Week 2.01 Adverse Reactions Flashcards
What is mean by an adverse effect
Side effect: undesired effect of medication extraneous to the intended therapy
Adverse effect: negative side effect
If you have a rich blood supply and small mass of the eye are you more or less likely to have advserve effects
More likely
In the cornea what may the drugs bind to
In cornea – drugs may bond in the stroma to glycosaminoglycans which could result in swelling and decrease in transparency
What are the two ways drugs can enter the eye and leave the eye
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
What is the WHO scale
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
What might you see in a px eye if u suspect drug adverse effects
- 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
Aye and adverse reactions
- 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
What is ED50
Median therapeutic dose of a drug
Narrow therapeutic index
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
What is the TD50 value
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
What does large therapeutic index tell us
Large therapeutic index means u would have to have a significant increase in dose, way above therapeutic levels to see any toxic effects
Need to consider drugs that may affect:
- cornea
- occulomotor system - eye movements, accommodation
- tear film
- intraocular pressure
- lens
- retina
- visual field
- colour vision effects
What are drugs that affect the cornea
- amiodarone
- chlorpromazine (Thorazine) - antipsychotic
What is amiadarone, side effects, progression
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
What are the 3 stages to development and progression of amiodarone keratopathy
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
What are the other ocular effects of amiodarone
Lens opacities
Retinal and optic nerve deposits
Optic neuropathy
What is amiodarone optic neuropathy
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
What is chlorpromazine and what are the side effects
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
What are the drugs that affect anterior angle
- topiramate - aka topamax
What is topiramate and what are the side effects
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
What drugs affect oculomotor
- tricyclic antidepressants - amitriptyline hydrochloride
- motion sickness drugs - hycosine, scopolamine
- over counter cough and cold - contains sympathomimetic phenylephrine
- thyroid hormone replacements - levothyroxine
- heroin - methadone
What’s are tricyclic antidepressants and what are the side effects
• 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
What are motion sickness drugs and what are the side effects
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
What are over counter cough and cold and what are side effects
- 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
What is nystagmus
Nystagmus – is an involuntary oscillation of one or both of the eyes, about one or more axes.
What can cause vertical, vestibular nystagmus and ocular muscle palsies
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
What are thyroid hormone replacements and what are the side effects
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
What is heroin and what are the side effects
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
What are some drugs that affect the tear film
Atrophine
Antihistamines
Beta blockers
Oral contraceptives
Adverse reactions affecting the tear film
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
Increase in tear production seen with:
Parasympathomimetics - pilocarpine, neostigmine and number of anti-hypertensive drugs
Drugs that lower blood pressure/ IOP
- 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
Examples of drugs that lower IOP
• 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
Example of drugs that increase IOP
- 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
What is central serous chorioretinopthy
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
Drugs affecting the crystalline lens
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
What are some drugs associated with myopic shift
Topiramate
Diuretics
Carbonic anhydrase inhibitors
Sulphonamides
What is a drug that affects the anterior segement
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
What drugs affect the retina
- chloroquine
- hydroxychlorquine
- tetracyclines
- tamoxifen
- anti-coagulant drugs
- vigabatrin
- ethambutol
What is chlorquine and what are potential side effects
- 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
What is hydroxychloroquine and what are the side effects
- reduces activity of immune system
- used as antimalarial
- retinal toxicity rare but can be irreversible
What is tetracycline and what are potential side effects
Still affects retina
- group of antibacterial drugs
- cause hyperpigmentation in area around eyes but also on palpebral conjunctiva
