Week 2.01 Adverse Reactions

Question 1

What is mean by an adverse effect

Answer 1

Side effect: undesired effect of medication extraneous to the intended therapy

Adverse effect: negative side effect

Question 2

If you have a rich blood supply and small mass of the eye are you more or less likely to have advserve effects

Answer 2

More likely

Question 3

In the cornea what may the drugs bind to

Answer 3

In cornea – drugs may bond in the stroma to glycosaminoglycans which could result in swelling and decrease in transparency

Question 4

What are the two ways drugs can enter the eye and leave the eye

Answer 4

When drugs enter eye via uveal circulation they exit eye via canal of schlemm or ciliary body

Drugs entering via retinal circulation may leave the eye by systemic circulation or diffuse into vitreous

Question 5

What is the WHO scale

Answer 5

1) Certain – is a definite relationship between the time drug taken and which effects occurred/ cannot be explained by any other disease present
2) Probable/likely
3) Possible
4) Unlikely
5) Conditional/unclassified
6) Un-assessable/unclassifiable

Question 6

What might you see in a px eye if u suspect drug adverse effects

Answer 6

• deposition of pigmentation on the eyelids or conjunctiva or changing transparency of the cornea or lens
• Deposits on px retina
• Drugs might affect ANS - changes to size of pupil, inhibit accommodation, deviation in position of eyes or eyelids (extraocular muscles/eyelids)
• visual hallucinations
• notice a change in VA, constriction of visual field, strange colour vision effects
• vascular effects - leakage or occlusion

Question 7

Aye and adverse reactions

Answer 7

• Older px more likely to be taking systemic medications
• Polypharmacy – taking 4 or more medications
• Blood-retina barrier becomes less effective with age – usually the retinal vascular endothelium and retinal pigment epithelium blocks the drug molecules entering
• Reduced ocular perfusion pressure – a value calculated by taking 2/3rds of the mean arterial blood pressure and subtracting from that the interocular pressure and it gives an indication of ocular blood flow
• If this reduces then a sign that blood flow has reduced and eye more susceptible to ocular disease

Question 8

What is ED50

Answer 8

Median therapeutic dose of a drug

Question 9

Narrow therapeutic index

Answer 9

Drugs with a narrow therapeutic index are more likely to cause an adverse reaction

Narrow therapeutic index: when toxicity occurs at less than twice the ED50

Question 10

What is the TD50 value

Answer 10

TD 50 value which is the dose of the drug which produces toxicity (e.g. unwanted side effects) again in 50% of individuals who have been given that specific dose

Question 11

What does large therapeutic index tell us

Answer 11

Large therapeutic index means u would have to have a significant increase in dose, way above therapeutic levels to see any toxic effects

Question 12

Need to consider drugs that may affect:

Answer 12

• cornea
• occulomotor system - eye movements, accommodation
• tear film
• intraocular pressure
• lens
• retina
• visual field
• colour vision effects

Question 13

What are drugs that affect the cornea

Answer 13

• amiodarone
• chlorpromazine (Thorazine) - antipsychotic

Question 14

What is amiadarone, side effects, progression

Answer 14

Drug that affects cornea
- used to treat cardiac arrhythmia- irregular heartbeat
- works by prolonging reploarisation in heart
- main ocular side effect is appearance of corneal micro deposits - corneal verticillata

Px taking 400 - 1000mg daily will probably develop keratopathy
- dose dependent
Therapy duration dependent

Question 15

What are the 3 stages to development and progression of amiodarone keratopathy

Answer 15

Amiodarone keratopathy

Corneal deposits seen 6 days after
Increasing severity

Lower doses typically stage 1
Stage 3 more higher dose px
Bilateral
Px wont notice change in vision minority may notice halos

Stage 1: fine grey deposits on inferior cornea, linear pattern
Stage 2: additional horizontal lines, plus arborising (tree like branching deposits
Stage 3: verticillate “whorl-like” pattern

