Exam 4 Flashcards
What are the different parts of the eye and what are the different formulations of ocular medications?
Cornea - Refracts light
Aqueous humor - Provides nutrients and gets rid of waste
Ciliary muscle - Changes the shape of the lens
Iris - Color of the eye
Lens - Focuses light
Vitruous body - Maintains eye shape (inside)
Optic nerve - Transmits sensory information
Retina - Essential for vision
Sclera - Maintains shape of the eye (outside)
- Injections can be given sub-conjunctival, peri- and latero-bulbar, retrobulbar, and intravitreal.
- Also ointment, solution, suspension, and gel
What are the steps to administering eye drops and ointment
Eye drops -
1. Wash hands and remove contacts if needed
2. Remove the cap and shake the bottle vigorously
3. Tilt head back slightly and pull lower eyelid down to form a pocket
4. Hold the dropper above the pocket, look up, and squeeze the bottle gently
5. Let go of the eyelid, close eye for 1-2 minutes, blot excess with a tissue
6. Recap the bottle and wash hands
Eye ointment -
1. Wash hand and remove contacts if needed
2. Remove the cap and shake vigorously
3. Tilt head back slightly and pull the lower eyelid down to form a pocket
4. Hold the tube above the pocket, look up, and squeeze gently to release a thin line of the ointment
5. Release eyelid and close eye for 1-2 mins, blink to spread the ointment
6. Recap and wash hands
- wait at least 5 minutes in between 2 drops of the same medication, 5-10 mins if different medication
- apply gels last and wait 10 minutes after the last eye drop
- wait 15 minutes to reinsert contacts
What are the side effects, dosing schedules, and cost among prostaglandin analogs for glaucoma?
- Increase aqueous humor outflow
- Absolute first line
- $ Bimatoprost (Lumigan), Travoprost (Travatan Z, Travatan)
- $$$ Latanoprost (Xalatan, Xelpros), Lantanoprostene bunod, tafluprost; Stored in fridge until opened, then lasts 6 weeks
Side effects: Iris pigmentation, increased eyelash length, mild to moderated eye irritation, conjunctival hyperemia
Dosing: 1 drop qHS
What are the side effects, dosing schedules, and cost among beta blockers for glaucoma?
- Reduce aqueous humor production
- First line, esp. if prostaglandin analog can’t be used
- $ Timolol (Timoptic, timoptic XE, Istalol), Betaxolol, Carteolol, Levobunolol; All non-selective, except betaxolol
Side effects: Stinging, bradycardia/fatigue, bronchospasm
Contraindications: Sinus bradycardia, 2nd or 3rd degree heart block
Dosing: 1 drop daily or BID
What are the side effects, dosing schedules, and cost among alpha-2 agonists for glaucoma?
- Reduce aqueous humor production and increase aqueous humor outflow
- Use if prostaglandin analog and beta-blocker can’t be used
- Brimonidine (Alphagan P)
- Brimonidine (Lumify); OTC for eye redness, dosing up to 4x/day
Side effects: Fatigue, conjunctival blanching, lid retraction
Warning: Can cause CNS depression, caution when operating heavy machinery
Dosing: 1 drop TID
What are the side effects, dosing schedules, and cost among carbonic anhydrase inhibitors for glaucoma?
- Reduce aqueous humor production
- $ Dorzolamide (Trusopt)
- $$$ Brinzolamide (Azopt)
Side effects: Dysgeusia (metallic taste), drowsiness/malaise, paresthesia
Dosing: 1 drop TID
**bottle has to be recapped due to risk of crystallization, caution in sulfonamide allergy
What are the side effects, dosing schedules, and cost among rho kinase inhibitors for glaucoma?
- Increase aqueous humor outflow
-Netarsudil (Rhopressa)
Side effects: Hyperemia, corneal changes, pain on instillation
Dosing: 1 drop qPM
What are the side effects, dosing schedules, and cost among cholinergics for glaucoma?
- Increase aqueous humor outflow
- $ Carbachol (Milostat); 1-2 drops up to TID
- Pilocarpine (Isopto carpine); 1-2 drops up to 4x/day
Side effects: Poor night vision, eye pain/irritation, increased lacrimation
**last line due to these side effects
Warning: Use in caution in patients with hx of retinal detachment or corneal abrasion
How do we decide on treatment for patients with glaucoma?
