OptoP: Drug Admin to Eye - Week 9

Question 1

In general terms, describe pharmacokinetics

Answer 1

getting drugs to and from their sites of action

Question 2

What are the 4 key pharmacokinetic related issues in clinical drug use?

Answer 2

What form is drug in
Where do you put it
How much do you use
How often do you use it

Question 3

What are the 4 steps of pharmacokinetics?

Answer 3

Administration: giving the drug
Absorption: drug enters circulation
Distribution: drug spreads through body
Elimination: drug is removed from body

Question 4

What factors influence the choice of route of administration of a drug? (4)

Answer 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

Question 5

What makes an ideal local administration of a drug? (2)

Answer 5

Drug exerts effect at or near site of admin

Access to limited tissues (limited by absorption)

Question 6

What makes an ideal systemic administration of a drug? (2)

Answer 6

Drug enters bloodstream

Will access many tissues (determined by distribution)

Question 7

How can you make a drug only have limited access to tissues? (2)

Answer 7

Use poorly absorbed drug

Choose concentration so that if drug is absorbed, concentration will be too low for systemic effect

Question 8

What features of the eye make affect pharmacokinetics, making it unique from the rest of the body? (5)

Answer 8

tears
cornea
sclera and conjunctiva
anterior chamber/aqueous humour
Ciliary body

Question 9

How do tears affect drugs?

Answer 9

They excrete drugs from the eye

• remove them from corneal surface
• therefore unavailable for absorption into the eye

Question 10

How can topical drugs be systemically absorbed? (3)

Answer 10

Tears can offer up drugs for systemic absorption via the nasolachrymal duct

• absorbed through nasal mucosa
• swallowed and absorbed through gut

Question 11

What is the normal tear flow rate?

Answer 11

0.5 to 2.5 ul/min

Question 12

What happens to drugs when tear flow rate increases?

Answer 12

drug excretion increases, therefore drug absorption into the eye is reduced

Question 13

What happens to drugs when tear flow rate decreases/people with dry eyes?

Answer 13

drug excretion decreases, therefore drug absorption into the eye is increased

Question 14

Starting from the exterior inwards, what are the 5 layers of the cornea?

Answer 14

Epithelium
Bowman's membrane
Stroma
Descement's Membrane
Endothelium

Question 15

What is the major site of drug absorption in the eye?

Answer 15

Cornea

Question 16

How do drugs cross cell membranes? (3)

Answer 16

simple diffusion across cell membrane
driven by concentration gradient
drug must be soluble in lipid

Question 17

Is lipid solubility affected by pH?

Answer 17

yes

Question 18

Can you have too much lipid solubility?

Answer 18

Yes. Too much lipid solubility means less absorption, just like too little does. Need an optimal amount of lipid solubility

Question 19

What proportion of drug is absorbed by sclera and conjunctiva?

Answer 19

Less than 20% of the total absorption into the eye

Question 20

How vascularised is the sclera and conjunctiva?

Answer 20

Highly

Question 21

What happens to the drug while it is being absorbed by the sclera and conjunctiva?

Answer 21

drug enters the circulation as it is being absorbed

effectively contributes to excretion from eye

Question 22

What part of the eye is the main part involved in drug distribution?

Answer 22

Anterior chamber and Aqueous humour

Question 23

Which part of the body is considered the “Liver of the eyeballs”? Explain

Answer 23

Ciliary body
= major source of drug metabolising enzymes
– phase I (cytochrome p450)
– phase II (conjugation)

Question 24

How are drug metabolites removed/excreted in the eye?

Answer 24

via uveal circulation

Question 25

What does drug metabolism achieve?

Answer 25

increases water solubility of the drug to facilitate excretion

Question 26

How does drug metabolism occur?

Answer 26

Biotransformation: a chemical change to the drug

Question 27

Phase I vs Phase II metabolism. What do they do?

Answer 27

Phase I: add functional group

Phase II: conjugate with water

Question 28

Drugs are eliminated by excretion and metabolism. Where in the eye do these processes occur? (2 and 1 respectively)

Answer 28

Excretion: Tears and scleral/conjunctival absorption
Metabolism: Ciliary body

Question 29

Where in the eye do you want the maximum concentration of your drug?

Answer 29

in the tear film

Question 30

Where in the eye do you want maximum contact time with your drug? How can you achieve this? (3)

Answer 30

Cornea. Achieve by using: viscous solutions, gels, ointments

Question 31

How can you maximise the degree of drug contact with the cornea?

Answer 31

Get px to look down. This avoids drug landing on vascularised sclera

Question 32

How many drops of drug do you generally add? Why?

Answer 32

1-2 drops. This minimizes nasolachrymal loss (any more and you would get more of this loss)

Question 33

How can you reduce nasolachrymal drainage of a drug?

Answer 33

Tip head back and occlude puncta

Question 34

What effect does keeping your eyes closed have on the administered topical drug?

Answer 34

maximises time for absorption

Question 35

Is toxicity always systemic, or can it be local?

Answer 35

It can also be local

Question 36

Does toxicity arise from acute or chronic use?

Answer 36

can be either, depending

Question 37

What is on-target toxicity?

Answer 37

When toxicity is related to the mechanism of action

Question 38

What is off-target toxicity?

Answer 38

When toxicity occurs by a mechanism unrelated to the therapeutic mechanism

Question 39

What 3 things should you consider in relation to drug toxicity and the eye?

Answer 39

ocular toxicity following ocular admin
ocular toxicity following systemic admin
systemic toxicity following ocular admin

Question 40

What is the effect of long term use of topical proparacine? (2)

Answer 40

corneal opacification

damage to corneal epithelium

Question 41

What is the purpose of hydroxychloroquinine?

Answer 41

treatment of rheumatoid arthritis and systemic lupus erythematosus

Question 42

What is the main side effect of hydroxychlorquinine?

Answer 42

Retinopathy

Question 43

What is timolol and what is it used for?

Answer 43

A (topical) beta-adrenoceptor antagonist used for glaucoma tx

Question 44

What are the side effects of timolol? (3)

Answer 44

Cardiac effects: hypotension, bradycardia

Bronchospasm in asthmatics