Chemotherapeutics Flashcards
Which interphases do cell spend most of their time
G1
S
G2
In interphase, cells will
Double; cytoplasm synthesis DNA
What happens is G0 phase?
Performing normal functions; not going through process of dividing
When is G0 phase signaled?
Signaled to progress through cell cycle by presence of growth factors & other signals
In G0 phase, mutated cells are
Permanent (avoids replication which is a good thing)
What happens in G1 phase
Cells recruited into the growth faction start G1
Which phase starts prior to DNA synthesis?
G1
Cell characteristics in G1 phase
Cells increase in mass & organelles in preparation for cell division; diploid w/2 sets of chromosomes
What happens in the S (synthesis) phase?
DNA synthesis
Duplication of chromosomes
Continued cell growth
DNA check point
Normally, if an error is found, what happens to the cell?
Either repaired or cellular apoptosis
When does G2 phase begin
Between DNA replication & start of miosis
Characteristics of cells in G2 phase
Synthesis of additional proteins & cellular mitotic materials
Continued cell growth
Additional DNA checkpoint
What happens in M phase
Cell divided into 2 daughter cells (4 phases)
In mitosis (M phase), prophase is when
Chromatin condenses into distinct chromosomes
Chromosomes migrate to center of cell
Nuclear envelope breaks down & spindle fibers form
In mitosis (M phase), metaphase includes
Nuclear membrane disappears
Spindle develops
Chromosomes align
In mitosis (M phase), anaphase involves
Paired chromosomes separate
Spindle fibers lengthen the cell
In mitosis (M phase) l, telophase involves
Chromosomes sectioned off into distinct new nuclei
Genetic content distributed equally
Cytokinesis begins
Cytokinesis involves
Division of cytoplasm in o form 2 new cells
Begins after anaphase & finishes after telophase
How are males giant cells characterized
Rapid division & synthesis of DNA
Multiply without growth factor
Genetic mutations (oncogenes)- overactive ; CA promoting
Problems with encoding regulator proteins
Mutations promote
Increased cell growth & division
Mutations escape
Internal & external division controls
Avoids programmed cell death (apoptosis)
Additional mutations are often required in
Tumor progression
Malignant tumors are insensitive to
Anti-growth signaling
Malignant tumors are
Groups of cells that divide excessively (self-sufficient)
What is sustained angiogenesis?
Growth of new blood vessels
Source of O2 & nutrients
What is the role of P53 (protein)?
A tumor suppressor
Triggers production of cell cycle inhibitor
Allows activation of DNA repair enzymes
When is p53 activated?
At G1 checkpoint which controls transition to S phase
Telomeres are
DNA end caps that prevents loss of genes as chromosome end
Shortened & losses related to cellular aging
What is telomerASE
Enzyme that extends telomeres
Reverses telomere shortening
Contemporary therapy aims to
Harness the power of intrinsic immune system actions
What is the target of chemotherapy?
Cells that are actively undergoing DNA synthesis or mitosis
4 anesthetic considerations of chemo
N/v or diarrhea
Kidney issues
Liver issues
Fluid balance
What is CIPN
Common (chemo induced peripheral neuropathy) which can effect pain management & regional anesthesia
Alkylating agents work where?
In all phases
MOA for Alkylating agents
Form covalent alkyl bonds w/ nucleus acid (DNA) bases
Forms intra/interstrand DNA crosslinks
Impairs DNA structure
Inhibits replication & transcription
Alkylating agents are indicated for
Hematologic malignancy
Solid tumors
Alkylating agents adverse effects
Bone marrow suppression (lymphocytopenia w/in 24h & hemolytic anemia
Gonadal dysfunction
GI disturbance (hypertrophy & shedding)
Alkylating agents effects on CNS
N/v
Muscle weakness
Seizure
Alkylating agents can cause
Follicular damage (alopecia)
Alkylating agents effects on pulmonary
Pneumonitis
Pulmonary fibrosis
Decreased diffusion capacity
Alkylating agents effects on heart
Cardiotoxic
Pericarditis, pericardial effusion (tamponade)
Hemorrhagic myocarditis w/CHF
Alkylating agents can cause
Hepatotoxic
New/secondary malignancy
Phlebitis & thrombophlebitis
Alkylating agents can inhibit
Plasma cholinesterase for up to 2-3 weeks which can lead to a prolonged paralysis with Suxx
Alkylating agents can cause this with the kidney
Nephropathy related to uric acid
(Allopurinol)
Alkylating agents can have acquired
Resistance to alkylating therapy
Decreased cell permeability
Increased production of competitive substances
Common Platinum Complexes
Cisplatin
Carboplatin
Platinum Complexes are
Non cell specific and are alkylating like agents (Damaging all phases)
MOA of Platinum Complexes
Crosslinks adjacent or opposing bases to disrupt DNA
Inhibit essential cellular processes
Inhibit enzyme involved in replication & division
Which Platinum Complexes is mostly used?
