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05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
Basic principles ofBasic principles of
chemotherapychemotherap...
- Antibiotics are substances produced byAntibiotics are substances produced by
some microorganisms that kill or inhibit th...
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...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
CytoplsmCytoplsm
Contains soluble proteins mostly withContains...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
Con.Con.
Some bacteria have additionalSome bacteria have addit...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
Biochemical reactions involved inBiochemical reactions involve...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
Con.Con.
These classes constitute targets for theThese classes...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
Biochemical reactions as potentialBiochemical reactions as pot...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
Con.Con.
Class II: Bacteria ,unlike humans, canClass II: Bacte...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
Con.Con.
The sequential blockade with aThe sequential blockade...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
Con.Con.
Class III :There are distinct differencesClass III :T...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
Con.Con.
ii/ Protien synthesis : Ribosomes, which areii/ Proti...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
Con.Con.
iii/ Nucleic acid synthesis starts by the activation ...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
Cell-structure targeted therapyCell-structure targeted therapy...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
Con.Con.
Microtubules and/or microfilaments:Microtubules and/o...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
Resistance to antibioticsResistance to antibiotics
Organisms a...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
Con.Con.
These mechanisms are important for :These mechanisms ...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
Genetic determinants of antibioticGenetic determinants of anti...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
Con.Con.
Extra-chromosomal where many bacteriaExtra-chromosoma...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
The transfer of resistance genesThe transfer of resistance gen...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
Con.Con.
Between bacteria through conjugation ,Between bacteri...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
Biochemical mechanisms forBiochemical mechanisms for
antibioti...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
Selection of antimicrobial agentsSelection of antimicrobial ag...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
Laboratory methods for microbialLaboratory methods for microbi...
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 o...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
Status of the patientStatus of the patient
Including :Includin...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
Safety of the antimicrobial agentSafety of the antimicrobial a...
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 havi...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
Classification of antimicrobial drugsClassification of antimic...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
Combinations of antimicrobialCombinations of antimicrobial
dru...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
Prophylactic antibioticProphylactic antibiotic
Used in :Used i...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
Folate antagonistFolate antagonist
Folic acid co-enzymes are r...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
Con.Con.
Bacteria synthesize folate from PABA,Bacteria synthes...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
Con.Con.
Sulfonamides are bacteriostatic forSulfonamides are b...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
Inhibitors of folate reductionInhibitors of folate reduction
T...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
Inhibitors of folate synthesis &Inhibitors of folate synthesis...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
Inhibitors of cell-wall synthesisInhibitors of cell-wall synth...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
1/1/ββ-lactams-lactams
Include :Include :
- Penicillins .- Pen...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
PenicillinsPenicillins
The most widely effective and less toxi...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
Con.Con.
Their efficiency depends on their size ,Their efficie...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
Classification of penicillinsClassification of penicillins
a/ ...
Penicillium chrysogenum MoldPenicillium chrysogenum Mold
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
Con.Con.
d/Extended-spectrum penicillins e.g.d/Extended-spectr...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
CephalosporinsCephalosporins
These areThese are ββ-lactamantib...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
Classification of cephalosporinsClassification of cephalospori...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
CarbapenemsCarbapenems
These are syntheticThese are synthetic ...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
MonobactamsMonobactams
Where theWhere the ββ-lactam ring is no...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
2/ Vancomycin2/ Vancomycin
Is a glycopeptide effective against...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
3/ Bacitracin3/ Bacitracin
It is a mixture of polypeptides use...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
Protein-synthesis inhibitorsProtein-synthesis inhibitors
The b...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
i / Tetracyclinsi / Tetracyclins
They consist of 4 fused rings...
They may cause gastric discomfort,They may cause gastric discomfort,
deposition in bone and primary teeth indeposition in ...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
ii / Aminoglycosidesii / Aminoglycosides
These are two aminsug...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
iii/ Macrolidesiii/ Macrolides
Microcyclic lactone-structured ...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
iv/ Chloramphenicoliv/ Chloramphenicol
It is used against gram...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
v/ Clindamycinv/ Clindamycin
This resembles erythromycin in th...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
Quinolones & UTantiseptivesQuinolones & UTantiseptives
i/ Flur...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
Con.Con.
ii/ Quinolones e.g. Nalidixic acid acts theii/ Quinol...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
Antimycobacterial drugsAntimycobacterial drugs
i/ Treatment of...
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...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
Con.Con.
Pyrazinamide is asynthetic antitubercularPyrazinamide...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
Chemotherapy of leprosyChemotherapy of leprosy
HansenHansen,,
...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
Antiprotozoal drugsAntiprotozoal drugs
Amebiasis: *luminal tre...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
Con.Con.
Systemic invasionSystemic invasion
Colon wallColon wa...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
Antifungal drugsAntifungal drugs
Drugs for subcutaneous and sy...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
Con.Con.
Amphoteracin B treatsAmphoteracin B treats Streptomyc...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
Drugs for superficial mycoticDrugs for superficial mycotic
inf...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
Chemotherapy of malariaChemotherapy of malaria
Infective mosqu...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
Con.Con.
Ruptured RBCsRuptured RBCs
Gametocytes gametocytic fo...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
TrypanosomiasisTrypanosomiasis
American form caused by Trypano...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
OthersOthers
Leishmaniasis is treated with sodiumLeishmaniasis...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
Anthelmintic drugsAnthelmintic drugs
Nematodal infections are ...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
Antiviral drugsAntiviral drugs
Drugs used for respiratory infe...
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 ...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
Con.Con.
*Famciclovir resembles ganciclovir spectrum*Famciclov...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
Treatment of AIDsTreatment of AIDs
Zidovudine increase the abs...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
Con.Con.
Stavudine decrease mitochondrialStavudine decrease mi...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
InterferonsInterferons
These are a family of naturally occurin...
Chemotherapy of CancerChemotherapy of Cancer
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
Cancer TreatmentCancer Treatment
involves the use of anti cancer medicinesinvolves the use of anti cancer medicines
(cytot...
The choice of an anticaner depends onThe choice of an anticaner depends on
many factors e.g. the kind of cancer themany fa...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
Application of chemotherapy may be inApplication of chemotherapy may be in
various ways, based on the cancer type.various ...
Drugs given in the form of capsules orDrugs given in the form of capsules or
tablets is called “oral chemotherapy”. Atable...
To treat certain kind of cancers,To treat certain kind of cancers,
chemotherapy drugs may be required tochemotherapy drugs...
In many of the above-mentioned methods,In many of the above-mentioned methods,
the chemotherapy drugs are most likely toth...
CLASSIFICATION OF
ANTICANCER DRUGS
1/ Drugs acting directly on cells = cytotoxic:1/ Drugs acting directly on cells = cytot...
Antagonists e.g. 5- fluorouracil and cytarabine.Antagonists e.g. 5- fluorouracil and cytarabine.
c/ Vinca alkaloids e.g. v...
g/ Antibiotics e.g. actinomycin D ,g/ Antibiotics e.g. actinomycin D ,
doxorubicin daunorubicin and bleomycin .doxorubicin...
GnRH e.g. neferelin and goserelin andGnRH e.g. neferelin and goserelin and
progestins e.g. hydroxyprogestroneprogestins e....
Oral complications of cancer chemotherapyOral complications of cancer chemotherapy
The oral mucosa id particularly suscept...
Neutropenia and depression of immunityNeutropenia and depression of immunity
may lead caused indirectly by drugs maymay le...
Dental check up may minimize complicationsDental check up may minimize complications
induced by drugs before applying andi...
Systemic antibiotics may cover organismsSystemic antibiotics may cover organisms
e.g. Pseuomonus ,Klebsiella , and E. coli...
Oral cancerOral cancer
OralOral cancercancer is abnormal (malignant) growthis abnormal (malignant) growth
of body cells in...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
Symptoms of oral cancer may include red,Symptoms of oral cancer may include red,
white and/or a mixture of these colors in...
Methods of treatment for oral cancer includeMethods of treatment for oral cancer include
surgery,surgery, radiation therap...
Rehabilitation after oral cancer surgeryRehabilitation after oral cancer surgery
consists of regaining strength, developin...
Oral cancer treatment can resultOral cancer treatment can result
in significant lifestyle changes;in significant lifestyle...
Oral and oropharyngeal cancer can often beOral and oropharyngeal cancer can often be
cured, especially if the cancer is fo...
A treatment team may include medicalA treatment team may include medical
oncologists who specialize in treatingoncologists...
Systemic chemotherapy is deliveredSystemic chemotherapy is delivered
through the bloodstream to reach cancerthrough the bl...
Chemotherapy may be used as the initialChemotherapy may be used as the initial
treatment before surgery, radiation therapy...
Each drug or combination of drugs canEach drug or combination of drugs can
cause specific side effects. While some cancaus...
Immunotherapy, also called biologicImmunotherapy, also called biologic
therapy, is designed to boost the body’stherapy, is...
Glucocorticoids like prenisolone andGlucocorticoids like prenisolone and
antibodies like muromonab CD3,antibodies like mur...
Targeted therapy is a treatment that targetsTargeted therapy is a treatment that targets
the cancer’s specific genes, prot...
Currently, antibodies directed against aCurrently, antibodies directed against a
cellular receptor called the epidermalcel...
05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
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Basic principles of chemotherapy

