Cytotoxic Drugs BY Kenneth Chisamanga Pharmacist
Cytotoxic Drugs BY Kenneth Chisamanga Pharmacist
Cytotoxic Drugs BY Kenneth Chisamanga Pharmacist
BY
KENNETH CHISAMANGA
PHARMACIST
These are drugs that are used to control or kill
neoplastic cells.
Anti cancer drugs can be classified into two;
Cell cycle specific agents CCS. effective only
against rapidly dividing (cycling) cells e.g. anti
metabolites, Vinka alkaloids, anti neoplastic
antibiotics.
Cell cycle non specific (CCNS). they kill
whether resting or actively cycling cells e.g.
alkylating agents and antibiotics e.g.
Cytotoxic drugs are generally directed at
metabolic sites essential replication. Ideally, these
drugs should interfere only with cellular processes
unique to malignant cells.
The ultimate goal of cancer treatment is cure,
cure requires complete eradication of tumor
cells.
If cure is not attainable, the goal is palliation
(alleviation of symptoms and avoidance of life
threatening toxicity)
Drug therapy is a balance between toxic effects
of drugs and their efficacy
Combination therapy is more efficacious than
single drug therapy in most cancers for which
chemotherapy is effective
In combination therapy, agents with
qualitatively different toxicities and different
molecular sites and mechanisms of action are
usually combined at full doses; while those
with similar dose limiting toxicities can be
combined safely only by reducing the doses of
each
Provide maximum cell kill within the range of
tolerated toxicity.
May slow or prevent the development of drug
resistance.
Combination therapy requires to use low doses
therefore preventing the risk of toxicity.
Therapy aimed at killing rapidly proliferating cells
also affect normal cells undergoing rapid
proliferation. E.g. buccal mucosa, hair cells, GIT,
bone marrow
ANTIMETABOLITES
Generally interferes with availability of normal purine
and pyrimidine nucleotide precursors by inhibiting
their synthesis or competing with them in DNA or
RNA synthesis.
Cytarabin
Fludarabin
6-Thiogiuanine
METHOTREXATE
Tablet 2.5mg, 20mg, Injection 2.5mg/ mL
Absorption; Readily absorbed from GIT, but can
also be given PO, IM, IV, Intrathecal routes.
Distribution; crosses placenta, found in breast
milk. High concentrations of the drug are found in
liver, kidneys and intestinal epithelium
Metabolism;T1/2 2-4 hrs. Metabolised in the liver
Excretion; urine
Side effects;
Myelosuppression, increased susceptibility to
infection
Alopecia
Erythema
Rash
Diarrhoea, drowsiness
Anaemia
Drug Interaction;
Increased risk of toxicities with Phenytoin,
Probenecid, Sulphonamides
Increase serum levels of digoxin, may decrease
theophylline clearance
History; allergy to MTX, hematopoietic
depression, severe hepatic or renal disease,
infection, peptic ulcer, pregnancy, psoriasis,
lactation.
Physical; weight, T, skin lesions, colour; hair,
LFTs, urinalysis,
Arrange to have leucovorin readily available as
antidote for methotrexate over dose.
Arrange for an anti emetic if nausea and
vomiting are severe.
Arrange for adequate hydration during
therapy to reduce risk of hyperuricemia
Do not administer any other medications
containing alcohol
Inhibits DNA and RNA synthesis by
intercalating between base pairs of the
DNA/RNA strand.
Inhibits topoisomerase II enzyme
Creates iron mediated free oxygen radicals that
damage the DNA, protein synthesis and cell
membranes
ANTHRACYCLINES OTHER
ANTIBIOTICS
Bleomycin Doxorubicin
Dactinomycin Daunorubicin
Mitomycin Idarubicin
Mitoxantrone Epirubicin
Has three major activities;
Intercalation in DNA- inhibit topoisomerase
Administration;
Given as injection into fast running infusion
At 21 day interval
Absorption; not absorbed by the GIT
Distribution; quickly and widely distributed in
the extravascular compartment. Does not cross
BBB in detectable amounts
Metabolism; metabolised to a significant extent
by the liver
Excretion; largely excreted in bile
Available forms;
Doxorubicin hydrochloride 10mg/5mL,
20mg/10mL
Side effects;
Bone marrow suppression
Alopecia
Cardiotoxicity
DI s
Reduces absorption of digoxin
CI s
Pregnancy
Myocardial infarction
Severe arrhythmia
Monitor Complete Blood Count (CBC) and
temperature (cytotoxic drugs may cause blood
discrasias and decreased immune function.
