Antimicrobial Drugs Flashcards
Chemotherapy
The use of drugs to treat a disease.
Antimicrobial drugs
Interfere with growth of microbes within a host
Antibiotic
A substance produced by a microbe that, in small amounts, inhibits another microbe
Selective toxicity
Killing harmful microbes without damaging the host.
Who discovered Penicillin, produced by Penicillium?
Fleming (1928)
What is Prontosil red dye used for?
Streptococcal infections- a sulfanilamide: sulfur based
When were the first clinical trial of penicillin?
1940
Today there’s a growth problem of:
Antibiotic resistance
In 1940, who performed the first clinical trials of penicillin?
Howard Florey and Ernst Chain
Narrow spectrum of microbial activity:
Drugs that affect a narrow range of microbial types
Broad-spectrum antibiotics
Affects a broad range of gram + or gram - bacteria.
Bacteriocidal
Kills microbe directly (a drug used to kill bacteria)
Bacteriostatic
Prevents microbes from growing
Superinfection
overgrowth of normal microbiota that is resistant to antibiotics
5 major action modes of antimicrobial drugs
1st action
- inhibition of cell wall synthesis: penicillins, cephalosporins, bacitracin, vancomycin
5 major action modes of antimicrobial drugs
2nd action:
Inhibition of protein synthesis: erythryomycin, tetracyclines, streptomycin, chloramphenicol.
5 major action modes of antimicrobial drugs
3rd action
- Inhibition of nucleic acid replication and transcription: quinolone, rifampin. (Drugs that are usually specific t viruses)
5 major action modes of antimicrobial drugs
4th action
- Injury to plasma membrane: polymyxin B
5 major action modes of antimicrobial drugs
5th action:
Inhibition of essential metabolite synthesis: sulfanimide, trimethoprim
Inhibitors of cell wall synthesis (inhibit new cell wall formation)
-penicillin
-natural penicillins
-semisynthetic penicillins
-extended-spectrum penicillins
Penicillin contains:
β-lactam ring: active ingredient that prevents cross-linking
The types are differentiated by the chemical side chains attached to the ring
Penicillin prevents
The cross-linking of peptidoglycans, interfering with cell wall construction (especially gram positives)
Natural penicillins extracted from:
Penicillium cultures: penicillin G (injected) and penicillin V (oral)
Natural penicillins are susceptible to:
penicillinases (β-lactamases)
- narrow spectrum of activity
Semisynthetic penicillins
• Contain chemically added side chains, making them resistant to penicillinases
Oxacillin:
Narrow spectrum, only gram-positives, but resistant to penicillinase
Ampicillin:
Extended spectrum, many gram-negatives
Penicillinase-resistant penicillins
Methicillin and oxacillin
Extended-spectrum penicillins
Effective against gram-negatives as well as gram-positives
• Aminopenicillins: ampicillin, amoxicillin
Penicillins plus β-lactamase inhibitors
Contain clavulanic acid, a noncompetitive inhibitor of penicillinase
Carbapenems
Substitute a C for an S and add a double bond to the penicillin nucleus
• Broad spectrum
• Primaxin, doripenem
• Monobactam
Synthetic; single ring instead of the β-lactam double ring
• Low toxicity; works against only certain gram-negatives
• Aztreonam
Cephalosporins
Work similar to penicillins
• β-lactam ring differs from penicillin
• Grouped according to their generation of development
Polypeptide antibiotics
Bacitracin (wounds; first aid ointment
• Topical application; works against gram-positives
• Vancomycin
• Glycopeptide
• Last line against antibiotic-resistant MRSA
Antimycobacterial Antibiotics:
Isoniazid (INH)
• Inhibits the mycolic acid synthesis in mycobacteria
Antimycobacterial Antibiotics
Ethambutol
• Inhibits incorporation of mycolic acid into the cell wall
Inhibition of Cell Wall Synthesis
Prevent bacteria from increasing amount of peptidoglycan
• Have no effect on fully formed bacteria
• Effective only for growing, young populations
Inhibition of Cell Wall Synthesis= No effect on plant or animal cells; Why?
Cross bridges are already in place
None of these cell walls have peptidoglycan
Inhibiting Protein Synthesis
Target bacterial 70S ribosomes
• Large or small subunit
• Chloramphenicol, erythromycin, streptomycin, tetracyclines
Chloramphenicol inhibits
Peptide bond formation
Chloramphenicol binds to:
50S subunit of the 70S ribosome
Chloramphenicol can suppress ______ and affect ________
Bone marrow
Blood cell formation
Can be synthesized chemically; broad spectrum
Aminoglycosides are
• Amino sugars linked by glycoside bonds
Aminoglycosides change
the shape of the 30S subunit of the 70S ribosome
Aminoglycosides can cause
auditory damage (not recommended for pregnant) • Streptomycin, neomycin, gentamicin
• Teratogenic – harmful to a pregnancy
Some antibiotics are known to be teratogenic and should be avoided entirely during pregnancy. These
include ____________ and _____________ (which may cause hearing loss) and tetracycline (which can lead to weakening, hypoplasia, and discoloration of long bones and teeth).
