NBEO - Part 1 Ocular Pharmacology

which types of drugs penetrate the cornea the best

weak bases

small, uncharged (non-ionized), lipid soluble molecules

sympathetic cell bodies are located in the

thoraco-lumbar regions

parasympathetic cell bodies are located in the

cranio-sacral region

sympathic preganglionic neurons release

Acetylcholine

parasympathetic preganglionic neurons release

acetylcholine

sympathic postganglionic neurons release

norepinephrine and epinephrine

parasympathic postganglionic neurons release

acetylcholine

preganglionic neurons are longer in which division?

parasympathetic pathway

postganglionic neurons are longer in which division?

sympathetic pathway

organs that innervate the sympathetic division have ___ receptors(s)?

alpha and beta

organs that innervate the parasympathetic division have ___ receptors(s)?

muscarinic

SLUD

major actions of the parasympathetic nervous system

Salvation

Lacrimation

Urination

Defecation

(also bronchoconstriction, mitosis and "rest and digest" functions)

major actions of the parasympathetic nervous system

Salvation

Lacrimation

Urination

Defecation

(SLUD)

also bronchoconstriction, mitosis and "rest and digest" functions

major actions of the sympathetic nervous system

bronchodilation, mydriasis, decrease in secretions, and "fight or flight" functions

iris sphincter receptor

M3 - cholinergic

Causes: miosis

ciliary muscle accommodation receptors

M2, M3 - cholinergic

Causes: constriction, increases accommodation

B2 - adrenergic

Causes: relaxation, opposes accommodation

lacrimal gland receptor

M2, M3 - cholinergic

Causes: increase tear production

iris dilator receptor

trabecular meshwork receptor

B2 - adrenergic

Causes: relaxation, increase outflow

NPCE receptors

B2, B1 - adrenergic

Causes: increase aqueous formation

Ciliary Body vasculature receptors

A2 - adrenergic

Causes: constriction, reduction aqueous formation

pilocarpine reduces IOP by

30% (first ever glaucoma med - 1870s)

3rd nerve palsies will ___ with 1% pilocarpine

constrict

(use 1% pilocarpine to differentiate a 3rd nerve palsy vs sprinter tear)

in Adie's tonic pupil the iris sphincter is ___

super sensitized (wil constrict to 0.125% pilocarpine)

0.125% pilocarpine is used in the diagnosis of _________, and is effective in constricting the pupil because of a supersensitized sphincter muscle that is a result of a _______ lesion.

A. Adie`s tonic pupil, sphenopalatine

B. Horner`s syndrome, lung

C. Adie`s tonic pupil, ciliary ganglion

C

pilocarpine main side effects

broaches, headaches and myopic shifts (HA more common with pre-presbyopes)

cataracts are from longterm use and are only problematic if located centrally

RD (uncommon but well-recognized)

secondary angle-closure glaucoma (due to lens movement forward during accommodation - PAS or PS - pupillary block)

Edrophonium (Enlon) is used in diagnosis of

Myasthenia gravis (Tensilon Test) - rapid onset (30-60 sec) and short duration (10 min)

inhibits acetylcholesterase

if ptosis improves after 1-2 min of injection, (+)myasthenia gravis

"Ed Dx"

Neostigmine (Prostigmin) is used for the treatment of

Myasthenia gravis

also limb strength evaluation (neostigmine test)

Echothiophate (Phospholine)is used in the diagnosis and/or treatment of

accommodative esotropia (direct simulation of CB muscle, decrease CNS accommodation and accommodation convergence)

also rarely used to treat glaucoma

Pyridostigmine (Mestinon) is used to treat

Myasthenia gravis

"get pyRID of the Myasthenia - tx it"

echothiophate and isofluorophate are __ acetylcholinesterase inhibitors, and they are not used for __ because of their high incidence of side effects. They are also found in ___.

