Term
|
Definition
decreased cardiac output->
decreased renal flow->
decreased drug filtration->
decreased drug excretion |
|
|
Term
|
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
|
|
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
|
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
|
Definition
-constant percentage of drug eliminated per unit time
-how most drugs are eiliminated |
|
|
Term
|
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
|
Definition
| regulatory proteins that interact with a drug or hormone and initiate a cellular response |
|
|
Term
|
Definition
-dose that works in 50% of the population 50% of the time.
-threshold dose |
|
|
Term
|
Definition
| dose below which, no response |
|
|
Term
|
Definition
| half of possible maximum response |
|
|
Term
|
Definition
| dose to produce 1/2 of the possible maximum response: ED50 |
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
| The ability to produce a response is |
|
Definition
| intrinsic activity (i.a.) |
|
|
Term
|
Definition
|
|
Term
| Agonist also have _________ and ___________ |
|
Definition
|
|
Term
|
Definition
| how well the drug fits into binding sites |
|
|
Term
|
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
|
|
Term
|
Definition
| drugs that interact with a receptor to produce a response |
|
|
Term
|
Definition
these can produce the full response
I.A.= 1 |
|
|
Term
|
Definition
| these can produce a response less than that of full agonists. I.A> 0 and <1 |
|
|
Term
|
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
|
Definition
| how well the drug turns on receptors |
|
|
Term
|
Definition
| how well a drug relieves symptoms |
|
|
Term
| what is the formula for the therapeutic index? |
|
Definition
|
|
Term
|
Definition
| the difference between the therapeutic effect and the lethal effect. The further apart the curves are, the safer the drug. |
|
|
Term
|
Definition
| This tells you how far apart the tails of the curves are, the bigger the number, the safer the drug. |
|
|
Term
|
Definition
| The study of medications in patients |
|
|
Term
|
Definition
A quantitative approach to describe the behavior of a
Drug in the Body |
|
|
Term
|
Definition
The impact of
Drugs in the Body |
|
|
Term
|
Definition
Absorption
Distribution
Metabolism
Excretion |
|
|
Term
|
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
|
Definition
The fraction % of drug available in the bloodstream after administration as compared to IV route.
Note: IV route is 100% Bioavailable |
|
|
Term
|
Definition
| The movement of a drug into the various body fluids and tissues |
|
|
Term
|
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
|
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
|
Definition
| Biotransformation----The chemical alteration of the parent compound usually resulting in enhanced excretion, inactivation, or sometimes active metabolites |
|
|
Term
|
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
|
|
Term
|
Definition
Inactive compound that must be metabolized in order to become active.
ex:Plavix |
|
|
Term
|
Definition
| Hepatic microsomal enzyme system: Cytochrom p450 |
|
|
Term
|
Definition
| Usually no change with age |
|
|
Term
|
Definition
| The process by which the drug is eliminated from the body. Some drugs are excreted after metabolism. some drugs are excreted unchanged. |
|
|
Term
|
Definition
| A general term used to describe the volume of blood which is completely cleared of a drug per unit of time. |
|
|
Term
|
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
|
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
|
Definition
| Levels lower than the minimum effective level will not be effective |
|
|
Term
|
Definition
| Levels higher than the maximal safe level offer no additional efficacy, but may cause more adverse effects |
|
|
Term
|
Definition
| Levels near this dose may cause dramatic, unusual adverse effects, even death. |
|
|
Term
|
Definition
| "Therapeutic Window" is a measure of the drug's safety. It is the relationship between beneficial and adverse effects of a medication |
|
|
Term
|
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
|
Definition
| the ability of the drug to produce a desired therapeutic effect |
|
|
Term
|
Definition
measure of amount of drug required to produce a given degree of effect.
