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Basic Pharmaceutics

What kind of effects do drugs produce in the body? desired or undesired
where are drugs circulated throughout the body
what influences where the in the body the drug will go? properties of both the drug and the body
site of action the place where a drug causes an effect to occur
what is the objective of drug therapy to deliver the right drug, in the right concentration, to the right site of action, and at the right time to produce the desired effect.
what happens when most drugs produce an effect? they are interacting at a molecular level with cellular material or structure
Receptor the cellular material directly involved in the action of the drug
how would you describe the receptor a lock into which the drug molecule fits as a key, and only those drugs able to interact with the receptors in a particular site of action can produce effects at that site
specific cells only respond to certain drugs even though what their receptors are exposed to any drug molecules that are present in the body
drugs are selective in their action meaning they only act on specific targeted receptors and tissues
where are receptors located the surface of cell membranes and inside cells
Selective action the characteristic of a drug that makes its action specific to certain receptors and tissues
When drugs interact with the site of action they can: (7) through physical action, react chemically, modify metabolic activity, change the osmolarity of blood, incorporate cellular material, join with other chemicals to form a complex, and modify the biochemical or metabolic process
some drugs work by what changing the ability of ions to move into or out of cells
some drugs do what modify the creation, release, or control of nerve cell hormones that regulate different physiological processes
Antagonists job Block Action
Agonists job Activate receptors
Antagonists Drugs that bind with receptors but do not activate them. they block receptor action by preventing other drugs or substances from activating them
Agonists drugs that activate receptors to accelerate or slow normal cellular function
What can happen when drug molecules bind with a receptor they can cause a reaction that stimulates or inhibits cellular functions
what are the pharmacological effects of the interaction between molecules and receptors agonism and antagonism
Examples of epinephrine-like drugs act on the heart to increase the heart rate, and acetylcholine-like drugs act on the heart to slow the heart rate Agonists
What will the number of receptor available to interact with a drug mean it will directly influence the effect
to produce an effect, what has to happen a minimum number of receptors have to be occupied by drug molecules to produce and effect
what happens If there is little to no effect there were too few drug molecules to occupy the necessary number of receptors
once all the receptors are occupied, what will increasing the dosage do? increasing the dosage will not increase the effect
Can receptors be changed by drug use? Yes
Extended stimulation of cells with an agonist can reduce the number/sensitivity of what? What happens? receptors, the effect of the drug is reduced
Extended inhibition of cell functions with an antagonist can do what? increase the number/sensitivity of receptors
if the antagonist is stopped abruptly, what happens? the cells can have an extreme reaction to an agonist
it is difficult to measure the amount of a drug at the site of action and therefore what? therefore to predict an effect based upon that measurement
what factors influence a drugs movement from site of administration to the site of action Absorption, elimination, membrane permeability and that affect how a drug product behaves in them. more
why could it be impossible to measure the drug at the site of action unknown location or small size
Dose response curve a way to monitor the amount of a drug in the body and its effect at the site of action
what would you come to expect using a dose-response curve? a certain effect for any given dose
human variability different people have different characteristics that affect how a drug product behaves in them.
when are dose response curves not helpful? when relating the amount of drug in the body to its effect
why is determining drug concentration in the bodys fluid its a better way to relate the amount of drug in the body
why is blood generally used because of its rapid equilibrium between the site of admin. and the site of action
what can knowing a drugs concentration in the blood be directly related to? its effect; the most common way to analyze the potential effect of a drug
biopharmaceutics the study of the factors associated with drug products and physiological processes and the resulting systemic concentrations of drugs
Minimum effective concentration (MEC) the blood concentration needed for a drug to produce a response
onset of action the time MEC is reached and the response occurs
therapeutic window a drugs blood concentration range between its MEC and MTC
Which applications of Blood concentration do Manufacturers, pharmacy professionals, Researchers and clinicians, and physicians and pharmacists use? Manufacturers use data to evaluate drug products,Pharm. prof. use them to see the consequences of incorrectly compounding a formulation/wrong route of administration, researchers/clinicians measure human variable, Physicians/Pharm. monitor drug therapy
Where does the blood concentration number begin? At zero, at the time the drug is administered, before it has been absorbed in the blood
what happens when the drug leaves the formulation and enters the blood it causes concentrations to rise
What has to happen to produce an effect in blood concentrations they must achieve a (MEC)Minimum effective concentration
What happens during an MEC there is enough drug at the site of action to produce a response
When the MEC happens, it is called the onset of action
When blood concentrations increase what happens so does the intensity of the effect, since blood concentrations at the site of action that produce the response
What is it called when some drugs have an upper blood concentration limit betond which there are undesired or toxic effects the limit is called the MTC or Minimum toxic concentration
the range between the MEC and MTC is called the therapeutic window
As absorption completes, what happens blood concentrations are declining as absorbtion completes and eliminatation is proceeding
the time between the onset of action and when MEC is reached by declining blood concentrations is called the is the duration of action
what is an advantage of using blood concentrations as a measure of the drug amount in the body blood can be sampled repeatedly
When can a blood concentration time profile be developed when sampling covers several hours or more
what else can be used for blood concentration time profiles? serum or plasma
When changes in the blood concentration time profile reflect changes in the concentration at the site of action, what happens changes effect
how are these drugs typically monitored? by determining the the blood concentration Peak and Trough at the beginning and end of a doing interval
Examples of drugs that are monitored vancomycin, phenytoin, gentamycin, digoxin, and valproic acid
ADME Absorbtion, distribution, metabolism, excretion
Blood concentrations are the result of 4 simultaneously occurring processes Absorbtion, distribution, metabolism, excretion
what is another name for the 4 processes other than ADME processes Disposition
What are the metabolism and excretion processes combined called elimination
Absorption the transfer of drug into the blood from an administered drug product
what is the primary process when a drug product is first administered Absorption
why do the processes of distribution, metabolism and excretion have much less of the drug available for the processes? because absorption Is the primary process.
