Term
| drug receptors properties |
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Definition
the interface for the actions of most drugs- usually a MEMBRANE BOUND MOIETY
receptors provide selectivity for drugs action |
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Term
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Definition
| provides the basis for why they do what they do and act where they act |
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Term
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Definition
| a definite physical interactions |
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Term
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Definition
| the typical situation where the two elements are held together through a combination of weak bonds (ionic, hydrophoic, van der waals) |
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Term
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Definition
rare to see this- covalent bonds
ex: nitrous oxide and aspirin- these will block a particular enzyme and your body has to make more |
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Term
Drug Properties (2)
and relationship between these two properties |
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Definition
1) typically ionizes at the pH of biological fluids- either a weak acid or a weak base
2)has a relative solubility preference for water or lipid which depends on the degree of ionization in the body compartments
the greater the percent of ionization the great the water solubility
not ALL drugs are ionized, but most are |
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Term
complementary binding
3 importand factors of it |
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Definition
the ability of drug to recognize its specific receptor. "lock and key"
1) postive and negative charge alignment
ex: weak acid on a protein
2)steric factors- size and shape
3)probabilty-random motion- this is the reason you use massive amounts of the drug |
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Term
structure-activity relationships
example of this? |
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Definition
change the molecular structure of the drugs increases or decreases the biological activity of the drug by changing its affinity to the receptor. This is a big division of pharmceutical chemistry
ex: |
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Term
theories of drug action
action vs effect |
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Definition
action: biological changes initiated by drug/receptor binding
effect: the measurable endpoint of these changes |
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Term
| occupation theory of drug action |
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Definition
| the magnitude of a drug effect is directly proportional to the number of receptors occupied |
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Term
perturbation theory of drug action
example |
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Definition
when a drug binds to a protein receptor it changes the protein conformation (TERTIARY) by negating charges. Alteration in microenvironment surrounding the receptor that initiates chain of events in the cell. If enough receptors are occupied the sume of these changes ultimately leads to tissue changes and monitorable physiological effects.
ex: change in permeability- leads to ca++ influx- leads to muscle contraction |
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Term
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Definition
| the ability of a drug to produce a specified effect- sometimes referred to as INTRINSIC ACTIVITY |
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Term
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Definition
| a drug that can produce the monitored effect ie is HAS efficacy. frame of reference is important here- an agonist in one situation may not be in another situation |
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Term
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Definition
| does NOT have efficacy and CAN inhibit the actions of a known agonist |
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Term
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Definition
has efficacy but cannot produce the maximal effect of an agonist
ex. analgesics |
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Term
| true or false- one drug to one receptor? |
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Definition
| false- drugs often show degrees of selectivity over a range of receptors |
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Term
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Definition
these show the lowest order of selectivity, simply bind many unrelated drugs usually on the basis of ionic attractions
ex. plasma proteins bind acids AND bases, throw a drug in a system and it invariably binds to plasma proteins |
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Term
| there are drugs with no receptors: true or false? |
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Definition
| true- but not many in dentistry |
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Term
| What is the major factor under a dentist's control that can effect the magnitude of a drugs response? |
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Definition
| concentration of drug at the site of action |
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Term
| the magnitude of a drug's response is directly related to what? |
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Definition
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Term
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Definition
| the maximum effect acheivable by the agonist under the immediate circumstances - helps determined the magnitude of a drug response |
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Term
responsiveness of target tissue
ex |
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Definition
the ability of a tissue to response- can be affected by disease, physiological conditions
ex:atropine on a heart affects in differently if the heart is under parasympathetic or sympathetic control |
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Term
| what are the four things that determined the magnitude of a drug's response? |
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Definition
| conc of a drugs at site of action, efficacy of the drug, responsiveness of target tissue, and opposing reflex actions |
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Term
opposing reflex actions
equation?
