Opthalmic pharmacology - Dersh Flashcards
The anterior and posterior chambers of the eye are filled with what?
What is the composition?
acqueous humor - similar in composition to cerebrospinal fluid
What produces aqueous humor and where is it secreted into?
Aqueous humor is secreted by the epithilial cells that cover the ciliary body and it is secreted into the posterior chamber
In what two ways does the aqueous humor exit the anterior chamber?
- Canal of Schlemm –> that is a venous sinus
- Reabsorption into the ciliary muscle –> uvoscleral flow
Genetically, what can put someone at an increased risk of developing acute angle closure glaucoma?
Give an example of what can precipitate the glaucoma
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
What are the two types of open angle glaucoma?
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)
What is the gold standard technique to measure intraocular pressure?
Describe the procedure
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.
What is the general mechanism used by medication in the treatment of primary open angle glaucoma?
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)
Pilocarpine
Mechanism?
AE?
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
Carbachol
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
Echothiophate
Mechanism?
AE?
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
Physostigmine
An irreversible cholinesterase inhibitor
An alternative to echothiophate
Formation of aquoeus humor is dependant on the reaction catalyzed by which enzyme?
carbonic anhydrase
Inhibition of this enzyme inhibits the formation of aqueous humor
Azetazolamide
Mechanism?
Why is it rarely used?
AE?
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
Dorzolamide
What is the only potential problem with this drug
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
What is the effect of beta agonists on the eye?
Agonists lower intraocular pressure by increasing aqueous outflow through the canal of Schlemm
What is the effect of beta antagonists on the eye
They lower intraocular pressure by decreasing aqueous synthesis
Its complex and paradoxical that both beta antagonists and agonists lower intraocular pressure
How does epinephrine lower intraocular pressure
- 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
Dipivefrin
AE?
diester prodrug of epinephrine
AE:
- tachycardia
- hypertension
- long term therapy - pigmented granular deposits on the eye***
Timolol
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
What two mechanisms do alpha-2 adrenoreceptors use to decrease IOP?
Examples of such drugs?
What are their side effects?
- 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
Latanoprost
Mechanism?
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!!
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?
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.
What is the two mechamisms of H1 antagonists in the eye?Give
examples of such drugs?
Indications or Use?
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
Olopatadine
Histamine H1 antagonist
Ketotifen
Histamine H1 antagonist
When is the likelihood of developing an allergic response to an antibiotic the greatest?
When the antibiotic was applied topically (especially bata lactams and aminolgycosides)
Antibiotics used systemically are best avoided in the eye
Name a common antiobiotic preparation that is an ointment
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
What are the ocular vasocontrictors?
Cosmetic use?
Other uses?
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
Oxymetazoline
These are combination vasoconstrictor and antihistamine
Used to reduce redness and extensive tearing
What two muscles determine the size of the pupil?
- Iris radial muscle - causes mydriasis (stimulated by alpha-1 agonists)
- Iris sphincter muscle - causes miosis (stimulated by muscurinic agonists)
What kind of agents can you use to achieve mydriasis?
alpha adrenergic agonist
muscurinic antagonists
What muscle is involved in accomodation and what does it respond to
What is accomodation
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
What is cycloplegia?
What kind of an agent stimulates it?
Cycloplegia is the opposite of accomodation
Makes the lens concave and shifts backward to focus on far objects (the sympathetic response)
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)?
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
What drug is used for reversal of phenylephrine-induced mydriasis?
Dapiprazole
It is easier to reverse mydriasis after using phenylephrine as compared to tropicamide or cyclopentolate
What is the chemical composition of artificial tears?
What are they used for?
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.