- Start with prostaglandin analog or maybe beta blocker
- If contraindicated, use brimonidine (a2-agonist)
- Assess response in 2-4 weeks
- If inadequate response: ensure compliance, increase concentration or increase dose frequency, or switch to alternative first-line agent if no response, add second first-line if there’s a partial response
- If intolerant: reduce concentration, change formulations, switch to alternative class, switch to different first-line agent
- Assess response in 2-4 weeks
- Keep adding/switching/removing as is necessary and reassessing in 2-4 weeks
- If nothing works, laser or surgical procedure is needed
What is the treatment options for iritis and what are the side effects?
Treatment is for 4-6 weeks
- Prednisolone acetate 1%
- Fluorometholone acetate 0.1% (FML)
- Suspension is the best formulation option
Side effects: Itching, burning, difficulty focusing, decreased vision, etc.
Risk factors: Primary open-angle glaucoma, ocular hypertension, elderly, children, connective tissue disease, type 1 diabetes with myopia
Which corticosteroids are in the low, intermediate, and high category? What is the treatment options for iritis and what are the side effects?
Low -
- Dexamethasone 0.05%, 0.1%
- Medrysone 1%
Intermediate -
- Dexamethasone alcohol 0.1%
- Difuprednate 0.05%
- Fluorometholone 0.1%, 0.25%
- Loteprednol 0.2%, 0.5%
- Prednisolone acetate 0.12% (Pred Mild)
- Prednisolone sodium phosphate 0.125%, 1%
High -
- Fluorometholone acetate 0.1%
- Prednisolone acetate 1% (Pred Forte)
- Rimexolone 1%
**prednisolone acetate 1% is the most efficacious, but causes biggest increase in intraocular pressure
*fluorometholone acetate 0.1% is not quite as efficacious, but is better for ocular pressure
What is the difference between dry and wet macular degeneration and its respective treatments?
Dry - Common over 50yo, seen in 90% of cases, affects both eyes, has slow onset of symptoms
Wet - Develops once pt has dry eye already, new blood vessels grow into the macula, need drug therapy
VEGF inibitors/photodynamic therapy for wet macular degeneration:
1. Bevacizumab (Avastin) - cheaper; intravitreal 1.25mg q4, 6, or 8 weeks for 1 year
1. Ranizumab (Lucentis) - FDA approved; intravitreal 0.5mg q4 weeks
- Aflibercept (Eylea)
- Pegaptanib (Macugen)
What is the difference in duration for medications used for cataract surgery?
Atropine 1% - Up to one week
Homatropine 2% - 12 hours
Scopolamine (hyoscine) - 96 hours
Cyclopentolate 1% - 12-24 hours
Tropicamide 0.5% - Up to 6 hours
- phenylephrine 2.5% as an addition increases these effects
What are the classifications of bacterial, viral, and allergic, or chemical conjunctivitis based on patient characteristics?
Bacterial -
- Yellow discharge signifies bacterial presence
- Need to get prescription antibiotics
Viral -
- Diffuse, non-patterned redness
- Don’t hurt, but maybe itchy/gritty
- Don’t need to send to ER
Allergic -
- Diffuse, non-patterned redness
- Don’t hurt, but maybe itchy/gritty
- Don’t need to send to ER
Chemical -
- Blisters on the inner eye
- Probably irritating to the patient, probably due to some allergy
Questions to ask yourself:
- What do you see? Describe the pattern of redness
- Do you think it hurts? What kind of hurt?
- Would you send this pt to the emergency room?
What are the different classes and dosages of ocular allergy medications?
Mast Cell stabilizers:
- Cromolyn Sodium: 4-6 times daily
- Lodoxamide: 4 times daily
- Nedocromil: 2 times daily
Antihistamines:
- Olopatadine: daily or BID
- Azelastine: BID
- Epinastine: BID
Multiple-acting agents:
- Ketotifen: BID
- Alcaftadine: Daily
What is the duration of treatment for ocular vasoconstrictors?
Naphazoline (Naphcon): Dosage 6-8 times daily
Tetrahydrozoline (Visine): 3-4 times daily
How do you know when to refer a patient with ocular problems?
- If they are more sensitive to light
- If their vision has decreased recently
- If bacterial infection (need rx)
Are are some medications that may cause drug-induced ophthalmic disorders?
