thoracolumbar, generalized distribution and response. In orbit

• after synapsing in the superior cervical ganglion, dilator muscle,
• blood vessels- uveal tract
• smooth muscles (Mueller's lid muscles)
• lacrimal gland (vessels)

more specific innervation

in the orbit:

• fibers start in Edinger-westphal nucleus,
• CN III oculomotor never,
• ciliary ganglion,
• ciliary muscles
• sphincter muscles
• CN VII facial nerve
• lacrimal gland

α₁

α₂

 β₁

β₂

(NE and EPI)*

* post ganglinoic, sympathetic fibers release NE at the synapses in the eye. NE does NOT act on beta 2 receptors.

circulating EPI from adrenal glands act on beta 2 receptors

• all ganglia from SNS & PNS preganglionic fibers have ACh released to act on post-ganglionic cell bodies (nicotinic receptors that respond to ACh) as well as neuromuscular junctions.

beta 1 or beta 2

SNS stimulation/aqueous humor: more beta 2

• high SNS-= higher aqueous humor production

low SNS (sleep)= low aqueous humor production

all BV's = alpha and/or beta

alpha 1 constrict: mucious membr, conj vessels, laricmal apparatus. in retina, low O2 tension = dilate, high O2 tension =constrict

Beta 2 relax:

bit as significant dilation, alpha1 predominant

alpha 1 receptor activated by NE = retraction lid muscle-- widen palperal fissure.

lack of NE: PTOSIS associated with horner's syndrome (denervation of sympathetic)

ptosis

miosis,

anhydrosis (lack of sweating on same side_ 

pupil size

aquous production: alpha2 decrease it when stimulated,

beta 2 stimulated will increase aqueous production

Mydriatic

alpha 1 agonist --> iris dilator muscle

alpha1 agonist: phenylephrine = decrease aqueous humor production

alpha 2 agonist: decrease aqeuous huumor prodution

beta 2 agonist= INCREASE aqueous humor production.

vasoconstrictor=

decongestant of conjunctiva

Norephineprine and

receptors NE acts on

alpha  and beta1 receptors,

little clinical use

MOA: good systemic vasoconstrictor ACTS on alpha1, alpha2 & beta1 receptor

Weak mydriatic,

potent vasoconstrictor.

Decreases IOP,

alhpha and beta receptors play role

1. vasoconstriction (vasoconstricts area of injection to prevent local anesthetics from being too rapidly absorbed),
2. mydriasis not very effective,
3. glaucoma tx: OPEN ANGLE ONLY (no longer used) [ cos narrow angle pt will have mydriasis with EPI and close the angle)

receptor: alpha1 direct agonist

MOA: adrenergic mydriatic

clinical uses: decongestant-vasoconstriction, mydriasis (most common), active light reflex so add cycloplegic tropicamide, decreased sympathetic tone in old folk, decreased effect in dark irrides,

max effects in 60min; recovery in 5-7 hrs.

Effects in eye: counteract miotic agents, treat ptosis from sympathetic denervation, dianosis of horner's syndrome,  break posterior synechia formed during inflammation (disrupts aqueous humor ouflow, can increase iop),

decrease ciliary spasm,

treat miotic cysts from ACh-esterase inhibtior.

Toxicities of Phenylephrine (neo-synephrine)

Toxicities:

• thyrotoxicosis (thyroid storm = incr blood pressure)
• Coronary artery disease: occluded vessels worse off by increase in BO
• untreated HTN,
• CV effects: hypertension, subarachnoid hemorrhage (incr BP), ventricular arrythmia, tachycardia, reflex bradycardia, blanching of the skin.

• transient pain & excess lacrimation
• keratitis
• liberation of iris pigment- floaters esp in ptwith dark irides that looks like pigment dispertion (contracting dilator muscle breaks 
• post dilation miosis- older pt
• rebound congestion(after blood vessels go back to normal after being constricted)
• conjunctival hypoxia
• angle closure

alpha agonist: alpha 2 selective.

