General properties of antimicrobial agents Flashcards
Are fungi classified as eukaryotes or prokaryotes and what problems are caused by this
Classified as Eukaryotes so there is no specific toxicity
Attacking common targets can cause side effects.
List classes of anti-fungal drugs
Polyenes
Azoles
Echinocandins
Amorolfine
List examples of drugs in the azole categories
Imidazole Triazole Clotrimazole Miconazole Ketoconazole, fluconazole Itraconazole
MOA of azoles
Inhibit the production of sterols in cell membrane
What are the best Azoles to use and why?
Fluconazole and itraconazole
Less toxic than ketoconazole and has good activity again fungi
Safe to use systemically
Used widely for fungal infection and oral/vaginal infcetions
Examples of Echinocandins
Caspofungin
Micafungin
MOA of echinocandins
Inhibit the enzyme beta-glucan synthase which produced cross link constituent of fungal cell wall
MOA of Amorolfine
Affects sterol production: reduced sterols causes accumulation of related compounds
Used of amorolfine
Fungal nail infections only- topically
MOA of polyenes
Interact with sterols and increase the permeability of fungal membrane.
Where are polyenes produced
in the soil
Examples of polyenes and their properties
Amphotericin B: High renal toxicity, Liposomal formulation reduces but is more expensive
Nystain: topical only
why is there a lack of development of antiparasitic drugs
Infections were rare
There was no money in it.
List some antimalarial drugs
Quinines: Chloroquine, mefloquine, Halofantrine
Artemisinin
List some conversional anti-bacterial drugs used as antiparasitic and how they work
- doxycycline: Malaria prophylaxis (“anti-protein” NB up to 15% photosensitisation)
- metronidazole : amoebae, giardia, trichomonas (reduced, then nucleic-acid disruption)
- co-trimoxazole: toxoplasma (and PCP) prophylaxis
- clindamycin: toxoplasma (and PCP) treatment (50s “anti-protein”)
- pyrimethamine toxoplasma (and PCP) treatment (DHFR, similar to trimethoprim)
*Toxoplasma gondii and Pneumocystis carinii Pneumonia (PCP)
What are helminths
Worms or flukes
causes of worms (parasitic infections)
Increased world travel has also increased helminth infections (or detection at least)
Hygiene / sewage management
Sushi/sashimi and poorly managed meat but water supplies and raw unwashed veg/fruit are the major contributor in many countries
List some anti-Helminths against Threadworm/pinworms/Ascaris/Roundworm and how they work
-albendazole / mebendazole
Disrupt microtubule formation and glucose uptake which affects the motility and attachment of the worm
-nitazoxanide or ivermectin are alternatives
nitazoxanide disrupts energy transfer processes
ivermectin disrupts the nervous system
Anti-Helminths against taenia/Tapeworm
-niclosamide: Inhibits ATP production
-praziquantel (broad-spectrum anti-helminthic)
>Increases the Ca permeability of plasma membranes
>Induces muscle spasms, affects retention, motility and exposes antigenic sites to immune system
Anti-helminth treatment against Toxocara/ Roundworm
Albendazole: For parasitic worms of cats and dogs
What is Aciclovir used to treat
Effective against both genital, oral and more serious herpes simplex (HSV) infections
Also used with some success in treatment of varicella virus (chickenpox and shingles)
It can be given intravenously or orally or used topically
Lists some new variations of Aciclovir
valaciclovir,
famciclovir,
penciclovir
How does Aciclovir work
-Nucleoside analogue produced as a prodrug (acycloguanosine)
>Phosphorylated once in the patient’s cells *IF virally coded thymidine kinase is present
>Affects DNA polymerases encoded by viral genes, so effective “only” in infected cells:
>Blockade and termination of viral DNA replication
steps of Aciclovir mechanisms
1: Aciclovir + ATP to create aciclovir phosphate using HSV and Thymidine kinase
2: aciclovir phosphate with human enzymes creates Aciclovir triphosphate
3: Aciclovir triphosphate with HSV and DNA polymerase which causes it to be incorporated into viral DNA
4: Viral DNA synthesis inhibited
What are the uses of Aciclovir derivatives (different from the)
Ganciclovir: treat cytomegalovirus (CMV) infections
- Used effectively for cytomegalovirus in immunocompromised patients
- More toxic, particularly to bone marrow (classified teratogen, mutagen, carcinogen)
valganciclovir is more well absorbed prodrug of Ganciclovir
Mechanism of Foscarnet and what does it treat
acts against DNA replication by inhibiting pyrophosphate binding to DNA polymerases
Treats herpes/CMV when aciclovir/ganciclovir is unsuitable
Side effects/ caution of Foscarnet
Toxic to kidneys, principally (approx 40% pts)
Anti-viral drugs that aren’t ciclovir
Oseltamivir
Zanamivir
Mechanism of oseltamivir, zanamivir
Selective ininhibitor of viral neuraminidase (NA)
Use of oseltamivir, zanamivir
Used to prevent infection after exposure, or treat
Glycoproteins on the virion surface, important for entry into cells and for the release of recently formed virus particles from cells, allowing spread within the body.
In uncomplicated influenza, slightly shorter duration of symptoms but may be significant in patients at risk of severe complications
Mechanism of viruses
- They are obligate intracellular parasites
- Because they “hijack” many host cellular processes, selective toxicity is more difficult
- Many viruses difficult to culture - more difficult to test potential antiviral drugs
- The lack of easy, rapid tests means it is difficult to differentiate between various viral infections
- Many viruses have multiple strains and also will readily mutate
What are the types of HIV antiretrovirals
Entry/fusion inhibitors
Nucleoside Reverse Transcriptase Inhibitors (RTIs
Integrase Inhibitors (INIs)
Protease inhibitors (PIs)
How do RTIs work
This is a viral enzyme, so useful target. HIV nucleic acid is RNA, so must be “translated” into DNA. In slightly different ways, these drugs all inhibit the process
The “base mimics” are included in the DNA chain but can’t be added to (no 3’OH), so formation is stoppedNon-base inhibitors bind directly to the enzyme
Which type of antiviral mechanism is rarely longer used and why
Entry/ fusion inhibitors
Not used due to resistance
How do Integrase inhibitors work
Integrase is a viral enzyme that “integrates” the newly transcripted DNA into host DNA.
The current drugs interact with two Mg2+ ions in the enzyme’s active site structure
How to protease inhibitors work
Protease is a viral enzyme that is involved in building new virus particles from the various parts that the host cell has manufactured.
These drugs tend not to stop the assembly but the resulting virus particles (virions) are defective
