CHEMOTHERAPY OF URINATY

TRACT INFECTIONS
Introduction and types of urinary
tract infection
A urinary tract infection is an infection in any
part of the urinary system, i.e.,
kidney ,urethra, and bladder. Most infections
involve the lower urinary tract i.e., the
bladder and urethra.
UTIs are of following types:-
 Complicated UTI:- Pregnant women,
men ,obstruction, renal transplantation,
immunosuppressive ,and renal failure from
neurological disease and individuals with
risk factors, at least one symptomatic UTI
is being experienced by about 60% of
women and 25% have instantaneous
resolution of symptoms.
 Uncomplicated UTI :- Healthy non
pregnant women show symptoms of lower
UTI ,like dysuria ,frequency and urgency.

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  CA-UTI (Catheter-Associated UTI): Urinary
catheters are indwelled in person’s body
with sign and symptoms of UTI.
 Asymptomatic:-
Women: Two repeated emptied urine
specimens with seclusion of similar bacteria
in >105 CFU/ml.
A single catheterised urine specimen
showing 1 bacteria isolated in > 102
CFU/ml.
Pathophysiology of UTIs

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 Signs and symptoms:-
UTI shows similar sign and symptoms as
that of many other conditions and does not
mean that patients have an infection.
Depending on the location of urinary tract
infection (upper and lower),the symptoms
are as follows:-
 Upper UTI
Nausea
Vomiting
High temperature
Moderate to severe pain in back and
Diarrhoega .
 Lower UTI
Pelvic area pain and Fever
Abdominal with feeling of bloating.
Back pain
Blood in urine
Feeling of uncomfortable and Fever.

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4
Common urinary tract infection UTI
symptoms in the children include:
Urge to urinate frequently, often in small
amounts Burning with urination
Cloudy urine
Strong unpleasant smell of urine (not as
reliable in children)
Dark or bloody urine.
Factors that may make increase the risk
for UTI:-
 Infrequent voiding – The bacteria spends
a greater amount of time in the bladder
allowing it time to replicate and take
hold.
 Incomplete voiding – An excess
amount of urine is left in the bladder
and the bacteria is not completely
flushed out with each void.
 Personal Hygiene – Perineal
contamination with faeces increases the
risk of coliform bacteria in the vagina

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 and near the urethra will increase the
risk of urinary tract infections.
 Sexual Activity – Trauma to the
urethra and surrounding tissue may
increase susceptibility to infection and
also the bacteria can be mechanically
pushed into the urethra.
 Use of spermicidal contraception – The
actual spermicide changes the normal
flora in the vagina and more coliform
bacteria colonize the area. The presence
of these strains of bacteria leads to a
greater risk of a UTI.
 Genetics – Certain cells on the vaginal
mucosa and the urethra can express
receptors that actually allow certain
bacteria to attach and pull themselves
into the bladder causing an increase risk
of a UTI.
 Diabetes – Persistently high blood
sugar levels cause immunosuppression
which allows for greater susceptibility to
UTIs.

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  Immunosuppression – There are a
variety of causes of immunosuppression
which decreases a person’s ability to
fight off infections.

Most commonly used Antibiotics for UTIs

and its possible side effects:
1. Marcomanni (Macro bid or nitrofurantoin)
–Side effects of long-term use may include
fibrosis or scarring of the lungs and
peripheral neuropathy. Generally, the
medication is considered safe during
pregnancy, except with rare genetic metabolic
deficiencies.
2. Bactrim (Septra or sulfa/TMP) –This drug
should not be taken early during pregnancy
and may affect the effectiveness of oral
contraceptives.
3. Trimethoprim –It should not be taken
during pregnancy. 4. Quinolones (Levaquin,

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Levofloxacin, or Cipro) – This drug should not
be taken during pregnancy.
5. Cephalosporin (Keflex) – This may affect the
effectiveness of oral contraceptives.
6. Doxycycline –It is not safe during
pregnancy or breastfeeding.
Treatments and drugs
If your symptoms are typical of a urinary tract
infection and you’re generally in good health,
antibiotics are the first line of treatment.
Which drugs are prescribed and for how long
depends on your health condition and type of
bacteria found in urine.