because distribution, metabolism and excretion use much less of the drug, what happens to the effect? much less of an effect
where does blood deliver the drug to the body tissue
what happens when the blood delivers the drug to the body tissue, if the drug cannot penetrate the tissues membrane it will not interact with the receptors
when a drug is delivered to the body tissue, and is able to penetrate the membranes,what happens if there is not enough blood flow to the tissue? little of the drug will be available
Distribution is influenced by what factor a drug binding to proteins in the blood or tissues
ADME processes are illustrated by what blood concentration time curves
Blood concentrations do what during absorption? they rise
what happens as absorption begins completetion metabolism and elimination become the primary processes
what happens as blood concentrations finish absorption, and metabolism and elimination become the primary processes? they cause BC to decline
Why are the ADME processes studied separately as they occur simultaneously to understand the critical factors responsible for each process
Half Life the amount of time it takes for the blood concentration of a drug to decline to one-half an initial value
What should be done to estimate how long it takes to essentially remove the drug from the body via the process of eliminaton 5x the half life is used
Why will most drugs dissociate and associate in solutions? because they are weak organic acids and bases
Dissociate come apart
Associate Attach to other chemicals
What happens when acids dissociate? they become ionized
What happens when bases dissociate they unionize
why do unionized drugs penetrate biological membranes more easily than ionized drug unionized drugs are: More lipid soluble,charges on biological membranes bind or repel ionized drugs,Ionized drugs associate with water molecules-creating larger particles with reduced penetrating capability
Passive diffusion The movement of drugs from an area of higher concentration to lower concentration
Active transport The movement of drugs from an area of lower concentration to an area of higher concentration. Cellular energy is required.
What is a critical factor of drug concentration and effect how drugs move through biological membranes
Biological membranes complex structures composed of lipids and proteins
3 types of biological membranes those made up of several layers of cells (skin), those made up of a single layer of cells(intestinal lining),those of less than one cell of thickness (as in the membrane of a single cell)
How do most drugs penetrate biological membranes? by passive diffusion
Drugs in the bodys fluids usually move from a higher area of concentration to a lower area of concentration, until the concentrations in each area are what balanced or in a state of equilibrium
What is a primary factor in the distribution process passive diffusion
The movement of higher drugs to lower concentration causes oral meds to do what move from the intestine to the blood, and from the blood to the site of action
Other than drug concentration, what else is a factor influencing diffusion Drugs that are lipid soluble- they will penetrate biological membranes better than those that will not
Membranes are lipoidal or fat-like
Drugs that are lipoidal are hydrophobic drugs, they hate or repel water
Hydrophilic drugs can also penetrate membranes, however they use water filled passages called aqueous pores which allow water and any drug contained in it, to move through the membrane
Ways to carry other drugs through/across membranes other than passive diffusion Specialized transport
Active transport is thought to explain what how certain substances that do not penetrate membranes by passive diffusion nevertheless succeed in entertaining a cell
Absorption occurs with how many routes of administration to some extent, with all administration routes
stomach ph 1-2
large intestine 7-8
small intestine 5-7
what is one of the primary factors affecting oral drug absorption the gastric emptying time
Gastric emptying time the time drug will stay in the stomach before it is emptied into the small intestine
what happens if a drug is left in the stomach too long it can be degraded or destroyed and the effects decreased
What are some factors affecting gastric emptying times the amount or type of food in the stomach,the presence of other drugs, the persons body position and their emotional condition
once a drug leaves the stomach how does it affect absorption the rate of movement through the intestines
what does slower than usual movement of the drug through the intestines do to the rate of absorption? can lead to increased absorption because the drug is in contact with the intestinal membrane longer
what does faster than usual movement through the intestines do to the rate of absorption? it goes through the intestinal track too rapidly to be fully absorped
