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Ocular Pharmacology > Antibacterial Treatment of Ocular Disease Pt II > Flashcards

Antibacterial Treatment of Ocular Disease Pt II Flashcards

1
Q

What are the most common bacteria found ‘inhabiting’ the eye?

A

Staphylococcus epidermidis (15-45%)
Moxrella
(Older population - Corynebacterium xerosis)

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2
Q

What are the most common causes of ocular bacterial infection?

A

Staphylococcus aures and Staphylococcus epidermidis
Streptococcus pneumonia and pygens
Moxarella lacunta
Haemophilus aegyptius (Koch-Weeks)

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3
Q

What is the most frequent cause of bacterial blepharitis?

A

Staphylcoccus –> Seborrheic bleph

Moxarella –> Angular bleph

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4
Q

Between bacterial, viral and fungi, what is the most common cause of an ocular infection?

A

Bacterial/viral

Fungi

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5
Q

What is toxic conjunctivits?

A

This isn’t an infection at all, it is an ocular inflammation of conjunctiva and rather than being caused by an infection, it is the drug causing an inflammatory response in the eye

Manifests when patient is given the drug and they seem to get better but suddenly they get worse.

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6
Q

Briefly describe Staphylococcus

A

Gram (+) cocci
Cause epithelial damaging purulent discharge
Grape like cluster and susceptible to penicillin to a degree

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7
Q

Briefly describe Streptococcus

A

Gram (+) cocci

Straight chain and tend to occur in pairs

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8
Q

Briefly describe Neisseria

A

Gram (-) cocci
Found in pairs and causes purulent discharge hyperacute bacterial conjunctivitis
Penicillin effective

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9
Q

Briefly describe Moxarella

A

Gram (-) bacilli

Largest of the bacilli and occur in pairs

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10
Q

Briefly describe Haemophilus

A

Gram (-) bacilli

Very hard to culture, must use fortified cultures or blood

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11
Q

Briefly describe Pseudonomas

A

Gram (-) bacilli

Small and has high corneal penetration to cause significant damage

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12
Q

Discuss and describe the MOA, toxicities and preparations for Bacitracin

A

Bacteriocidal
Narrow spectrum - Gram (+) and some (-) cocci
Disrupts cell wall synthesis by affecting carrier protein transport for peptidoglycan precursors
Minimal Resistance
Some infrequent allergies and rare toxic conjunctivitis
Topical only.

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13
Q

Discuss and describe the MOA, toxicities and preparations for Gramicidin

A

Same MOA as Bacitracin but stable as a solution

Similar spectrum, narrow with gram (+) and some gram (-)

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14
Q

Discuss and describe the MOA, toxicities and preparations for Neomycin (and all other aminoglycosides)

A

Bacteriocidal
Inhibits protein synthesis by binding to 30s ribosome and causes mRNA misreading
Narrrow spectrum - Gram (-) (no pseudomonas)
Resistance is frequent (can lead to toxic conjunctivitis)
Frequent Allergic Sensitizer (Like all aminoglycosides)
Topical; not orally effective

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15
Q

What is the classic toxicity seen with ALL aminoglycosides?

A

Allergic sensitizer against other aminoglycosides

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16
Q

Discuss and describe the MOA, toxicities and preparations for Gentamicin

A

Bacteriocidal
Aminoglycoside
Some gram (+) including staph, some gram (-) including pseudomonas, moxarella, haemophilus
Binds to 30s ribosome to inhibit protein synthesis
Resistance possible via increased drug metabolism by organism
Topical and IV
Topical Toxicities - Rare but include corneal toxicities (epi erosions, delayed healing, ulcers, conj toxicity and infrequent allergies)
IV Toxicities - Pseudotumor cerebri, oto and nephrotoxicity
If fortified - Depigmentation and/or keratitis

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17
Q

Which antibacterial category does Tobramycin fall under, and which drug does it share a duplicate MOA/toxicity profile with? What are some differences between the two?

