Pharm.ther. Eye, Ear & Skin

8/13/2019 Pharm.ther. Eye, Ear & Skin

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Pharmacotherapy of the eye,

ear and skin disordersSutomo Tanzil

Department of Pharmacology, Facultyof Medicine, Sriwijaya University


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Fig. 9.2 Rang & Dale pg 124


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Ocular physiology/pharmacology

Vision depends upon the eye converting light falling on theretina into an electrical signal to the brain

The ciliary muscle is a circular smooth muscle attached tothe 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 blurringof near vision, a state known as cycloplegia.

Pupil size is determined by 2 smooth muscle layers of theiris. The constrictor muscle is more powerful and receivesparasympathetic innervation. The radial (dilator) muscle issympathetically innervated (1-receptors).


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Ocular physiology/pharmacology

Miosis occurs in response to muscarinic agonists

Mydriasis can occur in response muscarinic antagonists or to1-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 irisand the cornea. This can reduce aqueous humour outflowthrough the canal of Schlemm.

The intraocular pressure rises if drainage of the aqueoushumour is impaired, leading to the occurrence of glaucoma,that may cause prrogressive loss of vision


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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 largelyreplaced 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).


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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 : Pgderivatives ( latanoprost, travoprost);

2

-agonists (brimonidine, dipivefrine);muscarinic agonists (pilocarpine).


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Mechanisms of action of drugs used in

open-angle glaucoma

Cholinomimetics(eg.pilocarpin): ciliary musclecontraction, opening of trabecular meshwork;increased outflow

-agonists (eg.dipivefrine) : increased outflow

2-agonists (eg.brimonidine): decreased aqueoussecretion

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


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The clinical pharmacology of

antimuscarinics

Atropine, homatropine, cyclopentolate, tropicamide

Antimuscarinics should never be used for mydriasisunless cycloplegia or prolonged action is required.

1-agonists, eg. phenylephrine, produce a short-lasting mydriasis that is usually sufficient forfunduscopic examination.

It is also used to prevent synechia (adhesion)

formation in uveitis and iritis. The longer-lastingpreparation, such as homatropine, are valuable forthis indication.


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Carbonic anhydrase inhibitors

Acetazolamide (oral), brinzolamide (eyedrops), 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 iscontraindicated

Acetazolamide is a sulfonamide derivative,therefore, do not use it in people w/ a historyof severe allergy to sulfonamide


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Other topical applications for the eye

Antibacterials : gentamicin, chloramphenicol, fusidicacid, neomycin & chlortetracycline

Antivirals : acyclovir

Corticosteroids : dexamethasone. Prolonged use can

lead to thinning of the sclera or cornea, or formationof a steroid cataract

Antiallergics : antazoline

Local anaesthetics : lidocaine/oxybuprocaine for

tonometry, removal of cataracts. NSAIDs : diclofenac, flurbiprofen & ketorolac

Artificial tears : hydroxypropyl methylcellulose,carbomers


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ARMD (age-related macular degeneration)

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

Wet (exudative) form produces severe loss ofvision in 70% of eyes within 2 years

Th/:high-dose of anti-oxidants, laserphotocoagulation of neovascular tissue,photodynamic th/ using photosensitizing

agent verteportin, intravitreal injection ofbevacizumab/ranibizumab (vascular growthfactor inhibitors)


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Vertigo

Hallucination of motion, usually perceived as

spinning, which is generated in the vestibular

system of the inner ear

Caused by Menieres disease, benign positionalvertigo, migraine, vestibular neuronitis, multiple

sclerosis, brainstem ischaemia, temporol lobe

epilepsy, cerebellopontine angle tumours


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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)


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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)


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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 beattempted for persistent synptoms.

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 causevertigo.


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