rarely clinically important |
|
|
Term
|
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
|
Definition
| a drug that mimics some natural compound by binding with the receptor from stimulation and prevents it from being triggered normally |
|
|
Term
|
Definition
| a drug that binds to the receptor, blocks the receptor from stimulation, and prevents it from being triggered normally |
|
|
Term
|
Definition
| measure of the strength of attraction between a drug and its receptor. describes the tightness of the bond |
|
|
Term
|
Definition
| The more selective a drug is, the fewer adverse effects it will cause |
|
|
Term
|
Definition
| any undesired, unintended response to a drug |
|
|
Term
| Exaggerated drug response |
|
Definition
| an exaggerated, undesireable response |
|
|
Term
|
Definition
| causes increased adverse effects or decreased efficacy |
|
|
Term
|
Definition
| adverse effect of a drug that limits its usefulness or acceptance in a patient |
|
|
Term
|
Definition
| immune system response to a drug |
|
|
Term
|
Definition
| Narrow therapeutic window, high incidence of adverse effects, high incidence of allergic reactions |
|
|
Term
|
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
|
Definition
| chemical bonding that prevents absorption |
|
|
Term
| Drug induced mucosal damage |
|
Definition
|
|
Term
|
Definition
| protein displacement-drugs bound to plasma proteins are pharm. inactive and exist in equilibrium between bound and unbound forms |
|
|
Term
|
Definition
| high metabolism = lower drug levels = loss of efficacy |
|
|
Term
|
Definition
| decreased cardiac output->decreased renal flow->decreased drug filtration->decreased drug excretion |
|
|
Term
|
Definition
| low metabolism = higher levels = increased effects, adverse effects, and toxcicity |
|
|
Term
|
Definition
| occurs when the effects of two drugs are greater than would have been predicted from each of their effects alone. |
|
|
Term
|
Definition
| occurs when the effects of two drugs are less than predicted from their effects when given alone |
|
|
Term
|
Definition
| isonaizid and rifampin both cause hepatic injury |
|
|
Term
|
Definition
| the general area of study concerned with the formulation, manufacture, stability, and effectiveness of pharmaceutical dosage forms. |
|
|
Term
|
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
|
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
|
Definition
| is the relative amount of administered dose that reaches the general circulation and the rate at which it reaches the general circulation. |
|
|
Term
|
Definition
| a phenomenon where a substance may be capable of crystallizing in more than 1 crystalline form. |
|
|
Term
|
Definition
| the time (hr., min., etc) at which the administered drug reaches the therapeutic range or it (drug) begins to produce the effect. |
|
|
Term
|
Definition
| the time span (hr., min., etc), beginning the onset of action up to the termination of action. |
|
|
Term
|
Definition
| the time (hr., min.) at which the drug concentration in the plasma falls below the minimum effective concentration (MEC). |
|
|
Term
|
Definition
| process by which a drug proceeds from the site of administration to the site of measurement (usually blood, plasma or serum). |
|
|
Term
|
Definition
| the process of reversible transfer of drug to and from the site of measurement (usually blood or plasma). |
|
|
Term
|
Definition
| the process of conversion of one chemical species to another. |
|
|
Term
|
Definition
| the irreversible loss of drug from the site of measurement. Elimination of drugs occurs by two processes: metabolism and/or excretion. |
|
|
Term
|
Definition
| the irreversible loss of a drug in a chemically unchanged form. |
|
|
Term
|
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
|
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
|
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
|
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
|
Definition
| the drug or fraction thereof that is removed from the blood (plasma/serum) by the process of hepatic metabolism. |
|
|
Term
|
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
|
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
|
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
|
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
|
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
|
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
|
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
|
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
|
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
|
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
|
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
|
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
|
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
|
Definition
| the buildup of drug in the blood or body due to sequential dosing |
|
|
Term
|
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
|
Definition
describes the relationship between drug concentration and pharmacologic response
what the drug does to the body |
|
|
Term
|
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
|
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 |
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|
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 |
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|
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 |
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|
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 |
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|
Term
| drugs that are inactive when ingested and require metabolic activation to exert their action |
|
Definition
| prodrugs ex: cortisone, prednisone, azathiopne, fosphenytoin |
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|
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 |
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|
Term
| what enzyme family is responsible for most enzymatic drug metabolism? |
|
Definition
