Basics of Chemotherapy and Antibiotic Resistance

05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
Basic principles ofBasic principles of
chemotherapychemotherapy
-Chemotherapy is the use of chemicals, eitherChemotherapy is the use of chemicals, either
natural or synthetic to inhibit the growth of othernatural or synthetic to inhibit the growth of other
microorganism.microorganism.
-Chemotherapy is also used with otherChemotherapy is also used with other
treatments like biological therapies, hormonaltreatments like biological therapies, hormonal
therapy, radiotherapy and surgery.therapy, radiotherapy and surgery.

- Antibiotics are substances produced byAntibiotics are substances produced by
some microorganisms that kill or inhibit thesome microorganisms that kill or inhibit the
growth of other organisms.growth of other organisms.
- Chemotherapeutic agents are chemicalsChemotherapeutic agents are chemicals
intended to be toxic for the parasitic cell orintended to be toxic for the parasitic cell or
cells, but innocuous to the host .Theircells, but innocuous to the host .Their
feasibility depends on the existence offeasibility depends on the existence of
exploitable biochemical differencesexploitable biochemical differences
between the parasitebetween the parasite

Con.Con.
and the host and microorganism on theand the host and microorganism on the
evolutionary development ( prokaryotic orevolutionary development ( prokaryotic or
eukaryotic ) .eukaryotic ) .
-Viruses do not have their own biochemical-Viruses do not have their own biochemical
machinery to generate energy or anymachinery to generate energy or any
synthesis .synthesis .
- Cancer cell has escaped from the- Cancer cell has escaped from the
regulating devices that control the normalregulating devices that control the normal
cells .cells .

CytoplsmCytoplsm
Contains soluble proteins mostly withContains soluble proteins mostly with
enzymatic functions and ribosomesenzymatic functions and ribosomes
involved in protein synthesis and all theinvolved in protein synthesis and all the
small molecule intermediates involved insmall molecule intermediates involved in
metabolism and inorganic ions, containmetabolism and inorganic ions, contain
the genetic material-unlike eukaryotes- inthe genetic material-unlike eukaryotes- in
the form of a single chromosome thatthe form of a single chromosome that
holds all the genetic information .Thisholds all the genetic information .This
chromosome contain no histones and nochromosome contain no histones and no
mitochondria.mitochondria.

Con.Con.
Some bacteria have additionalSome bacteria have additional
components which may preventcomponents which may prevent
penetration of the antibacterial agents andpenetration of the antibacterial agents and
any access of lyosomal enzymes.any access of lyosomal enzymes.

Biochemical reactions involved inBiochemical reactions involved in
the formation of bacterial cellthe formation of bacterial cell
structuresstructures
Class I : is the utilization of a carbonClass I : is the utilization of a carbon
source to liberate ATP and simplesource to liberate ATP and simple
compounds as precursors for the nextcompounds as precursors for the next
step.step.
Class II: is the utilization of ATP and theClass II: is the utilization of ATP and the
precursors to yield small molecules.precursors to yield small molecules.
Class III: is the assembly of smallClass III: is the assembly of small
molecules to macromloecules.molecules to macromloecules.

Con.Con.
These classes constitute targets for theThese classes constitute targets for the
attacks by chemotherapeutic agents inattacks by chemotherapeutic agents in
addition to the formed structures.addition to the formed structures.

Biochemical reactions as potentialBiochemical reactions as potential
targetstargets
Class I : Do not help a lot:Class I : Do not help a lot:
- No marked difference between bacteria- No marked difference between bacteria
and human cells in the mechanism ofand human cells in the mechanism of
obtaining energy .obtaining energy .
- If these are to be blocked , bacteria can- If these are to be blocked , bacteria can
use a variety of compounds asuse a variety of compounds as
alternatives.alternatives.

Con.Con.
Class II: Bacteria ,unlike humans, canClass II: Bacteria ,unlike humans, can
synthesize the essential amino-acids and thesynthesize the essential amino-acids and the
growth factors or vitamins .So this a potentialgrowth factors or vitamins .So this a potential
target for a chemotherapeutic agent .target for a chemotherapeutic agent .
Some times the pathway is the same inSome times the pathway is the same in
bacteria and man ,but with differentbacteria and man ,but with different
sensitivities to drugs.sensitivities to drugs.
An antimalarial pyrimethamine has an ICAn antimalarial pyrimethamine has an IC5050 forfor
FHFH22 reductase higher in human than inreductase higher in human than in
protozoa.protozoa.

Con.Con.
The sequential blockade with aThe sequential blockade with a
combination of two drugs at lowercombination of two drugs at lower
concentrations affecting the sameconcentrations affecting the same
pathway at different points of the parasitepathway at different points of the parasite
life cycle.life cycle.

Con.Con.
Class III :There are distinct differencesClass III :There are distinct differences
between bacterial cells at this level:between bacterial cells at this level:
i/ Peptidoglycans of the cell wall ofi/ Peptidoglycans of the cell wall of
bacteria does not occur in eukaryotesbacteria does not occur in eukaryotes
.The synthesis of peptidoglycans needs.The synthesis of peptidoglycans needs
cytoplasmic components passed throughcytoplasmic components passed through
transport systems .This synthesis can betransport systems .This synthesis can be
blocked at several points by antibiotics.blocked at several points by antibiotics.

Con.Con.
ii/ Protien synthesis : Ribosomes, which areii/ Protien synthesis : Ribosomes, which are
cytoplasmic nucleoprotiens, are thecytoplasmic nucleoprotiens, are the
machinary for the synthesis of protiens onmachinary for the synthesis of protiens on
mRNA templates and are different inmRNA templates and are different in
prokaryotes form eukaryotes leading toprokaryotes form eukaryotes leading to
selective antimicrobial action.selective antimicrobial action.

Con.Con.
iii/ Nucleic acid synthesis starts by the activation ofiii/ Nucleic acid synthesis starts by the activation of
the enzyme which unwind the supercoil leadingthe enzyme which unwind the supercoil leading
to a negative supercoil ,then unwind the positiveto a negative supercoil ,then unwind the positive
supercoil.supercoil.
-Interference occur by:-Interference occur by:
*Inhibition of the synthesis of nucleotide.*Inhibition of the synthesis of nucleotide.
*Altering the base-pairing property of the*Altering the base-pairing property of the
templates.templates.
*Inhibiting DNA or RNA polymerases.*Inhibiting DNA or RNA polymerases.
*Inhibiting DNA- gyrases.*Inhibiting DNA- gyrases.
*Directly affecting DNA by alkylation to make*Directly affecting DNA by alkylation to make
covalent bondswith the bases in DNA andcovalent bondswith the bases in DNA and
prevent replication.prevent replication.

Cell-structure targeted therapyCell-structure targeted therapy
Membranes : polymixins are cationicMembranes : polymixins are cationic
bacteriocidals that act by disrupting thebacteriocidals that act by disrupting the
membranes of bacteria.Polyene antibioticsmembranes of bacteria.Polyene antibiotics
act on fungi and protozoa.Imidozoles actact on fungi and protozoa.Imidozoles act
against fungi and gram ( +ve ) bacteria.against fungi and gram ( +ve ) bacteria.
DNA : Bleomycin lead to free radicalDNA : Bleomycin lead to free radical
formation and hence fragmentation offormation and hence fragmentation of
DNA strands.DNA strands.

Con.Con.
Microtubules and/or microfilaments:Microtubules and/or microfilaments:
Griseofluvin interfere with microtubuleGriseofluvin interfere with microtubule
function and cell division.Colchicine andfunction and cell division.Colchicine and
vinca alkaloids disrupt the function ofvinca alkaloids disrupt the function of
microtubules during cell division.microtubules during cell division.
Muscle fibres :Piperazine hyperpolarizes theMuscle fibres :Piperazine hyperpolarizes the
muscle fibre membrane and paralysesmuscle fibre membrane and paralyses
worms. Levamisoles lead to muscleworms. Levamisoles lead to muscle
contraction followed by paralysis.contraction followed by paralysis.

