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196 Cards in this Set
- Front
- Back
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There are three TIGR/MYOC mutations found in 1q linked glaucoma families in Juvenile Open Angle Glaucoma. Name them.
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Two point mutations: Tyr430His and Gly357Val
One nonsense mutation: Gln361Stop |
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What are the three common underlying features of POAG?
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1. an elevated IOP that is too high for function of the optic nerve head
2. Progressive atrophy of the optic nerve 3. visual field loss |
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What are the two common underlying features of normal tension open angle glaucoma (NTOAG)?
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1. Progressive atrophy of the optic nerve
2. Visual field loss |
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What is the most likely cause of elevated IOP in POAG?
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From impaired outflow of aqueous humor due to degeneration and subsequent collapse of TM. In a smaller percentage, due to excessive secretion of aqueous humor.
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What are risk factors of POAG?
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1. Age
2. Family History (increase 3-5x) 3. Race (afro 4-5x more than whites) 4. Systemic diseases: diabetes, hypertension |
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Ocular risk factors of POAG?
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1. elevated IOP
2. large cup to disc ration (>0.5) 3. optic nerve damage or loss 4. high myopes |
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What is the major therapeutic effort for POAG?
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To prevent progressive visual loss
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Describe the adrenergic innervation to the radial muscle of the iris (iris dilator)
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a. mainly alpha 1; very few beta
b. secondary innervation maintains persistent tone 3. contraction results in mydriasis |
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Describe the adrenergic innervation to the sphincter muscle of the iris.
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a. alpha and beta in small, but equal amounts
b. responds poorly to adrenergic stimulation c. beta activation causes relaxation:mydriasis |
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Describe the adrenergic innervation to the ciliary muscle.
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a. mainly beta, very few or no alpha
b. relaxation: far vision |
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Decribe the adrenergic innervation of the aqueous humor (Posterior Trabecular meshwork and Schlemm's canal).
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a. Beta2: increased outflow
b. Alpha2: sligh decrease in production |
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Describe the adrenergic innervation to the conjunctival blood vessels.
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a. alpha: vasoconstriction
b. beta: vasodilation |
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Describe the cholinergic muscarinic innervation of the sphincter muscle of the iris.
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a. primarily determines pupil size
b. contraction:miosis c. predominantly AChM3 and some AChM2 receptors |
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Describe the cholinergic muscarinic innervation of the ciliary muscle.
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a. Contraction: accommodation and increased aqueous outflow
b. Predominantly AChM2 receptors |
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Describe the cholinergic muscarinic innervation of the ciliary body and process
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a. produces aqueous humor
b. predominantly AChM3 with some AChM2 receptors and traces of AChM4 |
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Name the type of cholinergic nicotinic receptors found in:
a. all autonomic ganglia b. adrenal medulla c. NMJ |
a. all autonomic ganglia: C6 Type
b. Adrenal Medulla: C6 Type c. NMJ: C10 Type |
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Name and describe the cholinergic muscarinic receptors found in the parasympathetic postganglions of the heart
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AChM2 have inhibitory effects such as decreasing heart rate. It can open K+ channels and inhibit adenylate cyclase
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Name and describe the cholinergic muscarinic receptors found in the parasympathetic postganglions of the smooth muscles
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AChM2
AChM3: can activate PLC-beta causing contraction of smooth muscle |
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Name and describe the cholinergic muscarinic receptors found in the parasympathetic postganglions of the secretory glands
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AChM3 can activate PLC-beta causing exocrine secretion
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Name and describe the cholinergic muscarinic receptors found in the parasympathetic postganglions of the CNS
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AChM1: have stimulatory effects, can close K+ channels, activate PLC and activate PLA2
AChM2: can open K+ channels and inhibit adenylate cyclase AChM3: have stimulatory effects: can activate PLC-beta AChM4: inhibit adenylate cyclase, inhibit Ca2+ channels causing presynaptic inhibition of neurotransmitter release AChM5: can activate PLC-beta with unknown effects |
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In the ANS, where are the (i) alpha1-adrenergic receptors and (ii) alpha2-adrenergic receptors found?
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(i) postsynaptic
(ii) presynaptic |
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In general (except the heart and gut) what does stimulation of alpha adrenergic receptor result in?
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CONTRACTION of smooth muscle in erector pili, iris radial muscle, splenic capsule, uterus, ureter, vasculature, vas deferens, etc.
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Rank the order of potency for alpha1 receptors to ligands
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Epinephrine > Norepinephrine > Dopamine > Isoproterenol
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Where are (i) beta1 and (ii) beta2 receptors found?
