General Principles Flashcards
What does iatrogenic mean?
condition caused by medical examination or treatment
What is the lock and key model?
a protein (or drug) finds appropriate receptor and causes an intracellular response
What is affinity?
potential for drug-receptor binding
What is a receptor?
a binding site with biological effect (any cellular macromolecule which a drug binds to and initiates effect) - can also be enzymes
What is intrinsic activity?
capacity to produce a biological effect
What is an agonist?
affinity + intrinsic activity for receptor
What is an antagonist?
has affinity but no intrinsic activity –> decreases or blocks the effectiveness of the agonist
What is allostery?
stereo-specific phenomenon where a bound ligand influences the specificity of a second site
What is efficacy?
affinity x intrinsic activity (dose dependent - for antagonists this is zero)
What is hypersensitivity?
result of chronic antagonism
What is max dose?
minimum amount of drug to produce a maximum therapeutic effect (less side effects)
What is a partial agonist?
has low intrinsic activity with potency and affinity in the therapeutic range (binds loosely - can’t give maximal response)
what is pharmacodynamics?
action of a drug on the body - focuses on biochemical and physiological effects of drugs and their mechanisms of action, potency, efficacy, affinity, and toxicity
what is pharmacokinetics?
action of drug on the body (ADME)
What is pharmacotherapeutics?
what the drug does for/to the disease
What is potency?
amount of drug needed to produce an effect (inversely related to EC50 and IC50) - dose dependent
What is resistance?
loss of pharmacological effects
what is selectivity?
ability to produce a desired effect vs. an adverse effect (how good is the drug at eliminating pain without causing nausea)
what is specificity?
ability to act at a specific receptor (side effects can occur if not specific enough)
what is tachyphylaxis?
RAPIDLY decreasing therapeutic response
what is bioavailability?
amount of active drug reaching the target tissue/organ (distribution) –> not related to potency
What is the therapeutic index?
animals = LD50:ED50 humans = TD50:ED50
Which drug is safer to take, one with a high or low therapeutic index?
want high therapeutic index - want the TD (toxic dose) to be higher than the ED (effective dose)
What is a supplemental type drug?
the addition of a substance that is normally required by the body but exists in insufficient amounts to achieve a desired state (ex: insulin)
what is a supportive type drug?
aimed at relieving symptoms or helping patients cope rather than cure - it is normally found in body but in insufficient amounts (ex: glucose/sugars)
what is a prophylactic type drug?
prevents or reduces the likelihood of a condition or symptom developing (ex: ASP)
what is a symptomatic type drug?
used to treat symptoms (not designed to heal/cure) and should be used with a therapeutic drug and eventually weaned off of (Ex: artificial tears)
What is a diagnostic type drug?
used to aid in a diagnosis (ex: dilation drops)
what is a therapeutic type drug?
used to treat condition, attempt to cure (ex: methotrexate - stops DNA synthesis)
What is a nuclear receptor motif?
intracellular receptors with DNA binding domain → effects what occurs in the nucleus and can cause changes in the physiology of the body (ex: steroids, hormones)
What is a G-protein coupled receptor motif?
most common target of ophthalmic therapeutic and diagnostic agents – when receptor is activated it binds GTP and hydrolyzes it to GDP + phosphate (aka GTPase) → downstream events in the cell (ex: rhodopsin or AChM)
what is an ion channel receptor motif?
can be active, passive, facilitated (ex: GABA, AChN, glutamate) - voltage gated respond to changes in cell membrane
what is an enzymatic receptor motif?
lipophilic agents that can enter cell nucleus and cause transcriptional changes (ex: insulin, epidermal growth factor)
what is a calcium release receptor motif?
play a key role in regulating how much Ca is inside a cell (toxic to cells - causes apoptosis) (ex: calcineurin, nitric oxide synthase)
what is a direct agonist?
acts directly on the receptor (same receptor as endogenous substance)
what is an indirect agonist?
doesn’t target key receptor responsible for the mechanism - acts on the pathway in a separate fashion to enhance the endogenous substance (ex: cocaine)
what is a mixed agonist?
acts as an agonist and antagonist (stimulatory and inhibitory properties)
what is an inverse agonist?
an agent that binds to the same receptor binding-site as an agonist for that receptor and inhibits the constitutive activity of the receptor
what is a partial agonist?
bind and activate a given receptor, but have only partial efficacy at the receptor relative to a full agonist, even at maximal receptor occupancy
what are the 2 types of binding integrity’s for an antagonist?
