Pharmacology Exam 1 Lecture 1-3 Flashcards
What is the study of pharmacology
the study of drugs and their interactions with the human body
What does the topic of pharmacology embrace
it embraces the knowledge of the source, physical and chemical properties, compounding, physiological actions, absorption, fate and excretion, and therapeutic use of drugs
A drug is defined as what?
any chemical agent that affects living protoplasm
What is an adverse drug reaction?
-any response to a drug in which is harmful and unintended -occurs at doses used in man for prophylaxis, diagnosis or treatment -side effects, drug allergies and drug interactions
What are the four main processes of pharmacokinetics?
Absorption, distribution, metabolism(biotransformation), and elimination of drugs
Pharmacokinetics is defined as what?
the action of the body on the drug. It is the study of the fate of drugs on the body
Why is it important to understand and apply pharmacokinetic principles?
it can increase the probability of therapeutic success and reduce the occurrence of adverse drug effects in the body
What is the tool used to design optimally beneficial drug therapy regimens?
proper drug, route of administration and dosing schedules
absorption is defined as
movement of a drug from its site of administration into the central compartment and the extent to which this occurs
If you have a solid dose form of a drug what must happen before the drug can be absorbed
there must be dissolution of the tablet or capsule thus liberating the drug
What are clinicians more concerned with when it comes to ADME?
bioavailability rather than absorption
What must occur in order for a drug to be absorbed?
it must be lipid soluble in order to have site access
Absorption occurs by what mechanisms
Active or passive transport Ionized or non-ionized
What is active transport
against a concentration gradient and requires energy
what is passive transport
diffusion from higher to lower concentration
What is a site where there is a high probability for drug interactions
during movement through the GI tract
What is distribution
when a drug is transported to site where is reacts with various body tissues or receptors
After absorption or systemic administration where does a drug go
it is distributed into interstitial and intracellular fluids
What are the factors that affect distribution of a dug into tissue
Cardiac output, regional blood flow, capillary permeability and and tissue volume
What parts of the body would receive most of a drug
Initially Liver, Kidney, Brain and other well perfused organs
The second distribution phase is faster or slower?
slower
What parts of the body do the second distribution phase affect
it involves delivery to muscle, most viscera, skin and fat
Where does most of the drug get delivered from second phase distribution?
extravascularly
What are important factors that determine distribution
Lipid solubility Transmembrane pH gradients
What happens when a drug is bound to plasma proteins and tissue macromolecules?
it limits the concentration of free drug
Lipid soluble drug have a high affinity for what
adipose tissue
Why do drugs get stored in the adipose tissue
there is low blood flow there creating a drug resivoir
What are highly lipid soluble class of drugs
Barbiturates, Phenothiazines, Benzodiazepines
What is the function of metabolism
to convert active lipid soluble compounds and convert them to inactive water soluble substances to be excreted by the kidneys
Where are most drugs metabolized?
in the liver, but it can also happen in the kidneys, lungs and intestinal tract
What happens during Phase I of metabolism
Hepatic microsomal enzymes first oxidize, demethylate and hydrolyze drugs
During what phase of metabolism do more drug interactions happen?
Phase I hepatic enzymes
Where do drug with a short half life and inactive metabolites get metabolized
they are metabolized during phase I which causes them to be less effected by drug interactions
What happens during Phase II of the metabolism
large water soluble substances(glucuronic acid, sulfate) are attached to the drug.
How many times may drugs circulate thru the phases of metabolism
drug can circulate through one or both phases multiple times until the water soluble characteristic is present
What are the important hepatic microsomal enzymes of Phase I metabolism
CYP 450
What is the CYP classification for enzymes
CYP #X# #=family denoted by a number X=subfamily denoted by letter or arabic number X=individual gene denoted by a number
What are the CYP families primarily involved with drug metabolism?
CYP1,CYP2,CYP3,CYP4
How does enzyme inhibition effect the concentration of drugs?