ex. |
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Definition
ie. homeostasis. the body's compensatory reflex mechanisms will always oppose change produced by drug action
NET EFFECT = GROSS EFFECT - REFLEX EFFECTS
older patients have lower reflex effects so a drug will affect them more greatly |
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Term
| What are the three types of responses you can have to a drug? |
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Definition
1) therapeutic response
2) side effects
3) placebo effect |
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Term
| therapeutic response and 3 characteristics |
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Definition
the rationale for giving the drug in the first place- the desired effect
1) effect us dose related
2) results from drug-receptor interaction in almost all instances for dental drugs
3) occurs in every patient if you give enough of the drug (can be fleeting or obscure) |
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Term
| true or false? a drug can have one effect |
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Definition
| NO DRUG HAS JUST ONE EFFECT |
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Term
| what are the two theories of drugs action? |
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Definition
| occupation theory and perturbation theory |
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Term
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Definition
1) beneficial side effects- icing on the cake
2)adverse side effects- toxic, harmful- dose related response
risk: is the benefit of taking the drug worth the risk of adverse side effects? |
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Term
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Definition
| physiological or psychological effects from the anticipation of beneficial effects of drug taking. significant and valuable |
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Term
| how is the effect measured on a graded dose response curve? |
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Definition
| represented on the y axis- measured in discreet units- mmHg, grams tension etc |
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Term
| is a graded dose response curve measured in one subject or the average of a number of subjects? |
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Definition
| normally an average of responses from a number of subjects |
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Term
| how is the dose measured in a dose response curve? what shape does it make the graph? |
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Definition
| on the x axis in log units- takes on a sigmoidal shape |
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Term
| what is the threshold represent in a graded dose response curve? |
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Definition
| the first measured response |
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Term
| what is affinity? what does it mainly depend on? |
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Definition
| the force of attraction between the drug and the receptor- depends on the SHAPE of the drug and the receptor |
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Term
| what is potency? and where is it measured on a dose response curve? |
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Definition
| measure of how much drug is needed to produce a particular effect- typically measured at the threshold or the midpoint- NOT THE MAXIMAL EFFECT achievable by the drug |
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Term
| if potency is related to the threshhold and midpoint of a dose response curve what part of the graph is related to efficacy |
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Definition
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Term
| true or false? high affinity translates into high efficacy? |
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Definition
| false- the drug could be an antagonist |
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Term
| if you have two identical graphs, just moved along the x axis- what is the same about these two graphs and what is diff? |
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Definition
| same efficacy, diff potency |
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Term
| in a quantal dose response curve how is the effect measured? |
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Definition
| all or none- arbitrary end point chosen. ex: numb or not, dead or not |
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Term
| what are the x axis and y axis in a quantal dose response curve? |
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Definition
x axis- log dose
y axis- percent of test population responding |
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Term
| what is ED50 and what type of graph can you get it from? |
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Definition
ED50- dose which produces desired effect in 50% of the population
measured in a quantal dose response curve |
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Term
| what is LD50 and what graph is it determined from? |
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Definition
| the dose that produces death in 50% of the population- measured in quantal dose response curve |
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Term
| what is a TD50 and what kind of graph is it measured in? |
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Definition
| does which produces a toxic effect in 50% of the population- measured in a quantal dose response curve |
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Term
| what is the equation for therapeutic index and what does it mean? |
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Definition
| LD50/ED50- a quick, crude indicator of relative safety of drug. the LARGER the TI the SAFER the drug |
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Term
| what is an NTI and what are they used for? |
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Definition
| NTI- Narrow Therapeutic Index- bellweather drugs for assessing interaction potential of new drugs (?) |
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Term
| what represents the point of LEAST variability on a quantal dose response curve? |
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Definition
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Term
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Definition
| the difference in dose units between the ED99 and TD1 generates the margin of safety. |
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Term
| true or false- every drug just has one quantal dose response curve |
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Definition
| FALSE- every drug has at least two quantal dose response curves- one for the therapeutic effect and one for toxic effect(s) |
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Term
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Definition
the ultimate margin of safety- LD1-ED99
if the toxic effect you are comparing is death |
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Term
| what is often the basis for clinical problems? |
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Definition
| variability of population response |
