quiz 1: module 1 PHARM Flashcards
pharmakon=
drug/poison
kinesis=
motion
pharmacokinetics=
the study of drug movement throughout the body and what happens to this drug on its journey
what are the four basic pharmacokinetic processes
- absorption
- distribution
- metabolism/ biotransformation
- excretion
what is absorption
the movement of a drug from its site of administration into the blood
what is distrubtion
drug movement from the blood to the interstitial space of tissues and from there into cells
what is metabolism
enzymatically mediated alteration of drug structure
what is excretion
the movement of drugs and metabolites out of the body
the 4 processes determine..
the concentration of a drug at its site of action
by knowing pharmacokinetics we can..
maximize beneficial effects and minimize harm
intensity of the response to a drug is directly related to the?
concentration of the drug at its site of action
to maximize beneficial effects, a drug must?
achieve concentrations that are high enough to elicit desired responses, to minimize harm must avoid conc that is too high
balance is achieved by?
selecting the most appropriate route, dosage, and schedule
all four phases of pharmacokinetics involve drug movement, and thus..
membrane crossing
drugs must cross membranes to enter the blood from their site or once in the blood they must..
cross the membrane to leave the vascular system and reach their site of action and must cross membranes to undergo metabolism and excretion
describe the membrane structure
composed of layers of individual cells
- cells so close together that drugs usually pass through the cells rather than going between them
- therefore, ability of drugs to cross a membrane is determined primarily by its ability to pass through single cells
what is the major barrier of crossing a cell?
its cytoplasmic membrane- contains double layer of molecules (phospholipids, have round head and two tails w/ proteins embedded in the layer)
three ways to cross a cell membrane?
- passage through channel or pores
- passage with aid of a transport system
- direct penetration of the membrane itself (not common)
channels and pores?
very few drugs use this way bc channels are very small, specific for certain molecules
-for example sodium and potassium
transport systems?
carriers that move drugs from one side of membrane to another, some require energy
all transport systems are selective based on structure!
-orally would not be able to be absorbed without transport systems
-p glycoprotein is the multidrug transporter protein
p-glycoprotein ? (PGP)
- in liver it transports drugs into bile for elimination
- in kidneys it pumps drugs into urine for excretion
- in placenta it pumps drugs back into maternal blood
- in intense it transports drugs into intestinal lumen
- in the brain capillaries it pumps drugs into the blood
direct penetration of the membrane?
- most drugs the movement is dependent on ability to penetrate membranes directly because
- most drugs are too large to pass through channels or pore
- most drugs lack transport systems
- to directly penetrate must be lipid soluble because membranes are mostly lipids
- polar molecules and ions can not penetrate membranes
what are quaternary ammonium compounds?
contain at least one atom of nitrogen and carry a positive charge at all times
- constant chare is because of atypical bonding to the nitrogen
- unable to cross most membranes, so these compounds must be injected cuz cant get out of lumen of intestine
what is meant by pH dependent ionization?
most drugs are either weak organic bases or weak organic acids and exist in charged and uncharged forms
- whether or not they carry a charge is determined by the pH of the surrounding medium
- acids give up a proton, bases accept protons
- when acid gives up, it becomes nagatively charged
- when base accepts a proton it becomes positively charged
- acids tend to ionize in basic
- basics tend to ionize in acidic
what is meant by ion trapping (pH partitioning)?
because the ionization of drugs is pH dependent, when the pH of the fluid on one side of a membrane differs from the pH of the fluid on the other side, drug molecules will tend to accumulate on the side where the pH favours their ionization
- acidic drugs will accumulate on the alkaline side where there is a pH gradient between 2 sides of a membrane
- basic drugs will accumulate on the acidic side where there is a pH gradient between two sides of a membrane
the rate of absorption determines..
how soon the effects will begin
amount of absorption determines how..
intense effects will be
drug absorption rate is affected by?
the physical and chemical properties of the drug itself and by physiologic and anatomic factors at the absorption site
factor that affect drug absorption?
