pharmacology - concentration response curves

what relationship is described by concentration-response curves

drug effects are quantified by studying the relationship between drug concentration/dose and the response produced by the drug

graph a regular concentration response curve aswell as a log version

(will be a rectangular hyperbola for the normal one)

how is log used in pharmacology

1. log(concentration) in formula for receptor binding

2. linear scales compress low drug concentrations making it difficult to distinguish effects at nanomolar levels

3. log scales evenly space wide ranging concentrations improving visualisations of pharmacodynamic profiles

4. log scales reveal sigmoid response curves aiding identification and comparison of EC50 and E90 for different drugs

state the 3 main types of pharmacological experiments

1. in vitro

2. ex vivo

3. in vivo

how are experiments conducted in vitro

• drug effects are studied on a piece of tissue dissected from an animal and kept alive outside of the body

• most common experiment type and includes experiments on cells grown in tissue culture

• responses that might be measured include changes in cell phenotype, changes in enzyme activity or changes in hormone or neurotransmitter secretion

how are in vivo experiments conducted

• drug effects are studied on living animals

• include clinical trials

• tightly regulated by the home office in the UK

• responses that are measured include increase in blood pressure, reduction in pain treshold, reduction in allergen induced bronchoconstriction

how are ex vivo experiments conducted

• a tissue or organ is removed from an animal that has been treated with a drug and the effects the drug has had on organ fuction are tested in vitro

• effects of drug contraction of tissue

• tightly regulated by home office

• examples include seeing whether long term treatments with a drug induce liver damage of change brain biochemistry

how are drug concentrations measured in vivo

it is not possible to use molar concentrations for experiments in vivo because the volume of solvent (blood) is unknown

thus these experiments express dose as weight of drug per weight of kg

allows for approximate extrapolation of the dose

what does Emax indicate

indicates maximum response the drug can produce i.e. the top of the concentration, response curve. increasing the concentration of drug produces no greater effect as all receptors are bound

define EC50

the molar concentration of a drug that produces 50% of the maximum response for that drug

define potency and outline its relation to EC50

describes the concentration at which a drug is effective

→ potent drugs are perscribed in small amounts as they are highly effective

• lower EC50 means more potent drug

what is the equation used to compare a new test drug with an already available, standard drug in potency ration

M (potency ration) = EC50(test) / EC50(standard)

or

logM = logEC50(test) - logEC50(standard)

blurt: therapeutic index

the ratio between the toxic dose of a drug and the dose producing the desired therapeutic effect

• higher therapeutic index = less chance of the drug producing toxic side-effects in therapeutic use

therapeutic index = LD50 / ED50

LD50= lethal dose in 50% of the population

ED50= effective dose in 50% of the population

• no longer used as the experiments can cause death and it is not ethical to experiment in animals. hence this is a meaningless definition from a clinical perspective

• drugs can have different ED50 vales depending on the condition being treated