Download Pharm II-Ch 8-PPT

ANTI-INFECTIVE AGENTS
CHAPTER 8
DEVELOPMENT OF ANTI-INFECTIVE THERAPY
• 1920S
• PAUL EHRLICH WORKED ON DEVELOPING A SYNTHETIC CHEMICAL
EFFECTIVE ONLY AGAINST INFECTION-CAUSING CELLS
• SCIENTISTS DISCOVERED PENICILLIN IN A MOLD SAMPLE
• 1935
• THE SULFONAMIDES WERE INTRODUCED
DRUG THERAPY ACROSS THE LIFESPAN
MECHANISMS OF ACTION
• INTERFERE WITH BIOSYNTHESIS OF THE BACTERIAL CELL WALL
• PREVENT THE CELLS OF THE INVADING ORGANISM FROM USING
SUBSTANCES ESSENTIAL TO THEIR GROWTH AND DEVELOPMENT
• INTERFERE WITH STEPS INVOLVED IN PROTEIN SYNTHESIS
MECHANISMS OF ACTION (CONT.)
• INTERFERE WITH DNA SYNTHESIS
• ALTER THE PERMEABILITY OF THE CELL MEMBRANE TO ALLOW
ESSENTIAL CELLULAR COMPONENTS TO LEAK OUT
MECHANISM OF ANTI-INFECTIVE AGENTS
ANTI-INFECTIVE ACTIVITY
• ANTI-INFECTIVES VARY IN THEIR EFFECTIVENESS AGAINST
INVADING ORGANISMS.
• SOME ARE SELECTIVE – ONLY EFFECTIVE FOR A FEW
NUMBER OF ORGANISMS
• BACTERICIDAL – KILL THE CELL
• BACTERIOSTATIC – PREVENT REPRODUCTION OF THE CELL
• SEVERAL DRUGS ARE BOTH-DEPENDING ON THE
CONCENTRATION
NARROW SPECTRUM VS. BROAD SPECTRUM
• NARROW SPECTRUM OF ACTIVITY
• EFFECTIVE AGAINST ONLY A FEW MICROORGANISMS WITH A VERY
SPECIFIC METABOLIC PATHWAY OR ENZYME (WHEN THE ORGANISM IS
IDENTIFIED)
• EX: AZITHROMYCIN, VANCOMYCIN, CLINDAMYCIN
• BROAD SPECTRUM OF ACTIVITY
• USEFUL IN TREATING A WIDE VARIETY OF INFECTIONS
• INTERFERE WITH THE BIOCHEMICAL REACTIONS IN MANY DIFFERENT KINDS
OF MICROORGANISMS
• EX: AMOXICILLIN, TETRACYCLINE, CHLORAMPHENICOL
HUMAN IMMUNE RESPONSE
• GOAL OF ANTI-INFECTIVE THERAPY IS REDUCTION OF THE POPULATION OF
THE INVADING ORGANISM.
• DRUGS THAT WOULD ELIMINATE ALL TRACES OF ANY INVADING PATHOGEN
MIGHT BE TOXIC TO THE HOST AS WELL.
• IMMUNE RESPONSE IS A COMPLEX PROCESS INVOLVING CHEMICAL
MEDIATORS, LEUKOCYTES, LYMPHOCYTES, ANTIBODIES, AND LOCALLY
RELEASED ENZYMES AND CHEMICALS.
PROBLEMS WITH TREATING INFECTIONS IN
IMMUNOSUPPRESSED PATIENTS
• ANTI-INFECTIVE DRUGS CANNOT TOTALLY ELIMINATE THE
PATHOGEN WITHOUT CAUSING SEVERE TOXICITY IN THE HOST.
• THESE PATIENTS DO NOT HAVE THE IMMUNE RESPONSE IN PLACE
TO DEAL WITH EVEN A FEW INVADING ORGANISMS.
QUESTION
WHICH OF THE FOLLOWING HAS BEEN FOUND TO BE AS IMPORTANT AS DRUG
THERAPY WHEN TREATING INFECTIONS IN THE IMMUNOSUPPRESSED?
A. MAINTAINING STANDARD PRECAUTIONS
B. PROPER NUTRITION
C. GOOD HAND WASHING
D. EXERCISE
ANSWER
B. PROPER NUTRITION
RATIONALE: IN HELPING THESE PEOPLE (THE IMMUNOSUPPRESSED)
COPE WITH INFECTIONS, PREVENTION OF INFECTION AND
PROPER NUTRITION ARE OFTEN AS IMPORTANT AS DRUG
THERAPY.
RESISTANCE
• ANTI-INFECTIVES ACT ON SPECIFIC ENZYME SYSTEM OR
BIOLOGICAL PROCESS, MANY MICROORGANISMS THAT DO NOT
ACT ON THIS SYSTEM ARE NOT AFFECTED BY THIS PARTICULAR
DRUG.
• THIS IS CONSIDERED NATURAL OR INTRINSIC RESISTANCE TO THAT
DRUG.
ACQUIRED RESISTANCE
• MICROORGANISMS THAT WERE ONCE SENSITIVE TO THE
PARTICULAR DRUG HAVE BEGUN TO DEVELOP ACQUIRED
RESISTANCE.
