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Pharmacology and Pharmacodynamics
Test 1 clinical pharmacology
278
Pharmacology
Graduate
02/12/2012

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Term
Altered renal excretion
Definition

decreased cardiac output->

decreased renal flow->

decreased drug filtration->

decreased drug excretion 

Term
geriatric patients
Definition
a dispropotionately high prescription drug use exists in the elderly
experience more adverse drug reactions and drug-drug interactions
altered pharmacokinetics
multiple and severe illnesses
multiple-drug therapy
poor adherence
Term
altered pharmacokinetics in geriatric patients
Definition
more sensitive to drugs than younger adults and have wider variation
Term
what is multiple-drug therapy?
Definition
excessive prescribing
Term
treatment and geriatric patients
Definition
individualization of treatment is essential
each patient must be monitored for desired and adverse responses
regimen must be adhered to
goal of treatment is to reduce symptoms and improve quality of life
Term
treatment and geriatric patients
Definition
individualization of treatment is essential
each patient must be monitored for desired and adverse responses
regimen must be adhered to
goal of treatment is to reduce symptoms and improve quality of life
Term
drug therapy in geriatric patients
Definition
pharmacokinetic changes
pharmacodynamic changes
adverse drug reactions and drug interactions
promoting adherence
Term
pharmacokinetic processes in geriatric patients
Definition
absorption
distribution
metabolism
excretion
Term
absorption in geriatric patients
Definition
altered GI absorption is not major factor to drug sensitivity
percentage of an oral dose that is absorbed does not change with age
rate of absorption may slow
delayed gastric emptying and reduced splanchnic blood flow occur
Term
distribution in geriatric patients
Definition
increased percentage of body fat
decreased percentage of lean body mass
decreased total body water
reduced concentration of serum albumin
Term
body fat
Definition
storage depot for lipid-soluble drugs
Term
total body water in geriatric patients
Definition
distributed in smaller volume, thus concentration is increased and effects are more intense
Term
explain the reduced concentration of serum albumin in geriatric patients
Definition
may be significatnly reduced in the malnourished
causes decreased protein binding of drugs and increase in levels of free drugs
Term
metabolism in geriatric patients
Definition
hepatic metabolism declines with age
reduced hepatic blood flow, reduced liver mass, and decreased activity of some hepatic enzymes occur
half-life of some drugs may increase, and responses are prolonged
responses to oral drugs (first-pass effect) may be enhanced
Term
excretion in geriatric patients
Definition
renal function undergoes progressive decline beginning in early adulthood
drug accumulation secondary to reduced renal excretion is the most important cause of adverse drug reactions in the elderly
Term
what renal functions undergo progressive decline beginning in early adulthood
Definition
reduction in renal blood flow, GFR, active tubular secretion, and number of nephrons
Term
what drugs should you use in elderly patients to assist with excretion?
Definition
drugs that are eliminated primarily by the kidneys
creatine clearance, not serum creatine
Term
pharmacodynamic changes in the elderly
Definition
alterations in receptor properties may underlie altered sensitivity to some drugs
Term
what drugs have more intense effects in the elderly?
Definition
warfarin
certain CNS depressants
Term
beta blockers in the elderly
Definition
less effective in the elderly, even in the same concentrations
reduction in number of beta receptors
reduction in the affinity of beta receptors for beta-receptor blocking agents
Term
dverse drug reactions in the elderly
Definition
7 times more likely
16% of hospital admissions
50% of all medication-related deaths
majority are dose related, not idiosyncratic
symptoms are often nonspecific like dizziness and cognitive impairment
Term
predisposing ADR factors in the elderly
Definition
drug accumulation secondary to reduced renal function
polypharmacy
greater severity of illness
multiple pathologies
greater use of drugs that have a low therapeutic index(digoxin)
increased individual variation secondary to altered pharmacokinetics
inadequate supervision of long-term therapy
poor patient adherence
Term
measures to reduce ADRs in the elderly
Definition
take thorough drug history, including OTCs
consider pharmacokinetic and dynamic changes due to age
monitor for clinical response/plasma drug levels
use the simplest regimen possible
monitor for drug-to-drug interactions
periodically review the need for continued drug therapy
encourage patient to dispose of old meds
take steps to promote adherence adn avoid drugs on the Beers List
Term
promoting adherence with unintentional nonadherence in the elderly
Definition
simplified drug regimens
clear, concise verbal and written instructions
appropriate dosage form
clearly labeled and easy-to-open containers
daily reminders
support system
frequent monitoring
Term
ntentional nonadherence in the elderly
Definition
most cases (75%) of nonadherence are intentional
reasons include: expense, side effects, patient's conviction that the drug is unnecessary or the dosage too high
Term
first order elimination
Definition
-constant percentage of drug eliminated per unit time
-how most drugs are eiliminated
Term
plasma half-life
Definition
time to reduce plasma levels by one half
Term
how many half lives does it take to reach a steady state?
Definition
6 per lecture.
4-5 other resources
Term
capacity limited (zero order) elimination
Definition
-constant amount of drug eliminated per unit time
-can cause drug accumulation
Term
receptors
Definition
regulatory proteins that interact with a drug or hormone and initiate a cellular response
Term
ED50
Definition
-dose that works in 50% of the population 50% of the time.
-threshold dose
Term
threshold dose
Definition
dose below which, no response
Term
mid range
Definition
half of possible maximum response
Term
potency
Definition
dose to produce 1/2 of the possible maximum response: ED50
Term
ceiling
Definition
maximum response
Term
AFFINITY
Definition
how well the drug binds
Term
The ability to produce a response is
Definition
intrinsic activity (i.a.)
Term
Agonist have __________
Definition
intrinsic activity
Term
Agonist also have _________ and ___________
Definition
affinity and efficacy
Term
affinity
Definition
how well the drug fits into binding sites
Term
efficacy
Definition
how well the drug turns on the receptor after binding
Term
a partial agonist in the presence or a full agonist is an ___________
Definition
antagonist
Term
agonist
Definition
drugs that interact with a receptor to produce a response
Term
full agonist
Definition
these can produce the full response
I.A.= 1
Term
partial agonist
Definition
these can produce a response less than that of full agonists. I.A> 0 and <1
Term
competitive antagonist
Definition
these have affinity, no intrinsic activity, block the binding by an agonist to its receptor, blockade can be overcome, and reduce the potency of the agonist
Term
pharmacological efficacy
Definition
how well the drug turns on receptors
Term
therapeutic efficacy
Definition
how well a drug relieves symptoms
Term
what is the formula for the therapeutic index?
Definition
LD50 / ED50
Term
Therapeutic Index
Definition
the difference between the therapeutic effect and the lethal effect. The further apart the curves are, the safer the drug.
Term
Certain Safety Index
Definition
This tells you how far apart the tails of the curves are, the bigger the number, the safer the drug.
Term
Clinical Pharmacology
Definition
The study of medications in patients
Term
Pharmacokinetics
Definition
A quantitative approach to describe the behavior of a