Blood discrasias may indicate over dose
Monitor GI status and nutrition, administer
anti emetics 30-40min prior administration of
anti neoplastic or at first sign of nausea
Monitor vital signs, cardiorespiratory status,
pitting edema.
Side effects;
Bone marrow suppression
Fatigue
Hair loss
Mouth ulcer
Loss of appetite
Diarrhea
Stomatitis
Cardiotoxicity
DIs
Erythromycin will increase the plasma level of
Bleomycin.
CIs;
Myelosuppression
Hypersensivity
Herpes Zoster
Act by forming covalent bonds (intrastrand linking
or cross linking or ) between bases in DNA chain
thus interfering with transcription.
Ifosfamide
Carmustine
Lomustine
Cyclophosphamide
Chlorambucil
Administration and Pharmacokinetics;
Given either IM, IV, PO. Tabs. 50mg, powder
500mg vial for reconstitution
Absorption; well absorbed orally
CIs
Haemorrhagic cystitis
Severe Myelosuppression
hypersensitivity
Paclitaxel (taxol)
Vinblastine
Vincristine
Vinorelbine
Vinflumine
The drugs bind to tubulin and inhibit its
polymerisation into microtubules, preventing
spindle formation in dividing cells and causing
arrest at metaphase. Their effects become manifest
only during mitosis. Mitotic spindle is essential for
equal partitioning of DNA into two daughter cells
formed when the cells divides.
Administration and Pharmacokinetics;
Presentation ; 1mg/ml
Dose; Vincristine 1.5mg/m2 IV
Absorption; absorbed from the GIT
Alopecia
Diarrhea
Peripheral neuropathy
DIs;
Vincristine possibly reduces the absorption of
digoxin
Concomitant use with clozapine increases the
risk of Agranulocytosis
Metabolism inhibited b itraconazole
CIs;
Hypersensitivity
Charcot-Marie-Tooth Syndrome. IT admin may
result in death
Pregnancy
Asparaginase-An enzyme that depletes
asparagine, on which leukemic cells depend
Cisplastin & Carboplatin
Etoposide
Interferones
Procarbazine
Suppress growth of hormone dependant tumors.
Estrogen promotes the growth of cancers that are
hormone receptor-positive.
Anti androgens; e.g. Bicalutamide
Anti estrogen; Tamoxifen used in pre menopausal
breast cancer
Corticosteroids;
To reduce inflammation, to reduce immune
response e.g. after transplant, relief or treatment of
certain symptoms that may be caused by cancer
Mood changes
Insomia
Nausea
Muscle weakness
Increased blood sugar
Weight gain
Stomach ulcers
Anti androgens; e.g. Bicalutamide
Oral non steroidal anti androgen drug use to treat
prostate cancer.
MoA;
competes with testosterone for binding to
androgen receptors in prostate cancer. By doing so
it prevents them from stimulating the prostate
cancer cells.
Anti estrogen; Tamoxifen used in pre menopausal
breast cancer
Given orally
Presentation; Tablet 50mg
Dose; 150mg once daily
Side effects
Gynaecomastia
Inidication ;
Prostate cancer,
Available Forms; Tablet 2.5mg, 20mg, Injection
2.5mg/ mL
CMF; Dose
Cyclophosphamide 100mg/m2 PO D1-14,
Methotrexate 40mg/m2 IV D1 & 8,
Folinic Acid 192mg/m2 IV starting from the
12hour of MTX infusion, then 12mg/m2 IV 6hours
for the next 48hours every
5 Fluorouracil 600mg/m2 IV D1 & 8 every 28days
for 6 cycles
Available Forms; Inj Doxorubicin hydrochloride
10mg/5mL, 20mg/10mL
DBV;
Doxorubicin 20mg/m2 IV D1
Bleomycin 15 units IV D1
Vinblastine 6mg/m2 IV D1