• THIS RESULTS IN SERIOUS CLINICAL PROBLEMS.
WAYS ANTI-INFECTIVE AGENTS RESISTANCE
DEVELOPS
• PRODUCING AN ENZYME THAT DEACTIVATES THE ANTIMICROBIAL DRUG
• CHANGING CELLULAR PERMEABILITY TO PREVENT THE DRUG FROM ENTERING
THE CELL
• ALTERING TRANSPORT SYSTEMS TO EXCLUDE THE DRUG FROM ACTIVE
TRANSPORT INTO THE CELL
• ALTERING BINDING SITES ON THE MEMBRANES OR RIBOSOMES, WHICH THEN
NO LONGER ACCEPT THE DRUG
• PRODUCING A CHEMICAL THAT ACTS AS AN ANTAGONIST TO THE DRUG
PREVENTING RESISTANCE
• LIMIT THE USE OF ANTIMICROBIAL AGENTS TO THE TREATMENT OF SPECIFIC
PATHOGENS SENSITIVE TO THE DRUG BEING USED
• MAKE SURE DOSES ARE HIGH ENOUGH, AND THE DURATION OF DRUG
THERAPY LONG ENOUGH (PATIENT EDUCATION)
• BE CAUTIOUS ABOUT THE INDISCRIMINATE USE OF ANTI-INFECTIVES
IDENTIFICATION OF THE PATHOGEN
• IDENTIFICATION OF THE INFECTING PATHOGEN IS DONE BY CULTURE
• A CULTURE OF A TISSUE SAMPLE FROM THE INFECTED AREA IS DONE
• A SWAB OF INFECTED TISSUE IS ALLOWED TO GROW ON AN AGAR PLATE
• STAINING TECHNIQUES AND MICROSCOPIC EXAMINATION IDENTIFY THE
BACTERIUM
• STOOL CAN BE EXAMINED FOR OVA AND PARASITES
SENSITIVITY OF PATHOGEN
• SHOWS WHICH DRUGS ARE CAPABLE OF CONTROLLING THE PARTICULAR
MICROORGANISM
• IS IMPORTANT WITH MICROORGANISMS THAT HAVE KNOWN RESISTANT
STRAINS
• ALONG WITH A CULTURE, IDENTIFIES THE PATHOGEN AND APPROPRIATE DRUG
FOR TREATMENT
FACTORS AFFECTING PRESCRIBING
ANTI-INFECTIVE AGENTS
• IDENTIFICATION OF THE CORRECT PATHOGEN
• SELECTION OF THE RIGHT DRUG
• ONE THAT CAUSES THE LEAST COMPLICATIONS FOR THAT PARTICULAR
PATIENT
• ONE THAT IS MOST EFFECTIVE AGAINST THE PATHOGEN INVOLVED
COMBINATION THERAPY
• USE OF A SMALLER DOSAGE OF EACH DRUG
• SOME DRUGS ARE SYNERGISTIC
• IN INFECTIONS CAUSED BY MORE THAN ONE ORGANISM, EACH PATHOGEN
MAY REACT TO A DIFFERENT ANTI-INFECTIVE AGENT
• SOMETIMES, THE COMBINED EFFECTS OF THE DIFFERENT DRUGS DELAY THE
EMERGENCE OF RESISTANT STRAINS
PROPHYLAXIS OF ANTI-INFECTIVE AGENTS
• PEOPLE TRAVELING TO AN AREA WHERE MALARIA IS ENDEMIC
• PATIENTS WHO ARE UNDERGOING GI OR GENITOURINARY SURGERY
• PATIENTS WITH KNOWN CARDIAC VALVE DISEASE, VALVE REPLACEMENTS, AND
OTHER CONDITIONS REQUIRING INVASIVE PROCEDURES
ADVERSE REACTIONS TO ANTI-INFECTIVE
THERAPY
• KIDNEY DAMAGE
• GASTROINTESTINAL (GI) TRACT TOXICITY
• NEUROTOXICITY
• HYPERSENSITIVITY REACTIONS
• SUPERINFECTIONS
QUESTION
YOU ARE CARING FOR A PATIENT WHO HAS JUST BEEN DIAGNOSED WITH A
PSEUDOMONAS INFECTION. YOU KNOW THAT IN DECIDING WHAT
MEDICATION TO ORDER FOR THIS PATIENT THE PHYSICIAN WILL TAKE WHAT
INTO ACCOUNT?
A. THE PATIENT’S AGE
B. THE PATIENT’S GENDER
C. THE DRUG THAT CAUSES THE LEAST COMPLICATION
D. THE DRUG THAT HAS THE LONGEST HALF-LIFE
ANSWER
C. THE DRUG THAT CAUSES THE LEAST COMPLICATION
RATIONALE: IDENTIFICATION OF THE CORRECT PATHOGEN
SELECTION OF THE RIGHT DRUG
• ONE THAT CAUSES THE LEAST COMPLICATIONS
FOR THAT PARTICULAR PATIENT
• ONE THAT IS MOST EFFECTIVE AGAINST THE
PATHOGEN INVOLVED