Resistance to antibioticsResistance to antibiotics
Organisms adapt themselves gentically toOrganisms adapt themselves gentically to
changes in their environment imposing seriouschanges in their environment imposing serious
constrains on the options available for medicalconstrains on the options available for medical
treatment of many bacterial infections .Thistreatment of many bacterial infections .This
resistance can develop also in protozoa,resistance can develop also in protozoa,
multicellular parasites and in populations ofmulticellular parasites and in populations of
malignant cells.malignant cells.
This can occur at three levels by transfer of :This can occur at three levels by transfer of :
- Bacteria between people.- Bacteria between people.
- Resistant genes between bacteria on plasmids.- Resistant genes between bacteria on plasmids.
- Resistance genes between genetic elements- Resistance genes between genetic elements
within bacteria on transposons.within bacteria on transposons.

Con.Con.
These mechanisms are important for :These mechanisms are important for :
- The sensible use of antibiotics clinically.- The sensible use of antibiotics clinically.
- Further discovery of new drugs .- Further discovery of new drugs .
- R- plasmids lead to the development of- R- plasmids lead to the development of
new techniques in DNA coloning.new techniques in DNA coloning.

Genetic determinants of antibioticGenetic determinants of antibiotic
resistanceresistance
Chromosomal where the mutation rate forChromosomal where the mutation rate for
a particular bacteria is very low .This ratea particular bacteria is very low .This rate
will increase during infection ,althuogh fewwill increase during infection ,althuogh few
mutants are not enough to producemutants are not enough to produce
bacterial resistance against a drug.Thisbacterial resistance against a drug.This
can be antagonized by the host naturalcan be antagonized by the host natural
defences,unless the infection is caused bydefences,unless the infection is caused by
all the microorganismall the microorganism,,
s resistants resistant
population.population.

Con.Con.
Extra-chromosomal where many bacteriaExtra-chromosomal where many bacteria
contain extrachromosomal geneticcontain extrachromosomal genetic
elements called plasmids that exist free inelements called plasmids that exist free in
the cytoplasm and can replicate on theirthe cytoplasm and can replicate on their
own.They consist of closed loops of DNAown.They consist of closed loops of DNA
.They may carry R-genes and are so.They may carry R-genes and are so
referred to as R-plasmids causing most ofreferred to as R-plasmids causing most of
the drug resistance found in medicine.the drug resistance found in medicine.

The transfer of resistance genesThe transfer of resistance genes
Between genetic elements within theBetween genetic elements within the
bacterium : Some parts of DNA can bebacterium : Some parts of DNA can be
transposed from a plasmid to another andtransposed from a plasmid to another and
also from a plasmid to a chromosome oralso from a plasmid to a chromosome or
vise versa. This transposon integration tovise versa. This transposon integration to
DNA can occur independantly of normalDNA can occur independantly of normal
genetic recombination and then copy togenetic recombination and then copy to
the donor or acceptor ofDNA.Transposonsthe donor or acceptor ofDNA.Transposons
can hitch-hike on a plasmid to yield a newcan hitch-hike on a plasmid to yield a new
bacterium.bacterium.

Con.Con.
Between bacteria through conjugation ,Between bacteria through conjugation ,
transduction or transformation stages.transduction or transformation stages.

Biochemical mechanisms forBiochemical mechanisms for
antibiotic resistanceantibiotic resistance
By production of enzymes that inactivateBy production of enzymes that inactivate
the drug.the drug.
By alteration of drug binding sites.By alteration of drug binding sites.
By reduction of drug up-take by bacteria.By reduction of drug up-take by bacteria.
By alteration of enzymes .By alteration of enzymes .

Selection of antimicrobial agentsSelection of antimicrobial agents
Selective antimicrobial therapy depends onSelective antimicrobial therapy depends on
the biochemical differences betweenthe biochemical differences between
microorganisms and human beings. Thismicroorganisms and human beings. This
requires knowledge of the organismrequires knowledge of the organism,,
ss
identity and its sensitivity to a particularidentity and its sensitivity to a particular
agent, the site of infection , the safety ofagent, the site of infection , the safety of
the agent , the patient factors , the cost ofthe agent , the patient factors , the cost of
therapy and the need empiric therapy.therapy and the need empiric therapy.

Laboratory methods for microbialLaboratory methods for microbial
identificationidentification
By sensitivity testing : if the zone ofBy sensitivity testing : if the zone of
inhibition is large, the organism is sensitiveinhibition is large, the organism is sensitive
to the particular antibiotic. If there is noto the particular antibiotic. If there is no
zone, it is resistant to the antimicrobialzone, it is resistant to the antimicrobial
drug.drug.

The effect of the site of infection onThe effect of the site of infection on
therapytherapy
To eradicate the microorganism ,enoughTo eradicate the microorganism ,enough
antibiotic should reach the infected site .antibiotic should reach the infected site .
Inflammation may cause more drugs toInflammation may cause more drugs to
penetrate the body barriers.penetrate the body barriers.

Status of the patientStatus of the patient
Including :Including :
-The immune system .-The immune system .
- Renal function.- Renal function.
- Hepatic function .- Hepatic function .
- Perfusion .- Perfusion .
- Pregnancy .- Pregnancy .
- Lactation .- Lactation .
- Age .- Age .

Safety of the antimicrobial agentSafety of the antimicrobial agent
Some antimicrobial agents interfere onlySome antimicrobial agents interfere only
with the site of infection and are hencewith the site of infection and are hence
safe.safe.
Some are less specific and are henceSome are less specific and are hence
reserved for life threatening infections asreserved for life threatening infections as
they are toxic.they are toxic.

Cost of therapyCost of therapy
Drugs vary in cost even if having similarDrugs vary in cost even if having similar
efficiency.efficiency.

Classification of antimicrobial drugsClassification of antimicrobial drugs
Antimicrobial drugAntimicrobial drug
Bactericidal BacteriostaticBactericidal Bacteriostatic
• Bactericidal agents kills bacteria .Bactericidal agents kills bacteria .
• Bacteriostatic agents arrest the growth andBacteriostatic agents arrest the growth and
replication of bacteria at therapeutic serum levelsreplication of bacteria at therapeutic serum levels
achieved by the patient.achieved by the patient.

Combinations of antimicrobialCombinations of antimicrobial
drugsdrugs
It is better to treat the patient with a singleIt is better to treat the patient with a single
specific antimicrobial.specific antimicrobial.
Certain antibiotics show synergism.Certain antibiotics show synergism.
A number of antibiotics work only whenA number of antibiotics work only when
organisms are growing , thus administrationorganisms are growing , thus administration
of a second agent as a bacteriostatic canof a second agent as a bacteriostatic can
lead to interference with the action the firstlead to interference with the action the first
drug .drug .

Prophylactic antibioticProphylactic antibiotic
Used in :Used in :
- Prevention of streptoccocal infection in patient- Prevention of streptoccocal infection in patient,,
ss
with history of rheumatic heart diseases .with history of rheumatic heart diseases .
- Pretreatment of patients who implanted- Pretreatment of patients who implanted
prosthetic devices .prosthetic devices .
- Prevention of tuberculosis or meningitis in- Prevention of tuberculosis or meningitis in
patients in contact with infected people.patients in contact with infected people.
- Prior to surgical procedures .- Prior to surgical procedures .
-In mothers with ziovundine, to protect the foetus-In mothers with ziovundine, to protect the foetus
in HIV infected pregnant women.in HIV infected pregnant women.

