midterm Flashcards
pharmacodynamics
effects of a drug on the body
-biochemical and physiologic actions of drugs and mechanisms of drug actions at the molecule, cellular, tissue and organisms level
drugs do not create new functions, but they …..
produce the same action as the body’s own chemicals and they block the action of the body’s own chemicals (when something goes wrong)
what is the importance of a drug receptor
a response results when the drug or ligand binds to its given receptor
-drugs attaches to the sites through varying bonds
what are the most common bonds seen at receptor sites
hydrogen and ionic bonds
-as there is little energy and can be easily broken
two types of receptors
free (unoccupied) or reversibly (occupied)
lock and key model
the receptor is the lock and the drug is the key meaning each drug has to fit into the right receptor
-occurs within the body naturally
induced fit model
the receptor can change the shape slightly meaning the drug does not have to fit exactly
-however, too much change will cause ineffectiveness
functions of ion channels
neurotransmission, cardiac condition and muscle contraction due to different ion channels
-these channels are selective for the ions they conduct
what are the various forms of cell signal
heat, light, water, odors, touch and sound
-remember, without signaling nothing would happen properly
conformational change
when signals from receptor activation/inhibition cause functional or structural changes within the cell
-can cause ion channels to open, formation of intracellular messengers, alterations within gene expressions or alterations in cell growth
agonist
ligand that activates the receptors
-results in an active conformation after the drug has binded to its receptor
-the reaction will occur and will cotninue to occur
antagonists (inhibitors)
preventing the action of the agonist at the receptor site but there is no effect without agonists
-results in inactive conformation after the receptor binds
-stopping of the reaction
what are the subtypes of antagonists
receptor, noncompetitive and competitive
receptor antagonists
can bind to either the active or allosteric receptor site and can be reversible or irreversible
noncompetitive antagonists
can bind to either the active or allosteric site and they are irreversible
-often occur through covalent bonds (which do not easily go away)
competitive antagonists
competes with the agonist for the same receptor site and can block that receptor from binding which maintains its being inactive
-there needs to be an agonsit present, so has to be at an active site
active receptor site
where agonist can bind to cause action
-antagonist will prevent binding of an agonist to the receptor
allosteric site
can be impacted by function
-antagonist will prevent conformational change
therapeutic window
range of doses of a drug that elicits a therapeutic response without adverse effects
-with a smaller window, plasma drug levels must be monitored closely
therapeutic index
what quantifies the therapeutic window
-TD50 / ED50
graded dose response
effects of various drugs on an individual
-potency (affinity of a drug) and efficacy (receptor occupancy of drug molecules) are important parameters
affinity
liking receptors
-the higher affinity, the more likely they will bind to that receptor to produce the effect
quantal dose response
describes the effects of various drug doses on a population
-describes concentrations that produce a given effect in a population
-defined as present or not present
TD50
toxic dose 50% of the time
ED50
effective dose 50% of the time
LD50
lethal dose 50% of the time
ADME
big part of what the body does with the drug consisting of absorption, distribution, metabolism and excretion
-these impact the free drug
absorption
how the drug overcomes obstacles or barriers before a drug can reach its intended target
-needing to get through barriers in order to get into circulation for where the drug is carried where it needs to go
what are some examples of barriers within the body
cell membrane, blood brain barrier, blood labyrinth barrier and the blood placental barrier
factors that impact the ability to cross a cell membrane
lipid solubility, degree of ionization, molecular size and shape of the drug molecule
-more lipid soluble, the easier it will cross
-charged molecules must use a channel
-small molecules can cross easily
blood brain barrier
selective barrier that separates circulating blood from the brains extracellular fluid
-allows passage of water, gases and lipid soluble molecules by passive diffusion
blood labyrinth barrier
homeostatic mechanism that protects the inner ear through maintaining the composition of the inner ear fluids
-small molecular weight molecules can enter the periplymph in a dose and time dependent manner
blood placental barrier
barrier between maternal and fetal circulation that protects the fetus from noxious agents
-antigens and antibodies can cross both ways
common route of administration
enteral, topical and parenteral
benefits and negatives of enteral route
benefits : self administration, portable, less likely to introduce infections
negatives : drug is exposed to harsh environments (pH of stomach, food in stomach may impact it, and presence of other drugs may impact it)
what do all enteral administration drugs go through
first pass metabolism
first pass metabolism
drugs that are passed orally pass from the GI tract to portal veins and enter the liver prior to the systemic circulation
-protects individuals from the effect of ingested toxins which are detoxified within the liver
what is dangerous about parenteral administration
greater risk for addiction, fear of needles, high risk for hepatitis and is the most dangerous route as it bypasses all the body’s natural defenses
-intrathecal is part of this and it is dangerous as it passes through all barriers and allows no time to react if adverse reaction occurs
distribution
taking the drug from the site of administration to the site of action through the circulatory system
drugs are found within two forms of the blood, these are ….
bound to plasma proteins, free or unbound drugs
-plasma proteins binding reduces available for transport to target site
-free drug form can pass across gaps between capillary cells to leave plasma and enter interstitial fluids
-as the free drug leaves the plasma the bound drugs becomes unbound
bound forms remain in the compartment for ……..
