Parang Pharmacist alerts

How can you reduce skin toxicity of alkylating agents

administer with 2% sodium thiosulfate, thiosulfate removes chlorine groups and ionizes drug = excretion

Which alkylating agents are orally administered

mustards with aromatic group = nitrogen electrophile site is less electron dense due to EWG (aromatic rings) = increased stability

Which agent causes bladder toxicity and how can you mitigate it

cyclophosphamide and ifosfamide = generates toxic metabolite acrolein that can cause hemorrhagic cystitis. Reduce toxicity by increasing hydration and administering with mesna: Mesna gets alkylated instead of bladder cells. Mesna alkylated product is ionized and therefore excreted

Which nitrogen mustard is the most toxic and can only be administered IV

mechlorethamine = aliphatic group

True or false Cyclophosphamide is a prodrug

True, requires oxidative deamination in liver followed by beta elimination to produce phosphoramide mustard (active drug) + acrolein (toxin)

How is amifostine activated

alkaline phosphatase

Which of these is a prodrug, procarbazine or dacarbazine

dacarbazine

T/F all platinum agents are prodrugs

true, need activation with water

Which nitrosourea is administered IV only

carmustine: two alkylating groups = less stable

Cisplatin associated toxicity and how to avoid

nephrotoxicity, administer with amifostine: prodrug with sulfur that can bind to alkylating electrophiles or free radicals generated from cisplatin

Why is capecitabine more selective than 5-FU

capecitabine requires activation via thymidine phosphorylase which is highly concentrated in tumor cells compared to normal cells

How can you avoid MTX toxicity in non cancer cells

administering with leucovorin: folinic acid that provides substrate for SHMT to form 5, 10 methyl THF

What is the component of vyxeos

cytarabine and daunorubicin in a nanoliposome

How can you increase the water solubility of of purine analogs that inhibit DNA replication

administer as a monophosphate nucleotide

Why does gemcitabine have a longer half life than cytarabine

gemcitabine still has an active metabolite after initial phosphorylation

How is paclitaxel formulated

solution with alcohol and kolliphor (hypersensitivity), albumin nanoparticle

How can you help with reactions for paclitaxel

antihistamine + corticosteroid

What is abraxane

albumin nanoparticle of paclitaxel

Why is paclitaxel administered with capecitabine

paclitaxel upregulates thymidine phosphorylase to increase activation of capecitabine

Docetaxel formulation

formulated with tween 80 instead of castor oil

Cabazitaxel vs other taxanes

cabazitaxel has lower P-gp affinity and is used for drug resistant prostate cancers to taxanes

Issue with taxanes (reaction and resistance)

low water solubility since it is hydrophobic, high P-pg efflux (except cabazitaxel)

Why can epothilones overcome resistance to taxanes

different binding site, enhanced water solubility and lack of P-gp affinity

Which vinca alkaloid has the longest half life

vincristine

What is marqibo

cholesterol and sphingomylein nanoformulated vincristine

What is onivyde

pegylated liposomal irinotecan to increase half life and fewer ADRs

What polymorphism may increase toxicity from camptothecin analogs

UGT1A1 poor metabolizer

Epipodophyllotoxins are hydrophilic or lipophilic

super lipophillic, etoposide is solubilized in polysorbate/Tween, teniposide is formulated in castor oil

How can you reduce hypersensitivity from etoposide

epinephrine, antihistamine and CCS premedication

How can you reduce cardiotoxicity of doxorubicin

administer with dexrazoxane

What DDI are associated with irinotecan and topotecan

reduced clearance: azoles and cyclosporine increased clearance: PHB PHT

Why does resistance result from BCR-ABL TKI

some BCR-ABL enzymes have a T315I mutation that generates a gatekeeper at the hydrophobic binding pocket of the TKI

What TKI can overcome BCR-ABL TKI resistance

ponatinib

Why is dasatinib more active than other BCR ABL TKIs

it binds to both the active and inactive conformation (still cannot overcome T315I)

What DDI is associated with BCR ABL TKIs

antacids/PPI, must separate by 2 hours or avoid,

3A4 inhibition can lead to life threatening toxicity (antibiotics, azoles, HIV Protease inhibitors, antidepressants)