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Spring OD1- Pharmacology > MT2 > Flashcards

MT2 Flashcards

1
Q

What are examples of Topical administrations that causes Localized Ocular Effects/Reactions?

A

Topical Steroids* - can cause catract/increase IOP
Topical Anti-glaucoma medications * - conjunctival changes
Ophthalmic ointments and gel * - temporary blur
Topical anesthetic drops for analgesia (relief of pain) - corneal epithelial cell loss

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2
Q

Ocular preservatives?

A

Causes localized ocular effects –> leads to superficial punctate keratitis (SPK)

Contact Sensitivity/Dermatitsis

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3
Q

Antibiotic Drug Classes:
Classes of Systemic Effect/Reactions

A
  • Penicillin (beta-lactam class)**
  • Cephalosporins (beta-lactam class) **
  • Sulfonamides (sulfa drugs)**
  • tetracycline
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4
Q

Non- Antibiotic Drug Classes:
Classes of Systemic Effects/reactions

A

Anticonvulsants
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
Allopurinol
Antihypertensives

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5
Q

CYP 450 Substrates

A

Anti-HIV Agents
Benzodiazepines **
Calcium Channel Blockers
Immunosuppressants **
Macrolide Antibiotics
Statins

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6
Q

CYP 450 Inhibitors

A

Erythromycins
Grapefruit Juice
Antifungal Agents
Anti-HIV agents
Calcium channel blockers
Macrolide Antibiotics

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7
Q

CYP 450 Inducers

A

Antiepileptics
Anti-Seizure medications
Anti-HIV agents
Rifamycin
Anti-TB medication

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8
Q

Three Main Categories of ADEs

A

Allergy or Drug Hypersensitivity reactions
Infection
Drug Toxicity: Ocular

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9
Q

What is the more severe drug-related skin reaction

A

Drug Induced Exfoliative dermatitis**
- stevens Johnson syndrome (SJS)*
- Toxic epidermal necrolysis (TEN)*
- Erythema Multiforme (less severe than SJS and TEN)

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10
Q

Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN)

A

*severe mucocutaneous reactions by medications
*Characterized by extensive epidermal necrosis and detachment of epidermis, sloughing of mucous membranes

signs: Hemorrhagic crusts on lips, extensive sloughing of epidermis

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11
Q

Erythema Multiforme (EM)

A

acute, immune mediated condition characterized by distinctive target-like lesions on skin

commonly induced by infection (herpes simplex virus)

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12
Q

Difference between Minor vs Major Erythema Multiforme

A

Minor EM - without mucosal involvement

Major EM - with mucosal involvement

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13
Q

How can Infection (ADEs) occur?

A

Contamination of the dropper or applicator tip – need to educate patients on sterile technique

dispose of expired/unused medications

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14
Q

Drug Toxicity: Ocular

A

SPK secondary to preservatives
SPK leads to Corneal inflammation, punctate corneal epithelial loss or damage

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15
Q

Decisions for Healthcare Providers

A
  • Patient presentation: SIGN and SYMPTOMS
  • Knowledge of natural disease process
  • potential for morbidity: Risk Vs Benefit
  • ID any ocular or medical contraindications based on review of pt’s medical and medicine hx
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15
Q

Choice of Drug

A

Efficacy in relation to alternatives
- side effects (ADEs)
Drug Interactions
- Warnings or Precautions relative to co-morbidities/other diseases
- Compliance with dosage regiment
- Cost and insurance coverage

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16
Q

Communicating with Other providers of Care

A

SBAR
Situation, Background, Assessment, Recommendation

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17
Q

Baseline Measurements are taken PRIOR to administration of diagnostic or therapeutic ocular drugs

A

Biomicroscopy - topical anesthetics can compromise corneal epithelium & evaluation of aqueous and anterior chamber angle depth is ESSENTIAL before mydriatic agents

