ophthalmic drugs: anti-inflammatory drugs Flashcards
which type go optometrists can only supply corticosteroids
optometrists with a independent prescribing qualification
what is the lowest prescribed ophthalmic drug in the UK
NSAIDs
what is the highest prescribed ophthalmic drug in the UK
Glaucoma treatments
what type of compound is corticosteroids
a naturally occurring compound: hormones
what are corticosteroid hormones produced by
the adrenal cortex
name 2 types of corticosteroid hormones/chemicals produced by the adrenal cortex
- glucocorticoids
- mineralocorticoids
what are the levels of corticosteroid hormones such as glucocorticoids and mineralocorticoids regulated by
by hormones also such as the adrenocorticotrophic hormone ACTH from the pituitary gland
what is the properties of the glucocorticoids (type of corticosteroid) and give an example of a glucocorticoid that does this
maintains normal levels of blood glucose and promotes recovery from injury - so has important anti-inflammatory properties
e.g. hydrocortisone
what is the properties of the mineralocorticoids (type of corticosteroid) and give an example of a mineralocorticoid that does this
they affect (control electrolytes) the Na+ balance causing Na+ reuptake and water retention, and so influence blood pressure
e.g. aldosterone
why are corticosteroids used by athletes
because they promote recovery in injury
what are the two main pharmacological actions of glucocorticoids
- anti-inflammatory and immunosuppressive effects
- metabolic effects in carbohydrates, proteins and fat
what are the anti-inflammatory and immunosuppressive effects of glucocorticoids done through and name 3 examples
reduction in the activity of inflammatory mediators
e.g. eicosenoids, platelet-activating factor and interleukins
what type of formulation is topical corticosteroids available as
a highly insoluble substance, so doesn’t dissolve in water, therefore is a emulsion which needs to be shaken before use
where is the receptor for corticosteroids found
it is found within the cytoplasm of the cell
as opposed to being on the cell surface
why is a corticosteroid able to get inside the cell cytoplasm in order to reach its receptor
because it is lipophilic and therefore insoluble
so it is able to pass through the cell membrane in order to encounter its receptor
state the process of how corticosteroids influences the secretion of anti-inflammatory proteins
- the corticosteroid passes through the cell membrane to bind to its receptor in the cytoplasm
- the receptor-steroid complex is translocated to the nucleus
- this is where it influences the secretion of anti-inflammatory proteins
where are phospholipids found
in all plasma membranes
how do steroid block inflammatory mediators and name an example
by the corticosteroid inhibiting the synthesis of the inflammatory mediator: Eicosanoid, which then blocks/inhibits the enzyme phospholipase A2
what do phospholipids turn into under the the action of the phospholipase A2 enzyme and what pathway does this substance enter
arachidonic acid
which enters the inflammatory pathway
what is the 2 enzymes that arachidonic acid is converted into, and therefore what do these 2 enzymes form
converted into: cyclo-oxygenase and lipoxygenase
they form inflammatory mediators and therefore induces inflammation
we block these enzymes in order to inhibit inflammation
what drug blocks cyclo-oxygenase and enzymes in order to inhibit inflammation and formation of inflammatory mediators
NSAIDs
which inflammatory mediator forming enzyme do NSAIDs still have and therefore what is there still a production of
- lipo-oxygenase
- still get the production of leukotrienes
e.g. ibuprofen
which inflammatory mediator forming enzyme do NSAIDs block
cyclo-oxygenase
list the 4 therapeutic uses of systemic corticosteroids
- anti-inflammatory effects (systemic or topical) e.g. asthma, eczema, inflammatory bowel disease or rheumatic disease
- replacement therapy for diseases of the adrenal gland
- chemotherapy e.g. acute leukaemia/hodgkin lymphoma
- immunosuppression e.g. post transplantation
adverse effects of corticosteroids are _________ and can be _________
adverse effects of corticosteroids are common and can be severe
what 2 things are the adverse effects of corticosteroids dependent on
