immunosupressants and anticancer

Question 1

Epidemiology of Cancer
 # associated disease processes
 leading cause of the death in the U.S.?
 Nearly ? deaths a day
 % of all deaths
 Many causes of cancer are mediated by ?
 theories on cancer pathophysiologic process?

Answer 1

 150+ associated disease processes
 Second leading cause of the death in the U.S.
 Nearly 1,500 deaths a day
 25% of all deaths
 Many causes of cancer are mediated by the environment
and lifestyle of a person
 Smoking
 Obesity
 Alcohol consumption
 Multitude of theories on cancer pathophysiologic process

Question 2

 Neoplasia

Answer 2

 Process of altered cell differentiation and growth
 Uncoordinated
 Autonomous
 Lacks normal regulatory control

Question 3

 Neoplasm

Answer 3

 New growth
 “Tumor”

Question 4

Cancer

Answer 4

 Disease resulting from altered cell differentiation and growth

Question 5

Review: Cell Growth & Proliferation

Answer 5

Question 6

Cell Differentiation
 Proliferating cells become progressively?
 Cells have a specific set of?
 As cells differentiate, what deminishes?
 Undifferentiated cells are hallmark of?

Answer 6

 Proliferating cells become progressively more specialized
 Cells have a specific set of structural, functional, and life-expectancy characteristics
 As cells differentiate, their capacity or proliferation diminishes
 Undifferentiated cells are hallmark characteristic of cancer cells

Question 7

Cell Growth Gone Wrong: Cancer

Answer 7

 Unchecked growth that progresses toward limitless expansion
 Abnormal and rapid proliferation
 Loss of differentiation> anaplasia
 Causation – genetic & external

Question 8

Comparison of Characteristics: normal cells and cancer cells

Answer 8

Question 9

Carcinoma

Answer 9

Carcinoma
 Arise from the cells that cover external and internal body surfaces such as lung,
pancreatic, breast, and colon

Question 10

Sarcoma

Answer 10

 Arise from cells found in the supporting tissues of the body such as bone, cartilage,
fat, connective tissue, and muscle

Question 11

Lymphoma

Answer 11

 Arise in lymph nodes and tissues of the body’s immune system

Question 12

Leukemia

Answer 12

 Cancers of the immature blood cells that grow in the bone marrow

Question 13

Invasion & Metastasis

Answer 13

 Solid tumors secrete enzymes that break down proteins and contribute to infiltration, invasion, and penetration of surrounding tissues
 Complete surgical removal difficult
 Cancer cells may travel and “seed” into different body cavities where they can proliferate and cause tumor growth (metastasis)
 Blood vessel and lymphatic spread
 Finely orchestrated; selected cells only
 Angiogenesis

Question 14

Metastasis & Use of Bisphosphonates in Cancer

current tx guidelines

Answer 14

Question 15

Metastasis & Use of Bisphosphonates in Cancer
 Bone health?
 bone pain?
 Reduction of ?

Answer 15

 Bone health maintenance
 Reduce bone pain due to hypercalcemia
 Reduction of bone metastasis (breast & prostate cancer)

Question 16

bisphosphonates in prostate cancer

Answer 16

70% of breast and prostate cancer patients develop bone metastases
 15-30% of other common solid cancers

Question 17

bisphophonates in breast cancer

early onset and when metatstisized

Answer 17

Question 18

bisphosphonate names

Answer 18

Question 19

Clodronate

moa, route, potentcy

Answer 19

BP
given oral/IV
10 potentcy factor

Question 20

Pamidronate

moa, route, potentcy

Answer 20

BP, IV, 100

Question 21

Alendronate

moa, route, potentcy

Answer 21

BP ,oral, 500

Question 22

Ibandronate

moa, route, potentcy

Answer 22

BP , oral/IV, 1000

Question 23

Risedronate

moa, route, potentcy

Answer 23

BP, oral, 2000

Question 24

Zoledronate*

moa, route, potentcy

Answer 24

BP, IV, 10000

Question 25

MOA: Bisphosphonates

Answer 25

 Inhibit osteoclast  Attach to bony surfaces undergoing active resorption  Bisphosphonates released during resorption by osteoclasts impairs ability of osteoclasts to form the ruffled border, to adhere to the bony surface  Reduce osteoclast genesis and recruitment  Promoting osteoclast apoptosis

