Pharm 2 - Final 6

msteele2211's version from 2015-12-05 14:43


Question Answer
What are the anatomical entities that serve as a drug reservoir?(Ie, where do drugs get 'stuck' in the eye?)
Uveal pigment (Melanin)
What is a biochemical characteristic of the eye, which when combined w/ the physical barriers, makes drug delivery to the eye difficult?Outward ABC transporters
Fluid in the ant chamber is? Post chamber is?Ant = Aqueous humor
Post = Vitreous humor
What is the particular substance in the eye that some drugs will bind to?Melanin
What is metabolism of drugs in the eye like?There is enzymatic biotransformation in the eye, esp w/ esterases (use of prodrugs for Epinephrine & Prostaglandin F2-α)
What kinda vD do eye drugs need?Large
What is the main route of entry when drugs are topically administered?Cornea
How can you change the elimination half-life of drugs in tears? (2 ways) (& what is the t1/2?)(3-6 min). (1) Changes in tear production
(2) Changes in drainage & blinking rate
If drugs cross the conjunctiva & the sclera, how are they eliminated?Eliminated mainly by choroidal circulation (pic on slide 9). (BVs btwn retina & sclera)
Explain the 3 paths a drug can take to get from topical admin (tears) to SYSTEMIC circulation?(1) Tears → CORNEA(main route) → aqueous humor → iris(lots of BVs) → systemic
(2) Tears → conjunctiva → sclera → ciliary body(lots of BVs) → systemic
(3) Nasolacrimal route (mucous membs w/ lots of BVs) → systemic
(Note: Cornea & sclera can have the drug go back & form from sideways, same thing w/ iris & ciliary bodies)
What are the 2 diff types of liquid topical drugs? Explain what they are(1) Solutions (drugs dissolved in a solute)
(2) Suspensions (drugs as solid particles suspended in a solute - NEED TO SHAKE THESE)
4 advantages to solutions/suspensions?(1) Less effects on vision (most are see through & can be blinked away if can't see)
(2) Less incidence of contact dermatitis (isnt staying in 1 place for super long- I think the 3-6min tear t1/2 plays into this)
(3) Less toxic to ocular structures
(4) easier to apply
What are the 4 disadvantages to solutions/suspensions?(1) SHORT contact time
(2) Dilution effects
(3) Expense
(4) ↑ systemic absorption
What are the 4 advantages of ointment?(1) Longer contact time
(2) Not diluted
(3) Protects cornea from drying
(4) Less expensive
What are the 5 disadvantages of ointment?(1) Difficult to dose precisely
(2) ↑ ocular discharge
(3) More difficult to admin
(4) More contact dermatitis
(5) May delay epithelial wound healing
Which type of topical drug is less expensive? Which 1 delays epithelial wound healing? Which 1 has more systemic absorption?Ointment less expensive
ointment delays healing
solutions/suspensions have more systemic absorption
5 things which determine absorption after topical admin?(1) Time the drug stays in the cul-de-sac & precorneal tear film
(2) Elim by nasolacrimal drainage
(3) Drug binding to tear proteins
(4) Drug metabolism by tear & tissue proteins
(5) Diffusion across cornea & conjunctiva
What is/are ways a topically administered drug can get into systemic circulation? (Not path, just the structure)Nasal mucosal absorption (mentioned twice), iris, ciliary body
Transcorneal distribution leads to the drug going where?Cornea → aqueous humor → intraocular structures & systemic circulation
How does SC therapy work? What must you do?Medication is injected under the conjunctiva. Requires SEDATION & TOPICAL ANESTHETIC
What kinda drugs is SC therapy used for?ABx n corticosteroids
What are the 3 main disadvantages of subconjunctival therapy?(1) Limited # of injxns
(2) Scar tissue
(3) Can't be removed once given
What is the benefit of Intracameral therapy?You can achieve very high drug conc
What are the 4 big risks of Intracameral therapy?Hemorrhage
Retinal detachment/degradation
*How do you tentatively diagnose a bacterial eye infxn?Corneal ulcer scrapings → gram staining
*Which animals are usually infected by G+? G-?G+(staph/strep) usually dogs/cats/horses
G- usually rumis (ruminants are rated more negatively than the other animals)
*1st choice antimicrobials for corneal ulcers & bacterial conjunctivitis (non-specific infxns)? (2)(1) NPB - this is Bacitracin+Neomycin+Polymyxin B.(aka NeoPolyBac) (neo & poly do G- & baci(Penicillin equivalent) does both bc cell wall destruction)
(2) NPG - this is Neomycin+Polymyxin B+Gramicidin (In short - combine G- & G+ shit to cover your ass)
*What is the 1st choice ABx for SMALL ANIMALS? Note about this? SFx?Chloramphenicol. NOTE: DOES NOT WORK ON PSEUDOMONAS. Look out for HYPERSENSITIVITIES (1st choice - throw chlorine in their eyes! Excellent!)
