CYTOTOXIC DRUGS

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

 5-Fluorouracil- pyrimidine antagonist

 6-Mercaptopurine- purine antagonist

 Methotrexate –folic acid antagonist

 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

 Nausea & vomiting

 Erythema

 Rash

 Diarrhoea, drowsiness

 Renal damage in high doses.

Contra Indications;
 Pregnancy category X

 Anaemia

 Severe renal impairment

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

 Binding to cell membranes

 Generation of oxygen radicals

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

 Nausea & vomiting

 Cardiotoxicity
DI s
 Reduces absorption of digoxin

 CCBs- verapamil increases plasma conc.. Of

Doxo
 Inhibits the effect of stavudine

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

 Distribution; more than 75% BA after oral

administration
 Metabolism; metabolised by the liver

 Excretion; via urine

Side effects;
 Anorexia, Cardiotoxicity at high dose

 N & V, Pancreatitis, urethral toxicity

 Darkening of skin and fingernails

A urinary metabolite of cyclophosphamide,

acrolein can cause haemorrhagic cystitis rare but
serious complication. Mesna reacts with this
metabolite to prevent toxicity in the U.tract
DIs
 Reduces absorption of digoxin

 Side effects increased itraconazole

 Cyclo…Enhances effects of suxamethonium

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

 Distribution; rapidly and widely distributed

through out the body
 Metabolism; metabolised by the liver

 Excretion; billiary excretion

Side effects;
 Cellulitis,

 Nausea & vomiting

 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

 Mild liver injury

 N & V, weight gain, decreased libido,

 Impotence, Diarrhea, Jaundice, anaemia

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

 Repeat cycle every 14-21 days tapered to the

best response 15mcg/kg/Day IV
CVP;
 Cyclophosphamide 400mg-600mg/m2 D1 IV

 Vincristine 1.4mg/m2 D1 IV (max 2mg)

 Prednisolone 100mg PO D1-5 Repeat every 21

days
Presentation Injection; 1mg/ml IV
VLM;
 Vincristine 1.5mg/m2 D1 weekly for 3
consecutive weeks
 Lomustine 75mg/m2 orally D1

 Cisplastin 75mg/m2 IV D1 Repeat every 6

weeks for 8 cycles
Thank You!!!