Question 26

Tumor Cell and Osteoclast Symbiotic Relationship * tumor cell releases:

Answer 26

Question 27

Tumor Cell and Osteoclast Symbiotic Relationship * bone resobrtion releases:

Answer 27

Question 28

Result of Tumor Cell and Osteoclast Symbiotic Relationship

Answer 28

Symbiotic relationship further increases bone destruction and tumor growth. [do not need to memorize hormones]

Question 29

Tumor Cell and Osteoclast Symbiotic Relationship diagrammed

Answer 29

Question 30

Dental Concerns: Bisphosphonates | associated with? mechanism? precipitated by?

Answer 30

Question 31

risk factors of dental concerns for BP

Answer 31

 Hx of bisphosphonates especially IV  Hx of Cancer  Corticosteroid therapy  Diabetes  Smoking  Alcohol use  Poor oral hygiene  Chemotherapuetic drugs

Question 32

what often preceeds MRONJ

Answer 32

extractions

Question 33

Study on ONJ Risk

Answer 33

increased incidence with increased duration of tx (1% per yr)

Question 34

what bp has the highest risk for MRONJ

Answer 34

zolendronate

Question 35

Non-Cancer pts on BP's and dental tx

Answer 35

 Low-risk for osteoporosis dosed bisphosphonates – 0.1%  ADA – “recommends that a patient with active dental or periodontal disease should be treated despite the risk of developing ARONJ, because the risks and consequences of no treatment likely outweigh the risks of developing ARONJ.”

Question 36

Additional Considerations of BP's  Education  drug holidays?  chlorohexidine use?  Prophylactic antibiotics?

Answer 36

 Education  Avoid drug holidays  0.2% Chlorhexidine: rinse for 1-minute prior to dental treatment and continue rinsing twice daily for 7-days after treatment  Prophylactic antibiotics: no specific dose/agent recommendations  Amoxicillin (Amoxil) or amoxicillin/clavulanic acid (Augmentin) has been successful in studies

Question 37

Retrospective analysis for prevention of ONJ in multiple myeloma pts using abx prophylaxis? | abx used and dose?

Answer 37

Question 38

Prospective case series, for prevention of ONJ in patient requiring tooth extraction and on IV bisphosphonate | abx/dose?

Answer 38

Question 39

Cancer pts ADA/AAOMS dental tx and using BP's

Answer 39

High-risk for oncologically dosed bisphosphonates – 2-18%  ADA – does not address  AAOMS – “procedures that involve direct osseous injury should be avoided. Nonrestorable teeth may be treated by removal of the crown and endodontic treatment of the remaining roots. Placement of dental implants should be avoided in the oncologic patient receiving IV antiresorptive therapy”

Question 40

BP duration and MRONJ

Answer 40

increased incicdence when used over longer times

Question 41

Mechanism of Action: Denosumab (Xgeva, Prolia)

Answer 41

 Inhibit osteoclast activation  RANKL is secreted by bone marrow cells and osteoblasts  RANKL binds to the RANK receptor on osteoclasts and promotes osteoclast differentiation and activity.  Denosumab is a fully human monoclonal antibody that binds to RANKL  Bound RANKL cannot attach to RANK receptors (i.e. inhibiting activation of osteoclast)

Question 42

Monocolonal Antibodies: Denosumab | production

Answer 42

Murine antibody that recognizes specific antigen

Question 43

Murine Antibody:

Answer 43

 induce a human anti-mouse antibody immune response  activate human immune effector mechanisms poorly  short t1/2 in humans Chimerized by substituting major portions of the human IgG molecule

Question 44

Ab types and immunogenicity scale

Answer 44

Question 45

Toxicities – Infusion Reactions with Ab's  Typical symptoms?  time frame  Premedication