A

Aminoglycoside
Gentamycin
Better against pseudomonas; less nephrotoxicity with systemic injection than gentamycin

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18
Q

What class of antibiotic is Amikacin? Describe its MOA, toxicities and contraindications

A

Aminoglycoside
Very effective against strains resistant to gentamycin or tobramycin (Normally they affect gram +, staph, and some gram - like pseudomonas, moxarella and haemophilus)
Very similar toxicity profile
Not available as a topical ocular preparation

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19
Q

Discuss and describe the MOA, toxicities and preparations for Polymyxin B

A

Bactericidal
Narrow spectrum - Only Gram (-)
Disrupts outer cellular membrane found only in Gram (-) with a detergent like solubilization of membrane to greatly alter permeability.
Resistance very unlikely
Toxicities - generally non-irritating, rare allergic reaction/topical irritation however
Not available on its own, only found in combo products and rarely in an isolated powder form to allow for compounding

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20
Q

Discuss and describe the MOA, toxicities and preparations for Sulfacetamide

A

Sulfa-based AB (synthetic); Bacteriostatic
Broad spectrum - Gram (+/-)
Mimics para-Aminobenzoic acid (PABA) and uses competitive inhibition (dose dependent) to prevent utilization of folic acid in creation of nucleic acids
Resistance is FREQUENT
That said, great for treating UTI due to being actively concentrated in the urine.
Toxicities - Frequent sensitizer; photosensitivity as seen with all sulfa drugs (very rapidly formed ‘sunburn’), severe agranulocytosis, transient myopia, hemolytic anemia

21
Q

Discuss and describe the MOA, toxicities and preparations for Trimethoprim

A

Bacteriostatic (unless comboed with polymyxin B)
Broad spectrum - Gram (+/-)
Competitive inhibition during folic acid (after it is formed unlike before like sulfacetamide)
Resistance still happens
Do not experience cross allergic sensitivity if allergic to other sulfa drugs
Toxicities - mild transient ocular irritation

22
Q

Discuss and describe the MOA, toxicities and preparations for Pyrimethamine

A

Very closely related to trimethoprim. Used as an anti-malarial drug

23
Q

Discuss and describe the MOA, toxicities and preparations for Tetracycline

A

Tetracycline; Bacteriostatic
Broad spectrum - Includes chlamydia
Inhibits protein synthesis by binding to 30S ribosome unit
Resistance is common
NO TOPICAL OCULAR AGENTS AVAILABLE
Toxicities - Contraindicated in children under 8 and pregnant mothers due to permanent tooth/bone discoloration malformation.
Systemic - Photosensitivity, can sunburn body, transient myopia, pseudotumor cerebri, EOM paresis
Topical - Very rarely see these

24
Q

Discuss and describe the MOA, toxicities and preparations for Doxycycline and Minocycline, and name the class these drugs fall under

A

Tetracycline; bacteriostatic
Broad spectrum - including chylamida
Blocks the binding of 30S ribosome during protein synthesis
Has anti-inflammatory action at a lower dose than the AB related one.
Can be used to treat cases of severe acne

25
Q

Discuss and describe the MOA, toxicities and preparations for Tetracycline

A

Tetracycline; Bacteriostatic
Broad spectrum - Includes chlamydia
Inhibits protein synthesis by binding to 30S ribosome unit
Resistance is common
NO TOPICAL OCULAR AGENTS AVAILABLE
Toxicities - Contraindicated in children under 8 and pregnant mothers due to permanent tooth/bone discoloration malformation.
Systemic - Photosensitivity, can sunburn body, transient myopia, pseudotumor cerebri, EOM paresis
Topical - Very rarely see these

26
Q

Discuss and describe the MOA, toxicities and preparations for Doxycycline and Minocycline, and name the class these drugs fall under

A

Tetracycline; bacteriostatic
Broad spectrum - including chylamida
Blocks the binding of 30S ribosome during protein synthesis
Has anti-inflammatory action at a lower dose than the AB related one.
Can be used to treat cases of severe acne

27
Q

Discuss and describe the MOA, toxicities and preparations for Erythromycin

A

Macrolide AB; Bacteriostatic
Similar spectrum to penicillins (Gram +/- with neiserria and chlamydia)
Inhibits translocation during protein synthesis, binds to 30S ribosome to disrupt protein synthesis
Resistance common
Few toxicities when used topically
Used to treat neonatal conjunctivitis
Only available as a 0.5% ointment

28
Q

What are the macrolide ABs that are used systemically and not as an ointment?

