2 - Pharmacology of Drugs Acting On The Eye (Updated)
2 - Pharmacology of Drugs Acting On The Eye (Updated)
2 - Pharmacology of Drugs Acting On The Eye (Updated)
Objectives:
11:24 min
1
To understand better
Accommodation for light intensity:
Pupillary Muscles
Miosis Mydriasis
2
Extra recall: 1st year, MSk block
Constrictor pupillae is
important for:
1- Adjusting the pupil in response
to change in light intensity.
2- Regulating the intraocular
pressure.
( aka: canal
Regulating the intraocular pressure: of Schlemm )
In the healthy eye:
• Aqueous humour is secreted by the cells of the epithelium covering the
ciliary body.
• Increased tension in the ciliary body removes the Aqueous humour
continuously by drainage into the canal of Schlemm.
• Normal intraocular pressure is 10-15mmHg above atmospheric pressure.
In some people:
• Dilatation of their pupil will block canal of schlemm, therefore it impeds
drainage of aqueous humour.
• The accumulation of aqueous humour leads to an increase in intraocular
pressure.
• IOP may lead to glaucoma, and retinal detachment.
Treatment:
When using cholinergic drugs (e.g.
pilocarpine), constrictor pupillae causes
miosis, which contracts the pupil away
from canal of schlemm, leading to
increased filtration of Aqueous humour.
Thus, activation of constrictor pupillae
decreases intraocular pressure in
patients with glaucoma.
Development of Glaucoma Animation. 4
To understand better
Autonomic Nerve supply of the Eye:
Parasympathetic N.S.
Sympathetic N.S.
= Cholinergic drugs action
• Constriction of the pupillary • Contraction of dilator “radial” Pupillae
sphincter “constrictor/circular” (Active mydriasis)* α1 mean the iris
muscle (miosis) go to the back.
• Contraction of the ciliary muscle • Relaxation of ciliary muscles
(accommodation for near vision). (accommodation for far vision) β2 **
= reduce filtration angle.
• Decrease in intraocular pressure
↓ IOP. increases aqueous outflow • Increase in intraocular pressure
through the trabecular meshwork • Lacrimation α1
into canal of Schlemm by ciliary • Vasoconstriction of conjunctival blood
muscle contraction. vessels α1 . “α & β receptors in the
blood vessels of the ciliary processes
• Increased lacrimation )(التدمع
help in regulation of aqueous humour
• Conjunctival Vasodilatation formation.”
* Active vs. passive mydriasis:
• Atropine (anticholinergic): Blocking muscarinic receptors relaxing circular muscles
Passive Mydriasis
• Sympathetic stimulation: activation of receptors in radial muscles contraction
Active mydriasis
** in the sympathetic system, activation of receptors leads to smooth muscle contraction, and
activation of 2 receptors leads to smooth muscle relaxation.
Locally (Topically):
Systemically:
*more common*
- Eye drops.
- Ointments.
- Injections:
- Periocular injection. - Orally.
- Intraocular injection.
Advantages:
- IV.
- Convenient ()مريح, Economic ()رخيص, Relatively safe.
Disadvantages:
- Compliance, Corneal & conjunctival toxicity.
First – locally:
The contact time between the drug The drug has to be high lipid soluble to
Disadvan
tages
and the eye is low due to fast have the maximum effect as ointment.
removal by tears. Thus has to be
used several times.
6
First – locally (cont.):
Eye injections:
1- Intra-cameral: E.g. ADRs
Intra-ocular injections
For anterior segment surgery, infections & retinitis
E.g.
• Intravitreal antibiotics in cases - Retinal toxicity.
of endophthalmitis (an - Intraocular toxicity.
2- Intra-vitreal inflammation of the internal coats of - Corneal toxicity.
the eye)
"inside the eye" • Intravitreal steroid in macular
edema (the build-up of fluid in the
3:06 min macula, an area in the center of the
retina.)
1- Subconjunctival
0:4 min
Techniques
2- Retro-bulbar
Peri-ocular injections
0:34 min
3- Peri-bulbar
“above and below
the orbit”
Advantages:
- Reach behind iris-lens diaphragm better than topical application.
- Drugs penetration is generally weaker for low lipid-soluble drugs, however
injections can bypass the conjunctival and corneal epithelium which is good
for drugs with low lipid solubility (e.g. penicillins)
- Steroid and local anesthetics can be applied this way.
- Used for infection of anterior segment and inflammation of uvea.
Disadvantages:
- Local toxicity, tissue injury, globe perforation, optic nerve damage. 7
Pharmacokinetics of topical drugs:
ducts or change formulation. (residence time = the time in which drug will still in
the eye).
Metabolism.
Elimination by nasolacrimal drainage or binding to tear protein.
Diffusion across cornea & conjunctiva.
Metabolism Distribution
Second- systemically:
lipid solubility
• Protein binding: more effect
with low protein binding
(inverse proportion)
• Eye inflammation: more
penetration with ocular
inflammation.