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(i) in the heart and fat tissues
(ii) located everywhere else |
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Rank of the order of potency for beta1 receptors to ligands
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Isoproterenol > Epinephrine = Norepinephrine > Dopamine
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Rank the order of potency for beta2 receptors to ligands
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Isoproterenol > Epinephrine >> Norepinephrine > Dopamine
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There are six major groups of agents used in the management of POAG. What do they each differ in?
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1. mechanism of decreasing IOP
2. degree of decreasing IOP below baseline 3. duration of action 4. effects on pupil size 5. effects on ciliary muscle |
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TOPICAL BETA-BLOCKERS
Mechanism of action? |
Reduce aqueous humor formation by reducing the volume of plasma filtrate that passes through ciliary body blood vessels - decreases aqueous humor production
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TOPICAL BETA-BLOCKERS
Does is affect accommodation or pupil size? |
no significant change in accommodation or pupil size
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TOPICAL BETA-BLOCKERS
(i) Initial hypotensive effect (ii) Peak effect (iii) Duration |
(i) within one hour
(ii) 1-2 hours (iii) 12-24 hours |
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TOPICAL BETA-BLOCKERS
What are two reasons why Afro-Americans show a decreased efficacy to these? |
1. They bind strongly to melanin (greater in those with dark irides)
2. It is metabolized by CYP2D6 and CYP1A2 which 20-30% of Afro-Americans show "ultra-metabolizers" |
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TOPICAL BETA-BLOCKERS
Metabolized by? |
CYP2D6 and CYP1A2
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TOPICAL BETA-BLOCKERS
Systemic side effects |
CNS: headache, fatique, light-headedness, memory loss, psychic disorientation, confusion, suicidal depression
CV: bradycardia, palpitation, hypotension, CHF, arrythmia's Respiratory: respiratory distress in bronchial asthmatics, apnea in infants, pulmonary edema Other: GI distress, skin rashes |
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TOPICAL BETA-BLOCKERS
Ocular side effects |
1. dry eye
2. allergic blepharoconjunctivitis 3. pain on instillation 4. superficial punctate keratitis |
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TOPICAL BETA-BLOCKERS
Contraindications |
1. bronchial asthma
2. moderate to severe COPD 3. moderate to severe heart block 4. bradycardia 5. labile diabetes (IMPT: CAN MASK ACUTE HYPOGLYCEMIC ATTACKS) 6. children and infants due to possibility of systemic overdose |
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TOPICAL BETA-BLOCKERS
Drug List |
1. Timolol maleate (Timoptic: 0.25% and 0.5%): beta1 and beta2
2. Timolol hemihydrate (Betimol: 0.25% and 0.5%): beta1 and beta2 3. Timolol maleate in gelrite vehicle (Timoptic-XE: 0.25% and 0.5%): beta1 and beta2 4. Carteolol (Ocupress): beta1 and beta2 5. Levobunolol (Betagan): beta1 and beta2 6. Metipranolol (OptiPranalol): beta1 and beta2 7. Betaxolol (Betaoptic-solution form): beta1 |
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TOPICAL BETA-BLOCKERS:
TIMOLOL MALEATE Trade name? |
Timoptic in 0.25% and 0.5%
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TOPICAL BETA-BLOCKERS:
TIMOLOL MALEATE Decrease in IOP with monotherapy? |
Depresses IOP 18-34% below baseline within first few treatments. However, tolerance can develop with long-term use.
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TOPICAL BETA-BLOCKERS:
TIMOLOL MALEATE Percentage of reduction in diurnal IOP? |
50%
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TOPICAL BETA-BLOCKERS:
TIMOLOL MALEATE Side effects? |
5-10x more potent than propranolol.
