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Ocular Pharmacology > General Principles > Flashcards

General Principles Flashcards

1
Q

What does iatrogenic mean?

A

condition caused by medical examination or treatment

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2
Q

What is the lock and key model?

A

a protein (or drug) finds appropriate receptor and causes an intracellular response

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3
Q

What is affinity?

A

potential for drug-receptor binding

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4
Q

What is a receptor?

A

a binding site with biological effect (any cellular macromolecule which a drug binds to and initiates effect) - can also be enzymes

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5
Q

What is intrinsic activity?

A

capacity to produce a biological effect

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6
Q

What is an agonist?

A

affinity + intrinsic activity for receptor

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7
Q

What is an antagonist?

A

has affinity but no intrinsic activity –> decreases or blocks the effectiveness of the agonist

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8
Q

What is allostery?

A

stereo-specific phenomenon where a bound ligand influences the specificity of a second site

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9
Q

What is efficacy?

A

affinity x intrinsic activity (dose dependent - for antagonists this is zero)

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10
Q

What is hypersensitivity?

A

result of chronic antagonism

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11
Q

What is max dose?

A

minimum amount of drug to produce a maximum therapeutic effect (less side effects)

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12
Q

What is a partial agonist?

A

has low intrinsic activity with potency and affinity in the therapeutic range (binds loosely - can’t give maximal response)

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13
Q

what is pharmacodynamics?

A

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

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14
Q

what is pharmacokinetics?

A

action of drug on the body (ADME)

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15
Q

What is pharmacotherapeutics?

A

what the drug does for/to the disease

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16
Q

What is potency?

A

amount of drug needed to produce an effect (inversely related to EC50 and IC50) - dose dependent

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17
Q

What is resistance?

A

loss of pharmacological effects

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18
Q

what is selectivity?

A

ability to produce a desired effect vs. an adverse effect (how good is the drug at eliminating pain without causing nausea)

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19
Q

what is specificity?

A

ability to act at a specific receptor (side effects can occur if not specific enough)

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20
Q

what is tachyphylaxis?

A

RAPIDLY decreasing therapeutic response

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21
Q

what is bioavailability?

A

amount of active drug reaching the target tissue/organ (distribution) –> not related to potency

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22
Q

What is the therapeutic index?

A 
animals = LD50:ED50
humans = TD50:ED50
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23
Q

Which drug is safer to take, one with a high or low therapeutic index?

A

want high therapeutic index - want the TD (toxic dose) to be higher than the ED (effective dose)

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24
Q

What is a supplemental type drug?

A

the addition of a substance that is normally required by the body but exists in insufficient amounts to achieve a desired state (ex: insulin)

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25
Q

what is a supportive type drug?

A

aimed at relieving symptoms or helping patients cope rather than cure - it is normally found in body but in insufficient amounts (ex: glucose/sugars)

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26
Q

what is a prophylactic type drug?

A

prevents or reduces the likelihood of a condition or symptom developing (ex: ASP)

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27
Q

what is a symptomatic type drug?

A

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)

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28
Q

What is a diagnostic type drug?

A

used to aid in a diagnosis (ex: dilation drops)

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29
Q

what is a therapeutic type drug?

A

used to treat condition, attempt to cure (ex: methotrexate - stops DNA synthesis)

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30
Q

What is a nuclear receptor motif?

A

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)

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31
Q

What is a G-protein coupled receptor motif?

A

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)

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32
Q

what is an ion channel receptor motif?

A

can be active, passive, facilitated (ex: GABA, AChN, glutamate) - voltage gated respond to changes in cell membrane

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33
Q

what is an enzymatic receptor motif?

A

lipophilic agents that can enter cell nucleus and cause transcriptional changes (ex: insulin, epidermal growth factor)

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34
Q

what is a calcium release receptor motif?

A

play a key role in regulating how much Ca is inside a cell (toxic to cells - causes apoptosis) (ex: calcineurin, nitric oxide synthase)

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35
Q

what is a direct agonist?

A

acts directly on the receptor (same receptor as endogenous substance)

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36
Q

what is an indirect agonist?

A

doesn’t target key receptor responsible for the mechanism - acts on the pathway in a separate fashion to enhance the endogenous substance (ex: cocaine)

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37
Q

what is a mixed agonist?

A

acts as an agonist and antagonist (stimulatory and inhibitory properties)

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38
Q

what is an inverse agonist?

A

an agent that binds to the same receptor binding-site as an agonist for that receptor and inhibits the constitutive activity of the receptor

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39
Q

what is a partial agonist?

A

bind and activate a given receptor, but have only partial efficacy at the receptor relative to a full agonist, even at maximal receptor occupancy

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40
Q

what are the 2 types of binding integrity’s for an antagonist?

A

reversible (ionic, van der walls, H-bonding)

irreversible (covalent bonding)

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41
Q

what is a competitive antagonist?

A

binds to same receptor as endogenous substance/agonist but with greater affinity - no intrinsic activity (dose dependent)

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42
Q

what is a non-competitive antagonist?

A

binds to a secondary receptor site - changes the structure of the site for agonist and indirectly blocks it (doesn’t require agonist binding)

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43
Q

what is an un-competitive antagonist?