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Term
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Definition
| sum of all intangibles that influence an individuals response to a drug. Sometimes referred to as innate variability because it is not well understood and thus unpredictable. Even cloned animals have it!! |
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Term
| the population sensitivity to a drug is distributed how? |
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Definition
| NORMALLY- ie takes on a bell curve. this means there are 5% HYPORESPONDERS and 5% HYPERRESPONDERS. drug companies compound their drugs to serve 90% of patients in the middle |
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Term
| what is the percent change a patient will not response normally? |
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Definition
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Term
Identifiable sources of variation
examples |
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Definition
allows clinician to adjust drugs to patient
body weight, age, tolerance, drug interactions |
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Term
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Definition
caution- risk may be outweighed by benefit
contraindication- risk definitely outweighs benefit!! do NOT use!! |
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Term
| antagonism of an effect-what is it and what are the 4 types of antagonism? |
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Definition
the effects of one drug inhibit the effects of a second drug-
1)chemical antagonism
2)biochemical antagonism
3)physiological antagonism
4)pharmacological antagonism |
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Term
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Definition
an agonist's physical or chemical properties are altered by the presence of an antagonist
ex:tetracycline precipitation by ca++ in stomach |
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Term
biochemical antagonism
ex. |
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Definition
the actions of one drug increases the metabolism or excretion of a second drug
ex. bc pill |
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Term
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Definition
two drugs acting on different sets of receptor produce opposing effects
ex. drug A increases blood pressure
drug B drops it- tug of war |
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Term
| pharmacological antagonism |
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Definition
| both agonist and antagonist have affinity for same receptors- both have affinity but only one displays efficacy |
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Term
competitive antagonism
and what does it do to the dose response curve? |
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Definition
-antagonism and agonist are competing for the same receptor site- binding is REVERSIBLE
dose response curve shifts to the RIGHT
agonist has less potency, not efficacy.
same slope and maximum |
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Term
| can you overcome competitive antagonism? |
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Definition
| yes- since binding is weak for both agonist and antagonish- so when 1 falls off the other goes on.it just takes more of the drug to see threshold effect |
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Term
| noncompetitive antagonism - 2 instances |
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Definition
more rare: agonist and antagonist either
1) bind to the same receptor but the antagonist binds irreversably
2) the antagonist binds toa different site which alters access of the agonist to the receptor |
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Term
| what are the three types of augmentation effects? |
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Definition
1) additive effects
2) potentiation
3) synergism |
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Term
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Definition
| the combined effect of two or more drugs acting simultaneously is equal to the sum of the expected individual effects |
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Term
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Definition
a situation when the effects (usually toxic effects) of an agonist are enhanced by the PRESENCE of an antagonist agent
ex: drug A blocks elmination of drug B so you see an increase in drug B |
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Term
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Definition
a situation where two agonists when coadministered produce an effect greater than the sum of their individual effects
ex: alcohol and sedatives |
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Term
| onset time and what it depends on |
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Definition
| delay between administration of drug and first observable effects- dependent largely on the route of administration |
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Term
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Definition
| delay between administration of the drug and the time of greatest effect. an increase in dose can cause a slight decrease in this parameter |
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Term
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Definition
| timed from point where effect is first seen until effect can no longer be measured. this is the parameter most affected by a change in dose |
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Term
| true or false- you can get maximal effect with the usual therapeutic doses? |
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Definition
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Term
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Definition
| the study of how drugs move in the body- includes considerations of absorption, distributions, biotransformation (metabolism), and excretion |
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Term
| what two things determine the route of administration to be used? |
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Definition
therapeutic characteristics
drug characteristics |
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Term
| therapeutic characteristics that determine route of administration |
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Definition
| various patient specific considerations will impact the final decision - location where drug is needed - the convenience of use -the likelihood of compliance - the severity of situation |
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Term
| drug characteristics that determined route of administration |
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Definition
| the physical characteristics of the drug may dictate that it not be administered by a particular route. for example- the drug may be destroyed by stomach acid or might cause tissue damage if injected into muscle etc |
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Term
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Definition
| all routes where drug is ultimately absorbed from some part of gastrointestinal system |
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Term
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Definition