Folate antagonistFolate antagonist
Folic acid co-enzymes are required for theFolic acid co-enzymes are required for the
synthesis of purines and pyrimidine and othersynthesis of purines and pyrimidine and other
compounds needed for cellular growth andcompounds needed for cellular growth and
replication.replication.
Sulfa drugs, which are derived from the dyeSulfa drugs, which are derived from the dye
prontosil,are folic acid synthesis inhibitors .prontosil,are folic acid synthesis inhibitors .
Inhibitors of folate synthesis are mafenide, silverInhibitors of folate synthesis are mafenide, silver
sulfadiazine , succinylsulfathiazole, sulfacetamidesulfadiazine , succinylsulfathiazole, sulfacetamide
, sulfadiazine ,sulfamethoxazole , sulfasalzine, sulfadiazine ,sulfamethoxazole , sulfasalzine
sulfisoxazole.sulfisoxazole.

Con.Con.
Bacteria synthesize folate from PABA,Bacteria synthesize folate from PABA,
petridine and glutamate, while man obtainpetridine and glutamate, while man obtain
the readily made folic acid from the diet.the readily made folic acid from the diet.
Sulfonamides are structural analogues toSulfonamides are structural analogues to
PABA, so they compete with this substratePABA, so they compete with this substrate
for the enzyme dihydropteroate synthetase.for the enzyme dihydropteroate synthetase.

Con.Con.
Sulfonamides are bacteriostatic forSulfonamides are bacteriostatic for
enterobacteria , chlamydia, actinomycesenterobacteria , chlamydia, actinomyces
and nocardia.and nocardia.
They may cause crystaluria, hypersensitivityThey may cause crystaluria, hypersensitivity
, hemopoietic disturbances and kernicterus, hemopoietic disturbances and kernicterus
(a(a bilirubin-induced brain dysfunction).bilirubin-induced brain dysfunction).

Inhibitors of folate reductionInhibitors of folate reduction
Trimethoprim with a spectrum similar to that ofTrimethoprim with a spectrum similar to that of
sulfonamides is often compounded withsulfonamides is often compounded with
sulfamethoxazole.sulfamethoxazole.
Folate dihydrofolate dihydrofolateFolate dihydrofolate dihydrofolate
reductase Tetrahydrofolatereductase Tetrahydrofolate
This reaction is inhibited by trimethoprim reducingThis reaction is inhibited by trimethoprim reducing
folate co-enzyme, purines,pyrimidines andfolate co-enzyme, purines,pyrimidines and
aminoacids.Trimethoprim is used in acute UTI andaminoacids.Trimethoprim is used in acute UTI and
bacterial prostatitis.It can cause folate defficiency.bacterial prostatitis.It can cause folate defficiency.

Inhibitors of folate synthesis &Inhibitors of folate synthesis &
reductionreduction
Co-trimoxazole =Co-trimoxazole =
trimethoprim+sulfamethazole.It hastrimethoprim+sulfamethazole.It has
greater antimicrobial activity than eachgreater antimicrobial activity than each
drug alone.It is given orally.drug alone.It is given orally.
It can cause severe dermatological signs ,It can cause severe dermatological signs ,
nausia , vomiting , glossitis ,stomatitis andnausia , vomiting , glossitis ,stomatitis and
anaemias.In HIV patients it can causeanaemias.In HIV patients it can cause
fever ,rashes ,diarrhoea and/orfever ,rashes ,diarrhoea and/or
pancytopenia.pancytopenia.

Inhibitors of cell-wall synthesisInhibitors of cell-wall synthesis
ββ-Lactams (due to the presence of-Lactams (due to the presence of ββ--
Lactam ring which is inhibited byLactam ring which is inhibited by
clavulanic acid,sulbactam ,tazobactam).clavulanic acid,sulbactam ,tazobactam).
Vancomycin.Vancomycin.
Bacitracin.Bacitracin.

1/1/ββ-lactams-lactams
Include :Include :
- Penicillins .- Penicillins .
- Celphalosporins .- Celphalosporins .
- Carbapenems.- Carbapenems.
- Monobactams .- Monobactams .

PenicillinsPenicillins
The most widely effective and less toxicThe most widely effective and less toxic
antibiotic .antibiotic .
They differ from each other in the R-They differ from each other in the R-
component attached to the 6-component attached to the 6-
aminopenicillanic acid residue that affect itsaminopenicillanic acid residue that affect its
antimicrobial spectrum, stability to theantimicrobial spectrum, stability to the
stomach acids ,susceptibility to bacterialstomach acids ,susceptibility to bacterial
degenerative enzymes.degenerative enzymes.
They affect the last step of cell wallThey affect the last step of cell wall
synthesis.synthesis.

Con.Con.
Their efficiency depends on their size ,Their efficiency depends on their size ,
charge and hydrophobicity.charge and hydrophobicity.
Their spectrum is determined by their abilityTheir spectrum is determined by their ability
to cross the bacterial peptidoglycan cell wallto cross the bacterial peptidoglycan cell wall
and reach the penicillin-binding protienand reach the penicillin-binding protien
located in the periplasmic space.located in the periplasmic space.
All gram (+) bacteria and gram (- ) bacteriaAll gram (+) bacteria and gram (- ) bacteria
with protiens inserted in thewith protiens inserted in the
lipopolysaccharides are susceptible tolipopolysaccharides are susceptible to
penicillins.penicillins.

Classification of penicillinsClassification of penicillins
a/ Natural derived from fermentation ofa/ Natural derived from fermentation of
Penicillium chrysogenumPenicillium chrysogenum mold.mold.
b/ Synthetic derived by fermenting the brothb/ Synthetic derived by fermenting the broth
of the mold to yield a different R-residue ofof the mold to yield a different R-residue of
the aminopenicillanic acid :the aminopenicillanic acid :
- Penicillin G (benzylpenicillin).- Penicillin G (benzylpenicillin).
- Penicillin V .- Penicillin V .
c/ Antistaphyloccocal penicillins.c/ Antistaphyloccocal penicillins.

Penicillium chrysogenum MoldPenicillium chrysogenum Mold

Con.Con.
d/Extended-spectrum penicillins e.g.d/Extended-spectrum penicillins e.g.
ampicillins and amoxicillins pevented fromampicillins and amoxicillins pevented from
enzyme hydrolysis byenzyme hydrolysis by ββ-lactam inhibitors.-lactam inhibitors.
e/ Antipseudomonal e.g.carbencillin,e/ Antipseudomonal e.g.carbencillin,
ticarcillin and piperacillin.ticarcillin and piperacillin.
f/ Penicillin and aminoglycosides causef/ Penicillin and aminoglycosides cause
synergism,but never give in an infusion.synergism,but never give in an infusion.

CephalosporinsCephalosporins
These areThese are ββ-lactamantibiotics ,related-lactamantibiotics ,related
structurally and functionally to penicillins,structurally and functionally to penicillins,
that are produced semi-synthetically by athat are produced semi-synthetically by a
side chain chemical attachés of 7-amino-side chain chemical attachés of 7-amino-
cephalosporanic acid to liberatecephalosporanic acid to liberate
cephalosporins and cephamycin.cephalosporins and cephamycin.

Classification of cephalosporinsClassification of cephalosporins
They are classified into:They are classified into:
* First generation e.g. cefazolin and* First generation e.g. cefazolin and
cefadroxil.cefadroxil.
* Second generation e.g. cefactor and* Second generation e.g. cefactor and
cefmetazole.cefmetazole.
* Third generation e.g. ceftibule and* Third generation e.g. ceftibule and
cefdinir.cefdinir.
* Fourth generation e.g. cefipime.* Fourth generation e.g. cefipime.
** All are given considering allergy and** All are given considering allergy and
bleeding.bleeding.

