Transcript of Basic principles of chemotherapy
- 1. 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.
- 2. - 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 05/10/1505/10/15 Dr. Medani A.B.
,2006Dr. Medani A.B. ,2006
- 3. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
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 .
- 4. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
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.
- 5. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
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.
- 6. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
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.
- 7. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
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.
- 8. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
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.
- 9. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
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.
- 10. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
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.
- 11. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
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.
- 12. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
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.
- 13. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
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.
- 14. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
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.
- 15. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
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.
- 16. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
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.
- 17. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
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.
- 18. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
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.
- 19. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
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.
- 20. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
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.
- 21. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
Con.Con. Between bacteria through conjugation ,Between bacteria
through conjugation , transduction or transformation
stages.transduction or transformation stages.
- 22. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
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 .
- 23. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
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.
- 24. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
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.
- 25. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
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.
- 26. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
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 .
- 27. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
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.
- 28. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
Cost of therapyCost of therapy Drugs vary in cost even if having
similarDrugs vary in cost even if having similar
efficiency.efficiency.
- 29. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
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.
- 30. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
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 .
- 31. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
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.
- 32. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
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.
- 33. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
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.
- 34. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
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).
- 35. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
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.
- 36. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
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.
- 37. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
Inhibitors of cell-wall synthesisInhibitors of cell-wall synthesis
-Lactams (due to the presence of-Lactams (due to the presence of --
Lactam ring which is inhibited byLactam ring which is inhibited by
clavulanic acid,sulbactam ,tazobactam).clavulanic acid,sulbactam
,tazobactam). Vancomycin.Vancomycin. Bacitracin.Bacitracin.
- 38. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
1/1/-lactams-lactams Include :Include : - Penicillins .-
Penicillins . - Celphalosporins .- Celphalosporins . -
Carbapenems.- Carbapenems. - Monobactams .- Monobactams .
- 39. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
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.
- 40. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
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.
- 41. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
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.
- 42. Penicillium chrysogenum MoldPenicillium chrysogenum Mold
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
- 43. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
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 -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.
- 44. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
CephalosporinsCephalosporins These areThese are -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 attachs of 7-amino-side
chain chemical attachs of 7-amino- cephalosporanic acid to
liberatecephalosporanic acid to liberate cephalosporins and
cephamycin.cephalosporins and cephamycin.
- 45. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
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.
- 46. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
CarbapenemsCarbapenems These are syntheticThese are synthetic
-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 .
- 47. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
MonobactamsMonobactams Where theWhere the -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
-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.
- 48. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
2/ Vancomycin2/ Vancomycin Is a glycopeptide effective against
methicillinIs a glycopeptide effective against methicillin
resistant staphylococci and enterococci byresistant 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.
- 49. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
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.
- 50. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
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.
- 51. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
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 .
- 52. 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. 05/10/1505/10/15 Dr.
Medani A.B. ,2006Dr. Medani A.B. ,2006
- 53. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
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 ..
- 54. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B.
,2006
- 55. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
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.
- 56. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
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.
- 57. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
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..
- 58. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
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.
- 59. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
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 .
- 60. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
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.
- 61. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
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
- 62. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
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.
- 63. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
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.
- 64. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B.
,2006
- 65. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
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
- 66. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
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
- 67. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
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.
- 68. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
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.
- 69. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
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.
- 70. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
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)
- 71. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
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.
- 72. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
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.
- 73. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
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 .
- 74. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
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.
- 75. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
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.
- 76. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
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.
- 77. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
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.
- 78. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
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.
- 79. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
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.
- 80. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
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 ,, or gamma to
degrade viral mRNA andor gamma to degrade viral mRNA and
Trna.Trna.
- 81. Chemotherapy of CancerChemotherapy of Cancer
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
- 82. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B.
,2006
- 83. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B.
,2006
- 84. 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. 05/10/1505/10/15 Dr. Medani
A.B. ,2006Dr. Medani A.B. ,2006
- 85. 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
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
- 86. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B.
,2006
- 87. 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. 05/10/1505/10/15 Dr. Medani A.B.
,2006Dr. Medani A.B. ,2006
- 88. 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 isintramuscular injection. When it is injected
just below the skin, it is calledinjected just below the skin, it
is called subcutaneous injection. The drugssubcutaneous 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. 05/10/1505/10/15 Dr. Medani
A.B. ,2006Dr. Medani A.B. ,2006
- 89. 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. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr.
Medani A.B. ,2006
- 90. 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. 05/10/1505/10/15 Dr. Medani A.B.
,2006Dr. Medani A.B. ,2006
- 91. 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
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
- 92. 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.. 05/10/1505/10/15
Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
- 93. 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- reductase inhibitor
e.g.reductase inhibitor e.g. finasteride ,finasteride ,
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
- 94. 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 05/10/1505/10/15 Dr. Medani A.B.
,2006Dr. Medani A.B. ,2006
- 95. 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. 05/10/1505/10/15 Dr. Medani A.B.
,2006Dr. Medani A.B. ,2006
- 96. 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. 05/10/1505/10/15 Dr. Medani
A.B. ,2006Dr. Medani A.B. ,2006
- 97. 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 05/10/1505/10/15 Dr.
Medani A.B. ,2006Dr. Medani A.B. ,2006
- 98. 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.
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
- 99. 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. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B.
,2006
- 100. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B.
,2006
- 101. 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. 05/10/1505/10/15
Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
- 102. 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..
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
- 103. 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
- 104. 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. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr.
Medani A.B. ,2006
- 105. 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
persons quality of life, such asmight affect a persons quality of
life, such as how the person feels, looks, talks, eats, andhow the
person feels, looks, talks, eats, and breathes.breathes.
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
- 106. 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. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani
A.B. ,2006
- 107. 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. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani
A.B. ,2006
- 108. 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. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani
A.B. ,2006
- 109. 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. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B.
,2006
- 110. Immunotherapy, also called biologicImmunotherapy, also
called biologic therapy, is designed to boost the bodystherapy, is
designed to boost the bodys 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
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
- 111. Glucocorticoids like prenisolone andGlucocorticoids like
prenisolone and antibodies like muromonab CD3,antibodies like
muromonab CD3, antithymocteglubulin ATGantithymocteglubulin ATG
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
- 112. Targeted therapy is a treatment that targetsTargeted
therapy is a treatment that targets the cancers specific genes,
proteins, or thethe cancers 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. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr.
Medani A.B. ,2006
- 113. 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.
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
- 114. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B.
,2006