Opthalmic pharmacology - Dersh

Question 1

The anterior and posterior chambers of the eye are filled with what?

What is the composition?

Answer 1

acqueous humor - similar in composition to cerebrospinal fluid

Question 2

What produces aqueous humor and where is it secreted into?

Answer 2

Aqueous humor is secreted by the epithilial cells that cover the ciliary body and it is secreted into the posterior chamber

Question 3

In what two ways does the aqueous humor exit the anterior chamber?

Answer 3

1. Canal of Schlemm –> that is a venous sinus
2. Reabsorption into the ciliary muscle –> uvoscleral flow

Question 4

Genetically, what can put someone at an increased risk of developing acute angle closure glaucoma?

Give an example of what can precipitate the glaucoma

Answer 4

A genetically closed angle of Schlemm –> medical emergency

A topical mydriatic medication can cause the radial muscle to contract to increase the diameter of the pupil, and the iris may acutely obstruct the flow of aqueous humor from the posterior to the anterior chamber –> the eye becomes painful and red

Temporary treatment is a diuretic (IV mannitol or glycerol)

Definite treatment is surgical iridectomy

Question 5

What are the two types of open angle glaucoma?

Answer 5

Primary (idiopathic) Open Angle Glaucoma POAG - painless and essentially asymptomatic. Accompanied by chronic elevation of IOP. If untreated it leads to, initially loss of visual fields, then later blindness

Secondary (following trauma or inflammation)

Question 6

What is the gold standard technique to measure intraocular pressure?

Describe the procedure

Answer 6

Goldman applanometry

Before the measurement, a drop of solution containing a fluorescent dye (fluorescein) and a local anesthetic is instilled in the eye. The patient places his/her chin in a rest and the probe is advanced to contact and indent (i.e. applant) a specified area of the corneal surface (a circle with diameter 3.06 mm). The force used to indent the cornea may be converted to IOP.

A normal value for IOP is taken to be less than 21 mm Hg. There is significant diurnal variability in IOP in both normal persons and persons with POAG; ideally pre- and post-treatment IOP values are obtained at several different times during the day in order to confirm the diagnosis and verify adequacy of treatment.

Question 7

What is the general mechanism used by medication in the treatment of primary open angle glaucoma?

Answer 7

Decrease synthesis of aquoeus humor

Increase the outflow of aqueous humor (either by increasing flow in the canal of Schlemm or by increasing uveoscleral flow)

Question 8

Pilocarpine

Mechanism?

AE?

Answer 8

Muscurinic agonist - causes miosis and thereby increases aqueous outflow through the canal of schelmm

Adverse effect (PDS):

• Poor vision at night or in poorly illuminated areas
• Decreased visual acuity
• Spasm of the ciliary muscle may lead to orbital pain or headache

Question 9

Carbachol

Answer 9

Stimulates both muscarinic and nicotinic receptors.

In topical ocular and intraocular administration its principal effects are miosis and increased aqueous humour outflow.

Its an alternative to pilocarpine

Question 10

Echothiophate

Mechanism?

AE?

Answer 10

Acetycholinesteras inhibitor - not commonly used today because it is an irreversible inhibitor of AChE

Adverse effects:

• Painful ciliary spasms
• Pinpoint pupils

With chronic use:

• Thickening of conjuctivae
• Obstruction of the nasolacrimal canals

Systemic adverse effects?

• Excessive parasympathetic activity
  
  • bradycardia
  • bronchospasms
  • GI smooth muscle spasms

Question 11

Physostigmine

Answer 11

An irreversible cholinesterase inhibitor

An alternative to echothiophate

Question 12

Formation of aquoeus humor is dependant on the reaction catalyzed by which enzyme?

Answer 12

carbonic anhydrase

Inhibition of this enzyme inhibits the formation of aqueous humor

Question 13

Azetazolamide

Mechanism?

Why is it rarely used?

AE?

