Pharm I: Exam III

Topical otic anti-infectives

Includes agents that make the environment inhospitable for pathogens to reproduce - analgesics, abx (erythromycin, aminoglycosides), antineoplastic, loop diuretics

Fluoroquinolones - broad coverage, affect pseudomonas species

May contain corticosteroids for anti-inflammatory, anti-pruritic, and anti-allergenic effects

Risk of ototoxicity

Anti-infectives without steroids

Ofloxacin, neomycin, bacitracin, mupirocin, polymyxin B/neomycin/bacitracin

Anti-infectives with steroids

Ciprofloxacin/hydrocortisone, ciprofloxacin/dexamethasone, hydrocortisone/neomycin/polymixin B, hydrocortisone/neomycin,colistin, chloroxylenol/pramoxine/hydrocortisone

Topical otic anti-infective

MOA: bacteriostatic or bactericidal

Clinical use: inflammatory skin diseases and pruritic dermatoses

Adverse reactions: ear pain, ear discomfort or irritability, ear residue; cytotoxicity with neomycin (reversible)

Considerations: ototoxicity with neomycin, especially if TM perforated

Acid-alcohol solutions

Acetic acid/aluminum acetate, acetic acid/propylene glycol, acetic acid/propylene glycol/hydrocortisone, isopropyl alcohol/glycerine, isopropyl alcohol/propylene glycol

Supplements ears slightly acidic environment

Induces a drying out of cellular infective agents

Acid-alcohol solutions MOA

Provides a topical, antibacterial, and antifungal effect

Acid-alcohol solutions clinical use

Treatment of superficial infections of the auditory canal caused by organisms susceptible to the action of the antimicrobials and complicated by inflammation (ex. otitis externa)

Acid-alcohol solutions adverse reactions

Stinging or burning due to the acidic pH, local irritation

Otic analgesics

Acetic acid/benzocaine/antipyrine/glycerine, benzocaine/antipyrine/propylene glycol

Numb, increase pH, dry out ear

Antipyrine MOA

Otic analgesic

Effects the prostaglandin system (anti-inflammatory effects)

Benzocaine MOA

Otic analgesic

Blocks the nerve sodium channel and terminates signal propagation

Glycerin MOA

Otic analgesic additive

Hydroscopic

Attracts/absorbs moisture from the air, dries out the ear

Otic analgesic clinical use

Tx of mild pain along external auditory canal

Ceruminolytics

Carbamide peroxide, triethanolamine polypeptide oleate

Soften and remove cerumen from the external auditory canal

Water-based, oil-based, or non-water-based/non-oil-based

Ceruminolytics MOA

Water-based: soften wax by swelling dried ear canal epithelium

Oil-based: soften wax by placing oily glandular material in solution

Ceruminolytics clinical use

Removal of excess or impacted cerumen

Ceruminolytics adverse reactions

Mild itching, burning, ear pain, erythema of the ear canal

Ceruminolytics contraindications

Perforated TM

Ear discharge, pain, rash, or irritation around the ear

Ceruminolytics consisderations

If drops remain in ear longer than 30min, inflammation can occur

Do not use for longer than 4 days as it can damage TM

Ophthalmic anesthetics

Proparacaine 0.5% solution, tetracaine 0.5% solution, lidocaine

Ophthalmic anesthetics MOA

Agents penetrate to sensory nerve endings in corneal tissue

Once applied topically, these work within 20-30 seconds and for a period of up to 15min

Ophthalmic anesthetics clinical use

Produce local anesthesia of short duration for ophthalmic procedures, including measurement of intraocular pressure, removal or foreign bodies and sutures, and conjunctival and corneal scraping in diagnosis and gonioscopy

Produce local anesthesia prior to surgical procedures such as cataract extraction, usually as an adjunct to locally injected anesthetics

Ophthalmic anesthetics adverse reactions

Tetracaine may cause burning or stinging sensation when first applied

With repeated use over several days, proparacaine may cause severe keratitis, opacification, and scarring of the cornea resulting in loss of vision

