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Human Disease > Chemotherapy and Immune Suppression > Flashcards

Chemotherapy and Immune Suppression Flashcards

1
Q

What do chemotherapy drugs expoit in order to be effective

Consequence of this

A
  • Malignant cells behave differently to normal cells as they divide more rapidly
  • Oral tissues with rapidly dividing cells are therefore often affected
  • Oral Mucosa
  • Hair Follicles
  • Bone marrow
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2
Q

Future of chemotherapy

A

-Molecular biology is revealing subtle differences between malignant cells and other rapidly dividing tissues leading to development of targeted therapy

  • eg.
  • Cytotoxic monoclonal antibodies

Understanding of unique tumour architecture has allowed development of new therapy:
-Angiogenesis inhibitors

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3
Q

Chemotherapy for breast and prostate cancer

A
  • Drugs developed that target the external processes that drive malignant growth
  • Tamoxifen (Eostrogen Receptor Blocker): Breast Cancer
  • Abiraterone (CYP17A1 enzyme inhibitor): Prostate Cancer
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4
Q

How do chemo drugs affect the cell cycle and benefit of this

A
  • Different chemo drugs attack different parts of the cell cycle
  • Multiple targets which they can attack
  • Very useful having multiple sites of attack because cancers can mutate around it
  • But we can just use another drug that attacks another part of the cell cycle
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5
Q

Types of Chemo and examples examples

A

Primary:

  • Main modality of treatment
  • For eg, leukaemia because it is everywhere
  • Cannot be operated on surgically

Concurrent:

  • Given with radiotherapy to increase radiosensitivity of the tumour
  • So the tumour becomes more sensitive to the chemotherapy

Adjuvant:

  • Given after surgery or radiotherapy
  • Eliminates micrometastasis
  • Prevents secondary tumours

Neo-adjuvant:

  • Given before surgery or radiotherapy
  • Reduces the tumour bulk
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6
Q

Aims of chemotherapy

A

To Cure:

  • Acute Lymphoblastic Leukaemia (ALL)
  • Burkitt’s Lymphoma

To Control:

  • Prolonged remission
  • Prevent relapse

Pallation:

  • Prolong life
  • Relieve symptoms
  • Improve Quality of Life
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7
Q

Why are chemotherapy drugs given in combination

A
  • If you give too much of any one of these drugs
  • It will kill you as highly toxic
  • Need to be given in low doses in combination
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8
Q

Hormone therapy and chemotherapy
Advantages and disadvantages
Dental Significance

A

Hormones are implicated in the aetiology and growth of some malignant tumours

  • Breast
  • Prostate
  • Remove or reduce the hormone driving cell proliferation
  • Block the hormone to cell receptor

Tamoxifen for breast blocks oestrogen eg

  • Effect is confined to the target organ with minimal side effects
  • Some tumours are resistant or develop resistance

-Minimal Oral effects

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9
Q

Targeted and Biological therapies goal

A

Target differences between normal tissue and tumours

Ideal Goal

  • Specifically kill malignant cells
  • No development of tumour resistance
  • Minimise damage to other tissues
  • Prolonged activity for maintenance therapy
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10
Q

Philadelphia Chromosome and significance of chemotherapy

A
  • 90% of patients with Chronic Myeloid Lymphoma have a balanced translocation between chromosome 9 and 22
  • Resultant oncogene with tyrosine kinase activity
  • Lead to first targeted therapy for leukaemia
  • Imatinib (tyrosine kinase inhibitor)
  • Tyrosine kinase have a critical role in cell division and cell death
  • Can be found on both the cell surface and intracellularly
  • Sunitinib
  • Imatinib
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11
Q

Tyrosine Kinase Inhibitors examples and side effects

A
  • Imatinib
  • Sunitinib

Sunitnib side effects include osteonecrosis of the jaw

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12
Q

Sunitinib drug definition, treatment and side effects

A
  • Tyrosine Kinase Inhibitor
  • First targetted treatment of CML
  • Essentially starves the tumour of its blood supply

-Can cause osteonecrosis of the jaw because the jaw also requires a lot of blood supply

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13
Q

Significance of monoclonal antibodies in modern day chemotherapy

A

-Tumour associated with monoclonal antibodies

  • Initally used for diagnosis
  • Now used as a targeted treatment
  • Often added to conventional chemotherapy
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14
Q

When can tumour vaccines be used

Examples

A
  • Effective against virally induced tumours
  • For example:

