C7 Flashcards
Types of antimicrobial drugs
- Synthetic: salvarsan & sulpha
- Natural: penicillin
- Semi synthetic: semi synthetic penicillin
General properties of antimicrobial drugs
Selective toxicity
- Drug able to kill or inhibit organism without causing damage to host
Spectrum of activity
- Range of different microbes against antimicrobial agent
Modes of action of antimicrobial drugs
- Antibacterial
- Antiviral
- Antifungal
Spectrum of antibacterial drug
- Broad spectrum agent
- Narrow spectrum agent
2 category of anti bacterial drugs
- Bactericidal agent: kill
- Bacteriostatic agent: stunt growth
Mechanism of action of antibacterial agents
- Inhibition of cell wall synthesis: Penicillin
- Disruption of cell membrane function: Polymyxin
- Inhibition of protein synthesis: Tetracycline
- Inhibition of nucleic acid synthesis: Rifamycin
- Action as metabolites: Sulfonamides & Trimethoprim
Example of cell wall inhibitors
- Beta lactam
- Penicillin
- Cephalosporin
- Penem antibiotic
Mechanism of penicillins in cell wall synthesis
- Cell wall synthesis catalyst by transpeptidase
- Penicillin bind to transpeptidase & inhibit cross linking
- Newly synthesis cell wall no longer cross linked & not strong
- Induce autolysin that digest existing cell wall to cause cell lysis
Mechanism in semi synthetic penicillin
- Made by changing the R side chain on Penicillin G molecule
- Acid stable & resistant beta lactamase
- Eg: ampicillin & methicillin
Explain cephalosporin
- Produce by Cephalosporium
- More resistant to beta lactamase
- Use to combat Neiserria
Explain bacitracin & vancomycin
Bacitracin
- Small polypeptide produce by B.lichenoformis
- Inhibit symptoms of peptidoglycan strand
- Use topically
Vancomycin
- Quite toxic
- Use as last line defence
Explain mechanism of cell membrane disruptor
- 5 types of polymyxins (A,B,C,D &E)
- Binding to lipid in outer membrane
- Tyrocidins similar to polymyxin & toxic
- Daptomycin bind to bacterial cytoplasmic membrane, form pore & induce depolarisation
- Cell lose ability to synthesis proteins & nucleic acid results in cell death
Explain mechanism antibiotic affecting protein synthesis
- Inhibit protein synthesis on bacterial ribosome
- Bacteria has 70S ribosome consist of 50S & 30S
- Eukaryotic has 80S ribosome consist of 60S & 40S
Inhibitor 30S ribosomal unit
Aminoglycosides
- Bind irreversibly to 30S
- Stop initiation complex
- Seldom use due to resistance
- Can act synergistically with other drugs
Tetracycline
- Inhibit binding of aminoacyl tRNA to acceptor
- Widest spectrum
- Destroy normal intestinal microflora
Inhibitor of 50S ribosomal unit
Erythromycin
- Bind to 23SRNA of 50S
- Inhibit function of peptidyl tRNA
- Macrolide ring structure with sugars
Inhibitor of nucleic acid synthesis
Quinolones
- Inhibit enzyme DNA gyrase
- DNA gyrase catalyst supercoiling of DNA
- Prevent DNA synthesis
Rifampin/ Rifamycin
- Block DNA dependent RNA polymerase enzymes
- Inhibit intiation of RNA transcription
- Treat TB
Example of antimetabolite
- Sulfonamides
- Trimethoprim
Explain sulfonamides & trimethoprim
Sulfonamides
- Growth factor analogs
- Block use of growth factor by competing same enzyme
- Bind to PABA & bacteria stop grow w/o folic acid
Trimethoprim
- Bind to dihydrofolate reductase & inhibit formation of tetrahydrofolic acid
- Use in combination with sulfonamides
- Prevent emergence of resistant strain
Why fungi difficult to treat
- Difficult to find target unique to fungal cell
- Drug inhibit metabolic pathways also effect human cell
- Most drug are toxic & topical application only
Antifungal drug mechanism
- Membrane function: Polyenes
- Nucleic acid synthesis: 5-Fluorocytosine
- Microtubules formation: Griseofulvin
- Ergosterol synthesis: Azoles
- Cell wall synthesis: Polyoxins
Explain membrane function disruptor in antifungal drug
- Bind to ergosterol in fungal cell membrane
- Cause membrane permeability & cell death
- Azoles & allylamides inhibit ergosterol synthesis
- Broad spectrum
Explain inhibitor of cell wall synthesis in antifungal drug
- Polyoxin interfere with chitin synthesis
- Cell wall also contain glucan polymer synthesis by enzymes 1,3 b-D glucan synthase
Example of inhibitors of nucleic acid synthesis
- Nucleotide analog
- Eg: 5-fluorocytosine
- Effective inhibitors of nucleic acid synthesis
Explain disruption of microtubule formation
- Griseofulvin disrupt microtubule assembly during mitosis
- Cell cannot divide
- Useful as anticancer drug
- Expensive cuz source difficult to find
Drug use to target virus entry
- Enfuvirtide
- Amantadine & Rimantadine
Drug use in virus genome replication
- Ayclovir
- Ganciclovir
- Foscarnet
Explain acylovir, ganciclovir & foscarnet
Acylovir
- Need to be phosphorylated before inhibit DNA polymerase
- Blocking further elongation in DNA replication
Ganciclovir
- Similar mechanism to acylovir
- More toxic
- Reduce amount of CMV
Foscarnet
- Directly inhibit enzymatic activity of herpesvirus DNA polymerase
Example of nuclease inhibitor in HIV & HBV
Zidovudine (ZDV/ AZT) or nucleoside transcriptase inhibitors (NRTI)
Explain ZDV
- First anti HIV drug
- Analog of thymidine
- Inhibit the HIV & prevent elongation of viral nucleic acid
Explain nonnucleoside inhibitors of HIV RT
- Include delavirdine, efavirenz & nevirapine
- Inhibit HIV reverse transcriptase
- Inhibit catalytic step in RT by binding directly to reverse transcriptase & inactivating enzyme
Mechanism of neuramidase (NA) inhibitors
- Inhibit virus release from infected cell
- Removal of sialic acid vital for release of virus from infected cell & spread effectively
- Absence of NA cleavage or terminal sialic acid, virus aggregate as it release & cannot spread efficiently
- Eg NA inhibitor is tamiflu
Explain interferons
- Small protein that prevent viral multiplication by stimulating production of antiviral protein
- Natural molecules
- 3 types: IFN-a, IFN-y & IFN-B
- Host specific activities
Why interferon fail to provide broad spectrum antiviral activity
- Production of interferon different in response to different virus, thus its not effective
- Active against RNA virus only which do not cause disease and not DNA
Explain prophylaxis vaccine
- Introduce antigen to body
- Goal to induce immune system to create antibodies for antigen hence become immune to the illness
- Encourage body to fight harder against illness it already has
Types of immunisation
Passive
- Acquire from maternal antibodies, antitoxin
- Temporary
Active
- Acquire from natural infections, vaccine & toxoid
- Permanent