Answer 45

 Typical include fever, chills, nausea, dyspnea, and rashes  within 30 minutes to two hours of initiation of drug infusion, symptoms may be delayed for up to 24 hours  Premedication with diphenhydramine and acetaminophen is indicated

Question 46

Denosumab Risk of MRONJ | high and low doses

Answer 46

 High Dose Denosumab : High prevalence (2-5% Osteonecrosis)

Question 47

Mechanism of MRONJ

Answer 47

 Profound and prolonged inhibition of bone resorption with over-suppression of bone remodeling (ie, low bone turnover), and infection are the main mechanisms  Postulated that MRONJ is a form of avascular necrosis, possibly caused by inhibition of angiogenesis.

Question 48

MRONJ and inhibition of angiogenesis

Answer 48

 In vitro experiments consistently demonstrate inhibition of angiogenesis by zoledronic acid, and cancer patients treated with this agent have decreased circulating VEGF levels  Growing body of evidence linking MRONJ to antiangiogenic drugs, including bevacizumab and orally active tyrosine kinase inhibitors.

Question 49

Angiogenesis and Cancer  Angiogenesis =  Key factor in the?  Solid tumors secrete ?  stimulates?

Answer 49

 Angiogenesis = the development of new blood vessels  Key factor in the growth and metastasis of certain solid tumors  Solid tumors secrete proangiogenic factors, vascular endothelial growth factor (VEGF)  stimulate new vessel development via downstream signaling pathways

Question 50

inhibitors of angiogenesis introduced into oncology practice

Answer 50

 monoclonal antibodies against VEGF (e.g., bevacizumab),  tyrosine kinase inhibitors (e.g., sorafenib, sunitinib),  mammalian target of rapamycin (mTOR) pathway inhibitors (e.g., everolimus)  immunomodulatory agents (e.g., thalidomide, lenalidomide).

Question 51

bevacizumab

Answer 51

monoclonal antibodies against VEGF

Question 52

sorafenib

Answer 52

tyrosine kinase inhibitors

Question 53

sunitinib

Answer 53

tyrosine kinase inhibitors

Question 54

everolimus

Answer 54

mammalian target of rapamycin (mTOR) pathway inhibitors

Question 55

thalidomide

Answer 55

immunomodulatory agents

Question 56

lenalidomide

Answer 56

immunomodulatory agents

Question 57

Bevacizumab moa | used in what cancers?

Answer 57

Bevacizumab (Avastin)- humanized; binds VEGF-A  Used in solid tumor cancers  Specifically recognize and bind to VEGF.  Once bound, the complex is unable to activate the VEGF receptor.

Question 58

Bevacizumab  Most effective when?  kills tumors? role?  Reduces?  possible adrs?

Answer 58

 Most effective when combined with additional therapies, especially chemotherapy.  Do not necessarily kill tumors; they instead may prevent tumors from growing.  Reduce formation of new blood vessels; reduce nutrient delivery  Increases in bleeding and reduced wound healing

Question 59

Note on ONJ and antiangiogenic rx's  Association of ONJ with therapies that target angiogenesis is?  Especially with?  Risk for MRONJ when recieiving both antiabsorb and antiangio?

Answer 59

 Association of ONJ with therapies that target angiogenesis is more controversial  Especially monotherapy with an antiangiogenic agent  Risk for MRONJ more clearly established for use of antiangiogenic agents in patients ALSO receiving antiresorptive agents

Question 60

# International Task Force on Osteonecrosis of the Jaw For patients whose cancer management includes treatment with denosumab or IV bisphosphonates, recommends:

Answer 60

 “a thorough dental examination with dental radiographs should be ideally completed prior to the initiation of antiresorptive therapy in order to identify dental disease before drug therapy is initiated”  “Any necessary invasive dental procedure including dental extractions or implants should ideally be completed prior to initiation of [bisphosphonate] or [denosumab] therapy.”