irreversible, glaucoma, pesticides

"echo's on and on - irreversible"

atropine is used to reverse __ side effects

muscarinic

Pralidoxime (Protopam) reverses the effects of ____

irreversible acetylcholinesterase inhibitors

Phenelzine (Nardil) is a ___ inhibitor

MOA (mono-amino oxidase) - the enzyme that breaks down epinephrine and norepinephrine

want to be caution when taking these with adrenergic agonists

Donepezile (Aricept)

acetylcholinesterase inhibitor (Tx: Alzheimer's)

2 main symptoms of myasthenia gravis

ptosis and diplopia at the end of the day (diplopia is more common)

Which drug classification exacerbates myasthenia gravis symptoms?

beta-blockers (i.e timolol)

[-stigmine]

Neostigmine and pyridostigmine

(AChE inhibitors - reversible)

"STop ACH"

cholinergic antagonists

Scopolamine

Tropicamide

Atropine

Cyclopentolate

Homatropine

CNS toxicity is ___ likely in scopolamine vs atropine

more

Tropicamide has the ___ onset and the ___ duration of mydriatic effects. It has ___ mydriatic effect than cycloplegic - making it the standard drug for ___.

fastest, shortest, stronger, dilation.

adverse side effects for Tropicamide are ___

rare. very safe drug, even with patients with cardiovascular disease

Atropine toxicity (anticholinergic toxicity)

Mad as a hatter (confusion or disorientation due to CNS effects on the hypothalamus - rapid pulse), dry as a bone, hot as a hare, red as a beet, blind as a bat

Which patient(s) should you proceed with caution when using atropine?

patients with Down syndrome, small children, and elderly

cycloplentolate has the ___ onset and the ___ duration of cycloplegic effects. It is the standard drug for ___.

fastest, shortest, cycloplegia

Standard drop for anterior uveitis treatment?

Homatropine

Duration of mydriasis effects with atropine

7-10 days

Duration of mydriasis effects with homatropine

1-3 days

Duration of mydriasis effects with scopolamine

3-7 days

Duration of mydriasis effects with cyclopentolate

24 hours

Duration of mydriasis effects with tropicamide

4-6 hours

Duration of cycloplegic effects with atropine

7-12 days

Duration of cycloplegic effects with homatropine

1-3 days

Duration of cycloplegic effects with scopolamine

5-7 days

Duration of cycloplegic effects with cyclopentolate

24 hours

Duration of cycloplegic effects with tropicamide

4 hours

atropine onset

60-180 minutes (cycloplegic)

tropicamide onset

20-35 minutes (max cycle at 20-45 minutes)

cyclopentolate onset

20-45 minutes for mydriasis and cyclo max effects

Botox MOA

indirect muscarinic and nicotinic cholinergic receptor antagonist (block Ach at the neuromuscular junction)

True or false: epinephrine acts on all 4 adrenergic receptors?

true (acts on A1, A2, B1, B2)

true or false norepinephrine acts on all 4 adrenergic receptors?

false; does not act on B2 (acts on A1, A2, B1)

phenylephrine is a ___ agonist

alpha 1 - adrenergic agonist

(dilation only, no cyclo)

phenylephrine is used to differentiate between?

episcleritis and scleritis (blanching of conj vessels on application = (+)episcleritis)

drop will not be able to penetrate and blanch scleral vessels

muller's muscle responds to

alpha 1 receptor stimulation - phenylephrine causes palpebral widening

phenylephrine 10% is used to

break posterior Synechiae only - high dose has adverse cardiovascular effects (HTN crisis, cardias arrhythmias)

Phenylephrine is contraindicated in patients ....

taking MAOIs (monoamine oxidase inhibitors), tricyclic antidepressants (TCAs) and atropine. Also patients with Graves' (increases sympathetic innervation)

[-zoline]

naphazoline (naphcon) and tetrahydrozoline (visine)

topical ocular decongestants

greater alpha than beta effect - potential to depress CNS

nephcon A - OTC drug that contains nephazoline and antihistamine

in isolation phenylephrine is __ to provide a a fixed dilated pupil.