Drug in the Body
Term
Pharmacodynamics
Definition
The impact of
Drugs in the Body
Term
ADME
Definition
Absorption
Distribution
Metabolism
Excretion
Term
Absorption
Definition
The movement of a drug from its site of administration into the bloodstream.

Absorption is not always desired (inhailed or topical steroids and antibotics)
Term
Commonly Used Routes of Administration
Definition
Oral, Enteral, Parenteral, Inhalation, Intranasal, Topical
Term
Drug Passages Across Membranes:
Channels or Pores
Definition
Only very small drugs
ex:Na+ and K+
Term
Passage Across Membranes:
Direct Penetration
Definition
Most common method of drug movement across membranes, must be lipid soluble
Term
Bioavailability
Definition
The fraction % of drug available in the bloodstream after administration as compared to IV route.

Note: IV route is 100% Bioavailable
Term
Distribution
Definition
The movement of a drug into the various body fluids and tissues
Term
Volume of Distribution
Definition
Mathematical concept describing the amount of drug in the body in relation to the concentration of drug in the plasma.

Note: VD is useful in estimating the loading dose
Term
Drug Distribution
Blood Brain Barrier:
Placental Barrier:
Breast Milk:
Fluid areas & Lipid tissues
Definition
BBB: Only lipid soluble drugs can cross the bbb to reach the central nervous system
PB: lipid soluble drugs can cross and reach the developing fetus
BM: most drugs can enter the nursing mother's milk supply
F&L: Self explanatory
Term
Protein Binding
Definition
Some drugs are bound to the plasama proteins, mostly albumin. Drugs bound to these proteins are phamacologically inactive while bound.
Term
Variables affecting VD & Distribution
Definition
Body composition of infants
Obese Patients store more in adipose tissues
Significant changes in body weight
Malnourished patients have fewer albumin proteins available for protein binding
Neonates and elderly have more permeable BBBs
Term
Metabolism
Definition
Biotransformation----The chemical alteration of the parent compound usually resulting in enhanced excretion, inactivation, or sometimes active metabolites
Term
First Pass Metabolism
Definition
Drugs absorbed into the small intestine are first exposed to the liver and may be extensively metabolized before reaching systematic circulation
Term
First Pass Metabolism lowers _____?
Definition
Bioavailability
Term
Prodrug
Definition
Inactive compound that must be metabolized in order to become active.
ex:Plavix
Term
Phase 1 Reactions
Definition
Hepatic microsomal enzyme system: Cytochrom p450
Term
Phase 2 Reactions
Definition
Usually no change with age
Term
Excretion
Definition
The process by which the drug is eliminated from the body. Some drugs are excreted after metabolism. some drugs are excreted unchanged.
Term
Clearance
Definition
A general term used to describe the volume of blood which is completely cleared of a drug per unit of time.
Term
Half Life (t 1/2)
Definition
The time required for the drug's plasma concentration to be reduced by ONE HALF
Term
How many half lives does it take to "clear" a drug?
Definition
4-5 books
or
6 per PPT lecture
Term
Linear Kinetics
Definition
Most drugs' half lives are concentration and dose INDEPENDANT
Half Life DOES NOT depend on dose
Term
Dose Response Relationship
Definition
The relationship between size of dose and intensity of response
Term
Minimal effective level
Definition
Levels lower than the minimum effective level will not be effective
Term
Maximal safe level
Definition
Levels higher than the maximal safe level offer no additional efficacy, but may cause more adverse effects
Term
Toxic Levels
Definition
Levels near this dose may cause dramatic, unusual adverse effects, even death.
Term
Therapeutic Index
Definition
"Therapeutic Window" is a measure of the drug's safety. It is the relationship between beneficial and adverse effects of a medication
Term
Duration of action
Definition
length of time a drug can be expected to exhibit its pharmacological effect
Term
Duration of Action and Half Life
Definition
Usually correlate, but not always
Term
Efficacy
Definition
the ability of the drug to produce a desired therapeutic effect
Term
Potency
Definition
measure of amount of drug required to produce a given degree of effect.
rarely clinically important
Term
Receptor Theory
Definition
a drug produces an effect by combining with some specific molecular constituent (receptor). the function of the receptor cell is modified to produce a measureable effect
**(Lock and Key Theory)**
Term
Agonist
Definition
a drug that mimics some natural compound by binding with the receptor from stimulation and prevents it from being triggered normally
Term
Antagonist
Definition
a drug that binds to the receptor, blocks the receptor from stimulation, and prevents it from being triggered normally
Term
Affinity
Definition
measure of the strength of attraction between a drug and its receptor. describes the tightness of the bond
Term
Selectivity
Definition
The more selective a drug is, the fewer adverse effects it will cause
Term
Adverse Drug Reaction
Definition
any undesired, unintended response to a drug
Term
Exaggerated drug response
Definition
