L3 - Concentration Response curve

What famous quote regarding poisons is attributed to Paracelsus?

"All substances are poisons: There is none which is not a poison. The right dose differentiates a poison and a remedy"

. What shape is a drug concentration-response curve on a linear concentration scale?

A rectangular hyperbola

. What shape is a drug concentration-response curve on a logarithmic concentration scale?

A symmetrical sigmoid curve

. Why are logarithmic scales preferred over linear scales in concentration-response curves?

Linear scales compress low concentrations, whereas logarithmic scales space wide-ranging concentrations evenly to identify EC50 and EC90

. What defines an in vitro pharmacological experiment?

Drug effects are studied on tissues or cells dissected from an animal or human and kept alive outside the body

. What is the most common type of pharmacological experiment?

In vitro experiments, including cell culture studies

. What defines an in vivo pharmacological experiment?

Drug effects are studied directly inside a living animal or human

. What regulatory body tightly regulates in vivo and ex vivo animal experiments in the UK?

The Home Office

. What defines an ex vivo pharmacological experiment?

A tissue or organ is removed from an animal pre-treated with a drug, and drug effects on organ function are tested in vitro

. Give an example of an ex vivo experiment.

Testing whether long-term drug treatment in an animal induces liver damage or alters brain biochemistry

. How are drug concentrations typically expressed in in vitro experiments?

In Moles per litre, also known as Molar (M)

. How many molecules are present in one Mole of a drug?

6.02 x 10^23 drug molecules

. What concentration range do most clinically useful drugs act within?

Between 1 x 10^-6 M and 1 x 10^-12 M

. What do the prefixes milli (m), micro (µ), and nano (n) represent in Molar concentrations?

10^-3 M, 10^-6 M, and 10^-9 M, respectively

. How many drug molecules are present in a 1 nanomolar (1 nM or 10^-9 M) solution per litre?

6.02 x 10^14 drug molecules

. How are drug doses expressed in in vivo experiments?

As weight of drug per weight of animal, such as mg per kg (mg kg^-1)

. Why are in vivo drug doses expressed as mg/kg rather than Molar concentrations?

Because the exact volume of solvent or blood in a living organism is unknown

. How does expressing in vivo doses in mg/kg aid drug development?

It allows approximate extrapolation of doses from small animals to humans

. What is the difference between a standard and a cumulative concentration-response curve in an organ bath?

Standard curves wash out the drug between additions, whereas cumulative curves add increasing concentrations sequentially without washing

. What is Emax in pharmacodynamics?

The maximum response or effect a drug can produce, represented by the plateau at the top of the concentration-response curve

. What is EC50?

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

. What does a lower EC50 value indicate about a drug?

The lower the EC50, the higher the potency of the drug

. What is drug potency?

A measure of the concentration at which a drug is effective, where a potent drug produces an effect at very small amounts

. What is the formula for the potency ratio (M) comparing a test drug to a standard drug?

M = EC50(test) / EC50(standard)

. What does a potency ratio (M) value of less than 1.0 signify?

It means the test drug is more potent than the standard drug

. What is the Therapeutic Index?

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

. Why is a higher Therapeutic Index desirable for a drug?

A higher Therapeutic Index means there is less chance of the drug producing toxic side effects during clinical use

. What was the historical definition of Therapeutic Index, and why was it abandoned?

Defined as LD50 / ED50; it was abandoned because death is clinically irrelevant and animal LD50 testing is ethically indefensible

. How is Therapeutic Index defined in human studies?

As TD50 / ED50, where TD50 is the dose producing signs of toxicity in 50% of the population

. What are two major limitations when interpreting Therapeutic Index values?

Wide person-to-person variation in response, and the fact that ED50 varies depending on the specific condition being treated

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