Simple infection
Drugs commonly recommended for simple
urinary tract infections include:
Amoxicillin (Anoxic, Trim ox)
Nitrofurantoin (Furadantin, Macrodantin)
Ciprofloxacin (Cipro)

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Levofloxacin (Levaquin)
Sulfamethazine-trimethoprim (Bactrim)

Usually, symptoms clear up within a few days

of treatment. But you may need to continue
antibiotics for a week or more.
For an uncomplicated urinary tract infection
that occurs when you’re otherwise healthy,
your doctor may recommend a shorter course
of treatment, such as taking an antibiotic for
three days. But whether this short course of
treatment is adequate totreat your infection
depends on your particular symptoms and
medical history. Your doctor may also
prescribe a pain medication (analgesic) that

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numbs your bladderand urethra to relieve
burning while urinating. One common side
effect of urinary tract analgesics is
discoloured urine — bright blue or orange.
Recurrent infection
If you have recurrent urinary tract infections,
your doctor may recommend a longer course
of antibiotic treatment or a self-treatment
program with short courses of antibiotics at
the outset of your urinary symptoms. Home
urine tests, in which you dipa test stick into a
urine sample, are now available that are
highly sensitive and may be helpful if you
experience recurring infections. For infections
related to sexual activity, your doctor may
recommend taking a single dose of antibiotic
after sexual intercourse. If you’re
postmenopausal, your doctor may
recommend vaginal oestrogen therapy to
minimize your chance of recurrent urinary
tract infections.
Severe infection

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 For severe urinary tract infections,
hospitalization and treatment with
intravenous antibiotics may be necessary.
Lifestyle and home remedies
Urinary tract infections can be painful, but
you can take steps to ease your discomfort
until antibiotics clear the infection. Follow
these tips:
 Drink plenty of water
To dilute your urine and help flush out
bacteria. Avoid coffee, alcohol, and soft drinks
containing citrus juices and caffeine until your
infection has cleared. They can irritate your
bladder and tend to aggravate your frequent
or urgent need to urinate.
 Use a heating pad
On your abdomen to minimize bladder
pressure or discomfort.
Prevention
Take these steps to reduce your risk of urinary
tract infections:

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  Drink plenty of liquids, especially water.
Cranberry juice may have infection-fighting
properties. However, don’t drink cranberry
juice if you’re taking the blood-thinning
medication warfarin. Possible interactions
between cranberry juice and warfarin may
leading to bleed.
 Empty your bladder as soon as possible
after intercourse.
Also, drink a full glass of water to help flush
bacteria.
 Avoid potentially irritating feminine
products.
Using deodorant sprays or other feminine
products, such as douches and powders, in
the genital area can irritate the urethra.

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SEXUALLY TRANSMITTED DISEASE

Sexually transmitted infection:-

An infection that can be transferred from one
person to another through sexual contact. In
this context, sexual contact is more than just
sexual intercourse (vaginal and anal) and also
includes kissing .
Sexually transmitted disease (STD) symptoms
If you have sex
Oral, anal or vaginal intercourse and genital
touching
You can get an STD,also called a sexually
transmitted infection (STI). Straight or gay,
married or single, you’re vulnerable to STIs
and STI symptoms. Thinking or hoping your
partner doesn’t have an STI is no protection.
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 And although condoms, when properly used,
are highly effective for reducing transmission
of some STDs, no method is foolproof.STI
symptoms aren’t always obvious. If you think
you have STI symptoms or have been
exposed to an STI, see a doctor. Some STIs
are easy to treat and cure; others require
more-complicated treatment to manage them.
It’s essential to be evaluated, and
If diagnosed with an STI
Get treated. It’s also essential to inform your
partner or partners so that they can be
evaluated and treated. If untreated, STIs can
increase your risk of acquiring another STI
such as HIV. This happens because an STI can
stimulate an immune response in the genital
area or cause sores, either of which might
raise the risk of HIV transmission. Some

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untreated STIs can also lead to infertility,
organ damage, certain types of cancer or
death.