an exaggerated, undesireable response
Term
Drug interaction
Definition
causes increased adverse effects or decreased efficacy
Term
Intolerance
Definition
adverse effect of a drug that limits its usefulness or acceptance in a patient
Term
Drug Allergy
Definition
immune system response to a drug
Term
High Risk Drugs
Definition
Narrow therapeutic window, high incidence of adverse effects, high incidence of allergic reactions
Term
Drug-Drug interaction
Definition
modification of the effects of one drug by the prior or concomitant administration of another
Term
Direct Chemical Interaction
Definition
precipitation, inactivatio
Term
Pharmacokinetic Interactions
Definition
Altered Absorption due to altered ph, or altered intestinal flora (bacteria)
Term
Chelation
Definition
chemical bonding that prevents absorption
Term
Drug induced mucosal damage
Definition
ex: chemotherapy
Term
Altered Distribution
Definition
protein displacement-drugs bound to plasma proteins are pharm. inactive and exist in equilibrium between bound and unbound forms
Term
Enzyme induction
Definition
high metabolism = lower drug levels = loss of efficacy
Term
Altered renal excretion
Definition
decreased cardiac output->decreased renal flow->decreased drug filtration->decreased drug excretion
Term
Enzyme Inhibition
Definition
low metabolism = higher levels = increased effects, adverse effects, and toxcicity
Term
Synergistic Effects
Definition
occurs when the effects of two drugs are greater than would have been predicted from each of their effects alone.
Term
Antagonist effects
Definition
occurs when the effects of two drugs are less than predicted from their effects when given alone
Term
combined toxicity
Definition
isonaizid and rifampin both cause hepatic injury
Term
Pharmaceutics
Definition
the general area of study concerned with the formulation, manufacture, stability, and effectiveness of pharmaceutical dosage forms.
Term
Pharmacokinetics
Definition
the study of kinetics of absorption, distribution, metabolism and excretion (ADME) of drugs and their corresponding pharmacologic, therapeutic, or toxic responses in man and animals.
Term
Biopharmaceutics
Definition
he study of the factors influencing the bioavailability of a drug in man and animals and the use of this information to optimize pharmacological and therapeutic activity of drug products.
Term
Bioavailability
Definition
is the relative amount of administered dose that reaches the general circulation and the rate at which it reaches the general circulation.
Term
Polymorphism
Definition
a phenomenon where a substance may be capable of crystallizing in more than 1 crystalline form.
Term
Onset of Action
Definition
the time (hr., min., etc) at which the administered drug reaches the therapeutic range or it (drug) begins to produce the effect.
Term
Duration of Action
Definition
the time span (hr., min., etc), beginning the onset of action up to the termination of action.
Term
Termination of Action
Definition
the time (hr., min.) at which the drug concentration in the plasma falls below the minimum effective concentration (MEC).
Term
Absorption
Definition
process by which a drug proceeds from the site of administration to the site of measurement (usually blood, plasma or serum).
Term
Distribution
Definition
the process of reversible transfer of drug to and from the site of measurement (usually blood or plasma).
Term
Metabolism
Definition
the process of conversion of one chemical species to another.
Term
ELIMINATION
Definition
the irreversible loss of drug from the site of measurement. Elimination of drugs occurs by two processes: metabolism and/or excretion.
Term
Excretion
Definition
the irreversible loss of a drug in a chemically unchanged form.
Term
Dispositon
Definition
s defined as all the processes that occur subsequent to the absorption of the drug in extravascular route. Hence, by definition, the components of disposition phase are: distribution and elimination.
Term
Linear pharmacokinetics
Definition
describes the directly proportionality between the observed plasma concentration and the amount of drug eliminated and the dose administered.
Term
Rapid drug distribution equilibrium
Definition
simply suggests that the rates of transfer of drug molecules from blood to all organs and tissues and back to blood have become equal or almost equal (i.e. differences in rates are insignificant) instantaneously after administration of a drug.
Term
Apparent volume of distribution (V or Vd)
Definition
s simply a proportionality constant, whose sole purpose is to relate the plasma concentration (Cp) and the amount or mass of drug (X) in the body at a time.
Term
Elimination Half-life (biological half-life
Definition
is the time (hr., min., day, etc.) at which the mass (amount) of unchanged drug in the body (blood) becomes 1/2 or 50% of the initial mass of drug as soon as the equilibrium is established after administering a dose.
Term
Clearance
Definition
(mL/hr or mL/min)

is a proportionality constant that describes the relationship between a substance's rate of elimination (amount per unit time) at a time and its corresponding concentration in an appropriate body fluid or concentration at that time.

