Drug Targeting and Resistance

Question 1

What is an advantage of a very lipophillic drug in terms of entering the target cell?

Answer 1

Can cross lipid membranes including penetrating the blood brain barrier and through the skin (e.g. steriods)

Question 2

What is a disadvtange of a very lipophillic drug in terms of distrubution?

Answer 2

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

Question 3

What does facillitated diffusion involve?

Answer 3

Transporting water soluble drugs via a transport protein

Question 4

Facilltated diffusion is equillibrative; what does this mean?

Answer 4

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

Question 5

Facillitated diffusion and active transport both have specific targetting; what does this mean?

Answer 5

They will only allow entry of the drug to cells that express the appropriate transporters

Question 6

Active transport is concentrative; what does this mean?

Answer 6

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

Question 7

If a transport is concentrative is it energy dependent?

Answer 7

yes as is involved in active transport

Question 8

If a transporter is equillibrative is it energy dependent?

Answer 8

No as is involved in facillitated diffusion

Question 9

Why does active transport require energy?

Answer 9

The combination of high affinity and high rates of uptake as well as allowing the substate to cross against the concentration gradient

Question 10

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

Answer 10

Pentamidine enters trypanosome and is given in a dose of 1um which accumulates to 1mM inside the cell

Question 11

What are the three types of active transport?

Answer 11

1. ATP dependent (primary)
2. Sodium pumps (secondary)
3. Protozoan H+ gradient

Question 12

What are the transporters of the blood brain barrier?

Answer 12

Active transporter, unidirectional transporters

Question 13

What are benzimidazoles?

Answer 13

Anti-worm drugs (anthelminthics)

Question 14

What is an example of a benzimidazole?

Answer 14

Thiabendzole

Question 15

How do benzimidazoles work?

Answer 15

They bind to B-tubulin and prevent polymerisation of tubulin which is used to make microtubules which disrupts the cytoskeleton

Question 16

What is resistance to benzimedazole associated with?

Answer 16

A single phenylalanine to tyrosine change at position 200 of B tubulin - worm with tyrosine is resistant

Question 17

How do macrolide antibiotics inhibit protein synthesis?

Answer 17

They bind to the 23S subunit of the ribosome

Question 18

How is does resistance to macrolides occur?

Answer 18

1. Methlyation in places of the rRNA that stops macrolides binding
2. Efflux of the macrolide by a pump encoded by a plasmid

Question 19

What is the cause of sleeping sickness and what fly transmits it?

Answer 19

Trypanosomes brucei transmitted by the tsete fly

Question 20

What is used to treat sleeping sickness and what kind of drug is thing?

Answer 20

An organo-arsenic drug called malrsoprol