principles of toxicology Flashcards
what is the process of finding out about any adverse reactions of a drug
process called pre licensing testing
- it starts off with the synthesis of a molecule that is shown to be effective in a lab
- it then goes through a testing process and during then, a number of adverse reactions come to light
what is another way of finding out about any adverse reactions of a drug other than pre licensing testing
post marketing surveillance
what happens subsequently after the drug comes out into the market and this is based on the vigilance of healthcare professionals identifying those adverse reactions
what is the definition of a adverse drug reaction ADR
any unwanted or harmful reaction experienced following the administration of a drug (or combination of drugs)
systemic drugs can cause _________ ___________
systemic drugs can cause ocular toxicity
why is the eye most sensitive to adverse reactions
- as it has a very rich blood supply therefore the drug concentrations in ocular tissue are potentially higher
- and also contains a diversity of different tissue types which can be damaged by drugs
what 2 things are our knowledge of the toxicity of a particular drug based on
pre-licensing testing and post-marketing surveillance
what is the limit of pre marketing assessment of new drugs
it can only give limited information regarding drug safety
what do clinical trials involve
- small highly - selected groups of patients who take the drug for a short time
- during this process, common ADRs are identified
when are common ADRs identified
during clinical trials (pre marketing assessment of new drugs)
when do certain reactions of drugs come to light and why
- until a large number of people have received the medication following product launch
- as may need to take the drug for a long time for a side affect to happen
how do drug companies maximise their profit during pre marketing assessment of new drugs and what implications can this have
- the clinical trials will have a small amount of patients who are highly selected and only take the drug for a short time, all common short term acute reactions are identified
- however long term reactions may not be picked up during this time
most OARs are ___________ if detected _______
most OARs are reversible is detected early
what may undetected OARs progress to
cause irreversible ocular damage (as they are allowed to progress)
why is it important for optometrists to recognise and manage known OARs
as we see the same patients multiple times for their routine eye checks so we take repeated observations on them, therefore we are well placed to screen for OARs to new medicines
what is the name of a cardiovascular drug used to treat cardiac arrhythmias and what OAR does it cause
- Amiodarone
- Corneal epithelial deposits in 70-100% of patients
after how long of taking the cardiovascular drug Amiodarone, do corneal epithelial deposits develop and what can this depend on
may occur within 2 weeks
it is dose dependent
what does the appearance of Corneal epithelial deposits associated with the cardiac drug Amiodarone start off as
- a horizontal line usually at junction of middle and lower third of cornea
- Usually bilateral
what is the outcome of the Corneal epithelial deposits associated with the cardiac drug Amiodarone if the drug is not being taken
the OAR is reversible and takes a minimum of 3 months to clear
but they rarely stop taking the drug
what is not usually affected with the Corneal epithelial deposits associated with the cardiac drug Amiodarone
visual acuity therefore patients are not usually symptomatic
how many grades are there of the Corneal epithelial deposits associated with the cardiac drug Amiodarone
3 grades
following the linear patterns running horizontally across the cornea with the Corneal epithelial deposits associated with the cardiac drug Amiodarone found as grade 1, what signs start to occur with grade 2
- multiple branches, branching away from the horizontal line
- referred to as vortex pattern as the beaches arc around
how many patients experience visual symptoms from the cardiac drug Amiodarone and what are these symptoms
- 1-12%
- halos around lights, blurred vision and glare effects
- Other OARs associated with amiodarone include punctate lens deposits and rarely optic neuropathy
what is the rare OAR of the cardiac drug Amiodarone that causes symptoms, and what are these symptoms
- optic neuropathy
- causes dramatic change in their vision
what drug is used for cardiac glycoside used in the treatment of cardiac arrhythmias and heart failure
Digoxin
how many % of OARs occur in patients taking cardiac glycosides
11-25% of patients - they are common with this drug
what are the most common OARs of Digoxin
- disturbance of colour vision
- various entopic phenomena
what type of colour disturbance is experienced with Digoxin
complain of yellow vision
objects have a yellow/green tinge
which plant is the drug Digoxin derived from
