?

A

When symptoms resolve; consider dose reduction of drug

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16
Q

Diet modifications for uncomplicated CID

A

a. Oral hydration with 8-10 large glasses of clear liquids
b. Loperamide
c. If diarrhoea improve after 12-24 hours, continue with diet modifications and begin to add solid food

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17
Q

If diarrhoea persists after 12–24 hours

A

1) Schedule loperamide 2 mg every 2 hours
2) Start oral antibiotics.
3) For diarrhoea that progresses to severe or complicated, treat as such.
4) For diarrhoea that persists as uncomplicated 12– 24 hours after scheduled loperamide, begin octreotide or other second-line agent.

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18
Q

Administration of Loperamide

A

Loperamide 4 mg by mouth, then 2 mg by mouth every 4 hours or after every episode of diarrhoea. Continue until 12 hours free of diarrhoea, then stop.

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19
Q

Management of complicated CID

A

1) Withhold chemotherapy
2) Restart at decreased dosage
3) Administer octreotide
4) Start IV fluid hydration
5) Start IV antibiotics

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20
Q

Administration of octreotide

A

SC 100–150 mcg TDS or
IV with dose escalation up to 500 mcg TDS

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21
Q

MOA of loperamide

A

Opioid that inhibits smooth muscle contraction of intestine to decrease motility (primary neurotransmitter is acetylcholine)

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22
Q

Adverse effects of Loperamide

A

a. Constipation
b. Abdominal pain
c. Dizziness
d. Rash
e. Bloating
f. N/V
g. Dry mouth
h. Drowsiness

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23
Q

Which grade does Loperamide has limited efficacy?

A

Grade 3-4

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24
Q

High dose of Loperamide has been associated with ______.

A

Paralytic ileus

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25
Q

Maximum daily dose of Loperamide

A

16mg

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26
Q

MOA of Octreotide

A

Causes decreased hormone secretion, which
- increases transit time within intestine
- decreases secretion of fluid
- increases absorption of fluid and electrolytes

27
Q

Adverse effects of Octreotide

A
  1. Bradycardia
  2. Arrhythmias
  3. Constipation
  4. Abdominal pain
  5. Enlarged thyroid
  6. N/V
  7. Headache and dizziness
28
Q

When is Octreotide beneficial?

A

5-FU and irinotecan-induced CID

29
Q

Recommended dose of Octreotide

A

100-150 mcg SC TDS
May increase at 50 mag increments after 24 hours to 500 mcg TDS of continuous IV

30
Q

Non-pharmacological management of CID

A
  1. Probiotics with lactobacillus to prevent
  2. Diet modification
31
Q

Diet modification

A
  1. Avoid caffeine, alcohol, fruit juice, foods that contain lactose, foods that are spicy or high in fat or fibre, or dietary supplements with high osmolarity
  2. Up to 10% of patients experience 5-FU–induced lactose intolerance because lactase activity can be lost temporarily
  3. Lactose-containing foods should be avoided for at least a week after CID has resolved
  4. Eat small, frequent meals
  5. BRAT diet (bananas, rice, applesauce, toast)
  6. More than 3 L of clear fluids containing salt and sugar
  7. Electrolyte-containing fluids are ideal
32
Q

Irinotecan-associated diarrhoea MOA

A

Irinotecan is a selective, reversible inhibitor of acetylcholinesterase leading to a cholinergic response
MOA: inhibits acetylcholine at muscarinic receptor as a competitive antagonist

33
Q

Management of Irinotecan-associated Diarrhoea

A

Early (within 24 hours): Atropine 0.25-1 mg (maximum 1.2 mg) SC or IV
Late (after 24 hours): Loperamide

34
Q

Adverse effects of Atropine

A
  1. Insomnia, dizziness
  2. Tachycardia, blurred vision, dry mouth
  3. Constipation
35
Q

Contraindication of atropine

A

Glaucoma

36
Q

Symptoms of Constipation

A
  • Bloating/ feeling of fullness
  • Cramping or pain
  • Gas/ flatulence
  • Belching
  • Loss of appetite
  • No regular bowel movement for ≥2 days
  • Straining to have a bowel movement
  • Small hard stools that are difficult to pass
  • Rectal pressure
  • Leakage of small amounts of stool resembling diarrhoea
  • Swollen, or distended, abdomen
  • N/V
37
Q

