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Presented By-
RAJAN KUMAR KURMI
M. Pharm (1st sem)
Ram-Eesh Institute of Vocational & Technical Education
Strategies to combat drug resistance in
antibiotics and anticancer therapy
ABNEGATION
This presentation is made only for
educational purpose only as well as to
give you a general preview about the topic.
Any point ,picture and content mentioned in this presentation may be modified.
There is no relation of this presentation for their
original documentation
CONTENT
Introduction
Drug resistance
Antibitotic resistance
Strategies to Combat Antimicrobial Resistance
Mechanisms of Resistance Gene Transfer
Strategies to Combat Anticancer therapy
ATP-binding cassette (ABC) transporters
Introduction
DRUG RESISTANCE :-
It is the ability of microbes, such as bacteria, viruses, parasite or fungis, to grow it the
presence of chemical that would normally kill it or limit its growth.
WHY RESISTANCE IS A CONCERN:-
• RESISTANT ORGANISMS LEAD TO TREATMENT FAILURE
• RESISTANT BACTERIA MAY SPREAD IN COMMUNITY
• LOW LEVEL RESISTANCE CAN GO UNDETECTED
Antibitotic resistance :-
some micro-organisum may ‘born’resisitant, some ‘achieve’resistance by mutation or some have resistance by plasmid
(A)Intrinsic resistance
(1)Lack target :-pencillin
(2)Innate efflux pumps:-e.coil
(3)Drug inactivation :-cephalosporinase
(B)Acquired resistance:-
(1)Chromosomal method mutation :- mycobacterium lepra
(2)Extra chromosomal plasmid
strategies to combat drug resistance in anticancer thrapy - Bing images
1. Bacteria cells in the human
body. Some are drugs resistant.
2. Antibiotic kill bacteria but
resistant strains remain.
3. Antibiotic resistant bacteria
multiply.
4. Antibiotic resistance spreads.
Timeline ofAntibiotic resistance
time line of antibitotic resistance - Bing images
Strategies to Combat Antimicrobial Resistance
strategy to overcome resistance will be individual patient's therapy prospectively.
employing both knowledge of the patient's somatic mutation in drug, drug receptors, and
drug targets
Strategies to Combat Antimicrobial Resistance
Strategies to Combat Antimicrobial Resistance (nih.gov)
1. International Measures
Increased collaboration between governments, nongovernmental organizations professional
groups and international agencies
New networks that undertake surveillance of antimicrobial use andAMR.
2. National Strategies
2.1 National committee with intersectoral coordination and regulatory actions
2.2 NationalAntimicrobial Resistance Policy, India
3. Action at Community Level
3.1 Rational use of antibiotics
3.2 Over-the-counter (OTC) antibiotics
3.3 Guidelines for use of antibiotics at local level
3.4 Standards of hygiene
4. At Hospital or health care setting
4.1 Infection prevention and control within health-care facilities
5.At Personal / Patient level
(a) Role of Physician
(b) Role of Nurses/health care providers
(c) Role of Pharmacist
(d)At patient level
-Aseptic protocol for any procedures
-Breaking the chain of infectivity
-Compliance to the antimicrobial regime and antibiotic
Mechanisms of Resistance Gene Transfer
• Transfer of r-genes from one bacterium to another
Conjugation :- make a connecting tube between the 2 bacteria through which plasmid itself can pass.
Transduction:-bacteriophage contain plasmid DNA is transferred to another bacterium of same species
Transformation:-Free DNA is picked up from the environment i.e.. From a cell belonging to closely
related
• Transfer of r-genes between plasmids within the bacterium
By transposons
By Integrons
Strategies to Combat Anticancer therapy
Anti-cancer therapy is a field of medical specialization which today makes use of the full range of
armamentarium of therapeutic approaches including surgery, radiation, nuclear therapy etc.
Infusion of anti-cancer drugs is still today a mainstay of therapy, whereby most of the drugs applied are
exerting their effects as cytostatics or cytotoxics.
ATP-binding cassette (ABC) transporters
For developing more effective therapies Identifying the mechanisms leading to intrinsic or
acquired multidrug resistance (MDR) is important.