Do not fade away if stopped. Don’t usually stop this medication as heart more important than corneal deposits

Question 16

What are the other ocular effects of amiodarone

Answer 16

Lens opacities
Retinal and optic nerve deposits
Optic neuropathy

Question 17

What is amiodarone optic neuropathy

Answer 17

More serious
Occurs in 2% prescribed this med and more common in men
Swelling of disc - borders appears less distinct
Can lead to bilateral vision loss
Occur within first 12 months

Question 18

What is chlorpromazine and what are the side effects

Answer 18

Antipsychotic medication - affects px cornea and lens
- treats schizophrenia
- can cause skin and ocular pigmentation at high doses over long period of time
- pigmentary deposits in descemets membrane and endothelium white, brown, black
- Changes are dose dependent
- IRREVERSIBLE changes - deposits
- may be see on surface of lens

Px can have a chlorpromazine stellate cataract - looks like a star shape

Question 19

What are the drugs that affect anterior angle

Answer 19

• topiramate - aka topamax

Question 20

What is topiramate and what are the side effects

Answer 20

Affects anterior angle
• Antiepileptic drug
• Has also been used for: migraine prophylaxis, trigeminal neuralgia, bipolar disorder, idiopathic intracranial hypertension
• Used in adults and children >2yrs

Side effects:
• Acute onset angle closure glaucoma – ciliary body oedema pushes iris forward blocking drainage
• Acute myopia
• Peri-orbital oedema
• Scleritis
• Blepharospasm
• Nystagmus
• Diplopia

Maj females age 34 who suffered glac attack, range of refractive errors, link with px prescribed SSRIs

Look out for headaches, blurred vision, vomiting

Question 21

What drugs affect oculomotor

Answer 21

• tricyclic antidepressants - amitriptyline hydrochloride
• motion sickness drugs - hycosine, scopolamine
• over counter cough and cold - contains sympathomimetic phenylephrine
• thyroid hormone replacements - levothyroxine
• heroin - methadone

Question 22

What’s are tricyclic antidepressants and what are the side effects

Answer 22

• Tricyclics exert antimuscarinic effect – therefore will have a cycloplegic and a mydriatic action
• Risk of closed angle glaucoma in “at risk” individuals
• Px may complain of blurred vision and photophobia
• May need near add, tinted spectacles
• Dry mouth, blurry vision, increased body temp
Effects are transient and reversible – so if stop med side effects will reduce

Question 23

What are motion sickness drugs and what are the side effects

Answer 23

Hyoscine, scopolamine
- scopoderm - patch applied to skin behind ear
- help treat motion sickness or travel sickness
- exerts an antimuscarinic effect - therefore will have a cycloplegic and a mydriatic action

Side effects
- blurred vision and photophobia
- reversible when stop drug

Question 24

What are over counter cough and cold and what are side effects

Answer 24

• contains sympathomimetic phenyelphrine

Side effects:
- dilation of the pupils
- photophobia
- risk of ACG
- reduces conjunctiva hyperaemia as blood vessels constricted however could then be masking an imp anterior eye sign

Question 25

What is nystagmus

Answer 25

Nystagmus – is an involuntary oscillation of one or both of the eyes, about one or more axes.

Question 26

What can cause vertical, vestibular nystagmus and ocular muscle palsies

Answer 26

Vertical nystagmus – from use of barbiturates (used as sedatives/induce sleep). Also associated with ptosis or drooping of eyelids

Streptomycin antibiotic associated with vestibular nystagmus – interaction between the drug and 8th cranial nerve

Chloroquine- also associated with extra ocular muscle palsies

Question 27

What are thyroid hormone replacements and what are the side effects

Answer 27

E.g. levothyroxine
Still oculomotor
- used to treat px with reduced thyroid function

Side effects:
- droopy eyelids - due to paralysis of lavatory muscle
- some noticed visual hallucinations
- more serious conditions such as papiloedema
- conjunctival hyperaemia and oedema
- dry eye
- photophobia
- visual hallucinations