| all routes other than enteral ei. when a drug is given outside the GI tract |
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Term
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Definition
| this term refers to the movement of drug from the site of administration into the blood |
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Term
| passive processes. and how common is this method or drug absorption? |
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Definition
| passive diffusion- through lipid and water barriers until drug is in blood. most common mechanism |
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Term
| in what two forms do drugs exist in the body? |
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Definition
| in ionized and nonionized forms |
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Term
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Definition
| since most drug absorption occurs through passive diffusion, you can increase the amount of drug passing into the blood over a given time by simply increasing the number of molecules at the site of administration ie increasing the conc. gradient. |
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Term
| in what form do drugs typically move through cell membranes? |
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Definition
| lipid soluble or nonionized forms |
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Term
| what are the three passive processes that a ionized drug can use to get through a membrane? which process is saturable? |
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Definition
1) through aqueous pores in cells
2) through gaps between cells- requires a molecular weight of less than 200 gm
3)facilitated diffusion- charged drug binds to a carrier protein which causes a conformational change that pulls the binding site inside the cell where the drug falls off. this process is saturable and can reach a maximum rate |
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Term
| what are two characteristics of active processes |
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Definition
1) movement of drugs occurs against a concentration gradient
2) to do this breaking of high energy bonds is necessary |
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Term
| biological factors that affect absorption rate |
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Definition
1)circulation - the greater the amt of vasculature around the site the greater the likelihood the drug will finds its way into the bloodstream
2) SA the greater the contact area of the drug the greater the probability it will move into the blood ex- lungs and intestinal villi |
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Term
| distribution of drugs relies on three factors- |
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Definition
1) binding
2) compartamental pH
3)biotransformation |
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Term
| how binding affects distribution to body tissues |
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Definition
| drugs vary in binding to various proteins in blood- binding is an ionic interaction between the charged form of the drug and opposite charges on the proteins. competition between drugs for binding to plasma or tissue binding sites can lead to adverse drug interactions by cuasing an increase in free drug concentrations |
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Term
| true or false- bound drugs can pass through membranes to move towards receptors |
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Definition
| FALSE- only free drugs can pass through on their membrane gradient |
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Term
| weak acids bind to what plasma proteins and weak bases bind to what |
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Definition
weak acids- albumin
weak bases- Alpha-1 glycoprotein |
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Term
| compartamental pH or ion trapping |
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Definition
| if the predominant form of a drug is the ionized form- then it will have difficulty passing membranes to move out of the compartment it is in. the predominant form depends on pKa of drug and pH of the fluid |
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Term
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Definition
| altering the molecular structure of a parent drug usually by enzymatic actions that add moieties or cleave sections |
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Term
| true or false- drugs have specific enzymes for biotransormation |
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Definition
| false- the enzymes for biotransformation are general and may act on many diff drugs |
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Term
| where are the most important biotransformation enzymes found? |
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Definition
| the smooth endoplasmic reticulum of the liver - although it can also occur in liver, kidney, and intestine. ex. grapefruit blocks the metabolic enzymes of statin in GI and you can overdose |
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Term
| where are the most important biotransformation enzymes found? |
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Definition
| the smooth endoplasmic reticulum of the liver - although it can also occur in liver, kidney, and intestine. ex. grapefruit blocks the metabolic enzymes of statin in GI and you can overdose |
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Term
| what are the two main pharmacological significances of biotransformation? |
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Definition
1)change in pharmacological activity
2)changes in elimination rates |
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Term
| how does change in pharmacological activity affect drug binding? |
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Definition
| the change in molecular structure will influence the drug's complementary binding to its receptors and thus alter the drug's effects |
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Term
| what are the 2 outcomes of change in a drug's complementary binding? |
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Definition
inactivation of the drug (termination of drug response)
inactive drug is activated and where the activity of the drug is diminished but not obliterated |
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Term
| changes in elimination rate |
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Definition
| most biotransformation processes render the resulting molecule more polar which makes it more water soluble. this can be considered the goal of biotransformation because- Water soluble compounds are excreted more readily by the kidneys |
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Term
| what are the two general types of transformation |
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Definition
1) nonsynthetic reactions
2) synthetic reactions |
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Term
| non synthetic reactions- what are they referred to as and why and what are the three types of non synthetic reactions |
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Definition
referred to as phase I reactions because they often occur first and produce changes in molecular structures that facilitate phase II rxns.