Light-sensitivity; preserved with 0.01% benzalkonium Cl |
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TOPICAL BETA-BLOCKERS:
TIMOLOL MALEATE Additional decrease in IOP with use of: a. 4% pilocarpine b. 2% pilocarpine c. topical CAI (Dorzolamide) d. epinephrine |
a. additional 37% below baseline
b. additional 25% below baseline c. additional 20% below baseline d. no further decrease |
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TOPICAL BETA-BLOCKERS:
TIMOLOL MALEATE Indication |
Beneficial for patients under 40 or those with cataracts: eliminated pupillary constriction and accommodative spasm
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TOPICAL BETA-BLOCKERS:
TIMOLOL HEMIHYDRATE What's so special about it? |
same as timolol maleate, except reduced cost due to simpler purification step for the R-enantiomer
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TOPICAL BETA-BLOCKERS:
TIMOLOL HEMIHYDRATE Trade name? |
Betimol in 0.25% and 0.5%
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TOPICAL BETA-BLOCKERS:
TIMOLOL MALEATE IN GELRITE VEHICLE Trade name? |
Timoptic-XE in 0.25% and 0.5%
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TOPICAL BETA-BLOCKERS:
TIMOLOL MALEATE IN GELRITE VEHICLE What's so special about it? |
a. in polysaccharide gel and gum that forms a clear gel in presence of cations found in tear fluid. Prolongs duration of action and thus enhances penetration of drug
b. same as Timolol maleate except single dose. Enhance patient compliance. c. Only transient blurring. Suggested for younger patients |
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TOPICAL BETA-BLOCKERS:
CARTEOLOL Trade name? |
Ocupress (1%)
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TOPICAL BETA-BLOCKERS:
LEVOBUNOLOL Trade name? |
Betagan (0.25% and 0.5%)
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TOPICAL BETA-BLOCKERS:
METIPRANOLOL Trade name? |
OptiPranolol (0.3%)
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TOPICAL BETA-BLOCKERS:
BETAXOLOL Trade name? |
Betaoptic - solution form (0.5%)
BetaopticS - suspension form (0.25%) |
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TOPICAL BETA-BLOCKERS:
BETAXOLOL What's so special about it? |
Respiratory side effects significantly less than with Timolol
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CHOLINERGIC AGONISTS
What are the two types and their drug duration? |
1. Direct-acting ACh like drugs : 4-8 hours duration
2. Indirect-acting AChEase inhibitors: 8-72 hours duration |
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CHOLINERGIC AGONISTS
Mechanism of action |
Increases aqueous humor outflow by causing contraction of ciliary muscle which exerts a force on the scleral spur: stretching the trabeculum, thereby increasing the size of the spaces and reducing the resistance to aqueous outflow.
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CHOLINERGIC AGONISTS
Is there a direct correlation between the amount of miosis and increase in outflow? |
NO
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CHOLINERGIC AGONISTS
What limits this from being used a lot? |
It's poor corneal penetration
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CHOLINERGIC AGONISTS
Mostly used in the management of? |
acute angle closure glaucoma
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CHOLINERGIC AGONISTS
Can it be used in adjunct with other meds? |
Useful adjunctive agents that are additive to either beta-blockers of the sympathomimetics. Combinations of miotics are not recommended due to competitive antagonism
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CHOLINERGIC AGONISTS
Name the direct-acting drugs |
1. Pilocarpine
2. Carbachol |
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CHOLINERGIC AGONISTS
PILOCARPINE a. initial hypotensive effect b. peak effect c. duration d. schedule |
a. within one hour
b. 1.25-2 hours c. generally 8 hours d. tid or qid |
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CHOLINERGIC AGONISTS
PILOCARPINE What is the decrease in IOP with monotherapy? |
depresses IOP 10-41% below baseline, although 20% is usual
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CHOLINERGIC AGONISTS
PILOCARPINE What is the additional decrease in IOP with adjunct use of a. 4% pilocarpine and timolol b. 2% pilocarpine and timolol |
a. additional 37% below baseline
b. additional 25% below baseline |
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CHOLINERGIC AGONISTS
PILOCARPINE Systemic side effects |
a. Rare with usual dosage, however 10 ml of a 1% solution can be fatal
b. ANS: SLUD, sweating, nauseau, vomiting c. Respiratory: bronchioloar spasm and pulmonary edema (dangerous) d. Anomalous increase in BP and HR |
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CHOLINERGIC AGONISTS
PILOCARPINE Ocular side effects |
1. irritation or pain on instillation
2. mild spasm of accommodation causing browache and myopia 3. transient headaches 4. ocular allergy 5. pupillary miosis: can reduce VA 6. The miosis can increase the IOP if conventional outflow pathway is significantly reduced or absent. This occurs because miotics induce contraction of ciliary body and therefore decrease uveoscleral outflow |
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CHOLINERGIC AGONISTS
