14 - Anti Inflammatory drugs Flashcards
what are some anti inflammatory drugs
- corticosteroids
- non-steroidal anti-inflammatory drugs (NSAIDs)
- ciclosporin
what are corticosteroids and what are they produced by
hormones naturally occuring in the body, produced by the adrenal cortex
what 2 groups to corticosteroids consist of
- glucocorticoids
- mineralocorticoids
what are corticosteroid levels regulated by
hormones (e.g ACTH) produced in the pituitary gland
what do glucocortisoids do and give an example of one
- maintain normal levels of blood glucose and promote recovery from injury.
- so used therapeutically
e.g cortisol
what do mineralocortisoids do and give an example
- Affect Na+ balance causing Na+ reuptake and water retention and so influence blood pressure
e.g aldosterone
2 main pharmacological action of glucocorticids
- anti inflammatory and immunosuppressive effects through reduction in activity of inflammatory mediators e.g. eicosanids, interleukins
- metabolic effects on carbohydrates, proteins and fat
corticosteroids action
- steroid binds to receptor, steroid receptor complex moves to cell nucleus
- binds to glucocorticoid response element
- GRE controls transcription of particular genes that control the synthesis of inflammatory mediators
- go to cytoplasm & inhibitory proteins are manufactured
components of the inflammatory response are under the control of
inflammatory mediators
- vascular events of vasodilation
- cellular event
corticosteroids: action Eicosanoid synthesis
inhibition of an enzyme
which enzyme does corticoisteroid inhibit
phospholipase a2 (key enzyme in arachidonic acid pathway)
what does the enzyme phospholipase a2 do
converts phospholipids in cell membranes into arachidonic acid
arachidonic acid - what happens after its been converted
further metabolised to generate a series of pro inflammatory mediators
what happens when steroids inhibit phospholipase a2
they reduce the synthesis of all the mediators which are downstream of that particular enzyme
the non-steroidal anti-flammatories (NSAIDS) inhibit a specific enzyme
Cyclo-oxygenase further down pathway.
corticosteroids therapeutic uses systemic
- anti inflammatory effects e.g asthma/eczema/IBS
- replacement therapies for diseases of the adrenal gland
- chemotherapy
- immunsupression
Corticosteroids-Adverse effects
common and can be severe
dependant on dose and duration
- impaired glucose tolerance (sometimes diabetes)
- osteoporosis:brittle bones
- cushings syndrome
- immune suppression
indications of ophthalmic corticosterids
- treatment of acute + chronic inflammation e.g. anterior uveitis, vernal conjunctivitis
- reduce post-operative inflammation
what does the efficacy of a particular glucocortisoid dependant on
-strength (how much you want drug to penetrate into eye
- what salt is used
- integrity of cornea: drug will penetrate eye better if cornea is damaged
what are the 2 salts of gluco cortisoids called
- prednisolone acetate
- prednisolone sodium phosphate
prednisolone acetate
- reduces inflammation more effectively than prednisolone sodium phosphate
- more lipid soluble, penetrates deeper into tissues
- prednisolone sodium phosphate
- contains charged groups, less likely to penetrate in eye
when are prednisolone acetate and dexamethasone used
when inflammation is severe
what is used in mild inflammation and why
- low strength prednisolone sodium phosphate (0.05% or 0.1%)
- hydrocortisone
glucocorticoid side effects need to be minimal e.g. presence of viral infection
Available preparations of ophthalmic corticosteroids
- BETAMETHASON
DEXAMETHASONE
FLUOROMETHALONE
PREDNISOLONE
Ophthalmic corticosteroids -advserse reaction LONGTERM use
prolonged use: increased risk of posterior sub-capsular cataract
- dose dependant
- account for 4% of cataract
- usually only occur in px taking high dose >1 year
Ophthalmic corticosteroids -advserse reaction (ACUTE- short term use)
- raised IOP in steroid responsive individuals
- can occur with topical inhaled or systemic steroids
non-steroidal anti-inflamm drugs -NSAIDS
- Topical NSAIDs provide mild to moderate anti-inflammatory potency without the side effects of corticosteroids