Question 61

American Society of Clinical Oncology (ASCO) – 2017  “All patients should have what before using a Bone-modifying agent (BMA).”  “in the setting of invasive dental procedures, it is advisable, whenever possible to?  “If an invasive manipulation of the bone underlying the teeth is clinically indicated before starting BMA therapy...initiation of BMA therapy should be ideally delayed for?

Answer 61

 “All patients should have a dental examination and preventive dentistry before using a Bone-modifying agent (BMA).”  “in the setting of invasive dental procedures, it is advisable, whenever possible to delay the starting of therapy with BMA until the initial bone healing process of the tooth socket bone has taken place”  “If an invasive manipulation of the bone underlying the teeth is clinically indicated before starting BMA therapy...initiation of BMA therapy should be ideally delayed for 14 to 21 days to allow for wound healing, if the clinical situation permits.”

Question 62

Cancer Treatment  Goal of therapy based on severity of illness:  Multiple modalities utilized:  Supportive care for ?

Answer 62

 Goal of therapy based on severity of illness: Curative, Control, Palliative  Multiple modalities utilized: Surgery, Radiation therapy, Chemotherapy, Hormonal therapy, Biotherapy  Supportive care for clinical manifestations and/or treatment adverse reactions

Question 63

Chemotherapy Agents  forms?  moa's  Reaches

Answer 63

 Adjuvant (given after therapy) vs. neoadjuvant (before tx to reduce size)  Various mechanisms of action> slow/stop cell proliferation  Reach ‘microscopic’ cancer cells 2 log kill desired

Question 64

what limits chemotherapeutics use?

Answer 64

Adverse reactions limit use  GI disturbances (N/V/D)  Hair loss  Bone marrow suppression (anemia, increased infection risk)

Question 65

Antineoplastic Medications forms

Answer 65

Question 66

Alkylating Agents  moa?  cell cycle specific?  Can be used in?

Answer 66

 Directly damage cell DNA  Impairs replication & transcription= cell death  Work in all phases of the cell cycle  Can be used in many different cancers * carbonium ion highly reactive>binds dna

Question 67

alkylating agents ADRs/toxicity

Answer 67

oppurtunistic infections possible=thrush

Question 68

alkylating agents classes

Answer 68

Nitrogen Mustards Platinum Compounds Nitrosoureas Alkyl sulfonates Triazines Ethylenimines

Question 69

Nitrogen Mustards:

Answer 69

 cyclophosphamide, chlorambucil, ifosfamide, melphalan

Question 70

 cyclophosphamide class/moa

Answer 70

N mustard | akylarting agent

Question 71

chlorambucil class/moa

Answer 71

N mustard | alk agent

Question 72

ifosfamide class/moa

Answer 72

N mustard | alk agent

Question 73

melphalan class/moa

Answer 73

N mustard | alk agent

Question 74

Platinum Compounds:

Answer 74

 cisplatin, carboplatin, oxaliplatin

Question 75

cisplatin class/moa

Answer 75

Plat compound, alk agent

Question 76

carboplatin class/moa

Answer 76

Plat compound, alk agent

Question 77

oxaliplatin class/moa

Answer 77

Plat compound, alk agent

Question 78

Nitrosoureas:

Answer 78

 streptozocin, carmustine and lomustine

Question 79

Nitrosoureas often used with?

Answer 79

brain tumors

Question 80

streptozocin class/moa

Answer 80

nistrosourea, alk agent

Question 81

carmustine class/,moa

Answer 81

nistrosourea, alk agent

Question 82

lomustine class/moa

Answer 82

nistrosourea, alk agent

Question 83

Alkyl sulfonates:

Answer 83

 busulfan

Question 84

busulfan class/moa

Answer 84

Alkyl sulfonates, alk agent

Question 85

Triazines:

Answer 85

 dacarbazine and temozolomide

Question 86

dacarbazine (DTIC) class/moa

Answer 86

triazine, alk agent

Question 87

temozolomide (Temodar®)

Answer 87

triazine, alk agent

Question 88

Ethylenimines:

Answer 88

 thiotepa and altretamine (hexamethylmelamine)

