Chp 10- Controlling Microbial Growth: Antimicrobial Drugs

chemotherapy

refers to any chemicals used to treat diseases

antibiotic

a drug produced naturally (from living organisms) that curbs growth of microorganisms

antimicrobial

stops growth of microorganisms

combination chemotherapy

the usage of more than one drug to increase effectiveness

chemotherapeutic index equation

maximum dose tolerated by the body per kg/ minimum dose that will cure per kg

chemotherapeutic index meaning

• a high index means a larger difference b/w dose and needs more to be toxic

  • selective toxicity: drugs should kill microbe without harming the body

what are the best characteristics should an agent have

1. solubility

2. selective toxicity

3. stable

4. non-allergenic

5. not cause resistance

6. cheap

examples of drugs that inhibit cell wall synthesis

1. penicillin

2. cephalosporins

3. carbapenems

4. bacitracin

5. vancomycin

6. isoniazid, ethambutol

penicillin description

• made by fungus

• inhibits the peptide cross-linkages between NAM-NAG layers of peptidoglycan cell wall

• causes faulty cell wall and lysis bacteria (bactericidal)

• used for staph (Gram +), strep, and syphilis

problems with penicillin

• overuse has caused resistance

• narrow spectrum

• anaphylactic reaction

solution to penicillin problems

• new synthetic and expensive penicillins

• adding clavulanic acid: inactivates pencillinase made by bacteria

• Augmentin (amoxicillin and clavulanic acid)

• some penicillin are penicillinase resistant: methicillin

cephalosporins description

• resistant to beta-lactamase enzyme

• 1st gen: for gram +

• 2nd gen: gram + and enterics

• 3rd fen: kills Pseudomonas

• Examples: Keflex, C-Chlor, Keflin, etc

carbapenems description

• broad spectrum- modified beta-lactam structure

• effective in nosocomial infections

bacitracin description

• non-beta lactam drug

• for gram +

• topical application (ointments)

vancomycin description

• non-beta lactam drugs

• toxic drug

  • last line of drugs against Staph. aureus parenteral administration

• only against gram +

• concern: VRSA

isoniazid & ethambutol

• inhibits synthesis of mycolic acid

• effective in tuberculosis as first-line drugs

• often used in combination

examples ofd drugs that inhibit protein synthesis

• aminoglycosides

• tetracyclines

• chloramphenicol

• macrolides (erythromycin)

• clindamycin

• oxazolidinones (linezolid)

• streptogramins

aminoglycosides description

• attach irreversibly to bacterial 30s ribosomes

• best for gram -, used in combination

• problem: parenteral application

• resistance: can not always penetrate the bacterial cell

• toxicity: hearling loss & kidney loss

examples of aminoglycosides

• tobramycin (eye drops and aerosol)

• amikacin (nosocomial infections)

• streptomycin (anti-Tb)

tetracyclines description

• combines with 30s ribosome component and inhibits tRNA from attaching

• broadest spectrum of activity

• for Chlamydia, Rickettsia (intracellular), and Mycoplasma (atypical pneumonia)

• problem: toxicity (not given to children bc it discolors teeth, affects bone, liver damage, GI irritation)

• used for acne and in animal feeds

chloramphenicol description

• binds to ribosome but 50s component; inhibits formation of peptide bonds

• gets through blood brain barrier→ meningitis

• used for Rickettsia, Chlamydia

• problem: toxicity in children → aplastic anemia

macrolides (erythromycin) description

• binds to ribosome component 50s

• effective against gram +, mycoplasma, and chlamydia

• chosen when patient is allergic to penicillin or resistant to penicillin

• used for Legionnaire’s disease, atypical pneumonia

clindamycin

• binds to 50s ribosomes

• against gram + and gram -

• problems: blamed for pseudomembranous colitis (increases in # Clostridium difficile) which produces a toxin, complications (antibiotic-associated colitis)

oxazolidinone (linezolid)

• for vancomycin resistant bacteria

• inhibits 50s and translation

streptogramins description

• for vancomycin resistant bacteria

• combination of drugs that bind to 50s unit of gram +

examples of drugs that inhibit nucleic acid synthesis

• rifampin

• quinolones (cipro)

rifampin description

• blocks RNA transcription: inhibits RNA polymerase in bacteria

• penetrates into CSF/ abscesses

• problem: resistance occurs quickly, “red man syndrome," drug interactions, and orange-red urine

quinolones (cpro) description

• inhibits DNA gyrase in prokaryotes

• broad spectrum (gram - and gram +)

• not for pregnant women: cartilage development of newborns affected

sulfa drugs (sulfonamides) description

• antimetabolites: mimics PABA compound needed by bacteria to make folic acid (competitive inhibition of folic acid synthesis)

• sulfa drug + trimethoprim → in combination, blocks two steps of folic acid synthesis

• used for urinary tract infections, pneumocystis pneumonia

• examples. bactrim, septra

polymyxin description

• gram -

• cell membrane injury

• in Neosporin; given in topical application due to toxicity

what drugs are given to treat TB? what is the timeline the drugs are given? what is problem that aries with TB?

• first line of defense: rifampin, ethambutol, isoniazid, streptomycin and pyrazinamide (blocks fatty acid synthesis in mycobacteria)

• the drugs are given over several months due to degranulation of mast cells and histamine release. another issue is Multi-drug resistance TB

what antifungals distrupt cell membranes

1. amphotericin B

2. imidazoles

3. terbinafine

4. nystatin

amphotericin B description

• for systemic fungal infections (degrade membrane by binding ergosterol)

• parenteral application

• toxic to kidney

imidazoles description

• skin fungal infections

• blocks synthesis of ergosterol in cell membranes

• applied topically or new oral meds (ketoconazole, triazole)

terbinafine description

• blocks enzymes in making ergosterol nail fungus

nystatin description

• degrades cell membranes- not absorbed by body, given orally

echinocandins description

• disrupts cell wall synthesis

• new systemic drugs for fungal infections such as Candida or Aspergillus

Griseofulvin description

• disrupts cell division

• for skin fungi

base-analogs (Acyclovir, virazole, AZT) description

• blocks nucleic acid synthesis

• incorporates wrong base into DNA and no protein synthesis and no viral replication

reverse transcriptase inhibitors description

• block nucleic acid synthesis

• effective against HIV

amantadine description

• blocks viral uncoating

• after exposure to influenza A, it stops penetration of virus into new cells

protease inhibitors description

• blocks viral replication

• stops spread of HIV by inhibiting protease enzymes required for replication and release of virus

interferon description

• blocks viral replication

• blocks formation of viral proteins at the ribosome (hepatitis C)

neuraminidase inhibitors description

• blocks viral replication

• used against influenza virus

metronidazole description

• used against anaerobic protozoa, and anaerobic bacterial infections

• prevents replication and transcription

chloroquine description

• used to prevent and treat malaria

• mechanism not understood

• accumulates in RBCs which affects Plasmodium

niclosamide description

• used against tapeworms