Factors that Increase Risk of Developing Constipation (1)

A

Lowered fluid intake and dehydration

38
Q

Factors that Increase Risk of Developing Constipation (2)

A

Loss of appetite (anorexia)

39
Q

Factors that Increase Risk of Developing Constipation (3)

A

Lack of fibre or bulk-forming foods in the diet

40
Q

Factors that Increase Risk of Developing Constipation (4)

A

Vitamin or mineral supplements such as iron or calcium pills

41
Q

Factors that Increase Risk of Developing Constipation (5)

A

Overuse of laxatives

42
Q

Factors that Increase Risk of Developing Constipation (6)

A

Low level of physical activity/alot of bed rest

43
Q

Factors that Increase Risk of Developing Constipation (7)

A

Thyroid problems

44
Q

Factors that Increase Risk of Developing Constipation (8)

A

Depression

45
Q

Factors that Increase Risk of Developing Constipation (9)

A

High levels of calcium or potassium in the blood

46
Q

Factors that Increase Risk of Developing Constipation (10)

A

Cancer growing into the large intestine (bowel)/pressing on spinal cord

47
Q

Factors that Increase Risk of Developing Constipation (11)

A
  • Pain relievers, especially opioid narcotic medicines (morphine/ codeine)
  • Chemotherapy drugs (eg. vinca alkaloids – vincristine vinblastine/ vinorelbine)
  • Antinausea drugs (ondansetron, granisetron/ anticonvulsant drugs)
48
Q

Preventing Constipation

A
  • Eat more fibre
  • Eat natural laxatives (vegetables, caffeine, prunes)
  • Increase physical activity
  • Ensure sufficient caloric intake
49
Q

Managing Constipation

A
  1. Stool softeners
  2. Laxatives
    - Promote or stimulate bowel activity
    - Increase fibre or product bulk
    - Suppository foam that help promote bowel activity
  3. Enemas
50
Q

When should suppository/enema not be recommended?

A

When WBC or platelet counts are low → risk of infection or bleeding

51
Q

Pathophysiology of Mucositis

A

Damage to mucosa of the oral cavity, pharynx, larynx, oesophagus and GI tract due to cancer therapy

52
Q

How does chemotherapy/radiation cause mucotitis?

A

Direct damage to epithelial stem cells
- Tissue response varies by seasonal and circadian changes
- Targeted therapies (eg. cetuximab, bevacizumab, rituximab) and a variety of small-molecule inhibitors have demonstrated the potential to cause a variety of GI toxicities, including mucositis

53
Q

Epidermal growth factor

A

Maintain mucosal integrity
- EGFR can be found in the oesophagus and levels are increased in inflamed mucosa

54
Q

Five stages of mucositis

A
  1. Initiation
  2. Upregulation
  3. Signalling and amplication
  4. Ulceration
  5. Healing
55
Q

Initiation

A
  • Direct toxicity to cells, tissues and vasculature
  • Generation of oxidative stress and ROS
  • Increased vascular permeability → accumulation of toxic drugs
56
Q

Upregulation

A
  • ROS damage DNA → epithelial cell death
  • Production of pro-inflammatory cytokines
57
Q

Signalling and amplification

A
  • Pro-inflammatory cytokines (TNF⍺,
    IL1β, IL6) are released
  • Positive feedback
58
Q

Ulceration

A
  • Atrophy and mucosal breakdown
  • Oxidative stress leads to inflammatory infiltrates
  • Macrophages activated by colonising bacteria
59
Q

Healing

A
  • Proliferation of epithelial cells
  • Return of local flora
60
Q

Grading of Mucositis

A

0: no evidence of mucositis
1: erythema and soreness
2: ulcers; eating solids
3: ulcers; requires liquid diet
4: ulcers; not able to take PO

61
Q

API of oracare suspension

A

Nystatin 125.000U
Tetracycline 62.5mg
Hydrocortisone 5mg
Diphenhydramine 11.5mg/10mL

62
Q

Administration of oracare suspension

A

Administer after food, must swallow
Counsel patient that swallowing can help to coat the throat and enter the gut, allowing for full protection (especially for throat ulcers)

63
Q

What is the antibiotic regimen for complicated CID?

A

Ciprofloxacin for 7 days

Multi-morbid (5 decks)

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