general principles lect 1 Flashcards
pharmacodynamics
biochemical and physiological effects and mechanisms (what drugs do to the body)
pharmacokinetics
absorption, distribution, metabolism, and elimination of drugs (what body does to drugs)
measures the ability of a drug to bind to a receptora
affinity
Kd
equilibrium dissociation constant: concentration of free drug when binding is at 50%
relationship between Kd and affinity
the lower the Kd, the higher the affinity
efficacy (intrinsic activity)
measure of biological response resulting from binding of a drug - determines maximal response that can be obtained with a drug
potency
dose (amount of drug) required to produce a desired effect
EC50
concentration required for half-maximal effect
relationship between EC50 and potency
lower the EC50 the more potent the drug
binds to receptor and initiates a response
agonist (full vs partial)
binds to receptor but does not initiate a response
antagonist (inhibits response to an agonist) -competitive vs non-competitive
binds to different receptor site than agonist and alters the reponse to agonist
allosteric activators and inhibitors
interaction between drug and receptor is reversible unless they are bound by what kind of bond
covalent
at drug-receptor equilibrium, how many receptors are bound?
half of the receptors are bound; half are free
efficacy (alpha; intrinsic activity) is the ability of a drug to initiate a response; if there is a 100% response, Alpha = ?; if there is a 0% reponse, alpha = ?
1; 0
what type of agonist have affinity and intrinsic activity (alpha = 1)
full agonist
what type of agonist have affinity but no intrinsic activity (alpha = 0)
antagonist
what type of agonist have affinity but lower intrinsic activity (0
partial agonist
What Emax?
Emax: response produced will increase with increasing drug concentration until a maximal response is reached
what is Emax a function of
- amt of drug - ability to evoke a response - the number of available receptors
plotting %biological effect vs log[drug] gives what types of curve. what effect does this have on theraputic effect and toxicity
sigmoid curve - expands the scale at low concentrations where the response increases rapidly (theraputic effect) and contracts at high concentrations where the response is not changing as quickly (toxicity)
in graded dose-response curves, what does the slope of the curve indicate
how rapidly the response changes when the dose in increased. Steep slopes are risky (small theraputic window)
What do quantal dose-response curves measure
frequency with which a response will occur to a given dose within a population - “all or none effect” - frequency of response is measured - determines doses that produce therapeutic and lethal effects
How is therapeutic ratio measured in humans
TD50 (toxic dose)/ED50: (LD50= dose that is toxic in 50% of population that recieves the drug). ex: if TR = 4 and 100mg is effective in 50% of population; then 400mg is lethal in 50% of population
* animal studies can use LD50: lethal dose
Margin of safety
= LD1/ED99 - higher the margin of safety, safer the drug
how does number of receptors affect sensitivity of a cell to a drug
the more receptors, the more sensitive a cell is to a drug
when do spare receptors exist
when it is possible to elicit a maximum biological response without occupying all of the available receptors
when spare receptors exist, the concentration-response curve (ED50) is shifted to what side
shifted to smaller concentrations-> to the left
what is the relationship between EC50 and Kd when there are spare receptors
EC50 is lower than Kd * maximal response still produced due to amplification of the cell signaling mechanism
clinical implications of spare receptors
use a lower dose
how is potency determined on a dose response curve
postion along the x-axis; a drug is more potent if a curve is located near the left side of the x-axis; a drug is less potent is a curve is located near the right side of the x-axis
ex: Drug X is more potent than Drug Y
Drug + receptor -> [DR]; what is the rate constant for DR association
K1
[DR] -> Drug + receptor; what is the rate constant for DR dissociation
K2
What is Kd in terms of K1 and K2
Kd=K2/K1; if Kd is low; dissociation is slow and binding affinity is high and vice versa
in most cases, ED50 and Kd are the same; name a case in which they aren’t
spare receptors; ED50 is lower than Kd
drugs that act on the same receptor but have a lower affinity for the receptor will show what ED50 compared to a drug that has a high affinity for a receptor
lower ED50
threshold dose
dose below which no response is observed
what is theraputic ratio
range of concentrations in which likelihood of efficacy is high and the probability of adverse effects is low