extracted from leaves of the fox glove - is a naturally occurring compound
what is a asymptomatic side effect of Digoxin
significant number of colour deficiency which is only found in colour vision tests
what are the different colour vision tests used to detect someone with a colour deficiency whilst using Digoxin used to treat cardiac glycosides
- ishihara
- city test
- HRI test
- D15 test
OARs can occur with _________ digoxin levels in the ______________ range
OARs can occur with serum digoxin levels in the therapeutic range
what happens to OARs following discontinuation or dose reduction of Digoxin therapy used to treat cardiac glycosides
disturbances of colour vision subside
name 2 drugs used as antimalarials
chloroquine and hydroxychloroquine
what 2 conditions is the drug chloroquine used to treat
- may be used in treatment of rheumatoid arthritis, if other drugs have failed
- used to treat some forms of malaria
to what drug has there been an increases resistance to in the case of treating malaria
chloroquine
what 2 conditions is the drug hydroxychloroquine used to treat
- Used in malaria prophylaxis
(AORs very, very unlikely) - Much more widely used in rheumatoid arthritis
what is the chemical modification of the drug chloroquine and what advantage does this drug have over chloroquine
hydroxychloroquine
side effects are less common
what OAR can the use of both antimalarials - chloroquine and hydroxychloroquine cause
a serious OAR - retinal toxicity leading to a pigmentary retinopathy and maculopathy called bulls eye maculopathy
how does the antimalarials - chloroquine and hydroxychloroquine cause retinal toxicity and pigmentary retinopathy and maculopathy
because the drug binds to the melanin of the RPE
with which antimalarial drug is retinal toxicity more common and by how much
- chloroquine
- affects 2-3%
very rare with hydroxychloroquine
what does the appearance of a bulls eye maculopathy, caused by the antimalarial drugs chloroquine and less commonly hydroxychloroquine appear
a central dark spot surrounded by a lighter halo
first appears as a retinopathy wth fine pigment mottling within the macula
the fundus changes goes through stages
in how many patients is chloroquine keratopathy also commonly observed
~ 30%
which drug is most commonly used in rheumatology and why
hydroxychloroquine
as it is associated with fewer OARs
what type of screening method for OARs is carried out on patients in the rheumatology clinic taking hydroxychloroquine
- record reading performance with each eye with a reading spectacle correction if worn, using a near vision test type, at baseline
- reviewed annually
- If the patient can read a small print size such as N8 or N6 at baseline assessment, treatment with hydroxychloroquine can be commenced
- Patient may be issued with Amsler chart (ideally red on black)
- If visual impairment suspected patient should see Optometrist
- If impairment corrected with refraction then start treatment
- Optometrist should refer any abnormality/unexplained disturbance to ophthalmologist
What tests should optometrist carry out to best detect abnormality that may be caused by the antimalarial drug hydroxychloroquine
- Amsler chart (red)
- Central fields - HFA 10-2, Or test with red stimuli
- Colour vision testing
- Fundus photography (to document clinical signs)
what type of amsler chart is used when detect abnormality that may be caused by the antimalarial drug hydroxychloroquine and why
a red on black ambler chart
as this test is more sensitive than the standard ambler chart
what is the drug Chlorpromazine (Largactil) used to treat
Antipsychotic drug mainly used in the treatment of schizophrenia and bipolar disorder
it is a major tranquilliser
what OARs are associated with the antipsychotic drug Chlorpromazine (Largactil)
pigmentary deposition in the eyelids, conjunctiva, cornea, lens and to a lesser extent the retina
what are the OARs of corneal and lenticular changes caused by the antipsychotic drug Chlorpromazine (Largactil) dependent on
the dose
what are the lenticular changes that can occur when taking the antipsychotic drug Chlorpromazine (Largactil) an what symptoms will patients report
- initially observed as fine deposits under the anterior capsule
- progressing to a stellate opacity (i.e. can progress into a cataract)
- glare, halos around lights and hazy vision
what conditions are corticosteroids used to treat
allergic, rheumatic and inflammatory disease etc
Steroids are most important __________ group with regard to potential for _________ significant __________ _________
Steroids are most important therapeutic group with regard to potential for inducing significant adverse effects
which drug is the most frequently prescribed corticosteroid for administration by mouth for long-term disease suppression
Prednisolone
name 3 other corticosteroids other than prednisolone associated with OARs
Betamethasone
Dexamethasone
