CHEMOSH1 Flashcards
Cell Cycle and what drugs work where
M phase : cell mitosis ( cell division ) - [ Vinca Alkaloids ; Taxanes )
G1/G0 phase: cell makes enzymes for dna synthesis [ ( Alkylating agents and Anti Tumor ABX - these are non cell cycle specific and realize they work on multiple phases )
S Phase: cell replication of DNA ( Antimetabolites ) ( MTX , 5FU, Capcetabine ( xeloda ), 6 mercaptopurine )
G2: RNA and other proteins are synthesized to prepare for cell division during M phase ( plant alkaloids- Etoposide, Teniposide, Irinotecan )
Cell cycle specific and cell cycle non specific
Cell cycle specific:
• eg ) Antimetabolites ( MTX ) ; Vinca Plant Alkaloids
Cell cycle non specific :
• alkylating agents , cytotoxic ABX
problems associated with chemo
N/V ( most NV is cisplantin ( platinol )
Bone Marrow : neutropenia , thrombocytopenia, Anemia
Tumor lysis syndrome
Chemo induced peripheral neuropathy
Treat N/V
1 ) 5- HT3 serotonin R blockers
• Dolasetron ( Anzemet ), Granisetron ( kytril ), Ondansetron ( zofran ), palonsetron ( aloxi )
2) Corticosteroids: dexamethasone
3) Neurokinin ( NK ) - 1 Receptor antagonists
• aprepitant ( Emend ) ( PO ) / Fosaprepitant ( IV ), Rolapitant ( Varubi ) ( PO )
4) Cannabinoids: dronabinol ( Marinol ), Nabilone ( Cesamet )
5) Dopaminergic antagonists: metoclopramide ( reglan ) [[[ dont give to Parkinsons pts. Dont want to decrease dopamine in parkisons patients )
6) antihistamines, Benzodiazepines - antihistamines can be used but really not used bc not strong enough / benzodiazepines is off label use. Can be used if you see question.
7) pts on CISPLATIN or other highly emetogenic can add olanzapine ( off label)
5HT3 inhibitors
All of these you worry about qt prolongation
Dolasetron- anzemet
IV and PO. Due to qtc prolongation IV is contraindicated for CINV
Granistron : IV/ SQ/ PO / tabs / transdermal
• IV ( kytril ) : 1 mg 30 mins prior to tx
• PO ( Granisol ) : 1 hour prior
• ER SQ ( Sustol ) : Q7 days 30 mins before chemo
• Transdermal ( Sancuso ) : 24 - 48 hours before chemo for up to 7 days. Avoid sun
Ondansetron :
Zofran: IV/ IM. / PO ( odt )
Zuplenz ( thin strip odt like )
Palonsetron - ALoxi ( Use ALOXI if worrying about QT prolongation )
IV only
COMBO: neutapitant + palonsetron ( alkynzeo )
CORTICOSTEROIDS
Used alone or w/5HT3 antagonists
Dexamethasone ( decadron )
Methylprednisolone ( medrol )
NK-1 receptor blocker
Add on
Neurokinin 1
• aprepitatn ( emend ) PO -sub of 3a4 ( also inhibitor of 3 a4 )
• Fosaprepitant ( Emend IV ) - sub of 3A4 ( also inhibitor of 3a4)
- 1) 2) need to give day 2 and 3 bc not long half life
- Rolapitant ( Varubi PO ) ( not a 3 a4 inhibitor bud does effect 2d6 inhibitory ) - what med goes through 2d6 to get activated? Tamoxifen
- Rolapitant: long half life ( give day1 only )
NK1 R Antagonists work by blocking substance P, which activates a pathway in the brain that causes N/V
Cannabinoids
Dronabinol ( marinol / syndros ) ( schedule 3 )
Marinol refrigerated have to give 1- 3 hours before then q2-4 hrs
Syndros
Nabilone ( cesamet ) c2 used BID
Dopamine antagonists
Metoclopramide ( reglan ) : blocks dopamine in the brain vomiting center
- never give to Parkinson’s patients
SE: diarrhea, drowsiness, extrapyramidal side effects ( spasms )
- if they get extrapyramidal side effects then give Benadryl bc it’s anticholinergic
Prochlorperazine
- PO tabs
- rectal suppository ( Compro )
Antihistamines
Commonly used to control N/V but not very effective for cancer induced N/V
Diphenhydramine
Hydroxyzine : vistaril ; atarax
S/E: mild relaxation, drowsiness, dry mouth, constipation ( anticholinergic)
Benzodiazepines
NOT FDA approved but off label
Lorazepam ( Ativan )
Usually add on. Not effective at all alone for chemo induced N/V
Chemo induced anemia
No FDA approval for patients that have a cure for cancer. If no cure you may use can cause thromboembolic effects and tumor growth
Erythropoietin ( epogen, Procrit ) ( also used in ESRD ) ( zidovudine induced anemia ) ( and patients without a cure )
Discard vial after 21 days. Given once weekly
Darbepoetin Alfa ( aranesp ) : benefit not given as often. Once every 3 weeks.