longer and the drug will exhibit high levels of protein binding that required higher concentration
metabolism
process of biochemical reactions in the body that convert lipid soluble drugs to water soluble metabolites so the drugs can be more easily excreted by the kidneys
-liver contains the greatest amount of metabolic enzymes
what are the biotransformation reactions
oxidation/reduction or phase 1 AND conjunction/hydrolysis or phase 2
oxidation/reduction or phase 1
modifies the chemical structure of a drug through oxidation/reduction
-liver has the enzymes to do these reactions
-CYP is the common enzyme
cytochrome P450 (CYP) enzyme
determines the rate and extent to which individuals can metabolize various drugs
-if they are induces, increases rate of metabolism
-if they are inhibited, decreases the rate of metabolism
conjunction/hydrolysis or phase 2
inactivates the drug or enhances the drug solubility and excretion rate into urine or bile
-conjugation : forming a compound by joining two or more chemical compounds
-hydrolysis : reaction involving the breaking of a bond in a molecule using water
excretion (elimination)
movement of a drug and or its metabolites out of the body
-through renal excretion but can also happen through biliary excretion with minor amounts through respiratory or dermal routes
what happens if a drug reaches the kidneys and is fat soluble
it will be reabsorbed by the kidneys and placed back into the bloodstream due to the kidneys not being able to excrete this type of drug
what can happen if kidney function is affected
excretion of the drug will take longer and can increase drug toxicity
-kidney function can be altered by age, drug toxicity, or from diseases such as diabetes, hypertension, renal disease or cancers
drug clearance
rate of elimination of a drug from the body that is relative to the concentration of the drug within the plasma
- (metabolism + excretion) /drug
two ways drugs are eliminated out of the body
zero order elimination kinetics and first order elimination kinetics
zero order elimination kinetics
elimination of a constant quantity per time unit of the drug
-as you get more drug, the same amount
-a constant amount of drugs will be cleared
first order elimination kinetics
elimination of a constant fraction per time unit of the drug
-as you get more drug, more will be cleared
-adaptive with the amount within the body
what is half life and how does it relate to drug clearance
defined as the time required for the serum drug concentration to decrease by 50%
-when half life is too short, removed too quickly from the body
-when half life is too long, removed too slowly from the body
-a drug is cleared from the body in around 4-5 half lives
therapeutic dosing
seeks to maintain the peak plasma concentration below toxic levels and the trough plasma concentration above minimally effective levels
-can be steady state accumulation, loading dose and maintenance dose
steady state accumulation
at regular dosing frequency, the drug does not accumulate and a steady state is reached because elimination process is concentration dependent
-higher the concentration, greater the amount eliminated is
loading dose
higher initial or loading dose of drugs administered to compensate for drug distribution in the tissues from plasmas
maintenance dose
once steady state is reached, subsequent drug doses must replace only what is lost through metabolism and excretion
medical history
important to understand where the patient is being seen and why
-any previous treatment or ongoing treatment going on
-are there any barriers such as HL, vision issues, speech problems, cognitive or memory issues, language or cultural diversity
drug metabolism can be impacted by what factors
age, pregnancy and lactation, diet and environment, disease, preexisting auditory and vestibular disorders, pharmacogenomics, and metabolic drug interactions
how does age impact drug metabolism
children and older adults are impacted
-children have slow reactions
-older adults have a general decrease within metabolic capacity
how does pregnancy/lactation impact drug metabolism
teratogenicity and the side effects (mainly during first trimester is the highest risk) as well as the transfer of drugs to the infant through breast milk
what is an example of how something in a diet can alter drug metabolism
grapefruit juice can inhibit the CYP enzyme within the small intestine and decrease phase 1 metabolism
compliance
degree to which a patient behavior matched medical advice
-degree of correlation of actual dosing history with the prescribed medical therapy
noncompliance
any behavior that does not follow medical advice
factors impacting compliance
parent/caregivers, type of illness or disease, intellectual status, physical status and many others
improving compliance
education!
-also ensure that the patient understands fully what is expected of them as well as what the plan is
polypharmacy
taking five or more medications at the same time, meaning in the same 24 hour time period
-more common within older adults and younger people with chronic medical conditions such as diabetes, arthritis and autoimmune conditions
what is the risk with polypharmacy
increase the risk of drug-drug or drug-disease interactions with the risk of prescription cascade
what are the 4 mechanisms of drug interactions
drugs have similar effects, metabolic effects, absorption effects and displacement from plasma proteins
phase 1 vs. first pass metabolism
first pass : only with oral medications, after absorption and before it gets to blood stream
phase 1 : occurs in metabolism, within the liver and occurs with any drug despite the route of administration
what are the major organs involved with metabolism and excretion
metabolism : liver
excretion : kidneys
all NT’s are __________ at their respective sites
agonists
the _________ the potency, the _________ medicine you need to take
higher ; less
how does the drug dosage you take compare to what you need for an effective dose
the dosage you take is not necessarily what you need to be an effective dose, but during the process some of the dosages may not be available to hit the target
what type of molecules can easily cross the cell membrane? which ones cannot easily cross the membrane?
nonpolar molecules (i.e. steroids) can easily diffuse through however polar molecules need some type of active function to cross the membrane
bioavaliability
amount of drug available within the circulation
-dependent on route, chemical form and patient factors such as GI enzymes/pH metabolism