It decreases the rate of metabolism of object drug by obstruction metabolizing enzymes. This leased to an increase in drug concentration
How would enzyme inhibition effect half life
it increases half life, which causes it to accumulate
What is the effect on the clearance of a drug when you induce an enzyme. What does this do to the concentration of the drug?
stimulates the increase in CYP 450 enzyme activity which increases the clearance of drug. This decreases the concentration of a drug
What is an example of a prototypical inducer
Phenobarbital it induces all enzymes
What is excretion/elimination?
process that removes the drug and its metabolites from the body
What are the primary ways drugs are excreted?
through the urine, feces, skin
How are drugs eliminated from the body?
they are eliminated either unchanged or converted to its metabolites
Excretory organs excluding the lungs eliminate what type of compounds more efficiently?
they eliminate polar compounds more efficiently that substances with high lipid solubility
What organ is the most important organ for excreting drugs and their metabolites?
the kidney
What happens to a drug when it is excreted through the feces?
substances are usually unabsorbed orally ingested drugs
how are unabsorbed drug metabolites excreted?
either in the bile or directly into the intestinal tract and not reabsorbed
why is excretion of drug through breast milk important?
because the excreted drugs are a potential source of unwanted pharmacological effects in a nursing infant
The lungs are important mainly for the excretion of what?
anesthetic gases
What are factors about a patient that can effect the basic pharmacokinetic principles
age, sex, weight, disease states and genetic factors
What is pharmacodynamics
action of the body on the drug
Pharmacodynamics is the study of what
biochemical and physiological effects of drugs and their mechanisms of action
What are the most common mechanism for drug interactions?
synergism, antagonism, altered cellular transport and effects on receptor sites
What is the benefit of understanding pharmacodynamics?
provides the basis for the rational therapeutic use of a drug and the design of a new superior therapeutic agents
What are the 4 most important parameters governing drug disposition are?
Bioavailability Volume of distribution Clearance Elimination
What is Bioavailability?
(F) The fractional extent to which a dose of drug reaches its site of action
What are factors that decrease bioavailability (F)
GI absorption 1st pass effect Metabolism (enzymes, active transport)
What is the route of administration based on
the understanding of the factors that decrease bio-availibility
What is volume of distribution?
it related the amount of drug in the body to the concentration (it doe not necessarily refer to an identifiable physiological volume but rather to the fluid volume that would be required to contain all of the drug in the body at the same concentration measured in the blood or plasma
What is half-life (t1/2)
the time is takes for the plasma concentration to be reduced by 50%
How many half life’s does it take to get to a steady state?
5
What does half life reflect in systemic concentration
reflects the decline of a systemic drug during a dosing interval at steady state
Steady state is defined as
rate in = rate out
In steady state the amount of drug in a given period is equal to what?
it is equal to the amount eliminated in that same period
What is a drug interaction?
pharmacological result whether it is desired or undesired the effect of one drug is changed by another drug
What are the classification of DI
Pharmacokinetic Pharmacodynamic
What types of DI are there
Drug-Drug Drug-Food Drug-Disease
What is a Pharmacokinetic DI
occurs when ADME of one drug is affected by another drug/agent
What way does absorption effect drug interaction
through GI, pH, Binding, Increase or decrease in motility and changes in GI flora
How does distribution affect drug interactions
drugs can interact with plasma proteins which can cause the drug to be bound vs unbound (free drug)
What are factors that effect the elimination of drugs
Urinary pH and competition examples when you give a person probenecid and penicillin probenecid competes for excretion and thus the concentration of Penicillin in the body increases
What is synergism/potentiation
they are additive effects between two or more drugs that result in a pharmacologic response that is greater than the sum of the individual responses to each drug ex: beer+valium these two combined have higher than expected effects
Antagonistic
are opposing effects. smaller effect than individual agents Ex: tenormin+sudafed
what is a receptor
a molecule to which a drug bonds to bring about a change in function of the biologic system
receptor site
specific region of the receptor molecule to which the drug binds
What is an inert binding molecule or site
a molecule to which a drug may bind without changing any function
spare receptor