1) oxidation
2) reduction
3) hydrolysis |
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Term
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Definition
| most common fate of drugs- this process utilizes molecular oxygen and the mixed function oxidase system (cytochrome p450 system) and requires NADPH |
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Term
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Definition
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Term
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Definition
| includes cleaving of the molecule |
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Term
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Definition
| almost always lead to inactivation of the drug because make dramatic changes to the parent compound by adding organic groups- eg. glucuronic acid (causes steric problems), glycine |
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Term
| altering biotransformation rate |
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Definition
| responses to drugs are frequently influenced by changes in biotransformation caused by disease and drugs |
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Term
| induction of drug metabolizing system |
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Definition
| physiological process where there is an actual increase in the number of biotransformation enzymes in the liver and elsewhere |
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Term
| 2 pharmacological significances of induction |
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Definition
1) drugs can induce enzymes involved in their own metabolism which leads to tolerance
2)drugs can induce enzymes involved in the metabolism of other drugs which leads to biochemical antagonism |
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Term
| interference with biotransformation can cause increases in drug activity and what 3 things can cause this interference with biotransformation |
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Definition
1) liver damage or decreased blood flow to the liver which can limit ability of hepatocytes
2)two drugs competing as substrates for the same enzymes will usually decrease the metabolic rate of each durg and cause a rise in blood levels of both agents causing synergism or potentiation
3)one drug may simply inhibit the catalytic activity of an enzyme that is the major path of biotransformation of a second drug causing synergism or potentiation also |
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Term
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Definition
| elimination of a parent durg and its metabolites is the ultimate way of terminating drug activity- some actions will inger after the drug is no longer detectible |
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Term
| renal excretion- 4 basic physiological processes |
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Definition
renal excretion is the major route of drug excretion
1) glomerular filtration- movement of drug with water through gaps in capillary cells into the tubules- this depends on blood flow through bowman's capsule (proportional to cardiac output) AND degree of drug binding to plasma proteins
2)passive diffusion- uncharged form of drug can move down conc. gradient into tubules. toward tubule in prox region, away from tubule in distal region
3)active secretion and reabsorption- utilization of high energy bonds to move drugs against conc. gradient- susceptible to saturation and competition (ex- gout - uric acid will compete with iv prophin for carriers)
4)ion trapping- a drug is trapped in its ionized form- determined by acid/base characteristics of drug and pH of uring |
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Term
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Definition
| an acid in an acid crosses- a weak acid in a weak environment will remain in its noncharged form and be able to cross back into the body |
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Term
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Definition
process whereby lipid soluble drugs that are very slowly metabolized are recycled a number of times throug the gi system- show long duration of action and excreted thru feces
1) drug absorbed from GI tract and travels via the portal blood system to the liver
2)small amt in liver metabolized but since the drug is very lipid soluble some enters systemic circulation and some goes into the bile
3) the drug in the bile in dumped into the small intesting through oddi and reabsorbed to start all over again |
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Term
| other routes of excretion besides kidney |
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Definition
| ANY bodiliy fluid - including mother's miulk |
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Term
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Definition
| time it takes for the amount of drug in the body to be reduced by 50% most drugs are considered essentially eliminiated from the body after 4 half lives have passed |
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