what factors from the intestinal track affect absorption? Bile salts and enzymes
Bile salts improve the absorption of certain hydrophobic drugs
Enzymes added to the intestinal tracts contents from pancreatic secretions do what destroy certain drugs and consequently decrease their absorption; can also destroy drugs as they pass from the gut to the blood
why does the small intestine benefit absorption? large surface area
protein binding the attachment of a drug molecule to a plasma or tissue protein, effectively making the drug inactive, but also keeping it within the body
Complexation when different molecules associate or attach to eachother
Protein binding can be considered what a type of drug storage or depot within the body
When are drugs released after being bound exensively to proteins in fat and muscle, what happens to the blood concentration the drug is gradually released as the blood concentration falls
What kind of duration to protein bound drugs have they remain in the body a long time, and have a long duration of action
Once drugs become distributed in the blood stream, they have action that is selective to certain tissues or organs
How can drugs be targeted for specific t herapeutic effects? receptors have a specific nature about them which affects the distribution of the drug to the right tissue
Why would drugs have multiple effects most receptors can be found in multiple tissues throughout the body and used for different therapies
Bolus Rapidly administered intravenous solutions
What is something that a rapidly administered intravenous solution doesn't have an absorption site
Distribution involves the movement of a drug within the body once the drug has reached the blood
Where does blood carry the drugs throughout the body, to the site of action, as well as to the organs responsible for metabolism and excretion
how do blood flow rates effect distribution with different organs? drugs are rapidly distributed to the organs with higher blood flow such as heart, liver, kidneys. distribution to areas with lower blood flow would be less
High blood flow organs kidneys,liver,heart
Ares with low blood flow muscle, fat and skin
Why is the permeability of the tissue membranes to a drug important? most tissue membranes are easily penetrated by most drugs. Small drug molcules + hydrophobic drugs diffuse through tissue membranes easily.
What assists the tissue membrane in letting the drugs penetrate Specialized transport mechanisms
The blood-brain barrier Limits drug access to the brain and the cerebral spinal fluid
Protein binding can also affect distribution by: drugs binding to proteins and forming a complex, which prevents the bound drug from entering its sites of action, metabolism and excretion, making the drug inactive
What kind of drugs can move through tissue membranes and cellular openings Only a free or unbound drug
What makes a weaker drug unbound from a protein and what does it do another drug with a stronger binding capacity can displace a weaker bound drug from a protein, making the weker bound drug unbound and available for pharmacological activity
What does metabolism refer to the bodys process of transforming drugs
metabolite the substance resulting from the bodys transformation of an administered drug
what are most metabolites inactive molecules that are excreted
What do metabolites of some active drugs do they will produce effects in the patient until they are further metabolized or excreted
What is the primary site of drug metabolism in the body the liver
Enzymes complex proteins that catalyze chemical reactions
What do the enzymes in the liver do? interact with drugs and transform them into metabolites
How does the liver respond to chronic administration of certain drugs the liver will increase its enzyme activity
What does an enzyme induction result in? Greater metabolism of the drug
What is a result of enzyme induction Larger doses of the drug must be administered to produce the same therapeutic effect
Enzyme inhibition When some drugs decrease enzyme activity
What needs to be done for enzyme inhibition smaller doses of the drug will be needed to avoid toxicity from drug accumulation
Where would the liver secrete drugs or metabolites into the bile that is stored in the gallblader
What is the gallbladders job to empty bile with any drugs or metabolites in it, into the intestinal tract.
What happens to any drugs or metabolites contained in the bile they may be reabsorbed or simply eliminated within the feces
enterohepatic cycling If the drugs or metabolites are reabsorbed back into the blood circulation
enzyme induction the increase in hepatic enzyme activity that results in greater metabolism of drugs
first pass metabolism the substantial degradation of an orally administered drug caused by enzyme metabolism in the liver before the drug reaches the systemic circulation
What happens if the kidneys process of excretion becomes impaired excretion is reduced and some drugs will accumulate in the blood.
