Module A Flashcards
Heparin is largely confined to the plasma compartment because of its __________
high molecular weight
Maintenance doses are designed to maintain a steady state of plasma concentration and for convenience are often administered in intervals equal to _________
the drug’s half life
this will lead to a mximum two-fold fluctuation in the drug’s plasma concentration which is seen as acceptable in most cases
By definition, drugs delivered by the IV route have ____% bioavailability
100%
Drug clearance (Cl) is defined as:
The volume of body fluid from which the drug is removed per unit time.
an antagonist that binds to a receptor irreversibly through covalent bonding is said to be _________
non-competitive
In the dose-response relationships shown here, drug B would act as a ___________ in the presence of drug C
antagonist
Drug B is an incomplete agonist and will act as a competitive inhibitor in the presence of a drug with higher efficacy
In general, acidic drugs bind to plasma _________
albumin - A for Acid and Albumin
npo means:
nothing by mouth
“nil per os”
ED50 is used to measure _________ (potency / efficacy) and is defined as:
ED50 (median effective dose) measures drug potency and is the dose that produces 50% of the maximal effect of the drug
qh means
every hour
“quaque hora”
Drugs that are eliminated by Zero-order kinetics have a _______ (constant / variable) half-life and a ________ (constant / variable clearance) relative to plasma concentration of the drug.
variable half-life and variable clearance. The half-life is proportional to plasma concentration while the clearance is inversely proportional
desensitization/tachypylaxis is a ________-term adaptation to exposure to a drug, while down-regulation is _________-term reaction
desensitization is short term, down-regulation is long term
Aqueous diffusion of a drug is limited by __________
Molecular weight (only small molecules can diffuse through aqueous pores)
A drug that has affinity for a receptor and only incomplete efficacy is a(n) _________
partial agonist
pc means
after meals
“post cibum”
Weakly acidic drugs absorb best in the (stomach / intestine)
intestine - there is a greater surface area available for diffusion, which is more important than acid/base ionization effects
ex aq means:
in water
bid means
twice per day
“bis in die”
The organs most involved in excretion are the _____
Kidneys
Phosphorylation of receptors in response to repeated exposure to ligand is an underlying mechanism of
____________
desensitization
phosphorylation may reduce the affinity of ligand for receptor or may mark the receptor for cellular internalization, reducing receptor density on the cell surface
Define enterohepatic cycling
The phenomenon whereby drugs excreted through the biliary pathway are metabolized by gut flora and reabsorbed into the circulation
The main purposes of biotransformation are:
reduce the toxicity of drugs and make them more soluble to facilitate excretion
Describe what a prodrug is and why it may be given
a prodrug is inactive until metabolized by the body. It may be given because the prodrug molecule is better absorbed than the active molecule (ex: elanapril).
The time indicated by E in this drug plasma concentration curve is called ______ and represents _____
Onset represents the time after drug administration until the MEC is reached, i.e. the time until a measurable therapeutic effect is observed
compare and contrast the therapeutic index (TI) and certain safety factor (CSF) of a drug
Both are measures of a drugs safety in relation to its potency
Therapeutic index (TI) is the ratio between LD50 and ED50
Certain safety factor (CSF) is the ratio between LD1 and ED99 of a drug. It is a more restrictive and perhaps more practical measure of the safety of a drug.
A drug that has both affinity and efficacy with a receptor is a(n) _________
agonist
List the 4 types of drug receptors
- G-Protein coupled (GPCRs)
- Ligand-gated ion channels
- Membrane-bound enzymes
- Intracellular (nuclear)
qd means:
every day
In the dose-response relationships shown here, ED50 of drug B is ______
1 mg/kg
Compare and contrast G-Protein signal transduction for Gαs, Gαi, and Gαq containing G-proteins
All pathways are activated by a ligand binding to a GCRP which causes G-protein activation by GTP-binding and GDP release. They differ in the effector system and second messengers used.
Gαs and Gαi either stimulate or inactivate adenylyl cyclase, leading to up or down-regulation of cAMP production
Gαq activates phospholipase C which produces IP3 and diacylglyerol (DAG). These two cause an elevation of intracellular Ca2+
upregulation in CYPs that metabolize opioids in response to chronic opioid exposure is an example of __________ (pharmacokinetic / pharmacodynamic) tolerance
pharmacokinetic
changes in number of enzymes for metabolism is a pharmacokinetic change. Changes in number of receptors is a pharmacodynamic change with regards to tolerance.