Question 89

thiotepa class/moa

Answer 89

Ethylenimines, alk agent

Question 90

altretamine (hexamethylmelamine) class/moa

Answer 90

Ethylenimines, alk agent

Question 91

platinum compounds nn adr

Answer 91

Neurotoxicity  Drugs enter into the dorsal root ganglion and binds to DNA, causing apoptosis.  Platinum compounds form intrastrand adducts and interstrand crosslinks altering tertiary structure of DNA. This promotes alterations in cell-cycle kinetics, leading to an attempt of differentiated postmitotic dorsal root ganglion neurons to re-enter cell cycle, which leads to the induction of apoptosis Regardless of the mechanism, apoptosis results in secondary damage to peripheral nerves

Question 92

Oxaliplatin association with:  Cold-induced?  breathing?  Mm?  Jaw?  swallowing?  mm appearence?  Voice?  Ocular?

Answer 92

pain triggered by exposure to cold liquids  **Cold-induced perioral paresthesias – 95%**  Cold-induced pharyngolaryngeal dysesthesia – 92%  Dyspnea – 40%  Muscle cramps – 34%  Jaw stiffness – 34%  Dysphagia – 30%  Visible fasciculations – 30%  Voice changes – 6%  Ocular changes – 0.7%

Question 93

Antimetabolites:

Answer 93

 Antimetabolites are structurally related to normal compounds that exist within the cell

Question 94

antimetabolites moa

Answer 94

Antimetabolites interfere with DNA and RNA growth by substituting for or competing with the normal building blocks of DNA and RNA  i.e. the availability of normal purine or pyrimidine nucleotide precursors  May either by inhibiting the synthesis of normal nucleotides or compete with them in the formation of DNA or RNA

Question 95

are antimetabolites cell phase specific

Answer 95

Their maximal cytotoxic effects are in S-phase  Synthesis – DNA replicates, yielding two separate sets

Question 96

Antimetabolites types

Answer 96

 Folate antagonists  Pyrimidine antagonists  Purine antagonist

Question 97

Folate antagonists names | moa

Answer 97

methotrexate, pemetrexed inhibit folate syn=no nucleic acids

Question 98

methotrexate

Answer 98

folate antagonist

Question 99

pemetrexed

Answer 99

folate antag

Question 100

Pyrimidine antagonists:

Answer 100

5-Fluorouracil (5FU), Cytarabine, gemcitabine

Question 101

5-Fluorouracil (5FU),

Answer 101

Pyrimidine antagonists:

Question 102

Cytarabine

Answer 102

Pyrimidine antagonists:

Question 103

gemcitabine

Answer 103

Pyrimidine antagonists:

Question 104

Purine antagonists

Answer 104

Mercaptopurine, Fludarabine

Question 105

Mercaptopurine

Answer 105

Purine antagonist:

Question 106

Fludarabine

Answer 106

Purine antagonist

Question 107

 Folate antagonists, Pyrimidine antagonists, Purine antagonist moa

Answer 107

Inhibit precursors to DNA synthesis

Question 108

Methotrexate moa, used in? phase? affected tissues?

Answer 108

 Antineoplastic; immunosuppressant (psoriasis; RA)  Target S-phase (DNA replication), inhibit rapid proliferating cells  Bone marrow and intestinal epithelium  Myelosuppression risk for hemorrhage and infection

Question 109

methotrexate dental note  can cause?  what agents are most stomatotoxic  whiich rx known to be secreted into the saliva, result of this?

Answer 109

Dental Note: oral mucositis  Oral pain; Erythema; Difficulty opening the mouth  DNA cycle specific agents are most stomatotoxic  Methotrexate, etoposide known to be secreted into the saliva  further increasing stomato toxicity potential

Question 110

DNA cycle specific agents associated with oral mucositits

Answer 110

Methotrexate 5FU Cytarabine Doxorubicin Etoposide Bleomycin

Question 111

Cytotoxic Antibiotics moa

Answer 111

 Bind to and break DNA inside cancer cell to keep them from growing and multiplying | produce radicals