CarbapenemsCarbapenems
These are syntheticThese are synthetic ββ-lactams .-lactams .
Imipenem / cilastatin is the most broad-Imipenem / cilastatin is the most broad-
spectrumed antibiotic used in empiricspectrumed antibiotic used in empiric
therapy.therapy.
They can cause nausea, vomitting ,They can cause nausea, vomitting ,
diarrhea and some times easinophilia anddiarrhea and some times easinophilia and
neutropenia or siezures .neutropenia or siezures .

MonobactamsMonobactams
Where theWhere the ββ-lactam ring is not fused to-lactam ring is not fused to
another ring and hence ,they are resistant toanother ring and hence ,they are resistant to
ββ-lactamases e.g. aztreonam.-lactamases e.g. aztreonam.
They are used in empiric therapy of aerobicThey are used in empiric therapy of aerobic
gram ( + ) rods and enterobacter infections .gram ( + ) rods and enterobacter infections .
They may cause phlebitis ( inflammation ofThey may cause phlebitis ( inflammation of
the veins of legs) , skin rashes and abnormalthe veins of legs) , skin rashes and abnormal
liver testing results.liver testing results.

2/ Vancomycin2/ Vancomycin
Is a glycopeptide effective against methicillinIs a glycopeptide effective against methicillin
–resistant staphylococci and enterococci by–resistant staphylococci and enterococci by
inhibiting bacterial cell-wall phospholipidsinhibiting bacterial cell-wall phospholipids
and polymerization of peptidoglycans.and polymerization of peptidoglycans.
It is used prophylactically in dental patientsIt is used prophylactically in dental patients
with prosthetic devices.with prosthetic devices.
It is synergistic with aminoglycosides inIt is synergistic with aminoglycosides in
enterococcal endocarditis.enterococcal endocarditis.

3/ Bacitracin3/ Bacitracin
It is a mixture of polypeptides usedIt is a mixture of polypeptides used
topically for gram ( + ) organisms to inhibittopically for gram ( + ) organisms to inhibit
bacterial cell-wall synthesis.bacterial cell-wall synthesis.

Protein-synthesis inhibitorsProtein-synthesis inhibitors
The bacterial ribosomes are smaller thanThe bacterial ribosomes are smaller than
the mammalian ribosomes , but thethe mammalian ribosomes , but the
bacterial mitochondria resemble that ofbacterial mitochondria resemble that of
host.host.

i / Tetracyclinsi / Tetracyclins
They consist of 4 fused rings by conjugated doubleThey consist of 4 fused rings by conjugated double
bonds with small variations in substitution of ringsbonds with small variations in substitution of rings
e.g. demecolocycline.doxycycline ,minocycline ande.g. demecolocycline.doxycycline ,minocycline and
tetracycline.tetracycline.
They are known to cause resistance by drugThey are known to cause resistance by drug
accumulation in the bacteria .accumulation in the bacteria .

They may cause gastric discomfort,They may cause gastric discomfort,
deposition in bone and primary teeth indeposition in bone and primary teeth in
kids ,fatal hepatotoxicity ,phototoxicitykids ,fatal hepatotoxicity ,phototoxicity
,vestibular problems pseudotumor,vestibular problems pseudotumor
cerebris and super infection.cerebris and super infection.

ii / Aminoglycosidesii / Aminoglycosides
These are two aminsuges joined inThese are two aminsuges joined in
glycosidic linkage to a central amino-glycosidic linkage to a central amino-
cyclitol nucleus e.g. gentamicincyclitol nucleus e.g. gentamicin
,tobramycin ,streptomycin and amikacin.,tobramycin ,streptomycin and amikacin.
Treat infections due to gram ( - ) bacilliTreat infections due to gram ( - ) bacilli
and can be replaced by the thirdand can be replaced by the third
generation of cephalosporins,generation of cephalosporins,
fluroquinolones and imipenems/cilastatins.fluroquinolones and imipenems/cilastatins.
They are derived fromThey are derived from StreptomycesStreptomyces andand
MicromonosporaMicromonospora ..

iii/ Macrolidesiii/ Macrolides
Microcyclic lactone-structured antibioticMicrocyclic lactone-structured antibiotic
e.g. erythromycin , clarithromycine.g. erythromycin , clarithromycin
,azithromycin and dirithromycin.,azithromycin and dirithromycin.
Erythromycin is resisted by staphylococciErythromycin is resisted by staphylococci
and cross-resistance is common betweenand cross-resistance is common between
macrolides .macrolides .
They interact with theophylline ,warfarinThey interact with theophylline ,warfarin
,terfenadine ,carbamezapine and,terfenadine ,carbamezapine and
cyclosporin and may increase thecyclosporin and may increase the
accumulation of digoxin.accumulation of digoxin.

iv/ Chloramphenicoliv/ Chloramphenicol
It is used against gram ( + ) and gram ( - )It is used against gram ( + ) and gram ( - )
organisms.organisms.
Being toxic, it is used in life-treateningBeing toxic, it is used in life-treatening
infections .infections .
It inhibits peptidyl-transferase reaction andIt inhibits peptidyl-transferase reaction and
can hence lead to bone marrow toxicity.can hence lead to bone marrow toxicity.
It can interact with warfarin ,phenytoinIt can interact with warfarin ,phenytoin
,tolbutamide and chlorpropamide leading to,tolbutamide and chlorpropamide leading to
their accumulation.their accumulation.

v/ Clindamycinv/ Clindamycin
This resembles erythromycin in the modeThis resembles erythromycin in the mode
of action.of action.
It is used in anaerobic bacterial infections.It is used in anaerobic bacterial infections.
It does not cross CSF.It does not cross CSF.
It is excreted in urine and bile.It is excreted in urine and bile.
It is resisted byIt is resisted by Colstridium difficileColstridium difficile..

Quinolones & UTantiseptivesQuinolones & UTantiseptives
i/ Fluroquinolones are completely synthetici/ Fluroquinolones are completely synthetic
and related to nalidixic acid ( a non-and related to nalidixic acid ( a non-
flurinated bactricidal quinolone that isflurinated bactricidal quinolone that is
ineffective in systemic infections ) to treatineffective in systemic infections ) to treat
UTI infections as broad spectrumUTI infections as broad spectrum
antibiotics.Ciprofloxacin treats resistantantibiotics.Ciprofloxacin treats resistant
respiratory , GIT and UTI infections.respiratory , GIT and UTI infections.

Con.Con.
ii/ Quinolones e.g. Nalidixic acid acts theii/ Quinolones e.g. Nalidixic acid acts the
same way as the fluroquinolones. It issame way as the fluroquinolones. It is
used for UTI caused by gram ( - ) bacteria.used for UTI caused by gram ( - ) bacteria.
It is protein-bound , hydrolyzed to yield aIt is protein-bound , hydrolyzed to yield a
bactericidal metabolite.bactericidal metabolite.
iii/ UTI antiseptives e.g. methenamine areiii/ UTI antiseptives e.g. methenamine are
used in the elderly and child-bearingused in the elderly and child-bearing
women to be then excreted in urine .women to be then excreted in urine .

Antimycobacterial drugsAntimycobacterial drugs
i/ Treatment of tuberculosisi/ Treatment of tuberculosis
Mycobacterium tuberculosis infection thatMycobacterium tuberculosis infection that
occur in the lung ,genitourinary tractoccur in the lung ,genitourinary tract
,skeleton and meninges ,is treated by,skeleton and meninges ,is treated by
aminosalicylic acid, cycloserineaminosalicylic acid, cycloserine
,ethambutol ,ethionamide,ethambutol ,ethionamide
,isoniazid,pyrazinamide and rifampin.,isoniazid,pyrazinamide and rifampin.
Multiple drug therapy is employed forMultiple drug therapy is employed for
resistant strains for variable periods afterresistant strains for variable periods after
signs disappear.signs disappear.