To facilitate excretion of a weak base drug, the clinician should target a _____ (acidic/basic) tubular pH
acidic. drugs can not be passively reabsorbed in their ionized form, so the ionized weak base will be excreted more readily.
non rep means:
do not repeat
List three ways that drug receptors are classified:
- Drug specificity
- Tissue location
- Primary amino acid sequence
glucuronosyltransferases, acetyltrasnferases, and sulfotransferases are associated with phase _____ (i/ii) biotransformation
phase ii. phase ii reactions are conjugation reactions and thus all involve a “transferase” enzyme
The time indicated by B in this drug plasma concentration curve is called ______ and represents _____
Tmax represents the time until the maximum plasma concentration (Cmax) of the drug is reached
The organ that is most involved in biotransformation is the _____
Liver
compare an allosteric to orthosteric drug-binding site
allosteric = a different binding site than the endogenous ligand
orthosteric = same binding site as the endogenous ligand
_______ is the ability of a drug to bind with its receptor or target
affinity
When GDP is bound to a g-protein, it is _______ (activated / inactivated)
inactivated
g-protein alpha-subunit activation is marked by GTP-binding
Clearance is defined as _____________
the rate of elimination divided by the plasma concentration
in the presence of a complete agonist, a partial agonist may act as a ______
antagonist through competitive inhibition
An advantage of the inhalational route is it has a _____ (high/low) local effect and a _____ (high/low) systemic effect
high, low
bioavailability of a PO drug is calculated by:
dividing the AUC of the PO drug by the AUC of the same dose of the drug given IV
Drugs that have a high fraction bound to plasma proteins will have a ______ (high/low) glomerular filtration rate
low
Explain the difference between phase I, II, and III clinical trials
Phase I: drug administered to healhty individuals to study pharmacokinetics and pharmacodynamics
Phase II: Drug administered to individuals with condition of study to establish dosing, efficacy, safe use, etc.
Phase III: large-scale trials to study drug therapeutic benefit
ADME stands for:
Absorption, Distribution, Metabolism, Excretion
a.c. means
before meals
“ante cibum”
Describe differences between the one-compartment and two-compartment models of pharmacokinetics
the two component model treats blood plasma and tissues/organs as two separate compartments and describes a third rate constant for determining movement of drugs between these two.
A pharmacodynamic drug interaction where the effect of two drugs given together is greater than the sum of their individual effects is called
a synergistic effect
po means
by mouth
“per os”
List 5 methods of excretion that are not renal:
bile, sweat, saliva, tears, feces, breast milk, exhaled air
___________ tolerance is caused by a change in number/density of receptors, whereas __________ tolerance is caused by a change in the number of enzymes responsible for drug elimination
pharmacodynamic** tolerance is caused by a change in number/density of receptors, whereas **pharmacokinetic tolerance is caused by a change in the number of enzymes responsible for drug elimination
hs means:
at bedtime
“hora somni”
Adenylyl cyclase is stimulated by the G-protein _______ and catalyzes production of _______
Gαs and catalyzes production of cAMP
What is the importance of AUC in pharmacokinetics?
AUC (area under curve) represents the total amount of drug made available to the systemic circulation for therapeutic effect
To facilitate excretion of a weak acid drug, the clinician should target a _____ (acidic/basic) tubular pH
basic. drugs can not be passively reabsorbed in their ionized form, so the ionized weak acid will be excreted more readily.
qid means
4 times a day
“quater in die”
Drugs that are weak acids have best absorption in ______ (acidic / basic) environments
acidic
In the dose-response relationships shown here, the drug with the highest potency is ______
drug A as it has the lowest ED50
alt hor means:
every other hour
“alternis horis”
prn means
as needed
“pro re nata”
A synergistic drug interaction is:
A pharmacodynamic drug interaction where the effect of two drugs given together is greater than the sum of their individual effects
describe the distribution and elimination phases of pharmacokinetics
after administration of a drug, there is a rapid decrease in plasma concentration (ditribution phase) as the drug is ditributed in body fluids. After that, the plasma concentration decreases more slowly as the drug is metabolized and excreted
The primary determinant of drug efficacy is ______
receptor affinity
Phase i biotransformation involves the processes _____, _____, and _____
reduction, oxidation, and hydrolysis
Biliary excretion tends to only include drugs with a _____ (high / low) molecular weight
high
The time interval indicated by D in this drug plasma concentration curve is called ______ and represents _____
Duration represents the amount of time that the drug will have a measurable therapeutic effect
List the 4 steps of renal excretion and an important factor in determining the rate of each one
- glomerular filtration - depends on level of drug-albumin binding
- active tubular secretion - depends on competitive inhibition by other drugs/metabolites
- passive tubular reabsorption - Depends on tubular pH (ionized forms will not reabsorb)
- excretion - depends on urine flow rate
An antagonist that binds to the receptor reversibly is said to be __________
competitive
Bioavailability is defined as:
the fraction of the administered dose of a drug that reaches the systemic circulation in an active form
Define elimination
Elimination = metabolism + excretion
all adrenergic receptors belong to the class ______
G-Protein coupled receptors (GPCRs)
CYP isozymes are primarily associated with phase _____ (i/ii) biotransformation
phase i
Define Volume of distribution (Vd)
The volume of fluid a certain dose of drug would need to be dissolved in to achieve the same concentration as it has in plasma
The concentration indicated by C in this drug plasma concentration curve is called ______ and represents _____
Minimum Effective Concentration (MEC) represents the minimum plasma concentration required to have a measurable therapeutic effect
In general, basic drugs bind to plasma _________
glycoproteins and Beta-globulins - B for Base and Beta-Globulin
Organs receiving the highest proportion of cardiac output, like ___________ (list 4) will receive drugs at the highest rate.