does not bind drug when the drug concentration is sufficient to produce maxima effect
Kd>EC50
this is present when there is spare receptor
effector
component that accomplishes the biologic effect after the receptor is activated by an agonist
efficacy, maximal efficacy Emax
the maximum effect that can be achieved with a particular drug regardless of does
potency
the amount of drug needed to produce a given effect, determined mainly by the affinity of the receptor for the drug and number of receptors available
What is a graded does curve
a graph of increasing response to increasing drug concentration or dose
what is a quantal dose-response curve
a graph of the fraction of a population that shows a specified response at progressively increasing doses
EC50
the concentration that causes 50% of the maximum effect or toxicity
ED50
the dose that causes 50% of maximum effect or toxicity
TD50 (TC50)
the median toxic dose or concetration at which toxicity occurs in 50% of cases
LD50 (LC50)
the median lethal dose or concentration required to kill hald the members of a tested population after a specified test duration
Kd
the concentration of a drug that binds 50% of the receptors in the system
Bmax
maximal number of receptors bound
agonist
a drug that activates its receptor upon binding
partial agonist
a drug that binds to its receptor but produces a smaller effect at full dosase than a full agonist
Allosteric agonist
a drug that binds to a receptor molecule without interfering with normal agonist binding but alters the response to normal agonist
antagonist
pharmacologic antagonist that binds without activating its receptor and thereby prevents activation by agonist
competitive antagonist
a pharmacologic antagonist that can be overcome by increasing the concentration of agonist
Irreversible antagonist
a pharmacologic antagonist that cannot be overcome by increasing agonist concentration
Physiologic antagonist
a drug that counter effects of another by binding to a different receptor and causing opposing effects
chemical antagonist
a drug that counters effect of another by binding the agonist drug not the receptor
Allosteric antagonist
a drugthat binds to a receptos molecule without interfering with normal antagonist binding but alters the response to the normal antagonist
What is transmembrane diffiusion
a type of signaling mechanism when a a drug diffuese across a membrane and binds to intracellular receptor
what is a transmembrane enzyme receptor
a receptor that is imbedded in the membrane where the outer domain provides the receptor function and inner domain provides the effector mechanism converting A to B
What are ligand transmembrane receptors
receptors that spans through the cells membrane and after the outer receptor is activated by the appropriate ligand activating separate cytoplasmic tyrosine kinase molecule (JAKs) that phosphorylate STAT molecules
What are transmembrane channels
are gated channels that are opend or close by binding of a drug to the receptor site
What is a g protein coupled receptor
its a receptor that uses a coupling protein to activate a separate effector molecule
What types of drugs are able to reach intracellular receptors
more lipid soluble or diffusable agents
How do drugs effect intracellular receptors
they may cross the membrance and combine with an intracellular receptor that affects an intracellular effector molecule
Are the receptor and effector are the same in the cell
NO, they may or may not be the same
what type of transmembranse signaling do intracellular receptors need to activate them
there isnt a specialized transmembrane signaling device because the drugs that act on them pass through the membrane
How do receptors located on membrane spanning enzymes function
drugs that affect them combine with a receptor site on the extracellular portion of the molecule and modify its intracellular activity
what type of drug activates extracellualr receptor site
cytokine
how do receptors located on membrane ion channels work
they bind to the receptor on the channel which causes the channel to open
how do channel molecules act
they act as both a receptor and effector which will cause a change in transmembrane electrical potential
How do receptors linked to G protein work
drug binds to receptors that are linked by coupling proteins to intracellular or membrane bound effectors
when a G-coupled receptors bind agonist, the G protein is activated
How are receptors regulated
by number, location and sensitivity
how long can changes in receptor regulation occur
changes can occur over short period of time (minutes) or long periods (days)
What is tachypylaxis
an acute decrease in the response to a drug after administration
What does a frequent or continious exposure to agonist affect result in
short term reduction of receptor response
what are the mechanism that can result in short term reduction of receptor response
The G proteins can be blocked which stops receptor activation and sensitization.
