Principles of Chemotherapy Flashcards
what underlies immunity
the body’s ability to recognise and remove non-self material
what underlies the action of anti-microbial drugs
ability of drugs tp recognise and destroy non-self cells
what principle is chemotherapy based off
selective toxicity
selective toxicity
drugs directed against targets that are involved in the function of abnormal cell/invading organism but aren’t required for host function
chemotherapeutic index
lowest dose toxic to patient divided by the dose typically used for therapy
different types of antimicrobial drugs
antibacterial drugs
anti fungal drugs
anti protozoan drugs
antihelminthic drugs
antimicrobial drug
drug used to control bacteria, fungus, parasites, etc
why are bacteria useful targets
because drugs show selectivity for isoforms
trimethoprim chemistry
MW 290
trimethorprim pharmacology
primary activity is via inhibition of dihydrofolate reductase
interaction between enzyme and substrate is via hydrogen bonding and antibiotic is a structural analogue of the substrate DHF
trimethoprim physiology
dihydrofolate reductase DHFR is an essential enzyme
catalyses the reduction of dihydrofolate acid
to tetrahydrofolic acid
role of DHFR is related to the biosynthesis pathways of thymidylate and purines
inhibition leads to disruption of DNA replication
causes cell death
trimethoprim clinical
often used in conjunction with sulfamethoxazole
treat infections: urinary, respiratory,ghastrointestinal tracts
also treat malaria and has anti proliferative effects (cancer)
class 3 reactions
many are targets for selective toxicity
what are class 3 reactions
pathways that convert small class 2 molecules into macromolecules
what are class 2 reactions
pathways that utilise ATP and class 1 substrates to make small molecules
cell wall synthesis
D-cycloserine
vancomycin
bacitracin
pincillins
cephalosporins
ephamycins
cell wall integrity
beta-lactamases
DNA synthesis
metronidazole
DNA gyros
quinolones
RNA polymerase
rifampicin
phospholipid membranes
polymyxins
two types of protein synthesis
50S and 30S
30S inhibitors
tetracyclins
streptomycin
spectinomycin
kanamycin
examples of beta lactam antibiotics
penicillins
cephalosporins
monobactams
carbapenems
synthesis of cell walls as a target for antibacterial drugs
synthesis of N-acetylmuramic
acid-pentapeptide units
synthesis of peptidoglycan
polymers
cross-linking of peptidoglycan
chains
PBP’s
penicillin binding proteins
example of a PBP
transpeptidase enzyme that normally catalyses cross-linking of peptidoglycan polymers
beta-lactam mechanism of action
structural analogs of D-ala-D-ala
covalently bind to PBPs (transpeptidase)
leads to inhibition of transpeptidation reaction essential for peptidoglycan synthesis
what type of drug is trimethoprim
diaminopyrimidine
ligand and target for trimethoprim §
10931
dihydrofolate reductase
what type of drug is amoxicillin
beta lactam
amoxicillin ligand and target
10865
bacterial penicillin binding protein
chemistry of amoxicillin
MW 365
pharmacology amoxicillin
primary activity inhibition of transpeptidases (specialised acyl serine transferases)
beta lactams mimic the d-ala-d-ala sequence and act as a false substrate for d-alanyl-d-alanine transpeptidases
physiology amoxicillin
competitively inhibits penicillin binding proteins
leads to up regulation of autolytic enzymes and inhibition of cell wall synthesis
causes cell lysis
cidal
causes cell lysis
clinical amoxicillin
treatment of susceptible bacterial infections in: ear, nose, genitourinary tract, skin, skin structure and lower respiratory tract
used with omeprazole to treat helicobacter pylori
ribosomal synthesis of proteins
potential target for antibacterial drugs
aminoglycosides
targets 30S subunit gentamicin
16 S rRna
induces misreading, halt protein synthesis at high concentrations
tetracycline
targets 30S subunit
16 S rRNA
block aminoayl tRNA binding
macrolides
targets 50 S subunit
clarithromycin
23 S rRNA
inhibits translocation
fusidic acid
50S subunit
23 S rRNA
inhibits translocation
what type of drug is clarithromycin
macrolide
chemistry of clarithromycin
MW 748
semisynthetic macrolide
derived from erythromycin
ligand and target clarithromycin
10903
23S ribosomal RNA
pharmacology clarithromycin
reversibly binds to 23S rRNA component of 50S ribosomal subunit of the ribosome
inhibits the translocation of aminoayl transfer-RNA
prevents peptide chain elongation
physiology clarithromycin
inhibition of protein synthesis causes ell death
due to cell inability to produce new proteins