Amiodarone - corneal deposits
Digoxin - Yellow halo
Anticholinergics - Blurred vision
Antidepressants - Blurred vision
PDE5-inhibitors - Color changes/blue tint
Bisphosphonates - redness/inflammation
Topiramate - closed angle glaucoma
SSRIs - eye twitches
What are the key questions to ask an ocular patient when interviewing them?
Does your eye hurt?
- Describe the hurt - sharp, stabbing pain? or scratchy gritty feeling?
Is your eye sensitive to light?
Is your vision reduced?
How long have you experienced symptoms?
What are the top 2 risk factors for macular degeneration? What is significant about beta-carotene in eye vitamins?
Risk factors: Age and smoking
- Beta-carotene has increased risk of lung cancer in smokers
What’s the difference between open and closed angle glaucoma?
Open -
- The build up of fluid ends up causing too much pressure to the optic nerve
Closed -
- Cloudy cornea with somewhat patterned redness
- Pt probably experiencing significant pain, particularly upon exposure to sunlight, and he/she may feel like vomiting
- Pt’s eye may be bulging forward and it would feel very hard
- This requires immediate referral
- Treated by hyperosmotic agents (mannitol, glycerin, isosorbide) and other agents (timolol for reduction of flow of aqueous humor, pilocarpine to help dilate pupil)
What are the ocular antibacterial medications and dosing?
Moxifloxacin: 2 or 3 times daily
Neomycin/Polymixin B/Dexamethasone: 4-6 times daily
Ofloxacin: 4 times daily
Trimethoprim/Polymyxin B: 4-6 times daily
What are the 6 environmental factors that can contribute to dry eye?
Age
Medications
Electronic Devices
Smoking
Humidity
Diet
What are the steps to treating dry eye?
- Address environmental factors, warm compress, artificial tears
- Tear conservation, in-office procedures, topical drug therapy (Secretagogues BID)
- Liftegrast (Xiidra): inhibits ocular surface inflammation that is associated with dry eye disease
- Cyclosporine (Restasis): Reduces inflammatory response - Oral drug therapy, CF 101 to reduce inflammation, autologous serum eye drops, therapeutic contact lenses, surgical punctal occlusion
What are the options for artificial tears?
Aqueous supplementing -
- Carboxymethylcellulose, hydroxypropylcellulose, polyethylene glycol, propylene glycol
Lipid supplementing -
- DMPG propylene glycol, Mineral oil
How do we manage a stye?
Warm compress may be helpful
No stye ointment
Possible topical antimicrobial, need to refer
What is pseudomonas aeruginosa?
Happens when people wet their contacts with their own saliva
How do you treat if someone gets an acid/base in their eye?
- Rinse the eye for at least 5 minutes
- Tap water is fine
- Be careful not to rinse the eye with a strong stream of fluid that directly hits the cornea
- Patient needs to be referred for emergency care immediately
How do you treat drug-induced dry eye?
Nonpharm therapy: warm compress, increase fluid intake, use humidifier
Increase tear volume: conisder artificial tears or other lubricants, punctal occlusion
Decrease inflammation: 0.05% cyclosporine ophthalmic drugs, LFA-1 antagonist ophthalmic drops (xiidra), short-term ophthalmic glucocorticoids
Medication changes: D/c medication, use preservative free ophthalmic drops
What is the treatment/management for these drug-induced ophthalmic disorders? What causes these? (cataracts, floppy iris syndrome, optic neuropathy, retinopathy)
Cataracts - Surgical removal of the cataract
- Alkylating agents, antiestrogens, corticosteroids, statins
Floppy iris syndrome - Preop screening for previous/current use of causative agents
- Alpha-1 antagonists, benzodiazepines
Optic neuropathy - D/c of causative agent
- Amiodarone, ethambutol, linezolid, PDE5 inhibitors
Retinopathy - Monitor through regular eye exams. Vision loss is irreversible
- Aminoquinolones, antiestrogens, phenothiazines, retinoids
What is the role that platelets play in hemostasis?
Hemostasis - Stopping the bleeding from a damaged blood vessel.
Platelets are activated when collagen is exposed to the blood stream. Platelets are then activated, and through secretion of other molecules and platelet adherence/aggregation, a plug is formed. In secondary hemostasis, a blood clot forms and is then degraded.
