Ocular Allergies and Inflammation/Pain Flashcards
(24 cards)
State 4 reasons why the eyes are particularly prone to allergens
exposed to environment
conjunctiva is highly vascularised/has large surface area
lots of special immune cells
Describe 4 types of hypersensitivty reactions with their mediators and examples
I: Ige-Mediated (mast cells, histamine) - rhinitis, asthma
II: IgG/IgM mediated cytotoxicity (complement, ADCC) - Autoimmune hemolytic anemia
III: immune complex deposition (complements, neutrophils) - SLE, RhArthiritis
IV: T-cell mediated (cytokines, macrophages) - contact dermatitis
Explain the MoA for T1 hypersensitivity
- Initial sensitisation: allergen + APC combines with Th2 stimulating B cell to produce IgE antibody which binds to mast cell Fc receptor stimulating
- Subsequent exposure: IgE cross links with mast cell so a Ca2+ influx detabsilises the cell releasing histamine/inflammatory mediators
Describe types II/III hypersensitivity antigens/appearance and diseases
TII: cell surface (mins-hour) - cell lysis/necrosis (dermititis, OCP)
TIII: soluble (3-8hrs) - erythema, oedema, necrosis (RhArthiritis)
Describe type IV hypersensitivity
T-cell mediated (nuetrophils/macrophages) by cytokines/interleukins/prostaglandins ~ antigens present in local tissue/organ
delayed 2-3 day response
contact dermitis, HSV(K), stroma keratitis, uveitis, GPC
Describe the use of astrigent eye washes/drops
temporary relief for mild irritation (0.9% saline)
State 4 common causes of ocular pain
dry eye
corneal abrasion
uveitis
corneal ulcer
Describe 3 types of ocular inflammation
Traumatic (physical damage - abrasion)
Neurogenic (toxic substances release neuropeptides - onions/chilli)
Immunogenic (foreign substance coupled with immune cells - bact. conj.)
Describe the stages/components of acute vs chronic inflammatory response
Acute: vascular response (cell access to site), cellular response (neutrophils)
Chronic cellular (macrophages/lymphocytes) and resolution (repair/scarring via fibroblasts)
Humoral (activated complement system), Chemical (eicosonoids - PGs/thromboxanes, LKs), Cellular (neutrophils, macrophages, natural killers, eosinophils)
Describe how prostaglandins are synthesised
stimulus activates phospholipase A to convert membrane phospholipids to arachidonic acid
Lipoxygenases convert it to HETE/Leukotriens
cyclooxygenases/synthetases convert acid to prostaglandins (PGE2, PGF2)
Describe the function of PGs and which processes they’re involved in
act via receptor family
gastric acid synthesis, inflammation, lung contraction, blood flow to kidney, thrombosis
State the physiological/pathophysiological roles of COX-1/2 enzymes
Physiological -
COX-1: GI protection, platelet aggregation, regulate blood flow
COX-2 CNS/renal function, tissue repair, reproduction, uterine contraction, BV dilation, pancreas, inhibits platelet aggregation
Pathophysiological - inflammation
COX-1: chronic pain, raised BP
COX-2: chronic pain, fever, BV permeability
State 5 topical NSAIDs and the indications
Diclofenac (both)
Flurbiprofen (single)
Ketoralac (multi)
Nepafenac (multi)
Bromfenac (multi)
intra/postoperative use, SAC, cystoid macula oedema
State 6 systemic NSAIDs and their legal categories
aspirin (GSL/P)
Ibuprofen (GSL/P/POM)
Diclofenac
Naproxen
Piroxicam
Indometacin all POM
Explain how adrenal steroids are synthesised with 2 examples
from cholesterol in adrenal gland on demand, immunosuppressant/anti-inflammatory action
Glucocorticoids (cortisol/corticosterone) via hypothalamus/ant. pituitary create -ve feedback in metabolism
Mineralcorticoids (aldosterone) via renin-angiotensin system for electrolyte/water balance
State 7 topical SAID drugs
betamethasone
dexamethasone
fluorometholone
hydrocortisone
loteprednol
prednisolone
rimexolone
Describe 3 local side effects of topical SAIDs
Raised IOPs via TIGR (trabecular meshwork-inducible glucocorticoid response increased myocilin expression preventing extracellular matrix breakdown increasing aq outflow resistance
slows wound healing, more risk of infection
cataracts (covalent adduct formation with steroid/lens protein)
State 3 other drugs SAIDs can be used in combo with
Mydriatics (uveitis) to relieve pain (immoblised iris) and prevent iris adhering to cornea/lens capsule stabilising blood aq barrier
Anti-muscarinics (cyclo, tropic)
Phenelephrine (break down recalcitrant posterior synechiae)
Explain the clinical considerations and (contra)indications for NSAIDs vs SAIDs (corticosteroids)
Px specific factors (age, severity, px education/adherence)
NSAIDs: indicated by mild/moderate inf. CME, pain, contraindicated to corneal defects/ NSAID allergy
side effects: corneal melting/sting/blur
SAIDs: severe inf. uveitis, post-op, contraindicated for glaucoma, corneal infections
side effects, raised IOP, cataracts, infection
Briefly describe the general pain pathway
Trauma to peripheral nociceptors stimulate NSAID mediator release through peripheral nerve/dorsal root ganglion
P/glutamate released through spinothalamic tract to thalamus/cortex in brain
Explain the ocular pain pathway (trigeminal convergence pathway for oculofacial pain)
Corneal innervation supplies CN V opthalmic division. 1st order neurones synapse at trigeminal nucleus (brainstem).
2nd order synapse at thalamus nuclei.
3rd order project to primary somatosensory cortex
Describe the mechanism for pyresis (fever)
endogenous pyrogens (interleukin-1) released from leukocytes increase PG synthesis
PGE2 raises thermostat in thermoregulatory centre (hypothalamus) so core temp sensed as too cold increasing heat production/conservation
Describe 2 effects of NSAIDs/paracetamol
inhibits all COX enzymes decreasing PGE2 production
anti-pyretic action resets core thermostat to normal (vasodilation/sweating)
analgesic activity prevents inflammatory response (PG-induced nociceptor sensation on nerve endings)
Describe the effects of opioids at 2 sites of action
CNS: brain (analgesia, cough suppression, resp. depression, convulsions, hallucinations, euphoria, nausea, vomiting) and spinal cord (analgesia)
Peripheral: gut (decreased gut motility - constipation) and eye (pupil constriction - no reaction)
