prostaglandin based drugs

phospholipase A2 

• cleaves phospholipid at second position (arachidonic acid at second position of phospholipid)

  • arachidonic acid in cell membrane → free arachidonic acid in cell 

cyclooxygenase 

• converts arachidonic acid → prostaglandin H2 

  • fate of prostaglandin H2 depends on the cell 

what are the 3 types of eicosanoids (derivatives of arachidonic acids)

1. thromboxane A2 (TXA2)

2. Prostaglandin E2 (PGE2)

3. prostacyclin (PGI2)

prostaglandin H2 in platelets produce …

• thromboxane A2 

  • thromboxane synthase enzyme in platelets 

prostaglandin H2 in endothelial cells produce…

• prostacyclin 

  • prostacyclin synthase enzyme in endothelial cells

autacoids

• eicosanoids 

• molecules in between NT + hormone 

  • produced in area + effect in area

T/F: the eicosanoids activate various G-protein coupled receptors

• true

T/F: PGE2 receptor has 4 different types of receptors

• true

  • dependent on tissue

what type of drug is dinoprostone?

• PGE2 analog 

  • structure is related to PGE2 

how is dinoprostone administered? 

• intravaginal suppository 

what is the effect of dinoprostone

• contraction of uterine smooth muscle

  • Prostaglanding E2 receptor (EP1 receptor) → increases Ca+ 

indications for dinoprostone

• stimulate contractions for women near term/ LD

• following birth to reduce blood loss (constrict uterine tissue) 

• high doses → evacuate uterus abortifacient 

what receptor do dinoprost and carboprost stimulate?

• stimulate PGF receptor 

  • Gq → increases Ca+ 

what are dinoprost and carboprost used for?

• same as dinoprostone 

  • intravaginal suppository 

  • cause uterine contractions

what is the difference between dinoprostone vs dinoprost + carbosprost 

• work at different receptors but both receptors are in the same location (Uterine smooth muscle) 

• dinoprost + carboprost = prodrugs 

  • converted into PGF2-alpha 

  • activate PGF Receptors

• dinoprostone = NOT a prodrug

  • activate PG2 EP1 receptors  

SATA: which of the following are administered locally into the eye? 

a) latanoprost 

b) tafluprost

c) dinoprost

d) carboprost

e) travoprost

f) bimatoprost

a) latanoprost 

b) tafluprost

e) travoprost

f) bimatoprost

SATA: which of the following are administered locally into the vagina? 

a) latanoprost 

b) tafluprost

c) dinoprost

d) carboprost

e) travoprost

f) bimatoprost

c) dinoprost

d) carboprost

what receptor do the PGF2alpha analogs used locally in the eye target ? 

• activate PGF2 receptor

  • activate PGF receptor, like the same receptor in uterine smooth muscle, but in eye 

effect of activating PGF2 receptor in eye 

• increase Ca+ →

how are PGF2a analogs used for the treatment of glaucoma?

• activation of PGF2 receptor → increase Ca+ → activation of a number of downstream enzymes → increase in transcription factors → increase gene expression for MMP enzymes 

  • MMPs = metalloproteinases → break down collagen/connective tissue 

  • breaks down the sclera → uvoscleral pathway revealed → allows outflow of aqueous humor 

what are the 2 pathways for aqueous h=outflow

1. canal of Schlemm 

2. uvoscleral pathway 

T/F: PGF2a analogs (for the eyes) have a primary effect on the uvoscleral pathway but also have a minor effect in increasing outflow through the canal of schlemm 

• true 

ADE of PGF2a analogs for the eyes 

• increase in conjunctivitis 

• change in color of iris 

• increase length of eyelashes (not really known why) 

  • side effect, not really ADE 

T/F: often times eye drops (PGF2a) have to be refrigerated to improve stability 

• true 

  • short-lived intermediate 

Latisse

• brand name of bimatoprost

  • formulation that is brushed onto eyelashes → increase growth of eyelashes 

latanoprost (PG analog) vs pilocarpine ( muscarinic agonist) 

• both treat glaucoma by increasing outflow of aqueous humor 

  • pilocarpine = change shape of lens → can lead to blurry vision, miosis from activation of circular muscle  → hard to see in dim light

  • latanoprost = no effect on pupil size or lens shape 

T/F: prostaglandins are delivered systemically 

• false 

  • locally administered (intravaginal suppositories or ophthalmic drops)

  • can not be systematically administered because they are unstable