Chemotherapy
The use of drugs to treat a disease
Antibiotics
A substance produced by microbe that, in small amounts, inhibit another microbe (Natural)
Synthetic drugs
drugs created in a laboratory
Selective toxicity
A drug that kills harmful microbes without damaging the host
Sources of naturally occurring antibiotics
-Gram(+) rods
-Actinomycetes
-Fungi
spectrums of antimicrobial
Broad- cover multiple microbes
narrow-cover specific microbes
superinfection-A new infection in addition to one already present.
Actions of antimicrobial drugs
>Actions are either bactericidal (Kills) or bacteriostatic (inhibits growth)
1.Inhibition of cell wall synthesis
2.Inhibitions of protein synthesis
3.Ijury to plasma membranes
4.Inhibition of nucleic acid
5.Inhibition of essential metabolites (nutrients n
Inhibitors of cell wall synthesis
-Penicillin
-Cephalorsporins
-polypeptide antibiotics
-Antimycobacterial antibiotics
Natural penicillin
(antibiotic)
-inhibitor of cell wall synthesis
~Rapidly excreted
~Narrow spectrum of activity
~Susceptible to penicillinases
~Ex. Penicillin G (Injected)/Penicillin V (oral)
Semisynthetic
(antibiotic)
-inhibitor of cell wall synthesis
~Usually more broad
~Greater retention time
~More resistant to penicillinases
~Ex.
*Oxacillin
>Narrow spectrum
>only gram(+), but resistant to
penicillinase
*Ampicillin
>Extended spectrum, many Gram(-)
Extended spectrum penicillin
****
...
??Lactam Antibiotics
(antibiotic)
-Inhibitor of cell wall synthesis
-Antibiotics that contain ??Lactam ring (may be used at once in one pill)
-Penicillin
~Penicillinase: resistant penicillins
(methacillin)
~ Penicillins+ ??Lactamase inhibitors
(Augmentin)
-Carbapenems
~Broad
Cephalosporins
(antibiotic)
-Inhibitor of cell wall synthesis
-First-generation: Narrow spectrum, gram-positive
-Second-generation: Extended spectrum
includes gram-negative
-Third generation: Includes pseudomonads;
injected
-Fourth-generation: Oral
Polypeptide antibiotic
(antibiotic)
-inhibitor of cell wall synthesis
-Bacitracin (Bacillus)
~Topical application
~Against gram-positives
-Vancomycin
~Glycopeptide
~Important "last line" against antibiotic-
resistant
*S. aureus
Antimycobacterial antibiotics
(antibiotic)
-inhibitor of cell wall synthesis
-Isoniazid (INH)
~Inhibits mycolic acid synthesis
-Ethambutol
~Inhibits incorporation of mycolic acid
Inhibitors of protein synthesis (antibiotic)
-Chloramphenicol
-Aminoglycosides
-Tetracycline
-Streptogramins
-Macrolides
-Oxazolidinones
Chloramphenicol
(antibiotic)
-Inhibitor of protein synthesis
-Broad spectrum
~Binds 50S subunit; inhibits peptide bond
formation
~Serious side effects: aplastic anemia
Aminoglycosides
(antibiotic)
-inhibitors of protein synthesis
-Streptomycin, neomycin, gentamycin
~Broad spectrum
~Changes shape of 30S subunit
Tetracyclines
(antibiotic)
-inhibitor of protein synthesis
-Broad spectrum
~Interferes with tRNA attachment
~Treat Urinary infections
~Side effects: Liver damage and tooth
discoloration
Streptogramins
(antibiotic)
-inhibitor of protein synthesis
-Gram-positives
~Binds 50S subunit; inhibits translation
~Used to treat MRSA
Macrolides
(antibiotic)
-inhibitor of protein synthesis
-Gram-positives
~Binds 50S; prevents translocation
~Often a substitute for penicillin
*Erythromycin
Oxazolidinones
(antibiotic)
-inhibitor of protein synthesis
-Linezolid
~Gram-positives
~Binds 50S subunit; prevents formation of
70S ribosome
~Synthetic used to treat MRSA
Polymyxin B
(antibiotic)
-Injury to plasma membrane
-Topical
-Combined with bacitracin and neomycin in
over-the-counter preparation
Inhibitors of nucleic acid (antibiotic)
-Rifamycin
-Quinolones
-fluoroquinolones
Rifamycin
(antibiotic)
-Inhibitor of nucleic acid
-Inhibits RNA synthesis
-Antituberculosis
Quinolones and fluoroquinolones