- other symptoms include myopia and changes in colour vision and possible diplopia, conj deposits, staining of contact lenses due to secretion of drug into tear film
- penetration of drug into cerebrospinal fluid can lead to papiloedema
What to do if suspect papiloedema
Px need to be seen at hospital within 24hours
Some symptoms of bilateral optic disc swelling
Caused headaches and bilateral visual loss
What is tamoxifen and what are the side effects
Still retinal
- used in treatment of breast cancer
- bilateral maculopathy
Side effects:
- yellow/white opacities around macula
- Cyrstoid macular oedema may also form
- parafoveal haemorrhage
- RPE changes in peripheral area
- progressive VA loss
- incidence 1-2%
- visual effects are irreversible
What are anti-coagulant drugs and what are the side effects
Used to prevent thrombosis
E.g. warfrin, used for venous thrombosis
Thins the blood therefore increases risk of retinal haemorrhage (+subconjunctival haemorrhage)
Side effects:
- optic atrophy
- cataract
- micropthalmia (small, underdeveloped eye) of foetus if warfrin is taken during pregnancy
What is vigabatrin used for and what are the side effects
Drugs used to control epilepsy
- prevalence of vision loss 40-50% px taking this
- VFT before starting therapy
- VA remains normal
- greater field loss nasally
- visual field loss usually asymptomatic unless defect encroaches well within the central area
What is ethanbutol and what is it used for, what are the side effects
Used to treat tuberculosis
Side effects:
- Colour vision changes - px presents with similar to red-green colour defect
- visual field changes
- optic neuropathy occur 2-8 months after starting therapy
Basic colour vision defects
- Can be classified as red/green or blue/yellow
- R/G: anomalous trichromatic (protanomalous trichromacy, deuteranomalous trichromacy
- B/Y: tritanomalous trichromacy
- R/G defects generally associated with optic nerve changes
- B/Y defect associated with retinal changes
What is digoxin what is it used for and what are the side effects
Cardiac glycoside
- treats cardiac arrhythmia or congestive heart failure
- colour vision defect noted
- narrow therapeutic effect
- sxs colour vision can occur within 2 weeks of starting therapy - reverse sxs if stopped taking
- may lead to R/G or B/Y
- may also show deficiencies in dark adaptation and abnormal electro-retinogram
What is slidenafil citrate and what are the side effects
Aka viagra
Medication to help combat erectile dysfunction in males
Side effects:
- changes in CV (cyanosis)
- 10% px taking 100mg experienced blue haze in their vision up to 4 hours after
- blurred vision
- photosensitivity
How do you test for drug induced CV defects
Ishihara limited as no tritan facility
City test ok
D25 ok
Farnsworth mussel 100 hue good
Anomalscope better but not really practical for optometric practice and difficult to interpret results
What is a brief overview of the D15 test
15 caps of a certain colour sequence with subtle changes
FM-100 hue test - similar test, extended version
What’s a drug that affects intracranial pressure
Retinoids/isotretinoin
What’s retinoids/isoretinoin and what are the side effects
- Used in treatment of severe acne &psoriasis
- Includes vitamin A
- Minor: dry eye, photophobia
- Major: raised intra-cranial pressure, papilloedema
- Watch out for unexplained H/A or blurred vision in these patients
What is papiloedema
Papilloedema is optic disc swelling that is caused by increased intracranial pressure. It is usually bilateral
Initially asymptomatic —> enlargement of blind spot, blurring vision, visual field loss
Kinds of things we see on optic nerve head are engorgement of blood vessels, loss of spontaneous venous pulsation, haemorrhages around and next to optic disc, blurring of disc margin and elevation
Illegal substances ocular adverse effects
Heroin – pupil miosis, increased accom response, reduced VA
Cocaine – pupil mydriasis, decreased accom response, reduced VA
Marijuana – pupil mydriasis, reduced accom response, reduced IOP
Solvent abuse – pupil mydriasis, reduced accom response, toxic amblyopia
If detect OAR what to do
- Inform GP
- Consider reporting via yellow card
- NEVER tell px to stop taking meds because of OAR
What is yellow card scheme
Use yellow card scheme to report:
- All suspected reactions to medicines under intensive surveillance (black triangle)
- Serious suspected reactions to established medications
- All adverse reactions in those under 18 or pregnant female
Yellow cards available in BNF (British national formulary) and online
Newly licensed meds
Usually remains under black triangle for a period of 5 years
What drugs are kept under intensive surveillance
- new active substances
- new combination of active substances
- existing medicine licensed for a different use
- existing medicine licensed for a different route of administration