CARBACHOL What are the differences between Carbachol and Pilocarpine? |
Similar to pilocarpine except
1. lowers IOP more 2. has longer duration of action 3. decreases range of diurnal IOP 4. instill tid |
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CHOLINERGIC AGONISTS
Name the indirect acting drugs |
1. Echothiopate iodide
2. Demecarium bromide 3. Physostigmine |
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CHOLINERGIC AGONISTS
ECHOTHIOPATE IODIDE a. max miosis b. peak iop lowering c. duration d. schedule |
a. 10-20 min and remains for 96 hours
b. 4-6 hours c. 24 hours d. once a day |
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CHOLINERGIC AGONISTS
ECHOTHIOPATE IODIDE a. The 0.03% is comparable to? b. The 0.06% is comparable to? |
a. 1-2% pilocarpine
b. 4% pilocarpine |
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CHOLINERGIC AGONISTS
ECHOTHIOPATE IODIDE What special instruction must you tell the patient? |
They need to refrigerate it
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CHOLINERGIC AGONISTS
DEMECARIUM BROMIDE Similar to Echothiopate iodide, except that it is: |
1. reversible
2. more potent |
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CHOLINERGIC AGONISTS
PHYSOSTIGMINE Similar to Echothiopate iodide, except that it is: |
1. reversible
2. less potent and shorter duration of action 3. instilled qid |
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CHOLINERGIC AGONISTS
Side effects for indirect-acting drugs |
1. spasm of accommodation
2. severe headaches 3. iris cysts in children (rare in adults) 4. lens opacities (anterior subcapsular cataracts) with long term use of echothiopate iodide and demecarium bromide 5. ciliary body contraction can cause shallowing of the anterior chamber angle and therefore predispose patients to angle closure. Therefore these are often used in aphakic eyes 6. Possible ACh systemic toxicity |
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ADRENERGIC AGONISTS
Mechanism of action of beta agonists |
1. increase aqeous humor outflow
2. increase uveoscleral outflow 3. initial effect after instillation 4. seldom used clinically |
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ADRENERGIC AGONISTS
Mechanism of action of alpha agonists |
1. Vasoconstriction of blood vessels of the ciliary body and decrease aqeous humor production
2. onset of decreased aqeuous production takes about 3 hours 3. also mediated pupillary dilation |
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ADRENERGIC AGONISTS
ALPHA AGONISTS What is the potential decrease in IOP with monotherapy? |
depresses IOP 10-15% below baseline within first few treatments. The effects are generally less than with other treatments.
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ADRENERGIC AGONISTS
ALPHA AGONISTS Pharmacokinetics after one drop of Dipivefrin (Prodrug) a. peak IOP lowering b. duration c. schedule |
a. 2-4 hours
b. 12-24 hours c. bid |
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ADRENERGIC AGONISTS
ALPHA AGONISTS Systemic side effects |
1. headaches
2. palpitations 3. tachycardia 4. cardiac arrhythmias 5. acute increase in blood pressure |
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ADRENERGIC AGONISTS
ALPHA AGONISTS Ocular side effects with long-term use |
1. irritation
2. reactive conjunctival hyperemia accompanied by follicle formation |
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ADRENERGIC AGONISTS
ALPHA AGONISTS Contraindications |
1. CVD
2. Hyperthyroidism 3. patients taking MAO inhibitors or TCA 4. narrow angles 5. hydrogel contact lens wear 6. halogen containing general anesthetics |
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ADRENERGIC AGONISTS
ALPHA2-ADRENERGIC AGONISTS Mechanism of action |
1. decrease aqueous humor production
2. increase uveoscleral outflow 3. may reduce episcleral pressure |
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ADRENERGIC AGONISTS
ALPHA2-ADRENERGIC AGONISTS Drug List |
1. Brimonidine tartarate
2. Apraclonidine 3. Combigan |
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ADRENERGIC AGONISTS
BRIMONIDINE TARTARATE What is the potential decrease in IOP with monotherapy? |
0.2% depresses IOP 27% below baseline during peak effect. Same as timolol maleate
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ADRENERGIC AGONISTS
BRIMONIDINE TARTARATE a. Duration b. Schedule |
a. 8 hours
b. tid |
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ADRENERGIC AGONISTS
BRIMONIDINE TARTARATE Systemic side effects |
1. dry mouth
2. fatique 3. decrease in systolic BP at rest and during exercise. |
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ADRENERGIC AGONISTS
BRIMONIDINE TARTARATE Ocular side effects |
1. mild miosis
2. eyelid elevation 3. conjunctival and eyelid margin hyperemia 4. toxic medicomentosa (follicular conjunctivitis due to drug) - decreased from 40% with 0.2% to 15% with 0.1% |
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ADRENERGIC AGONISTS
BRIMONIDINE TARTARATE Useful in the treatment of... |
normal tension glaucoma
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ADRENERGIC AGONISTS
APRACLONIDINE What is the potential decrease in IOP with monotherapy? |
0.25% and 0.5% depresses IOP 15-30% below baseline during peak effect.
