Pharmacotherapy

of the eye, ear and

skin disorders
Sutomo Tanzil
Department of Pharmacology,
Faculty of Medicine,
Sriwijaya University

Fig. 9.2 Rang & Dale pg

124

Ocular
physiology/pharmacology

Vision depends on the eye converting light falling on

the retina into an electrical signal to the brain
The ciliary muscle is a circular smooth muscle
attached to the lens. It has a parasympathetic (PS)
nerve supply and contracts in response to PS
stimulation.
Muscarinic agonists fix the lens for near vision, while
antimuscarinic drugs fix the lens for far objects with
blurring of near vision, a state known as cycloplegia.
Pupil size is determined by 2 smooth muscle layers of
the iris. The constrictor muscle is more powerful and
receives parasympathetic innervation. The radial
(dilator) muscle is sympathetically innervated ( 1receptors).

Ocular
physiology/pharmacology

Miosis occurs in response to muscarinic agonists

Mydriasis can occur in response muscarinic
antagonists or to 1-adrenoceptor agonists.
Miosis also accompanies accommodation for near
vision, a response mediated by the PS nervous system
Mydriasis has the effect of moving the iris towards
the cornea and narrowing the anterior angle between
the iris and the cornea. This can reduce aqueous
humour outflow through the canal of Schlemm.
The intraocular pressure rises if drainage of the
aqueous humour is impaired, leading to the
occurrence of glaucoma, that may cause prrogressive
loss of vision

Clinical pharmacology of
the cholinomimetics

In the past, glaucoma was treated w/ either

direct agonists (pilocarpine, carbachol) or
cholinesterase inhibitors
(physostigmine,echothiophate). For chronic
glaucoma, these drugs have been largely
replaced by topical beta-blockers and
prostaglandin derivatives.
Acute angle-closure glaucoma is a medical
emergency that is frequently treated initially
w/ drugs but usually requires surgery for
permanent correction (iridectomy).

Drugs used for chronic

th/of simple (open-angle)
glaucoma

Reducing aqueous humour production :

BB (betaxolol, timolol); 2-agonists
(brimonidine, dipivefrine); carbonic
anhydrase inhibitors ( acetazolamide,
brinzolamide, dorzolamide).
Increasing aqueous humour outflow : Pg
derivatives ( latanoprost, travoprost); 2agonists (brimonidine, dipivefrine);
muscarinic agonists (pilocarpine).

Choice of th/for simple

glaucoma

BB and Pg analogues are first-line treatments,

because they are effective and have less ADRs.
Other drugs are added to first-line th/ for
patients who have inadequate response. They
are not considered first-line drugs because of
limited efficacy (carbonic anhydrase inhibitors)
or a high incidence of local adverse effects (eg.
transient blurred vision, local stinging, and
painful ciliary spasm)
Acute closed-angle glaucoma is a medical
emergency and the patient should be referred
to a specialist.

Mechanisms of action of
drugs used in open-angle
glaucoma

Cholinomimetics(eg.pilocarpin): ciliary muscle

contraction, opening of trabecular meshwork;
increased outflow
-agonists (eg.dipivefrine) : increased outflow
2-agonists (eg.brimonidine): decreased aqueous
secretion
Beta-blockers (eg.timolol, betaxolol) : decreased
aqueous secretion from ciliary epithelium
Diuretics(eg.acetazolamide) : decreased aqueous
secretion due to lack of bicarbonate ions.
Prostaglandins (eg.latanoprost, travoprost):
increased outflow

The clinical pharmacology

of antimuscarinics

Atropine, homatropine, cyclopentolate, tropicamide

Antimuscarinics should never be used for mydriasis
unless cycloplegia or prolonged action is required.
1-agonists(eg. Phenylephrine), produce a shortlasting mydriasis that is usually sufficient for
funduscopy.
It is also used to prevent synechia (adhesion)
formation in uveitis and iritis. The longer-acting
preparation, such as homatropine, are valuable for
this indication.