MOA: alpha 2 post-synaptic receptors

inhibit adenylate cylase, decrease cAMP,

decreased aqueous production,

increased uveoscleral outflow.

beta 2 receptor not affected by apraclonidine but can be used to increase the same effects by further decreasing aqueous humor production via a beta blocker.

decrease IOP

treat Primary open angle glaucoma,

used in horner's syndrome dx: will dilate

• allergic reaction: itching & irritation like hypersensitivity
• alpha1 stimulation
• mydriasis
• lid retraction
• conjunctival blanching
• systemic effects of dry mouth, fatigue
• lethargy, HA, symptoms of head cold

alpha 2 selective adrenergic receptor agonist:

MOA decrease adenylate cylcase and cAMP, decreased aqueous production, increased uveoscleral outflow, neuroprotictive.

P = purite stays in tear film longer

frequent:

hyperemia,

stinging,

burning,

blurred vision,

foreign body sensation,

allergic reactions: 5-10% (less than apraclonidine/iopidine)

systemic: drymouth, headache, fatigue, lethargy, drowsiness

OTC: 0.012%, 0.035%

Rx- 0.1%

OTC: 0.05%

OTC 0.025%

Relieve minor irriation, harmless, unless narrow angle&/ abraded cornea

risk of rebound hyperemia,

naphazoline + antihistamine (OTC)

0.0125%, 0.03%, Rx- 0.1%

other sympatomimetics hydroxyamphetame 1%, Paredine

hydroxyamphetamine + tropicamide, 0.25% = Paremyd

MOA

indirect acting:

stimulates release of NE, blocks reuptake and some inhibition of MAO.

1% soln: mydriatic

no dilation in post-ganglionic SNS (yes dilation in preganglionic damage) denervation

same onset and duration of action as phenylephrine

non slective beta blocker!

decrease sympathetic= decreased aqueous production,

fewer adverse reactions,

last 24hrs,

7x more potent than propranolol

good penetration, dark & light irides respond well,

no change in pupil size or accomodation,

decreased CNS effects vs propranolol.

indirect

block NE reuptake

does mydriasis, vasoconstriction,

anesthesia

Horners diagnosis: reduced dilation or absent in horner's eye regardless of location of lesion

hydroxyamphetamine 1% (in post),

cocaine (in pre and post)

alpha BLOCKER, discontinued

reverse phenylephrine mydriasie, actions on tropicamide induced mydriasies

Conjunctival hypermia (80%), burning (50%)

corneal edema,

ptosis,

lid edema,

erythema

0.5% solution better than pilocarpine since less risk of secondary pupil block angle closure.

use in all oen angle glaucoma,

not appropriate for chronic treatment of narrow angle glaucoma, used in acute angle closure attacks,

more effective, less toxicity comprd to pilocarpine

1. irritation & lacrimation
2. dry eye
3. allergic blepharoconjunctivitis
4. corneal anesthesia/ superficial punctuate keratitis
5. blurred vision w/ or w/o transient myopia
6. uvieitis
7. myasthenic sx: diplopia, ptosis, EOM paresis
8. escape/tolerance; short term = w/in a couple weeks toleracne happens, take them off it. long term drift= as they continue taking drugs for mos to yrs the IOP starts to creep back up

1. Cardiovascular & respiratory =DEADLY
2. CNS: most frequent
3. GIT, dermatologic, hypoglycemia

deadly cardiovascular side effects: bradycardia, conduction arrhythmias, hypotension, raynaud's phenomenon = pain in extremeties due to decrease oxygen from beta blocking of vasodilation,

fluid retention

Deadly pulmonary toxicities: bronchoconstriction/bronchospasm, asthma, dyspnea

frequent CNS: amnesia, derpession, confusion, HA, migraine prophylazis,

imptoence, insomnia, myasthenia gravis

bronchial asthma, history of bronchial asthma, severe chronic obstructive pulmonary disease,

bardycardia, severe heart block, overt cardiac failure,

children & infants

which of these beta blockers that are selective?

a) levobunolol (betagan)0.5%, 0.25%

b) timolol (alphagan-P)0.25%,0.5%

c) metipranolol (optipranolog) 0.3%

d) betaxolol (betoptic-S) 0.25% suspension

e) carteolol (ocupress) 1% soln

1. Combigan (brimonidine 0.2% + timolol 0.5%)

2. Cosopt (dorzolamide 2.0% and timolol 0.5%)

generic timolol,

metipranolol,

timolol hemihydrate

timpotic-XE or timoptic in ocudose,

alphagan P,

Travatan Z