Question 28

What is heroin and what are the side effects

Answer 28

Methadone

Side effects:
- pupil miosis
- dip and/or blurred vision
- reduced VA, convergence, stereo acuity during immediate post-detox
- deviations become less exo/more eso
- if undergo detox px may still suffer from double vision and or blurred vision
- reduction in px ability to converge

Question 29

What are some drugs that affect the tear film

Answer 29

Atrophine
Antihistamines
Beta blockers
Oral contraceptives

Question 30

Adverse reactions affecting the tear film

Answer 30

Atrophine - antimuscarinic activity, inhibit glandular secretion, causing a reduction in tear volume
Antihistamines, beta blockers and oral contraceptives can also inhibit tear production - can be a major problem for contact lens wearers

Question 31

Increase in tear production seen with:

Answer 31

Parasympathomimetics - pilocarpine, neostigmine and number of anti-hypertensive drugs

Question 32

Drugs that lower blood pressure/ IOP

Answer 32

• drugs used to control systemic hypertension also lower IOP
• px with glac might not need second dose then

RULE OF THUMB: 10mmHg reduction in systolic BP gives a 1-2mmHG reduction in IOP

Question 33

Examples of drugs that lower IOP

Answer 33

• Systemic beta blockers – used to reduce cardiac output in systemic hypertension e.g. atenolol
• Vasodilators (used to relax smooth muscle of arteriole walls in cases of systemic hypertension) e.g. captopril
• Drugs for dementia (acetylecholinesterase inhibitors used in Alzheimer’s) e.g. rivastigmine – reduce IOP by increasing aqueous outflow facility

Question 34

Example of drugs that increase IOP

Answer 34

• corticosteroids - increase IOP by reducing aqueous outflow facility
• px receiving steroids should have their IOPs measure med prior to commencement of steroid and short intervals to monitor changes

Question 35

What is central serous chorioretinopthy

Answer 35

Shows up on OCT scan as area of fluid beneath the neurosensory retina and is typically seen in middle aged males or px experiencing stress.
Px reported reduced VA
Hyperopic shift

Question 36

Drugs affecting the crystalline lens

Answer 36

Corticosteroids
- Appearance of a posterior sub capsular cataract which can be present in around 1 in 3 patients
- Is dose dependent
- 10mg a day for less than a year very low risk of cataract
- 16mg per day for several years = PSC in ~75% of px
- Greater effect during near vision due to pupil constriction
- Can occurs in children who have been prescribed corticosteroids
- Need to keep a close watch on kids who have been given these medications a because cataract at this stage could lead to amblyopia, irreversible change to vision

Question 37

What are some drugs associated with myopic shift

Answer 37

Topiramate
Diuretics
Carbonic anhydrase inhibitors
Sulphonamides

Question 38

What is a drug that affects the anterior segement

Answer 38

Bisphosphonates - e.g. alendronate sodium, risedronate sodium
• Used in treatment of osteoporosis (increases risk of broken bones)
• Helps to increase bone thickness
• Ocular effects usually inflammatory

Reported to cause:
- Anterior uveitis – sometimes have to stop drug for uveitis to resolve
- Conjunctivitis
- Episcleritis
- May get more than one AE at once

Question 39

What drugs affect the retina

Answer 39

• chloroquine
• hydroxychlorquine
• tetracyclines
• tamoxifen
• anti-coagulant drugs
• vigabatrin
• ethambutol

Question 40

What is chlorquine and what are potential side effects

Answer 40

• used to treat arthritis
• narrowing of blood vessels and a bullseye ring of pigment in the perimacular region
• VA may remain normal until the late stages of toxicity, so its important to check retina of these px if they are asymptomatic
• early withdraw leads to reversal

Question 41

What is hydroxychloroquine and what are the side effects

Answer 41

• reduces activity of immune system
• used as antimalarial
• retinal toxicity rare but can be irreversible