Con.Con.
First –line drugs :First –line drugs :
Isoniazid is a synthetic pyridoxine analogue used forIsoniazid is a synthetic pyridoxine analogue used for
M. tuberculosisM. tuberculosis andand M. kansasiiM. kansasii .It interact with.It interact with
phenytoin .phenytoin .
Rifampin : From the soil mold streptomyces withRifampin : From the soil mold streptomyces with
high spectrum forhigh spectrum for M. tuberculosisM. tuberculosis ,,M.lepraeM.leprae ,gram,gram
( + ) and gram( - ) organisms and prophylactic for( + ) and gram( - ) organisms and prophylactic for
house suceptible individuals for meningococci .house suceptible individuals for meningococci .
Rifabutin :ForRifabutin :For M. intracellulareM. intracellulare
Interaction occurs with drugs metabolized by P-450Interaction occurs with drugs metabolized by P-450

Con.Con.
Pyrazinamide is asynthetic antitubercularPyrazinamide is asynthetic antitubercular
used with isoniazid and rifampin.used with isoniazid and rifampin.
Ethambutol is an antitubercular used forEthambutol is an antitubercular used for
M.tuberculosis and M.kansasii that does notM.tuberculosis and M.kansasii that does not
incorporate to resistance if given inincorporate to resistance if given in
combination with other agents.combination with other agents.
Second alternate –line drugs are amino-Second alternate –line drugs are amino-
salicylic acid ,ethionamide and cycloserine.salicylic acid ,ethionamide and cycloserine.

Chemotherapy of leprosyChemotherapy of leprosy
HansenHansen,,
s disease is caused bys disease is caused by M.lepraeM.leprae via skinvia skin
or respiratory tract.or respiratory tract.
Treated due to WHO regimen for 6-24 monthsTreated due to WHO regimen for 6-24 months
by:by:
- Dopasone for- Dopasone for M.lepraeM.leprae and Pseudocytisand Pseudocytis
pneumonia in HIV patients .pneumonia in HIV patients .
- Clofazimine is a phenazine dye that is- Clofazimine is a phenazine dye that is
bactericidal tobactericidal to M.lepraeM.leprae andand M.aviumM.avium
intercellulareintercellulare . It causes red-brown. It causes red-brown
discolouration of skin and eosinophilic entritis.discolouration of skin and eosinophilic entritis.

Antiprotozoal drugsAntiprotozoal drugs
Amebiasis: *luminal treatment= diloxanideAmebiasis: *luminal treatment= diloxanide
-turoate,paromomycin and tetracycline. *systemic-turoate,paromomycin and tetracycline. *systemic
treatment=emetine,dehydroemetine and chloroquine.treatment=emetine,dehydroemetine and chloroquine.
Ingestion of cystIngestion of cyst
Formation of trophozoitesFormation of trophozoites
*luminal treatment*luminal treatment
Penetration of intestinal wallPenetration of intestinal wall
*systemic treatment*systemic treatment
Multiplication of trophozoites within the colon wallMultiplication of trophozoites within the colon wall
Systemic invasionSystemic invasion

Con.Con.
Systemic invasionSystemic invasion
Colon wallColon wall
Colon ( cyst formation)Colon ( cyst formation)
* Mixed treatment* Mixed treatment
RectumRectum
Feaces and cystFeaces and cyst
*Mixedtreatment=systemic+luminal=metronidazole*Mixedtreatment=systemic+luminal=metronidazole

Antifungal drugsAntifungal drugs
Drugs for subcutaneous and systemicDrugs for subcutaneous and systemic
mycosis: e.g. amphotericinB,fluconazolemycosis: e.g. amphotericinB,fluconazole
,flucytosine ,itraconazole and ketoconazole.,flucytosine ,itraconazole and ketoconazole.
Systemic infections are life-threateningSystemic infections are life-threatening
(eukaryotic bacteria + immune-supressed(eukaryotic bacteria + immune-supressed
patients) e.g.cryptococcal meningitis andpatients) e.g.cryptococcal meningitis and
aspergillosis.aspergillosis.
Azole antifungals are used for blastomycosis,Azole antifungals are used for blastomycosis,
coccidiomycosis and histoplasmosis.coccidiomycosis and histoplasmosis.

Con.Con.
Amphoteracin B treatsAmphoteracin B treats StreptomycesStreptomyces
nodosus ,Candida albicans ,Histoplasmanodosus ,Candida albicans ,Histoplasma
capulatum ,Cryptococcus neoformanscapulatum ,Cryptococcus neoformans
,Coccidoides immitis ,Aspergillus sp and,Coccidoides immitis ,Aspergillus sp and
Blastomyces dermatitidis .Blastomyces dermatitidis .
Flucytosine treats chromoblastomycosis.Flucytosine treats chromoblastomycosis.
Ketaconazole treats candidiasis and non-Ketaconazole treats candidiasis and non-
meningeal coccido- and blasto-mycosis.meningeal coccido- and blasto-mycosis.
Fluconazole treatsFluconazole treats Cryptococcus neoformansCryptococcus neoformans
and cadidemia.and cadidemia.
Itraconazole treats blastomycosis.Itraconazole treats blastomycosis.

Drugs for superficial mycoticDrugs for superficial mycotic
infections :infections :
Griseofluvin is fungistatic forGriseofluvin is fungistatic for
dermatophytes ,mainly tinea infections.dermatophytes ,mainly tinea infections.
Nystatin is a polyene antibiotic used forNystatin is a polyene antibiotic used for
candidiasis .candidiasis .
Miconazole is used topically with the sameMiconazole is used topically with the same
spectrum of ketaconzole.spectrum of ketaconzole.

Chemotherapy of malariaChemotherapy of malaria
Infective mosquitoes inject sporozoitesInfective mosquitoes inject sporozoites
Sporozoites exoerythrocyticSporozoites exoerythrocytic
Liver formLiver form
MerizoitesMerizoites
RBCs erythrocytic formRBCs erythrocytic form
(Ruputued)(Ruputued)

Con.Con.
Ruptured RBCsRuptured RBCs
Gametocytes gametocytic formGametocytes gametocytic form
Gametocytes picked by mosquitoesGametocytes picked by mosquitoes
Treatment of:Treatment of:
i/Exoerythrocytic=primaquinei/Exoerythrocytic=primaquine
ii/ Erythrocytic =chloroquine, quinineii/ Erythrocytic =chloroquine, quinine
,mefloquine,primaquine and,mefloquine,primaquine and
chloroguanide.chloroguanide.
iii/Gametocytic= primaquine.iii/Gametocytic= primaquine.

TrypanosomiasisTrypanosomiasis
American form caused by TrypanosomaAmerican form caused by Trypanosoma
cruzi (Chagas, disease ) and is treated bycruzi (Chagas, disease ) and is treated by
nifurtimox.nifurtimox.
African form caused by TrypansomaAfrican form caused by Trypansoma
brucei and is treated by suramin andbrucei and is treated by suramin and
pantamidine in early stages andpantamidine in early stages and
melarsoprol in case of CNS invasion.melarsoprol in case of CNS invasion.

OthersOthers
Leishmaniasis is treated with sodiumLeishmaniasis is treated with sodium
stibogluconate .stibogluconate .
Toxoplasmosis is treated withToxoplasmosis is treated with
pyrimethamine.pyrimethamine.
Gardiasis is treated with quinacrine orGardiasis is treated with quinacrine or
metronidazole .metronidazole .

Anthelmintic drugsAnthelmintic drugs
Nematodal infections are treated withNematodal infections are treated with
ivermection ,mebendazole ,thiabendazoleivermection ,mebendazole ,thiabendazole
or pyrantel pamoate.or pyrantel pamoate.
Trematodes are treated with praziquantel.Trematodes are treated with praziquantel.
Cestodes are treated with niclosamide.Cestodes are treated with niclosamide.