Question 112

cytotoxic abx groups

Answer 112

 Anthracyclines: Doxorubicin, daunorubicin, epirubicin, idarubicin.  Other: bleomycin, plicamycin, mitomycin

Question 113

Doxorubicin moa

Answer 113

Bind to and break DNA inside cancer cell to keep them from growing and multiplying | Cytotoxic Antibiotics

Question 114

daunorubicin moa

Answer 114

Bind to and break DNA inside cancer cell to keep them from growing and multiplying | Cytotoxic Antibiotics

Question 115

epirubicin moa

Answer 115

Bind to and break DNA inside cancer cell to keep them from growing and multiplying | Cytotoxic Antibiotics

Question 116

idarubicin moa

Answer 116

Bind to and break DNA inside cancer cell to keep them from growing and multiplying (via radical production) | Cytotoxic Antibiotics

Question 117

bleomycin moa

Answer 117

Bind to and break DNA inside cancer cell to keep them from growing and multiplying | Cytotoxic Antibiotics

Question 118

plicamycin moa

Answer 118

Bind to and break DNA inside cancer cell to keep them from growing and multiplying | Cytotoxic Antibiotics

Question 119

mitomycin moa

Answer 119

Bind to and break DNA inside cancer cell to keep them from growing and multiplying | Cytotoxic Antibiotics

Question 120

what can be seen orally with cytotoxic abx?

Answer 120

mucositis

Question 121

Mitotic Inhibitors

Answer 121

 Work in M-Phase to prevent cell division

Question 122

mitotic inhibitor groups include:

Answer 122

 Vinca Alkaloids: Vincristine, Vinblastine  Taxanes: Paclitaxel, Docetaxel

Question 123

Vincristine moa  Derived from ?

Answer 123

 Derived from Madagascar periwinkle  MOA: bind β tubulin & block its polymerization with α tubulin into microtubules  Cell division arrests in metaphase  Absence of intact mitotic spindle, chromosomes cannot align, disperse throughout the cytoplasm  Apoptosis

Question 124

vinka alkloids/ vincristine toxicity

Answer 124

 Peripheral neuropathy-numbness, tingling  Neurotoxicity may also be persistent, deep aching and burning pain that mimics a toothache

Question 125

Side Effects: Cell Replication Inhibition

Answer 125

 Primarily GI tract, Bone marrow, Oral cavity  Mucositis painful inflammation along GI  Develops within 1-week of chemotherapy initiation  Stomatotoxic (toxic effects on the oral tissues)  Impairment of bone marrow (myelosuppression)  suppressing white blood cells, red blood cells, and platelets  GET LABS THE DAY BEFORE ANY PROCEDURE  WBC >2000  ANC >2000  Platelets >75,000

Question 126

Oral Complications Common to Chemotherapy & Radiation

Answer 126

Oral mucositis (20-40%) Infection Xerostomia/salivary gland dysfunction Functional disabilities Taste alterations Nutritional compromise Abnormal dental development

Question 127

Oral mucositis with Chemotherapy & Radiation

Answer 127

inflammation and ulceration of the mucous membranes  can increase the risk for pain, oral and systemic infection, and nutritional compromise

Question 128

Infection with Chemotherapy & Radiation

Answer 128

viral, bacterial, and fungal  from myelosuppression, xerostomia, and/or damage to mucosa from chemotherapy or radiotherapy

Question 129

Xerostomia/salivary gland dysfunction with Chemotherapy & Radiation

Answer 129

dry mouth d/t thickened, reduced, or absent salivary flow  increases the risk of infection and compromises speaking, chewing, and swallowing  persistent dry mouth increases the risk for dental caries

Question 130

Functional disabilities with Chemotherapy & Radiation

Answer 130

impaired ability to eat, taste, swallow, and speak  due to mucositis, dry mouth, trismus, and infection

Question 131

Taste alterations with Chemotherapy & Radiation

Answer 131

changes in taste perception of foods, ranging from unpleasant to tasteless

Question 132

Nutritional compromise with Chemotherapy & Radiation

Answer 132

eating difficulties due to mucositis, dry mouth, dysphagia, and loss of taste

Question 133

Abnormal dental development with Chemotherapy & Radiation

Answer 133

altered tooth development, craniofacial growth, or skeletal development in children secondary to radiotherapy and/or high doses of chemotherapy before age 9

