Phamacokinetics

Question 1

What factors have a effect on ocular absopriton of a drug?

Answer 1

Tear volume
Tear turnover time
Spontaneous blink rate

Corneal thickness
Ratio of conjunctival:corneal surface area (17:1)

Question 2

How long do drugs remain in the conjunctival sac?

Answer 2

3-5 minutes

Question 3

What reduced the time a drug is in conjunctival sac?

Answer 3

If medication is irritative
Increased tear production an blinking

Question 4

What is the range of absoption of ocular medication?

Answer 4

1-7%

mount of drug entering eye over the instilled dose

Question 5

What is the the greatest barrier to ocular drug penetration and how can drugs enter the eye?

Answer 5

Corneal epithelium - lipophilic layer

Intracellular route for lipophylic drugs

Paracellular route for hydrophilic drugs

Question 6

Do the stroma and endothelium give resistance to drug transport?

Answer 6

Stroma provides little resistance - one quarter that of an aqueous system

Endothelium provides no significant resistance

Question 7

How else can drugs penetrate into the eye?

Answer 7

Transconjunctival
Transscleral

Vascular nature of episclera and conjunctiva also faciliatates transport of drugs to deeper ocular tissues

Question 8

What factors influene the availability of drugs in ocular tissues?

Answer 8

1. Binding of drug to MELANIN in iris and ciliary body causes slow release of drug from this reservoir
2. Drugs may bind to proteins in the aqueous
3. Rapid turnover of aqueous humour will reduce the availability of a drug to the intraocular tissues.

Question 9

What does melanin binding result on drug release?

Answer 9

Slow release resulting in prolonged but reduced effect
E.g. atropine in darker irises

Question 10

What drugs accumulate in the cornea?

Answer 10

NSAIDs
Pilocarpine (muscarinic agonist)

Question 11

Why do topical antibiotics no achieve minimal inhibitory concentrations in the vitreous?

Answer 11

Penetration of topical medications into vitreous is poor - mustdiffuse against an aqueous humour gradient and diffusion of drugs throught he vitresou is slow

Question 12

Why can fluorescein be used to assess the retinal circulation?

Answer 12

Does not cross the blood retinal barrier

Question 13

What happens to drugs once they enter the aq humour?

Answer 13

Eliminated by aq humour turnover

Turnover time is about 1.5% per minute of the anterior chamber volume giving an aqueous half life of 46 minutes

Question 14

What does a drug half life of <46mins mean? >46mins?

Answer 14

<46minutes suggests metabolism of the drug and uptake by blood is contributing the ocular elimination

> 46minutes suggests there is significant tissue binding resulting in reduced elimination

Question 15

What is Fick’s law

Answer 15

Rate of diffusion = (diffusion coefficient x concentration gradient) / membrane thickness

Question 16

What is diffusion coefficient dependent on

Answer 16

Lipid solubility (higher if more soluble)
Ionization of drug (lower if more ionized)
Molecular size

Question 17

How does acid/alkaline pH affect drug absorption and clearance?

Answer 17

Drug is more un-ionized if more acid or alkaline so more lipid soluble, increasing drug absorption

Acidic/alkaline pH can cause increased irritation and lacrimation causing increased drug clearanceH

Question 18

How does blink rate affect drug clearance?

Answer 18

More blnking, more drug clearance