What are the three phases of platelet activation?
Platelets start out really small. Contact with the extracellular maxtrix (collagen) starts the platelet reactions.
1. Adhesion and shape change - GP Ia bind to collagen, GPIb binds to vWF that’s bridged to collagen. (normally, the epithelium produces PGI2 [prostacyclin] to keep platelets in their inactivated state)
2. Secretion reaction - Degranulation occurs and platelets granules secrete ADP, thromboxane A2 (TXA2), and serotonin (5-HT). These recruit other platelets. TXA2 and 5HT are also vasoconstrictors.
3. Aggregation - GPIIb/IIIa receptors undergo a shape change to bind to fibrinogen, which crosslinks the platelets and forms a temporary hemostatic plug. As platelets contract and the fibrin stabilizes/achors aggregated platelets, a clot forms.
What is the role of collagen, vWF and GP 1a/1b receptors in platelet activation?
Collagen - Exposure of collagen to the blood is what triggers the platelet activation. GP Ia/IIa binds to collagen.
vWF - Binds to collagen, then binds to GP Ib to activate platelets
GP Ia/Ib receptors - GP Ia binds to collagen, GP Ib binds to vWF that’s bound to collagen
What are the 3 molecules that are secreted by platelets and what’s their role in hemostasis?
ADP - Activate and recruit other platelets
Thromboxane A2 (TXA2) - Activate and recruit other platelets, also vasoconstrictor
Serotonin (5-HT) - Activate and recruit other platelets, also vasoconstrictor
The activation of ADP, 5-HT, and TXA2 induces the conformational change of GP IIb/IIIa receptors to bind to fibrinogen, which is the start of platelet aggregation,
What is the role of fibrinogen and GP IIb/IIIa receptors in platelet function?
Once GP IIb/IIIa receptors are activated, they bind to fibrinogen, which crosslinks the platelets.
What is the role of aspirin as an antiplatelet drug and why does it have a preferential effect on platelets over the endothelium?
MOA: Aspirin irreversibly inhibits platelet COX-1 by acetylation. It blocks the conversion of arachidonic acid to PGG2, which inhibits the formation of TXA2. This interferes with platelet aggregation, prolongs bleeding time, and prevents arterial thrombi formation.
- The main pathway for aspirin is to inhibit COX-1, but at higher concentrations, it affects the COX-2 pathway, inhibiting the formation of prostacycline (which keeps platelets inactive/vasodilates)
- Indicated for prophylaxis and treatment of arterial thromboembolic disorders (ex. stroke).
- Hemostasis returns to normal after 36 hours of last dose of aspirin. Prolongs bleeding time, but not PT time.
- Doses above 500mg/kg can be fatal
What is the MOA of clopidogrel, prasugrel, ticagrelor, and cangrelor? What differentiates them?
The activation of both P2Y1 and P2Y12 is needed for platelet activation due to activating GP IIb/IIIa downstream.
Prasugrel - Prodrug that requires esterases. It irreversibly binds to the P2Y12 receptor. It’s not associated with genetic differences in 2C19.
Clopidogrel - Requires metabolism by CYP2C19 to be active. It irreversibly binds to the P2Y12 receptor. It has more genetic variability than prasugrel due to relying in CYP2C19.
Ticagrelor - Binds to an allosteric site, so this is a reversible inhibitor. It is not a prodrug and therefore has faster onset.
Cangrelor - is IV, but binds to the same site at prasugrel and clopidogrel, but is reversible. Not a prodrug. Fast onset and short 1/2 life.
**Loading doses of prasugrel or clopidogrel should only be given after cangrelor is stopped due to cangrelor blocking their active site. Ticagrelor can be given at any time because it’s acting on an allosteric site.
What is the MOA of abciximab and eptifibitide and tirofiban? What is their role in therapy and what are their differences in structure?
Abciximab - inhibit GP IIb/IIIa receptor, which is the receptor for fibrinogen that anchors platelets to each other. This is a chimeric mouse-human monoclonal Ab
- Given IV, long duration of action (increases bleeding risk)
Eptifibitide - inhibit GP IIb/IIIa receptor, which is the receptor for fibrinogen that anchors platelets to each other. Synthetic peptide that selectively blocks BP IIb/IIIa, reversibly.