A

Azithromycin and Clarithromycin

29
Q

Discuss and describe the MOA, toxicities and preparations for Azithromycin

A

Macrolide AB; bacteriostatic (Orally, most prescribed AB in the US)
Spectrum like the pencillins (Gram +/- with neiserria and chlamydia)
Inhibits translocation duriong protein synthesis, binds to 30S ribosome
Most frequent toxicity is ocular irritation (1-2%) with some cases of stinging, keratitis, contact dermatitis, dry eye, nasal congestion, sinusitis
Not big difference with anti-inflammatory action compared to other tetracyclines

30
Q

Discuss and describe the MOA, toxicities and preparations for Chloramphenicol

A

Bacteriostatic
Broad spectrum with very good ocular penetration and can obtain near therapeutic levels in the AC
Inhibits transpeptidation of new proteins; inhibits protein synthesis
Resistance common
Available for IV, not topical ocular
Many toxicities, systemic and topical - Aplastic Anemia, optic atrophy, allergic reactions

31
Q

Name the fluroquinolones, distinguishing the ones that are 4th generation

A

Ciprofloxacin
Ofloxacin
Levofloxacin

4th generation
Moxifloxcin
Gatifloxcin
Besifloxcin

32
Q

Discuss and describe the MOA, toxicities and preparations for the Fluroquinolones

A

Very potent, bacteriocidal and the go to topical ocular drug
Broad spectrum
Affects DNA gyrase (Topoisomerase II) to prevent DNA synthesis and supercoiling.
Resistance possible, especially with pseudonomas and staph. 4th gen less likely
Used to treat SEVERE corneal ulcers
Toxicity - Allergy possible with long term use and disrupts GI tract flora
Crusting, FBS, itching and bad taste. Some chance of super infection with long term use.
GIT upset, headaches, dizziness, restlessness, depression, insomnia, photosensitivity
Black Box Warning - Tendinitis, worsens myasthenia gravis

33
Q

Discuss and describe the MOA, toxicities and preparations for the Penicillins

A

Bactericidal
Spectrum depends on specific pencillin:
Natural - Pencillin G/Pen VK - Narrow gram (+)
Penicillinase resistant - Methicillin, Floxacillin, Dicloxacillin - Narrow but effective against the resistant versions
Aminopencillins - Aminopencillin, ampicillin - susceptible to pencillinase, but extends spectrum into some gram (-)
Extended Spectrum - Tiacarcillin - Antipseudonomal and many gram (+/-) but must be injected
Inhibits cell wall synthesis; new gen can penetrate gram (-) outer cell membrane to inhibit enzymes/formation of peptide links
Resistance common, especially with staphlycoccus
Toxicity - Not used topically, frequent allergies otherwise. Massive sensitizer
Oral use of amoxicillin is a leading Rx
If taken orally can cause GI upset, diarrhea

34
Q

Discuss and describe the MOA, toxicities and preparations for the Cephalosporins

A

Similar to natural pencillins but more resistant to beta-lactose/pencillinase
Spectrum depends on class of cephalosporin
1st gen - Cephalexnin, Cefadroxil - gram (+)
2nd gen - Cerfuroxime, Cefaclor - gram (+/-)
3rd gen - Cefdiner - mostly gram (-) not so much gram (+)
MOA much like pencillin, but more against pencillinase producers.
Oral or IV not topical
Toxicitiy - Few toxicities but there is occassional cross allergy with pencillin.

