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OD2 S1 > OptoP: Drug Admin to Eye - Week 9 > Flashcards

OptoP: Drug Admin to Eye - Week 9 Flashcards

1
Q

In general terms, describe pharmacokinetics

A

getting drugs to and from their sites of action

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2
Q

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

A

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

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3
Q

What are the 4 steps of pharmacokinetics?

A

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

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4
Q

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

A

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

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5
Q

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

A

Drug exerts effect at or near site of admin
Access to limited tissues (limited by absorption)

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6
Q

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

A

Drug enters bloodstream
Will access many tissues (determined by distribution)

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7
Q

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

A

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

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8
Q

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

A

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

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9
Q

How do tears affect drugs?

A

They excrete drugs from the eye
- remove them from corneal surface
- therefore unavailable for absorption into the eye

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10
Q

How can topical drugs be systemically absorbed? (3)

A

Tears can offer up drugs for systemic absorption via the nasolachrymal duct
- absorbed through nasal mucosa
- swallowed and absorbed through gut

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11
Q

What is the normal tear flow rate?

A

0.5 to 2.5 ul/min

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12
Q

What happens to drugs when tear flow rate increases?

A

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

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13
Q

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

A

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

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14
Q

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

A

Epithelium
Bowman’s membrane
Stroma
Descement’s Membrane
Endothelium

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15
Q

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

A

Cornea

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16
Q

How do drugs cross cell membranes? (3)

A

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

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17
Q

Is lipid solubility affected by pH?

A

yes

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18
Q

Can you have too much lipid solubility?

A

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

19
Q

What proportion of drug is absorbed by sclera and conjunctiva?

A

Less than 20% of the total absorption into the eye

20
Q

How vascularised is the sclera and conjunctiva?

A

Highly

21
Q

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

A

drug enters the circulation as it is being absorbed
effectively contributes to excretion from eye

22
Q

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

A

Anterior chamber and Aqueous humour

23
Q

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

A

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

24
Q

How are drug metabolites removed/excreted in the eye?

A

via uveal circulation

25
Q

What does drug metabolism achieve?

A

increases water solubility of the drug to facilitate excretion

26
Q

How does drug metabolism occur?

A

Biotransformation: a chemical change to the drug

27
Q

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

A

Phase I: add functional group
Phase II: conjugate with water

28
Q

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

A

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

29
Q

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

A

in the tear film

30
Q

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

A

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

31
Q

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

A

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

32
Q

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

A

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

33
Q

How can you reduce nasolachrymal drainage of a drug?

A

Tip head back and occlude puncta

34
Q

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

A

maximises time for absorption

35
Q

Is toxicity always systemic, or can it be local?

A

It can also be local

36
Q

Does toxicity arise from acute or chronic use?

A

can be either, depending

37
Q

What is on-target toxicity?

A

When toxicity is related to the mechanism of action

38
Q

What is off-target toxicity?

A

When toxicity occurs by a mechanism unrelated to the therapeutic mechanism

39
Q

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

A

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

40
Q

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

A

corneal opacification
damage to corneal epithelium

41
Q

What is the purpose of hydroxychloroquinine?

A

treatment of rheumatoid arthritis and systemic lupus erythematosus

42
Q

What is the main side effect of hydroxychlorquinine?

A

Retinopathy

43
Q

What is timolol and what is it used for?

A

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

44
Q

What are the side effects of timolol? (3)

A

Cardiac effects: hypotension, bradycardia
Bronchospasm in asthmatics

OD2 S1 (47 decks)

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