reversible (ionic, van der walls, H-bonding)
irreversible (covalent bonding)
what is a competitive antagonist?
binds to same receptor as endogenous substance/agonist but with greater affinity - no intrinsic activity (dose dependent)
what is a non-competitive antagonist?
binds to a secondary receptor site - changes the structure of the site for agonist and indirectly blocks it (doesn’t require agonist binding)
what is an un-competitive antagonist?
only binds in the presence of an agonist (requires both) - shuts down the response (slows ligand dissociation and response rate)
what is a physiological mode of action?
utilizes drugs that take advantage of normal hormones/substances within the body that have a profound effect on physiology (ACh, E, His)
what is a biological mode of action?
produces an effect through biological mechanisms (ex: PCN degrades cell membrane)
what is a chemical mode of action?
produces an effect through chemical reactions (ex: alka seltzer)
what is absorption influenced by?
first pass metabolism or enterohepatic circulation (not a concern with topical ophthalmic drugs)
what is a barrier of absorption of a drug?
degree of vascularity at site of administration (inflammation/red eye: be cautious of systemic absorption due to leakiness of vessels → use a vasoconstrictor first)
what is volume of distribution?
Vd = drug dose/[drug in plasma]
what does a high Vd mean?
it shows that the drug isn’t remaining in bloodstream and more of it is distributed in tissue (i.e. not in plasma)
what is Vd influenced by?
route of administration (less of a concern if given topically vs oral)
what happens to Vd if patient is dehydrated?
decreases Vd - lower plasma volume artificially enhances drug plasma concentration
what is metabolism of a drug influenced by?
the health of the metabolizing organ (reflected by the half-life)
what are the 5 routes of elimination?
fecal, urinary, sweat, respiration, and saliva
what is drug clearance?
drug volume eliminated/time
how many half-lives does it usually take to eliminate/metabolize a drug?
usually 3-4
what are the 2 key barriers to drug passage (absorption) in the eye?
corneal epithelium and RPE (due to zonula occludens)
what is the average amount of tear film on the eye? and what is the maximal volume the eye can hold?
10 microliters on the eye
30 microliters maximum
which tear layer is both hydrophilic and lipophilic?
mucin layer
how many microliters does the average eye drop contain?
25-56 microliters - a single drop will probably exceed the maximum volume of the eye and excess will fall off
what is the basal tear flow of the eye?
0.5 - 2.2 microliters per min (at least 60 min in low tear flow to replace all 30microliters)
what part of the eye is the major absorption site for drugs?
cornea
If a drug penetrates the cornea, what plays a role in determining how long the drug stays in the eye?
the aqueous outflow and pigment protein binding of the iris
what does inflammation do to the pH of the eye?
produces acidity
what percentage do the conjunctiva and sclera contribute to drug passage to iris and ciliary body?
less than 20% of drug passage to the iris and ciliary body (about 1/5 overall absorption)
what role does the iris play in drug barriers?
the lipophilic pigment is color-sensitive depot (brown will absorb more than blue)
what is the volume of the anterior chamber? how often is it recycled?
200 microliters - recycled every 50min
what do steroids do to the drug clearance?
they may decrease blood aqueous barrier permeability and reduce drug clearance at ciliary body
how is the crystalline lens a drug barrier?
has a lipophilic epithelium - involved in cationic transport and cell division (prone to toxicity)
what is the primary drug metabolism site in the eye?
ciliary body
how do systemic drugs enter the ciliary body?
through vasculature - uveal circulation
what does the vitreous humor do to drugs?
hydrophilic drugs won’t pass the BRB so the half-life is prolonged
what 4 things limit the influx of locally administered drugs into the posterior segment of the eye?
cornea, tear drainage, episcleral blood flow, and intraocular convection current
what is the normal pH of the tears?
slightly basic = 7.1 to 7.6
what are the characteristics of a zero order drug?
concentration independent, rate limiting barrier (saturable carrier), constant amount of clearance and elimination per unit of time = linear
what are the characteristics of a first order drug?
*majority of drugs
concentration dependent, non-saturable carrier, constant proportion of clearance and half-life, and elimination per unit of time = exponential
what is a mixed-order drug?
behaves like a first order drug until it reaches high concentration - then acts as zero order and is saturable
which type, zero or first order, can lead to toxicity?
zero order (ex: alcohol - doubling a dose = takes twice as long to metabolize)
what type of dosing schedules do zero order kinetic drugs need?
need dose modification: either loading or maintenance
what is steady state?
achieved when rate of intake = rate of elimination (result is a therapeutic response)
what are 2 ways to increase the steady state?
