Week 8 - Adverse drug reactions

Question 1

What are ADR’s and side effects?

Answer 1

• ADRs
- A noxious and unintended response to a drug
- An undesired outcome for the patient

• Side effects
- An unintended effect
- Not necessarily undesirable

Question 2

Most common ocular medications which cause ADR:

Answer 2

• Brimonidine
• Dorzolamide
• Atropine
• Lanolin
• Benzalkonium Chloride

Question 3

Clinical presentation of ADR’s: (SS)

Answer 3

Delayed reaction: can be weeks or months of uneventful us
• Symptoms: irritation, redness, stinging, burning
• Signs: Hyperaemia, lid oedema, diffuse SPK

Severity is dose-dependent

Question 4

Mechanism of ADR:

Answer 4

Hypersensitivity
•Type IV hypersensitivity
• Mediated by T cells
• T cells release cytokines
• Cytokines promote inflammation

Chemical Toxicity
• Direct irritation of ocular surface
• Irritation triggers inflammation
• Benzalkonium chloride

Question 5

Benzalkonium Chloride

Answer 5

• Used as a preservative in ocular medications
• Found in up to 75% of ocular preparations available within the EU
• Mode of action: disrupts permeability of cell membrane
• May demonstrate a mild toxic effect on ocular surface
• Concentration-dependent irritation

Question 6

Management of allergy to preservatives:

Answer 6

• Switch to unpreserved preparation, if possible

• Single dose units/filtered multi-dose bottles

• Preservative free prescribing?
- History of sensitivity to preservatives
- Very frequent dosing (6 X Day +)

• Change to alternative medication

• Symptomatic relief:
- Cold compresses, Artificial tears, topical steroid (preservative free)
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Question 7

What ranges of corticosteroids are available?

Answer 7

• Non-Penetrating (soft)
- Fluorometholone

• Penetrating (hard)
- Prednisolone (1%)

1 drop 4x a day for 1 week then taper

Question 8

How to treat ADR hypersensitivity?

Answer 8

• Mast cell stabiliser: sodium cromoglicate, lodoxamide
• Topical (ocular) antihistamine: azelastine, olopatadine

Question 9

Tetracycline antibiotics:

Answer 9

• An effective second-line treatment for blepharitis
• Highly effective against chlamydia (but this needs referral)

• Doxycycline 100mg
• Minocycline 50/100mg
• Oxytetracycline 500mg
• Tetracycline 500mg

Question 10

Tetracycline ADRs

Answer 10

• Photosensitivity
- advise against prolonged sun exposure
- advise use of sun protection

• Tooth discolouration
- Contraindicated in under 12s, pregnancy and breast feeding

• GI Disturbance
- Nausea
- Diarrhoea
- Vomiting

• Headaches

• Stevens-Johnson syndrome

• Kidney/liver damage
- avoid in patients with renal/hepatic impairment

Question 11

Topical corticosteroids are used for:

Answer 11

Effective short-term measure to control ocular inflammation:
• Uveitis
• Allergic eye disease
• Marginal keratitis

Often used intensively (every hour)

Question 12

ADRs with topical corticosteroids

Answer 12

• Suppress immune response and ability to fight infection
- Exclude infectious cause

• Corneal/scleral thinning
• Delayed wound healing
• Cataract development

Question 13

Steroid glaucoma: Describe; guidance on iop monitoring;management

Answer 13

Significant elevation of IOP associated with corticosteroid use in approximately 35% of patients

Guidance on IOP Monitoring
• Measure baseline IOP
• Recheck at 2 weeks
• Recheck every 4 weeks for 2-3 months
• Then 6 monthly if therapy is to continue

Management
• IOP elevation typically subsides within 1-4 weeks
• Urgent referral back to prescriber
• Change to alternative medication
• Add glaucoma medication

Question 14

Why should topical steroids be tapered?

Answer 14

Severe ocular inflammation (e.g. uveitis) carries risk of:
• Posterior synechiae
• Secondary glaucoma
• Cataract
• Cystoid macular oedema

Risk of flare up

Question 15

Topical corticosteroids: how do risk vary between each potency?

