Lab 8 Flashcards
drug-receptor interactions occur via which bonds
ionic
hydrogen
van der Waals
covalent
drugs with a ____ duration of action generally have WEAKER bonds
short
what kind of drug-receptor interactions may have stronger bonds?
long duration or irreversible interactions (such as covalent)
define drug receptors
generally proteins that bind endogenous molecules to elicit physiological effects
define an agonist
a chemical that activates a receptor to produce a biological response
define a full agonist
activates a receptor with the maximum response that an agonist can elicit at the receptor
define a partial agonist
binds and activates a given receptor, but only has PARTIAL EFFICACY at the receptor (relative to a full agonist)
EVEN AT MAXIMAL RECEPTOR OCCUPANCY
define an inverse agonist
binds to a receptor and produces the opposite of its normal response (agonist response)
define an antagonist
blocks or dampens a biological response by binding to and blocking a receptor
pharmacodynamics relates to what properties of the drug?
pharmacokinetics relates to what properties of a drug?
pharmacodynamics relates to drug EFFECT and CONCENTRATION
pharmacokinetics is related to concentration and time
TOGETHER, pharmaodynamics and pharmacokinetics provides…..
the relationship of a drug’s effects over time
called the TIME COURSE OF EFFECT
“Time course of drug action” is a function of…..
drug absorption, distribution, metabolism, excretion (pharmacokinetics)
the INTENSITY of a response elicited by a drug is a function of…
the dose administered and the concentration of the drug at the site where the action-effect sequence is initiated
the proportion of the dose that actually contributes to the concentration at the site of action is the NET RESULT OF THE RATE AND EXTENT OF—–
absorption - distribution - metabolism - excretion
define absorption
the rate at which a drug leaves its site of administration and becomes BIOAVAILABLE
name 5 factors that affect transport across membranes and influence absorption
-solubility
-concentration
-circulation to the site of -absorption
-surface area of absorption
-route of administration
binding to plasma proteins will _____ the rate of passive absorption.
how?
increase
by maintaining the concentration gradient of free drugs
after a drug is absorbed or injected into the bloodstream, what may happen
may be distributed into interstitial and cellular fluids
what organs receive most of the drug during the first few minutes after absorption?
heart
liver
kidney
brain
other well-perfused organs
deliver (distribution) to what parts of the body is slower?
to muscle and most other viscera
skin
fat
may require several minutes to several hours before a steady state is attained
binding to plasma proteins will _____ the distribution of drugs to other tissues
decrease
binding to plasma proteins will _______ the rate of metabolism
decrease
usually, the body transforms drugs into what kind of compounds?
does the opposite ever occur?
usually - more polar hydrophilic inactive compounds for elimination
SOMETIMES – the opposite occurs and metabolism activates a drug
what is the primary organ where most biotransformation/metabolism reactions take place?
explain the mechanism
liver
phase 1 and phase 2
explain phase 1 metabolism reactions
give an example
biotransformation generally results in the loss of pharmaceutical activity by the ADDITION OF A FUNCTIONAL GROUP
cyt-p450 oxidizes up to 80% of all drugs
explain phase 2 metabolism reactions
biotransformation is the CONJUGATION of the parent compound/phase 1 metabolite to glutathione, amino acid, sulfate, and glucuronic acid
generally results in the complete inactivation of the drug
how can drugs be excreted?
excreted from the body either unchanged or as metabolites
what is the most important organ for the excretion of water-soluble drugs and metabolites
kidney
renal excretion of drugs is dependent on several factors:
name 4
-protein binding
-GFR (glomerular filtration rate)
-tubular secretion and reabsorption
-blood flow
oral drugs that are not absorbed by the GI tract are excreted where
in the feces
some drugs and their metabolites are excreted where?
in the bile
this is the case for drugs absorbed in the GI
what 4 things are time course relationships?
latency
time of onset
time of peak effect
duration of action
what 4 things are dose-response relationships?
affinity
potency
efficacy
dose-response curve
define latency
the time between the administration and the first measurable signs of a response
define time of onset
the time of the first measurable response
define time of peak effect
peak effect usually occurs when the drug concentration at the site of action has reached its maximal level
define the duration of action
from the time of onset to the time when the response is no longer perceptible.(OFFSET)
duration of action depends on what 2 things
the dose
the rate of drug removal from the site of action
what is offset
the time when the response is no longer perceptible
define the dose response curve
analyzes the magnitude of a drug effect by plotting the magnitude of the response as a function of dose of the drug
the MAXIMUM EFFECT is when….
the dose response curve reaches a plateau
define affinity
the ability of a given drug to bind with a specific receptor
define potency
the dose needed to produce a response of a given intensity
a shift to the right in the dose response curve means a _______ in potency, while a shift to the left indicates a ____ in potency
to the right = decrease in potency
to the left = increase in potency
define efficacy
the ability of the drug to produce the desired response/effect upon binding to the receptor
efficacy describes the…….
maximal response that can be created by the drug
explain ED50
50% effective dose
the dose of a drug that produces an effect in 50% of the population (quantal)
graded - the dose that causes 50% of maximal effect
ED50 is a convenient way to do what
characterize a drugs and a useful way to compare DRUG POTENCY
what is LD50
the dose that kills 50% of an exposed population
what is therapeutic index
a measure of the drug’s safety
= LD50/ED50
higher value = safer drug
barbiturates bind to what?
this increases what?
what is the result?
barbiturates bind to GABA A receptors
this increases GABA-induced chloride currents
results in CNS depressant effects
barbiturates are used as what kind of drugs
sedatives
hypnotics
anesthetics
anticonvulsants
how are barbiturates classified?
on the basis of their duratiokn of actions
ultra short
short
intermediate
long acting
barbiturates are schedule —– depressants under what act?
schedule II, III, and IV
DEA Controlled Substances Act
explain the duration of all of the classes of barbiturates and give an example of each
Long acting - over 6 hours - PHENOBARBITAL
Intermediate acting - 3-6 hours - AMOBARBITAL
Short acting - under 3 hours - PENTOBARBITAL
ultra short acting (30 mins) - THIOPENTAL
the onset and duration of a drug are dependent on what?
ADME
the onset of thiopental CNS effects is equal to what
the time required to reach the CNS after IV injection
how does thiopental have such a short duration of action
thiopental is highly lipophilic and the brain is highly perfused and lipophilic.
thus, thiopental rapidly reaches effective blood levels.
HOWEVER, due to its high lipophilicity it also rapidly re-distributes into adipose and other tissues, so the blood levels decrease rapidly to subtherapeutic levels.
as a result, its duration of action is ULTRA SHORT
explain how phenoparbital and pentobarbital have a longer duration of action than thiopental
they are less lipophilic and thus cross the brain barrier less rapidly, and at the same time the drug is being distributed to other tissues
takes longer to reach effective CNS levels