Question 134

Taste Alterations - Chemotherapy

Answer 134

Common occurrence following chemotherapy administration  Lasts 3-4 weeks post-treatment

Question 135

common meds of taste of alterations

Answer 135

 Cisplatin  Cyclophosphamide  Doxorubicin  5-Fluorouracil  Methotrexate  Paclitaxel  Vincristine

Question 136

Neurotoxicity of chemo | side effects of what rx's

Answer 136

Persistent, deep aching and burning pain that mimics a toothache, but no dental or mucosal source can be found.  side effect of certain classes of drugs (vinca alkaloids; platinum compounds)

Question 137

Bleeding with chemo

Answer 137

oral bleeding from the decreased platelets and clotting factors

Question 138

Radiation caries:

Answer 138

Radiation caries: lifelong risk of rampant dental decay that may begin within 3 months of completing radiation treatment if changes in quality or quantity of saliva persist

Question 139

Osteonecrosis with radiation

Answer 139

blood vessel compromise and necrosis of bone exposed to high-dose radiation therapy; results in decreased ability to heal if traumatized

Question 140

Disease States for Immunosuppression

Answer 140

 Autoimmune, collagen, connective tissue and inflammatory disorders  Systemic Lupus erythematosus  Rheumatoid arthritis  Chronic active hepatitis  Inflammatory bowel disease  Glomerulonephritis  Nephrotic syndrome  Myasthenia gravis  ...among others...  Organ or tissue transplantation  Prevent rejection

Question 141

Target of Immunosuppression

Answer 141

 Inhibit mononuclear cells (lymph and blood cells)

Question 142

T-cell Inhibitors

Answer 142

 Cyclosporine (Sandimmune)  Tacrolimus (Prograf; FK506)  Sirolimus (Rapamune)  Everolimus (Zortress)

Question 143

Cyclosporine (Sandimmune)

Answer 143

t cell inhib

Question 144

Tacrolimus (Prograf; FK506)

Answer 144

t cell inhib

Question 145

Sirolimus (Rapamune)

Answer 145

t cell inhib

Question 146

Everolimus (Zortress)

Answer 146

t cell inhib

Question 147

T-cell and B-cell inhibitors

Answer 147

 Azathioprine (Imuran)  Leflunomide (Arava)  Mycophenolate (Cellcept)

Question 148

 Azathioprine (Imuran)

Answer 148

b and t cell inhib

Question 149

Leflunomide (Arava)

Answer 149

b and t cell inhib

Question 150

Mycophenolate (Cellcept)

Answer 150

b and t cell inhib

Question 151

Corticosteroids

Answer 151

Corticosteroids = Glucocorticoids  Prednisone, dexamethasone, prednisolone, et

Question 152

t cell inhibitors moa | used for?

Answer 152

Downstream inhibit helper and killer T-cell activation  Actively attack/destroy any invading/invaded cell (each T-cell is specific to virus/bacteria/protein)  To prevent and treat rejection of organ and bone marrow transplants; RA; Psoriasis

Question 153

Cyclosporine – Side Effects | suggested tx's? avoid?

Answer 153

Question 154

Cyclosporine AND Tacrolimus DDIs

Answer 154

 Cimetidine (Tagamet)  Clarithromycin (Biaxin)  Erythromycin  Corticosteroids  Fluconazole (Diflucan)  Itraconazole (Sporanox)  Ketoconazole (Nizoral)

Question 155

Cyclosporine AND Tacrolimus Cimetidine DDI

Answer 155

Reports implicate cimetidine and famotidine as increasing cyclosporine concentrations and/or decreasing cyclosporine clearance

Question 156

Clarithromycin and tarcolimus

Answer 156

One report describes 2 female patients (aged 37 and 69 years), who each experienced acute renal failure and more than a 2.3-fold increase in tacrolimus serum concentrations after 9 doses of clarithromycin therapy (250 mg daily)

Question 157

Corticosteroids and cyclosporine

Answer 157

Toxic effects of prednisone and/or cyclosporine, if agents combined

Question 158

Azoles and cyclosporine concentrations

Answer 158

Serum cyclosporine concentrations have been reported to increase as much as tenfold in transplant patients following the initiation of azole antifungal agents

Question 159

T-Cell and B-Cell Inhibitors moa | used for?