Antiviral drugsAntiviral drugs
Drugs used for respiratory infections :Drugs used for respiratory infections :
These are influenza viruses type A, B andThese are influenza viruses type A, B and
respiratory cyncytial virus (RCV) whenrespiratory cyncytial virus (RCV) when
patients are allergic to the vaccine, in casepatients are allergic to the vaccine, in case
of out breaks or in suceptibleof out breaks or in suceptible
patients.They are treated with amantadinepatients.They are treated with amantadine
,rimantidine and ribavirin.,rimantidine and ribavirin.

Con.Con.
Drugs used for Herpes- and Cytomegalo-Drugs used for Herpes- and Cytomegalo-
viruses infections :viruses infections :
*Acyclovir is used for Herpes-simlpex-1 (HSV-*Acyclovir is used for Herpes-simlpex-1 (HSV-
1) , HSV-2,Varicell-zoster virus and some1) , HSV-2,Varicell-zoster virus and some
Epstein-barr viruses. It is also usedEpstein-barr viruses. It is also used
prophylactically before bone marrow andprophylactically before bone marrow and
after heart transplantaions.after heart transplantaions.
*Ganciclovir is used for cytomegalic retinitis in*Ganciclovir is used for cytomegalic retinitis in
immunocompromised patients.immunocompromised patients.

Con.Con.
*Famciclovir resembles ganciclovir spectrum*Famciclovir resembles ganciclovir spectrum
especially Herpes-zoster ,but mayespecially Herpes-zoster ,but may
enhance adenocarcinomas and testicularenhance adenocarcinomas and testicular
toxicity.toxicity.
*Foscarnet is used against cytomegalic*Foscarnet is used against cytomegalic
retinitis inHIV-infected patients.retinitis inHIV-infected patients.
*Vidrarabine used in case of HSV-1, HSV-2*Vidrarabine used in case of HSV-1, HSV-2
and varicella-zoster virus .and varicella-zoster virus .
*Trifluridine is used topically for*Trifluridine is used topically for
keratoconjuctivitis.keratoconjuctivitis.

Treatment of AIDsTreatment of AIDs
Zidovudine increase the absolute number ofZidovudine increase the absolute number of
helper- induced T-cells and the protection ofhelper- induced T-cells and the protection of
foetus from becoming infected when HIV-infectedfoetus from becoming infected when HIV-infected
pregnant mother has being maintained on thepregnant mother has being maintained on the
drug.AZT interact with probencid ,lorazepam,drug.AZT interact with probencid ,lorazepam,
indomethacin acetaminophen and cimetidine.indomethacin acetaminophen and cimetidine.
Didanosine is used forresistant HIV- infection.Didanosine is used forresistant HIV- infection.
Zalcitabine is used in patients who cannotZalcitabine is used in patients who cannot
tolerate AZT.tolerate AZT.

Con.Con.
Stavudine decrease mitochondrialStavudine decrease mitochondrial
synthesis of DNA.synthesis of DNA.
Lamivudine inhibit transcriptases of HIVLamivudine inhibit transcriptases of HIV
and hepatitis B virus .It interact withand hepatitis B virus .It interact with
trimethoprim and sulfamethaxole.trimethoprim and sulfamethaxole.
HIV-protease inhibitors inhibit viralHIV-protease inhibitors inhibit viral
proliferation e.g. saquinvir ,ritonavir,proliferation e.g. saquinvir ,ritonavir,
indinavir and ampreavir.indinavir and ampreavir.

InterferonsInterferons
These are a family of naturally occuringThese are a family of naturally occuring
inducible glycoproteins that interfere withinducible glycoproteins that interfere with
the ability of viruses to infect cells (mainlythe ability of viruses to infect cells (mainly
in vitro) . They are synthesized byin vitro) . They are synthesized by
recombinant DNA technology eitherrecombinant DNA technology either αα ,,ββ
or gamma to degrade viral mRNA andor gamma to degrade viral mRNA and
Trna.Trna.

Chemotherapy of CancerChemotherapy of Cancer

Cancer TreatmentCancer Treatment
involves the use of anti cancer medicinesinvolves the use of anti cancer medicines
(cytotoxic drugs) to modify, destruct or(cytotoxic drugs) to modify, destruct or
remove the cancer cells. Chemotherapyremove the cancer cells. Chemotherapy
treatments may also be undertaken for non-treatments may also be undertaken for non-
cancerous patients, where the dosagecancerous patients, where the dosage
remains minimum, which also ensuresremains minimum, which also ensures
minimal side effects. More than 200 variousminimal side effects. More than 200 various
kinds of cancer is prevalent in people acrosskinds of cancer is prevalent in people across
the world and there are more than 50the world and there are more than 50
chemotherapy medicines that are used inchemotherapy medicines that are used in
various ways.various ways.

The choice of an anticaner depends onThe choice of an anticaner depends on
many factors e.g. the kind of cancer themany factors e.g. the kind of cancer the
patient is suffering from , the origin ofpatient is suffering from , the origin of
cancer in the body, the appearance ofcancer in the body, the appearance of
cancer-cells through a microscope, and if itcancer-cells through a microscope, and if it
has spread to other parts of the body.has spread to other parts of the body.
- They are used to cure prolonged remission- They are used to cure prolonged remission
as primary treatment modality , palliation ofas primary treatment modality , palliation of
symptoms and /or prolongation of life andsymptoms and /or prolongation of life and
as an adjuvant to mop up any residualas an adjuvant to mop up any residual
cancer cells after surgery or radiologycancer cells after surgery or radiology

Application of chemotherapy may be inApplication of chemotherapy may be in
various ways, based on the cancer type.various ways, based on the cancer type.
The chemotherapy drugs are usedThe chemotherapy drugs are used
accordingly. Mostly chemotherapy drugsaccordingly. Mostly chemotherapy drugs
are given intravenously i.e. through aare given intravenously i.e. through a
vein, using an injection or a drip. Thisvein, using an injection or a drip. This
method of chemotherapy administrationmethod of chemotherapy administration
is called “intravenous chemotherapy”.is called “intravenous chemotherapy”.

Drugs given in the form of capsules orDrugs given in the form of capsules or
tablets is called “oral chemotherapy”. Atablets is called “oral chemotherapy”. A
drug injected into the muscle is known asdrug injected into the muscle is known as
“intramuscular injection”. When it is“intramuscular injection”. When it is
injected just below the skin, it is calledinjected just below the skin, it is called
“subcutaneous injection”. The drugs“subcutaneous injection”. The drugs
infused into the body through the above-infused into the body through the above-
mentioned means reach the cancer cellsmentioned means reach the cancer cells
in the body through the blood.in the body through the blood.

To treat certain kind of cancers,To treat certain kind of cancers,
chemotherapy drugs may be required tochemotherapy drugs may be required to
reach the fluid present in the region ofreach the fluid present in the region of
spine, this method is called “intrathecalspine, this method is called “intrathecal
chemotherapy”. When certain bodychemotherapy”. When certain body
cavities like bladder or pelvic cavity arecavities like bladder or pelvic cavity are
injected with chemotherapy drugs, it isinjected with chemotherapy drugs, it is
called “intracavity chemotherapy”.called “intracavity chemotherapy”.

In many of the above-mentioned methods,In many of the above-mentioned methods,
the chemotherapy drugs are most likely tothe chemotherapy drugs are most likely to
stay in the injected area, resulting in nostay in the injected area, resulting in no
harm to the other parts of the body.harm to the other parts of the body.
Chemotherapy creams are also used forChemotherapy creams are also used for
certain skin-cancers, wherein only the cellscertain skin-cancers, wherein only the cells
in the region get affected.in the region get affected.
At times two kinds of chemotherapyAt times two kinds of chemotherapy
administration methods may also be used,administration methods may also be used,
such as intravenous chemotherapy andsuch as intravenous chemotherapy and
oral chemotherapy.oral chemotherapy.