Tonometry - record IOP before mydriatics

Assess BP prior to administration of drugs

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17
Q

Minimizing Systemic Adverse Drug Effects: General

A
  • systemic absorption with ocular administration is usually minimal
  • topically applied drugs avoid first pass
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18
Q

How would absorption into systemic circulation occur?
drugs enter into systemic circulation VIA blood vessels of :

A

*Conjunctival sac - conjuc. capillaries
*lacrimal drainage system - nasal mucosa –> oral pharynx –> GI tract
*Episclera (outermost layer of sclera) - via superficial and deep episcleral vessels

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19
Q

Ways to REDUCE systemic absorption of topical applied drugs

A

Mechanical or Physical
- wiping excess* or manual nasolacrimal occlusion*

Prescribing Strategies
- use lowest conc.* and least number of doses per day* (MINIMIAL DOSAGE FREQ)

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20
Q

Ways to reduce Accidental Drug Exposure

A
  • store all medication out of reach of children
  • consider lockable medication storage areas
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21
Q

Percentage Solution

A

% weight/volume = # grams of solute in 100ml

1% = 1gm/100ml
0.5% = 0.5gm/100ml

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22
Q

How many drops in 1 ml?

A

50microliter = 1gtt

**1ml = 20 drops (gtts)

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23
Q

Warnings & Precautions: Systemic vs Ocular Administration

A

types of patients included under warnings and precautions!
- Cardiac conditions
- Pulmonary conditions
- CNS conditions

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24
Q

Dangers of Atropine 1% - P.E.

A

Advise patients to store all medications out of reach of children
- twenty drops (=10mg) may be fatal

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25
Q

Pharmacokinetics (review)

A

eyes have speical pharmacokinetics properties

  • what the body does to the drug
  • drugs are ADME- absorbed, distributed, metabolized, eliminated -
  • determines onset, intensity, and duration of drug action
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26
Q

Drug Absorption of Eye depends on

A
  • Molecular properties of drug
  • viscosity of drug vehicle
  • function status of tissue (barrier to drug penetration)
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27
Q

What types of drugs have a better ability to pass through plasma membranes?

A

lipid-soluble drugs – smaller molecular structure – not ionized

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28
Q

Barriers of Eye : Static vs Dynamic

A

Static (like solids)
- cornea, sclera, blood aqueous and blood- retinal barriers
Dynamic (with movement)
- choroidal and conjunctival blood flows, lymphatic clearance, and tear dilution

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29
Q

Prodrug (review)

A

inactive or weakly active substance that has an active metabolite. Requires Metabolic conversion to a pharmacologically active product

Ex: Nepafenac (Nevanac and ilevro) - NSAID
Ex: Clopidogrel (Plavix)
Ex: Codeine

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30
Q

Drug metabolites may be inactive, less or more active than parent drug

A

*Metabolic enzymes are utilized in prodrug

*Some drugs undergo biotransformation by enzymes in the eye to an inactive form associated with fewer side effects than parent form

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31
Q

Ocular Tissue Structure and Pharmacokinetics

A

avascularity at clear tissues of the eye, allows for direct route for ocular drug penetration via topical meds without high degree of absorption of systemic circulation

32
Q

Tear Structure and Chemical Properties:
tears are responsible for supply ________ to the ______ ___________

A

Tears are responsible for supplying Oxygen requirements of Corneal Epithelium

33
Q

What are the layer of the tear film?

A

Oily Layer (Lipid)
Center layer (Aqueous)
Basal or Inner Layer (Mucinous)

34
Q

Outermost Lipid Layer

A
  • lipid monolayer, produced by meibomian glands
  • stabilizes surface to prevent evaporation
35
Q

Aqueous Layer

A
  • secreted by lacrimal glands
  • provides oxygen to corneal epithelium
  • antibacterial activity
  • wash away debris
36
Q

Mucinous Layer

A
  • composed of glycoproteins – secreted by goblet cells
  • lubricates - permits wetting
  • thin hydrophilic coating
  • cleanses the tears of particulate debris
37
Q

Tear Structure and Chemical Properties

A

tear pH = 7.4 (slightly basic)
normal volume = 8-10 ml
1 drop of medication is 0.05ml, 5-6x the normal tear reservoir

38
Q

Where does the excess drop of medication go?