8
Treatment of open angle glaucoma (chronic)
The main goal is to decrease IOP by: 3:39min
• GI upset, headache.
• Intraocular inflammation.
Metabolic acidosis, renal stone.
• Macular edema.
• Sulfa allergy bc they are sulfa
derivatives.
C.I
miosis in surgery.
angle • Accommodative esotropia ) (نوع من الحول
- Open angle
glaucoma ecothiophate. 0:23 min
glaucoma. * The drug of
• In lice infestation of lashes
Indications
Scopolamine
atropine homatropine cyclopentolate tropicamide
(Hyoscine)
7-10 days 3-7 days 1-3 days 24 hours 6 hours
Duration
of effect
•
(uses)
Dipivefrin
epinephrine (pro-drug of phenylephrine apraclonidine
epinephrine)
- Increase uveoscleral
cycloplegia). bc - uveoscleral outflow
outflow of aqueous their effect is on the of aqueous humor.
humor. radial muscle, not the
ciliary muscle which is
- Inhibits sympathetic
innervated by paraS. working.
administration
Route of
• Fundoscopic
examination of
• Open angle
Indications
the eye.
glaucoma treatment
• To prevent
• Prophylaxis against
Open angle glaucoma. adhesion in
IOP spiking after
uveitis & iritis.
glaucoma laser
• Decongestant in
procedures.
minor allergic
hyperemia of eye.
ation
Irritation.
12
Angle closure glaucoma
1:03 min
13
Treatment of narrow closed angle glaucoma (acute)
Treatment of narrow closed angle glaucoma (acute)
Oral = Systemic
The use of drugs is limited to:
Acetazolamide
Topical
e.g. Pilocarpine
cholinomimetics
Hypertonic solution
Osmotic agents (Mannitol, Glycerol).
Pethidine or
Analgesics morphine (for pain).
Anti- inflammatory
corticosteroid NSAID
Corticosteroids
MOA
Topical Systemic
E.g. prednisolone,
Indications
- Secondary infection.
- Delayed wound healing. (healing is slow bc it is an immune
suppression) 15
Corticosteroids side effect
NSAID
Ketorolac diclofenac Flurbiprofen
Drug
MOF
Preoperatively to
postoperative
Indications
16
Stinging (irritation), sterile corneal melt & perforation.
Drugs causing corneal deposits
Pigmented deposits
of cornea.
Amiodarone,
Chloroquine Optic neuropathy1,
Retinopathy.
Drugs causing corneal deposits
Brown pigmentary
Phenothizines deposits in the cornea,
conjunctiva & eyelid.
cataract formation4,
Steroids elevated IOP &
glaucoma (long term use)
optic neuropathy
Ethambutol5 characterized by gradual
Progressive central scotomas and
vision loss.
2- Systemically
- Factors influencing systemic drug penetration into ocular tissue:
- The more lipid solublity the more penetration.
- More effect w\ ↓ protein binding.
- Eye inflammation more penetration.
Treatment of glaucoma
Open angle glaucoma Narrow closed angle glaucoma
Cholinergic agonists
Direct agonist Indirect agonist
Drug
Glaucoma.
Adrenergic agonists
Non-selective Selective α1 agonists Selective α2 agonists
Drug
Epinephrine,
Phenylephrine Apraclonidine
Dipiverfin
- production of aqueous
- ↑ uveoscleral
Action
- Fundoscopic examination of
- Open angle glaucoma
Indication
the eye.
treatment
Open angle - To prevent adhesion in uveitis
- Prophylaxis against IOP
glaucoma. & iritis.
spiking after glaucoma laser
- Decongestant in minor allergic
procedures.
hyperemia of eye.
Irritation of eye.
19
- C.I: Asthma pts.
Summary-3
Drug Mech. Of action Indication ADRs
Carbonic anhydrase
iris (heterochromia
lesser adverse effects.
iridis.
- They have replaced beta
blockers.
- Intraocular
- They are used topically as eye inflammation.
drops & once a day. - Macular edema.
allergic conjunctivitis,
inhibiting phosphlipase A2 prevention and
cataract, mydriasis
- Topical: suppression of corneal - Skin atrophy.
E.g. prednisolone, graft rejection. - Secondary
dexamethasone, infections.
hydrocortisone - Systemic: - Delayed wound
- Systemic: posterior uveitis,
healing.
E.g. prednisolone, cortisone optic neuritis.
- Ketorolac Cystoid
macular edema occurring
after cataract surgery.
NSAID
Sources:
1- Dr.Hanan Hagar’s lecture & Dr.AbduLatif Mahesar’s lecture , 2016.
2- 435 MSK block
3- Wikipedia
4- Pharmacology (Lippincotts Illustrated Reviews Series), 5th edition.
5- Ganong’s Review of medical physiology, 25th edition.