CLASSIFICATION OF
ANTICANCER DRUGS
1/ Drugs acting directly on cells = cytotoxic:1/ Drugs acting directly on cells = cytotoxic:
a/ Alkylating agents :nitrogen mustards e.g.a/ Alkylating agents :nitrogen mustards e.g.
mechlorethamine, cyclophosphamidemechlorethamine, cyclophosphamide
,chlorambucil , melphalan and alkyl sulfonate,chlorambucil , melphalan and alkyl sulfonate
nitrosoureas triazines e.g. busulfan ,nitrosoureas triazines e.g. busulfan ,
lomustine ,decarbazinelomustine ,decarbazine
b/ Anitmetabolites : folate anatgonists e.g.b/ Anitmetabolites : folate anatgonists e.g.
methtrexate ; purine antagonis e.g. 6-methtrexate ; purine antagonis e.g. 6-
mercaptopurine ,6- thioguanine andmercaptopurine ,6- thioguanine and
azathioprine and pyrimidineazathioprine and pyrimidine

Antagonists e.g. 5- fluorouracil and cytarabine.Antagonists e.g. 5- fluorouracil and cytarabine.
c/ Vinca alkaloids e.g. vincrystine (oncovin) andc/ Vinca alkaloids e.g. vincrystine (oncovin) and
vinblastin.vinblastin.
d/ Taxane e.g. paclitaxel and docitaxel.d/ Taxane e.g. paclitaxel and docitaxel.
e/Epipodophyllotoxin e.g. etoposide.e/Epipodophyllotoxin e.g. etoposide.
f/Camptothecin analogues e.g topotecan andf/Camptothecin analogues e.g topotecan and
irinotecanirinotecan..

g/ Antibiotics e.g. actinomycin D ,g/ Antibiotics e.g. actinomycin D ,
doxorubicin daunorubicin and bleomycin .doxorubicin daunorubicin and bleomycin .
h/ Micscellaneous e.g.hydroxyurea ,h/ Micscellaneous e.g.hydroxyurea ,
procabrbazin, L-asparginase .cisplatin andprocabrbazin, L-asparginase .cisplatin and
carboplatin.carboplatin.
2/ Drugs altering hormonal milieu :2/ Drugs altering hormonal milieu :
glucocorticoids e.g. prednsolone ,glucocorticoids e.g. prednsolone ,
estrogens e.g. ethinylestradiolestrogens e.g. ethinylestradiol
,antiestrogens e.g. tamoxifen, antandrogen,antiestrogens e.g. tamoxifen, antandrogen
e.g. flutamide , 5-e.g. flutamide , 5-αα reductase inhibitor e.g.reductase inhibitor e.g.
finasteride ,finasteride ,

GnRH e.g. neferelin and goserelin andGnRH e.g. neferelin and goserelin and
progestins e.g. hydroxyprogestroneprogestins e.g. hydroxyprogestrone
acetate.acetate.
Cytotoxic drugs may cause generalCytotoxic drugs may cause general
toxicity on the bone marrow e.g.toxicity on the bone marrow e.g.
granulocytopenia , on lymphoreticulargranulocytopenia , on lymphoreticular
tissues e.g. lymphocytopenia , on GIT e.g.tissues e.g. lymphocytopenia , on GIT e.g.
diarrhoea , on skin e.g. alopecia , ondiarrhoea , on skin e.g. alopecia , on
gonads e.g. oligozoospermia , on foeti e.g.gonads e.g. oligozoospermia , on foeti e.g.
abortion hyperuricaemia ….etcabortion hyperuricaemia ….etc

Oral complications of cancer chemotherapyOral complications of cancer chemotherapy
The oral mucosa id particularly susceptibleThe oral mucosa id particularly susceptible
to cytotoxic drugs due to the high epithelialto cytotoxic drugs due to the high epithelial
cell turnover e.g. oral mucositis is an earlycell turnover e.g. oral mucositis is an early
menifestation of toxicity.menifestation of toxicity.
Gingival tissue is always subjected toGingival tissue is always subjected to
traumas during jewing,so breaches aretraumas during jewing,so breaches are
common.common.
Oral microflora is large and on theOral microflora is large and on the
presence of breaches can lead to local andpresence of breaches can lead to local and
blood-borne infections.blood-borne infections.

Neutropenia and depression of immunityNeutropenia and depression of immunity
may lead caused indirectly by drugs maymay lead caused indirectly by drugs may
lead to oral infections and bleedinglead to oral infections and bleeding
treated by antifibrinolytic drugs and iftreated by antifibrinolytic drugs and if
needed platelets transfusion.needed platelets transfusion.
Chemotherapy may also causeChemotherapy may also cause
xerostomia that may progress into dentalxerostomia that may progress into dental
caries. Angular cheilitis is anothercaries. Angular cheilitis is another
problem.problem.

Dental check up may minimize complicationsDental check up may minimize complications
induced by drugs before applying andinduced by drugs before applying and
regimen. Any carious cavities , periodontalregimen. Any carious cavities , periodontal
lesions , impacted last morals and otherlesions , impacted last morals and other
potetnial sources of infection.potetnial sources of infection.
Stomatitis and mouth ulcers can be treatedStomatitis and mouth ulcers can be treated
with chlorhexidine mouth wash and nystatinwith chlorhexidine mouth wash and nystatin
or clotrimazole for Candida infections .or clotrimazole for Candida infections .
Benzocaine lozenges, opioid analgesics orBenzocaine lozenges, opioid analgesics or
lignocaine may reduce pain caused bylignocaine may reduce pain caused by
mucositismucositis

Systemic antibiotics may cover organismsSystemic antibiotics may cover organisms
e.g. Pseuomonus ,Klebsiella , and E. colie.g. Pseuomonus ,Klebsiella , and E. coli
.Also gram positive cocci and anaerobes.Also gram positive cocci and anaerobes
should be considered for chemotherapyshould be considered for chemotherapy
related oral infections.related oral infections.
Dental procedures in case of patientsDental procedures in case of patients
receiving chemotherapy should be with duereceiving chemotherapy should be with due
regard to the immune and haemostaticregard to the immune and haemostatic
condition of the patient.condition of the patient.
Appropriate prophylactic to eliminate risk ofAppropriate prophylactic to eliminate risk of
infection is improtant in chepotherapyinfection is improtant in chepotherapy
compromising patients.compromising patients.

Oral cancerOral cancer
OralOral cancercancer is abnormal (malignant) growthis abnormal (malignant) growth
of body cells in any part of the oral cavity.of body cells in any part of the oral cavity.
Risk factors for oral cancer are many; forRisk factors for oral cancer are many; for
example, tobacco use alcohol use, sunexample, tobacco use alcohol use, sun
exposure (lips), anyone who has alreadyexposure (lips), anyone who has already
had some form of head and neck cancer,had some form of head and neck cancer,
and human papilloma virus infection.and human papilloma virus infection.

Symptoms of oral cancer may include red,Symptoms of oral cancer may include red,
white and/or a mixture of these colors inwhite and/or a mixture of these colors in
patches, a non-healing sore in the mouth orpatches, a non-healing sore in the mouth or
on the lips, bleeding, loose teeth, swallowingon the lips, bleeding, loose teeth, swallowing
problems, new denture problems, lumps orproblems, new denture problems, lumps or
bumps on the neck, and earaches.bumps on the neck, and earaches.
Oral cancer is diagnosed by the patient'sOral cancer is diagnosed by the patient's
history and physical exam and definitively byhistory and physical exam and definitively by
a biopsy of oral tissue; occasionally, CTa biopsy of oral tissue; occasionally, CT
scans,scans,MRIMRI scans or PET scans may bescans or PET scans may be
used.used.