Hydrocortisone (cream applied on the skin around the eye)
what OAR is Prolonged steroid therapy (oral, topical or inhaled) associated with, and what symptoms do patients complain of
- Posterior sub capsular cataract
- in predisposed individuals causes raised IOP
- Severe reduction in visual acuity is rare but patients may complain of glare and photophobia - due to the PS cataract
- common in patients taking high dose over a long period of time
which class of steroids is most likely to cause raised IOP compared to the other classes
- penetrating type of IOPs such as prednisolone acetate
- non penetrating steroids such as Fluorometholone are less likely to cause rise in IOP
how much % of severe increase in IOP is caused by steroids
4% to 6% severe increase
how much % of some increase in IOP is caused by steroids
30% some increase
what 2 things is the rise in IOP associated with
- topical steroids
- family history of glaucoma
what will most patients taking steroids develop later in life
glaucoma
other than posterior sub capsular cataract and raised IOP, what other adverse reactions can occur with the use of steroids
- potentiation of viral, bacterial and fungal ocular infections (as they’re immunosuppressants)
- scleral thinning
non-steroidal alternatives should be prescribed if feasible
Patients with ______ more sensitive to the ___________ ___________ effects of systemic steroids
Patients with POAG more sensitive to the pressure elevating effects of systemic steroids
what drug is used in the treatment of breast cancer and at what dosage
- Anti-oestrogen drug called Tamoxifen
- 20 mg daily
what OARs are associated with taking the Anti-oestrogen drug used to treat breast cancer
- retinopathy (called Tamoxifen retinopathy)
- macular oedema and yellow white refractile opacities within retina which may be associated with pigmentary changes and haemorrhage
- Keratopathy can also occur (similar to that seen with amiodarone)
- Possible dry eye problems
how common is retinopathy as a OAR from taking the Anti-oestrogen drug called Tamoxifen used to treat breast cancer
3% (very rare, but potentially serious)
what is the outcome of developing Tamoxifen retinopathy
Once VA reduced the effects are irreversible
how common is keratopathy as a OAR from taking the Anti-oestrogen drug called Tamoxifen used to treat breast cancer
4%
what would the ideal monitoring for patients taking the Anti-oestrogen drug called Tamoxifen used to treat breast cancer
- baseline screening before therapy is recommended (VAs, Amsler, central visual fields and fundus photography)
- then annual monitoring
what is the drug Vigabatrin (Sabril) used for
treatment of epilepsy
what are the 3 symptoms associated with taking the drug Vigabatrin (Sabril)
- field loss
- visual acuity
- colour vision
how many patients do field loss occur in with taking the drug Vigabatrin (Sabril)
and what type field defect occurs
- 30-50%
- Bilateral constriction that can take variety of forms in the central field
- In mild to moderate cases the loss in central field is a crescent-like loss at extremities of the nasal field
what is the prognosis of the visual field defect associated with taking the drug Vigabatrin (Sabril) used in the treatment of epilepsy
irreversible field loss
which can occur within 1 month of treatment and seldom becomes apparent beyond 3 years of therapy
what do the UK Royal College of Ophthalmologists recommend about patients taking the drug Vigabatrin (Sabril) used in the treatment of epilepsy
taking the drug Vigabatrin (Sabril) used in the treatment of epilepsy
- Patients should be warned to report new visual symptoms
- Recommended test is static suprathreshold perimetry, extending to at least 45 degrees eccentricity as peripheral FOV is mainly lost
what is the recommended visual field test in screening patients who are taking the drug Vigabatrin (Sabril) used in the treatment of epilepsy
static suprathreshold perimetry, extending to at least 45 degrees eccentricity
In addition to its use as an oral contraceptive what else may the contraceptive pill be prescribed for
menstrual and ovulatory disorders
what are the 2 OARs associated with the contraceptive pill
- Decreased tolerance to contact lens wear
- retinal vascular abnormalities (haemorrhage, thrombosis etc) - but this is not proven
what 10 things are factors involved in OARs
- nature of the drug
- dosage, duration and frequency
- age
- patient’s general health
- diseases of liver and renal system especially
- condition under treatment
- individual idiosyncrasy (allergies)
- interactions with other substances being consumed
- previous drug exposure
- route of administration
how is nature of the drug a factor involved in OARs
some drugs (e.g. amiodarone) have potential to affect ocular structures more than others
how is age a factor involved in OARs
rate of OARs peaks at 70
how is condition under treatment a factor involved in OARs
is ocular change caused by condition under treatment or by drug?
