BP 15 Selective toxicity Flashcards
What does selective toxicity mean?
being toxic towards invading species but not to surrounding tissues
What is chemotherapy?
2) Describe toxicity of effective chemotherapeutic agents to i)invading species/abnormal cells and ii) host cells:
3) Selectivity toxicity relies on what…
treating with chemicals, via elimination of cells/pathogens
2) Are toxic to the invading species/abnormal cells
Relatively non-toxic to the host/normal cells
3) Exploitable differences between invading species and host (dependent on evolutionary distance)
Why do dentists need to know about selective toxicity?
forms part of clinical due care and responsible prescribing.
Invading cells include:
- neoplastic cells
- bacteria e.g. Streptococcus species
- viruses e.g. herpes viruses
- fungi e.g. candida albicans - parasites e.g. protozoa, helminths
- cancer cells
What is general prophylaxis?
2) give an example when it would be used in dentistry
1) preventative measure, To prevent infection following surgery in susceptible individuals
2) e.g. diabetics, patients taking steroids, transplant patients
Simple say the mode of action of the following:
1) beta-lactam antibiotics
2) mactolides (erythromycin, tetracyline)
1) Inhibition of cell wall synthesis
2) Inhibition of protein synthesis
Simple say the mode of action of the following:
1) quinolones
2) metronidazole
Inhibition of bacterial nucleic acids
e.g. quinolones
Inhibits bacterial DNA synthesis/degrades DNA
e.g. metronidazole
1) Describe structure of bacterial cell walls:
2) Function of cell wall:
3) What links the polymers together?
4) What is the action of beta-latams
polypeptide chains linked together
2) peptidoglycan cell wall gives cell structure
3) polypeptide linked by transpeptidase action
4) inhibited by beta-lactams
1) What amino sugars make up the peptidoglycan chain?
2) Which amino acid residues are involved in the transpeptidation reaction?
1) N- acetyl glucosamine
2) N-acetyl-D-glucosamine (NAG) and N-acetylmuramic acid
(ask lecturer)
How do macrolide antibiotics as works?
2) What difference between pathogens and humans does this rely on?
inhibit ribosome (e.g. 50 s , erythryomycin)
2) Bacterial (prokaryotic) consist of 50S and 30S subunits
Mammalian (eukaryotic) consist of 60S and 40S subunits
What stage of protein synthesis does tetracycline inhibit?
tetracylince
How do fluoroquinoelines (antibiotic)?
1) inhibit DNA replication or nucleix acid synthesis,
2) inhibit topoisomerase II (bacterial specific DNA gyrase- DNA gyrase supercoils folded chromosomes) preventing normal DNA supercoiling process.
Other than inhibiting DNA super coiling or DNA replication or nucleic acid synthesis, what other ways do antibiotics target bacteria nucleic acid synthesis:
- Inhibit the synthesis of the nucleotides
- Altering the base pairing properties of the DNA template
- Inhibiting either DNA or RNA polymerase
- Directly inhibiting DNA itself
How many types of herpes virus are there relevant to dentistry:
2) name them:
3) WHat infected when latent?
1) 3
2) a) simplex (1) = cold sores
b) Varicella zoster = chicken pox (2)
c) Epstian Barr (EBV)= glandular fever
3) sensory ganglia
Aciclovir, whats it used to treat?
2) what is it?
3) high specificity for…
4) descirbe therapeutic index
5) how is it so specific?
1) herpes
2) A synthetic guanosine analogue
3) High specificity to simplex
4) high
5) Requires intracellular phosphorylation to activate
Only happens in an infected cell
What phosphorylates aciclovir and activates it in infected cells?
2) what is it converted to and from?
3) What does it do in this form?
simplex virus specific thymidine kinase -monophosphorylate aciclovir
2) mono to di to tri, tri is acitive form
3) a DNA chain terminator
Inhibitor of viral DNA polymerase
Inhibits DNA production until virus stops infecting
What are the 2 types of fungal infection in dentistry? (common or rate +e.g.)
Superficial (common) Candidiasis (oral cavity, tongue) → thrush Dermatomycoses (mouth) Systemic (rare) Systemic candiasis
What is the main component of
1) fungal cell membranes
2) mammalian cell membranes
1) sterol ergosterol
2) cholesterol
Which of the following work by a)ergosterol inhibition,or b)intracellular inhibition (interferes with fungal cytoskeleton, cannot mitotically seperate) :
1) azoles (imidazoles and triazoles)
2) polyenes (nystatin)
3) mitotic inhibitors 9griseofulvin)
1) a
2) a
3) b
What drug classes fall under azoles:
give examples of these
- imidazoles (e.g. ketoconozole, miconazole and clotrzole)
- triazoles (e.g.fluconazole)
out of the imidazoles, which do you have to be the most careful when prescribing? why?
ketoconozole , inhibits cytochrome P450 (steroid biosynthesis and drug metabolism)= liver function= hepatoxicity
What would you prescribe for a fungla meningitis why?
2) it inhibits P450 less than other azoles , do you still have to be worried about other drug interactions?
flucanozole, Well distributed and achieves high concentrations in CSF
2) yes
How do polyenes work?
2) Why doesn’t it effect host cells as much?
3) +2 e.g.
4) side effects?
5) describe absorbtion properties and how this effects route of administration:
binds to sterols in membraine= ion channel by breaking sterol
2) Higher affinity for binding to ergosterol compared with cholesterol.
3) nystatin, amphotericin (B)
4) variety (due to effect on membrane)
5) poorly absorbed thus IV, unless GI infection
how does Griseofulvin work?
2) how is it selective
nhibits cell division by interfering with spindle formation
2) taken up by cells synthesising keratin
