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Systemic medications and their ocular side effects

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Title: Systemic medications and their ocular side effects


1
Systemic medications and their ocular side effects
Systemic medications and their ocular side effects
  • Jennifer Tordilla-Wadia, M.D.
  • Vitreoretinal Surgeon
  • James A. Haley Veterans Hospital
  • Tampa, Florida
  • Assistant Professor
  • Department of Ophthalmology
  • University of South Florida
  • Tampa, Florida

2
OBJECTIVES
  • To review basic eye anatomy and physiology
  • To educate clinicians on ocular side effects from
    common systemic medications
  • To encourage providers to report ocular adverse
    effects to the National Registry of Drug-Induced
    Ocular Side Effects, Food and Drug
    Administration, World Health Organization, and
    the pharmaceutical industry

3
  • No Financial Disclosures

4
Anatomy of the Eye
Drug molecules reach the eye through
fenestrations in the choroid and retinal vessels
then diffuse to avascular structures such as lens
and cornea.
5
Systemic medication and their ocular side effects

6
WHO CLASSIFICATION SCHEME
  • Certain
  • A clinical event, including a laboratory test
    abnormality, occurring in a plausible time
    relationship to drug administration, and which
    cannot be explained by concurrent disease or by
    the presence of other drugs or chemicals. The
    response to withdrawal of the drug (dechallenge)
    should be clinically plausible. The event must be
    definitive pharmacologically or
    phenomenologically, using a satisfactory
    rechallenge procedure if necessary.
  • Probable/Likely
  • A clinical event, including a laboratory test
    abnormality, occurring within a reasonable time
    from administration of the drug, unlikely to be
    attributed to concurrent disease or other drugs
    or chemicals, and which follows a clinically
    reasonable response on withdrawal (dechallenge).
    Rechallenge information is not required to
    fulfill this definition.
  • Possible
  • A clinical event, including a laboratory test
    abnormality, that occurs within a reasonable time
    from administration of the drug, but which could
    also be explained by concurrent disease or the
    presence of other drugs or chemicals. Information
    on drug withdrawal may be lacking or unclear.

7
WHO CLASSIFICATION SCHEME
  • Unlikely
  • A clinical event, including a laboratory test
    abnormality, with a temporal relationship to drug
    administration which makes a causal relationship
    improbable, and for which the presence of other
    drugs, chemicals or underlying disease provides a
    plausible explanation.
  • Conditional/Unclassified
  • A clinical event, including a laboratory test
    abnormality, reported as an adverse reaction but
    about which more data is essential for a proper
    assessment or for which the additional data are
    under examination.
  • Unassessible/Unclassifiable
  • A report, suggesting an adverse reaction, which
    cannot be judged because information is
    insufficient or contradictory, and which cannot
    be supplemented or verified.

8
Report an adverse ocular effect
  • FDA MedWatch
  • www.fda.gov/medwatch
  • The World Health Organization Uppsala Monitoring
    Center
  • www.who-umc.org
  • Pharmaceutical industry
  • phone numbers are listed in the current PDR for
    Ophthalmic Medicines.
  • The National Registry of Drug-Induced Ocular Side
    effects www.eyedrugregistry.com

9
National Registry of Drug-Induced Ocular Side
Effects
  • Founded in 1976 and was initially funded by the
    Federal Food and Drug Administration.
  • The Registry is supported by the Casey Eye
    Institute at Oregon Health and Science University
    and the American Academy of Ophthalmology.
  • The goal is to maintain an international
    clearinghouse of information on adverse ocular
    events associated with drugs, chemicals and
    herbals.
  • The Registry accumulates data from spontaneous
    reports sent to the World Health Organization's
    Uppsala Monitoring Center (Uppsala, Sweden), the
    Food and Drug Administration (Rockville, MD),
    pharmaceutical companies, and screening of the
    world's literature.

10
  • What are drugs used to prevent clot formation in
    the disease associated with the EKG below?

11
ANTICOAGULANTS
  • Aspirin (salicylate)
  • Coumadin (warfarin)
  • Heparin (unfractionated heparin)
  • Lovenox (enoxaparin sodium)
  • Plavix (clopidogrel)
  • Pradaxa (dabigatran etexilate mesylate)
  • Ocular Side Effects
  • Subconjunctival and retinal hemorrhage
  • Recommend to be discontinued for a week prior to
    eye surgery
  • INR gt 5 prone to bleed
  • Chronic use of ASA may cause yelllowing of vision

12
  • What are drugs to alleviate the following
    symptoms?