OR

is the hypothetical volume of blood (plasma or serum) or other biological fluids from which the drug is totally and irreversibly removed per unit time.
Term
Systemic (Cls) or Total Body Clearance (TBC)
Definition
s the sum of all individual organ clearances that contribute to the overall elimination of drugs.
Term
Renal clearance (Clr)
Definition
the drug or the fraction thereof that is removed from the blood (plasma/serum) by the process of renal excretion.
Term
Metabolic clearance (Clm)
Definition
he drug or fraction thereof that is removed from the blood (plasma/serum) by the process of metabolism from whatever metabolic organ.
Term
Hepatic clearance (ClH)
Definition
the drug or fraction thereof that is removed from the blood (plasma/serum) by the process of hepatic metabolism.
Term
Therapeutic Range
Definition
the plasma or serum concentration (mcg/ml, ng/ml etc.) range, within which, the drug is likely to produce the therapeutic activity or effects.
Term
Optimum dosage form
Definition
a dosage form that provides the maximum therapeutic effect with least amount of the drug and achieves the best results consistently.
Term
Feathering, method of residual, or curve stripping
Definition
a method that allows the separation of the monoexponential constituents of a biexponential plot of plasma concentration against time.
Term
Lag time
Definition
the delay time in absorption following the administration of a drug by the oral or other extravascular route.
Term
Time of maximum drug concentration, peak time (tmax)
Definition
the time (hr, min, etc.) at which body displays maximum plasma concentration, (Cp)max, and it occurs when the rate of absorption is equal to the rate of elimination (i.e. KaXa = KX).
Term
Maximum Plasma Concentration (Cp) max (Peak Plasma Concentration)
Definition
the plasma concentration (Cp) when time is equal to tmax.
Term
Bioavailability
Definition
s the relative amount of administered dose that reaches the general circulation and the rate at which it reaches the general circulation.

is the rate and extent to which the active ingredient or therapeutic moiety is absorbed from a product and becomes available at the site of drug action.
Term
Pharmaceutically or Chemically Equivalent Products
Definition
two or more drug products that contain equal amounts of the same therapeutically active ingredient (s) in identical dosage forms, and that these dosage forms meet the requirements such as purity, content uniformity and disintegration time as established by the U.S.P. and/or N.F.
Term
Pharmaceutical Alternatives
Definition
these are drug products that contain the same therapeutic moiety, but differ in salt or ester of that moiety or in the dosage form or strength. Also, controlled or modified release dosage forms are pharmaceutical alternatives when compared with conventional formulations of the same active ingredients.
Term
Therapeutic Equivalence
Definition
signifies that two or more chemically or pharmaceutically equivalent products essentially produce the same efficacy and/or toxicity in the same individuals when administered in identical dosage regimen.
Term
Absolute Bioavailability
Definition
s assessed by comparing the values of (AUC)0∞ and/or cumulative mass of drug excreted in the urine (Xu)∞, obtained following the administration of a drug in a dosage form and an equivalent dose of the same drug intravenously (I.V. bolus).
Term
Comparative (relative) bioavailability
Definition
is assessed by comparing the bioavailability parameters ((AUC)0∞, (Cp)max and tmax) derived from plasma drug concentration- time plot data and/or urinary excretion data obtained following the administration of a drug in two different dosage forms (i.e. tablet and syrup, capsule and suspension, etc.) and/or by two different extravascular routes of administration (i.e. oral and intramuscular).
Term
Bioequivalence
Definition
two or more chemically or pharmaceutically equivalent products produce comparable bioavailability characteristics in any individual when administered in equivalent dosage regimen. (Parameters compared include (AUC)0∞, (Cp)max and tmax).
Term
First Pass Effect
Definition
Immediately following its absorption (through gut lumen and gut wall), a drug first passes via hepatic portal vein to the liver where metabolism of the drug, due to enzymes, may take place. This is called first pass effect.
Term
First pass effect
Definition
Immediately following its absorption (through gut lumen and gut wall), a drug first passes via hepatic portal vein to the liver where metabolism of the drug, due to enzymes, may take place. This is called first pass effect.
Term
Extraction Ratio
Definition
The ratio of the [rate of elimination] to the [rate at which drug enters an organ]. Extraction ratio is a dimensionless term that quantifies the efficiency of an organ with respect to drug elimination.
Term
True Steady State
Definition
when the rate of elimination and the rate of infusion become equal and it occurs, theoretically, only when time is equal to infinity
Term
Steady State Concentration (ug/ml)
Definition
the plasma concentration that corresponds to true steady state, attainable only at time infinity
Term
Practical Steady State Concentration (mcg/ml)
Definition
when plasma concentration of the drug in the blood or body is within 5% of true steady state plasma concentration
Term
Steady State Condition
Definition
when, under a given dosing regimen, the mass of drug administered or absorbed is equal to the mass of drug eliminated over a dosing interval
Term
Loading Dose (mg; mg/kg)
Definition
single dose administered to reach steady state concentration instantly
Term
Maintenance Dose (mg; mg/kg)
Definition
the dose administered every dosing interval to maintain the steady state concentration and condition
Term
Drug Accumulation
Definition
the buildup of drug in the blood or body due to sequential dosing
Term
Pharmacokinetics
Definition
describes the time-course of drugs in the tissues of the body, it is based upon the idea of drug disposition, and addresses absorption, distribution, metabolism, and elimination