Outlines on the Basics of Chemotherapy

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Basic principles of chemotherapy

  1. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 37. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006 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.
  38. 38. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006 1/1/ββ-lactams-lactams Include :Include : - Penicillins .- Penicillins . - Celphalosporins .- Celphalosporins . - Carbapenems.- Carbapenems. - Monobactams .- Monobactams .
  39. 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. 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. 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. 42. Penicillium chrysogenum MoldPenicillium chrysogenum Mold 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
  43. 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 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.
  44. 44. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006 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.
  45. 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. 46. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006 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 .
  47. 47. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006 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.
  48. 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 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.
  49. 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. 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. 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. 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. 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. 54. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
  55. 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. 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. 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. 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. 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. 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. 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. 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. 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. 64. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
  65. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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 αα ,,ββ or gamma to degrade viral mRNA andor gamma to degrade viral mRNA and Trna.Trna.
  81. 81. Chemotherapy of CancerChemotherapy of Cancer 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
  82. 82. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
  83. 83. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
  84. 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. 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. 86. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
  87. 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. 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 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. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
  89. 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. 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. 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. 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. 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-αα 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. 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. 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. 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. 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. 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. 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. 100. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
  101. 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. 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. 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. 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. 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 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. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
  106. 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. 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. 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. 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. 110. 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 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
  111. 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. 112. 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. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
  113. 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. 114. 05/10/1505/10/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006

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