01 Principles Flashcards
Affinity definition
potential for drug-receptor binding
Receptor definition
cellular binding site with a biological effect
Intrinsic activity definition
capacity to produce a beneficial biological effect
Agonist definition
substances that STIMULATE a receptor to produce a physiologic reaction (has intrinsic activity)
Antagonist definition
substances that INTERFERE with activity of a receptor and its endogenous substrate; does not produce a physiologic reaction itself (does not have intrinsic activity)
Allostery definition
bound ligand changes configuration of the molecule to influence specificity at a second site
Efficacy definition
[affinity] x [intrinsic activity]
Efficacy v. Potency
efficacy is dose independent; potency is dose dependent
What is the efficacy of an antagonist?
zero (because there is no intrinsic activity)
EC50 definition
effective concentration in 50% of subjects
ED50 definition
effective dose in 50% of subjects
IC50 definition
inhibitory concentration in 50% of subjects (antagonists)
Hypersensitivity definition
result of chronic antagonism
Maximum Dose definition
the MINIMUM amount of drug to produce the MAX therapeutic effect
Partial Agonist definition
LOW intrinsic activity with a therapeutic potency and affinity
Pharmacodynamics definition
how the drugs affect the body (MOA)
Pharmacokinetics definition
how the body affects the drug (ADME)
ADME definition
absorption, distribution, metabolism, elimination
Pharmacotherapeutics definition
how the drug affects disease processes
Concentration v. Dose
concentration is laboratory; dose is clinical
How is Pharmacodynamics measured?
potency, efficacy, affinity, toxicity
How is Potency related to EC50 and IC50?
potency is INVERSELY related to EC50 for agonists and IC50 for antagonists
Posology definition
science of drug dosing
Potency definition
biological response to a given dose
Resistance definition
loss of pharmacological effect
Selectivity definition
the ability to produce a desired effect versus an adverse effeict
Specificity definition
ability to act at a specific receptor
Tachyphylaxis definition
rapidly decreasing therapeutic response (can only be used short term)
Teratogenesis definition
congenital malformation
Bioavailability definition
amount of active drug to reach target tissue
Therapeutic Index definitioin
TD50:ED50 ratio (clinical) or LD50:ED50 ratio (laboratory)
LD50 definition
lethal dose for 50% treated (used in animal studies)
TD50 definition
toxic dose for 50% treated
What therapeutic index is safe?
high therapeutic indices are safest because it takes much more drug to create adverse effect than it does to treat
What therapeutic index is likely to produce a toxic effect?
low therapeutic indices are more likely to create toxic effect because the dose it takes to treat is nearly the dose that causes adverse toxicity
DPA definiton
diagnostic pharmaceutical agent
TPA definition
therapeutic pharmaceutical agent
What are six drug types?
supplemental, supportive, prophylactic, symptomatic, diagnostic, therapuetic
Supplemental drug definition
addition of a substance that is normally required but is insufficient in the patient
What is an example of a supplemental drug?
insulin
Supportive drug definition
aimed at resolving clinical signs
What is an example of a supportive drug?
glucose
Prophylactic drug definition
preventative/protection against potential issues
What is an example of a prophylactic drug?
low dose aspirin
Symptomatic drug definition
offers relief for patient symptoms, but does not cure
What is an example of a symptomatic drug?
olopatadine, artificial tears
Diagnostic drug definition
drug used only by doctor for diagnostic purposes
What is an example of a diagnostic drug?
fluorescein
Therapeutic drug definition
works to eliminate the cause of whatever problem the patient is having
What is an example of a therapeutic drug?
methotrexate
What are the receptor motif super families? (5)
nuclear, g-protein-coupled, ion channels, enzymatic, calcium release
What are characteristics of a Nuclear receptor?
LIPID SOLUBLE, with cholesterol backbones, ready to gain access into the cell nucleus
What are examples of Nuclear receptors?
steroids, hormones
What is the most common receptor type targeted by ophthalmic drugs?
g-protein-coupled
How do G-protein-coupled receptors work?
receptors inside the cell interact with proteins to cause conformational change that leads to opening of channels
What are examples of G-protein-coupled receptors?
ACh(M), rhodopsin
What are characteristics of Ion Channel receptors?
they are a tube in the cell membrane that is opened up by binding
What are examples of Ion Channel receptors?
ACh(N), glutamate, GABA
How do Enzymatic receptors work?
drug binds to the receptor which activates its enzymatic activity (usually in the cell membrane)
What are examples of Enzymatic receptors?
insulin, epidermal growth factor
How do Calcium Release receptors work?
stimulation of the receptor results in release of Ca++
What effect occurs with the release of Ca++?
in small can fuel production of nitric oxide (vasodilator), or in large amounts can cause apoptosis
What type of receptor is ACh(M)?
g-protein-coupled
What type of receptor is ACh(N)?
ion channel
Explain how drugs are designed according to the lock and key model.
when they leak out of the blood vessels, they designed to only bind to specific endogenous receptors, producing a cascade of events to evoke the desired effect
How does inflammation affect the lock and key model?
inflammation causes blood vessels to become dilated and “leaky” so that the drug will accumulate in the inflamed area, thus the drug will produce effect in that particular affected area rather than diffusing throughout the whole body
What are the modes of action of Agonists? (5)
direct, indirect, mixed, inverse, partial
How do direct agonists work?
