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Onco 2 Chemo

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sihirlifil's version from 2018-04-06 16:00

Basics

Question Answer
4 basic concepts of tumor growthGompertzian (exponential)
Goldie-Coldman Hypothesis
Skipper’s Log Kill Hypothesis
Cell Cycle Kinetics
Describe Gompertzian growthInitially high growth fraction (proportion of cells actively proliferating), short tumor doubling time. By the time it’s clinically detectable, contains at least 10^9 cells, undergone 30 doublings!
Growth type? How can we start tx at red?
Gompertzian
Screening test to detect early! even w/ no CS. or cytoreduction w/ radiation or sx
Describe Goldie-Coldman hypothesisSpontaneousmutation occurs in as many as 1 in 10,000 cells, so resistance is there before we even start therapy. early tx vital!
Describe Skipper’s Log Kill hypothesisCertain percentage of tumor cells (not set #) are killed with each tx ((e.g. drug that kilss 99.9% reduces lesion of 10^9 cells to 10^6, which is clinically undetectable. Pt considered to be in remission, but tumor cells remain. 2nd tx could reduce 10^6 to 1000 cells, etc)
Other factors including tumor cell sensitivity & cell cycle kinetics play a role, & cells continue to divide during therapy
Growth type?
Skipper’s Log Kill
Cell cycle kinetics: efficacy of cancer therapy depends on?Effects on progression through cell cycle
Phase of cycle cell is in at time of drug exposure
Cell cycle kinetics: what does it have to do w/ combo chemo protocols?Protocols designed to target different parts of cell cycle
Combos increase proportion of total tumor cells affected at any 1 tx time
What’s happening during the cell cycle?
How does drug resistance happen?MDR: induction of p-glycoprotein efflux pump (vinca alkaloids, steroids, anti-tumor antibx)
Mechanisms of drug resistance (3)Decreased influx
Increased detoxification of drug radicals (by glutathione)
Increased DNA repair
(Q’s to ask about chemo)
Treatment considerationsWhat type of therapy available? Is it the most effective? Potential SEffx? Can be tx by local vet or need referral? Most $-effective?
What to keep in mind when choosing chemo protocolsIf routinely consulting w/ oncologist, use their protocols
$$$ major factor; time, nursing care; geographic distance from tx
Safety issues: prep, admin, disposal, patient care/handling after tx
Demeanor, health/eval of patient (concurrent dz)
DO NOT USE COOKBOOK TECHNIQUE! every protocol tailored to patient
Client expectations & fears!
memorize