- rate of dissolution
- surface area
- blood flow
- lipid solubility
- pH partitioning
rate of dissolution & drug absorption
before a drug can be absorbed it must first be dissolved. some drugs allow faster dissolution and have faster onset
surface area & drug absorption
larger the surface area, faster the absorption
blood flow & drug absorption
drugs are absorbed the most rapidly where there is a lot of blood flow because blood containing newly absorbed drugs will be rapidly replaced by drug-free blood, thereby maintaining the concentration between the drug on the outside of blood and inside
lipid solubility & drug absorption
high lipid-soluble drugs are absorbed more rapidly than drugs whose lipids solubility is low because they can readily cross the membranes that separate them from blood
pH partitioning & drug absorption
absorption will be enhanced when the difference between the pH of plasma and the pH at the site of administration is such that drug molecules will have a greater tendency to be ionized in the plasma
two major groups of commonly used routes of administration
enteral (via GI tract)
parenteral (outside GI, but actually means by injection)- intravenous, subcutaneous, intramuscular
the route by which a drug is administered will significantly..
affect both the onset and intensity
barriers to absorption for intravenous?
none because IV puts a drug directly into bloodstream
advantages of IV
rapid onset (emergencies)
- nurse has percise control over levels of drugs in the blood
- permits use of large fluid volumes
- permits use of irritant drugs
disadvantages of an IV
high cost, difficulty, and inconvenience
- irreversibility, no turning back once administered
- fluid overload
- infection can occur from improper technique
- embolism (blood vessel blockage at site distant from point of administration)
intramuscular- barriers to absorption
-only barrier is the capillary wall, in the capillaries that serve muscles, there are large spaces between the cells that make it so drugs can pass through these spaces with ease and need not cross cell membranes, no significant barrier
absorption pattern of intramuscular
may be absorbed rapidly or slowly depending on:
- water solubility of the drug
- blood flow to the site of the injection
advantages to intramuscular
- can be used for administration of poorly soluble drugs (little harm will come from depositing a suspension of undissolved drug in interstitial space of muscle tissue)
- can be used for depot preparations (drug is absorbed slowly over an extended time)
disadvantages of IM
discomfort and inconvenience (pain, can cause local tissue injury)
-IM cannot be used for patients on anticoagulants
subcutaneous..?
very similar to IM, not significant barriers to absorption
- blood flow and circulation are major determinants of how fast absorption takes place
- similar advantages and disadvantages as iM
oral- barriers to absorption
- may be absorbed in stomach, intestine, or both
- 2 barriers: layer of epithelial cells that line the GI tract and the capillary wall
- drugs must pass through the cells rather than between them in the GI tract
- some drugs cause intestinal absorption to be reduced
absorption pattern of oral drugs
rate can be highly variable bc of factors:
- solubility and stability of drug
- gastric and intestinal pH
- food in the gut
- co-administration with other drugs
- special coatings on the drug prep
drug movement following absorption (oral)
- drugs absorbed from all sites along GI tract (except oral mucosa and distal segment of rectum) must pass through the liver before they can reach general circulation
- for many drugs this passage only involves going through the liver, enter inferior vena cava and eventually general circulation
- other drugs undergo extensive hepatic metabolism
advantages to oral
- easy and convenient
- safer than injections in terms of absorption (no risk of fluid overload, infection, embolism, potentially reversible
disadvantages to oral
- variability of absorption
- difficult to control the concentration, onset, intensity, and duration of response
- patient requirements
- local irritation
- inactivation of other drugs potentially
in general oral administration is preferred over parenteral, but there are situations where parenteral may be superior:
emergency requiring rapid onset
- plasma drug levels needing to be tightly controlled
- treating a systemic disorder than cannot cross membranes
- treating patients who cannot or will not take drugs orally
- treatment with drugs that would be destroyed by gastric acidity, digestive or hepatic enzymes
different formulations of drugs for oral administration?
tablets, enteric coated preparations, sustained release preparations
tablets are?
mixture of a drug plus binders and fillers compressed
- tablets made by diff manufacturers differ in rates of disintegration and dissolution
- as a result, 2 tablets that contain same amt of same drug may differ with response
enteric coated preparations are?
covered in material designed to dissolve in intestine but not stomach
- materials used are fatty acids, waxes, shellac
- general purposes: protect drugs from acid and pepsin in stomach, protect stomach from drugs that cause gastric discomfort
disadvantages of enteric coated preparations
- can make absorption even more variable because gastric emptying can vary from minutes up to twelve hours
- enteric coatings sometimes fail to dissolve, allowing meds to pass through GI tract without being absorbed
sustained-release preparations are?
filled with tiny spheres that contain the drug, the spheres have coatings that dissolve at variable rates
- released steadily throughout the day
- reduce number of doses and steady drug levels
- high cost though
distribution (movement of drug from blood to interstitial space of tissues and from there into cells) is determined by 3 factors?