Chemo doesn’t cause anemia right away. RBC live up to 120 days.
Both do not shake protect from light. Refrigerate. Any crystals, then discard.
Cannot use if BP high. REMS drug: increases risk of CV, thormboembolic events and tumor progression.
keep Hgb between 10-11 g/dl ( IF treating zidovudine induced anemia then up to 12g/dL )
MONITOR: BP, HgB 10 -11 ( zidovudine 12) , serum ferritin ( without iron bone marrow cant make RBC start iron if serum ferritin < 100 mcg/ml ) , folic acid level
Correct iron b12 and folate prior to tx
Chemo induced Thrombocytopenia
Neumega ( oprelvekin ) it’s DC’d
Neumega : megaplatelets
It’s DC’d but recognized it’s used for thromobocytopenia
Neutropenia
Neutrophils live 6- 8 hours
Chemo induced Leukopenia ( ↓WBC )
Filrastim ( Granix, Neupogen, zarxio( biosimilar form ) )
5mcgk/kg /day
24 hours RT
Pegfilgrastim ( * Neulesta ) : pegalated form. Benefit you dont give as often.
6mg 1x each chemo cycycle
48 Hours RT
SE for BOTH : Bone pain.
Can be really bad for certain patients.
Tumor lysis Syndrome:
Lysis of tumor cells results in rapid release of K+, purine nucleic acids, PO4, which leads to HYPERKALEMIA, HYPERURICEMIA, and HYPERPHOSPHATEMIA with secondary HYPOCALCEMIA
These metabolic abnormalities can subsequently lead to acute renal failure ( ARF ) and multiple organ failure —-> death
Can also cause cardiac arrhythmia ( hyperkalemia )
Tx: get k+ into cell. Give sodium bicarbonate, insulin and glucose, b2 agonists . Then kayexolate to actually get rid of k+ ( kayexolate takes time, thats why you first try to k into the cell )
HYPERPHOSPHATEMIA ( PhosLo : calcium acetate , other non ca agents Sevelamer , renagel )
HYPERURICEMIA: allopurinol ( watch out for DDI : 6MP ) and hydration
Azathiopurine : becomes 6MP
HYPERPHOSPHATEMIA
PhosLo: calcium acetate. ( SE: constipation, hypercalcemia )
- Sevelamer ( renagel; revela ) w/food
Aluminum hydroxide : AleenaGel ; amphogel ( never give amphogel to patient who has CKD; aluminum toxicity )
Hyperkalemia
( need to protect heart )
1) give IV calcium :
Calcium chloride has a lot more elemental calcium than calcium gluconate. However calcium gluconate easier to give and doesn’t irritate when giving IV.
If you need to give calcium chloride use a central line.
2) get k into cell. Sodium bicarbonate : shifts k intracellularly. Insulin and dextrose : IV regular insulin induces intracellu lar flux of k+.
Kayexalate: gets rid of extracellular k+ . Sodium polystyrene sulfonate : exchanges Na+ for K+ and binds it in the gut to ↓total body K+. Onset after
Beta2 agonists: drives K into the cells.
Veltassa: doesn’t increase sodium levels and binds to potassium.