- dose
- duration of treatment
list 4 adverse effects of corticosteroids
- impaired glucose tolerance/metabolism, so that blood glucose levels goes up and in extreme cases can cause diabetes mellitus
- osteoporosis = brittle bones
- cushings syndrome
- immune suppression
what must you take in addition to corticosteroids in order to avoid osteoporosis
calcium supplements
what implications does the adverse effects of corticosteroids, of immune suppression have
it reduces the body’s ability to defend against pathogens, therefore opens up the body to opportunistic infections
name 2 indications for ophthalmic corticosteroids
- treatment of acute and chronic inflammation e.g. anterior uveitis, vernal conjunctivitis
- to reduce post operative inflammation
there is no official _________ hierarchy for topical ________ ____________
there is no official potency hierarchy for topical ocular glucocorticoids
other than upon its strength, what 2 other things does the efficacy of a particular glucocorticoid preparation depend upon
- the salt used e.g. prednisolone acetate reduces inflammation more effectively than prednisolone sodium phosphate
- the integrity of the cornea, the drug will penetrate the eye better in the cornea is abraded
name the 2 variations of prednisolone
- prednisolone acetate
and - prednisolone sodium phosphate
which form of prednisolone will you use if treating ocular surface inflammation and which form of prednisolone will you use if treating a more deeper seated inflammation and state why
- ocular surface inflammation: use prednisolone sodium phosphate.
as it has a charged component which impairs it’d ability to transit through the cornea, this is based on the fact that the cornea is healthy and the ocular surface is intact - deeper seated inflammation: use prednisolone acetate.
as it is more lipophilic and therefore penetrates more readily than prednisolone sodium phosphate.
what correlation is their with the potency of a corticosteroid
adverse reactions
name the 2 corticosteroids which is used when inflammation is more severe
- prednisolone acetate
- dexamethasone
= strong steroids
name the 2 corticosteroids which is used when inflammation is less severe or when glucocorticoid side effects need to be minimal e.g. in the presence of a viral infection
- prednisolone sodium phosphate 0.05% or 0.1%
- hydrocortisone
= weak unpenetrating steroids
list 6 available preparations of ophthalmic corticosteroids with their trade name
- Betamethasone: Betnesol
- Dexamethasone: Maxidex
- Fluormetholone: FML
- Loteprednol Etabonate: Lotemax
- Prednisolone: Predsol, Pred Forte
- Rimexolone: vexol
name 3 corticosteroids that are combined with antibiotics
- Betnosol N
- Maxitrol
- Tobradex
however this is not prescribed often as it is not a good idea to combine corticosteroids with antibiotics
what is a NICE approved treatment for retinal venous occlusions
intravitreal corticosteroids
e.g. Ozurdex intravitreal implant for macula oedema following retinal venous occlusions
what can be 2 side effects of intravitreal corticosteroids used to treat retinal venous occlusions and how is this tackled
cataract and raised IOP causing glaucoma
but the drug is beneficial as it prevents the patient from becoming blind from RVO, therefore need to remove the cataract and treat the glaucoma
what is an adverse reaction of prolonged use of steroids
an increased risk of posterior sub capsular cataract
what does the risk of developing posterior sub capsular cataract from corticosteroid use depend on
the dose and duration
e.g. taking a high dose for >1 year
how many % of cataracts does corticosteroids account for
approx 4%
what is an acute adverse reaction from short term use of ophthalmic steroids
raised IOP
from topical or inhaled systemic steroids (not always eyedrops)
can an acute raised IOP from short term use of steroids be avoided and why
no
because you can’t tell ahead of time which patients will respond with a raised IOP
there is no characteristic that will tell you ahead of time
what do NSAIDs provide
a mild to moderate anti-inflammatory potency without the side effects of corticosteroids
whats do NSAIDs prevent
the formation of a family of compounds called eicosanoids