|
|
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
|
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
|
|
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 |
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Term
|
Definition
| Study of the action of the body on drugs. |
|
|
Term
|
Definition
| Study of the action of drugs on the body. |
|
|
Term
| Four principles of Pharmacokinetics |
|
Definition
| Absorption, Distribution, Metabolism, Elimination |
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|
Term
|
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. |
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|
Term
|
Definition
| The fraction or percentage of the drug that reaches the systemic circulation. |
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|
Term
|
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. |
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Term
|
Definition
| Administration route that bypasses the GI tract. (IV, IM, SC) |
|
|
Term
|
Definition
| A drug that will breakdown in an acidic environment like the stomach. |
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|
Term
|
Definition
| The apparent volume into which a drug distributes in the body at equilibrium. Amount in body(mg)/plasma drug concentration (mg/L) |
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|
Term
| Small volume of distribution |
|
Definition
| hydrophilic, trapped in plasma |
|
|
Term
| Large Vd (Volume of Distribution) |
|
Definition
| lipophilic, distributes to the tissues |
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|
Term
|
Definition
| Drug metabolized by the Cytochrome P450 system (most lipophilic drugs) |
|
|
Term
|
Definition
| Drug that causes more rapid metabolism of substrate drugs. |
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|
Term
|
Definition
| Drug that causes slower metabolism of substrate drugs. |
|
|
Term
|
Definition
| Drug is oxidized or reduced to a more polar form usually in the liver. |
|
|
Term
|
Definition
| Polar group in conjugated to the drug to increase polarity. |
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|
Term
|
Definition
| Inactive substance metabolized to an active substance in the body. |
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|
Term
|
Definition
| Metabolite that also has therapeutic activity. |
|
|
Term
|
Definition
| Drugs diffuse from blood into nephron if they are small, unbound, nonionic. |
|
|
Term
|
Definition
| Active transport of drugs into nephron, usually because they resemble something endogenous. |
|
|
Term
|
Definition
| Drugs reenter the blood stream by diffusion from the nephron tubule if they are small and nonionic. |
|
|
Term
|
Definition
| The time it takes the plasma concentration of a drug to decrease by 50% after a given dose. |
|
|
Term
|
Definition
| When absorption equals elimination. The drug in the body is in homeostasis. Generally reached in 5 half-lives. |
|
|
Term
|
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
|
Definition
| Alters the physiology of a cell by binding to the plasma membrane or intracellular receptors. |
|
|
Term
|
Definition
| Inhibits or blocks responses cause by agonists. |
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|
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
|
Definition
| 1 + 1 = 2, two drugs are taken together and both exert their effects |
|
|
Term
|
Definition
| 1 + 1 = 3, two drugs are taken together and they enhance each others effects |
|
|
Term
|
Definition
| 0 + 1 = 2, one drug has no clinical activity alone, but when added to a clinically active drug it enhances its effects |
|
|
Term
|
Definition
| 1 + 1 = 0, one drug negates the other |
|
|
Term
|
Definition
| Drugs that have the same effect on the body and a nearly identical chemical structure; same class |
|
|
Term
|
Definition
| Drugs that have essentially the same effect on the body, but do not have an identical structure |
|
|
Term
|
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
|
Definition
| The dose of drug that attempts to maintain a steady state plasma concentration in the therapeutic range. |
|
|
Term
|
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
|
|
Term
| What form of a drug may be transferred across the membrane via passive diffusion? |
|
Definition
|
|
Term
|
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
|
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
|
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
|
|
Term
| what are the routes for parenteral drug administration? |
|
Definition
| intavenous (IV), Intramuscular (IM), Subcutaneous (SC) |
|
|
Term
|
Definition
| drugs administered orally are first exposed to the liver and may be extensively metabolized before reaching the rest of the body |
|
|
Term
|
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
|
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
|
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
|
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
|
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
|
|
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
|
|
Term
| Bound drugs are pharmacologically _________ |
|
Definition
|
|
Term
| he primary serum protein responsible for drug binding. The strongest affinity for weak acid. |
|
Definition
|
|
Term
|
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
|
|
Term
| In the kidney, what types of drugs will undergo passive reabsorption? |
|
Definition
| unionized, lipid soluable |
|
|
Term
|
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
|
|
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
|
|
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
|
|
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
|
|
Term
|
Definition
Absorbing
Distributing
Metabolizing, and
Excreting the drug
Defined as what the body does to the drug |
|
|
Term
|
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
|
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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