13
ANTI-ALLERGY AGENTS
  • Claritin (Loratadine)
  • Zyrtec (cetirizine)
  • Allegra (fexofenadine)
  • Singulair (Montelukast sodium)
  • Benadryl (Diphenhydramine HCl)
  • Sudafed (pseudoephedrine)
  • Ocular Side Effects
  • Dry Eye, Keratitis sicca
  • Contact lens intolerance
  • Mydriasis
  • Angle closure glaucoma or Narrow angle glaucoma

14
ANTI-ALLERGY AGENTS
  • Claritin (Loratadine)
  • Zyrtec (cetirizine)
  • Allegra (fexofenadine)
  • Benadryl (Diphenhydramine HCl)
  • Sudafed (pseudoephedrine)
  • Mechanism of Ocular Side Effects
  • Block Histamine-1 (H1) receptors
  • Weak atropine action (cholinergic antagonist),
    causing mydiasis, anisocoria, decreased vision
    and blurred vision
  • Inhibit glandular secretion and reduce mucous and
    tear secretion which aggrevate keratitis sicca
    and contact lens wear
  • Anti-ulcer drugs also block histamine receptors

15
  • What are drugs to treat the condition?

16
ANTI-MIGRAINE AGENTS
  • Topamax (topiramate)
  • Indicated for migraines, seizures, mood disorder
  • Mechanism of action
  • blockage of voltage-dependent sodium channels, an
    augmentation of gamma-aminobutyric acid activity
    at some subtypes of the GABA- A receptors,
    antagonism of AMPA/kainate subtype of the
    glutamate receptor, and inhibition of the
    carbonic anhydrase enzyme, particularly isozymes
    II and IV

17
ANTI-MIGRAINE AGENTS
  • Ocular side effects
  • Acute Closed Angle Glaucoma
  • Diplopia
  • Acute Myopia 6-8 diopters
  • Suprachoroidal Effusion
  • Dry Eyes
  • Sulfa Allergy
  • Symptoms within 2-4 weeks

18
ANTI-MIGRAINE AGENTS
  • Serotonin receptor antagonist
  • Imitrex
  • Corneal opacity
  • Beta Blockers
  • Reduce tear lysozyme levels and immunoglobulin
    IgA
  • Dry eye, contact lens intolerance

19
  • Name some medications to treat depression.

20
ANTI-DEPRESSANTS
  • Prozac (fluoxetine)
  • Zoloft (sertraline)
  • Paxil (paroxetine)
  • Celexa (citalopram)
  • Effexor (venlafaxine hydrochloride)
  • Anticholinergic effects
  • blocking the binding of the neurotransmitter
    acetylcholine to its receptor in nerve cells
  • Ocular Side Effects
  • Blurred vision
  • Cycloplegia
  • Photophobia
  • Dry eye

21
  • Name some drugs to treat the following symtpoms.

22
Anxiolytics
  • Xanax (Alprazolam)
  • Valium (Diazepam)
  • Binds to the benzodiazepine receptor site on the
    GABA receptor and modulates function
  • Ocular Side Effects
  • Blurred Vision
  • Diplopia
  • Mydriasis
  • Conjunctivitis

23
  • What are some medications used for the following
    associated with CHF?

24
Antiarrhythmics
  • Amiodarone (Cordarone)
  • Photosensitizer, tendecy towards lipid storage in
    the cornea and lens
  • Dose and duration dependent, usually reversible
  • Ocular side effects
  • Vortex Keratopathy
  • Nearly 100 pts treated greater than 6 months
  • lt10 bothered by blurred vision or haloes
  • Anterior and posterior subcapsular lens changes
  • Optic neuropathy

25
Antiarrhythmics
  • Digoxin (Digitek)
  • Inhibition of NaK ATPase which plays a vital
    role in maintaining normal cone receptor funtion
    and
  • ciliary epithelium responsive for active
    transport of sodium necessary for aqueous
    secretton
  • Ocular Side Effects
  • Affects cone receptor function
  • 11-25 of patients red-green color defects
  • Yellow tinged vision (xanthopsia)
  • Snowy, hazy, or dimming vision
  • Flickering or flashes of light, and colored spots
  • Reduces acqueous secretion and IOP

26
Ever wonder why there is a predominance of the
color yellow in most of Van Goghs works?
  • In the 19th century, Digitalis was widely used
    its uses went beyond treating edema, including
    epilepsy, mania, asthma, and among others.
  • Vincent van Gogh was diagnosed as having Epilepsy
    and Mania
  • He was said to have been prescribed Digitalis by
    his attending physician, who was interestingly
    enough, painted by Van Gogh beside a Foxglove
    plant, where Digitalis is derived
  • Digitalis was widely used and plasma level
    controls were non-existent. One can, therefore
    imagine how easy it was to prescribe an overdose
    of digitalis at the time.
  • Van Gogh suffered from Xanthopsia, a distortion
    in color vision, in which objects appear more
    yellow than they truly are a usual sign of
    Digitalis Toxicity.

