What are the four aspects of pharmacokinetics?
absorptions, compartementalization, distribution, and elimination
What is disposition?
the study of the movement of drugs across biological membranse from the time of absorption until elimination
What is a prodrug?
an active drug
What is the First Pass Effect?
the drug enters the body and is introduced to factors that alter or destroy the drug before it reaches its site of action
What is distribution?
movement of the drug from the blood to the tissues
What is biotransformation?
chemical alteration of the drug molecule in the body
What is the most common biotransformation reaction?
What is the rate of absorption?
the time between administration and the arrival at peak plasma concentration (the higher the concentration the faster the absorption)
First order kinetics is associated with which compartment model?
What is half-life?
the time required for the body to eliminate one half of the drug it contains
What is plasma clearance (CLp)?
the volume of plasma completely freed of drug per unit time
What is total body clearance (CLb)?
the rate of drug elimination from the body, by all routes, realative to the concentration of drug in plasma
What is the excretion ratio?
the fraction of drug removed from the perfusing blood by an organ
What is pinocytosis?
the engulfment of molecules of drug dissolved in water
What is conjugation of a molecule?
the addition of an endogenous substrate to the drug or its metabolite (happens in phase II reactions)
What is an example of conjugation?
What is tachyphylaxis?
an ACUTE decrease in the response to a drug after administration
What is the partition coefficient?
describes the lipid solubility of the drug; if the drug is highly lipid soluble if is likely to cross the membrane by passive diffusion
What form are weak acids naturally in? What about weak bases?
weak acids are naturally in their protonated (non-ionized) form and weak bases are naturally in their non-protonaed (ionized ) state
What is the normal range of pKa?
What is the weak acid equation?
pH = pKa + Log (protonated/non-protonated)
What is the weak base equation?
pH = pKa + Log (non-protonated/protonated)
What is the chemical formula equation for weak acids? For weak bases?
acids: R-COOH <--> H + R-COO
base: R-NH3 <--> H + NH2
What is the Henderson-Hasselbalch equation?
pH = pKa + Log (non-protonated / protonated)
What is the Vd (litter)?
dose (mg) / drug concentration in blood (mg/l)
the larger the Vd the greater the extent of distribution
What is the permeability coeffiecient?
how easily the a drug enters the lipid phase from an aqeuous solution; important in determining the rate of approach to steady state byt not important for distribution at stready state
What is the equation for the rate of elimination?
constant x changes OR CL x C
What is the excretion ratio equation?
(concentration of drug in the arteries - concentration of drug in the veins) / concentration of blood in the arteries
OR ER = (CA-CV) / CA
What is the equation for single organ clearance?
CL = ER x Blood Flow
What is the equation for the constant of elimination?
Ke = CL / Vd
What three things is clearance related to?
Vd, T1/2, and the elimination constant
What is K (elimination constant) equal to?
K = 0.693
What is the equation for clearance?
rate of elimination devided by the concentration OR
CL = (0.693 x Vd) / T1/2
What is the equation for dosage rate?
CLb x Css
(Css is the desired steady state)
How do you calculate the loading dose?
(desired concentration) / Vd
What is idiosyncracy?
the genetically (or epigenetically) determined unpredicatble abnormla reactions to drugs usually caused by reactive drug metabolites
What are the effects of phenobarbital?
Phenobarbital increases the metabolization of enzymes and is the strongetst promoter of the p450 meatbolization patheway which leads to repid disappearance of the effects of drugs that use this pathway
Describe the purpose/effects of using urine alkalizers and acidifiers.
urine alkalizers are used on weak acids and urine adififiers are used on weak bases to quicken the excretion of certain drugs by trapping them in the urine
What is the only saturable mechanism when it comes to drug movment?
carrier mediated facilitated diffusion
How is facilitated diffusion different from simple passive diffusion?
they both use the concentration gradient but facilitated is faster because it uses carrier transporters
What is steady state?
the concentration of the drug when the maintenance rate of the drug administration is equal to the rate of elimination;
any condition in which the formaiton or introduction of substances just keeps pace with their destruction or removal so that all volumes, concentrations, pressures, and flows remain constant
How is tachyphylaxis different from other tolerance levels?
it is very acute, happens right away
*note that aquired tolerance happens over a period of time
What does the dosage regimen depend on?
dosage, route, frequency, an duration
As pH increases, H+ concentration ________, and the amount of protonated form __________
As pH increases, H+ concentration decreases, and the amount of protonated form decreases
What proteins to acidic drugs tend to bind to and what proteins to basic drugs tend to bind to?
acidic drugs tend to bind to albumin and basic drugs tend to bind to alpha-I-glycoproteins
At what percentage is protein binding and drug interactions important?