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ADRENERGIC AGONISTS
APRACLONIDINE What is the further potential decrease in IOP with adjunct therapy with timolol: a. With 1% apraclonidine b. With 0.25% and 0.5% apraclonidine |
a. an additional 7-14% below baseline
b. an additional 7-9% below baseline |
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ADRENERGIC AGONISTS
APRACLONIDINE a. duration b. schedule |
a. 8 hours
b. tid |
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ADRENERGIC AGONISTS
APRACLONIDINE What is it's main disadvantage? |
Useful in short term, but not well tolerated for long-term therapy as it is prone to "escape" over time
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ADRENERGIC AGONISTS
APRACLONIDINE Systemic side effects |
1. Few CNS effects, as it does not readily cross BBB
2. dry mouth 3. fatigue |
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ADRENERGIC AGONISTS
APRACLONIDINE Ocular side effects |
1. mild mydriasis
2. eyelid elevation 3. conjunctival and eyelid margin hyperemia |
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ADRENERGIC AGONISTS
APRACLONIDINE Contraindications |
Concomitant therapy with MAO inhibitors or tricyclic antidepressants
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CARBONIC ANHYDRASE INHIBITORS - SYSTEMIC
Side Effects |
1. Paresthesis in fingers
2. Anorexia 3. GI disturbances: diarrhea, nauseau, anorexia, bitter or metallic taste in mouth 4. skin eruptions 5. general malaise 6. sodium and potassium depletion, the predisposition to form renal calculi, increased urinary frequency, metabolic acidosis 7. impotence and loss of libido |
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CARBONIC ANHYDRASE INHIBITORS - SYSTEMIC
Drug List |
1. Acetazolamide
2. Methazolamide 3. Dichlorophenamide 4. Ethoxzolamide |
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CARBONIC ANHYDRASE INHIBITORS - TOPICAL
a. initial hypotensive effects b. peak effect c. duration d. schedule |
a. within one hour
b. 2 hours c generally 8 hours d. tid |
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CARBONIC ANHYDRASE INHIBITORS - TOPICAL
What is the potential decrease in IOP with monotherapy? |
depress IOP 10-26% below baseline
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CARBONIC ANHYDRASE INHIBITORS - TOPICAL
What is the further decrease in IOP when used in adjunct with: a. timolol maleate b. 4% pilocarpine |
a. additional 20% decrease in IOP
b. additional 20% decrease in IOP |
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CARBONIC ANHYDRASE INHIBITORS - TOPICAL
Mechanism of action |
Inhibition of CA II isozyme in ciliary process
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CARBONIC ANHYDRASE INHIBITORS - TOPICAL
Side Effects |
1. bitter or metallic taste in mouth
2. ocular irritation 3. pain on instillation 4. hyperemia 5. blurred vision |
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CARBONIC ANHYDRASE INHIBITORS
Contraindications |
1. Sulfa allergy
2. Renal or liver impairment 3. Adrenal insufficiency 4. Acidosis: diabetic ketoacidosis, respiratory acidosis, chronic aspirin 5. Diphenylhydantoin use 6. Thiazide diuretics |
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CARBONIC ANHYDRASE INHIBITORS - TOPICAL
Drug List |
1. Dorzolamide
2. Brinzolamide 3. Cosopt |
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PROSTAGLANDIN
Plays a role in: |
1. maintaining normal IOP
2. preventing the development of inflammation response to normal environmental stimuli |
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PROSTAGLANDIN
Mechanism of action |
1. activates matrix metalloproteinases (MMPs)
2. increases uveoscleral outflow 3. remodeling of extracellular matrix adjacent to the ciliary muscle cells. Dilates the spaces between ciliary muscle bundles |
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PROSTAGLANDIN
Drug list |
1. Latanoprost (Xalatan: 0.005%)
2. Travoprost (Travatan: 0.004%) 3. Bimatoprost (Lumigan: 0.03%) |
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PROSTAGLANDIN
LATANOPROST a. duration b. schedule |
a. long
b. once daily with nightly dosing preferred due to eye redness |
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PROSTAGLANDIN
LATANOPROST What is the potential decrease in IOP with monotherapy? |
depresses IOP 25-36% below baseline
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PROSTAGLANDIN
LATANOPROST What is the further potential decrease in IOP when used in adjunct with other drugs? |
Can also be used in adjunctive therapy with timolol maleate, dipivefrin or CAIs. Provides an additional 14% decrease in IOP
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PROSTAGLANDIN
LATANOPROST Ocular side effects |
1. stinging, itching, transiently blurred vision
2. conjunctival hyperemia 3. slowly increases pigmentation (darkens) of mixed-color irides: IRREVERSIBLE 4. increases pigmentation and growth of eyelashes (hypertrichosis): IRREVERSIBLE |
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PROSTAGLANDIN
LATANOPROST Contraindications |
1. any patients with risk or history of cystoid macular edema
2. any patients with history of uveitis or prior incisional ocular surgery 3. any patient with previous Herpes Simplex |
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PROSTAGLANDIN
LATANOPROST Which glaucoma is it most useful in treating? |
normal tension glaucoma because it improves perfusion to the nerve and therefore may be useful
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PROSTAGLANDIN
Which of the prostaglandin drugs has the lowest discontinuation rate? |
Latanoprost (Xalatan)
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LATANOPROST
TRAVAPROST What is the potential decrease in IOP with monotherapy? |
depresses IOP 25-32% below baseline
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PROSTAGLANDIN
TRAVAPROST What is special about Travoprost? |
states to work better in Afro-Americans than Caucasians
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PROSTAGLANDIN
Ocular Side Effects |
1. Stinging, itching, transiently blurred vision
2. conjunctival hyperemia 3. slowly increases pigmentation (darkens) of mixed-color irides: IRREVERSIBLE 4. increases pigmentation and growth of eyelases: IRREVERSIBLE 5. wide variety of non-ocular side effects |