Carbonic anhydrase
inhibitors

Acetazolamide (oral), brinzolamide (eye

drops), dorzolamide (eye drops)
Inhibition of carbonic anhydrase results in
reduced formation of aqueous humour
Used in the th/of glaucoma in patients who
are BB resistant or in whom a BB is
contraindicated
Acetazolamide is a sulfonamide, therefore,
do not use it in patients allergic to
sulfonamide.

Other topical applications

for the eye

Antibacterials : gentamicin, chloramphenicol,

fusidic acid, neomycin & chlortetracycline
Antivirals : acyclovir
Corticosteroids : dexamethasone. Prolonged use
can lead to thinning of the sclera or cornea, or
formation of a steroid cataract
Antiallergics : antazoline
Local anaesthetics : lidocaine/oxybuprocaine for
tonometry, removal of cataracts.
NSAIDs : diclofenac, flurbiprofen & ketorolac
Artificial tears : hydroxypropyl methylcellulose,
carbomers

ARMD (age-related macular

degeneration)

Dry (non-exudative) form : 85-90% of

cases
Wet (exudative) form produces severe loss
of vision in 70% of eyes within 2 years
Th/:high-dose of anti-oxidants, laser
photocoagulation of neovascular tissue,
photodynamic th/ using photosensitizing
agent verteportin, intravitreal injection of
bevacizumab/ranibizumab (vascular
growth factor inhibitors)

Vertigo

Hallucination of motion, usually perceived

as spinning, which is generated in the
vestibular system of the inner ear
Caused by Menieres disease, benign
positional vertigo, migraine, vestibular
neuronitis, multiple sclerosis, brainstem
ischaemia, temporol lobe epilepsy,
cerebellopontine angle tumours

Neurochemistry of
vertigo

Glutamate (excitatory via NMDA )

Acetylcholine (excitatory via M2 )
GABA (inhibitory via GABAA & GABAB)
Histamine (excitatory via H1 & H2)
NA (modulation of vestibular sensory
transmission)
Dopamine (excitatory)

Drugs for TH/ of Vertigo

Antihistamine (cyclizine, promethazine,

most widely used)
Antimuscarinic (hyoscine)
Benzodiazepine (short-term for severe
vertigo)
Cimetidine.
H-receptor agonist (betahistine)
D-receptor antagonist (prochlorprazine)

Management of vertigo

Acute vertigo (vest.neuronitis) : antiemetic

agents
Benign parox.vertigo : less responds to drugs,
effectively treated w/ vestibular exercises
Menieres disease : promethazine, cinnarizine or
prochlorprazine. Furosemide & HCT can be
attempted for persistent symptoms.
Betahistine is often co-prescribed w/ a diuretic.
For refractory symptoms, vestibular apparatus
can be ablated w/ local delivery of gentamicin ,
or w/ surgical treatment.
AHs , vasodilators and antiparkinsonians can
cause vertigo.

Skin pharmacology

Topical preparations have two components : a

base and the active ingredients, such as a
corticosteroid or an antifungal
Ointments : greases such as white/yellow
paraffin
Pastes : suspension of powder in an ointment
Creams : emulsions of water with a grease, less
greasy than ointments, absorbed more quickly
into the skin
Lotions : liquids, used on wet surfaces and hairy
areas, they do not make a mess.

References

Katzung, B.G. (2007).Basic And Clinical

Pharmacology, 10th Edition, The McGraw-Hill
Companies, Inc.,USA.
Richards, D. & Aronson, J. (2005). Oxford
Handbook of Practical Drug Therapy. Oxford
University Press Inc. , New York, USA.
Rang, H.P.et al.(2003). Pharmacology.Fifth
Edition.Churchill Livingstone, U.K.
Waller,D.G. et al.(2010).Medical Pharmacology
And Therapeutics. 3rd Edition, Elsevier
Saunders, UK.