Hepatocellular Carcinoma can be treated with a Hep B vaccine

Burkits Lymphoma can be treated with an Epstein Barr Virus

Cervical Carcinoma can be treated with Human Papilloma Virus

Oropharyngeal Carcinoma
Human Papilloma Virus Vacine

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15
Q

Active Immune Therapy

A

-Immunisation to elicit an immune reaction to eliminate or delay tumour growth

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16
Q

Acute Side Effects of Chemo

A

General:

  • Initially nausea and comiting (first few days)
  • Fatigue throughout

Gastrointestinal:

  • Oral mucositis
  • Diarrhoea

Bone Marrow:

  • Toxicity
  • Neutrophils most affected
  • Time course variable
  • Anaemia
  • Low platelets level
  • Coagulopathy

Hair Follicles
-Alopecia

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17
Q

Long Term Effects of Chemotherapy and significance

A
  • Patients now survive after advanced malignancy
  • Need to minimise long term toxicity of the treatment
  • Can detract from QoL (eg. osteonecrosis of the jaw), shorten life expectancy
  • Surveillance for long term toxic effects may need to be continued for many decades
  • Infertility
  • Premature menopause
  • Cardiotoxicity
  • Pulmonary Fibrosis
  • Teratogenicity
  • Neurological
  • Hearing Loss
  • Secondary Malignancy
  • Chronic Kidney Disease
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18
Q

Why is the oral cavity affected in chemotherapy

A

-High turnover rate of lining (Significantly higher than skin)

  • Non keratinised areas most affected
  • Highly sensate mucosa
  • Constant immunological challenge
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19
Q

Significance of oral effects

A
  • Low mood
  • Social isolation
  • Inability to complete cancer treatment
  • Impaired nutrition
20
Q

Oral complications of chemotherapyh

A

Oral Mucositis:

  • Acute complication
  • Most common

Oral Infection:

  • Viral, fungal or bacterial
  • Acute complication

Taste Disturbance:
-Acute complication

Salivary Gland Dysfunction:
-Acute

Neuropathy

  • Acute
  • Jaw pain may occur with vinca alkaloids

Haemorrhage

  • Acute complication
  • Haemorrhage may occur with oral mucositis
  • Oral infections and/or thrombocytopenia

Dental/Skeletal Developmental Problems

  • Chronic complication
  • Sometimes in paediatric patients

Second Malignancy
-Chronic complication

21
Q

Mucositis clinical features

A
  • Widespread ulceration
  • Intolerable pain
  • Worst side effect often
22
Q

Risk Factors for developing mucositis

A
  • Poor Oral Health (main one)
  • Female
  • Caucasian
  • Poor nutrition
  • Young age
  • Type of cancer
  • Type of chemo
  • Multicycle treatment
  • Genetic factors
  • Combined radiotherapy
23
Q

How do you classify severity of mucositis

A

Grade 1 -4
-Look at slides not sure we need to know but

1: Oral Soreness, Erythema
2: Can swallow foods but ulcers as well
3: Cannot swallow foods or extensive ulcers
4: Alimentation not possible

24
Q

How to manage a patient with mucositis

A
  • Optimum oral health (soft toothbrush and careful flossing )
  • Cryotherapy (chewing ice cubes)
  • Chlorhexadine mouth rinse
  • LA mouth rinse
  • Keratinocyte stimulator
  • Opiate pain killers
  • PEG feeding
  • Abandon chemotherapy if that bad
25
Q

Drugs used to support chemotherapy that we should be aware of

A
  • Bisphosphonates
  • Tyrosine Kinase Inhibitors such as Sunitinib

-Both can cause osteonecrosis of the jaw

26
Q

Things to be aware of if a patient says theyve had chemo

A
  • Was it to cure or control/palliate
  • Indicates QoL etc
  • Any drugs used to support chemo such as bisphosphonates or sunitinib which can cause osteonecrosis
  • Did the patient receive significant head and neck radiotherapy? Xerostomia/osteonecrosis
27
Q

Long term oral complications of chemo

A
  • Not many

- Minimal

28
Q

Immunosuppression v immunodeficient v immunocompromised

A

Immunosuppression
-Artificially depressed immune system

Immunodeficient
-Any state in which the immune system is below optimum level

  • Immunocompromised
  • Poor immune function due to disease/medications
29
Q

Types of immunodeficiency

A

Congenital (Innate)

  • Rare
  • Uncommon with significant variability in severity and oral impact

Acquired (Secondary)