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PROSTAGLANDIN
Contraindications |
1. any patients with risk or history of cystoid macular edema
2. any patients with history of uveitis or prior incisional ocular surgery 3. Any patient with previous Herpes simplex |
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PROSTAGLANDIN
TRAVAPROST Which type of glaucoma is it useful to treat? |
Normal tension glaucoma because it improves perfusion to the nerve
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PROSTAGLANDIN
TRAVAPROST Trade Name |
Travatan (0.004%)
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PROSTAGLANDIN
LATANOPROST Trade Name |
Xalatan (0.005%)
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PROSTAGLANDIN
BIMATOPROST What is the potential decrease in IOP with monotherapy? |
depresses IOP 26-30% below baseline
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SYSTEMIC HYPEROSMOTIC AGENTS
Name the drug used with each route a. oral route b. IV route |
a. glycerin, isosorbide
b. mannitol, urea |
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Describe the treatment protocol for glaucoma
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1st line: select either a prostaglandin or beta-blocker. If the first drug fails, then select another in the class. If this drug fails, select the next class
2nd line: try combination of front line drugs 3rd line: add Dorzolamide to the regimen 4th line: Pilocarpine, Dipivefrin, Apraclonidine, oral methazolamide |
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Name the neurotransmitter (ligand)-gated ionic channels
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1. AChN
2. Glutamate receptors: NMDA and non-NMDA 3. GABAa and GABAc receptors 4. Glycine receptor |
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Name the voltage-gated ionic channels.
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1. sodium channel
2. calcium channel 3. potassium channel |
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Name the Gs Family - activate adenylate cyclase
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beta1-adrenergic, beta2-adrenergic, dopamine D1, dopamine D5, glucagon, PGE1, serotonin 5-HT4, serotonin 5-HT7, histamine H2
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Name the Gi family - inhibit adenylate cyclase
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alpha2-adrenergic, AChM2, AChM4, Dopamine D2, D3, D4, GABAb, metabotropic glutamate (group II:mGlu2, mGlu3; group III: mGlu4, mGlu6, mGlu7, mGlu8), serotonin 5-HT1
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Name the Gq family - activate phospholipase C-beta
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a1-adrenergic, AChM1, AChM3, AChM5, dopamine D1, serotonin 5-HT2, metabotropic glutamate (group I: mGlu1, mGlu5)
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Which ligands inhibit phospholipase C?
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dopamine D2, adenosine A1
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Which ligands activate phospholipase A2
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Dopamine D4
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Name the agonist-regulated enzymes - enzymes with intrinsic enzyme activity
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a. Tyrosine kinase
b. Guanylyl cyclase c. Serine/Threonine Kinases d. Cytokine and Growth Hormone Receptor |
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What are the disadvantages of using solutions?
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1. decreased ocular contact time
2. imprecise and inconsistent delivery leading to lack of constant concentration 3. loss of drug due to ocular drainage and overflow 4. contamination 5. possible injury with eye dropper |
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Following the topical application of a solution, suspension, gel or ointment the drug will be distributed in one of three ways
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1. ocular drainage
2. vascular absorption 3. corneal penetration |
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Name the types of vehicles used to prolong ocular contact time in order to increase absorption into the eye
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1. saline
2. methylcellulose 3. polyvinyl alcohol 4. white petrolatum-mineral oil 5. polyvinyl pyrrolidine 6. poloxamers |
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Name the different types of preservatives
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1. Benzalkonium chloride (BAC)
2. Thimerosal 3. Chlorhexidine 4. Potassium sorbate |
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Which preservative is not compatible with hydrogel lenses?
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Benzalkonium chloride
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Which preservative is a cationic detergent with both antifungal and bactericidal actions?
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Benzalkonim chloride
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Which preservative reduces tear break-up time by 50% leading to the formation of oil droplets?
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Benzalkonium chloride
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Which preservative is an organic mercury compound with both antifungal and bactericidal actions?
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Thimerosal
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Which preservative is used with both rigid and hydrogel lenses?
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Thimerosal
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Which preservative can cause corneal damage?
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Thimerosal
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Which preservative is used with hydrogel lenses?
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Chlorhexidine and Potassium sorbate
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Which preservative does not decrease tear break-up time?