Heart, brain, liver, kidneys
In the dose-response relationships shown here, the drug with the highest efficacy is ______
drug C as it has the highest effect
Pulmonary drug kinetics are not well reflected by plasma concentration curves, so instead a _________ curve is used
time-clinical effects curve
Compare a potentiative effect to a synergistic effect
both are cases where two drugs combined have a greater effect than the sum of their individual effects. A potentiative drug interaction follows the formula (0 + 1 = 3) i.e. one of the drugs activates the other. A synergistic effect follows the formula (1 + 1 = 3)
The site of most drug metabolism is __________
the liver
Drug metabolites tend to be __________ (more / less) water-soluble than the parent molecule
more
Explain why it would be favorable for drugs delivered by the inhalational route to have a high first pass metabolism
We generally want these drugs to have a large local and small systemic effect. Some of these drugs will invariably be ingested enterally. We want there to be a high first-pass effect on the ingested fraction to avoid systemic effects
Lipid diffusion is facilitated by a drug having high ______________
Lipid solubility
Describe Fick’s law
The rate of diffusion of a substance is proportional to the concentration gradient and surface area of diffusion
Drugs that are weak __________ (acids / bases) absorb best in the stomach
acids
An additive or summative effect is:
A pharmacodynamic drug interaction where the effect of two drugs given together is equal to the sum of their individual effects
Metabolism is also called __________
Biotransformation
The attachment of polar groups to drugs to hasten excretion and inactivate the drug is called __________
conjugation
Phase ii biotransformation reactions involve adding a polar group, known as ______
conjugation
competitive inhibition may slow the excretion of drugs that are excreted through the process of _______
active tubular secretion. In this case active transporters are occupied by competing molecules.
conjugation
The attachment of polar groups to drugs to hasten excretion and inactivate the drug
A pharmacodynamic drug interaction where the effect of two drugs given together is equal to the sum of their individual effects is called:
An additive effect
cap means
community aquired pneumonia
compare and contrast potency and efficacy of drugs
both measure the effect of a drug on the body
potency measures the effect of a drug relative to the dose given. Drugs with high potency have their maximum effects at relatively low doses (this does not mean that they have a large effect!)
efficacy measures the effect of a drug relative to the maximum possible effect at a given receptor. A drug with high efficacy will have the highest possible effect for a given receptor type
ad lib means
as desired
“ad libitum”
chronic exposure to antagonists may cause ___________ of receptors as a compensatory mechanism
up-regulation
Define loading dose and explain how it is calculated
loading dose is a relatively large initial dose of a drug given to achieve a desired plasama concentration. It is calculated as:
Loading Dose = Vd X C
where Vd is the volume of distribution and C is the desired plasma concentration
Drugs administered by the sublingual or rectal route have __________ (more / less) first pass metabolization than those administered by the oral route
less
Zero-order elimination kinetics, as seen in ethanol, occur when __________
there is saturation of the enzymes responsible for elimination.
The concentration indicated by A in this drug plasma concentration curve is called ______ and represents _____
Cmax represents the maximum plasma concentration of the drug
Drugs that are eliminated by First order kinetics have a _______ (constant / variable) half-life and a ________ (cosntant / variable clearance) relative to plasma concentration of the drug.
constant half-life and constant clearance.
the rate of elimination changes with palsma concentration, but half-life and clearance remain cosntant
A drug that has affinity for, but no efficacy with a receptor is a(n) _________
antagonist
tid means:
three times daily
Describe the role of ABC transporters like Pgp in drug distribution
ABC transporters line the luminal side of endothelial cells in the GI tract, brain capillaries, and other tissues. They pump drugs into the luminal space, effectively reducing the tissue concentrations of drug. Pgp is inhibited by drugs like amiodarone and propranolol, which may increase potency of other drugs