Asymptomatic STIs:-
Many STIs have no signs or symptoms
(asymptomatic). Even with no symptoms,
however, you can pass the infection to your
sex partners. So it’s important to use
protection, such as a condom, during sex. And
visit your doctor regularly for STI screening,
so you can identify and treat an infection
before you can pass it on.
Some of the following diseases, such as
hepatitis, can also be transmitted without
sexual contact, by coming into contact with
an infected person’s blood. Others, such as
gonorrhoea, can only be transmitted through
sexual contact.
Causes

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Sexually transmitted infections can be caused
by:
 Bacteria (gonorrhoea, syphilis, chlamydia)
 Parasites (trichomoniasis)
 Viruses (human papillomavirus, genital
herpes,HIV)

Sexual activity plays a role in spreading many

other infectious agents, although it’s possible
to be infected without sexual contact.
Examples include the hepatitis A, B and C
viruses, shigella, and Giardia intestinalis.
HIV and AIDS
AIDS (acquired immunodeficiency syndrome)
is a syndrome caused by a virus called
HIV(human immunodeficiency virus). The
disease alters the immune system, making
people muchmore vulnerable to infections
and diseases. This susceptibility worsens if
the syndrome progresses.
HIV is found throughout all the tissues of the
body but is transmitted through the body

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fluids of an infected person (semen, vaginal
fluids, blood, and breast milk).
HIV is a virus that attacks immune cells called
CD-4 cells, which are a subset of T cells. AIDS
is the syndrome, which may or may not
appear in the advanced stage of HIV infection.

HIV is a virus.
AIDS is a medical condition.
HIV infection can cause AIDS to develop.
However, it is possible to contract HIV without
developing AIDS. Without treatment, HIV can
progress and, eventually, it will develop into
AIDS in the vast majority of cases.

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Causes
HIV is a retrovirus that infects the vital organs
and cells of the human immune system.
The virus progresses in the absence of
antiretroviral therapy (ART) – a drug therapy
that slows or prevents the virus from
developing.
The rate of virus progression varies widely
between individuals and depends on many
factors.
These factors include the age of the
individual, the body’s ability to defend against
HIV, access to healthcare, the presence of
other infections, the individual’s genetic
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inheritance, resistance to certain strains of
HIV, and more.
How is HIV transmitted?
Sexual transmission:- It can happen when
there is contact with infected sexual fluids
(rectal, genital, or oral mucous membranes).
This can happen while having sex without a
condom, including vaginal, oral, and anal sex,
or sharing sex toys with someone who is HIV-
positive.
Perinatal transmission:- A mother can
transmit HIV to her child during childbirth,
pregnancy, and also through
breastfeeding.
Blood transmission:- The risk of
transmitting HIV through blood
transfusion is extremely low in developed
countries, thanks to meticulous screening
and precautions. However, among people
who inject drugs, sharing and reusing

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syringes contaminated with HIV-infected
blood is extremely hazardous.

HIV symptoms
HIV is an infection with the human
immunodeficiency virus. HIV interferes with
your body’s ability to fight off viruses,
bacteria and fungi that cause illness, and it
can lead to AIDS, a chronic, life-threatening
disease.
When first infected with HIV, you may have no
symptoms. Some people develop a flu-like
illness, usually two to six weeks after being
infected. Still, the only way you know if you
haveHIV is to be tested.
Early signs and symptoms
Early HIV signs and symptoms may include:
 Fever
 Headache
 Sore throat
 Swollen lymph glands

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  Rash
 Fatigue .
These early signs and symptoms usually
disappear within a week to a month and are
often mistaken for those of another viral
infection. During this period, you’re highly
infectious. More- persistent or -severe
symptoms of HIV infection may not appear for
10 years or more after the initial infection.
As the virus continues to multiply and destroy
immune cells, you may develop mild
infections orchronic signs and symptoms such
as:
 Swollen lymph nodes
 Often one of the first signs of HIV infection
 Diarrhoea
 Weight loss
 Fever
 Cough and shortness of breath.
Late-stage HIV infection
Signs and symptoms of late-stage HIV
infection include:

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  Persistent, unexplained fatigue
 Soaking night sweats
 Shaking chills or fever higher than 100.4 F
(38 C) for several weeks
 Swelling of lymph nodes for more than
three months
 Chronic Diarrhoea
 Persistent headaches
 Unusual, opportunistic infections.
Chlamydia:
The agent of a sexually transmitted disease, a
type of bacteria found in the cervix, urethra,
throat, or rectum that acts very much like
gonorrhoea in the way it is spread, the
symptoms it produces, and its long-term
consequences. Chlamydia is destructive to
the Fallopiantubes, causing infertility, tubal
pregnancy, and severe pelvic infection.
Chlamydia is one of the reasons new-borns
are routinely treated with antibiotic eye drops.
Chlamydia can also cause inflammation of the
urethra, epididymis, and rectum in men. A
chronic form of arthritis, called reactive
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arthritis, can develop after chlamydia
infection.

Chlamydia is an infection with Chlamydia

trachomatis Bacteria. When an infection is
present, the bacteria can be present in the
cervix, urethra, vagina, and rectum of an
infected person. It can also live in the throat.
Any type of sexual contact (vaginal, anal, or
oral) with an infected person can spread the
infection.

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Young people who are sexually active are at
high risk for chlamydia.
An infected mother can also spread the
infection to her baby at the time of birth as
the baby passes through the vaginal canal.
The most common complications of chlamydia
acquired through the birth canal are eye
damage and pneumonia in the new-born.
Even after a person has been treated for
chlamydia, it is possible to get the infection
again. With chlamydia, repeat infection is
common.
Chlamydia symptoms
Chlamydia is a bacterial infection of your
genital tract. Chlamydia may be difficult to
detect because early-stage infections often
cause few or no signs and symptoms. When
they do occur, they usually start one to three
weeks after you’ve been exposed to
chlamydia. Even when signs and symptoms
occur, they’re often mild and passing, making
them easy to overlook.

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Signs and symptoms may include:
 Painful urination
 Lower abdominal pain
 Vaginal discharge in women
 Discharge from the penis in men
 Pain during sexual intercourse in women
 Bleeding between periods in women
 Testicular pain in men.
Gonorrhoea
A bacterial infection that is transmitted by
sexual contact. Gonorrhoea is one of the
oldest known sexually transmitted diseases
(STDs), and it is caused by the
Neisseriagonorrhoeae bacteria. Men with
gonorrhoea may have a yellowish discharge
from the penisaccompanied by itching and
burning. More than half of women with
gonorrhoea do not have any symptoms
Causes
Gonorrhoea is a sexually transmitted disease
(STD). It’s caused by infection with the
Bacterium
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 Neisseria gonorrhoea. It tends to infect
warm, moist areas of the body, including
 the Urethra (the tube that drains urine
from the urinary bladder)
 Eyes
 Throat
 Vagina
 Anus
 Female reproductive tract(the fallopian
tubes, cervix, and uterus)
Gonorrhoea passes from person to person
through unprotected oral, anal, or vaginal sex.
People With numerous sexual partners or
those who don’t use a condom are at greatest
risk of infection.
The best protections against infection are
abstinence, monogamy (sex with only one
partner),and proper condom usage.
Behaviours that make a person more likely to
engage in unprotectedsex also increase the
likelihood of infection. These behaviours
include alcohol abuseandillegal drug abuse,
particularly intravenous drug use.
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Gonorrhoea symptoms:-Gonorrhoea is a
bacterial infection of your genital tract. It can
also grow in your mouth, throat, eyes and
anus. The first gonorrhoea symptoms
generally appear within 10 days after
exposure. However, some people may be
infected for months before signs or symptoms
occur.
Signs and symptoms of gonorrhoea may
include:
 Thick, cloudy or bloody discharge from the
penis or vagina
 Pain or burning sensation when urinating
 Heavy menstrual bleeding or bleeding
between periods
 Painful, swollen testicles
 Painful bowel movements
 Anal itching
Genital herpes: An infection by human
herpes virus that is transmitted through
intimate contact with the moist mucous
linings of the genitals. This contact can
involve the mouth, the vagina, or the genital
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skin. Following infection, the virus travels to
nerve roots near the spinal cord and settles
there permanently. When an infected person
has a herpes outbreak, the virus travels down
the nerve fibbers to the site of the original
infection; when it reaches the skin, redness
and blisters occur. Commonly called herpes.