Drugs & Toxicity

Question Answer
What are the 3 common toxicities again?BM suppression, alopecia, GI upset (BAG)
BM suppression: which cells most susceptible?Shortest life span (neutrophils! so see neutropenia 1st on CBC, wont see anemia after just 1 week)
How long does it take for BM suppression? manageable?Predictable: 7-10d for most
Generally manageable
What is Neupogen (filgrastim)?Growth stim factor for BM. It’s a human product though so they can dev’p antiobodies (only uses if deaths door really)
Is alopecia common? in who?Uncommon due to differences in hair coats. happens with curly coats (poodles) b/c they actually have hair lol (alwo whiskers in cats)
How long does it take for GI effx?3-5 days. generally manageable
What is this table for?
Make sure no matter what breed/body size, still getting the same amount of medication
Chemo terminology: therapy? protocols?Systemic vs localized, 1ry vs adjuvant vs neoadjuvant
Induction vs maintenance vs rescue protocols
Alkylating agents: mechanismCell-cycle-phase nonspecific
Cross-link DNA, prevent replication
Alkylating agents: derived from?Nitrogen mustard (Chlorambucil, Cyclophosphamide, Melphalan)
Nitrosureas (Lomustine/CCNU)
!! Chlorambucil: which cancer?Chronic lymphocytic leukemia & lymphoma. PO only
Cyclophosphamide: which cancer?Part of many combo protocols, PO/IV (PO preferred b/c can stop right away if SEffx)
*** Cyclophosphamide: SEffxSterile hemorrhagic cystitis
!! Melphalan: which cancer?Multiple myeloma, PO
!! Lomustine: which cancer?Canine lymphoma, MCT, brain tumors PO ONLY!
*** Lomustine: SeffxPENETRATES CNS
Delayed myelosuppression
Thrombocytopenia, hepatotoxicity so CHECK ALT & ALP
(possible pulmonary tox in cats)
Antimetabolites: mechanismCell-cycle-phase SPECIFIC (S-phase)
Structurally similar to natural compounds required for synth of purines, pyrimidines, nucleic acids = interfere w/ DNA synth
Antimetabolites: which drugs?Cytosine arabinoside, 5-Fluorouracil, Azathioprine
!! Cytosine arabinoside: which cancer?Lymphoma (esp renal) CRI or SQ
*** Cytosine arabinoside: SEffxPenetrates CNS (used for GME)
!! 5-FU: which cancer?Carcinomas, sarcoids. IC or IV, topical cream avail
** 5-FU: SEffxFATAL NEUROTOXICITY IN CATS
Azathioprine: used for what?Immunosuppressive agent, ITP (immune thrombocytopenic purpura?). PO
Vinca alkaloids: mechanismCell-cycle-phase SPECIFIC (M-phase)
Inhibit microtubule formation, disrupt microtubule disassembly
Vinca alkaloids: which drugs?Vincristine, Vinblastine
Vincristine & Vinorelbine: derived from?Periwinkle plant :)
!! Vincristine: which cancer?Curative for TVT!
Lymphoma, chronic & acute lymphocytic leukemia
*** Vincristine: SEffxVesicant!
Thrombocytosis, peripheral neurotoxicity (reports dragging feet, scuffed toes. HL ataxia)
!! Vinorelbine: which cancer?Lung tumors, TCC
!! Vinblastine: which cancer?MCT!
***Vinblastine: SEffxVesicant
Peripheral neurotoxicity
!! Taxol: which cancer?Mammary tumors
Taxol: derived from?Pacific yew tree
*** Taxol: SEffxEstrus-like behavior. Vehicle (Cremophor EL) causes hypersensitivity reaction
What happened here?
Vinblastine extravasation *&^%@! (lol)
Antitumor antibx: mechanismCell-cycle-phase nonspecific
DNA dmg via free radical formation/interference w/ topoisomerase II activity (cut both strands of DNA helix simultaneously)
Antitumor antibx: which drugs?Doxorubicin, Mitoxantrone, Actinomycin D
!! Doxorubicin: which cancer?Numerous combo protocols (baytril of chemo) IV!
*** Doxorubicin: SEffxVESICANT!!! animal can lose leg!!! (used for OSA protocols)
Causes MC degranulation (some pre-tx w/ steroids)
DOGS: Dose-cumulative cardiotox (worry about dobies, CKCS, boxers), anaphylaxis
CATS: nephrotoxicity, anorexia
What is Dexrazoxane?Derivative of EDTA, chelates iron & interferes w/ Fe-mediated free radical generation though to be responsible for anthracycline-induced cardiomyopathy. Makes SEffx of Doxorubicin less severe, treats extravasation
!!Mitoxantrone: what does it do?Similar in action to Doxorubicin but less cardiotoxic & less severe tissue reaction to extravasation
More expensive & more myelosuppressive
IV, IC
!! Actinomycin D: which cancer?Used in some sarcoma protocols, rescue agent for lymphoma (IV)
Hormones: mechanismDepends on which hormone used
Glucocorts: Lymphocytotoxic (affect replication at nuclear lvl) so use for lymphoma
Hormones: which are used?Prednisone
Estrogens
Testosterone
Progesterones
*** Prednisone: SEffxPolyphagia, PU/PD, panting, GI ulcers
Misc chemo agentL-Asparaginase
L-Asparaginase: mechanismCell-cycle-phase SPECIFIC (G1)
Cleaves asparagine, a nucleic acid needed for protein synthesis (IM b/c hypersensitivity!)
Normal cells can synth asparagine, so aren’t affected
!! L-Asparaginase: which cancer?Lympoma (huge LN normal again w/in 6h! Good for BM issues)
*** L-Asparaginase: SEffxPancreatitis
Anaphylaxis
Hypersensitivity to E. coli
Platinum agents/Heavy metals: mechanismCell-cycle-phase nonspecific
Cross-link DNA & prevent replication
Platinum/heavy metals: which drugs?Cisplatin, Carboplatin
!! Cisplatin: which tumors?OSA, various carcinomas, sarcoids
*** Cisplatin: SEffxNephrotoxicity, acute emesis, ototoxicity
Saline diuresis required to prevent acute proximal tubular necrosis (90% drug excreted unchanged in urine)
FATAL PULMONARY EDEMA IN CATS
!! Carboplatin: which cancer?OSA, melanoma, various carcinomas
How does carboplatin differ from cisplatin?Less nephrotoxic, does not require saline diuresis! Reconstitute w/ D5Q & admin over 10-20 min
Safe for cats
How to manage BM tox? (Chart)
Which anti-emetics used to manage GI tox?Maropitant, Ondansetron, Metoclopramide, Butorphanol, Dolasaetron
Which anti-diarrheals used to manage GI tox?Metronidazol, dietary modification
Which appetite stiumulants are used for supportive care?Mirtazapine, Cyproheptadine, Valium, PRED!
If EXTRAVASATION: what do?Minimize amt of drug at site! Don’t remove catheter or needle, withdraw as much from tissue, tubing, & catheter
Admin antidote/sterile saline to neutralize or dilute drug (EXCEPT FOR DOCORUBICIN)
Warm or cold compress
If seeing effx of anemia early on in treatment…?It isn’t due to chemo effects! could be something else going on (same w/ GI bleeding (pancreatitis, parvo, garbage gut), IMHA, orthopedic disorders, pain vs dypshoria)
memorize