- blood flow to tissues
- ability of a drug to exit the vascular system
- ability of a drug to enter cells
blood flow to tissues and distribution?
- first phase of distribution
- rate determined by blood flow
- absecesses and tumors can cause low regional blood flow
exiting the vascular system and distribution?
- after a drug has been delivered to an organ or tissue via blood, next step is to exit the vasculature
- they leave the blood at capillary beds
typical capillary beds description
- offer no resistance to the departure of drugs
- drugs can leave the vasculature simply by passing throug pores in the capillary walls, the drugs pass between the capillary cells
what is the blood-brain barrier
- refers to the unique anatomy of capillaries in the CNS
- tight junction between the cells that compose the walls of most capillaries in CNS (so tight they prevent drug passage)
- protects brain from injury by potentially toxic substances, but can be a significant obstacle in therapy of CNS disorders
to leave the blood in blood brain barrier…
a drug must be able to pass through cells of capillary wall- only drugs that are lipid soluble or have a transport system
why is protein binding (specifically plasma-albumin binding important)
it is the most abundant protein in the plasma and it is very large
- always stays in the blood stream!
- forms reversible bonds with drugs
- bound molecules cannot reach their sites of action or undergo metabolism or excretion until drug protein bond is broken- this prolongs the distribution phase and increases drug half life
what is metabolism, where does it take place
- chemical alteration of drug structure
- most drug metabolism takes place in the liver
most drug metabolism that takes place in the liver is performed by?
hepatic microsomal enzyme system (p450 system) a group of 12 closely related enzyme families
drug metabolism does not always result in the breakdown of drugs into smaller molecules, can also result in?
synthesis of a molecule that is larger than its parent drug
therapeutic consequences of metabolism
- accelerated renal excretion of drugs
- drug inactivity
- increased therapeutic action
- activation of “prodrugs”
- increased toxicity or decreased toxicity
the most important consequence of metabolism?
promotion of renal drug excretion
-kidneys are unable to excrete drugs that are highly lipid soluble, coverts lipid-soluble drugs into more hydrophilic forms
what is the first pass effect
rapid hepatic inactivation of certain oral drugs
- when drugs are absorbed from GI tract, they are carried directly to the liver via hepatic portal vein
- if the capacity of the liver to metabolize a drug is extremely high, that drug can be completely inactivated on its first pass through the liver, so no therapeutic effects
- these drugs are therefore often administering parenterally to bypass the liver
induction?
the process of stimulating enzymes synthesis
-drugs that act on the liver to increase rates of drugs metabolism are inducers
drug metabolizing capacity of infants?
limit because liver does not develop its full capacity until about 1 year after birth
what is excretion
removal of drugs from body
-exit via urine, bile, sweat, saliva, breast milk, and expired air
most important organ in excretion
kidneys
steps in renal drug excretion?
- glomerular filtration (proteins filtered by the kidneys)
- passive tubular reabsorption (drugs that arent lipid soluble remain in the urine to be excreted)
- active tubular secretion (active transport systems including P-glycoprotein
factors that modify renal drug excretion
- ph dependent ionization
- competition for active tubular transport
- age
minimum effective concentration=
the plasma drug level below which therapeutic effects will not occur
-a drug must be present in conc at or above MEC
toxic concentration=
the plasma level at which toxic effects begin
therapeutic range of plasma levels of drug conc
falls between the MEC and toxic concentration
-objective of drug dosing is to maintain plasma drug levels within therapeutic range
what is drug half life
time required for the amount of drug in the body to decrease by 50%
how is plateau drug levels achieved?
administering repeated doses will cause a drug to build up in the body until a plateau has been achieved
-when amt of drug eliminated between doses equals amount administered, drug levels will remain constant and plateau will have been reached
peak concentration?
highest amount
trough concentration
lowest
what are pharmacodynamics
study of the biochemical and physiologic effects of drugs and the molecule mechanisms by which those effects are produced
-what drugs DO to the body, HOW they do it
dose-response relationship is?