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Chlorhexidine
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Mydriatics are also known as?
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sympathetics
sympathomimetics mydriatics |
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What is the effect of adrenergic stimulation to the eye?
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1. Pupillary dilation
2. Widening of the palpebral fissure 3. Vasoconstriction 4. Decrease IOP 5. Inhibition of accommodation (relatively small amount) |
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Name the topical adrenergic agonists
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Phenylephrine
Hydroxyamphetamine Cocaine Brimonidine |
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Which receptor does phenylephrine primarily act on?
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alpha1 receptors
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Phenylephrine is available in what doses?
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2.5% and 10% solution
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What are the clinical uses of Phenylephrine?
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1. pupillary dilation
2. breaking posterior synechiae 3. prevention of iris cysts with anticholinesterase use 4. ptosis management 5. diagnotstic testing for horner's syndrome |
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PHENYLEPHRINE
a. max mydriasis b. recovery |
a. 45-60 minutes
b. 6-7 hours |
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PHENYLEPHRINE
Ocular side effects |
1. transient pain, lacrimation, keratitis
2. allergic dermatitis/conjunctivitis 3. release of pigment granules from iris 4. rebound congestion with chronic use |
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PHENYLEPHRINE
Systemic side effects |
1. hypertension
when using 10% solution -increase in BP and HR -occipital HA -subarachnoid hemorrhage -ventricular arrhythmia -ruptured aneurysm -tachycardia/reflex bradycardia -blanching of skin |
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Which drugs can exacerbate phenylephrine?
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-methyldopa
-reserpine -guanethidine -MAO inhibitors -atropine -TCAs |
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Contraindications for 10% solution of phenylephrine
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-cardiac disease
-idiopathic orthostatic hypotension -hypertension -aneurysms -insulin dependent DM -advanced arteriosclerosis |
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HYDROXYAMPTHETAMINE
a. max mydriasis b. duration c. does it effect accommodation? |
a. 45-60 minutes
b. 6 hours c. little to no effect |
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How do you diagnose Horner's syndrome with hydroxyampethamine?
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- Central/Pre-Ganglionic Horners: post ganglionic fibers should have normal amounts of ep: DILATION
-Post-ganglionic Horners: no/little epi in post-ganglionic nerve fibers: NO DILATION |
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HYDROXYAMPHETAMINE
Side Effects |
1. little ocular irritation
2. can cause elevated blood pressure 3. may be safer to use for mydriasis in patients with phenylephrine CI |
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COCAINE
Clinical Uses |
1. limited due to significant corneal damage with topical use
2.diagnosis of Horner's syndrome 3. debridement of corneal epithelium |
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COCAINE
Side Effects |
1. CNS stimulation
2. death from respiratory failure 3. rapid absorption from mucous membranes 4. corneal damage with topical use |
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COCAINE
Contraindications |
1. cardiac disease
2. hyperthyroidism |
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Name the mydriolytics
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Thymoxamine (not availble in US)
Dapiprazole (Rev-Eyes) |
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What is Dapiprazole?
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-an alpha-adrenergic antagonist
-produces miosis -reduces IOP -no shallowing of the anterior chamber -may be useful in angle closure -may partially increase amplitude of accommodation caused by tropicamide -slower effect in dark irides -minimal systemic absorption |
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DAPIPRAZOLE
Clinical Uses |
1. reversal of pupillary dilation (phenylephrine)
2. partial reversal of pupillary dilation (tropicamide) 3. little effect on cycloplegic 4. possible in angle closure glaucoma |
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DAPIPRAZOLE
Trade name and dosing |
available in 0.5% solution (REV-EYES)
-dose 2 gtts followed by 2 gtts 5 minutes later |
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DAPIPRAZOLE
Side Effects |
-burning
-conjunctival hyperemia, chemosis -punctate keratitis, edema -ptosis -browache -no effect on blood pressure or pulse rate |
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DAPIPRAZOLE
Contraindications |
Anterior uveitis
Hypersensitivity |
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Increase in cholinergic activity results in...
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a. miosis
b. contraction of ciliary body c. decrease in IOP |
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Miotics are also known as...
