The principles of chemotherapy - anti-cancer and antimicrobial drugs

what are the four possible drug targets

• Receptors 

• Enzymes 

• Ion channels 

• Transporters 

define chemotherapeutic agents and chemotherapy

Chemotherapeutic agents are drugs intended to kill/ supress proliferation of target cells (cancer cells or pathogenic microorganisms) 

 

Chemotherapy employs the possibility of selective toxicity. Drugs should be toxic to infectious organism/ tumour but not healthy host cells 

 

how to cancer cells differ from normal, healthy host cells

• uncontrolled proliferation  

• De-differentiation and loss of func 

• Invasion into adjacent tissues (inc lymph nodes) 

• Metastasis 

in normal cells what happens when:

• DNA damage is detected

• what accumulates

• what is a result of this

• Damage to DNA during division causses arrest in G1  

• Accumulation of p53 protein : DNA repair/ apoptosis 

• Damage to DNA during synthesis causes arrest in G2: apoptosis 

in cancer cells what happens when:

• DNA checks are meant to happen

• damaged cells pass checkpoints

• what are the genes that are usually damaged

• Checks to progression through the cell cycle are impaired 

• Cells with damaged DNA may divide and proliferate 

• Damaged genes mainly involved in oncogenesis, tumour suppression, apoptosis or DNA repair 

what do chemotherapeutic agents target in the body, what is a consequence of this

Affect all rapidly dividing cells 

• Bone marrow suppression 

• Impaired wound healing 

• Hair loss 

• GI disturbance 

Cause accumulation of purine metabolites (uric acid) 

• Kidney damage 

what are the three types of drug groups that modify DNA structure

• Alkylating agents 

• Cytotoxic antibiotics 

• Topoisomerase inhibitors

what are the CLASS of drugs that inhibit DNA synthesis 2 examples

antimetabolites

• methotextrate

• mercaptopurine

what are the types of drugs that inhibit mitosis example of one

vinca alkaloids = VINCRISTINE and taxanes

what are the types of drugs that inhibit inflammation

glucocorticoids like DEXAMETHASONE

when it comes to antimicrobial drugs, what does MIC and MBC stand for

Minimum inhibitory concentration (MIC) 

• Lowest concentration that inhibits bacterial/fungal growth after 18-24hr in culture 

Minimum bactericidal concentration (MBC) 

• Lowest concentration that kills 99.9% of bacteria/ fungi after 18-24hr in culture 

If MBC is within the non-toxic range (to the host), the drug is bactericidal/fungicidal 

If MIC is within the non-toxic range but MBC isnt, the drug id bacteriostatic/fungistatic 

what are class I,II,III reaction antimicrobial drugs

Class I: reactions that use glucose and other carbon sources to produce ATP or substances for class II reactions 

Class II: pathways that use ATP and class I substrates to make small molecules eg: amino acids, nucleotides 

Class III: pathways that convert small class II molecules into macromolecules eg: proteins ,nucleic acids, polysaccharides, peptidoglycan 

what is a main example of targets for selective toxicity in antibacterial drugs

Many class III reactions are targets for selective toxicity  

• Synthesis of cell wall is a potential target for antibacterial drugs 

• Useful because host cells dont have cell walls 

explain the common mechanism of B-lactam drugs

• The B-lactam ring mimics D-ala-D-ala dimer 

• in the cell wall, bacteria has PBP (penicillin binding proteins) that catalyse cross linking

• the drug binds to the PBPs and prevents this

• Enzyme cannot catalyse peptidoglycan polymer cross linking 

• lysis of the bacteria cell

what is a consequence of the use of B-lactam drugs, how have we overcome this

• Widespread use of B-lactam antibiotics produced selection pressure  

• Bacterial strains expressing B-lactamase drug-metabolising enzymes 

• This can be overcome by co-formulating B-lactam antibiotics with B-lactamase inhibitors 

• Coamoxiclav

what is the difference between prokaryotic and eukaryotic ribosomal subunits

Prokaryotic ribosomes subunit:

50s + 30s = 70s 

Eukaryotic ribosomes subunit: 

60s + 40s = 80s 

what happens when bactericidal drugs target 30s subunit on ribosomes

• Induce misreading  

• Help protein synthesis at high concentrations 

• Block tRNA binding 

Doxycycline

what happens when bactericidal drugs target 50s subunit on ribosomes

• Inhibit translocation (when peptide chain moves along ribosome) 

what are the two spectrums of drug and what do they mean

BROAD SPECTRUM DRUGS -  

Useful when causative organism is unknown but likely to fall within a certain set of species 

 

NARROW SPECTRUM DRUGS -  

Less likely to produce GI side effects or drug resistant strains 

what are the three techniques bacteria uses to reject antibiotics

1. Mutation of drug targets produces functioning molecules but the drug cannot bind to it  

2. Expression of drug-destroying enzymes  

(B-lactamases inactivate penicillin) 

3. Development of drug-excluding mechanisms (rejects drug) 

how do we manage resistance

• review treatment based on microbiology

• avoid prescribing before knowing the organism

• use co-formulations for when you know there is resistance, coamoxiclav

describe what antifungal drugs target

these drugs target class II reactions

• Fungal cell membranes contain ergosterol rather than cholesterol (the main sterol, which is what we have) 

• Drugs that inhibit ergosterol synthesis impairs fungal membrane function without affecting host cell membrane  

• Fungistatic  

when antifungal drugs target class III reactions, what is disrupted in the cell

GRISEOFULVIN disrupts microtubule assembly into mitotic spindle  

• Antifungal drugs disrupt cell structure or division 

what are the 4 different stages in viral life cycle, that an antiviral drug can target VENE

• entry to host cells

• nucleic acid replication

• viral protein synthesis

• exit from host cells

explain how antiviral drugs target: what enzymes do they target in each

• entry to host cells

• nucleic acid replication

• viral protein synthesis

• exit from host cells

Entry to host cells 

• Drugs may inhibit fusion of virus with host cell membrane following binding to surface receptor  

Nucleic acid replication 

• Drugs may inhibit DNA/RNA polymerases – ACICLOVIR – or retroviral reverse trans 

• criptase  

Viral protein synthesis 

• Drugs can inhibit viral proteases involved in processing large polyproteins  

Exit from host cells  

• Drugs may inhibit neuraminidase- catalysed cleavage