what the body does to the drug
Term
Pharmacodynamics
Definition
describes the relationship between drug concentration and pharmacologic response
what the drug does to the body
Term
Therapeutic Range
Definition
the concentration range of a drug at which patients are most likely to respond
Term
what does ADME stand for?
Definition
absorption, distribution, metabolism, and excretion
Term
what are the 2 ways drugs enter the body?
Definition
1) IV (directly)
2) across membranes (indirectly)
Term
List the factors that influence oral drug absorption
Definition
1) molecular size
2)degree of ionization
3)relative lipid solubility
Term
Bioavailability
Definition
a term used to quantify the rate and extent of drug absorption
Term
how is the relative bioavailability of an oral drug determined?
Definition
by comparing its rate of absorption(area under the curve) to that of another accepted orally administered standard
Term
how is the absolute bioavailability determined?
Definition
when the oral drug is compared to the same drug administered intravenously ( IV route drugs are 100% available)
Term
What is F, and what values does it include?
Definition
F is the ratio of bioavailability of an oral doasage form to the IV dosage form

this value ranges from 1(completely available) to 0.

F aka the percent of unchanged drug that reaches the system circulation
Term
what 2 factors determine bioavailability?
Definition
1) absorption
2) degree of presystemic extraction
Term
what factors affect the distribution of a drug?
Definition
1) molecular weight
2) lipid solubility
3) pKa
4) protein binding
Term
what are the first organs to receive a drug?
Definition
the highly perfused ones: heart, liver, kidney, and brain
Term
term that describes the extent of drug distribution
Definition
apparent volume of distribution
Term
this term relates the total amount of drug in the body to the resulting plasma concentration, and does not correspond to an actual physiologic volume
Definition
apparent volume of distribution

-it is defined only by knowing the dose of the drug and the resulting plasma concentration sampled immediately after the drug administration is complete
Term
what are the units that volume of distribution is measured in?
Definition
liters, usually standardized to body weight (liters/kg)
Term
if a drug is highly lipid soluble, will the distribution volume exceed body water or have a smaller apparent volume of distribution?
Definition
lipid soluble will exceed body water, lipid INsoluble have smaller apparent volumes of distribution


extensive tissue binding of the drug will also elevate the apparent volume of distribution
Term
what sort of apparent volume of distribution would imply that tissue uptake and tissue storage is not extensive?
Definition
if the vol. of distribution corresponds in size to the plasma/blood volume or extracellular fluid
Term
drug bound to protein is ____
Definition
inactive: only free drugs interact with receptors and is available for clearance from the body
Term
drugs classified as weak acids typically bind to ___ while weak bases typically bind to ______
Definition
acids: albumin ex: salicylate, phenytoin, warfarin
bases: alpha acid glycoprotein ex: lidocaine, beta blockers, merperidine, methadone
Term
the total plasma drug concentration is usually reported as 2 fractions, what are they?
Definition
1) the amount of drug that exists bound to protein
2) the amount of drug that exists in the free state
Term
at low concentrations, the fraction of a drug bound to protein is a function of the ________, at high concentrations it is determined by ______
Definition
low: depends on number of binding sites
high: depends on number binding sites AND drug concentration
Term
metabolism/biotransformation
Definition
ny alteration of a drug by the body that results in the formation of metabolite (which may be active) with a different chemical structure from the parent compound
Term
What is " first pass metabolism?"
Definition
The liver receives the drug after absorption from the GI tract via the portal vein and as it goes on its first pass through the liver, most of the drug is metabolized despite good oral absorption, reducing the bioavailabiltiy

ex: lidocaine, propanolol, naloxone, hydralzine
Term
how does an oral dose of a drug compare to a parenteral dose if the drug has large first pass metabolism?
Definition
the oral dose is typically larger
Term
do IV drugs undergo first pass metabolism?
Definition
no, sublingual bypasses liver and 50% of a rectally absorbed drug bypasses the liver
Term
what primarily determines the extent of first pass metabolism?
Definition
1) the amount of drug degradation that occurs in the GI tract
2) the amount of metabolism that occurs in the liver
Term
drugs that are inactive when ingested and require metabolic activation to exert their action
Definition
prodrugs ex: cortisone, prednisone, azathiopne, fosphenytoin
Term
Describe phase 1 reactions that occur with drug metabolism
Definition
Phase 1: occur in the ER and introduce/expose a fxnl group on the parent drug

usually the parent compound becomes inactive or less active with metabolism

ex: N&O de-alkylation, aliphatic and aromatic hydroxylation, N&S oxidation, and de-amination
Term
describe phase 2 reactions that occur with drug metabolism
Definition
Phase 2: occur in the cytosol, also referred to as conjugation reactions

involve: covalent linkage of fxnl groups such as glucuronic acid, sulfate, aa's etc. (glucuronidation, sulfation, acetylation)

note: a drug can undergo a phase 1 rxn, then a phase 2, or just a phase 2
Term
what enzyme family is responsible for most enzymatic drug metabolism?
Definition
cytochromes p450
Term
what does "hepatic enzyme induction" refer to?
Definition
de novo synthesis of cytochrome P450 enzyme resulting in an increase rate of drug biotransformation