Answer 13

Primary systemic inhibitor of carbonic anhydrase

Rarely used because of its systemic adverse effect and because topical inhibitors of carbonic anhydrase are available

AE:

• Increases the pH of the urine therefore increasing the of developing kidney stones compromised of calcium phosphate
• The metabolic acidosis may be poorly tolerated by persons with chronic lung disease who manifest chronic respiratory acidosis
• Electrolyte changes may cause drowsiness and parasthesias
• Carbonic anhydrase inhibitors are sulfonamide derivatives and people allergic to sulfonamides may have cross sensitivity

Question 14

Dorzolamide

What is the only potential problem with this drug

Answer 14

Primary topical inhibitor of carbonic anhydrase used in the eye

Does not cause systemic effects

Used three times daily so compliance might be the problem

Question 15

What is the effect of beta agonists on the eye?

Answer 15

Agonists lower intraocular pressure by increasing aqueous outflow through the canal of Schlemm

Question 16

What is the effect of beta antagonists on the eye

Answer 16

They lower intraocular pressure by decreasing aqueous synthesis

Its complex and paradoxical that both beta antagonists and agonists lower intraocular pressure

Question 17

How does epinephrine lower intraocular pressure

Answer 17

• Decreases aquoeus humor formation (alpha 2 agonism)
• increasing uvoscleral outflow (alpha 2 agonism
• increasing outflow through the canal of Schlemm (beta 2 agonism)

Epi is poorly tolerated when applied topically in the eye because it causes hyperemia and irritation

Question 18

Dipivefrin

AE?

Answer 18

diester prodrug of epinephrine

AE:

• tachycardia
• hypertension
• long term therapy - pigmented granular deposits on the eye***

Question 19

Timolol

Answer 19

non-selective beta antagonist - lowers IOP by descreasing the synthesis of aqueous humor

AE:

• Symptoms related to systemic beta-adrenergic blockade
  
  • bronchospastic disease
  • Profound bradycardia in those with sick sinuss syndrome, or 2nd or 3rd degree atrioventricular block

Question 20

What two mechanisms do alpha-2 adrenoreceptors use to decrease IOP?

Examples of such drugs?

What are their side effects?

Answer 20

• decrease synthesis of aqueous humor
• increase uveoscleral outflow

Examples are:

• Brimonide
• Apraclonidine

AE:

• eye irritation
• cardiovascular effects systemically –> sedation, dry mouth

These drugs are often used three times daily

Question 21

Latanoprost

Mechanism?

Answer 21

A prodrug that is a prostaglandin analogue

It undegoes ester hydrolysis in the eye to yield thte free acid that is agonist at the PGF receptors

Lowers IOP by increasing uvoscleral outflow

AE:

• increasing brown pigmentation of the iris and eyelids
• Increasing the length and number of eyelashes (Dersh loves this one)

Few systemic side effects (not named) and used once daily

This is the recommended go to drug for glaucoma. but if the IOP is not lowered enough, its reasonable to add a topical beta blocker, carbonic anhydrase inhibitor or a selective alpha-2 agonist.

Two meds in different classes have greater effect than one!!

Question 22

Rules of applying two topical agents in the eye

What are the two ways (mechanisms) that a topical medication can lead to systemic effects?

What can you do to reduce the systemic effects of one of these mechanisms?

Answer 22

When more than one medication is applied topically in the eye, the patient should wait 5 - 10 minutes after the first drug before instilling the second one.

Although absorption from the eye into the systemic circulation is one mechanism by which a topical eye medication produces systemic effects, another mechanism is both more important (in magnitude) and more easily prevented.

This route is passage of the drug via the nasolacrimal duct into the pharynx followed by swallowing and absorption from the GI tract.

Nasolacrimal pressure (fingers pressed against the inner corners of lower eyelids) for 2 - 3 min after instillation of an eye drop may decrease the amount of systemic absorption by this latter route.

Question 23

What is the two mechamisms of H1 antagonists in the eye?Give

examples of such drugs?

Indications or Use?

Answer 23

Block the histamine H1 receptor

Decrease mast cell degranulation - this decreases the histmine released from mast cells in response to IgE

Olopatadine and Ketotifen

Use:

• Managing the itch
• Managin excessive lacrimation

-these are associated with hay fever and allergic conjuctivitis

Question 24

Olopatadine

Answer 24

Histamine H1 antagonist

Question 25

Ketotifen

Answer 25

Histamine H1 antagonist

Question 26

When is the likelihood of developing an allergic response to an antibiotic the greatest?