Streptomycin and kanamycin
Tetracyclines are produced by
Streptomyces spp.
Tetracyclines interfere with
the tRNA attachment to the ribosome
Tetracyclines can suppress:
Normal intestinal microbiota
Broad spectrum; penetrates tissues, making them valuable against rickettsias and chlamydias
Inhibitors of Protein Synthesis
Glycylcyclines:
Broad spectrum; bacteriostatic
Inhibitors of Protein Synthesis
Glycylcyclines bind to
30S ribosomal subunit
Inhibitors of Protein Synthesis
Glycylcyclines inhibits
rapid efflux; administered intravenously
Inhibitors of Protein Synthesis
Glycylcyclines useful against
MRSA
Inhibitors of Protein Synthesis
Macrolides contain:
Macrocyclic lactone ring
Inhibitors of Protein Synthesis
Macrolides:
• Narrow spectrum against gram-positives
• Erythromycin
Inhibitors of Protein Synthesis
Streptogramins attach to
the 50S subunit
Inhibitors of Protein Synthesis
Streptogramins work against
gram-positives that are resistant to other antibiotics
Inhibitors of Protein Synthesis
Oxazolidinones bind to the
50S/30S subunit interface
Inhibitors of Protein Synthesis
Oxazolidinones:
Synthetic; combat MRSA (linezolid)
Inhibitors of Protein Synthesis
Pleuromutilins
Retapamulin: topical and effective against gram- positives
Injury to the Plasma Membrane
Lipopeptides:
Structural changes in the membrane, followed by arrest of the synthesis of DNA, RNA, and protein
MRSA
Injury to the Plasma Membrane
Polymyxin B
Topical
Combined with bacitracin and neomycin in over-the-counter preparation
Injury to the Plasma Membrane
Amphotericin B (polyene):
attaches to ergosterol found in fungal membranes
• Humans somewhat susceptible because cholesterol similar to ergosterol
• Bacteria lack sterols; not susceptible
Inhibition of nucleic acid synthesis
Interfere with DNA replication and transcription • Nucleoside analogs (used against viruses)
• Inhibition of synthesis of essential metabolites
• Anti-metabolites compete with normal substrates for an enzyme
• Sulfanilamide competes with para-aminobenzoic acid (PABA), stopping the synthesis of folic acid
Nucleic Acid Synthesis Inhibitors
Rifamycin inhibits
mRNA synthesis
Nucleic Acid Synthesis Inhibitors
Rifamycin penetrates
tissues; antitubercular activity
Nucleic Acid Synthesis Inhibitors
Quinolone and fluoroquinolones
- Nalidixic acid
• Synthetic; inhibits DNA gyrase
• Norfloxacin and ciprofloxacin
• Broad spectrum; relatively nontoxic
Sulfonamides: folic acid synthesis
Sulfonamides inhibit
the folic acid synthesis needed for nucleic acid and protein synthesis
Sulfonamides competitively bind
to the enzyme for PABA production, a folic acid precursor
Sulfonamides are a Combination of
trimethoprim and sulfamethoxazole (TMP-SMZ) is an example of drug synergism
Inhibition of a metabolic function: Competitive Inhibitors
• Sulfonamides (sulfa drugs)
Inhibit folic acid synthesis
• Broad spectrum
Antifungal Drugs: Inhibition of Ergosterol Synthesis
Polyenes:
§ Amphotericin B
Antifungal Drugs: Inhibition of Ergosterol Synthesis
Azoles: topical ointment
- Miconazole
• Triazole
Antifungal Drugs: Inhibition of Ergosterol Synthesis
Allylamines
• For azole-resistant infections
Antifungal Drugs
Agents affecting fungal cell walls
Echinocandins
• Inhibit the synthesis of β-glucan
Antifungal Drugs
Agents inhibiting nucleic acids
Flucytosine
• Cytosine analog interferes with RNA synthesis
Antifungal Drugs
• Griseofulvin
• Produced by Penicillium
• Inhibits microtubule formation
• Active against superficial dermatophytes
Antifungal Drugs
• Tolnaftate
Athletes foot
Antifungal Drugs
Pentamidine
• Anti-Pneumocystis; may bind to DNA
Antiviral Drugs
Entry and fusion inhibitors
• Block the receptors on the host cell that bind to the virus • Block fusion of the virus and cell
• Uncoating, genome integration, and nucleic acid synthesis inhibitors
• Prevent viral uncoating
• Inhibit viral DNA integration into the host genome • Nucleoside analogs inhibit RNA or DNA synthesis
A nucleoside analog:
The structure and function of the antiviral drug acyclovir.