Methods of treatment for oral cancer includeMethods of treatment for oral cancer include
surgery,surgery, radiation therapyradiation therapy,,
and/orand/or chemotherapychemotherapy..
The side effects of oral cancer treatment mayThe side effects of oral cancer treatment may
include pain,include pain,weaknessweakness, altered facial, altered facial
appearance, difficulty in swallowing orappearance, difficulty in swallowing or
chewing food,chewing food, dry mouthdry mouth, tooth decay,, tooth decay, soresore
throatthroat, sore gums, bleeding, infections,, sore gums, bleeding, infections,
denture problems, voice quality, thyroiddenture problems, voice quality, thyroid
problems,problems, fatiguefatigue,, hair losshair loss,, nauseanausea,,vomitingvomiting,,
andand diarrheadiarrhea..

Rehabilitation after oral cancer surgeryRehabilitation after oral cancer surgery
consists of regaining strength, developingconsists of regaining strength, developing
a healthy diet the patient can tolerate, anda healthy diet the patient can tolerate, and
possiblypossibly dental implantsdental implants or facialor facial
reconstruction surgery.reconstruction surgery.
After treatment and rehabilitation (seeAfter treatment and rehabilitation (see
above), checkups are needed to maintainabove), checkups are needed to maintain
health and make sure that the oral cancerhealth and make sure that the oral cancer
does not recur.does not recur.
Oral cancer treatment can result inOral cancer treatment can result in
significant lifestyle changes; most patientssignificant lifestyle changes; most patients
are advised to discuss lifestyle problemsare advised to discuss lifestyle problems05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006

Oral cancer treatment can resultOral cancer treatment can result
in significant lifestyle changes;in significant lifestyle changes;
most patients are advised tomost patients are advised to
discuss lifestyle problems withdiscuss lifestyle problems with
professionals such as socialprofessionals such as social
workers to help patients get theworkers to help patients get the
care they may need.care they may need.

Oral and oropharyngeal cancer can often beOral and oropharyngeal cancer can often be
cured, especially if the cancer is found at ancured, especially if the cancer is found at an
early stage. Although curing the cancer is theearly stage. Although curing the cancer is the
primary goal of treatment, preserving theprimary goal of treatment, preserving the
function of the nearby nerves, organs, andfunction of the nearby nerves, organs, and
tissues is also very important. When doctorstissues is also very important. When doctors
plan treatment, they consider how treatmentplan treatment, they consider how treatment
might affect a person’s quality of life, such asmight affect a person’s quality of life, such as
how the person feels, looks, talks, eats, andhow the person feels, looks, talks, eats, and
breathes.breathes.

A treatment team may include medicalA treatment team may include medical
oncologists who specialize in treatingoncologists who specialize in treating
cancer with medication, radiationcancer with medication, radiation
oncologists who specialize in givingoncologists who specialize in giving
radiation therapy to treat cancer, surgeons,radiation therapy to treat cancer, surgeons,
otolaryngologists (ear, nose, and throatotolaryngologists (ear, nose, and throat
doctors), maxillofacial prosthodontists whodoctors), maxillofacial prosthodontists who
specialize in restorative surgery to the headspecialize in restorative surgery to the head
and neck area, dentists, physical therapists,and neck area, dentists, physical therapists,
speech pathologists, mental healthspeech pathologists, mental health
professionals, nurses, dietitians, and socialprofessionals, nurses, dietitians, and social
workers.workers.

Systemic chemotherapy is deliveredSystemic chemotherapy is delivered
through the bloodstream to reach cancerthrough the bloodstream to reach cancer
cells throughout the body. Common wayscells throughout the body. Common ways
to give chemotherapy include anto give chemotherapy include an
intravenous (IV) tube placed into a veinintravenous (IV) tube placed into a vein
using a needle or in a pill or capsule thatusing a needle or in a pill or capsule that
is swallowed (orally). A chemotherapyis swallowed (orally). A chemotherapy
regimen (schedule) usually consists of aregimen (schedule) usually consists of a
specific number of cycles given over a setspecific number of cycles given over a set
period of time. A patient may receive oneperiod of time. A patient may receive one
drug at a time or combinations of differentdrug at a time or combinations of different
drugs at the same time.drugs at the same time.

Chemotherapy may be used as the initialChemotherapy may be used as the initial
treatment before surgery, radiation therapy,treatment before surgery, radiation therapy,
or both, which is called a neoadjuvantor both, which is called a neoadjuvant
chemotherapy, or it can be given afterchemotherapy, or it can be given after
surgery, radiation therapy, or both, which issurgery, radiation therapy, or both, which is
called adjuvant chemotherapy.called adjuvant chemotherapy.
Chemotherapy for oral cavity cancer is mostChemotherapy for oral cavity cancer is most
often given as part of a clinical trial.often given as part of a clinical trial.

Each drug or combination of drugs canEach drug or combination of drugs can
cause specific side effects. While some cancause specific side effects. While some can
be permanent, most are temporary and canbe permanent, most are temporary and can
typically be well controlled. In general,typically be well controlled. In general,
chemotherapy may cause fatigue, nausea,chemotherapy may cause fatigue, nausea,
vomiting, hair loss, dry mouth, hearing loss,vomiting, hair loss, dry mouth, hearing loss,
loss of appetite (often due to a change inloss of appetite (often due to a change in
sense of taste), difficulty eating food,sense of taste), difficulty eating food,
weakened immune system, diarrhea and/orweakened immune system, diarrhea and/or
constipation, and open sores in the mouthconstipation, and open sores in the mouth
that can lead to infection.that can lead to infection.

Immunotherapy, also called biologicImmunotherapy, also called biologic
therapy, is designed to boost the body’stherapy, is designed to boost the body’s
natural defenses to fight cancer. It usesnatural defenses to fight cancer. It uses
materials made either by the body or in amaterials made either by the body or in a
laboratory to improve, target, or restorelaboratory to improve, target, or restore
immune system function.e.g. specific Tcellimmune system function.e.g. specific Tcell
inhibitors like cyclosporin and tarclimus,inhibitors like cyclosporin and tarclimus,
cytotoxic and antiproliferative drugs likecytotoxic and antiproliferative drugs like
azathioprine, cyclophosphamideazathioprine, cyclophosphamide
,methtrexate and chloambucil,methtrexate and chloambucil

Glucocorticoids like prenisolone andGlucocorticoids like prenisolone and
antibodies like muromonab CD3,antibodies like muromonab CD3,
antithymocteglubulin ATGantithymocteglubulin ATG

Targeted therapy is a treatment that targetsTargeted therapy is a treatment that targets
the cancer’s specific genes, proteins, or thethe cancer’s specific genes, proteins, or the
tissue environment that contributes totissue environment that contributes to
cancer growth and survival. This type ofcancer growth and survival. This type of
treatment blocks the growth and spread oftreatment blocks the growth and spread of
cancer cells while limiting damage tocancer cells while limiting damage to
healthy cells.healthy cells.

Currently, antibodies directed against aCurrently, antibodies directed against a
cellular receptor called the epidermalcellular receptor called the epidermal
growth factor receptor (EGFR) are beinggrowth factor receptor (EGFR) are being
used in combination with radiation therapyused in combination with radiation therapy
for head and neck cancers. Talk with yourfor head and neck cancers. Talk with your
doctor about the possible side effects ofdoctor about the possible side effects of
the specific treatment you will be receivingthe specific treatment you will be receiving
and how they can be managed.and how they can be managed.

Basics of Chemotherapy and Antibiotic Resistance

Recommandé

Recommandé

Contenu connexe

Tendances

Tendances (20)

Similaire à Basics of Chemotherapy and Antibiotic Resistance

Similaire à Basics of Chemotherapy and Antibiotic Resistance (20)

Plus de Amna Medani

Plus de Amna Medani (20)

Dernier

Dernier (20)

Basics of Chemotherapy and Antibiotic Resistance