Ophthalmic anesthetics considerations

Proparacaine is highly toxic if it enters systemic circulation

Agents interfere with healing processes when use is prolonged in acute injuries

Ophthalmic anti-infectives

Sulfactemide solution and ointment

Erythromycin ointment - commonly used in children

Tobramycin ointment and drops

Ciprofloxacin ophthalmic drops

Polymixin B/trimethoprim ophthalmic

Polymixin B/bacitracin ophthalmic ointment

Gentamicin ophthalmic

Moxifloxacin

Sulfacetamide MOA

Synthetic sulfonamide

Effective against E. coli, Klebsiella, and N. gonorrhoeae

Bacteriostatic, blocking the synthesis of folic acid in susceptible bacteria

Tobramycin MOA

Water-soluble, broad-spectrum aminoglycoside

Exact mechanisms as bactericidal agent unknown

Bacitracin MOA

Bacteriostatic

Inhibits the incorporation of amin acids and nucleotides into the bacterial cell

Wide spectrum of activity makes it useful against gram-positive and gram-negative bacteria

Erythromycin MOA

Bacteriostatic

Binds to the 50S ribosomal subunit, preventing protein synthesis in the bacteria

Use is mainly against gram-positive organisms - S. pyogenes, S. pneumoniae, S. viridans, Corynebacterium diphtheriae

Fluoroquinolones MOA

Bactericidal

Inhibit DNA synthesis in the invading bacteria which leads to cell death

Spectrum is mostly gram positive - staph, S. pneumoniae, H. flu, some species of enterobacter and Pseudomonas

Synthetic abx, chemically unrelated to penicillins and cephalosporins

Polymixin B MOA

Bactericidal

Used in ophthalmic preparations because of its high affinity for phospholipids in the cell wall

Binds to lipids increasing cell wall permeability leading to cell death

Ophthalmic anti-infective clinical use

Bacterial infections of the eye

Ophthalmic anti-infective adverse reactions

EENT: local irritation, super infections with long-term use

Misc: hypersensitivity reactions to sulfacetamide possible

Ophthalmic anti-infective contraindications

Ophthalmic tobramycin should not be used if systemic aminoglycosides are also being prescribed because serum concentrations may be affected, leading to toxicity

Ophthalmic anti-infective considerations

Monitor for hypersensitivity reactions, including lid itching, erythema, and congestion of conjunctiva

Bacitracin may induce transient blurry vision upon application

Fluoroquinolones have been found to create a white crystalline deposit/precipitate along the edges of the cornea

If sulfacetamide solution has turned dark, it has lost its potency and should be discarded

Ophthalmic mast cell stabilizers

Nedocromil 2% solution, cromolyn sodium 4% solution, lodoxamide 0.1% solution

Can be found in combinations with a corticosteroid to further reduce inflammation

Ophthalmic mast cell stabilizer MOA

Inhibit degranulation of mast cells after exposure to a specific antigen

Mast cell inhibition prevents inflammation because histamine and slow-releasing substances of anaphylaxis are unable to produce their profound characteristics

Ophthalmic mast cell stabilizer clinical use

Allergic conjunctivitis

Ophthalmic mast cell stabilizer adverse reaction

EENT: transient stinging or burning on application, blurry vision, photophobia mydriasis, rhinitis, sinusitis

Neuro: headache

Ophthalmic antihistamines

Azelastine, epinastine, emedastine, ketotifen, levocabastine, olopatadine

Ophthalmic antihistamine MOA

Exhibits noncompetitive H1-receptor antagonist and mast cell stabilizer properties

Blocks the effects of histamine released during allergic reactions and blunts symptoms

Ophthalmic antihistamine clinical use

Temporary relief of itching associated with seasonal and typical allergic conjunctivitis

Ophthalmic antihistamines adverse reactions

EENT: transient stinging or burning on application, blurry vision, photophobua mydriasis, rhinitis, sinusitis

Neuro: headache

Ophthalmic vasoconstrictors

Naphazoline, oxymetazoline, tetrahydrozoline

Ophthalmic vasoconstrictor MOA

Weak sympathomimetic agents

Constrict the blood vessels in the conjunctiva

Ophthalmic vasoconstrictor clinical use

Temporary relief of redness in the eye caused by minor irritants or allergic conjunctivitis

Ophthalmic vasoconstrictor adverse reactions

EENT: transient burning or stinging on application, transient blurry vision, rebound redness with frequent administration

Ophthalmic vasoconstrictor contraindications

Narrow-angle glaucoma - may increase IOP

Ophthalmic lubricants

Refresh Lacri-Lube eye ointment, Lacrisert, Allergen's Refresh Celluvisc, HypoTears, Visine Tears, Nature's Tears All Natural Eye Mist, Murine Tears

Contain agents that provide hydration, maintain moisture, and protect the eye

Viscous (ointment) or non-viscous

Contain combinations of inert agents: demulcents, hygroscopic agents, hypertonicity agents, polymers, surfactants