A

*nasolacrimal duct rapidly drains the excess
- some medication is blinked out of eye onto lid

39
Q

Does increasing drop size increase penetration of medication into the cornea?

A

increasing drop size does NOT result in penetration of more medication into cornea

  • excess via nasolacrimal duct
  • spillage
40
Q

What would be the impact of ocular irritation on absorption of ophthalmic medication?

A

conc. of drug available in the tears for transcorneal absorption is inversely proportional to the tear flow

Increase tear flow = increase washout = decrease conc.

Decrease tear flow = decrease washout = increase conc.

41
Q

Concentration of drug available in tears for transcorneal absorption is inversely proportional to tear flow due to

A
  • drug dilution*
  • drug removal by nasolacrimal duct*
  • eyelid spillover*
42
Q

Dry Eye Patients: a decrease in tear flow rate will lead to –>

A
  • lead to diagnosis of dry eye or keratoconjunctivitis sicca
43
Q

Patient groups more susceptible to keratoconjunctivitis siccca*

A
  • Elderly*
  • Rheumatoid arthritis*
  • Peri-menopausal and post-menopausal women*
  • exposure keratitis associated with dry climate*
44
Q

Potential for increased drug absorption with lower tear flow rate

A

Total tear volume with less than normal volume may:

  • increased drug absorption — as medication is not diluted well
  • prolonged residence time – increase absorption
  • *presence of epithelial surface damage –> increase absorption
45
Q

Corneal Layers

A

*Epithelium - Depot for lipophilic drugs
Boman’s Layer
*Stroma - Depot for hydrophilic drugs, stores lipophilic drugs in keratocyes
Descemet’s Membrane
Endothelium

46
Q

Cornea

A
  • major functional barrier to ocular penetration
  • Major site of absorption for topically applied medication
47
Q

Corneal Nutrients

A

diffusion from aqueous humor for metabolic needs

48
Q

What layer of the cornea have major influence on pharmacodynamics?

A

Epithelium and Stroma
- constitutes depots/reservoirs for lipophilic and hydrophilic drugs

49
Q

Corneal Epithelium

A

Surface Squamous Layer – resists penetration of hydrophilic drugs

Intermediate wing cells

basal “germinative” layer - source of new cells (regenerates)

50
Q

Surface Squamous Layer* – resists penetration of hydrophilic drugs

A
  • tight junctions or zona occludens *
  • lipid soluble drugs penetrate tight junctions due to phospholipid membrane
  • ionization decreases lipid solubility and increases water solubility

ex: sodium fluorescein

51
Q

What does a drug need to possess to effectively penetrate the cornea*** (transcorneal permeability)

A

drug must possess a BALANCE of hydrophilic and lipophilic properties

  • be able to partition between both media
52
Q

Partition Coefficient

A

U- Shaped Parabola curve –
- drugs with too low a P.C (low transcorneal permeability) – do not penetrate well
- Drugs with a too high P.C. (high transcorneal permeability) – tend to remain in epithelium and partition into anterior chamber slowly -

53
Q

Bowman’s Layer

A
  • tough and provides substantial resistance to corneal injury/infection
  • cannot regenerate – will scar if damage
54
Q

Cornea Stroma - 90% thickness of cornea

A
  • depots for hydrophilic drugs
  • stores lipophilic drugs in keratocytes
  • major determinant of corneal transparency
  • disruption of stroma –> potential scarring
54
Q

Cornea Stroma - 90% thickness of cornea

A
  • depots for hydrophilic drugs
  • stores lipophilic drugs in keratocytes
  • major determinant of corneal transparency
  • disruption of stroma –> some potential scarring, possible regeneration
55
Q

Which layers are not known to be drug depots?