(antibiotic)
-Inhibitor of nucleic acid
-Nalidixic acid: Urinary infections
-Ciprofloxacin
-Inhibits DNA gyrase
-Urinary tract infections
-More broad spectrum
-Unusual side effect-turns everything orange
Sulfonamides
(antibiotic)
-inhibitors of essential metabolites
-Inhibit folic acid synthesis
-Broad spectrum
-Most widely used is a combination of
trimethoprin and sulfamethoxazole (TMP-
SMV)
Antifungal Drugs
drugs that are used against fungal infections
(Fungal) Inhibition of plasma membrane
-Polyenes
-Azoles
-Allylamines
Polyenes
(inhibition of fungal plasma membrane)
-Amphotericin B
Azoles
(inhibition of fungal plasma membrane)
-Miconazole
-Triazoles
-Used to treat cutainious
Fungal infection
Allylamines
(inhibition of fungal plasma membrane)
-For azole-resistant infections
-Used to treat cutainious
Fungal infection
Echinocandins
(Fungal)
-Inhibitor to cell wall synthesis
-Inhibit synthesis of ?-glucan
-Cancidas is used against Candida and
Pneumocystis
Inhibition of Nucleic Acids
(Fungal)
-Flucytocine
-Pentamidine isethionate
Flucytocine
(fungal)
-inhibition of nucleic acid
-Cytosine analog interferes with RNA
synthesis
Pentamidine isethionate
(Fungal)
-inhibition of nucleic acid
-Anti-Pneumocystis; may bind DNA
Other Antifungal Drugs
-Griseofulvin
-Tolnaftate
Griseofulvin
(Fungal)
-Inhibits microtubule formation
-Superficial dermatophytes
Tolnaftate
(Fungal)
-Action unknown
-Widely used to treat athlete foot
Antiviral drugs
-Nucleoside analog
-Enzyme inhibitors
-Interferons
-Anti retroviral
Acyclovir
(Antiviral)
-Nucleotide Analog
-tricks phosphate into attaching to a false nucleotide so it stops the assembly of DNA for the virus.
Interferons
(Antivirals)
-Prevent spread of viruses to new cells
~Alpha interferon: Viral hepatitis (What we
can control)
-Imiquimod
~Promotes interferon production
Anti-Retrovirals: HIV/ AIDS
(Antiviral)
-Reverse transcriptase inhibitors
-Nucleoside analogs
-Zidovudine (AZT)
-Cidofovir ( also used to treat viral eye
infections and possibly smallpox)
-Tenovir
-Nevirapine ( non-nucleoside analog)
Antiprotozoan Drugs
-Chloroquine
-Diiodohydroxyquin
-Metronidazole
-Tinidazole
Chloroquine
(Antiprotozoan)
-Inhibits DNA synthesis
~Malaria
Diiodohydroxyquin
(Antiprotozoan)
-Unknown mode of action
~Amoebic diseases
Metronidazole
(Antiprotozoan)
-Damages DNA
~Entamoeba, Trichomonas
Tinidazole
(Antiprotozoan)
-Interferes with metabolism of anaerobes
Antihelminthic Drugs
-Niclosamide
-Praziquantel
-Mebendazole
-Ivermectin
Niclosamide
(Antihelminthic)
-Prevents ATP generation
~Tapeworms
Praziquantel
(Antihelminthic)
-Alters membrane permeability
~Flatworms
Mebendazole
(Antihelminthic)
-Inhibits nutrient absorption
~Intestinal roundworms
Ivermectin
(Antihelminthic)
-Paralyzes worm
~Intestinal roundworms
Kirby-Bauer Test
Used to test and see which antimicrobial would be best to treat the disease (theory is that the wider the zone of inhibition, the more affective it is at its job)
Broth Dilution Tests
Test to see the minimal amount of drug needed to treat the infection
>Tests
-Resistance
-MIC and MBC
-Susceptibility
Mechanisms of Antimicrobial resistance
1. Enzymatic destruction of drug
2. Prevention of penetration of drug
3. Alteration of drug's target site
4. Rapid ejection of the drug
Antibiotic Resistance: Human Practices
1.Overuse in immuno-suppressed patients
2. Patient demand for antibiotics for colds/ Flu
3. Misuse by physicians
4. Failure to follow prescribed treatments
5. Long-term low-dose treatment for acne
6. Use in animal feeds
7. Moving of resistant bacteria
8.
Synergism
-occurs when the effect of two drugs together is greater than the effect of either alone
~ 1+1=3
Antagonism
-occurs when the effect of two drugs together is less than the effect of either alone
~ 1+1= _< 0