What do you do when there is a build of of a drug in the blood due to impaired excretion from the kidneys dose must be decreased or the dosing interval lengthened
Factors affecting urinary excretion drug accumulation if kidney excretion is impaired, some drugs affect the excretion, the ph of urine can affect the reabsorption of some drugs,
the amount of drug excreted in the urine is the amount filtered + the amount secreted - the amount reabsorbed
High Ph in the urine has what effect will decrease excretion of weak bases
What does a high PH increase excretion of weak acids such as salicylates and phenobarbital
glomerular filtration the blood filtering process of the nephron
Most drugs and their metabolites are excreted in the urine by the kidneys
What is the result of some orally administered drugs not being absorbed by the gastrointestinal tract as a result, they are significantly excreted into the feces
If enteroheptic cycling does not occur, what can happen excretion can also occur through the bile, and certain drugs are removed through the lungs in the expired breath
What is the kidneys main job they filter the blood and remove waste materials in it, including drugs and metabolites
As blood flows through the kidney, what happens plasma water if filtered from the kidney into the nephron tubule, creating the process of glomerular filtration
What does filtered plasma water contain waste materials and drugs from other parts of the body
Urinary reabsorption when some drugs can be reabsorbed back into the blood from the urine/waste
What 3 processes have to happen for the remaining fluid in the kidneys to be excreted from the body as urine 1.glomeruler filtration 2.renal secretion 3.urinary absorption
Which is faster, urinary excretion or fecal excretion urinary excretion
How long does it take to excrete drugs through feces a day or 2
How long does it take to excrete drugs through urine within hours
what is called the bioavailability of a drug the amount of a drug the is delivered to the site of action and the rate at which it becomes available
How does the FDA measure bioavailability by determining the relative amount of an administered dose of a drug that reaches the general systemic circulation and the rate at which this occurs
what tool is used to measure bioavailability blood concentration profile
how is bioavailability often determined by comparing blood concentration time profiles from a product to that of an intravenous solution, called absolute bioavailability
How is relative bioavailability determined by comparing blood concentration time profiles of a product to any other product that is not an IV solution
What does comparing one bioavailability to another determine their bioequivalency
The fda requires manufacturers to do what to do what to their products before they are approved for marketing they have to preform bioavailability studies
how do you compare the bioequivalency of two drugs the bioavailability of the active ingredient in a test formulation is compared to that in a standard formultion
Uses for bioequivalency studies to compare bioavailability between different dosage forms, different manufacturers and different production lots
A pharmaceutical equivalent or alternative, which has essentially the same rate and extent of absorption when administered in the same dose of active ingredients under similar conditions Bioequivalent drug products
Why does bioequivalency between drug products not occur? to many variables contribute to the differences between product. the particle size may be different or manufacturing process may also produce different results in size hardness or other characteristics
Changes in some factors affect Bioavailability. There can be differences in bioavailability of different products when the changes are not significant, the products are bioequivalent
Bioavailability the relative amount of an administered dose that reaches the general circulation and the rate at which this occurs
Bioequivalency the comparison of bioavailability between two dosage forms
Pharmaceutical equivalents Same active ingredient/salt form, same amount of active ingredient, Same dosage form, Inactive ingredients can be different
Pharmaceutical equivalents have the following characteristics do not have to contain the same inactive ingredients, or have the same physical shape, release mechanisms,packaging, or expiration time
Pharmaceutical equivalents may have different inactive ingredients, different pharmaceutically equivalent products and may not be equally suitable for a given patient. Why one drug formulation may preform differently enough to change the overall effect
Pharmaceutical alternatives Same active ingredient/diff. salt form, Amount of active ingredient can be different,Dosage form can be different,Inactive ingredients can be different
Pharmaceutical alterntives have the following characteristics they do not have to have the same inactive ingredients or have the same shape, release mechanisms, packaging or expiration time
Therapeutic equivalents therapeutic equivalents are pharmaceutical equivalents which produce the same therapeutic effect in patient
What is the name of "the orange book" that the FDA publishes annually Approved Drug Products With Therapeutic Equivalence Evaluations
Def. Pharmaceutical equivalent drug products that contain identical amount s of the same active ingredients in the same dosage form
Def. Phrmaceutical Alternative Drug products that contain the same active ingredient, but not necessarily the same salt form, amount or dosage form
Def. Therapeutic equivalent Pharmaceutical equivalents that produce the same effects in patients
When can therapeutic drug monitoring be useful? when the blood concentration of the drug reflects the concentration at the site of action
Blood concentrations are the result of four simultaneously occurring processes- absorption, distribution, metabolism and excretion
Beside the 4 processes, what is a critical factor of drug concentration and effect How drugs move through the biological membranes.
Most drugs pass through biological membranes by passive diffusion
One of the primary factors affecting oral drug absorption is the gastric emptying time
Where are the proteins that many drugs bind to, found? in the blood plasma
Why do drugs bind to proteins in the blood plasma? to form a complex that is too large to penetrate biological membranes, essentially making a drug inactive
What is used as a catalyst in the transformation of drugs to metabolites Enzymes
Most metabolites are inactive molecules that are excreted
Urinary excretion formula glomerular filtration + renal secretion - Urinary reabsorption
Created by: megancarter



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