Pharm 1. Flashcards
drug action vs drug effects
drug action: molecular - invisible. drug effect - pharmacologic - visible
How do we measure drugs?
drug effect
pharmacokinetics
time course of drug absorption, actions and elimination
pharmacodynamics
types of drug actions
How are drugs created?
to mimic endogenous agonists
How are doses measured?
by weight (mg, mcg)
Where do pharmacodynamics and pharmacokinetics event occur?
at the molecular level
How much is a mole?
6.022 x 10^23 molecules
How many L of total body water?
40
How do you induce a change in tissue function with drugs?
affect the receptor which causes molecule events - enough of these events causes change in cell function
What is the effect of drug/receptor interaction?
production of a small change in the biochemical or electrochemical homeostasis of the cell - cumulative effects lead to change in function of cell
eMax
maximal response that is eventually achieved which is related to the number of drug-receptor interactions and the physiologic capacity of the tissue
What are reversible receptor bonds?
ionic, van der waals, hydrogen
What are irreversible receptor bonds?
covalent
G protein activity
lasts only for seconds before being turned off - stimulation by drugs can cause amplification of signals
Second messengers
produces amplification of the drug receptor interaction
How does the structure of the drug affect the activity of the drug?
structure determines how it will fit into the receptor - better the fit, the better the stimulation
How do stereoisomers affect drug interaction? (epi as example)
(-) form of epic more active than the (+) epic because hydroxyl group is facing towards the receptor as opposed to the -H in the (-) form
Why are stereoisomers a bad thing?
the “bad” stereoisomer can block the good isomer (competition)
How do we measure dose-response relationships?
log of drug concentration because it is easier to pick up EC50
What is the Michaelis Menten equation?
Effect = Emax [Dose] / Kd (dissociation constant = EC50) + [D]
threshold
the beginning of the curve - dose of agonist at which a response begins
maximal asymptote
top of the curve - represents EMax for a particular agonist
slope
rate of rise of the response on the steep portion of the curve, log of EC50 also relates to affinity
intrinsic activity
ability to stimulate the receptor once bound - relates to structure and influences efficacy and potency - greater intrinsic activity = greater efficacy
spare receptors
not all receptors need to be occupied to achieve Emax
secondary receptors
outside target tissuemay mediate other effects of the drug “side effects”
receptor regulation
a cell can up or down regulate a population of receptors by changing the total number of receptors or their sensitivity
agonists drugs
bing to the receptor and produce a pharmacologic effect - activate after binding
If the best agonist produces 100% effect at lowest dose, why do we sometimes use weak agonists?
the doses of the weak agonists can be less dangerous because harder to reach toxic levels - can still reach 100% effect as well
antagonist
receptor blocker - blocks effects of receptor and other drugs
How do weak agonists work?
only fits one of two binding sites - either effector site or binding site 1. fits binding site, but effector site not well = weak agonist or 2. only binds effector site, not binding sit, binds only briefly
Best agonists intrinsic activity
only some receptors are occupied to get 100% effect
two agonists with different intrinsic activity but same affinity
have same affinity for receptors but different intrinsic activity - know they are binding the receptor in the same way because the have the same E50
two agonists with different intrinsic activity AND different affinity
different e50, different effect (one doesn’t reach Emax)
efficacy
the ability of the drug to activate the effector portion of the receptor once the drug is bound to the receptor. depends upon structure of drug
potency
relates to the amount of drug needed for effect. depends on receptor density, efficiency of stimulus-response mechanisms of the tissue
relative potency
horizontal relationship (both reach eMax)
relative efficacy
vertical relationship (one doesn’t reach eMax)
competitive antagonists
antagonist effect can be overcome by increasing the dose of the agonist (weak bond)
noncompetitive antagonists
can’t be overcome by increasing doses of agonist (strong bond) - can change effector site or binding site