unable

alpha 2 agonists are used for glaucoma Tx for their effects on ____ and ____

aqueous humor production (decreases), uveoscleral outflow (increases)

brimonidine, apraclonidine

[-onidine]

alpha 2 agonist

brimonidine (alphagan), apraclonidine

brimonidine is 30x ___ selective than aproclinidine

more

Alphagan has showed

nueroprotective properties

Alphagan-P decreases the incidence of follicular (but allergic) conjunctivitis vs Alphagan with

purite as the preservative

Alphagan-P comes in 0.15% and 0.1%

Alphagan comes in 0.2%

brimonidine causes mydriasis or miosis

miosis

most common systemic side effect of brimonidine and apraclonidine

dry mouth

brimonidine is contraindicated in patients taking

monoamine oxidase inhibitors (MAOIs)

Tachyphylaxis

rapid decrease in response to a drug

which drug cannot be used for longterm glaucoma treatment due to tachyphylaxis

apraclonidine

not effective in chronic therapy - efficacy is reduced after 8 days of Tx

commonly used for IOP spikes before and after surgery

which drugs can be used to diagnose Horner's syndrome

apraclonidine, phenylephrine, cocaine, hydroxyamphetamine

when is anisocoria greatest in Horner's syndrome?

in the dark

True or false: If a ptosis and dilation lag exists then the diagnosis without pharmacological testing can be made for Horner's syndrome.

True. no pharmacological testing is needed if a biotic pupil is present it lags on dilation in the dark with a ipsilateral lid ptosis.

healthy eye will always ___ with cocaine

dilate

Horner's syndrome eye will ___ with cocaine

not dilate (regardless of the location of the sympathetic pathway lesion)

healthy eye will ___ with apraclonidine

remain unchanged (no effect)

Horner's syndrome eye will ___ with apraclionidine

dilate due to hyper-sensitized alpha 1 receptors

if the pupil does not dilate with hydroxyamphetamine then the lesion is

postganglionic

hydroxyamphetamine causes the release of norepinephrine from postganglionic neurons, so the postganglionic neuron must be damaged

if the pupil dilates with hydroxyamphetamine then the lesion is

preganglionic

hydroxyamphetamine causes the release of norepinephrine from postganglionic neurons, so the postganglionic neuron must still be intact

phenylephrine 1% causes full dilation in Horner syndrome patients with a ___ lesion

postganglionic

mech. unknown - believed to be hypersensitivity of postganglionic adrenergic receptors

why does brimonidine produce miosis?

A1 receptors on the radial dilator muscle cause mydriasis. Brimonidine is selective for α2 receptors, which are present on presynaptic sympathetic nerve terminals, and stimulation of these in a normal pupil causes miosis due to a reduction in norepinephrine production and release at the nerve terminal, combined with the unopposed action of the iris sphincter muscle.

"ASH CiTy"

order of cholinergic antagonistic from longest onset/duration of action

Atropine

Scopolamine

Homatropine

Cyclopentolate

Tropicamide

2 adrenergic receptors that can cause glaucoma if they are overstimulated by adrenergic agonists

B2 - increase secretion of aqueous

A1 - dilation --> PAS

3 MOA for TCA (tricyclic antidepressants)

increase epinephrine, anticholinergic, increase serotonin

"2 lungs, 2 eyes"

Beta-2 mainly in the lungs (bronchi) and eyes (NCPE)

"1 heart"

Beta-1 mainly in the heart

[-olol]

beta blocker

sympathetic nervous system is __ at night

off (causing pupillary miosis, and rendering adrenergic antagonist essentially ineffective at night)

timolol concentration for Caucasian pt

0.25% Qam

timolol concentration for African American pt

0.5% Qam

neuroprotective drugs

brimonidine and betaxolol