Agonist receptor complexes may be internalized which will remove them from further activation by agonist.
constant activation of the receptor effector could deplete the substrates needed to cause the effect.
what is receptor down regulation
long term reduction in receptor number which occurs in response to continuous exposure to agonist
what is receptor upregulation
it increases receptor number which occurs when receptor activation is blocked for long periods of time by pharacologic antagonists or denervation
kinetic interaction
changes in effect are the result in the relationship between dose and the concentration. the pharmacologic effect has changed as a result in a change in drug concentration
dynamic interaction
changes in effect are the result of changes in the relationship between the drug concentration and the effect.
the pharmacologic effect had changed despite a lack of change in the drug concentration
What is Bioavailability
measure of the amount of drug that reaches systemic circulation.
measure of systemic drug exposure
how is bio-availability measured
it is measured by making a graph of serum concentration vs. time where the area under the curve is the bioavailability.
the pharmacokinetic parameter which quantifies drug exposure
how is bioavailibility expressed
as a percentage or fraction of the drug administered which reaches systemic circulation
what are the factors that affect bioavailability of a drug through oral administration
absorption characteristics of the drug and dose form
amount of metabolism that occurs prior to drug reaching systemic circulation
where can metabolism occur before it reaches systemic circulation
intestinal wall
liver
presence of interacting substrates
drugs, food no food
what is absolute bioavailability
is the term that describes the situation when one of the areas under the curve being compared is in a dose from with which there is and “absolute” (100%) absorption (IV doseage)
relative availablility
is comparing the area under the curve from one dose form to another.
it answers the question of how the two dose forms compare in terms of the relative amount of drug that reaches systemic circulation
Neither drug form was administered IV
What are salt form differences
dosing conversion (from on preparation to another) must account for differences in the extent of the absorption and the amount of drug contained in that formulation
Cpmax
maximum concentration
what does it mean if the concentration of an administered drug is high in relation to volume of distribution
the volume of distribution is low
If an administered drug has a low concentration. what does that mean in terms of volume of distribution
the volume the drug appears to occupy is very large
what does Cpmax= dose/vd
apparent volume of distribution
what does understanding the physiologic volumes help us understand
tells us where the majority of the drug resides in the body
what factors affect a drugs volume of distribution?
degree of lipid solubility
degree of protein binding
extent of tissue binding
How would a drug with a high Vd look with lipid solubility, protein binding, tissue binding
higher lipid solubility
lower protein binding
greater tissue binding
having knowledge of a drugs volume of distribution can assist us with what
determining drug doses and provide clinicians with a sense of the extent of a drug distribution into the spaces/areas. compartments of the body
how can Vd be used to dertermine a drugs loading dose?
if you know the Vd of a drug you can calculate the dose required to achieve maximum concentration
what is the extent of distribution
it is a function of drug characteristics and patient characteristics
What factors will increase volume of distribution
durgs with higher lipid solubility
lower protein binding
greater tissue binding
what are the two ways that drugs are eliminated from the body?
biotransformation
excretion
what is biotransformation
drug is chemically altered to for a metabolite that is more excretable than parent
what is excretion
removal of a drug or metabolite from the body via an organ
what is a prodrug
is when a parent drug has no activity and the metabolite does
what enterohepatic circulation
a metabolite may be excreted into the small intestine via bile and then can get reabsorbed and re-enter systemic circulation
what is the most common phase I reaction
oxidation
what are the two parameters determing elimination rate
clearance
elimination half life
what is clearance
the volume of blood that is cleared of drug per time
what is elimination half life
the time it takes for the concentration of drug to reduce by one hald
what is the relationship between dose-serum concentration
there is a direct proportion between elimination rate to serum concentration. reffered to as a 1st order elimination
so as the elimination rate of a drug increase so does the serum drug cocentration
what is the realtionship for serum-dose concentration for oral drugs
they are not proportional because the % absorbed may decline with higher doese
what is zero order elimination
it is when elimination is independent of dose
what factors can affect steady state
anything that effects the input or output
at steady state what is the relationship between the rate of the drug going into a patient and the rate leaving a patient at steady state
rate going in= rate going out
the amount of drug eliminated over the dosing interval=the dose administered
at steady state what is happening with regard to drug accumulation during steady state
the drug has reached equilibrium
what determine how long it will take for a drug regimen to reach steady state?
dependent on its half life