27
Starry Night
Van Gogh also suffered from glaucoma making him
see haloes around lights
28
  • What class of drugs would you use to treat the
    following condition?

29
Diuretics
  • Thiazides or diuretics are often used to treat
    congestive heart failure and HTN
  • Hydrochlorothiazide (HCTZ)
  • Furosemide (Lasix)
  • Changes the tear film
  • Ocular Side Effects
  • Dry eye
  • Myopic shift
  • Band keratopathy

30
  • Name some agents to treat a condition related to
    the following picture.

31
Antihyperlipidemics
  • Mevacor (lovastatin)
  • Lipitor (atorvastatin)
  • Zocor (simvastatin)
  • The enzyme HMG-CoA reductase is inhibited,
    thereby preventing the rate-limiting step in the
    mevalonate pathway of cholesterol synthesis.

32
Antihyperlipidemics
  • Ocular Side Effects
  • localized myositis in the extraocular muscles or
    levator palpebrae superioris muscles
  • Diplopia
  • reversible on discontinuation of the statin as
    evidenced by the 62 positive rechallenge case
    reports.
  • Ptosis
  • Lid edema
  • Lens opacities
  • Dry eye
  • Blurred vision
  • Pseudo-cystoid macular edema

33
  • Name some meds for glycemic control.

34
Avandia/Actos
  • Avandia (rosiglitazone)
  • Actos (pioglitizone)
  • Thiazolidinedione class
  • Thiazolidinediones act as insulin sensitizers.
    They reduce glucose, fatty acid, and insulin
    blood concentrations.
  • Ocular Side Effect
  • Macular edema

35
  • What is a common drug to treat the following
    process?

36
Flomax (tamsulosin)
  • Flomax (tamsulosin)
  • alpha-adrenergic blockers, relaxes the muscles
    in the prostate and bladder neck, making it
    easier to urinate
  • Ocular Side Effects
  • Loss of tone in iris dilator smooth muscle
    causing poor pupil dilation
  • Iris prolapse during cataract surgery
  • Floppy Iris Syndrome

37
  • What drug is prescribed for breast cancer and
    reducing the incidence of breast cancer among
    high-risk women

38
Tamoxifen citrate
  • Tamoxifen citrate
  • Tamoxifen competitively binds to estrogen
    receptors on tumor cells and other tissue
    targets, producing a nuclear complex that
    decreases DNA synthesis and inhibits estrogen
    effects
  • Ocular Side Effects
  • Crystalline retinopathy
  • Treatment involves withdrawal of the drug as it
    is reversible
  • Ocular complications are rare (0.6)

39
  • What is the effect of hormones?

40
HORMONES
  • Synthroid (Levothyroxine)
  • Ocular Side Effects
  • Pseudotumor Cerebri (PTC)
  • Visual Hallucinations
  • Diplopia
  • Ptosis
  • Paralysis of EOM
  • Hyperemia
  • Side effects disappear with discontinuation of
    drug

41
Estrogen or Progesterone
  • Estrogen or Progesterone
  • Decreased aqueous production, microvacular
    occlusions from enhanced platelet adhesiveness,
    or increase in fibrinogen and clotting factors.
  • Ocular Side Effects
  • Microvascular complications like artery and
    venous occlusions
  • Dry Eye
  • Contact Lens Intolerance
  • Optic neuritis
  • Macular Edema
  • TIA (Transischemic attacks)
  • Pseudotumor cerebri

42
  • What is common drug to treat this teenager?

43
DERMATOLOGIC AGENTS
  • Accutane (isoretinoin)
  • This retinoid (a form of vitamin A) is used to
    treat psoriasis, cystic acne, and various other
    skin conditions.
  • Deficiency of the normal lipid layer in the tear
    film
  • Ocular Side Effects
  • Swollen optic disc, called "papilledema the
    result of increased intracranial pressure
    (pseudotumor cerebri).
  • Symptoms are headache and transient black-outs of
    vision upon assuming the upright posture.
  • The visual black-outs are caused by postural
    drops in blood pressure and secondary compromise
    of blood flow to the retina through the tightly
    packed optic disc.
  • Night blindness
  • Retinotoxicity
  • Keratitis

44
DERMATOLOGIC AGENTS
  • Minocycline
  • For severe acne vulgais
  • Ocular side effect
  • Swollen optic disc, called "papilledema the
    result of increased intracranial pressure.