Chemotherapy administration

Question Answer
OSHA =Occupational Safety & Health Administration
Published guidelines for safe handling of chemo drugs. Requires all involved be informed of appropriate safety precautions (should give chemo in private practice!
Greatest risk of exposure when?During drug preparation & admin
Primary routes of chemo exposureInhalation, direct contact, ingestion of improperly handled drugs
Handling of discarded items that have come into contact (syringes, catheters, gloves…)
Concact w/ excrement from patients
Important to have for patients receiving chemoNurse that you trust! They are the ones handling & administering the drug & monitoring the patient. Client sees them more! Need to have skills to get catheter into vein
Potential problem?
Drug bottles look the same! store separately, have limited access to these, ID with distinctive labels, store away from food!!!
Which vein for venipuncture? why?Jugular to save peripheral vv. for catheter
5 ‘rights’ of chemo adminRight patient, drug, dose, interval, route
Most common mistake with administrationForget to convert lb to kg! then to m2
At least 2 people should calculate beforehand
Chemo admin sheet should have?Lab values, weight, premed, routes of admin, site of cathteter, dose of drug & calculations, comments (animal behavior, dose reductions, client observations), NOTES (valuable when making future decisions about drug admin & dosing in each particular patient)
**What safety thing is the tech doing?
Give few mL of chemo, pull back & see blood flash to ensure catheter is still in the vein (no extravasation!)
What’s a venous access port?Long-term vascular access for delivery of chemo, sedation for radiation, antibx, anti-seizure meds, repeated blood draws (fractious patient, tortuous veins, long time, blew all veins & couldn’t do tx, etc)
Which safety features does PhaSeal (Closed System Drug Transfer Devices) have?Expansion chamber to capture dangerous aerosols & vapors (elim exposure to airborne contaminants), double membrane to ensure dry connections that avoid workspace contamination, Needle-Safe design for contained retrieval of all reconstituted meds from vial
memorize