Pharm Lecture 2: Development of Dosage and Potency, Efficacy and Therapeutic Index

bioavailabiltiy definition

Amount of drug that reaches the plasma in an active form

factors that decrease bioavailability

• First pass hepatic metabolism

• Drug formulation and incomplete absorption

• Plasma protein binding

drug distribution definition

Process by which a drug leaves the blood stream and enters body tissues

what is volume of distribution

How much a drug has distributed out of the blood and into the tissues

what is a loading dose

• Used to achieve a therapeutic effect quickly which targets the top of the therapeutic range

• Large amount to “prime” the blood with a drug level in the plasma large enough to get a quick response

plateau principle

• Plateau occurs after 4 x the ½ life of drug

• Amount of drug entering system equals eliminated

dosing interval

Amount of time between doses

clearance

Volume of plasma completely cleared of a drug per unit of time

maintenance dose

Drug dose required to maintain plasma concentrations within the therapeutic range

Pharmacodynamics

• Study of how a drug changes the body

• Mechanism of action of drugs

what question does quantal effect answer

Yes or no patient response

ED50

• dose required to produce a therapeutic response in 50% of patients, also called the standard dose

• ED50 helps describe drug potency

how to determine the ED50 in a log graph

• find the x value corresponding to a 50% response

• take the antilog to determine

LD50

dose of drug that will be lethal in 50% of test animals (not really relevant)

TD50

dose that will provide toxicity in 50% of patients

therapeutic index

ratio of a drug’s LD50 or TD50 to its ED50

three phases of dose response curve

phase 1: Negligible effect. Few target cells affected by the drug at the dose.

phase 2: Ideal, where there is a linear relationship between amount of drug administered and degree of patient response

phase 3: Plateau reached, increasing the dose can produce adverse effects. Binds to other unwanted receptors.

potency definition

How much of a drug is needed to produce 50% of maximum biological response

potency vs efficacy meaning

potency: How much drug is needed to produce an effect?

efficacy: The maximum effect the drug can produce

what questions do potency vs efficacy answer

potency: How much do I need?

efficacy: how well can it work?

potency vs efficacy on a graph

potency: Looking at how far left/right the curve goes

efficacy: looking at how high the curve goes

why would drugs that are equal in efficacy have a different ED50?

• it is because each drug has a different affinity for the target receptor

• drugs with a lower affinity for the receptor site will require a higher dose of drug to cause the intended effect.

what is [D]_o

top of therapeutic range or initial concentration

what is T

dose interval (time between doses)

what is [D]_pl

middle of therapeutic range

what is t1/2

half life

what is [D]

bottom of therapeutic range or the the concentration you are trying to find after certain number of hours

Quantal vs graded response curves

• Graded response curves measure data in a single individual

• Measures potency EC50 and efficacy

• Quantal responses measure data across population and whether or not they exhibit a response

• Measures ED50 (median effective dose for 50% of population)