True or False: As concentration increases, movement across the membrane is always first order kinetics.
What are the important characteristics of passive diffusion?
based on concentratin gradient from high to low concentration and high lipid solubility, and only involves drugs of the non-ionized state, no energy required
What are the important characteristics of facilitated diffusion?
does not involve energy but can involve transport proteins, drugs move at a faster rate from high to low concentration
What are the important characteristics of active diffusion?
moves from low to high concentration using energy from ATP
What is the difference between primary and secondary active transport?
primary uses ATP and secondary uses the Na electrochemical gradien created by ATP from primary
What are some consequences of negative tissue absorption?
a drug might be affected locally by inflammation (lower pH) or get trapped and diverted to fat tissue
What is the significance of repository or depot forms of a drug?
they have a slower absorption and therfore have a longer action in the body
What is the difference between dose and conentration?
the higher the concentration the faster the absoprtion, however the dose involved the form of the drug and the way the drug is given so it can affect this
True or False: The blood flow have less impact to drugs that cross the membrane slowly
How does sympathetic stimulation affect blood flow to skeletal muscle and blood flow to GI tract?
increase blood flow to skeletal muscle and decreases blood flow to the GI tract and subcutaneous sites and skin
How does epinerphrine effect local duration of a anesthetics?
epinephrine is an alpha-adrenergic that increases the local duration of action of local anesthetics by inducing vasoconstriction
How does shock affect blood flow to the GI and peripheral tissues?
increases blood flow to both GI and peripheral tissues
Intramuscular absorption is ________than IV and inhalation. (slower or faster)
Subcutaneous absorption is ________ than intramuscular. (slower or faster)
Oral absorption is usually _________ than injection (slower or faster)
What are the two fastest routes of administration?
intravenous and inhalation
Propylene glucol is a ______ pH vehicle. (low or high)
True or False: Sulfonamides in strongly alkaline solutions cause sterile abscesses and necrosis.
What part of the GI tract is the main site of absorption?
the upper part of the small intestine
What would you add to make an environment more acidic?
ammonium chloride, baflilomycin, chloroquine, and methionine
What would you add to make an environment more basic?
Which systems have a high blood flow?
heart, kidney, brain, liver, and endocrine glands
Which system have a moderate blood flow?
muscle and skin
Which systems have a low blood flow?
bone and adipose tissue
Which drugs boost/induce liver metabolism?
phenobarb, phenylbutazone, griseofulvin, rifampin
Which drugs inhibit liver metabolism?
chloramphenical, cimetidine, ketoconazole
What are the major sites of biotransformation?
liver and intestinal mucosa
Describe the phase I reactions.
oxidation, reduction, and hydrolysis; alters the basic structure of the nucleus; may activate or inactivate the drug
Describe the phase II reactions.
conjugation (glucoronidation); nearly always inactivates the drug
What are some major characteristics of the p450 system?
located in the microsome in the ER
targets lipophilic drugs
oxidizes drugs to a more hydrophilic form
is induced by phenoparb, barbituates, and NSAIDS
is inhibited by chloramphenical
What is the most common type of phase II reaction?
Who is defective in glucoronication?
felines and neonates
True or False: All molecules less than 7000 can be filtered
True or False: Ionization does not affect filtration rate
What makes active tubular secretion different from glomerular filtration?
active tubular secretion is faster, can move against the drugs electrochemical gradient, require energy provided by Na pump in the basolateral membrane, is carrier-mediated, is not affected by plasma protein binding, and equilibrium between free and unboudn frug can be rapidly re-established
True or False: plasma protein binding does not affect actvie tumular filtration
What does the cation transport system use? the anion transport system?
the cation transport system uses weak bases and the anion transport system uses weak acids
Why are weakly soluble non electrolytes slowly eliminated?
because they are usually reabsorbed
True or False: The purpose of reabsorption is to establish high concentration gradients.
What is the drug example for redistribution?