- From snake venom
- Large peptide with short duration of action delivered IV
Tirofiban - inhibit GP IIb/IIIa receptor, which is the receptor for fibrinogen that anchors platelets to each other. Nonpeptide tyrosine analogue.
- Given IV, 2 hour plasma life
- More than 90% inhibition of platelet aggregation after 30 min infusion
What is the MOA of dipyridamole and cilostazol and what differentiates them?
Dipyridamole - PDE5 inhibitor. Inhibits the uptake of adenosine, which keeps local adenosine concentrations high, which activates adenosine receptors (A2) on platelets. These are Gs coupled, so this increases cAMP. Along with inhibiting PDE5 degradation of cAMP to AMP, there is a lot more cAMP in the cell. This leads to decreased intracellular calcium and therefore decreases platelet activation and aggregation.
Cilostazol - PDE3 inhibitor, increasing cAMP in the cell, decreases Ca2 -> keeps platelet round and inactive.
What are the extrinsic and intrinsic clotting pathways?
Extrinsic - Requires a factor (tissue factor) that is not in the blood.
- Involves Tissue factor, factor VII, and factor X
- Tissue factor is on the surface of cells outside but near blood vessels. VII is usually in the blood, but TF binding to factor VII activates it. Then Factor VIIa binds and cleaves factor X.
- TF + VII -> VIIa/TF causes -> X -> Xa
Intrinsic - Triggered when collagen is exposed on the wall of the blood vessel
- Involves factor VIII, IX, X, XI, XIII
- Thrombin causes Factor XI -> XIa causes IX -> IXa -> also VIII -> VIIIa -> then IXa/VIIIa causes X -> Xa
What are the steps in the common clotting pathway?
As Xa is formed, Thrombin causes V -> Va; Xa/Va causes prothrombin -> thrombin; thrombin causes fibrinogen -> fibrin and XIII -> XIIIa; XIIa causes fibrin -> cross-linked fibrin
Thrombin activation plays major role. Eventually factor XIII is cleaved and then cross-links fibrin to form a stable clot incorporated into platelet plug
What are the conditions for laboratory tests for coagulation and what the normal time ranges?
Platelet count -
- Thrombocytopenia: too low, could be due to bone marrow malfunction or nutritional deficiencies.
- Thrombocytosis: too high
Prothrombin time (PT/INR) - Mixing plasma with thromboplastin and calcium, then seeing the time to clot.
- Normal is 11-14 seconds.
- INR = (PT test/ PT normal) ^ISI; normal is 0.8-1.2, and therapeutic INR is ~2-3. More than 3, risk of hemmorhage
aPTT - plasma + phospholipid (no TF) + activating agent
- Normal is 25-40 seconds.
- Used to monitor with heparin therapy
Fibrinogen: range from 200-400mg/dL
D-dimer: measures the products of fibrin breakdown
Why is Ticopidine not on the market anymore?
Ticlopidine (ADP receptor inhibitor) induces antibodies against ADAMTS13, which decreases the proteolytic activity of ADAMTS13. This means vWF doesn’t get cleaved and excessive platelet aggregation occurs. It causes depletion of platelets, hemolytic anemia, renal impairment, neurological symptoms, fever, and can be fatal.
What does Vorapaxar do?
Inhibits protease activated receptor inhibitors. These are normally activated by thrombin to activate platelets downstream. Thrombin binds to the PARs that are coupled to GPCRs. The PAR1 receptors are cleaves on the platelet surface and then downstream, the platelet is activated. Vorapaxar inhibits this.
- Half life is 3-4 days, so it lasts a few days after d/c
- Reversible, used prophylactically
What feedback mechanisms are present to regulate coagulation?
Increase coagulation:
- Thrombin: activates factor V and VIII, enhances platelet activation
- Platelet activation increases the activation of factor VII, factor X, and cleavage of prothrombin
Decrease coagulation:
- Antithrombin: Neutralizes procoagulant serine proteases like thrombin, Xa, and IXa.
- Protein C system: Activated by thrombin binding to thrombomodulin. The activated protein C complex (APC) forms a complex with protein S to inactivate factors Va and VIIIa.
- Factor Xa: activates tissue factor pathway inhibitor to block upstream activation of factor VII.
