Pharmacology. 21/02/20
Anti-infectives
1. Learning outcomes
Explain the rationale behind:
- Infective drug design
- Identification and exploitation of difference between host-pathogen
Be able to provide examples of the different classes of antipathogen drug classes, including their
mode of action
- Demonstrate why different drug classes work
- Understand the challenge of resistance
- How are we trying to mitigate this?
Understand the concept of risk verses benefit for drug prescription
2. Anti-pathogen chemotherapy
Use of drugs to damage an invading species
Can be bacteria, virus, fungi or protozoa
Selective Toxicity (severity of illness determines toxicity of the drug)
- Kill pathogen but leave host unharmed
- Exploit host/pathogen differences
o Biochemical or Morphological
3. What are the defining properties of bacteria?
No nucleus, cell wall, plasmids, different size ribosomes
Simplistic circular DNA structure, no “non-coding” information (no introns).
Express essential, structural proteins highly (at the beginning of transcription start site) but less
essential proteins at a lower level (dependent on orientation in the genome).
Expression of additional genes through presence of “plasmid DNA”
4. Antibiotics
In late 1920’s penicillin was discovered and is still used to date; the question is why are they interesting
again?
Drug companies not interested because of curative ability (not worth it).
Newly emerging “superbugs” with multi-drug resistance (MDR)
Gram – are hard to treat (gram + and – differences)
5. Inhibition of cell wall synthesis
b-Lactam Antibiotics
Large group including Penicillins, cephalosporins, carbapenems and monobactams
Bacteriocidal: Interfere with cell wall biosynthesis(peptidoglycans)
Cephalosporins can be used with or without beta-lactamase inhibitor
, Pharmacology. 21/02/20
Anti-infectives
6. Inhibition of nucleic acid synthesis
Sulphonamides (doesn’t work on our cells, it does not kill the
bacteria but helps making it weaker), Trimethoprim,
Cotrimoxazole-combo
Bacteriostatic
Bacteria must synthesize folates, but man can gain from diet
Sulphonamide use decreased as resistance has increased.
Cotrimoxazole acts at both steps (enzymes in picture)
Common side effects: GI tract hypersensitivity
Rare side effects: Anaphylactic shock
7. Inhibition of protein synthesis
Ribosome has 3 sites,
bacteria has 2 sites P site
8.
andDNA gyrase
A site. tRNA in A site,
inhibitors
chain assembles(similar
and goes
to
back to P site and cycle
continues. Blocking of
topoisomerase)
initiation complex
Bacterial DNA using
oxalizodonone,
gyrase prevents
recruitment by binding to
introduces
tRNA. Aminoglycosines
negative
preventsupercoils
recognition and
readinginto
of mRNA by
a relaxed
bindingclosed
in A site.
Inhibition of enzyme
circular DNA that
allows molecule
transpeptidation
by chloramphenicol.
DNA gyrase is
Macrolide movement
necessary for
from ADNAsite to P site also
synthesis to occur used if you’re allergic to
E.g. Nalidixicacid, coumermycin b-lactam such as penicillin
- Active against different subunits of DNA gyrase
Bacteriostatic (helps system kill bacteria)
Orally active
Useful in cases where bacteria have become resistant to penicillins, cephalosporins or
aminoglycosides
Common side effect: GI tract hypersensitivity
Inhibition can cause DSB and STB
Anti-infectives
1. Learning outcomes
Explain the rationale behind:
- Infective drug design
- Identification and exploitation of difference between host-pathogen
Be able to provide examples of the different classes of antipathogen drug classes, including their
mode of action
- Demonstrate why different drug classes work
- Understand the challenge of resistance
- How are we trying to mitigate this?
Understand the concept of risk verses benefit for drug prescription
2. Anti-pathogen chemotherapy
Use of drugs to damage an invading species
Can be bacteria, virus, fungi or protozoa
Selective Toxicity (severity of illness determines toxicity of the drug)
- Kill pathogen but leave host unharmed
- Exploit host/pathogen differences
o Biochemical or Morphological
3. What are the defining properties of bacteria?
No nucleus, cell wall, plasmids, different size ribosomes
Simplistic circular DNA structure, no “non-coding” information (no introns).
Express essential, structural proteins highly (at the beginning of transcription start site) but less
essential proteins at a lower level (dependent on orientation in the genome).
Expression of additional genes through presence of “plasmid DNA”
4. Antibiotics
In late 1920’s penicillin was discovered and is still used to date; the question is why are they interesting
again?
Drug companies not interested because of curative ability (not worth it).
Newly emerging “superbugs” with multi-drug resistance (MDR)
Gram – are hard to treat (gram + and – differences)
5. Inhibition of cell wall synthesis
b-Lactam Antibiotics
Large group including Penicillins, cephalosporins, carbapenems and monobactams
Bacteriocidal: Interfere with cell wall biosynthesis(peptidoglycans)
Cephalosporins can be used with or without beta-lactamase inhibitor
, Pharmacology. 21/02/20
Anti-infectives
6. Inhibition of nucleic acid synthesis
Sulphonamides (doesn’t work on our cells, it does not kill the
bacteria but helps making it weaker), Trimethoprim,
Cotrimoxazole-combo
Bacteriostatic
Bacteria must synthesize folates, but man can gain from diet
Sulphonamide use decreased as resistance has increased.
Cotrimoxazole acts at both steps (enzymes in picture)
Common side effects: GI tract hypersensitivity
Rare side effects: Anaphylactic shock
7. Inhibition of protein synthesis
Ribosome has 3 sites,
bacteria has 2 sites P site
8.
andDNA gyrase
A site. tRNA in A site,
inhibitors
chain assembles(similar
and goes
to
back to P site and cycle
continues. Blocking of
topoisomerase)
initiation complex
Bacterial DNA using
oxalizodonone,
gyrase prevents
recruitment by binding to
introduces
tRNA. Aminoglycosines
negative
preventsupercoils
recognition and
readinginto
of mRNA by
a relaxed
bindingclosed
in A site.
Inhibition of enzyme
circular DNA that
allows molecule
transpeptidation
by chloramphenicol.
DNA gyrase is
Macrolide movement
necessary for
from ADNAsite to P site also
synthesis to occur used if you’re allergic to
E.g. Nalidixicacid, coumermycin b-lactam such as penicillin
- Active against different subunits of DNA gyrase
Bacteriostatic (helps system kill bacteria)
Orally active
Useful in cases where bacteria have become resistant to penicillins, cephalosporins or
aminoglycosides
Common side effect: GI tract hypersensitivity
Inhibition can cause DSB and STB