35
Q

Discuss and describe the MOA, toxicities and preparations for the Vancomycin

A

Bacteriocidal
Narrow spectrum - Gram (+) such as MRSA (flesh-eating disease)
Inhibits cell wall synthesis by binding to precursor units and prevents crosslinking
IV use only

36
Q

Discuss and describe the MOA, toxicities and preparations for the Linezoid (Zyvox)

A

Bacteriostatic
Narrow spectrum - Gram (+) resistant strains (including those resistant to vanomycin like VREF)
Inhibits protein synthesis to prevent assembly of 30S and 50S ribosomes

37
Q

Discuss and describe the MOA, toxicities and preparations for the Daptomycin (Cubicin)

A

Bacteriocidal
Narrow spectrum - Staph and Strep resistant (effective against those resistant to vanomycin and linezoid)
Binds to membrane and depolarizes it to cause efflux of intracellular contents to kill cell

38
Q

Despite the relatively weak potency of sulfa-based ABs, what condition are they very good at treating?

A

Urinary Tract Infections (UTI)

39
Q

Before the advent of fluroquinolones, what did we do to treat severe corneal ulcers?

A

Fortified solutions of ABs

40
Q

What is the easiest AB to fortify?

A

Relatively highly concentrated injectable drop or a topical but low concentration drop.

A powder isn’t bad either

41
Q

How do antifungal agents differ from antibacterial?

A

Fungal infections are very slow growing and much harder to treat
Traumatized, debilitated or immune-suppressed eye very susceptible (AIDS/HIV, diabetic, inhaled steroids, poor peripheral circulation)
Easy to identify but hard to culture
Takes very long to treat

42
Q

What is the only antifungal drug we use in optometry?

A

Natamycin (Natacyn)

43
Q

Discuss and describe the MOA, toxicities and preparations for the Natamycin (Natacyn)

A

Broad specturm - Candida and Aspergillus
Polyene antifungal binds to sterols in cell membrane to create pores/holes allowing intracellular contents to spill out.
Minimal toxicity with topical use

44
Q

Discuss and describe the MOA, toxicities and preparations for the Amphotericin B (Amphotec)

A

Systemic antifungal (given IV)
Broad/Narrow spectrum
Polyene antifungal that binds to sterols in cell membrane to cause pores to make cellular contents leak out
Toxicity - Systemic administration causing reversible renal damage, hypotension and vomiting
0.5% and 1% toxic, but 0.15% topical solution is minimally toxic

45
Q

Discuss and describe the MOA, toxicities and preparations for the Miconazole (Monistat)

A

Very broad fungi action with some gram (+) action; good ocular penetration
Group of agents blocking ergosterol synthesis by inhibiting cytochrome P-450
Many drug-drug interactions
Toxicities - Low ocular toxicities
Systemic use can cause anorexia, anemia, nausea and fever

Used exclusively to treat mucocutaneous and cutaneous fungal infections

46
Q

Discuss and describe the MOA, toxicities and preparations for the Flucytosine (5-Flurocytosine)

A

Antifungal
Spectrum - Yeast-like (Candida)
Antimetabolite that substitutes for nucleic acids to disrupt metabolic processes
Severe toxicity that is dose dependent (myelosuppression)
Can be combined with amphotericin B for better synergistic action

47
Q

Discuss and describe the MOA, toxicities and preparations for the Griseofulvin

A

Spectrum - Only good for dermatophytes and must be actively taken up in cells
Inhibits fungal mitosis, very slowly acting (6 months to a year)
Toxicitiy - After oral use, CNS - headache, lethargy, confusion, impaired judgement, nausea, vomiting, bad taste, blood disorders and photosensitivity

48
Q

What are some for when an ocular infection walks into the clinic?

A

Suspect common bacteria, not fungi unless the history indicates it
Inquire about other infections like UTI
Keep in mind bacteria cause a thick mucopurulent discharge, fungi don’t make a mess and viruses make a serous discharge
Swab for gram and cultures
Start treatment based on clinical assessment and the gram stain. (Braod spectrum drugs or gentamicin and bacitracin are a good combination)
Recall the patient in a few days (next day if it’s a corneal ulcer)

Ocular Pharmacology (11 decks)

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