-substances that induce these enzymes can increase the metabolic degradation of other hepatically metabolized drugs

ex: phenobarbital, rifampin, carbamzepine
Term
what does "hepatic enzyme inhibition" refer to?
Definition
it typically refers to a competition between two drugs for the same metabolic pathway. This "competitive inhibition" slows the rate of drug metabolism, giving rise to a prolonged or slowed effect

ex: azole antifungals and macrolide antibiotics
Term
zero order elimination
Definition
means that a constant AMOUNT of drug is eliminated per unit of time
Term
how does zero order elimination plot on a graph?
Definition
straight line(linear) decay on an arithmetic scale, but with the log scale on the Y axis it is a curve so it is referred to as a NON-LINEAR KINETIC

ex: ethanol
Term
means that a constant FRACTION of drug is eliminated per unit of time
Definition
first order reaction
Term
describe the graph for a 1st order reaction
Definition
the rate the drug is removed is proportional to the concentration so on a log scale on the Y axis(concentration) vs X(time) the drug conc. decay curve plots as a straight line == LINEAR KINETICS
Term
Pharmacokinetics
Definition
Study of the action of the body on drugs.
Term
Pharmacodynamics
Definition
Study of the action of drugs on the body.
Term
Four principles of Pharmacokinetics
Definition
Absorption, Distribution, Metabolism, Elimination
Term
Therapeutic Range
Definition
The concentration of drug in the blood above which the risk of side effects or complications outweigh the benefits and below which therapeutic benefits are not seen.
Term
Bioavailability (F)
Definition
The fraction or percentage of the drug that reaches the systemic circulation.
Term
First Pass Effect
Definition
Blood from the GI tract passes through liver before systemic circulation; some drugs are significantly metabolized by the liver before reaching the systemic circulation.
Term
Parenteral
Definition
Administration route that bypasses the GI tract. (IV, IM, SC)
Term
Acid Labile
Definition
A drug that will breakdown in an acidic environment like the stomach.
Term
Volume of Distribution
Definition
The apparent volume into which a drug distributes in the body at equilibrium. Amount in body(mg)/plasma drug concentration (mg/L)
Term
Small volume of distribution
Definition
hydrophilic, trapped in plasma
Term
Large Vd (Volume of Distribution)
Definition
lipophilic, distributes to the tissues
Term
Substrate
Definition
Drug metabolized by the Cytochrome P450 system (most lipophilic drugs)
Term
Inducer
Definition
Drug that causes more rapid metabolism of substrate drugs.
Term
Inhibitor
Definition
Drug that causes slower metabolism of substrate drugs.
Term
Phase I Reactions
Definition
Drug is oxidized or reduced to a more polar form usually in the liver.
Term
Phase II reactions
Definition
Polar group in conjugated to the drug to increase polarity.
Term
Prodrug
Definition
Inactive substance metabolized to an active substance in the body.
Term
Active metabolite
Definition
Metabolite that also has therapeutic activity.
Term
Filtration
Definition
Drugs diffuse from blood into nephron if they are small, unbound, nonionic.
Term
Secretion
Definition
Active transport of drugs into nephron, usually because they resemble something endogenous.
Term
Reabsorption
Definition
Drugs reenter the blood stream by diffusion from the nephron tubule if they are small and nonionic.
Term
Half-Life
Definition
The time it takes the plasma concentration of a drug to decrease by 50% after a given dose.
Term
Steady State
Definition
When absorption equals elimination. The drug in the body is in homeostasis. Generally reached in 5 half-lives.
Term
Receptor
Definition
The component of a cell or organism that interacts with a drug and initiates the chain of biochemical events leading to a drug's observed effects.
Term
Agonist
Definition
Alters the physiology of a cell by binding to the plasma membrane or intracellular receptors.
Term
Antagonist
Definition
Inhibits or blocks responses cause by agonists.
Term
Absorption Drug Interactions
Definition
Increase or decrease the amount of drug absorbed. Avoid by taking at different times. (i.e. antacids decrease the amount of phenytoin absorbed)
Term
Distribution Drug Interactions
Definition
Caused by plasma protein binding competition which increases the concentration of unbound drug. This is transient and it will return to baseline. (i.e. If you take aspirin while on phenytoin, aspirin has a higher protein binding affinity than phenytoin so it will bind and displace phenytoin therefore increasing the unbound concentration)
Term
Metabolism Drug Interactions
Definition
Induction or inhibition of the Cytochrome P450 system. (i.e. if you take cimetidine while on phenytoin it is an inhibitor of P450 so it will increase the concentration of phenytoin because it isn't being metabolised as quickly; if you add carbamazepine it will decrease the concentration of phenytoin because it is an inducer of the P450 system and will speed metabolism)
Term
Metabolism Drug Interactions
Definition
Induction or inhibition of the Cytochrome P450 system. (i.e. if you take cimetidine while on phenytoin it is an inhibitor of P450 so it will increase the concentration of phenytoin because it isn't being metabolised as quickly; if you add carbamazepine it will decrease the concentration of phenytoin because it is an inducer of the P450 system and will speed metabolism)
Term
Elimination Drug Interactions
Definition
Decreased or increased elimination of a drug.
Term
Addition
Definition
1 + 1 = 2, two drugs are taken together and both exert their effects
Term
Synergism
Definition
1 + 1 = 3, two drugs are taken together and they enhance each others effects
Term
Potentiation
Definition