give an example of when are NSAIDs used
preoperatively
either given just before or just after a surgery
what are eicosanoids the important mediators of
the inflammatory response
what are the 2 principle eicosanoids
- prostaglandins
and - leukotrienes
list 4 ocular effects of eicosanoids
- vasodilation
- increased IOP
- miosis
- macular oedema
what is the anti-inflammatory action of NSAIDs primarily due to
the inhibition of the enzyme cyclo-oxygenase (COX)
list the 5 indications of ophthalmic NSAIDs
- Reduction of intra-operative and post-operative ocular inflammation
- Reduction of post-operative pain
- Reduction of pain following corneal trauma
- Allergic conjunctivitis
- Episcleritis (off license)
what is not a licensed indication of ophthalmic NSAIDs even though it is still used for that purpose
Episcleritis
list 5 ophthalmic NSAIDs
- Diclofenac sodium
- Flurbiprofen
- Ketorolac trometamol
- Nepafenac
- Bromfenac
list 4 indications of the ophthalmic NSAID Diclofenac sodium
- inhibition of intra-operative miosis
- reduction of post-operative inflammation
- pain following corneal epithelial trauma
- seasonal allergic conjunctivitis
what is the trade name and available preparations of the ophthalmic NSAID Diclofenac sodium
- Voltarol Ophtha: multi dose eyedrops and unit dose minims
list 2 indications of the ophthalmic NSAID Flurbiprofen
- inhibition of intra-operative miosis
- reduction of post-operative inflammation
what is the trade name of the ophthalmic NSAID Flurbiprofen
Ocufen
what is the indication of the ophthalmic NSAID Ketorolac trometamol
prophylaxis and reduction of inflammation and associated symptoms following ocular surgery
what is the trade name of the ophthalmic NSAID Ketorolac trometamol
Acular
what is the indication of the ophthalmic NSAID Nepafenac
prophylaxis and treatment of postoperative pain and inflammation
what is the name of the ophthalmic NSAID Nepafenac
- Nevanac
what is the indication of the ophthalmic NSAID Bromfenac
post operative inflammation following cataract surgery
what is the name of the ophthalmic NSAID Bromfenac
yellox
the eye is a common site of __________ inflammation
the eye is a common site of allergic inflammation
what part of the eye do the majority of ocular allergies affect
the conjunctiva
what cells play a central role in an ocular allergic response
mast cells
how do mast cells play a central role in an ocular allergic response
- the degranulation of mast cells releases several mediators including histamine
- the released mediators cause the signs and symptoms of ocular allergy
list 3 examples of allergic eye disease
- Acute allergic conjunctivitis
- Seasonal/perennial allergic conjunctivitis (SAC/PAC)
- Atopic keratoconjunctivitis (Giant papillary conjunctivitis or Vernal keratoconjunctivitis)
which example of allergic eye disease are sight threatening and need steroids
Atopic keratoconjunctivitis - Giant papillary conjunctivitis
which allergic eye disease is a mast cell mediated type 1 hypersensitivity response
Seasonal/perennial allergic conjunctivitis (SAC/PAC)
which 2 mechanisms can a drug used to treat conditions such as Seasonal/perennial allergic conjunctivitis (SAC/PAC) by targeting the mast cell
- by inhibiting the degranulation
- by binding to the histamine receptors when histamine is released
what are the 2 types of mast cell mediators
- pre formed ones that are stored in the granules which are mainly histamine and heparin
and - the ones that mast cells produce subsequent to mast cell degranulation, when it is degranulated it continues to produce the eicosenoids (inflammatory mediator)
these both induce the inflammatory response
list the 5 anti-allergy drugs
- Anti-histamines
- Mast cell stabilisers
- Corticosteroids
- NSAIDs
- Vasoconstrictors
which 2 forms is anti histamine available in
topical and systemic forms
what are systemic anti histamines predominantly used to treat and name 2 examples of drugs used
symptoms of hay fever
e.g diphenhydramine, and cetirizine
what are topical anti histamines predominantly used to treat
Seasonal/perennial allergic conjunctivitis (SAC/PAC)
what properties do newer/2nd generation anti histamines have and name an example of one
- posses antihistamine and mast cell stabilising properties, which makes them more effective