Causes
Two types of herpes simplex virus infections
can cause genital herpes:
HSV-1:-This is the type that usually causes
cold sores or fever blisters around your
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mouth.HSV-1 is often spread through skin-to-
skin contact, though it can be spread to your
genital area during oral sex. Recurrences are
much less frequent than they are with HSV-
2infection.
HSV-2:-This is the type that commonly causes
genital herpes. The virus spreads through
sexual contact and skin-to-skin contact. HSV-2
is very common and highly contagious,
whether or not you have an open sore.
Because the virus dies quickly outside of the
body, it’s nearly impossible to get the
infection through contact with toilets, towels
or other objects used by an infected person.
Genital herpes symptoms
Highly contagious, genital herpes is caused by
a type of the herpes simplex virus (HSV) that
enters your body through small breaks in your
skin or mucous membranes. Most people
withHSV never know they have it, because
they have no signs or symptoms or the signs
and symptoms are so mild they go unnoticed.

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When signs and symptoms are noticeable, the
first episode is generally the worst. Some
people never have a second episode. Others,
however, can have recurrent episodes for
decades.
When present, genital herpes signs and
symptoms may include:
 Small red bumps, blisters (vesicles) or
open sores (ulcers) in the genital, anal and
nearbyareas
 Pain or itching around the genital area,
buttocks and inner thighs.

Syphilis
Is an STD that has been around for centuries.
It is caused by a bacterial organism called a
spirochete. The scientific name for the

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organism is Treponema pallidum. The
spirochetes a wormlike, spiral-shaped
organism that wiggles vigorously when
viewed under a microscope. It infects the
person by burrowing into the moist, mucous-
covered lining of the mouth or genitals. The
spirochete produces a classic, painless ulcer
known as a chancre.
Syphilis is caused by a spirochete (a spiral-
shaped bacteria) called Treponema pallidum.
You can get the bacteria in the following ways:
 Direct contact with a syphilis sore (usually
found on the vagina, anus, rectum, in the
mouth, oron the lips)
 During vaginal, anal, or oral sex with
an infected person
 An infected mother can pass syphilis
to her unborn child, which can result in
serious complications or even death of
the unborn child .
The primary and secondary stages of
syphilis are extremely contagious. Tell

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 your previous sexual partners if you
are diagnosed with syphilis so that
they can get tested to see if they have
the disease.
You can’t catch syphilis from doorknobs,
toilet seats, swimming pools, clothing,
bathtubs, or
Silverware.
There is a high correlation between
syphilis and HIV, since HIV can be
transmitted through syphilitic sores. Since
the behaviours that lead to the spread of
STIs are the same for both syphilis and
HIV, having syphilis is an indicator that
you are also at risk for contracting HIV.
Syphilis symptoms
Syphilis is a bacterial infection. The disease
affects your genitals, skin and mucous
membranes, but it can also involve many
other parts of your body, including your brain
and your heart.
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The signs and symptoms of syphilis may
occur in four stages—Primary, secondary,
latent and tertiary. There’s also a condition
known as congenital syphilis, which occurs
when a pregnant woman with syphilis passes
the disease to her unborn infant. Congenital
syphilis can be disabling, even life-
threatening.
Primary syphilis
The first sign of syphilis, which may occur
from 10 days to three months after exposure,
may be small, painless sore (chancre) on the
part of your body where the infection was
transmitted, usually your genitals, rectum,
tongue or lips. A single chancre is typical, but
there may be multiple sores.
The sore typically heals without treatment,
but the underlying disease remains and may
reappearing the second (secondary) or third
(tertiary) stage.
Secondary syphilis

