Glaucoma Flashcards

Question

Explain the MOA and S/E's of alpha adrenergic agonists, give an example

Answer 1

- e.g. Apraclonidine, Clonidine* (admin. topical) - α 2−selective agonist - effective during day, not night. - stim. α 2-AR in ciliary body, inhibit adenylyl cyclase - decreases aqueous humour formation/secretion - side effects*: hypotension, cardiac arrhythmia, anxiety (systemic

Answer 2

- e.g. Timolol (admin. topical) (2 X daily drops) - Block β 2-AR activation of adenylyl cyclase (ciliary body) - decreases aqueous humour formation/secretion - effective during day, not night. - side effects: bronchospasm, brachycardia, CNS depression (systemi

Answer 3

- e.g. Acetazolamide (systemically), Dorzolamide (topical) - inhibit formation of HC0-3 - 2 nd line drugs for glaucoma. - effective during day & night. - decreases secretion of aqueous humour - side effects: K depletion, dermatitis, renal stones, acidosis End in -amide

Answer 4

1. Na + ,K + antiport 2. K + channel 3. Cl− channel 4. Na + ,H + antiport AqPO1 = aquaporin channel 1 CA = carbonic anhydrase

Answer 5

- e.g. Lantaprost (admin. topically) (1X daily admin) - prostaglandin F 2 analogue. - elicit their effects via GPCR (EP2 and EP4) - 1 st line drugs for glaucoma. - effective during day & night. - increase matrix metalloproteinase (MMP) activity - remodelling of uveoscleral ECM - increases AH outflow via non-conventional pathway - Side Effects: Iris Pigmentation. Eyelash Growth & Thickening

Answer 6

- e.g. Rhopressa, Ripasudil and Roclatan - Rho-associated coil-forming protein kinases (ROCK) are protein serine/threonine kinases - TM & CM express many components of Rho signalling (e.g ROCK) - ROCK activity is a key player in regulating cellular morphology & contractility of conventional outflow pathway - ROCKi reversibly modify cell morphology and interactions that facilitate greater outflow of AH through TM and lower IOP. - ROCKi uncouple actin from myosin, reducing contractile tone of tissues in conventional outflow pathway. Allow cells to relax creating space between cells which fluid can exit the eye. ROCKi are vasodilatory, which may reduce episcleral venous pressure

Answer 7

A.) Topical (via cornea or conjuctiva) -most common -non-invasive -simple -usually non-toxic to body -but low absorption B.) Systemic -can result in systemic side-effects -may not reach target site at effective [drug]… drug barriers C.) IntraOcular -risk of damage to retina/vision -typically for drugs targeted to posterior eye

Answer 8

drug absorption decreased by i) Tear secretion (normally 1-2 μl./min, can increase to 400 μl/min upon drug irritation) ii) Blinking iii) Drainage iv) Unwanted absorption to eyelids & muscles - drugs removed rapidly from cornea ⇨ poor absorption (1-7%) - Formulations developed to increase residence time……

Answer 9

distribution is decreased by i) drug binding to melanin pigment in iris/ciliary body ii) drug binding to protein in aqueous humour iii) drug elimination

Answer 10

-in anterior chamber most drugs eliminated by aqueous humour turnover = 1.5% anterior chamber vol. turned over per minute Breakdown of blood-ocular barriers in disease may increase drug elimination rate ⇨ higher drug dose required

Answer 11

1) 🡻 corneal contact time 🡻 drug penetration 🡻 ocular [drug] -some drugs optimal with initial high bolus e.g. antibiotics & steroid 2) 🡻 irritation 3) 🡻 systemic side-effects -some drugs optimal (🡻side effects) when present continuously e.g. pilocarpine

Answer 12

-pH, non-ionised drugs cross cellular barriers easier -tonicity, drugs isotonic with tears avoid irritation -viscosity, reduce Drainage = increase Residence -preservatives, can also increase penetrability

Answer 13

1. Aqueous Solns 2. Suspensions 3. Ointments 4. Contact Lenses 5. Corneal Shields & Gels 6. Liposomes 7. Systemic Admin 8. Intraocular Injection 9. Ocular Inserts & Implants 10. Encapsulated Cell Technology

Answer 14

-most common -cause less vision blurring than ointments -least expensive -easily admin. -but short contact time -methylcellulose can increase viscosity

Answer 15

-sterile preps of water insoluble drugs -increased residence time -must be resuspended before use

Answer 16

-become liquid at eye temp. -reduced drainage & dilution -increased residence time -can cause transient blurring -difficult to apply exact dose -can be a delay in drug deliver

Answer 17

-slow-release preparations -controlled release over time course -drug bordered by hydrophobic membranes permeable to drug -increase contact time -increase drug absorption -replaced weekly

Answer 18

-biodegradable films of cross-linked collagen impregnated with drug e.g. antibiotics (gentamicin), steroids (dexamethasone) -shape into form of a contact lens easily placed on eye surface -altering level of cross-linking alters drug release rates -Eye drop solutions which transit to thin in-situ gel on contact with ocular surface

Answer 19

-lipid vesicles with aqueous interior -carry drug across cell barriers -easily prepared -no blurring effect

Answer 20

-need to reach eye at therapeutic [drug] -need to cross blood-aqueous & blood retinal barriers -e.g. carbonic anhydrase inhibitors (Acetazolamide), some steroids & antibiotic

Answer 21

-for drugs that poorly penetrate cornea (topical) -for drugs needed in peripheral eye -for drugs not suitable for systemic admin. -used to treat some bacterial infections

Answer 22

The products solve compliance problems with existing therapeutics and could deliver drugs for a longer period than similar products in development

Answer 23

They are neuro-protectants, anti-apoptotics and the treatment for them is reversible

Glaucoma Flashcards

(47 cards)