A
  • Bowman’s Layer
  • Descemet’s Layer
  • Endothelium Layer
56
Q

Corneal Sclera and Conjunctiva

A

have limited drug penetration – less than 1/5 of all drug absorption - due to extensive vascularization

57
Q

Iris

A
  • pigmented tissue
  • Major function - adjust the amnt of light entering the retina
  • two groups of muscles - sphincter and ilator muscles
58
Q

Sphincter/Circular Muscle

A

Cholinergic innervation
- miosis -
- innervation by sympathetic

59
Q

Dilator/Radial Muscle

A

Adrenergic innervation
- mydriasis -
- innervation by parsympthetic

60
Q

Aqueous Humor Flow and Angle

A

fluid generated from ciliary body
exits via trabecular meshwork/conventional outflow

61
Q

Ciliary Body

A

Produces aqueous humor by pigmented and nonpigmented ciliary epithelium

*pigmented ciliary epithelium can store drugs
- major ocular source of drug metabolizing enzymes**

  • important for Phase I CYP 450 Metabolism
  • detoxification – via Phase II conjugation
62
Q

Anterior Lens Epithelium

A

Most active metabolic region of lens
* most prone to damage by drugs/toxic substances

  • major barrier for entry of hydrophilic, high molecular weight drugs
  • **lipophilic drugs can be absorbed slowly
63
Q

Phase I Metabolism

A
  • involve formation of new or modified functional group/cleavage
  • Oxidation, Hydrolysis, reduction
  • CYP450 enzyme is important – located in liver endoplasmic reticulum
64
Q

Phase II Metabolism

A
  • glucuronic Acid conjugation
  • sulfate conjugation
  • glutathione conjugation
65
Q

Lens associated with Cataracts

A

cataract formation can be increased by some miotics, *steroids, and phenothiazines

66
Q

blood-retinal barrier of Retina and Optic Nerve

A

(tight junctional complexes/ zonula occludens)

  • prevents most hydrophilic drugs from penetrating or being absorbed from blood to retina and vitreous
67
Q

Systemic Agents that cause Retinal Toxicity

A
  • Hydroxychloroquine
  • sildenafil = phosphodiesterase inhibitor
68
Q

Toxic Effects –> Optic Neuritis

A
  • Phosphodiesterase inhibitors
  • amiodarone
69
Q

Ocular Tissue: Removal of Drugs and Metabolites

A
  • two different circulatory pathways in the eye
  • retinal vessels
  • uveal vessels
  • one non-circulatory pathway - direct outflow pathway
70
Q

Retinal Blood Vessels (Circulatory Pathway)

A

removes drugs from vitreous humor and retina by ACTIVE transport

71
Q

Uveal Blood vessels (circulatory pathway)

A
  • removes drugs by BULK transport from iris and ciliary body (endocytosis/exocytosis)
  • requires energy
72
Q

Direct Outflow Pathway (non-circulatory pathway)

A
  • aqueous humor through trabecular meshwork and canal of schlem
73
Q

Compartment Theory

A
  • region of tissue or fluid which drugs can diffuse and equilibrate with relative ease
  • concentration gradients
74
Q

Fick’s Law of Diffusion

A

rate of diffusion across a barrier is proportional to the conc. gradient b/n compartments

75
Q

Drug Diffusion of Cornea - Corneal Absorption

A

Factors that affect drug bioavailability
- preservatives
- infection
- inflammation
- neuronal control

76
Q

First- Order Kinetics

A

More- common situation in ocular drug movements
- rate of drug movement is proportional to conc difference
- passive diffusion across non-saturated barrier

77
Q

Zero- Order Kinetics

A
  • release of drug is constant over time and is INDEPENDENT of conc. present
  • implantable device that releases drug at constant rate
  • ex: Fluocinolone (Iluvien and retisert)
  • ex: Dexamethasone (ozurdez)
    ^^ steroid ocular implants for diabetic macular edema

Spring OD1- Pharmacology (7 decks)

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