- NSAIDs prevent the formation of a family of compounds called eicosanoids (act as inflammatory mediator)
how do NSAIDS work
- by inhibiting a specific enzyme within the arachidonic pathway
Eicosanoids are important mediators of
the inflammatory response
what are the principle Eicosanoids
- prostoglandins
- leukotrines
ocular effects of Eicosanoids
- vasodilation
- increased IOP
- miosis
- macular oedema
what is the anti-inflammatory action of NSAIDs due t
inhibition of enzyme cyclo-oxygenase (COX)
(eicosanoids block it)
Ophthalmic NSAIDS: indications
- reduction of intra-operative and post-ocular inflammation
- sometimes used in reduction of post operative pain
- reduction of pain following corneal trauma (diclofenac sodium)
- allergic conjunctivitis diclofenac sodium)
- episcleritis
available topical NSAIDS
- Diclofenac sodium (volatrol)
- flurbiprofen (ocufen)
-ketrolac trometamol (acular) - nepafenac (nevanac)
- bromfenac (yellox)
what does ciclosporin do
- inhibits release of cytokines from T-lymphocytes so therefore suppresses the cell mediated immune response
what treatments is ciclosporin licenced for the for
- severe keratitis in dry eye if not improved with lubricants
- severe VKV
WHERE DO MAJORITY OF OCULAR ALLERGIES AFFECT
conjunctiva
which cell plays a major role in ocular allergic response
mast cells
- degranulation of mast cells releasing mediators including histamine
what do released mediators do
they cause the signs and symptoms of the ocular allergy
examples of allergic eye disease
- acute allergic conjunctivits
- seasonal / perennial allergic conjnctivitis
- GPC
- AKC
- VKC
what is the role of mast cells in ocular allergy
- antigens cross mucous membrane (conjunctiva)
- taken up by antigen presenting cell, and present to T helper cell
- series of cytokines are produced - interleukins
- B cells make igE antibodies
- igE binds to surface of mast cells
after first contact with antigen, what happens to px?
asymptomatic
what happens after 2nd exposure to antigen?
mast cell degranulation
when antigen + igE are binded on mast cell, what occurs? (mast cell degranulation)
cross linking of adjacent igE molecules, ca2+ influx
what is released after mast cell degranulation
2 forms of mediators
1) pre formed
2)newly formed
what are pre formed mediators
Histamine.
Stored in granules in mast cell.
quickly released + immediate effect
newly formed mediators
prostaglandins.
responsible for clinical effects of allergy such as redness/oedema
anti-allergy drugs
- anti histamines
- mast cell stabilisers
- corticosteroids ( life thratening)
- NSAIDS
- vasoconstrictors
what are topical antihistamines for
SAC and PAC
what are systemic antihistamines for
symtoms of hayfever
what do newer antihistamines possess
antihistamine and mast cell stabilising properties s- dual acting
availible topical antihistamines (most are POM)
- antazoline (P) not for <12
- azelastine (POM)
- epinastine (POM)
- ketotifen (POM)
- olopatadine (POM) (dual action)
what do topical mast cell stabilisers do
- block calcium influx into mast cell membrane to prevent degranulation
basically stabilises it
how long do topical mast cell stabilisers take ot produce symptomatic relief
7-14 days - warn px not instant relief as thye would get woth anti histamines
what are topical mast cell stabilisers effective in the management of
moderate to severe allergic eye disease
- SAC
- GPC
- VKC
available anti allergy preparations of topical mast cell stabilisers
- sodium cromoglicate
- lodoxamide
- nedocromil sodium
NSAID - which drug is lisenced for SAC
- diclofenac sodium (POM)
- well tolerated, symptomatic relief within 30 mins
what type of drug are vasoconstrictors
sympathomimetic drugs - mimic action on sympathetic nervous system
what do vasoconstrictors cause
- constriction of conjunctival blood vessels by direct stimulation of alpha adrenoreceptors on the conjunctival vasaluture
- decrease in conjunctival hyperaemia and oedema
use is limited, not advised
vasoconstrictor drugs
- cylometazoline
- naphazolien
- phenylephrine ( not in UK)
topical NSAIDS and vasoconstrictos have a limited role in treating alergic eye disease
cooool