- increase the frequency of dose but keep dose the same amount
- double dose (concentration) and keep frequency the same
what are the 4 types of common treatment malpractice drugs?
steroids, beta-blockers, miotics, and oral carbonic anhydrase inhibitors
what effect can long term or oral use of steroids cause?
topical = increase IOP --> glaucoma oral = cataracts occur faster
what effects do beta-blockers cause in patients with cardiovascular conditions or asthma?
reduce blood flow and pressure and can cause respiratory failure
what can miotics cause in patients? (especially in lattice degeneration)
ciliary spasm -> inflammation and retinal detachments
what is the most common treatment negligence? and what are the most common conditions?
failure to diagnose - OAG, tumors of visual system and retinal detachments
what are the 5 common treatment negligences?
failure to diagnose, delayed diagnosis, misdiagnosis, improper management, and failed/delayed referral or consultation
in the federal drug classification schedules, what schedule is the most safe?
schedule 5 (most safe - PCN) and schedule 1 (least safe - heroin)
what federal drug classification schedules are we allowed to prescribe in the state of CA?
schedules 3,4,5
which category of drugs are the safest for pregnant women according to the FDA?
class A is the safest and class X is the least safe
what are the 3 FDA requirements for drugs on the market?
minimum 90% activity level, at least 18 month self-life and need to have antimicrobial preservation or be non-preserved single dose units
what are the advantages to a gel drug formulation?
thicker - longer retention time, can carry more volume
what is an ointment?
oil based (penetrates fatty layers), enhance retention time
is a cream oil or water based?
water based
how is a CL used to deliver drugs?
impregnate lens with steroids, glaucoma meds - produces a constant steady state (hydrogel lens has first order kinetics)
what is a collagen shield?
a biodegradable substance - protects and then dissolves
how are filter strips used to deliver a drug?
placed on eye and slowly releases a drug (fluorescein strip or Schirmer strip)
what is a cotton pledget?
used to apply drugs to a localized area/region of the eye
what is lacrisert?
used for dryness - dissolves in fornix
what is a solution?
water soluble and homogenous
what is a suspension?
solute suspended in a solvent - needs to be shaken
what is a colloid?
oil/water mixture that is uniform in composition (every drop is uniform - no need to shake)
what are exipients and vehicles?
all elements of a preparation other than the active ingredient and the preservative
what are 4 examples of exipients?
emollient, emulsifier, demulcent, and buffer
what is an emollient?
soothes the skin (ex: mineral oil)
what is an emulsifier?
keeps solids in liquids well dispersed/mixed (similar to oil in water)
what is a demulcent?
soothes mucous membranes
what are 4 examples of vehicles?
viscosity enhancer, osmoprotectant, stabilizers, and tonicity stabilization
why are preservatives used in drugs?
meant to be antimicrobial - many patients are allergic or will have a reaction to them
what are 4 types of preservatives?
chelators, chemical toxins, surfactants, and disappearing oxidants
what are chelators?
bind metals and prevent availability to bacteria (ex: EDTA)
what are 2 chemical toxins used as preservatives?
alcohol (takes fluid out of cell), heavy metals (lead, mercury)
what is chlorobutanol?
a chemical toxin preservative used that is less allergenic than benzalkonium chloride (BAK) but more toxic
what are surfactants?
soaps - long chain fatty acids with a charged carboxyl group on the end - degrades membranes (can be ionic or bactericidal)
which type of surfactants may be toxic to the ocular surface?
cationic - due to interactions with negatively charged corneal cells
what are 2 classes of surfactants?
biguanides and quaternary ammonium compounds
what are disappearing oxidants?
preservatives that disappear after administration
what are 2 classes of disappearing oxidants?
sodium perborate (pH inactivated) and sodium chlorite (light inactivated)
how long after opening can single vial non-preservative vials be used?
can be re-capped and used up to 12 hours if not contaminated
what is the only self-preserved drug?
mocifloxacin
what color cap is used for beta blockers?
yellow
what drug has a dark blue cap?
beta blocker combos
what drug has a dark green cap?
miotics
what color cap do carbonic anhydrase inhibitors have?
orange
what drug has a gray colored cap?
non-steroidal anti-inflammatory
what drugs have a pink cap?
steroids
what drug has a tan cap?
anti-infective
what is a teal cap used for?
prostaglandin analogs
what is a purple cap used for?
adrenergic agonists