A

only binds in the presence of an agonist (requires both) - shuts down the response (slows ligand dissociation and response rate)

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44
Q

what is a physiological mode of action?

A

utilizes drugs that take advantage of normal hormones/substances within the body that have a profound effect on physiology (ACh, E, His)

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45
Q

what is a biological mode of action?

A

produces an effect through biological mechanisms (ex: PCN degrades cell membrane)

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46
Q

what is a chemical mode of action?

A

produces an effect through chemical reactions (ex: alka seltzer)

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47
Q

what is absorption influenced by?

A

first pass metabolism or enterohepatic circulation (not a concern with topical ophthalmic drugs)

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48
Q

what is a barrier of absorption of a drug?

A

degree of vascularity at site of administration (inflammation/red eye: be cautious of systemic absorption due to leakiness of vessels → use a vasoconstrictor first)

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49
Q

what is volume of distribution?

A

Vd = drug dose/[drug in plasma]

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50
Q

what does a high Vd mean?

A

it shows that the drug isn’t remaining in bloodstream and more of it is distributed in tissue (i.e. not in plasma)

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51
Q

what is Vd influenced by?

A

route of administration (less of a concern if given topically vs oral)

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52
Q

what happens to Vd if patient is dehydrated?

A

decreases Vd - lower plasma volume artificially enhances drug plasma concentration

53
Q

what is metabolism of a drug influenced by?

A

the health of the metabolizing organ (reflected by the half-life)

54
Q

what are the 5 routes of elimination?

A

fecal, urinary, sweat, respiration, and saliva

55
Q

what is drug clearance?

A

drug volume eliminated/time

56
Q

how many half-lives does it usually take to eliminate/metabolize a drug?

A

usually 3-4

57
Q

what are the 2 key barriers to drug passage (absorption) in the eye?

A

corneal epithelium and RPE (due to zonula occludens)

58
Q

what is the average amount of tear film on the eye? and what is the maximal volume the eye can hold?

A

10 microliters on the eye

30 microliters maximum

59
Q

which tear layer is both hydrophilic and lipophilic?

A

mucin layer

60
Q

how many microliters does the average eye drop contain?

A

25-56 microliters - a single drop will probably exceed the maximum volume of the eye and excess will fall off

61
Q

what is the basal tear flow of the eye?

A

0.5 - 2.2 microliters per min (at least 60 min in low tear flow to replace all 30microliters)

62
Q

what part of the eye is the major absorption site for drugs?

A

cornea

63
Q

If a drug penetrates the cornea, what plays a role in determining how long the drug stays in the eye?

A

the aqueous outflow and pigment protein binding of the iris

64
Q

what does inflammation do to the pH of the eye?

A

produces acidity

65
Q

what percentage do the conjunctiva and sclera contribute to drug passage to iris and ciliary body?

A

less than 20% of drug passage to the iris and ciliary body (about 1/5 overall absorption)

66
Q

what role does the iris play in drug barriers?

A

the lipophilic pigment is color-sensitive depot (brown will absorb more than blue)

67
Q

what is the volume of the anterior chamber? how often is it recycled?

A

200 microliters - recycled every 50min

68
Q

what do steroids do to the drug clearance?

A

they may decrease blood aqueous barrier permeability and reduce drug clearance at ciliary body

69
Q

how is the crystalline lens a drug barrier?

A

has a lipophilic epithelium - involved in cationic transport and cell division (prone to toxicity)

70
Q

what is the primary drug metabolism site in the eye?

A

ciliary body

71
Q

how do systemic drugs enter the ciliary body?

A

through vasculature - uveal circulation

72
Q

what does the vitreous humor do to drugs?

A

hydrophilic drugs won’t pass the BRB so the half-life is prolonged

73
Q

what 4 things limit the influx of locally administered drugs into the posterior segment of the eye?

A

cornea, tear drainage, episcleral blood flow, and intraocular convection current

74
Q

what is the normal pH of the tears?

A

slightly basic = 7.1 to 7.6

75
Q

what are the characteristics of a zero order drug?

A

concentration independent, rate limiting barrier (saturable carrier), constant amount of clearance and elimination per unit of time = linear

76
Q

what are the characteristics of a first order drug?

A

*majority of drugs
concentration dependent, non-saturable carrier, constant proportion of clearance and half-life, and elimination per unit of time = exponential

77
Q

what is a mixed-order drug?

A

behaves like a first order drug until it reaches high concentration - then acts as zero order and is saturable

78
Q

which type, zero or first order, can lead to toxicity?

A

zero order (ex: alcohol - doubling a dose = takes twice as long to metabolize)

79
Q

what type of dosing schedules do zero order kinetic drugs need?

A

need dose modification: either loading or maintenance

80
Q

what is steady state?

A

achieved when rate of intake = rate of elimination (result is a therapeutic response)

81
Q

what are 2 ways to increase the steady state?

A
  1. increase the frequency of dose but keep dose the same amount
  2. double dose (concentration) and keep frequency the same
82
Q

what are the 4 types of common treatment malpractice drugs?