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Signs and symptoms of secondary syphilis
may begin three to six weeks after the
chancre appears, and may include:
 Rash marked by red or reddish-brown,
penny sized sores over any area of your
body, including your palms and soles.
 Fever
 Enlarged lymph nodes
 Fatigue and a vague feeling of discomfort
 Soreness and aching.
These signs and symptoms may disappear
without treatment within a few weeks or
repeatedly come and go for as long as a year.
Latent syphilis
In some people, a period called latent syphilis
In which no symptoms are present May follow
the secondary stage. Signs and symptoms
may never return, or the disease may
progress to the tertiary stage.
Tertiary syphilis
Without treatment, syphilis bacteria may
spread, leading to serious internal organ
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damage and death years after the original
infection.
Some of the signs and symptoms of tertiary
syphilis include:
 Lack of coordination
 Numbness
 Paralysis
 Blindness
 Dementia
Neurosyphilis
At any stage, syphilis can affect the nervous
system. Neurosyphilis may cause no signs or
symptoms, or it can cause:
 Headache
 Behaviour changes
 Movement problems
Chemotherapy of Malignancy
Definition
Neoplasm or tumour is defined as the
growth or mass of abnormal tissue formed
due to excessive, autonomous and
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uncoordinated cell proliferation. This
phenomenon occurs as a result of loss of
control mechanism of cell and abnormality in
chromosomes or mutations in DNA. The term
neoplasm means new growth and the process
of cell proliferation is called neoplasia. The
branch of medicine which deals with the
extensive study of neoplasm (tumour) and its
development, diagnosis and treatment is
called oncology (Greek words ounces =
tumour and logy = study ). Generally the term
cancer is used for all malignant tumours.
Anticancer drugs are the drugs which
effectively kill the rapidly dividing cancer
cells. These drugs are ant proliferative and
damage the DNA resulting in cell death. As
these drugs act on rapidly dividing cells, there
is a chance of killing the normal cells also.
This is a major disadvantage resulting in
many adverse effects.

CLASSI FICATION

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 A. Drugs acting directly on cells (Cytotoxic
drugs)
 Alkylating agents
Nitrogen mustards: Mechlorethamine
(MustineHCl),Cyclophosphamide,Ifosf
amide,Choriambuses, Memphian
Ethylamine Thio-TEPA
Alkyl sulfonate Busulfan
Nitrosoureas Carmustine (BCNU),
Lomustine (CCNU)
Thiazine Dacarbazine (OTIC)
 Antimetabolites: Folate antagonist
Methotrexate (Mtx)
Purine antagonist6-
Mercaptopurine (6-MP), 6-Thioguanine (6-TG),
Azathioprine, Fludarabine
Pyrimidine antagonist: 5-
Fluorouracil (5-FU), Cytarabine, (cytosine
arabinoside)
 Vinca alkaloids Vincristine (Oncovin),
Vinblastine
 Taxanes Paclitaxel, Docetaxel

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  Epipodophyllotoxin: Etoposide
 Camptothecin analogues: Topotecan,
Irinotecan
 Antibiotics: Actinomycin D,
(Dactinomycin), Doxorubicin,
Daunorubicin,
(Rubidomycin)Mitoxantrone
Bleomycins, Mitomycin C
 Miscellaneous Hydroxyurea,
Procarbazine, L-Asparaginase,
Cisplatin, Carboplatin ,Imatinib .
B. Drugs altering hormonal m ilieu
 Glucocorticoids Prednisolone and
others
 Estrogens Fosfestrol, Ethinylestradiol
 Selective estrogen Tamoxifen,
 Receptor modulators Toremifene
 Selective estrogen receptor down
regulators: Fulvestrant
 Aromatase inhibitors Letrozole,
Anastrozole, Exemestane
 Antiandrogen Flutamide,
Bicalutamide

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  5-a reductase inhibitor Finasteride,
Dutasteride
 GnRH analogues Nafarelin,
Triptorelin
 Progestin’s Hydroxyprogesterone
acetate, etc.