- the relationship between the size of an administered dose and the intensity of the response produced
- it is graded, AKA, as dose increases, response becomes larger
3 phases of dose-response relationship
phase 1: occurs at low doses, curve is flat
phase 2: increase in dose elicits a corresponding increase
phase 3: as dose goes higher, reaches a point where increase in dose is unable to elicit further increase, curve flattens
dose response curves reveal two characteristic properties?
maximal efficacy and relative potency
what is maximal efficacy
largest effect that a drug can produce, indicated by height of dose-response curve
relative potency is?
amount of drug we must give to elicit an effect, indicated by positive of the dose-response curve along X axis
-potency and efficacy are completely independent qualities!
what are receptors
special chemical sites in the body that most drugs interact with to produce effects-usually hormones, NTs, other regulatory molecules
drugs cannot give cells new functions, only alter the rate ?
of pre-existing functions
when a drug binds to a receptor, all that it can do is?
mimic or block the actions of endogenous regulatory molecules
four primary receptor families?
- cell-membrane embedded enzymes: located on cell surface, binding activates the enzyme
- ligand gated ion channels:span the cell membrane, function is to regulate flow of ions into and out of cells
- g protein coupled receptor systems: binding of ligand or agonist activates G protein, which activates effector
- transcription factor: found within the cell, responses to activation of these receptors are delayed
selective drug action is possible is because?
drugs act through specific receptors, each type of receptor participates in the regulation of just a few processes
simple occupancy theory?
states that intensity of response to a drug is proportional to number of receptors occupied by that drug, maximal response will occur when avail receptors occupied by that drug
modified occupancy theory?
ascribes two qualities to drugs
- affinity: strength of the attraction between a drug and its receptor
- intrinsic activity: ability of a drug to activate the receptor following binding
what are agonists
molecules that activate receptors
what are antagonists
produce their effects by preventing receptor activation by endogenous regulatory molecules and drugs
-non-competitive and competitive
what are partial agonists
agonist that has only moderate intrinsic activity, so as result the maximal effect that a partial agonist can produce is lower than that of a full
what is interpatient variability
dose required to produce a therapeutic response can vary substantially from patient to patient, important to monitor individual response
ED50=
dose that is required to produce a defined therapeutic response in 50% of the population, can be considered a standard dose
what are drug-drug interactions
can occur whenever a patient takes 2 or more drugs, some are intended & desired, some not
three possible outcomes of drug-drug interactions
1) drug may intensify effects of the other
2) drugs may reduce the effects of the other
3) combination may produce a new response not seen with either drug alone
4 basic mechanisms of drug-drug interactions?
1) direct chemical or physical interactions
2) pharmacokinetic interaction: affects all four of the basic processes
3) pharmacodynamic interaction- at same site, or different sites
4) combined toxicity
body weight and composition and drug effects?
- significant determinant of drug effects
- higher the conc. more intense the response
- prescriber may base adjustment on SA of the body rather than weight to account of muscle or fat variations
age and drug affects?
drug sensitivity varies with age
-infants and older adults especially sensitive
liver disease and drug effect
- can cause drugs to accumulate
- rate of metabolism will decline
kidney disease and drug effect
- can reduce drug excretion, causing drugs to accumulate in the body
- may build up to toxic levels in the body
acid base imbalance and drug effects
changes in acid-base affect all pharmacokinetics
altered electrolyte status and drug effect
- K, Na, C, Mg, P important in cells
- when electrolyte levels disturbed, multiple cellular processes disruption
what is tolerance
decreased responsiveness to a drug as a result of repeated drug admin
what is pharmacodynamic tolerance
familiar tolerance, associated with long term admin of drug, result of an adaptive process that occur in response to chronic receptor occupation
what is metabolic tolerance
-defined as tolerance resulting from accelerated drug metabolism, causes increased metabolism
what is tachyphylaxis
reduction in drug responsiveness brought on by repeated dosing over a short time, not common
what is the placebo effect
any response the patient may have to a placebo is believed to be based solely on patients psychologic reaction
bioavailability?
amount of active drug that reaches systemic circulation
-different formulations of the same drug can vary in bioavailability
genetics and pharmacogenomics
a patients unique genetic makeup can lead to drug responses that are different from those of the population at large
genetic variants that alter drug metabolism
- most common mechanism by which genetic variants modify drug response
- reduction in benefits, or increase in toxicity
gender and drugs
men and women can respond differently to the same drug