Due to expression of particular proteins results in cancer cells resistance-
such as cell-membrane transporters, which can result in an increased efflux of the cytotoxic
drugs from the cancer cells, thus lowering their intracellular concentrations.
when overexpression of the membrane efflux pumps is involved in MDR The resistance
mechanism is called typical or classical MDR .
The classical MDR mostly increased the efflux pumps in the cell membrane of cells pumping
anticancer drugs out of cells
ATP-binding cassette (ABC) transporters are a family of transporter proteins that contribute to
drug resistance via adenosinetriphosphate (ATP)-dependent drug efflux pumps
These transporters use energy released from the hydrolysis of ATP to drive the transport of
various molecules across the cell membrane.
They are involved in the transport of many substances, including the excretion of toxins
from the liver, kidneys, and gastrointestinal tract.
 It has been recognized that transporter-mediated processes significantly modulate drug
absorption, distribution, metabolism and excretion.
In addition to their physiologic expression in normal tissues, many are over-expressed, in
human tumors.
Clinical trials helped to unravel the problems associated with combination chemotherapy of
anticancer drug(s) together with an MDR inhibitor.
 The first factor to be determined before embarking a clinical trial is to identify the ABC
transporter protein involved in drug resistance and to utilize an anticancer drug that would
benefit from inhibition of that transporter protein.
 The anticancer drug(s) utilized should match the transporter protein being inhibited
The second factor is to monitor the plasma concentrations and in vivo effectiveness of
the tested MDR inhibitor in order to verify that an effective inhibitory concentration
was in fact achieved in vivo.
 The pharmacokinetic interaction between the anticancer drug(s) and the MDR
inhibitor must be searched and avoided to prevent a reduction in anticancer drug
dosage.
Reference
Strategies to Combat Antimicrobial Resistance (nih.gov)
Antibiotic resistance (slideshare.net)
Drug resistance (slideshare.net)
Antibiotic resistance (slideshare.net)
Mechanisms and strategies to overcome multiple drug resistance in cancer - ScienceDirect
Thank You

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Strategies to Combat Drug Resistance in Antibiotics and Anticancer Therapy

  • 1. Presented By- RAJAN KUMAR KURMI M. Pharm (1st sem) Ram-Eesh Institute of Vocational & Technical Education Strategies to combat drug resistance in antibiotics and anticancer therapy
  • 2. ABNEGATION This presentation is made only for educational purpose only as well as to give you a general preview about the topic. Any point ,picture and content mentioned in this presentation may be modified. There is no relation of this presentation for their original documentation
  • 3. CONTENT Introduction Drug resistance Antibitotic resistance Strategies to Combat Antimicrobial Resistance Mechanisms of Resistance Gene Transfer Strategies to Combat Anticancer therapy ATP-binding cassette (ABC) transporters
  • 4. Introduction DRUG RESISTANCE :- It is the ability of microbes, such as bacteria, viruses, parasite or fungis, to grow it the presence of chemical that would normally kill it or limit its growth. WHY RESISTANCE IS A CONCERN:- • RESISTANT ORGANISMS LEAD TO TREATMENT FAILURE • RESISTANT BACTERIA MAY SPREAD IN COMMUNITY • LOW LEVEL RESISTANCE CAN GO UNDETECTED
  • 5. Antibitotic resistance :- some micro-organisum may ‘born’resisitant, some ‘achieve’resistance by mutation or some have resistance by plasmid (A)Intrinsic resistance (1)Lack target :-pencillin (2)Innate efflux pumps:-e.coil (3)Drug inactivation :-cephalosporinase
  • 6. (B)Acquired resistance:- (1)Chromosomal method mutation :- mycobacterium lepra (2)Extra chromosomal plasmid strategies to combat drug resistance in anticancer thrapy - Bing images 1. Bacteria cells in the human body. Some are drugs resistant. 2. Antibiotic kill bacteria but resistant strains remain. 3. Antibiotic resistant bacteria multiply. 4. Antibiotic resistance spreads.
