Basic Principles I and II Flashcards
types of receptors
membrane bound, enzymes, structural macromolecules, intracellular macromolecules, and cell membrane itself
reversible drug-receptor bonds
ionic, van der waals, and hydrogen bonds
irreversible drug-receptor bonds
covalent bonds
receptor amplification and transduction
fractions of seconds of drug-receptor interaction activate G protein activity that lasts for seconds
what do G proteins regulate activity of?
distinct effector proteins in the cell. Act as switches that are turned on by the receptor and turn themselves off a few seconds later.
second messenger
produce amplification of the drug receptor interaction. Converts an event that happens outside the cell into a change that happens inside the cell. Some second messengers can cause different effects in different tissues
structure-activity relationships
the structure of a drug determines how it will fit into the receptor. The better the ffit, the better the stimulation. Sublte changes in structure amongst a class of drugs can greatly influence the drug’s effects
dose-response relationships
how to measure and compare drug effects for given doses
michaelis menten equation for drugs
Effect = Emax[D]/Kd + [D] Kd is dissociation constant, or the EC 50
threshold
beginning of the curve. Dose of agonist at which a response begins
slope
rate of rise of the response on the steep portion of the curve. Log of EC50 also relates to affinity
maximal asymptote
top of curve. Represents E max for that particular agonist
receptor occupancy
intensity of response is proportional to the fraction of receptors occupied
intrinsic activity
ability to stimulate the receptor once bound. Relates to structure and influences efficacy and potency
spare receptors
not all receptors need to be occupied in order to achieve Emax. Less efficacious agonists may need to occupy more receptors that highly efficacious agonists
secondary receptors
outside of the target tissue, may 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
agonist drugs
bind to receptor and produce a pharmacologic effect. They bind to the receptor and activate the receptor after binding. Better fit to the receptor from more specific structure of the molecule results in more [DR] and an effect at lower doses
efficacy
ability of the drug to activate the effector portion of the receptor once the drug is bound to the receptor
potency
relates to the amount of drug that is needed for an effect
antagonist drugs
block the binding of agonists and prevent the pharmacologic response
competitive antagonist
can be overcome by increasing the dose of the agonist
simple competitive antagonism
binding of antagonist to receptor is a weak bond and is easily reversed
noncompetitive antagonism
receptors remain occupied by antagonist and not enough DR interactions occur to achieve E max. Strong bond
pharmacokinetics
time course of drug absorption, actions, and elimination
pharmacodynamics
types of drug actions, physiochemical and receptor interactions
3 steps to making a drug
- define physiology of the target tissue
- create drugs that mimic endogenous agonists
- test drugs in the target tissue
selectivity
property of drug to cause a specific effect, however, few drugs only cause one effect
