OptoP: Drug Admin to Eye - Week 9 Flashcards
In general terms, describe pharmacokinetics
getting drugs to and from their sites of action
What are the 4 key pharmacokinetic related issues in clinical drug use?
What form is drug in
Where do you put it
How much do you use
How often do you use it
What are the 4 steps of pharmacokinetics?
Administration: giving the drug
Absorption: drug enters circulation
Distribution: drug spreads through body
Elimination: drug is removed from body
What factors influence the choice of route of administration of a drug? (4)
Patient convenience (e.g. oral vs rectal)
Cost (injectable drugs need to be sterile)
Bioavailability (how much active drug gets to site of aciton)
Local vs Systemic effect
What makes an ideal local administration of a drug? (2)
Drug exerts effect at or near site of admin
Access to limited tissues (limited by absorption)
What makes an ideal systemic administration of a drug? (2)
Drug enters bloodstream
Will access many tissues (determined by distribution)
How can you make a drug only have limited access to tissues? (2)
Use poorly absorbed drug
Choose concentration so that if drug is absorbed, concentration will be too low for systemic effect
What features of the eye make affect pharmacokinetics, making it unique from the rest of the body? (5)
tears cornea sclera and conjunctiva anterior chamber/aqueous humour Ciliary body
How do tears affect drugs?
They excrete drugs from the eye
- remove them from corneal surface
- therefore unavailable for absorption into the eye
How can topical drugs be systemically absorbed? (3)
Tears can offer up drugs for systemic absorption via the nasolachrymal duct
- absorbed through nasal mucosa
- swallowed and absorbed through gut
What is the normal tear flow rate?
0.5 to 2.5 ul/min
What happens to drugs when tear flow rate increases?
drug excretion increases, therefore drug absorption into the eye is reduced
What happens to drugs when tear flow rate decreases/people with dry eyes?
drug excretion decreases, therefore drug absorption into the eye is increased
Starting from the exterior inwards, what are the 5 layers of the cornea?
Epithelium Bowman's membrane Stroma Descement's Membrane Endothelium
What is the major site of drug absorption in the eye?
Cornea
How do drugs cross cell membranes? (3)
simple diffusion across cell membrane
driven by concentration gradient
drug must be soluble in lipid
Is lipid solubility affected by pH?
yes
Can you have too much lipid solubility?
Yes. Too much lipid solubility means less absorption, just like too little does. Need an optimal amount of lipid solubility
What proportion of drug is absorbed by sclera and conjunctiva?
Less than 20% of the total absorption into the eye
How vascularised is the sclera and conjunctiva?
Highly
What happens to the drug while it is being absorbed by the sclera and conjunctiva?
drug enters the circulation as it is being absorbed
effectively contributes to excretion from eye
What part of the eye is the main part involved in drug distribution?
Anterior chamber and Aqueous humour
Which part of the body is considered the “Liver of the eyeballs”? Explain
Ciliary body
= major source of drug metabolising enzymes
– phase I (cytochrome p450)
– phase II (conjugation)
How are drug metabolites removed/excreted in the eye?
via uveal circulation
What does drug metabolism achieve?
increases water solubility of the drug to facilitate excretion
How does drug metabolism occur?
Biotransformation: a chemical change to the drug
Phase I vs Phase II metabolism. What do they do?
Phase I: add functional group
Phase II: conjugate with water
Drugs are eliminated by excretion and metabolism. Where in the eye do these processes occur? (2 and 1 respectively)
Excretion: Tears and scleral/conjunctival absorption
Metabolism: Ciliary body
Where in the eye do you want the maximum concentration of your drug?
in the tear film
Where in the eye do you want maximum contact time with your drug? How can you achieve this? (3)
Cornea. Achieve by using: viscous solutions, gels, ointments
How can you maximise the degree of drug contact with the cornea?
Get px to look down. This avoids drug landing on vascularised sclera
How many drops of drug do you generally add? Why?
1-2 drops. This minimizes nasolachrymal loss (any more and you would get more of this loss)
How can you reduce nasolachrymal drainage of a drug?
Tip head back and occlude puncta
What effect does keeping your eyes closed have on the administered topical drug?
maximises time for absorption
Is toxicity always systemic, or can it be local?
It can also be local
Does toxicity arise from acute or chronic use?
can be either, depending
What is on-target toxicity?
When toxicity is related to the mechanism of action
What is off-target toxicity?
When toxicity occurs by a mechanism unrelated to the therapeutic mechanism
What 3 things should you consider in relation to drug toxicity and the eye?
ocular toxicity following ocular admin
ocular toxicity following systemic admin
systemic toxicity following ocular admin
What is the effect of long term use of topical proparacine? (2)
corneal opacification
damage to corneal epithelium
What is the purpose of hydroxychloroquinine?
treatment of rheumatoid arthritis and systemic lupus erythematosus
What is the main side effect of hydroxychlorquinine?
Retinopathy
What is timolol and what is it used for?
A (topical) beta-adrenoceptor antagonist used for glaucoma tx
What are the side effects of timolol? (3)
Cardiac effects: hypotension, bradycardia
Bronchospasm in asthmatics