Both cause constipation
Calcium chloride has a lot more elemental calcium than calcium gluconate
T
CaCl: 1g = 270 mg of elemental calcium
Ca Gluconate: 1 g = 90 mg of elemental calcium
CIPN
Chemo induced pheripheral neuropathy
• Platinum drugs: cisplatin , carboplatin, oxaliplatin
• Taxanes: paclitaxel ( Taxol ), docetaxel ( taxotere ), and cabazitaxel ( Jevtana )
• Epothilones: ixabepilone ( ixempra )
•plant alkaloids : vinblastine, vincristine, vinorelbine, and etoposide ( VP -16)
• thalidomide ( Thalomid ), lenalidomide ( Revlimid ), and pomalidomide ( pomalysts )
• bortezomib ( Velcade ) and carfilzomib ( kyprolis )
• Eribulin ( Halaven )
3 major agents: 1) platinum drugs, Taxanes and last vinka alkaloids
Chemotherapy calculations
Based on BSA mg/mˆ2
mg/mˆ2
One inch = 2.54 cm
1kg = 2.2 pounds
BSA = √ [ height in cm x weight in kg ) / 3600 ]
Ex:
Doxorubicin dose: 60 mg / mˆ2
If BSA = 2 mˆ2
Dose= 120 mg
General policy and procedures of making chemo therapy
Fan/blower and requirements: LAFW operated continuously 24 hours or on 30 mins prior to compounding
Certified hood every 6 months
Yellow sharps for chemo 2/3 full max
Eye protection/ 2 pairs of gloves. Zip log bag.
Vertical flow hood to protect techs.
Alkylating agents
•cisplatin, carboplatin, oxaliplatin
• busulfan
• cyclophosphamide, Ifosphamide, Temozolomide = hepatotoxicity
• carmustine, lomustine
• streptozocin
• melphalan, mechlorethamine, altretamine,
• Dacarbazine, Procarbazine,
• Bendamustine ( Treanda )
- an alkylating agent for tx of chronic lymphocytic leukemia
Antimetabolites
•MTX methotrexate
• Fluorouracil ( 5-FU )
• Mercaptopurine ( 6-MP )
• Cytarbine, fludarbine, capecitabine, cladribine
• Pentostatin
• Thioguanine
• Hydroxyurea
ABX
• bleomycin
• dactinomycin, Daunorubicin, valrubicin,
•doxorubicin liposomal / non-liposomal
•epirubicin, idarubicin
•mitomycin, Plicamycin
• Mitoxantrone *
• idarubicin
Plant alkaloids
Docetaxel, Paclitaxel
Etoposide, Teniposide
Irinotecan, Topotecan
Tax= you know if you see that it’ll cause peripheral neuropathy
Cisplatin
Platinol
Nephrotoxic : give IV fluid, ( amifostine) given prophylactically to prevent nephrotoxicity ) and give mannitol to promote excretion
OTOTOXICITY ( dont give with vanco , aminoglycoside )
Peripheral neuropathy
this agent cause most GI upset
Mannitol
Amifostine
Osmotic diuretic ( if you see crystals in mannitol, warm it up , shake and it’ll dissolve )
Amifostine ( Ethyol ) start before chemo. SE: decreases pt BP
Carboplatin ( paraplatin )
Analog of cisplatin
BuSulfan
Busulfex; myleran )
Increases : uric acid use allopurinol ( watch out for other drugs thiazide & loops, niacin , asa )
Pulmonary fibrosis
Seizures , skin rash, bone marrow Suppression
Cyclophosphamide
( Cytoxan )
PO and IV
Hemorrhagic cystitis ( shedding of the bladder from metabolite acrelein ) give prophylactic MESNA ( binds to acrolein )
Heptoxic, renal tubular necrosis, alopecia ( frequent . 3 weeks after therapy )
Ifosfamide
IFEX ( IV )
Analog of cyclophosphamide
Use hydration and MESNA to protect bladder
Alopecia, CNS tox, nephrotox
Carmustine
And
Lomustine
Carmustine ( BiCNU) / Lomustine ( CeeNu / Gleostine )
Pulmonary fibrosis
- dose related. Can happen years later.
Hepatotox, nephrotox
Streptozocin
Melphalan
IV Zanosar to treat pancreatic cancer
SE: dose response: type 1 DM
Melphalan IV PO : ( alkeran )
Use within 60 mins of reconstitution
Mechlorethamine
( mustargen, Valchlor )
IV: mustargen
- extravasation associated with severe necrosis. Treat with Na - thiosulfate and ice compress. ( recall nitroprusside hypertensive emergency , nitroprusside can cause cyanide toxicity and for that toxicity we can use sodium thiosulfate )
Topical gel : Valchlor
Fertility impairment : Rph should not work with these meds if desiring to get pregnant
Altretamine
( hexalen )
Perpheral neuropathy
Used to treat ovarian cancer
If you add MAOI ( lenazolid, nardil ) may cause severe orthostatic hypotension
Procarbazine
Matulane
Is an MAOI.
Disulfiram like reaction
Bendamustine
( treanda )
IV
Make with NS
SE : myelosuprresion - infections
Tumor lysis syndrome
Allopurinol : purine in there can cause rash.