Answer 159

 MOA: inhibit purine (azathioprine and mycophenolate) and pyrimidine (leflunomide) nucleotide synthesis for lymphocyte production (T and B)  Prevent and treat rejection of organ and bone marrow transplants; RA

Question 160

b and t cell inhibitors dental notes:  what rx's? can reduce effectiveness of mycophenolate  Risk for?

Answer 160

 Antacids and PPIs can reduce effectiveness of mycophenolate  Risk for infection increased while taking

Question 161

 Directly damage cell DNA  Impairs replication & transcription= cell death  Work in all phases of the cell cycle  Can be used in many different cancers

Answer 161

Alkylating Agents  moa?  cell cycle specific?  Can be used in?

Question 162

Nitrogen Mustards Platinum Compounds Nitrosoureas Alkyl sulfonates Triazines Ethylenimines

Answer 162

alkylating agents classes

Question 163

 cyclophosphamide (Cytoxan®), chlorambucil, ifosfamide, melphalan

Answer 163

Nitrogen Mustards:

Question 164

 cisplatin, carboplatin, oxaliplatin

Answer 164

Platinum Compounds:

Question 165

 streptozocin, carmustine (BCNU), and lomustine

Answer 165

Nitrosoureas:

Question 166

 dacarbazine (DTIC) and temozolomide (Temodar®)

Answer 166

Triazines:

Question 167

 thiotepa and altretamine (hexamethylmelamine)

Answer 167

Ethylenimines:

Question 168

interfere with DNA and RNA growth by substituting for or competing with the normal building blocks of DNA and RNA  i.e. the availability of normal purine or pyrimidine nucleotide precursors  May either by inhibiting the synthesis of normal nucleotides or compete with them in the formation of DNA or RNA

Answer 168

antimetabolites moa

Question 169

 Folate antagonists  Pyrimidine antagonists  Purine antagonist

Answer 169

Antimetabolites types

Question 170

methotrexate, pemetrexed

Answer 170

Folate antagonists names

Question 171

5-Fluorouracil (5FU), Cytarabine, gemcitabine

Answer 171

Pyrimidine antagonists:

Question 172

Mercaptopurine, Fludarabine

Answer 172

Purine antagonists

Question 173

Inhibit precursors to DNA synthesis

Answer 173

 Folate antagonists, Pyrimidine antagonists, Purine antagonist moa

Question 174

 Bind to and break DNA inside cancer cell to keep them from growing and multiplying

Answer 174

Cytotoxic Antibiotics

Question 175

 Anthracyclines: Doxorubicin, daunorubicin, epirubicin, idarubicin.  Other: bleomycin, plicamycin, mitomycin

Answer 175

cytotoxic abx groups

Question 176

 Work in M-Phase to prevent cell division

Answer 176

Mitotic Inhibitors

Question 177

 Vinca Alkaloids: Vincristine, Vinblastine  Taxanes: Paclitaxel, Docetaxel

Answer 177

mitotic inhibitor groups include:

Question 178

 Cisplatin  Cyclophosphamide  Doxorubicin  5-Fluorouracil  Methotrexate  Paclitaxel  Vincristine

Answer 178

common meds of taste of alterations

Question 179

 Cyclosporine (Sandimmune)  Tacrolimus (Prograf; FK506)  Sirolimus (Rapamune)  Everolimus (Zortress)

Answer 179

T-cell Inhibitors

Question 180

 Azathioprine (Imuran)  Leflunomide (Arava)  Mycophenolate (Cellcept)

Answer 180

T-cell and B-cell inhibitors