Cisplatin for Solid tumors
Adverse effects for Cisplantin, a Platinum Complex
Black box- nephrotoxic ( decreased GFR, increased creatinine)
Renal tubular necrosis leading to renal failure
Effects of Cisplatin, a Platinum Complex on the ears
Ototoxic
Tinnitus
Hearing loss
Effects of Cisplatin, a Platinum Complex on periphery
Black box- peripheral neuropathy
Sensory neuropathy
Paresthesia
Loss of vibratory & position sensation
All reversible
Effects of Cisplatin, a Platinum Complex on bone
Myelosuppression
Leukopenia
Thrombocytopenia
Effects of Cisplatin, a Platinum Complex on GIT
n/v- black box
Effects of Cisplatin, a Platinum Complex, can cause hypersensitive reactions such as
Facial edema
Bronchoconstriction
Tachycardia
HOTN
Antimetabolites is cell cycle specific with a MOA of
Prevent synthesis of complementary DNA in S phase which acts as a FALSE nutrient (mimics folic acid)
Enzyme inhibition
Mimics nucleobases
Stops DNA replication & cell proliferation
Antimetabolites indications
Hematologic
Psoriasis (methotrexate)
RA
Solid tumors
Antimetabolites effects
High alert
Resistance to therapy risks
Bone marrow suppression (megaloblastic anemia)
Pulmonary toxicity
GI toxic
Nephrotoxic
Hepatotoxic
Caution with nasal ‘ oral airway
Ataxia
Drowsiness
Dermatological toxicity (photosensitive)
Topoisomerase inhibitors are cell cycle specific with a MOA of
Corrects DNA alterations during replication & transcription
Inhibits topoisomerase 1 or 2
Inhibits uncoiling of DNA during replication
Most active during S & early G 2 phase
Anthracycline anti tumors antibiotics
Create free radicals to break DNA strands
Topoisomerase inhibitors indications
Solid tumors
Hematologic
Topoisomerase inhibitors & antitumor adverse effects on CV
Cardiotoxic (doxorubicin & daunorubicin)
Free radicals disrupt cardiac protein & cell membrane components
Increased troponin T
CHF w/ impaired LV function
Acute myopathy w/arrhythmias
Fatal form associated w/ bronchitis & progressive ventricular failure
Dexrazoxane is a
Free radical scavenger & protective against damage
Topoisomerase inhibitors & antitumor adverse effects on lungs
Pulmonary toxic-Bleomycin
Free radical production in presence of O2 ‘ iron/copper
Capillary endothelial’ alveolar damage
Pulmonary fibrosis
Hypoxia dyspnea pneumonitis
Pulmonary lesions & infiltrates
Decreased pulmonary diffusion capacity
Topoisomerase inhibitors & antitumor anesthesia considerations
Post-op respiratory failure in bleomycin
Risk w/ excessive crystalloid (use colloid & minimize fluids)
Risk in presence of hyperoxia
Keep inhaled 02 concentration below 30%
Risk factors include pre-existing pulmonary damage or renal dysfunction
Topoisomerase inhibitors & antitumor adverse effects
Myelosuppression
GI disturbances
Alopecia
Microtubule inhibitors are cell specific & have a MOA of
Microtubules create cellular architecture & mediate cellular functions
Vinca alkaloids (bind & inhibit microtubule formation)
Taxanes (bind & inhibit microtubule breakdown)
Active in M phase
Mitosis phase fails & cell does w/o replicating
Microtubule inhibitors adverse effects
Myelosuppression
Autonomic neuropathy (ortho HOTN, decreased GI motility, laryngeal nerve paralysis-hoarseness, urinary retention, dry mouth, tachycardia
The Microtubule inhibitors, Taxanes effects on the heart
Dysrhythmias
Ischemia
Edema
Effusion
The neuromuscular effects of Microtubule inhibitors
Atonal demylenation
Sensory motor neuropathy
Areflexia
Paresthesia
Skeletal muscle pain weakness & ataxia
Microtubule inhibitors effects of periphery
Peripheral neuropathy
Smirks of worsening neuropathy w/ regional & general
Use lowest concentration of local
AVOID EPI additives
Use nerve location technique
Signal transduction modifiers (hormone) MOA
Variable
Normal cells require GF a/specific receptors
Hormonal tx disrupts growth factor- receptors interactions
Targets over expression
Signal transduction modifiers are indicated for
Solid tumors
Autoimmune disease
Signal transduction modifiers side effects
Thromboembolic events & stroke
Increased risk CV disease
Secondary malignancy (tamoxifen) leading to uterine CA
Hepatotoxic
Wt gain
Myalgia arthralgia fractures
Signal transduction modifiers can cause
GI disturbances
Hormonal changes
Immunomodylatory drugs
Treat multiple myeloma
Antiproliferative antiangiogenic imnunomodulatory effects
Thalidomide. Lenalidomide
Pomalidomide
Cancer immunotherapies
Bind immune checkpoints proteins
Reprogram T cells to attack cancer cells
Inflammatory side effect tx with corticosteroids & immunosuppressants
Adoptive cellular therapy autologous T cells
Genetically engineered to recognize & attack tumor cells
Risk for life threatening side effects such as release of cytokines & systemic inflammation