45
  • A patient travels back to the U.S. with night
    sweats.

46
Anti-tuberculosis drugs
  • Ethambutol HCL (Myambutol),
  • Isoniazid (Laniazid)
  • Rifampin (Rimactane)
  • Chelates copper, so the decreased levels impair
    mitochondrial activity of axonal transport in
    optic nerve leading to optic neuropathy
  • Ocular side effects
  • Optic neuritis/neuropathy and blindness.
  • Change tears, sweat, saliva,urine, feces and
    contact lenses a red-orange color.

47
Anti-tuberculosis drugs
  • Ophthalmic examinations are recommended by the
    PDR every month for doses of ethambutol greater
    than 15mg/kg/day.
  • No official standard of care exists in dosages
    less than 15 mg/kg/day.
  • Optic neuropathy can occur at any dose despite
    regular ophthalmic exams and that the vision loss
    can be severe and irreversible.
  • Obtain a baseline exam to include a visual field
    test, color vision test, dilated fundus and optic
    nerve exam, and visual acuity.
  • If any visual symptoms occur, patients should
    discontinue the medication and see an
    ophthalmologist.

48
Visual field test results obtained 3 months after
onset of visual symptoms. Both the left (A) and
right (B) visual fields show central scotoma with
inferior temporal quadrant defects.
49
  • Name a drug that can be used to treat the
    following pictures?

50
Antimalarials
  • Plaquenil (hydroxychloroquine)
  • Aralen phosphate (chloroquine)
  • Treats malaria, rheumatoid arthritis, and lupus
    erythematosis
  • High affinity to melanin, toxic to the retinal
    pigment epithelium
  • Ocular Side Effects
  • Bulls-eye maculopathy
  • This bulls-eye maculopathy starts as fine
    pigmentary mottling within the macular area.
  • The end result can range from reduced vision to
    blindness

51
Antimalarials
  • Patients at greatest risk are those on
    hydroxychloroquine for longer than 5 years and
    those with renal or liver
  • Elderly, thin patients may also be overdosed, as
    may obese patients.
  • Dosing regimens are based on body weight, but
    hydroxychloroquine is primarily absorbed by
    cellular tissue. Since adipose tissue is
    relatively acellular, obese patients may be
    overdosed.
  • Dosage exceeds 6.5 mg/kg
  • Examination
  • A baseline exam should be performed before the
    patient starts treatment.
  • Eye exam including Fundus Photos, HVF-10
    (red-white), OCT, Amsler grid, and color vision.

52
Antimalarials
  • Age lt40 who are not higher risk follow-up every
    2-4 years
  • Patients between 40 and 64 years follow-up every
    2-4 years
  • Age 64 and older follow-up(every 1-2 years
  • Annual eye examinations should be considered if
    patients have been on hydrochloroxyquine therapy
    for longer than 5 years, if they are obese, or
    lean and small (especially in the case of elderly
    patients), or if they have progressive macular
    disease of any type, significant renal or liver
    disease, or their dosage exceeds 6.5 mg/kg.

53
Antimalarials
  • Aralen phosphate (chloroquine)
  • Obtain tests as plaquenil exam.
  • See patients at least annually if dosage is less
    than 3.0 mg/kg of ideal body weight.
  • See every 6 months if dosage is greater than 3.0
    mg/kg body weight, or if patients are short,
    obese, or have renal and/or liver impairment.

54
  • Edward Calvin Kendall was awarded the 1950 Nobel
    Prize for Physiology or Medicine for discovery of
    this molecule.
  • First produced commercially by Merck Company on
    September 30, 1949.

55
Corticosteroids
  • Prednisone
  • To treat inflammatory and allergic conditions.
  • They are very effective for acute disease states
    as well as chronic conditions
  • Ocular Side Effects
  • Posterior subcapsular cataract
  • Elevated intraocular pressure
  • Papilledema
  • Exacerbation of herpetic keratitis

56
Corticosteroids
  • Cataracts resulting from steroid use are well
    known and occur with topical, systemic, and nasal
    administration.
  • The development of cataract is related to the
    cumulative dose of prednisone 25 of patients
    who use 15 mg/day for 1 year or more will get
    cataracts that interfere enough with vision to
    require surgical removal
  • The etiology is unknown, the drug may react with
    amino groups of crystalline lens fibers causing
    protein complexes to aggregate

57
  • What drugs are use for treatment/prevention in
    men and women?