give an example of interactions with other substances being consumed as a factor involved in OARs
antimuscarinics - causing the delayed recovery of pupil dilation
give examples of how route of administration is a factor involved in OARs
- steroids for skin conditions
- travel sickness patches (Scopoderm)
what 5 details will be needed from the patient about a drug
- name of drug(s)
- dosage
- frequency
- condition being treated
- period for which drug has been taken
what 4 things about a drug need to be known who considering that it has to do with a possible OAR
- Patient is taking a drug on your “hit list”
- Unexpected finding in the eye examination with no other obvious explanation
- Symptoms that a patient reports coincides with period of taking the medication (this has to be a suspect adverse reaction and cannot be proven)
- Sign coincides with period of taking the medication
what 4 things should have more focus with a “suspect” patient management
- consult the sources of information (look up standardised resources)
- special direction of attention during examination
- increased frequency of examination
- co-operation with patient’s GP
give examples of what should be done as a special direction of attention during examination on a “suspect” patient
- “red” fields with drugs from chloroquine and hydroxychloroquine groups
- OAG tests for steroid users
ame 5 sources of information on ADRs and OARs
- British National Formulary (BNF)
(available FREE online via MedicinesComplete website) - Patient information leaflets
- Summary of Product Characteristics (SPC)
(now available online as the electronic Medicines Compendium - eMC) - Fraunfelder F Drug-induced Ocular Side Effects 5th Edition
- EMedInfo (Thomson Software Solutions)
what 4 things needs to be taken into consideration when communicating with patients about OARs that are associated with drugs they may be taking
- do not alarm patient
- remember this is a “suspect” OAR
- do nothing to upset patient/GP relationship
(keep GP in the loop) - keep comments general - some OARs will have to be accepted as unavoidable
what is the yellow card scheme
a standardised system for reporting adverse reactions, both for health care professionals and patients
who are the yellow cards scheme jointly administered by
- the Medicines and Healthcare products Regulatory Agency (MHRA)
and - the Commission on Human Medicines (CHM)
what does the yellow card scheme rely on
on the voluntary reporting of ADRs by doctors, dentists, pharmacists and optometrists
what does the yellow card scheme cover
all marketed medicines as well as licensed and unlicensed herbal remedies
what is encouraged with the yellow card scheme
Electronic reporting - on MHRA website
where else other than online can the yellow card scheme be used
found in the paper based version of BNF
what 4 things are all optometrists asked to report about a drug to the MHRA
- all serious suspected OARs to established medicines
- all suspected OARs to new medicines
- all serious suspected adverse reactions to established ophthalmic medicines
- all suspected adverse reactions to new ophthalmic medicines
what 4 findings does Serious suspected adverse reactions to established medicines include and not include
- any change in acuity
- any significant change in IOP
- any change in ocular structures (cornea, lens, retina etc.)
- does NOT include allergies
_______ should be reported even if ______ _________
OARs should be reported even if well-known
what are new drugs indicated with the the BNF and MIMS to alert about any new released drugs
by a ▼(inverted black triangle)
where can the list of new drugs be accessed
the MHRA website
what must be reported in regards to All suspected OARs to new medicines
- even minor reactions
- including ocular allergies
what 3 Serious suspected adverse reactions to ophthalmic medicines include, and what does not need to be reported with serious suspected adverse reactions to ophthalmic medicines
- haemorrhage from any site
- severe skin reactions (also includes periocular/around the eye)
- any change in acuity, in ocular structures, or significant change in IOP
- do not report well-known, relatively minor adverse reactions
when must you Report all suspected adverse reactions to new ophthalmic medicines
- even if reaction is well-known
- even if other drugs have been given concurrently
what 2 things are the Devices Division of MHRA involved with
- Medical Devices, including Contact lenses, and contact lens care products are dealt with by the Devices Division of MHRA
- Electronic submission of adverse incident reports are encouraged (See MHRA website)