0 + 1 = 2, one drug has no clinical activity alone, but when added to a clinically active drug it enhances its effects
Term
Antagonism
Definition
1 + 1 = 0, one drug negates the other
Term
Bioequivalence
Definition
Drugs that have the same effect on the body and a nearly identical chemical structure; same class
Term
Therapeutic Equivalence
Definition
Drugs that have essentially the same effect on the body, but do not have an identical structure
Term
Loading dose
Definition
An initial dose that is larger than subsequent doses for the purpose of achieving therapeutic drug concentrations more rapidly. Equal to the volume of distribution of the drug times the plasma concentration you desire
Term
Maintenance Dose
Definition
The dose of drug that attempts to maintain a steady state plasma concentration in the therapeutic range.
Term
Prodrugs
Definition
these drugs are inactive upon administration, but the metabolites become the active form.
Term
What is the primary means by which drugs cross membranes?
Definition
Passive diffusion
Term
What form of a drug may be transferred across the membrane via passive diffusion?
Definition
only the unionized form
Term
filtration
Definition
Passage of molecules through pores or porous structures as in the renal glomerulus and capillary endothelium cells
Term
carrier-mediated transport
Definition
The drug combines with a transport protein in the membrane and the complex can move across the membrane
Term
Active transport
Definition
this type of carrier-mediated transport has reversible binding, it is selective, requires ATP, it's a one-way process, it can be saturated and it can be inhibited
Term
Facilitated diffusion
Definition
this type of carrier-mediated transport is selective, can be saturated, does not require ATP, and is bi-directional with no drug accumulation on either side
Term
What are the types of enteral administration routes?
Definition
oral, sublingual, rectal
Term
what are the routes for parenteral drug administration?
Definition
intavenous (IV), Intramuscular (IM), Subcutaneous (SC)
Term
first pass effect
Definition
drugs administered orally are first exposed to the liver and may be extensively metabolized before reaching the rest of the body
Term
Mouth
Definition
this drug absorption site is best for potent drugs that are lipid soluble. Transfer occurs by passive diffusion, and the drugs can bypass the first-pass effect.
Term
Stomach
Definition
Drugs absorbed here will experience first pass effect.
- Transfer occurs via passive diffusion
-Weak acids are absorbed better here, and weak base dugs will become trapped
Term
Small Intestine
Definition
Because of the large amount of surface area, this is the primary site of absorption for most drugs. Absorption occurs by passive diffusion, active transport, facilitated diffusion, endocytosis, and filtration
Term
Receptor-mediated endocytosis
Definition
The binding of some peptide hormones, growth factors, antibodies, and other substances to their receptors on the cell surface can trigger a process of endocytosis that brings both the receptor and the ligand into the cell.
Term
Large intestine
Definition
This site is not very important for drug absorption, it may occur if the drug is not absorbed effectively in the small intestine
Term
Bioavailability
Definition
fraction of administered drug that reaches the systemic circulation.
-reduced by first pass effect, and altered by changes in GI motility.
Term
If you have a 100mg drug and only 70mg is transported to the circulatory system, what is bioavailability?
Definition
70%
Term
When a drug does this, it can no longer go to its receptor at the site of action, cant be distributed to body tissues, cant be metabolized by enzymes, and cant be excreted from the body
Definition
binds to plasma proteins
Term
Bound drugs are pharmacologically _________
Definition
inactive
Term
he primary serum protein responsible for drug binding. The strongest affinity for weak acid.
Definition
albumin'
Term
Lipoproteins
Definition
Lipid-soluble drugs. The binding capacity is dependant on their lipid content.
Term
alpha 1-acid glycoprotein
Definition
this glycoprotein is produced by acute injury, trauma, or stress. It has a 5.5 day half time. This glycoprotein may interfere with basic drugs and cause side effects after the time of the half life.
Term
where are the primary sites for drug excretion?
Definition
kidney, liver
Term
In the kidney, what types of drugs will undergo passive reabsorption?
Definition
unionized, lipid soluable
Term
forced alkaline diuresis
Definition
administering a bicarbonate will increase renal excretion of a weak acid drug
Term
What types of drugs undergo excretion from the liver?
Definition
lipid insoluble or ionized drugs
Term
What types of drugs undergo excretion from the liver?
Definition
lipid insoluble or ionized drugs
Term
What happens to lipid soluble drugs in the liver?
Definition
eterohepatic cycling
Term
What are the two types of reactions in drug metabolism?
Definition
Non-synthetic reactions
Synthetic reactions
Term
Name the types of non-synthetic reactions
Definition
1. oxidation reaction
2. reduction
3. Hydrolysis
Term
This drug metabolism reaction is a direct insertion of a hydroxyl functional group into the drug molecule mostly by cytochrome P450. It occurs almost exclusively in the endoplasmic reticulum of the liver.
Definition
Oxidation reactions
Term
This drug metabolism reaction is a direct insertion of a hydroxyl functional group into the drug molecule mostly by cytochrome P450. It occurs almost exclusively in the endoplasmic reticulum of the liver.
Definition
Oxidation reactions
Term
this drug metabolism reaction is a conjugation with a cugar, and amino acid or sulfate- more water-soluable compounds and more excretion of the drug
Definition
synthetic reactions
Term
Pharmacokinetics:

ADME
Definition
Absorbing
Distributing
Metabolizing, and
Excreting the drug

Defined as what the body does to the drug
Term
Pharmacodynamics
Definition
The chemical and physiologic changes that the drug causes
Drug effect at a cellular level

"What the drug does to the body"
Term
Physiochemical properties that impact ADME
Definition
Drugs are typically acids or bases.

Weak acids: Easier and faster to absorb in acidic environments (e.g., stomach)

Weak bases: Easier to absorb in alkaline environments (i.e., intestine)

Chemical properties:
Ionized (polar) form is usually water soluble. Most weak bases are also ionized

Non-ionized (nompolar) form: more lipid soluble, apt to cross cell membrane
Term
Factors which affect drug absorption
Definition
Absorbing surface (e.g., intestine – microvilli provide a TON of surface area; vs skin)
Blood flow to site of administration
Drug solubility:
- Water: must dissolve in water to be absorbed in GI tract
- Lipid: affects all ADME
Ionization - Ionized solutions do not cross membrane easily
Stability of drug in acid or alkaline environment
pH
- Local environment (e.g., acidic stomach) enhances or retards diffusion of acid/base drugs
- In general, drugs are weak acids or weak bases
Term
Impact of other substances on drug absorption
Definition
ETOH in stomach - changes dissolution
Nicotine - Lowers plasma enzymes
- can increase or decrease metabolism
Caffeine - increases stimulation, including gastric motility
Term
Environmental impacts: Drug storage
Definition
Most at room temp
- cannot handle heat of a car in summer
Some need refridgeration
Some are light sensitive
- dark-color containers
Air/humidity sensitive
- require tight sealed containers
Term
Routes of drug administration
Definition
Oral—
- 80% of drugs are given orally swallowed, buccal, sublingual
Enteral
- nasogastric or gastric tubes, rectal
Parenteral
- SC, IM, IV, intrathecal, epidural, other fluids
Pulmonary
- gases, mists
Topical
- skin, eyes, ears, nose
Term
Route of administration:
Oral & Enteral Routes
Definition
Rich blood supply in GI tract
Presence of food in stomach
GI motility - can affect whether drug even stays down
Oral cavity - slightly acidic pH
Stomach - highly acidic (pH 1.4)
Upper portion of small intestine - highly alkaline (pH 7-8)
Term
Parenteral Routes of drug administration
Definition
SC (subcutaneous) - into adipose & connective tissue. Slow absorption
IM (intramuscular) - into skeletal muscle, absorption more rapid than SC (because of blood supply)
IV (intravenous) - directly into blood stream, direct absorption
Must have correct diluents: Water & saline are not interchangeable!
Term
Blood-brain barrier
Definition
Protective, many drugs can't enter, or are absorbed very slowly.

Heavy in lipid composition
Term
Drug administration:
Pulmonary Route
Definition
Lungs provide large surface area for absorption, rich capillary network
Nearly instantaneous effect - fast as IV
Drug must reach alveolar level, aerosolized with propellants

Examples:
Inhalants, nebulizers, endotracheal tubes
Term
Drug Administration:
Topical Route
Definition
Local or systemic effect (depending on skin factors)
Only lipid-soluble compounds are absorbedb
Precutaneous absorption is erratic:
- Massaging enhances absorption
- Heat can increase it
- "washed" away with sweat or friction
- dependent on intact capillary system

"fluffy" people - skin is farther from their major vessels than less "fluffy" people. Topical drugs will not travel well into capillaries because of high amount of adipose tissue surrounding them.
Term
Drug Administration:
Topical Route
Definition
Local or systemic effect (depending on skin factors)
Only lipid-soluble compounds are absorbedb
Precutaneous absorption is erratic:
- Massaging enhances absorption
- Heat can increase it
- "washed" away with sweat or friction
- dependent on intact capillary system

"fluffy" people - skin is farther from their major vessels than less "fluffy" people. Topical drugs will not travel well into capillaries because of high amount of adipose tissue surrounding them.
Term
Distribution
(Pharmacokinetic Activities)
Definition
Usually easier than absorption, more rapid
Depends on permeability of capillaries to the drug molecules, cardiac output, regional blood flow (most of drug is first distributed to major organs, then muscles and fat)
Term
Distribution
(Pharmacokinetic Activities)
Definition
Usually easier than absorption, more rapid
Depends on permeability of capillaries to the drug molecules, cardiac output, regional blood flow (most of drug is first distributed to major organs, then muscles and fat)
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