  • Common due to disease or treatment of disease
  • HIV, Leukaemia, Autoimmunity
  • Diabetes, Sickle Cell
  • Malnutrition
  • Post organ transplant
  • Treatment of Malignancy
30
Q

Common Drugs used in Immune Suppression

A

Corticosteroids
-Prednisolone

Calcineuric Inhibitors

  • Cyclosporin
  • Tacrolimus

Antiproliferative Agents
-Azathioprine

Antimetabolites
-Methotrexate

Antibodies/Anti TNF
-Inflixamab

31
Q

Common uses of immunosuppression

A

-Prevent transplant rejection
-Cancer chemotherapy
-Treatment of autoimmune diseases
eg
Multiple Sclerosis
Inflammatory Bowel Disease
Rheumatoid Arthritis
Systemic Lupus Erythematosis (SLE)
Sjorgens syndrome

32
Q

Corticosteroids examples, definition and side effects

A
  • Non SPECIFIC anti inflammatory
  • eg. Prednisolone
  • Trying to limit use and reduce dose because many side effects
  • Hypertension
  • Fluid Retention
  • Osteoporosis
  • Diabetes
  • Cushingoid Appearance
  • Infections
  • Weight Gain

-High doses of steroids may lead to Cushings Syndrome

33
Q

Immune Suppression drugs and affect in terms of dentistry

A
  • Often mask the symptoms of the infection
  • Might not feel too bad
  • Increased susceptibility to infection
34
Q

How can exogenous steroids lead to addisonian crisis

A
  • If they withdraw from taking exogenous steroids
  • Body is not used to making their own cortisol
  • For example prednisolone
  • Atrophy with reduced steroid production
  • Low glucocorticoids leading to low blood pressure and low blood sugar
  • Collapse
35
Q

Is Addisonian risk significant to dentists

A
  • Normally precipitated by a stressful event
  • Acute infection or major trauma
  • Dental treatment is not stressful enough
  • GA and major surgery may pose a risk

-No good evidence to support administering a booster dose of steroid in dentistry, despite what dental literature says

36
Q

Steroid sparing drugs and significance

A
  • Alternating drugs that help to reduce the steroid dose
  • Reducing side effects
Azathioprine 
Methotrexate 
Mycophenolate
Retuximab 
Inflixamab
37
Q

Specific and Generalised oral side effects of immunosuppressents

A

Specific:
Gingival Hyperplasia of Cyclosporin

Generalised

  • Candida
  • Oral ulceration
  • Herpes simplex/zoster, EBV and CMV
  • Delayed wound healing
  • Periodontal disease
  • Potential malignancies
38
Q

Herpes Simplex and immunosuppression, treatment/prevention

A
  • Most common viral pathogen causing oral infection
  • 2-6 weeks post transplant
  • More severe than in normal patients
  • May develop vesicles on keratinised areas

Tx:
-Acyclovir

39
Q

Epstein-Barr Virus Oral manifestations and treatment

A

Oral Hairy Leukoplakia

Antiviral meds or reduce immunosuppression

40
Q

Candida infection treatment

A
  • Nystatin Suspension

- Fluconazole

41
Q

Cyclosporin and gingival hyperplasia mechanism and tx

A
  • Increases collagen and glycosaminoglycan synthesis
  • Affects anterior regions most
  • Mandible>Maxilla

Treatment

  • Improve OH
  • Alternative drugs
  • Surgical reduction
42
Q

Graft Veruss Host Disease

A
  • Immunocompetent graft attacking immunodeficient host
  • Can be acute or chronic
  • Oral lesions in 80%
  • Lichenoid reactions
  • Ulcerations
  • Candida
  • Hyperkeratotic Leukoplakia
  • Fibrosis leading to trismus
  • Salivary gland dysfunction
43
Q

Common malignancies and relation to immunosuppresion

A
  • Occurs in 3-30% of transplant patients
  • Lip squamous cell cancer (SCC) most common
  • Intra oral SCC
  • Basal Cell cancer (BCC)
  • Kaposi’s Sarcoma
44
Q

Infection and immune suppression

A
  • Depends on type of immue suppression
  • Prophylactic antibiotics may be required for surgical/invasive procedures
  • Pt may feel well despite evidence of significant infection
45
Q

Relevant Blood Tests and Staging Extractions

A

-Aim to carry out extractions 10 days before neutrophil count <0.5

Human Disease (19 decks)

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