ALKYLATI NG AGE NTS

 These compounds produce highly reactive
carbonium ion intermediates which
transfer alkyl Groups to cellular
macromolecules by forming covalent
bonds. The position 7 of guanine Residues
in DNA is especially susceptible, but other
molecular sites are also involved.
Alkylation results in crosslinking/ abnormal
base pairing/ scission of DNA
stranstrand.Cross linking of nucleic (like
ionizing radiation) actions.
Mechlorethamine (Mustine HCI) It is the
first nitrogen mustard; highly reactive and
local vesicant-c an be given only by i v
route. It produces many acute effects like

39
 nausea, vomiting And haemodynamic
changes. Extravasation during i.v.
injection may cause sloughing.

ANTI MET ABO LITES

These are analogues related to normal
components of DNA or of coenzymes involved
in nucleic acid synthesis. They competitively
inhibit utilization of the normal substrate or
get themselves incorporated forming
dysfunctional macromolecules.
1. Folate antagonist Methotrexate (Mtx) It is
one of the oldest and highly efficacious
antineoplastic drugs; inhibits dihydrofolate
reductase (DHFRase)-blocking the conversion
of dihydrofolic acid (DHFA) to tetrahydrofolic
acid (THFA) which is the essential coenzyme
required for one carbon transfer reactions in
de novo purine synthesis and amino acid
interconversions. Methotrexate has cell cycle
specific action kills cells in S phase; primarily
inhibits DNA synthesis, but also affects RNA
and protein synthesis. It exerts major toxicity
40
on bone marrow-low doses given repeatedly
cause megaloblastic anaemia, but high doses
produce pancytopenia. Desquamation and
bleeding may occur in g.i.t.

Purine antagonists
Mercaptopurine (6-MP) and thioguanine (6-TG)
These are highly effective antineoplastic
drugs. They are converted in the body to the
corresponding monoribonucleotides which
inhibit the conversion of insomnia
monophosphate to adenine and guanine
nucleotides.

41
42
There is also feedbackinhibition of de novo
purine synthesis. They are especially useful in
childhood acute leukaemia, choriocarcinoma
and have been employed in some solid
tumours as well. In acute leukaemia, both
have been used in combination regimens to
induce remission and 6-MP to maintain it as
well.
Pyrimidine antagonists: Pyrimidine analogues
have varied applications as antineoplastic,
antifungal and antipsoriatic agents.
Fluorouracil U, -FU) is converted in the body to
the corresponding nucleotide 5-fluoro-2-
Deoxyuridine monophosphate, which inhibits
thymidylate synthase and blocks the
conversion of deoxyuridilic acid to
deoxythymidylic acid. Selective failure of DNA
synthesis occurs due to non-availability of
thymidylate: thymidine can partially reverse
its toxicity.Fluorouracil itself gets incorporated
into nucleic acids and this may contribute to
its toxicity.

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Even resting cells are affected, though rapidly
multiplying ones are more susceptible.

VINCA ALKALOIDS
These are mitotic inhibitors, bind to
microtubular protein-‘tubulin’, prevent its
polymerization and assembly of microtubules,
cause disruption of mitotic spindle and
interfere with cytoskeletal function. The
chromosomes fail to move apart during
mitosis:
metaphase arrest occurs. They are cell cycle
specific and act in the mitotic phase.
Vincristine and vinblastine, though closely
related chemically, have somewhat different
spectrum of anti tumour activity and toxicity.
Vincristine (oncovin) It is a rapidly acting
drug, very useful for inducing remission in
childhood acute leukaemia, but is not good for
maintenance therapy. Other indications are
Lymphosarcoma, Hodgkin’s disease, Wilms’
tumour, Ewing’s sarcoma and carcinoma lung.
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Prominent adverse effects are peripheral
neuropathy and alopecia. Bone marrow
depression is Minimal.

TAXANES
Paclitaxel It is a complex diterpin taxane
obtained from bark of the Western yew tree,
which exerts cytotoxic action by a novel
mechanism. It enhances polymerization of
tubulin: a mechanism opposite to that of
vinca alkaloids. The microtubules are
stabilized and their depolymerization is
prevented. This stability results in inhibition of
normal dynamicreorganization of the
microtubule network that is essential for vital
interphase andmitotic functions. Abnormal
arrays or ‘bundles’ of microtubules are
produced throughout the Cell cycle.

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