Answer 26

When the antibiotic was applied topically (especially bata lactams and aminolgycosides)

Antibiotics used systemically are best avoided in the eye

Question 27

Name a common antiobiotic preparation that is an ointment

Answer 27

A bacitrin and polymyxin B combination

Allergic reactions to these are rare and neither of them are used systemically

They are both bactericidal

Bacitrin -> effective against gram(+) organisms “B for P”

Polymyxin B –> effective against gram (-) organisms

Medications formulated in an ointment need to be applied less frequently than those in solution

This combination is typically applied twice a day

Question 28

What are the ocular vasocontrictors?

Cosmetic use?

Other uses?

Answer 28

alpha adrenoceptor agonists that decrease redness associated with conjuctival hyperemia

These can be used cosmetically to decrease hangover and sleeplessness

Can be used in combination with ocular antihistamines to treat uncomfortable redness and excessive tearing associated with hay fever

Question 29

Oxymetazoline

Answer 29

These are combination vasoconstrictor and antihistamine

Used to reduce redness and extensive tearing

Question 30

What two muscles determine the size of the pupil?

Answer 30

• Iris radial muscle - causes mydriasis (stimulated by alpha-1 agonists)
• Iris sphincter muscle - causes miosis (stimulated by muscurinic agonists)

Question 31

What kind of agents can you use to achieve mydriasis?

Answer 31

alpha adrenergic agonist

muscurinic antagonists

Question 32

What muscle is involved in accomodation and what does it respond to

What is accomodation

Answer 32

The ciliary muscle causes accomodation (lens becomes more convex and shifts forward) in response to muscurinic agonists

Accomodation allows you to focus on near objects

Question 33

What is cycloplegia?

What kind of an agent stimulates it?

Answer 33

Cycloplegia is the opposite of accomodation

Makes the lens concave and shifts backward to focus on far objects (the sympathetic response)

Question 34

What prototypical muscurinic antagonists are not used in eye exams because of their long lasting effects

What are medications clinically used to produce mydriasis (3)?

Answer 34

Prototypical - Atropine and scopolamine

Commonly used meds for producing mydriasis

• Tropicalmide - M antagonist
• Cyclopentolate - M antagonist
• Phenyelphrine - adrenergic agonist –> important because it produces mydriasis without causing cycloplegia because the ciliary muscle is not under alpha adrenergic control

Phenylephrine may be less effective in producing mydriasis in patients with black irides because there is significant nonspecific binding of phenyephrine to the dark pigment in the iris**

Systemic absorption of phenyephrine can result in HTN due to peripheral vasocontriction

Question 35

What drug is used for reversal of phenylephrine-induced mydriasis?

Answer 35

Dapiprazole

It is easier to reverse mydriasis after using phenylephrine as compared to tropicamide or cyclopentolate

Question 36

What is the chemical composition of artificial tears?

What are they used for?

Answer 36

An isotonic salt solution that may also contain:

• glycerol - increases the viscocity of the solution
• polyethylene glycol (PEG) - act as lubricants
• methylcellulose derivatives (carboxymethylcellulose, hydroxypropylmethylcellulose)

Use:

• Dry eye syndromes - keratoconjuctiva sicca. Common causes include:
  • Idiopathic
  • medications
  • advanced age
  • ocular surgery
  • radiation therapy
  • autoimmune disorders (RA, Sjogren syndrome)
• Soothing agents in persons with conjuctivitis

In persons with dry eye syndrome, artificial tears are typically instilled numerous times each day because the duration of comfort following a treatment is not very long.

Activities that typically decrease the rate of blinking (e.g., reading, computer work, watching television) also increase the need for artificial tears in affected patients.

Artificial tears may also be instilled to soothe the discomfort from viral conjunctivitis (that is almost never treated with antiviral agents and that does not respond to ocular antibiotics or antihistamines).

Artificial tears may be purchased without a prescription.