58
Bisphophonates
  • FOSAMAX
  • AREDIA
  • ACTONEL
  • ZOMETA
  • BONEFOS
  • DIDROCAL
  • Bisphosphonate molecules preferentially "stick"
    to calcium and bind to it.
  • They accumulate to a high concentration in
    bones, resulting in maintained or increased bone
    density and strength
  • Ocular Side Effects
  • Scleritis/Episcleritis
  • Blurred vision
  • Hyperemia
  • Anterior uveitis

59
  • What is the class of drugs to treat hepatitis and
    multiple sclerosis?

60
Interferons (Intron A/Avonex/Pegasys)
  • Interferons
  • Delayed type hypersensitivity reaction.
  • In many infectious and systemic diseases, the
    deposition of immune complexes with subsequent
    complement activation is a major pathogenic
    mechanism for the devolopment of uveitis
  • Ocular Side Effects
  • Cotton wool spots
  • Optic neuritis
  • Ocular pain
  • Conjunctivitis
  • Pronounced dry eye
  • Dilated Eye exam prior to treatment and 2-4 weeks
    after treatments

61
  • A man reports discoloration of vision after
    taking a medication from his pill box last night?

62
ERECTILE DYSFUNCTION
  • Viagra (sildenafil citrate)
  • Cialis (tadalafi)
  • Levitra(vardenafil)
  • Staxyn( vardenafil HCl)
  • Stendra (avanafil)
  • inhibits phosophodiesterase-5 (PDE-5) which
    results in vasodilation of smooth muscle.
  • Ocular Side Effects
  • Objects have color tingesusually blue or
    blue-green, may be pink or yellow
  • 11 of patients on 100mg perceive a blue haze up
    to four hours
  • Dark colors appear darker
  • Visual disturbances
  • NAION

63
ERECTILE DYSFUNCTION
  • The above ocular side effects are dose-dependent
    with all three drugs.
  • For sildenafil side effects occur at the
    following incidences
  • 50mg 3
  • 100mg 10
  • 200mg 40-50
  • The side effects based on dosage with sildenafil
    start 15-30 minutes after ingestion of the drug,
    and usually peak 60 minutes after ingestion.

64
ERECTILE DYSFUNCTION
  • Patients who should not take phosphodiesterase
    type 5 inhibitors are those who have previously
    suffered ischemic optic neuropathy (NAION) in one
    eye or anyone who experiences transitory visual
    loss while on these medications.
  • These patients may be more prone to developing
    NAION in the same or fellow eye if sildenafil or
    other medicines in this class are ingested.

65
Herbal Medicines and Nutrional Supplementation
  • Canthaxanthine
  • Tanning
  • crystalline retinopathy
  • Chamomile
  • Allergic conjunctivitis
  • one of the most ancient medicinal herbs known to
    mankind.
  • terpenoids and flavonoids
  • human ailments such as hay fever, inflammation,
    muscle spasms, menstrual disorders, insomnia,
    ulcers, wounds, gastrointestinal disorders,
    rheumatic pain, and hemorrhoids.
  • Essential oils of chamomile are used extensively
    in cosmetics and aromatherapy

66
Herbal Medicines and Nutrional Supplementation
  • Datura angels trumpet
  • Mydriasis from tropane alkaloids,
    atropine/scopolamine properties
  • poison
  • Echinacea purpurea
  • Conjunctivitis
  • Used for URI, yeast infection, and many other
    ailments

67
Herbal Medicines and Nutrional Supplementation
  • Ginkgo biloba
  • Spontaneous hyphema, retinal hemorrhage
  • Dementia, Alzheimers, memory
  • Licorice
  • visual loss associated with migraine-like
    symptoms
  • Vasospasm
  • hypertension

68
Herbal Medicines and Nutrional Supplementation
  • Niacin
  • Cystoid macular edema
  • Dry eyes, discoloration of the eyelids, eyelid
    edema,
  • proptosis, loss of eyebrows and eyelashes
  • superficial punctate keratitis
  • Vitamin A
  • Intracranial hypertension when taken in large
    doses , cause papilledema

69
Summary
  • A careful and detailed case history is important
    to reveal a patients medication history.
  • The ocular and visual side effects from a
    patients systemic medication can range from mild
    to severe.
  • Recognition of ocular and visual side effects is
    important for prompt management to prevent and
    minimize serious complications.
  • There are four resources to report ocular
    adverse events
  • National Registry of Drug-Induced Ocular Side
    Effects, Food and Drug Administration, World
    Health Organization, and the pharmaceutical
    industry.

70
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