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-cholinergics
-cholinergic agonists -parasympathetic agonists -parasympathomimetics |
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Name the types of miotics and drug names
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Direct Acting
-Pilocarpine -Carbachol Indirect Acting -Edrophonium (reversible) -DFB (irreversible) -Echothiophate (irreversible) |
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MIOTICS
Systemic side effects |
Salivation
Lacrimation Urination Defacation GI upset Emesis Bronchial constriction |
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MIOTICS
Ophthalmic Uses |
1. dx of some pupil abnormalities
- dx dilated pupil -anisocoria greater in the light 2. treatment of glaucoma 3. treatment of accommodative esotropia |
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MIOTICS
Mechanism of action in open angle glaucoma |
-stimulate longitudinal muscle of CB
-pull on scleral spur -opens spaces in trabecular meshwork -RESULT: increased aqueous outflow through trabecular meshwork |
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PILOCARPINE
Availabilty and Dosing |
Available 0.5%-10% solutions, 4% gel
Dosing: QID (solution), nightly (gel) |
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PILOCARPINE
Clinical Uses |
-POAG
-some secondary open angle glaucoma -acute angle closure glaucoma -used to stretch iris before iridotomy |
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PILOCARPINE
Contraindications |
-young age
-cataract (visual axis) -retinal disease -uveitis -neovascular glaucoma -asthma -prepresbyopes |
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What drugs are used in the cholinergic management of accommodative esotropia?
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DFP ung
Echothiophate (Phospholine Iodide) gtts |
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ACETYLCHOLINESTERASE INHIBITORS-IRREVERSIBLE
Side Effects |
-SLUDGE
-Iris cysts -anterior subcapsular cataracts -retinal detachment -acute angle closure glaucoma -uveitis -follicular conjunctivitis -decreased rate of hydrolysis of succinylcholine can lead to respiratory paralysis |
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What drug is used in the diagnosis of Myasthenia Gravis?
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Edrophonium (Tensilon)
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CYCLOPLEGIC AGENTS
Mechanism of action |
1. inhibit the actions of acetylcholine
- mydriasis - cycloplegia - can cause elevated IOP 2. affect autonomic effector sites 3. affect some smooth m. sites |
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Cycloplegic agents are also known as....
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-anti-muscarinics
-cholinergic antagonists -anticholinergics -mydriatics -cycloplegics -mydriatic-cycloplegics |
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CYCLOPLEGICS
Drug List |
Atropine
Homatropine Scopalamine Cyclopentolate Tropicamide |
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ATROPINE
Mydriasis a. max effect at b. recovery Cycloplegia c. Begins at d. max effect at e. recovery |
a. 30-40 minutes
b. 10 days c. 12 minutes d. 60-180 minutes e. 7-12 days |
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ATROPINE
Clinical Uses |
1. cycloplegic refraction
2. treatment of anterior uveitis/hyphema 3. treatment of myopia 4. treatment of amblyopia |
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ATROPINE
Ocular side effects |
1. allergic dermatitis
2. risk of angle closure 3. increased IOP in open angles 4. ocular side effects may occur with systemic use |
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ATROPINE
Systemic side effects |
Low doses
-depression of salivation/dry mouth -flushing of face -inhibition of sweating Higher doses -CNS effects -convulsions -cognitive impairment -delirium -death |
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ATROPINE
Contraindications |
-known hypersensitiviy
-POAG or angle clouse glaucoma -caution in infants, small children, elderly -Down's syndrome |
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HOMATROPINE
a. availabilty b. max mydriasis by c. duration d. recovery |
a. 2% and 5% solutions
b. 40 minutes c. one tenth the potency of atropine; shorter duration of action d. 1-3 days |
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HOMATROPINE
Clinical Uses |
-not typically used for cylcoplegic refraction
-primarily used to treat anterior uveitis |
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HOMATROPINE
Side Effects |
Same as atropine
- |
|
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HOMATROPINE
Contraindications |
Same as atropine
-known hypersensitivity -POAG or angle closure glaucoma -caution in infants, small children, and eldery -Down's syndrome |
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SCOPOLAMINE
Trade name and availability |
Hyoscine available as 0.25% solution
|
|
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SCOPOLAMINE
Mydriasis a. max at b. recovery Cycloplegia c. max at |
a. 20 minutes
b. 2-8 days c. 40 minutes |
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SCOPOLAMINE
Clinical Uses |
-not first choice for cyclo refraction or treatment of anterior uveitis
-more CNS effects |
|
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SCOPOLAMINE
Side Effects |
Similar to atropine but appears to have slightly higher CNS toxicity
-restlessness -confusion -incoherence -violence -drowsiness -vomiting -urinary incontinence |
|
|
SCOPOLAMINE
Contraindications |
Same as atropine
-known hypersensitivity -POAG or angle closure glaucoma -caution in infants, small children, elderly -Down's syndrome |
|
|
What are the available doses for cyclopentolate?
|
0.5%, 1%, and 2% solution
|
|
|
What is the difference between white patients and black patients when using cyclopentolate?
|
white patients: max mydriasis in 20-30 minutes
black patients: max mydriasis in 30-60 minutes |
|
|
CYCLOPENTOLATE
a. as early as b. max. cycloplegia c. recovery |
a. as early as 10 minutes in light colored irides
b. 30-60 minutes c. 24 hours |