Demulcents

Form a protective film on the ocular surface to allow epithelial repair

Hygroscopic agents

Draw water into the corneal cells to protect against hyperosmotic stress

Hypertonicity agents

Placed in ocular lubricants for relief of corneal edema

Polymers

Act as viscosity-increasing agents that bind to natural tears and to the mucosal surface of the eye to form a protective, lubricant film

Also prolong the contact time of the ophthalmic agent on the ocular surface

Surfactants

Surface active agents that act as wetting agents to lower fluid surface tension and lubricate the eye

Ophthalmic lubricants clinical use

Supplement natural tears

Act as viscosity enhancers to promote increased contact time of the ophthalmic agent with the ocular surface

Sooth corneal edema secondary to certain ocular diseases

Ophthalmic lubricant adverse reactions

discharge with long-term use

Miotics

Indirect Acting: Echothiophate (powder that must be reconstituted)

Direct Acting: Carbachol, Pilocarpine

Miotics MOA

Cause the sphincter muscle of the iris to constrict which causes constriction of the pupil (miosis)

Contracts the ciliary muscles attached to the trabecular meshwork: opens up Sclemm's canal, increases outflow of aqueous humor, decreases IOP

Miotics clinical use

Treatment of glaucoma - open angle

Pilocarpine used to treat dryness of the eyes caused by Sjogrens syndrome

Miotic adverse reactions

blurry vision

Systemic effects: abd cramps, diarrhea, watering mouth, excessive sweating, urinary incontinence, muscle weakness

Miotic considerations

Miosis makes it difficult for pts to adjust to shifts in light

Topical prostaglandin agonists

Latanorost 0.005% solution, bimatoprost 0.3% solution, travoprost 0.004% solution, unoprostone 0.15% solution

Topical prostaglandin agonist MOA

Selective agonists of RF receptor (prostaglandin receptor)

Increase the outflow of aqueous humor which reduces IOP by ~6-8mmHg (23-35%)

Topical prostaglandin agonist clinical use

Treatment of open-angle glaucoma

Topical prostaglandin agonist adverse reactions

Sensation of foreign body in the eye, permanent discoloration of the iris with brown pigment (when used over months), eyelash changes, conjunctival hyperemia

Topical prostaglandin agonist contraindications

Cannot be used during pregnancy or breastfeeding

Not to be used in children

Use with caution in those with asthma, COPD, or other pulm diseases

Topical prostaglandin agonist considerations

Can permanently discolor the iris with a brown pigment when used over a period of months

Carbonic anhydrase inhibitors

Brinzolamide 1% solution, dorzolamide 2% solution, methazolamide 25-50mg tab, acetazolamide 250-500mg tab

Carbonic anhydrase inhibitor MOA

Decrease the volume of sequestered fluid (especially aqueous humor) by slowing the action of the enzyme carbonic anhydrase

Decreases IOP

Carbonic anhydrase inhibitor clinical use

Treatment of open-angle glaucoma

Carbonic anhydrase inhibitor adverse reactions

EENT: burning sensation, eye discomfort, blurred vision, eye redness, lacrimation, photophobia, xerophthalmia (dorzolamide and brinzolamide)

Derm: rash, alopecia, SJS

GI: bitter or altered sense of taste with dorzolamide and brinzolamide

GU: kidney stones (crystalluria with acetazolamide)

Hem: blood dyscrasias, bone marrow depression (acetazolamide)

Carbonic anhydrase inhibitor interactions

Acetazolamide and methazolamide are sulfa derivatives and can cause drug interactions with salicylates, pheytoin, quinidine, and cyclosporine

Use cautiously in pts with DM, gout, or pulm disease

Sympathomimetic agents

Dipivefrin 0.1%, epinephrine 1-2%

Sympathomimetic agent MOA

Dipivefrin: readily absorbed through the cornea and into the anterior chamber of the eye because it is a more lipophilic compound than epi

Converted by enzyme hydrolysis to epi in the eye's ocular fluid where it serves as direct-acting to lower IOP by:

Decreasing aqueous humor production

Constricting conjunctiva blood vessels (mydriatic effect) thus increasing intraocular fluid outflow

Sympathomimetic agent clinical use

Treatment of open-angle glaucoma by reducing elevated IOP

Can be used to treat ocular hypertension

Sympathomimetic agent adverse reactions

Cv: tachycardia, palpitations, HTN

EENT: stinging, eye irritation, increase in tears, brow pain, colored spots on the inner lining of the eye or the surface of the eye may develop with chronic use but are harmless