A

steroids, beta-blockers, miotics, and oral carbonic anhydrase inhibitors

83
Q

what effect can long term or oral use of steroids cause?

A 
topical = increase IOP --> glaucoma
oral = cataracts occur faster
84
Q

what effects do beta-blockers cause in patients with cardiovascular conditions or asthma?

A

reduce blood flow and pressure and can cause respiratory failure

85
Q

what can miotics cause in patients? (especially in lattice degeneration)

A

ciliary spasm -> inflammation and retinal detachments

86
Q

what is the most common treatment negligence? and what are the most common conditions?

A

failure to diagnose - OAG, tumors of visual system and retinal detachments

87
Q

what are the 5 common treatment negligences?

A

failure to diagnose, delayed diagnosis, misdiagnosis, improper management, and failed/delayed referral or consultation

88
Q

in the federal drug classification schedules, what schedule is the most safe?

A

schedule 5 (most safe - PCN) and schedule 1 (least safe - heroin)

89
Q

what federal drug classification schedules are we allowed to prescribe in the state of CA?

A

schedules 3,4,5

90
Q

which category of drugs are the safest for pregnant women according to the FDA?

A

class A is the safest and class X is the least safe

91
Q

what are the 3 FDA requirements for drugs on the market?

A

minimum 90% activity level, at least 18 month self-life and need to have antimicrobial preservation or be non-preserved single dose units

92
Q

what are the advantages to a gel drug formulation?

A

thicker - longer retention time, can carry more volume

93
Q

what is an ointment?

A

oil based (penetrates fatty layers), enhance retention time

94
Q

is a cream oil or water based?

A

water based

95
Q

how is a CL used to deliver drugs?

A

impregnate lens with steroids, glaucoma meds - produces a constant steady state (hydrogel lens has first order kinetics)

96
Q

what is a collagen shield?

A

a biodegradable substance - protects and then dissolves

97
Q

how are filter strips used to deliver a drug?

A

placed on eye and slowly releases a drug (fluorescein strip or Schirmer strip)

98
Q

what is a cotton pledget?

A

used to apply drugs to a localized area/region of the eye

99
Q

what is lacrisert?

A

used for dryness - dissolves in fornix

100
Q

what is a solution?

A

water soluble and homogenous

101
Q

what is a suspension?

A

solute suspended in a solvent - needs to be shaken

102
Q

what is a colloid?

A

oil/water mixture that is uniform in composition (every drop is uniform - no need to shake)

103
Q

what are exipients and vehicles?

A

all elements of a preparation other than the active ingredient and the preservative

104
Q

what are 4 examples of exipients?

A

emollient, emulsifier, demulcent, and buffer

105
Q

what is an emollient?

A

soothes the skin (ex: mineral oil)

106
Q

what is an emulsifier?

A

keeps solids in liquids well dispersed/mixed (similar to oil in water)

107
Q

what is a demulcent?

A

soothes mucous membranes

108
Q

what are 4 examples of vehicles?

A

viscosity enhancer, osmoprotectant, stabilizers, and tonicity stabilization

109
Q

why are preservatives used in drugs?

A

meant to be antimicrobial - many patients are allergic or will have a reaction to them

110
Q

what are 4 types of preservatives?

A

chelators, chemical toxins, surfactants, and disappearing oxidants

111
Q

what are chelators?

A

bind metals and prevent availability to bacteria (ex: EDTA)

112
Q

what are 2 chemical toxins used as preservatives?

A

alcohol (takes fluid out of cell), heavy metals (lead, mercury)

113
Q

what is chlorobutanol?

A

a chemical toxin preservative used that is less allergenic than benzalkonium chloride (BAK) but more toxic

114
Q

what are surfactants?

A

soaps - long chain fatty acids with a charged carboxyl group on the end - degrades membranes (can be ionic or bactericidal)

115
Q

which type of surfactants may be toxic to the ocular surface?

A

cationic - due to interactions with negatively charged corneal cells

116
Q

what are 2 classes of surfactants?

A

biguanides and quaternary ammonium compounds

117
Q

what are disappearing oxidants?

A

preservatives that disappear after administration

118
Q

what are 2 classes of disappearing oxidants?

A

sodium perborate (pH inactivated) and sodium chlorite (light inactivated)

119
Q

how long after opening can single vial non-preservative vials be used?

A

can be re-capped and used up to 12 hours if not contaminated

120
Q

what is the only self-preserved drug?

A

mocifloxacin

121
Q

what color cap is used for beta blockers?

A

yellow

122
Q

what drug has a dark blue cap?

A

beta blocker combos

123
Q

what drug has a dark green cap?

A

miotics

124
Q

what color cap do carbonic anhydrase inhibitors have?

A

orange

125
Q

what drug has a gray colored cap?

A

non-steroidal anti-inflammatory

126
Q

what drugs have a pink cap?

A

steroids

127
Q

what drug has a tan cap?

A

anti-infective

128
Q

what is a teal cap used for?

A

prostaglandin analogs

129
Q

what is a purple cap used for?

A

adrenergic agonists

Ocular Pharmacology (10 decks)

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