What are the drug examples for tolerance?
morphine and beta-2-agonists
Which compartment model ONLY includes first order process and instantaneous mixing
What is the difference between the rate of distribution and the extent of distribution?
the rate of distribution is estimated by the distribution phase half-time in the two compartments while the extent of distribution is estimated by the apparent volume of distibution
What is the goal of the loading dose / maintenance dose system?
basically to give the loading dose first so that the drug reaches the concentration you want and then change to the maintenance dose to keep it there
How is elimination related to first order kinetics?
the rate of removal of a drug from plasma is proportional to the concetraion present at a given time; a constant percent of drug is eliminated per unit time
Half-life is the time required for the body to eliminate one-half of the drug it contains and determines the rate at which the plasma concentration of a drug rises using constant IV infusion to attain a stready state
What is the difference between pharmacokinetics and pharmacodynamics?
pharmacokinetics the ability and process of the drug reaching the are of action and pharmacodynamics is the ability of the drug to act at the site
What are the types of effects of drugs?
therapeutic effect = the desirable effect
side effect = the effect is not too bad and happens at therapeutic dose
adverse effect = bad effect still at therapeutic dose
toxic effect = happens at a dose above the therapeutic dose
Which one of the types of effecta can be irreversible?
Which mechanism of drug action includes saline purgatives?
What is a drug example of the chemical mechanism of drug action?
What is a drug example of the inhibition of stimulation of enzymes?
What mechanism of drug action is epinephrine an example of?
What drug example is used for interference with cell metabolism?
What drug is an example of replacement?
What are the mechanisms of drug interaction?
inhibition of stimulation enzymes
interference with cell metabolism
What are the levels of drug action?
system (ANS and cardiovascular)
tissues (secretion and contraction)
cellular (G protein and ion channels)
molecular (receptors and ion channels)
What is a pharmacological receptor?
cell constituent that binds to an agonis with high affinity and high chemical specificity; induces confirmational change
What is an example of a drug receptor?
GABA receptor complex
Where are the majority of receptors?
on the cell membrane
What type of receptors are in the cytoplasm?
steriod hormones; progesterone
What is an example of an up-regulator?
beta-1 adrenergic receptors in the heart; increase cardiac output by increasing heart rate, contractility, and conduction
What are examples of down regulation?
beta-2 adrenergic receptors on the bronchioles; bronchiodilation; turbutaline or albuterol
a drug that causes a physiological effect; has affinity and efficacy (intrinsic activity)
What are the characteristics of a full agonist?
produces a maximal response byt occupying all or a fraction of the receptors; 100% response and 100% efficacy
What is an example of a full agonist?
What are the characteristics of a partial agonist?
produces less than maximal reponse even when if occupies all of the receptors
What is an example of a partial agonist?
What are the characteristics of an inverse agonist?
a drug that binds to a spontaneously activated receptor resulting in inactivation of the receptor
What is an antagonist?
a drug that blocks the response produced by an agonist; has affinity but no efficacy
What are the characteristics of a competitive antagonist?
reversibly binds to the receptor at the same site as the agonist
What is an example of a competitive antagonist?
What are the characteristics of a non-competitive antagonist?
binds reversibly or irreversibly to any binding site preventing the agonist from binding to its binding site; has long action and covalent bonds
What is an example of non-competative antagonists?
What are the characteristics of uncompetitive antagonists?
binds to a different site than the agonist preventing it from producing a molecular response; can bind when the agonist is bound to the receptor; needs activatio of the receptor
What is an example of a mixed agonist-antagonist?
What is the only irreversible receptor binding and what type of bond does it have?
non-competitive, covalent bonds
What is the sequence of signal transduction?
activated receptors --> G protein --> effector --> effector substrate --> second messangers ion transport --> cellular response
What is graded dose response?
corellates the increase in dose with the increase in drug reponse
What is the maximal effect / efficacy / plateau / ceiling?
the increase in response is proportional to the number of receptors occupied
When is the maximal response reached?
when the drug occupies 100% of its receptors
What is Kd?
the concentration of the drug that results in binding 50% of the receptors; this is the equilibriu dissociation constant
When are spare receptors present in relation to EC50 and Kd?
EC50 < Kd
What is EC50?
the percentage of the dose that produces half the maximal effect
What is potency?
the function of the drug's affinity for its receptors; the smaller the dose the more potent the drug; measured by EC50
True or False: Efficacy and selectivity of the drug are more important than potency
What is the significance of the slope?
indicates the range or dosage over which the drug acts; drugs with a steeper slope tent obe more toxic; drugs with the same receptor must have similar slopes
What are the types of variability?
vertical = the administration of the same dose at different times
horizontal = the administration of variable doses
Describe the quantel-dose relationship. Give an example.
either there is a recsponse or not (all or none); used to study the minimal dose needed to produce a response
What is the threshold dose?
the minimum amound needed to produce a measurable reponse
What is the equation for the therapeutic index?
TI = LD50 / ED50
What is the equation for standard safety margin?
SSM = (LD1 - ED99) / ED99