pharmacology 1 - pharmacodynamics and pharmacokinectics

Question 0

pharmacokinetics is what? ADME.

Answer 0

determines what the body does to the drug. 
absorbtion
distribution 
metabolism
excretion

Question 1

drugs need to be? (4)

Answer 1

• efficacy
• safety
• minimal side effects
• least drug residues/legal issues

Question 2

what is the problem with pharmacokinetics? clinical:

Answer 2

drug companies work them out for healthy young animals, certain breed, certain sex etc.

Question 3

pharmacodynamics is what? at 2 levels?

Answer 3

what the drug does to the body. gross level - raise bp

cellular level - transporters etc.

Question 4

what are the kinetics? explain open and closed models. compartments?

Answer 4

open model - drug is eliminated from the body. common.
closed model - drug is re-circulated eg. enterohepatic recirculation

compartments - central (very vascular eg. kidney liver.
peripheral (muscle)
deep (fat, CNS, eye)

Question 5

explain entero -hepatic recirculation?

Answer 5

drugis released into the GI tract in the bile and a proportion may then be reasborbed from the GIT. - back into circulation and reabsorbed in active form. - lasts much longer in system.

Question 6

reaction rates and reaction orders? first order? zero order?

Answer 6

first order - good! the rate of drug elimination changes and is proportional to the drug concentration. rate depends on concentration.
zero order - bad! rate of elimination is fixed. independant of drug concentration. hard to predict the half life. eg. alchohol dehydrogenase system.

Question 7

what would 1st order look like on a graph?

Answer 7

linear relationship. route of entry is important. phase of absorbtion and phase of elinimation. one compartment only.

Question 8

two compartment open model 1st order? what would it look like?
what types of graph? steep bit? less steep? open = drug eliminated from the body!

Answer 8

eg. blood and muscle. an equilibrium is reached bwteeen the two compartments. but drug is also eliminated from the central. Biphasic graph! - steeper = distrinution and elimination
less steep = only eliminated from the central and at equilibrium with the peripheral. i/v administered and no absorbtion phase!!

Question 9

explain the movement of drugs around the body? what factors? (6) non-ionised = morelipid soluble!!!

Answer 9

only ‘free’ drug can move or be eliminated. some is bound to receptors or plasma proteins! /tissue resevoir.
movement depends on: molecular size, shape, ionisation degree, lipid soluble or not, protein binding, physio-chemical properties.

Question 10

explain how drug would move across a membrane? membranes are? have proteins? which are more leaky? which have tight junctions?

Answer 10

phospholipid bilayers = carriers, receptors, channels.
some are leaky - cappillaries
tight - BBB

Question 11

What are the characteristics of the BBB? what is the main control element?

Answer 11

tight junctions between endothelial cells. membrance transport via p-glycoproteins. (prevents toxicity in the CNS.) they block entry of drugs and are also involved in active transort of drugs out of the CNS.

Question 12

2 types of transfer of drugs across membranes?

Answer 12

1. passive transfer - lipid soluble drugs move down their concentration gradient. may be through aqueous pores for small drugs.
2. carrier mediated transport - across membranes -may become saturated.
   - active - moves against a conc gradient needs energy.
   - facilitated diffusion - relies on movement down a concentration gradient.

Question 13

Ph and ion trapping. whats are all drugs? which is more lipid soluble? what is ion trapping and when does it occur?

Answer 13

all drugs are weak acids or weak bases. non-ionised = lipid soluble. local PH can lead to ion trapping if most of the drug is ionised and so it cant move as easily away from that site.

Question 14

what is pka? what are the equations? base? acid?

Answer 14

pka = the ph at which 50% of the drug is ionised. acids = ph-pka = log(ionised/non-ionised)

base = ph-pka = log (non-ionised/ionised. ) need to know ph of the environment!!

Question 15

like for like!!!!! what does this mean with regards to ionisation of drugs? see equations on page 5.

Answer 15

acid in an acid environment = non-ionised
base in a basic environment = non-ionised!!
answer is always number that is ionised for every one that is non-ionised!!

Question 16

if a weak acid is taken orally what will happen?

Answer 16

this is good - it will be distributed throughout the body. quickly absorbed across the mmebrane. eg. may become trapped in the milk - erythromycin. in mastitis if give this drug!