Drug Targeting and Resistance Flashcards
What is an advantage of a very lipophillic drug in terms of entering the target cell?
Can cross lipid membranes including penetrating the blood brain barrier and through the skin (e.g. steriods)
What is a disadvtange of a very lipophillic drug in terms of distrubution?
It will cross any cell membrane and therefore a higher dose is required for it to have its effect so that leads to higher toxicity and cost
What does facillitated diffusion involve?
Transporting water soluble drugs via a transport protein
Facilltated diffusion is equillibrative; what does this mean?
The concentration on the inside is never higher than the concentration on the outside - allows passage across the plasma membrane until there is an equal intracelllular and extracellular concentration
Facillitated diffusion and active transport both have specific targetting; what does this mean?
They will only allow entry of the drug to cells that express the appropriate transporters
Active transport is concentrative; what does this mean?
It will continue to pump the substrate into the cell even against a very high concentration gradient meaning the intracellular concentration can be much higher than the extra cellular
If a transport is concentrative is it energy dependent?
yes as is involved in active transport
If a transporter is equillibrative is it energy dependent?
No as is involved in facillitated diffusion
Why does active transport require energy?
The combination of high affinity and high rates of uptake as well as allowing the substate to cross against the concentration gradient
What is an example of a drug that enters the cell via active transport; what does it target and how does active transport effect the concentration of it inside the cell
Pentamidine enters trypanosome and is given in a dose of 1um which accumulates to 1mM inside the cell
What are the three types of active transport?
- ATP dependent (primary)
- Sodium pumps (secondary)
- Protozoan H+ gradient
What are the transporters of the blood brain barrier?
Active transporter, unidirectional transporters
What are benzimidazoles?
Anti-worm drugs (anthelminthics)
What is an example of a benzimidazole?
Thiabendzole
How do benzimidazoles work?
They bind to B-tubulin and prevent polymerisation of tubulin which is used to make microtubules which disrupts the cytoskeleton
What is resistance to benzimedazole associated with?
A single phenylalanine to tyrosine change at position 200 of B tubulin - worm with tyrosine is resistant
How do macrolide antibiotics inhibit protein synthesis?
They bind to the 23S subunit of the ribosome
How is does resistance to macrolides occur?
- Methlyation in places of the rRNA that stops macrolides binding
- Efflux of the macrolide by a pump encoded by a plasmid
What is the cause of sleeping sickness and what fly transmits it?
Trypanosomes brucei transmitted by the tsete fly
What is used to treat sleeping sickness and what kind of drug is thing?
An organo-arsenic drug called malrsoprol