e. g. olopatadine
how do topical mast cell stabilisers work in order to prevent degranulation
Block calcium influx into the mast cell membrane
how long can a mast cell stabiliser take in order to produce symptomatic relief
7-14 days
how can a mast cell stabiliser be used in order to completely avoid allergic symptoms and name an advantage that this can have
to start the therapy 2-3 weeks before they become symptomatic e.g. in seasonal allergic conjunctivitis
so they can still wear their contact lenses and control their eye symptoms
what is topical mast cell stabilisers most effective in
the management of moderate to severe allergic eye disease e.g SAC, GPC, VKC
what is the original mast cell stabiliser and what category of medicine is it available as
- sodium cromoglicate
- available as a Pharmacy (P) Medicine
what is the disadvantage of the original mast cell stabiliser sodium cromoglicate, and give an example of a drug
that it must be given four times a day as a must
e.g. lodoxamide
which mast cell stabiliser may be preferred over sodium cromoglicate in seasonal and perennial allergic conjunctivitis and why
also what it the disadvantage to this drug over sodium cromoglicate
Nedocromil
because of its twice daily instillation frequency
disadvantage is it is far more expensive than sodium cromoglicate
what is the NSAID, Diclofenac sodium licensed for and what is its advantage for this purpose
- seasonal allergic conjunctivitis SAC
- it is well-tolerated and produces symptomatic relief within 30 minutes of instillation
what is there no evidence that the NSAID, Diclofenac sodium is more effective than for treating seasonal allergic conjunctivitis SAC
other anti-inflammatory drugs
name the 5 available anti-histamines used as anti-allergy preparations
- Antazoline (P)
- Azelastine (POM)*
- Emedastine (POM)
- Epinastine (POM)*
- Ketotifen (POM)*
- Olopatadine (POM)*
which is the only one anti-histamine that is used as a anti-allergy preparation that is available as OTC
Antazoline (P)
which anti-histamine that is used as a anti-allergy preparation is only licensed for children over the age of 12 and why
- Antazoline (P)
- because is also contains a vasoconstrictor
which 4 anti-histamines used as anti-allergy preparations have a dual action (mast cell stabiliser and anti histamine properties)
- Azelastine (POM)*
- Epinastine (POM)*
- Ketotifen (POM)*
- Olopatadine (POM)*
name the 3 available mast cell stabilisers used as anti-allergy preparations
- Sodium cromoglicate (GSL/P/POM)
- Lodoxamide (P/POM)
- Nedocromil (POM)
GSL - general sales drug
which mast cell stabiliser used as anti-allergy preparation is available as a general sales drug
Sodium cromoglicate (GSL/P/POM)
name the NSAID used as an anti-allergy preparation
Diclofenac sodium (POM)
who can supply to purchase P medicines
- optometrists
- staff
- pharmacy
what is the rationale behind the additional supply list
it allowed the optometrists to manage those conditions which present very frequently in primary care
conditions such as: allergic conjunctivitis, infective conjunctivitis, dry eye, superficial injury and corneal abrasion
what type of drugs are vasoconstrictors
sympathomimetic drugs (it mimics the action of the sympathetic nervous system, which is to cause vasoconstriction)
what structure of the eye do vasoconstrictors work on
constriction of conjunctival blood vessels
how do vasoconstrictors cause constriction of conjunctival blood vessels in the eye
by direct stimulation of alpha adrenoceptors on the conjunctival vasculature with a decrease in conjunctival hyperaemia and oedema
what hormone are sympathomimetic drugs such as vasoconstrictors agonists of
noradrenaline
name 3 vasoconstrictors available as anti-allergy preparations (in order to reduce appearance of red eyes)
- Xylometazoline (e.g. Otrivine Antistin)
- Naphazoline (e.g. Murine, Optrex Clear Eyes)
- Phenylephrine (currently not available preparation in the UK)
why is the vasoconstrictor Phenylephrine currently not available preparation in the UK
because it has many side effects
what can the repeated use of vasoconstrictors cause
a rebound hyperaemia, where it initially works but then causes red eye again
what 2 things are vasoconstrictors contraindicated with
- heart disease
- DM