Neuro: sweating, tremors, lighteheadedness, nervousness

Sympathomimetic agent interactions

If significant systemic absorption of ophthalmic epi occurs, then concurrent use of cyclopropane, halothane, or chloroform may increase risk of severe ventricular arrhythmia - not to be used in pts going to surgery

TCA’s potentiate cardiovascular effects of epi —> arrhythmia, HTN, tachy

Concurrent use of ophthalmic betaxolol, levobunolol, or timolol with ophthalmic dipivefrin may provide a beneficial additive effect in lowering IOP

Concurrent use of digitalis glycosides may increase risk of cardiac arrhythmias

Concurrent use of systemic anthistamines may result in potentiated effects of epi

Sympathomimetic agent considerations

Use in caution with cerebrovascular insufficiencies, cardiovascular disease, hyperthyroidism, HTN

Because of risk of severe ventricular arrhythmias with anesthetics, therapy with dipivefrin should be interrupted prior to pts receiving general anesthesia

Alpha-2 adrenergic agonist

Apraclonidine 0.5%, 1%, brimonidine 0.2%

Alpha-2 adrenergic agonist MOA

Mimic (by direct action) the activity of epi on the dilator muscle of the iris causing dilation (mydriasis)

Decreases congestion in the blood vessels of the conjunctiva which reduces IOP by reducing production of aqueous humor and increasing outflow

Alpha-2 adrenergic agonist clinical use

Treatment of glaucoma

Prophylactic measure to prevent IOP spiking following laser surgery

Alpha-2 adrenergic agonist adverse reactions

EENT: lid retraction, mydriasis, local irritation, conjunctival blanching, visual disturbances, dry mouth, allergic conjunctivitis

CNS: drowsiness, foreign body sensation in eye, headache

Alpha-2 adrenergic agonist interactions

Concurrent use with MAOIs may precipitate a hypertensive crisis

Beta blockers

Betaxolol, carteolol solution, levobunolol, timolol 0.25% and 0.5%

Selective (betaxolol, carteolol) vs. nonselective (levobunolol, timolol)

BB MOA

Reduce IOP by interfering with cAMP (used to help produce aqueous humor in the ciliary process of the eye)

BB clinical use

Treatment of open-angle glaucoma

BB adverse reactions

EENT: burning and stinging upon application, blurred vision, corneal staining, eye pruritus

CV: bradycardia, hypotension

Pul: bronchospasm after long-term use

BB interactions

Systemic and ophthalmic should not be used concurrently because of additive effect (bradycardia and asystole)

BB considerations

Caution with diabetes (interfere with glycogenolysis), hyperthyroidism (mask sx), Raynauds disease or any other peripheral vascular disorder (can exacerbate)

Ophthalmic osmotics

Mannitol

Used for acute interventions until surgical treatment is available

Ophthalmic osmotic MOA

Makes osmotic pressure of glomerular filtrate hypertonic, allowing water and electrolytes to be pulled passively out of cellular and interstitial spaces

Ophthalmic osmotic clinical use

Treatment of edema

Reduction of oliguric renal failure

Reduction of oliguric renal failure and intracranial and intraocular pressure.

Ophthalmic osmotic adverse reactions

EENT: blurred vision, rhinitis, rebound increased IOP

CV: transient volume expansion, CP, edema (initially), tachycardia

GI: nausea, vomiting, thirst

GU: renal failure

Meta: dehydration, hyperkalemia, hypernatremia, hypokalemia, hyponatremia

Misc: phlebitis at injection site

Neuro: confusion, headache

Ophthalmic osmotics interactions

Hypokalemia may result which increases risk of digitalis/digoxin toxicity

Ophthalmic osmotic contraindications

Drug hypersensitivity

Cardiac impairment

Pulm edema

Dehydration

Intracranial bleed

Kidney impairment

Pupillary dilation

Cyclopentolate 0.5%, 1%, 2% solution, homatropine 1%, 5% solution, tropicamide

Pupillary dilation MOA

Muscarinic antagnoists produce mydriasis by blocking parasympathetic receptors that if stimulated would normally cause pupils to constrict

Result is an overbalance toward sympathetic input which dilates the pupil

Pupillary dilation clinical use

Used as a cycloplegic before eye exams

Pupillary dilation adverse reactions

CV: tachycardia

Derm: flushing

EENT: blurry vision, photophobia

GI: dry mouth

Pupillary dilation contraindications

Closed-angle glaucoma

Infants