Antiviral Drugs
Interference with assembly and release of viral particles
• Protease inhibitors
• Block the cleavage of protein precursors
• Exit inhibitors
• Inhibit neuraminidase, an enzyme required for some viruses to bud from the host cell
Interferons (for RNA viruses)
• Produced by viral-infected cells to inhibit further spread of the infection
• Imiquimod
• Promotes interferon production
Antivirals for Treating HIV/AIDS
• Antiretroviral
• Nucleoside analog (zidovudine)
• Nucleotide analog (tenofovir)
• Non-nucleoside inhibitors (nevirapine) • Protease inhibitors (atazanavir)
• Integrase inhibitors (raltegravir)
• Entry inhibitors (miraviroc)
• Fusion inhibitors (enfuvirtide)
• Antiprotozoan drugs
• Quinine and chloroquine
• Treat malaria
Artemisinin
• Kills Plasmodium that causes malaria
Metronidazole (Flagyl): parasitic/c diff
Also interferes with anaerobic bacteria
• Treats Trichomonas, giardiasis, and amebic dysentery
Antihelminthic drugs
Niclosamide
• Prevents ATP production
• Treats tapeworms
Praziquantel
Alters membrane permeability • Treatstapewormsandflukes
Mebendazole and albendazole
Interfere with nutrient absorption • Treat intestinal helminths
Ivermectin (ppl thought it could decrease covid?)
Paralysis of helminths
• Treats roundworms and mites
Antibiotic Resistance
• A variety of mutations can lead to antibiotic resistance
• Resistance genes are often on plasmids or transposons that can be transferred between bacteria
Mechanisms of resistance (method of blocking or denaturing a drug)
- Blocking entry/: tougher cell wall
- Inactivation by enzymes
- Alteration of target molecule
- Efflux of antibiotic
Mechanisms of Resistance
Enzymatic destruction or inactivation of the drug
• Prevention of penetration to the target site within the microbe • Alteration of the drug’s target site
• Rapid efflux (ejection) of the antibiotic
• Variations of mechanisms of resistance
Resistance to antimicrobial drugs-
Persisted cells are:
microbes with genetic characteristics allowing for their survival when exposed to an antibiotic (this is why you must finish complete dose of antibiotic)
Resistance to antimicrobial drugs-
Superbugs:
bacteria that are resistant to large numbers of antibiotics
Resistance genes are
often spread horizontally among bacteria on plasmids or transposons via conjugation or transduction
Antibiotic resistance
Misuse of antibiotics selected for resistance mutants
Antibiotic resistance misuse includes:
• Using outdated or weakened antibiotics
• Using antibiotics for the common cold and other inappropriate conditions
• Using antibiotics in animal feed (slaughtered as a healthy animal for consumption)
• Failing to complete the prescribed regimen
• Using someone else’s leftover prescription (leaving the body susceptible to mutants)
Antibiotic Safety
• Therapeutic index: risk versus benefit
• Reactions of antibiotics with other drugs
• Damage to organs
• Risk to the fetus
Effects of combination drugs: SYNERGISM AND ANTAGONISM
SYNERGISM AND ANTAGONISM
Synergism
The effect of two drugs together is GREATER than the effect of either alone
Antagonism
the effect of two drugs together is LESS than the effect of either alone
Area of synergistic inhibition looks:
CLEAR
Area of growth=
CLOUDY
Methods of analyzing EFFICACY(safety+how much is needed to work)
DIFFUSION METHODS:
Disk-diffusion method (also called Kirby-Bauer test)
Disk-diffusion method (also called Kirby-Bauer test) tests the effectiveness of:
Chemotherapeutic agents
Disk-diffusion method (Kirby-Bauer test) are:
Paper disks with a chemotherapeutic agent are placed on agar containing the test organism
Disk-diffusion method (Kirby-Bauer test)
Zone of inhibition around the disk
determines the sensitivity of the organism to the antibiotic
The disk-diffusion method for determining the activity of antimicrobials:
Measure the diameter of zones in mm (no zone=no clear circle surrounding it)
> 22mm = susceptible
< 22mm = resistant
What is the E test in diffusion methods?
Determines the minimal inhibitory concentration (MIC)
(Always start with minimum)
E tests are lowest in ?
Lowest antibiotic concentration preventing bacterial growth
Broth dilution tests are used to determine:
The MIC and minimal bactericidal concentration (MBC) of an antimicrobial drug
Broth dilution tests are used to test:
An organism placed into the wells of a tray containing dilutions of a drug; growth is determined.
What are Antibiograms in broth dilution tests?
Reports that record the susceptibility of organisms encountered clinically
Future of chemotherapeutic agents
-target virulence factors
-sequester iron, which feeds pathogens
Antimicrobial peptides produced by various organisms
Phage therapy: bacterial virus
Bacteriocins: antimicrobial peptides produced by bacteria