  • 7. Timeline ofAntibiotic resistance time line of antibitotic resistance - Bing images
  • 8. Strategies to Combat Antimicrobial Resistance strategy to overcome resistance will be individual patient's therapy prospectively. employing both knowledge of the patient's somatic mutation in drug, drug receptors, and drug targets
  • 9. Strategies to Combat Antimicrobial Resistance Strategies to Combat Antimicrobial Resistance (nih.gov)
  • 10. 1. International Measures Increased collaboration between governments, nongovernmental organizations professional groups and international agencies New networks that undertake surveillance of antimicrobial use andAMR. 2. National Strategies 2.1 National committee with intersectoral coordination and regulatory actions 2.2 NationalAntimicrobial Resistance Policy, India
  • 11. 3. Action at Community Level 3.1 Rational use of antibiotics 3.2 Over-the-counter (OTC) antibiotics 3.3 Guidelines for use of antibiotics at local level 3.4 Standards of hygiene 4. At Hospital or health care setting 4.1 Infection prevention and control within health-care facilities
  • 12. 5.At Personal / Patient level (a) Role of Physician (b) Role of Nurses/health care providers (c) Role of Pharmacist (d)At patient level -Aseptic protocol for any procedures -Breaking the chain of infectivity -Compliance to the antimicrobial regime and antibiotic
  • 13. Mechanisms of Resistance Gene Transfer • Transfer of r-genes from one bacterium to another Conjugation :- make a connecting tube between the 2 bacteria through which plasmid itself can pass. Transduction:-bacteriophage contain plasmid DNA is transferred to another bacterium of same species Transformation:-Free DNA is picked up from the environment i.e.. From a cell belonging to closely related • Transfer of r-genes between plasmids within the bacterium By transposons By Integrons
  • 14. Strategies to Combat Anticancer therapy Anti-cancer therapy is a field of medical specialization which today makes use of the full range of armamentarium of therapeutic approaches including surgery, radiation, nuclear therapy etc. Infusion of anti-cancer drugs is still today a mainstay of therapy, whereby most of the drugs applied are exerting their effects as cytostatics or cytotoxics.
  • 15. ATP-binding cassette (ABC) transporters For developing more effective therapies Identifying the mechanisms leading to intrinsic or acquired multidrug resistance (MDR) is important. Due to expression of particular proteins results in cancer cells resistance- such as cell-membrane transporters, which can result in an increased efflux of the cytotoxic drugs from the cancer cells, thus lowering their intracellular concentrations. when overexpression of the membrane efflux pumps is involved in MDR The resistance mechanism is called typical or classical MDR .
  • 16. The classical MDR mostly increased the efflux pumps in the cell membrane of cells pumping anticancer drugs out of cells ATP-binding cassette (ABC) transporters are a family of transporter proteins that contribute to drug resistance via adenosinetriphosphate (ATP)-dependent drug efflux pumps These transporters use energy released from the hydrolysis of ATP to drive the transport of various molecules across the cell membrane.
  • 17. They are involved in the transport of many substances, including the excretion of toxins from the liver, kidneys, and gastrointestinal tract.  It has been recognized that transporter-mediated processes significantly modulate drug absorption, distribution, metabolism and excretion. In addition to their physiologic expression in normal tissues, many are over-expressed, in human tumors.
  • 18. Clinical trials helped to unravel the problems associated with combination chemotherapy of anticancer drug(s) together with an MDR inhibitor.  The first factor to be determined before embarking a clinical trial is to identify the ABC transporter protein involved in drug resistance and to utilize an anticancer drug that would benefit from inhibition of that transporter protein.  The anticancer drug(s) utilized should match the transporter protein being inhibited
  • 19. The second factor is to monitor the plasma concentrations and in vivo effectiveness of the tested MDR inhibitor in order to verify that an effective inhibitory concentration was in fact achieved in vivo.  The pharmacokinetic interaction between the anticancer drug(s) and the MDR inhibitor must be searched and avoided to prevent a reduction in anticancer drug dosage.
  • 20. Reference Strategies to Combat Antimicrobial Resistance (nih.gov) Antibiotic resistance (slideshare.net) Drug resistance (slideshare.net) Antibiotic resistance (slideshare.net) Mechanisms and strategies to overcome multiple drug resistance in cancer - ScienceDirect