1. -Adithya Phadnis
PROSTAGLANDINS AND
HYPOTENSIVE LIPIDS

2. What are prostaglandins?
 Prostaglandins, thromboxane and leukotriens are
eicosanoids which are metabolic products of 20-
carbon arachidonic acid.
 After they are synthesized they are transported
out of cells by transporters and are inactivated by
lungs and liver.

3. What are the prostanoid
receptors?
 There are 4 types EP,FP,IP and TP.
 FP receptor exists in two forms i) full length
receptor ii) splice variant.

4. How are prostaglandins made
bioavailable to FP receptor?
 Addition of a phenyl ring to the omega chain
improve d the selectivity to the FP receptor
agonist.
 To improve solubility the C-1 carboxyl group was
modified with an ethyl amide in case of
bimatoprost or an isopropyl ester for
latanoprost,travoprost.
 This modification at C-1 carboxy group creates a
lipophilic prodrug which is hydrolysed by the
cornea into the free acid drug form.

5. What is the mechanism of
action?
 FP receptors are G protein coupled receptors,
when stimulated it couples with phospholipase-C
which triggers the releae of the second
messenger induced phossphate production and
subsequently activates a molecular transduction
cascade that leads to IOP reduction.

6. What is the history of prostaglandins
in eye?
 In rabbits the topical application of 25 to 200
micro gram of prostaglandins caused initial
increase in IOP followed by reduction in IOP for
15-20 hours whereas 5 microgram produced
ocular hypotension without initial IOP rise.

7. How does PG descrease IOP?
 Increases the uveoscleral outflow(relaxation of
ciliary muscle)
 Remodelling of extracellular matrix of ciliary
muscle.
 Increase in matrix metalloproteinase that degrade
ecm substrates such as collagens,
fibronectin,laminin

8. Which are the ocular prostaglandin
analogs?
 Latanoprost-0.005%
 Travoprost-0.004%
 Bimatoprost-0.003%

9. What are the various uses of ocular
PG analogues
1) Chronic open angle glaucoma(superior to timolol
in IOP reduction in a 6 month study 31% vs 27%)
 Latanoprost (evening) vs (morning)-35% vs 31%
2) Safe in paediatric glaucoma

10. 3) Effective in angle closure glaucoma
4) Effective in IOP reduction even when trabecular
meshwork was not seen upto 180 degrees from
25.0 +5.5 mm Hg to 17.5 +5 mm Hg.
5) Even effective in lowering IOP from 30.3 +4.5
mmHg to 21.5 + 5.9 mm Hg with 360 degrees of
PAS after 3 months of treatment.

11. 6) In patients in whom peripheral iridotomy was
done and IOP reduction was not satifactory
latanoprost decreased IOP 34% vs timolol 23%.

12. Is bimatoprost superior to
latanoprost?
 In a community based Switch study in which
patients using latanoprost switched to
bimatoprost IOP reduction was 3.4 mm Hg after 2
months of treatment

13. How to store ocular PG analogs?
 Latanoprost- 25 degrees C upto 6 weeks
 Bimatoprost – 15 -25 degrees C
 Travoprost- 2 – 25 degrees C

14. What are the various drug
combinations?
1. With timolol- 13-37% additional reduction in IOP
2. With topical and oral carbonic anhydrase
3. With alpha 2 adrenergic agonist
(brimonidine+latanoprost vs timolol+ dorzolamide::
9.2 mmHg vs 6.7 mm Hg)
4. With pilocarpine- additional effect as it increases
trabecular outflow

15. When do you call latanoprost failure?
 When even after 6 to 8 months of Latanoprost
monotherapy there is <10% IOP reduction.
 Switch over to bimatoprost helps(24.1 mm Hg vs
18.2 mm Hg)
 Also note patients who have have high baseline
IOP Latanoprost monotherapy caused failure

16. What are the various side
effects?
1. Conjuctival hyperemia
 Latanoprost- 5-15%
 Bimatoprost-15-45%
 Travoprost-35-50%
 Unoprostone-10-25%

17. 2. Decrease in conjunctival epithelial cell size by its
effect on fibroblast and matrix metalloproteinases.
3. Reactivation of herpes simplex keratitis.
4. Anterior uveitis and CME(absorptive transport
system of ciliary process appear to prevent
topically applied prostaglandins to cause retinal
toxicity- )

18. 5. Increased pigmentation of periocular
skin(reversible and advise the patient to wipe off
excess drug)
6. Darkening of iris in 10%
7. hypertrichosis- beneficial cosmetically(stimulates
hair growth phase in dermal papilla)
8. Contact dermatitis, iri cyst

19. What is rhe reason for pigmentation?
 Prostaglandins increase the tyrosine kinase
activity in melanocytes thereby increases melanin
but not proliferation of melanocytes.