PHAR0002 - chemotherapy

Define chemotherapy

Finding a qualitative or quantitative difference between the host and parasite which can be exploited by a drug so it only causes a cytotoxic effect to the parasite

Define therapeutic index

measure of drug safety

How is the therapeutic index calculated?

Humans : TD50/ED50

^ dose that produces toxic effect in 50%/dose that produces therapeutic effect in 50% population

Animals : LD50/ED50

^ dose that produces lethal effect in 50%/dose that produces therapeutic effect in 50%

Give 2 issues with chemotherapy

1) bacteria have many differences but viruses only have a few

^ cancer : self-sabotaging, no differences

2) development of resistance

What are the 3 classes of chemotherapy?

Class 1 : targets energy production (glycolysis, respiration etc)

Class 2 : small molecule synthesis (amino acids, lipids)

Class 3 : macromolecule synthesis (DNA, RNA proteins)

Give some symptoms of malaria

headache, dry cough, nausea, fever, fatigue

State the 2 types of treatment for malaria

1 : sulfonamides & sulfones

2 : proguanil & pyrimethamine

Why are sulfonamides/sulfones effective?

- malaria synthesise their own folate and humans cannot

- attack dihydropteroate synthetase in the folate pathway

Why is proguanil/pyrimethamine effective?

- humans & malaria both have dihydrofolate reductase but they have different sensitivities to antagonists

Which process is targeted by chloroquine/quinine in malaria?

Heme catabolism

- malaria have heme polymerase but humans have heme oxygenase

Give some features of HIV

- retrovirus

- rapid viral evolution, infection not detected until late

State the difference between a nucleotide and a nucleoside

nucleotide : phosphate + base + sugar

nucleoside : base + sugar

State the 2 types of reverse transcriptase inhibitors

1 : Nucleoside RT inhibitors

2 : Non-nucleoside RT inhibitors

State some types of nucleoside RT inhibitors

AZT, DdC, Ddl, 3TC

State some non-nucleoside RT inhibitors

Nevirapine, C1-TIBO, L697-661

How can HIV be treated?

using RT inhibitors (nucleoside & non-nucleoside)

Integrase inhibitors (raltegravir)

HIV protease inhibitors (prevent splicing of viral proteins)

What was the first discovered antibiotic?

Salvarsan - treatment of syphilis

Name 6 antibacterial drug targets

1) Cell wall synthesis

2) Folate metabolism

3) Plasma membrane

4) DNA replication

5) RNA polymerase

6) Protein synthesis

Name some drugs which affect cell wall synthesis in bacteria

cycloserine

b-lactams

bacitracin

glycopeptides

Name some antibacterial drugs that affect protein synthesis

Chloramphenicol, tetracycline, erythromycin, streptomycin

Name 3 drugs for TB

1) Pyrazianamide

2) Isoniazid - targets mycolic acid synthesis

3) Rifampicin - targets DNA dependent RNA polymerase

Which factors affect antibacterial selection & action?

- mechanism of action

- concentration (minimum inhibitory/bactericidal)

- bacteriostatic or bactericidal

- inoculum size

- infection location

Describe the difference between bacteriostatic and bactericidal

Bacteriostatic : prevent bacterial growth

Bactericidal : kill bacteria

Give 4 mechanisms of resistance

Conjugation : chromosomal plasmid DNA

Transduction : virus, bacteriophage

Transformation : Naked DNA

Point mutation

Give some cellular effects of resistance

Drug conc (inactive, prevented uptake, promoted efflux)

Altered drug target

Bypass metabolic requirement for target

Which drug is used to treat MRSA?

Vancomycin

Give 4 ways that drugs interact in combinational therapy?

1) Additive - works a little bit

2) Synergistic - works very well

3) Antagonistic - works same as A or B alone

4) Suppressive - does not work at all

Give some features of HAART

consists of both types of RT inhibitor & protease inhibitor

- complex dosing regime

- expensive

- does not eradicate virus

Which 3 processes make up horizontal gene transfer?

Conjugation, transduction & transformation

Define MSC

Minimum selective concentration

Define MISsusc and MISres

MISsusc : minimum inhibitory conc susceptible strain

MISres : minimum inhibitory conc resistant strain