direct agonists stimulate a receptor and produce the desired effect through its actions on the receptor
How do indirect agonists work?
indirect agonists are intermediaries that interact with a receptor to promote a natural effect in the body
Cocaine is an example of what type of agonist?
indirect agonist (it binds to neurons to inhibit reuptake of catecholamines, but it is the norepinephrine that stimulates the true effect)
How do mixed agonists work?
they use both agonist and antagonist properties
How do inverse agonists work?
they STIMULATE a receptor which actually decreases activity
How do partial agonists work?
they have sub-maximal stimulation of receptors and efficacy
Which type of agonists are touted for reduced dependency and withdrawal effects?
partial agonists
What are the three characteristics of antagonists?
binding integrity, binding site selectivity, mode of action
What are the types of antagonist binding integrity?
reversible, or irreversible
Which type of antagonist binding uses covalent bonds?
irreversible antagonists
What are the types of binding site selectivity? (3)
competitive, non-competitive, uncompetitive
Competitive Antagonist definition
binding site is the same as the endogenous agonist
Non-Competitive Antagonist definition
binds at another site to produce allostery so that the endogenous agonist cannot bind
Uncompetitive Antagonist definition
binds at another site to produce allostery so that the endogenous agonist is still bound and locked in so that it cannot dissociate and be restimulated
What are the modes of action for antagonists? (3)
biological, chemical, physiological
Which type of antagonist binding requires presence of an agonist?
uncompetitive
What factors influence absorption of a drug?
first pass metabolism, barriers (degree of vascularity at administration site), patient (age, gender, weight, pregnancy, health)
What is first pass metabolism?
the drug is ingested and absorbed through the gut into the blood, travelling directly into the liver so it is there metabolized rather than having a therapeutic effect
What influences the distribution of a drug?
route of administration
How do you calculate the Volume of Distribution (Vd)?
Vd = dose/[drug in plasma]
What influences the metabolism of a drug?
health of metabolizing organ(s)
How is drug metabolism measured?
drug half life
What routes of drug elimination exist?
fecal, urinary, sweat, respiration, saliva
How is Drug Clearance calculated?
Clearance = [drug volume eliminated] / time
How will a “red eye” affect volume of distribution?
Vd is increased due to the increased vascularity of the tissue causing the drug to more easily get into systemic circulation
How does patient age affect dosing?
age usually requires a higher dose
How does fat affect drug absorption?
when overweight patients take lipid-based drugs, the drug can accumulate in the body fat without producing an effect
What does a high volume of distribution suggest?
the drug does not readily stay in the bloodstream, which may predispose patients to toxicity (often in patients with liver or renal disease)
How does dehydration affect volume of distribution?
it decreased vD since the low plasma volume artificially enhances drug plasma concentration
Which layer of the tears is both water and lipid soluble?
mucin layer
What are the layers of the tear film? (anterior to posterior)
lipid, aqueous, mucin
What type of drugs will dissolve on the first layer of tear film?
lipid-soluble drugs
Which layer will dissociate charged drugs into solution?
aqueous
In an inflammatory state, what happens to the tear film?
aqueous becomes more acidic, which prevents dissociation and action of the drug
What can prevent dissociation of a charged drug?
lower pH of aqueous
What are the two strongest barriers to drug passage in the eye?
corneal epithelium and RPE
What structure in the eye lacks tight junctions, making it a poor barrier to drug passage?
corneal endothelium
What prevents systemic drugs from causing toxicity in the eye?
while drugs can come through the choroid, they cannot cross the RPE
What is the primary site of drug elimination in the eye?
ciliary body
What is the surface volume of tear film?
10-30 microliters
What is the volume of a drop?
25-56 microliters
What is the rate of basal tear flow?
0.5-2.2 microliters/minute
How long does it take to completely replace tear film?
5-20 minutes
How do conjunctiva and sclera facilitate drug passage?
How does iris pigment affect ocular drug absorption?
pigment is lipophilic and becomes a depot for the drug; darker eyes require more drops and have great sustained effect
What is normal tear pH?
7.1-7.6 (slightly basic)
Which type of drugs accumulate in aqueous media?
charged drugs
Which types of drugs readily leave aqueous environments to cross lipid barriers?
uncharged drugs
What is the volume of the anterior chamber?
200 microliters
How long does it take for aqueous to be recycled in the anterior chamber?
50 minutes
What is the most metabolically active part of the crystalline lens?
anterior epithelium
How do steroids affect drug clearance?
decrease blood aqueous barrier permeability, reducing drug clearance
Which model of drug kinetics lconcentration dependent?
1st order
Which model of drug kinetics is concentration independent?
zero order
Which model of drug kinetics do most drugs follow?
1st order
Which model of drug kinetics has a linear rate of elimination?
zero order
Which model of drug kinetics has an exponential rate of elimination?
1st order
Which model of drug kinetics has a rate limiting barrier or saturable carrier?
zero order
Which model of drug kinetics has a constant amount of clearance?
zero order
Which model of drug kinetics has a constant proportion of clearance?
1st order
Which model of drug kinetics has a non-saturable carrier?
1st order
Which model of drug kinetics has a saturable carrier at high concentrations only?
mixed order
Alcohol and ASA follow which model of drug kinetics?
zero order
Steady State definition
drug in = drug out
Which model of drug kinetics requires a greater demand for dose modification?
zero order
How can plasma equilibrium be elevated?
increasing the dose, or increasing dosing frequency