Answer 15

• Reduced potency and corneal penetration reduces risk of ADRs
- Consider non-penetrating corticosteroid

• The higher the steroid potency, the greater the ocular hypertensive
- Dexamethazone and prednisolone acetate are more likely to result in increased IOP when compared to fluoromethalone and loteprednol

Question 16

What else could be considered instead of a cortical steroid?

Answer 16

Consider a topical Non-Steroidal Anti-Inflammatory Drug (NSAID)
• Diclofenac Sodium (Voltarol Ophtha)

Question 17

Topical NSAIDs:

Answer 17

•Anti-inflammatory action
• Analgesic action

• Reduced ADRs
- No concern about steroid glaucoma
- No cataract
- Immune response
- Wound healing

• Systemic NSAIDs
- Indirect administration
- ADRs: gastric ulceration, aspirin hypersensitivity

Question 18

ADRs with Glaucoma medications:

Answer 18

• Required for prescribing glaucoma medications
• Also useful when examining patients with glaucoma

1. Prostaglandin analogues
2. Beta blockers

Question 19

Prostaglandin Analogues

Answer 19

• Low risk of systemic ADRs
• Majority are local to the ocular region

Local ocular irritation and conjunctival hyperaemia
- Common, prevalence: 6.3 - 58%
- 63% of glaucoma patients who stopped or switched medication did so because of hyperaemia

Question 20

Prostaglandin Analogues: ADR’s with iris?

Answer 20

Iris Hyperpigmentation
• Common, prevalence: 7-50%
• More likely with mixed colour irides
• Typically within years 1 and 2 of treatment
- 90% of patients who will develop iris hyperpigmentation have done so by end of yr two
• Irreversible
• Cosmetic change only

Question 21

Prostaglandin Analogues: Side effects to eyelash

Answer 21

• Increase in lash length, thickness and pigmentation
Common, prevalence: up to 50%
• Associated increase in eyelid skin pigmentation
> Less common, prevalence up to 7%
• Reversible
• Cosmetic change only
- Monocular treatment?

Question 22

Prostaglandin Analogues: Macular ADR’s

Answer 22

Cystoid Macular Oedema- Inflammation: Intraretinal swelling
• Considerably rarer (significantly less than 1%)
• Typically in pseudophakic/aphakic patients, particularly if surgery was complicated
Recreated from Ahad et al.
• Macular edema resolves following cessation of PGA

Question 23

Prostaglandin Analogues: Uvea ADRs

Answer 23

Anterior Uveitis
• Rare (Horsley et al. 2011)
• Reports of exacerbation/flare-up of existing cases
• Also reports of new cases

This association remains controversial:
other studies have found no link

Question 24

Prostaglandin Analogues: Herpes ADR’s

Answer 24

Herpes Simplex Keratitis
• Rare
• Risk of reactivation with PGA use
• Supported by animal work
• BNF Contraindications (latanoprost):
- Active HSK
- History of recurrent HSK associated with prostaglandin anal

Question 25

Beta-Blockers: Ocular ADRs

Answer 25

• Several systemic, few ocular
• Dry eye
- Beta-blockers reduce production of the aqueous component of the tear film
- Common; prevalence: 10-25%
- Lower risk with preservative-free: 16% V 35%

Question 26

Beta-Blockers: Systemic ADR’s

Answer 26

• Sympathetic ANS
- Increase heart rate
- Bronchial dilation

• Block Sympathetic ANS
- Bradycardia
- Obstructive airway disease/asthma

• Contraindications
- Bradycardia (<60 bpm)
- Heart block
- Uncontrolled heart failure
- Asthma
- Obstructive airway disease

Question 27

Beta-Blockers: Other ADRs

Answer 27

CNS
• Depression
• Loss of libido
• Confusion

Peripheral Vascular
• Migraine
• Raynaud syndrome

Question 28

Reporting ADRs:

Answer 28

• ADRs can be reported through the MHRA’s ‘yellow card’ scheme
• Used to collect data about the risk profile of medicines
• May identify ‘new. ADRs which were not detected during the clinical trial research phase
• Particularly important for new drugs (marked by black triangle)