*Which ABx will penetrate intact cornea?Ciprofloxacin (Cipro, Cornea) (I will sip fluids through your cornea) (& so does Chloramphenicol, bc that's 1st choice for small animals, & so it does both)
NEOMYCIN/POLYMYXIN/BACITRACIN (NEOPOLYBAC) (NPB) is used to Tx what? What is its spectrum?Corneal ulcers, conjunctivitis, Broad Spectrum
Is Chloramphenicol static or cidal?Static (even though it's number 1 in small animals, that doesnt mean it's awesome at everything, like killing)
Are Fluoroquinolones (Ciprofloxacin) static or cidal?Cidal (flo will kill a bitch)
What does Tobramycin Tx best in the eye?Pseudomonas (toby will kill pseudo-posers)
How should you Tx Keratomycosis?AGRESSIVE Tx, surgical intervention usually required so drug can penetrate
Polyenes → Amphotericin B → penetration is like? Use against what? Spectrum?poor penetration, broad spectrum, more active against yeast (yeast on all my membranes, yo)
Polyenes → Natamycin → how is it administered? What does it work well against?Topical suspension, more effective against fungi, less against yeast, good against Fusarium(type of fungi) (FUNA)
How do you admin azoles for eye (Miconazole, Clotrimazole, Itraconazole)Derm cream
What is the penetration of polyenes like? How much binding do polyenes have?Highly tissue bound w/ poor penetration (they stick into the membrane & cz pores, which means they wont go inside, remember
What are the 2 polyenes used?Amphotericin B & Natamycin (many AMs for NAT)
Nucleoside analogues → which drug? (Spectrum? What 2 other things should we know about the drug?)FLUCYSTOSINE. Broad spectrum, Synergistic w/ Amphotericin B, & resistance can develop (too much AMP will give you the FLU)
What are the 3 azoles used on the eye?MICONAZOLE
(MY IT CLOTTED in my eye)
Miconazole → spectrum? How is it administered? How bioactive is it? Does it bind to things? What is it used to Tx?BROAD spectrum, administered via SC injxn, 30% bioactive, highly tissue bound, & used to Tx yeast & fungi (Mi overachiever antifungal doesnt wanna sit on the eye, it wants to GET IN THERE & Tx both!)
How is Clotrimizole administered? What is it used to Tx?Derm cream used on eye, Tx aspergillus (a clot of asparagus)
Combined w/ 1% DMSOItraconazole (It raDM SO hard)
What Tx aspergillus?Clotrimiazole
Which azole Tx yeast?Miconazole
What is the optimum Tx for corneal ulcers?Equal amounts of: Natamycin - Tobramycin - Cefazolin (combination is more effective than individual Tx) (1 antifungal & 2 ABx, tobra for Pseudomonas) (got an ulcer? I bet you're NotTooCarefree)
What are the main reasons youd use antivirals for the eye? Who does this usually pertain to?Herpes virus keratitis & keratoconjunctivitis. RARE in dogs. MORE COMMON but self-limiting in cats & horses
What are the 3 antivirals mentioned to be used on the eye?DEOXYURIDINE (eptheliotoxic - teratogenic), Acyclovir (less toxic), IFN γ (interferon gamma) (inhibits viral protein synth)
What is the pathogenesis of a corneal ulcer? (What 2 things happen?)Happens when there is an amplification of biochemical degradation of (1) Stromal collagen
(2) Extracellular matrix glycosaminoglycans (what holds the cornea together)
What are the 2 main causative agents of a corneal ulcer?(1) Host-derived proteinases (zinc metalloproteinases (MMPs), neutrophil serine proteinases)
(2) Exogenous microbial hydrolases
What are the 2 HOST proteinases which contribute to corneal ulcers?Zinc metalloproteinases (MMPs), neutrophil serine proteinases
Plasma α2-macroglobulin → spectrum? Works on what?(Proteinase Inhibitor), broad spectrum means it works on host & microbial proteinases (α & macro = the big #1 does everything!)
Why would you use a Chelating Agent to Tx a corneal ulcer? What are the drugs?Chelation = a particular way that ions & molecules bind metal ions.. My guess is that this means you're binding up the proteinase & rendering it useless
Drugs: EDTA, Acetylcysteine, Tetracyclines (Doxy)
What is a Systemic Proteinase Inhibitor used to Tx corneal ulcers? How do you apply it? What can you combine it with?Homologous (self) plasma or serum which is applied topically
Combo w/ EDTA or Acetylcysteine
Explain why we use heparin to Tx corneal ulcersHeparin has an indirect action impedes extravasation of leukocytes (which produce proteinases)
Explain Ilomastat (how does it work?)Inhibits endogenous & Pseudomonas proteinases (IL ma stat(fast) anti proteases, esp if theyre from Pseudomonas)
Polysulphated Glycosaminoglycans → used for what? How are they applied?5% solution in artificial tears. (Remember that glycosaminoglycans are what the extracellular matrix of the eye is made of. if you have them polysulphated, not incorporated back into eye matrix - provide anti-inflammatory action instead)
What are the 4 main choices in how to ↓ intraocular pressure in Glaucoma?(1) ↓ the production of aqueous humor
(2) ↑ outflow
(3) Do some neuroprotection: Prevent dmg by ↑ Glutamate(NMDA receptor) signaling (pressure on optic n → ↑ glutamic signaling → can lead to neurodegeneration)
(4) Decide if sx is needed
Trabecular outflow is mediated by what drugs?Muscarinic agonists (Alex TRABEC eating MUSHROOMS)
Uvealsclearal outflow is mediated by?Prostaglandin agonists
Aqueous humor inflow is mediated by?β-blockers
α2 agonists
Way to remember flow in eye stuffβ is only antagonist, rest are agonists
What are the 3 topical prostaglandin analogs? What do they do?(Uvealsclearal outflow)
Facilitates outflow through uveoscleral pathway (mechanism unknown - works on Gq) (Prostate has stuff flow OUT, & for U(uveo), Quick!) (Outflow is prostate carps. awesome.)
What are the β-adrenoceptor antagonists? What do they do?Timolol
Regulate aqueous humor production (B stoppin the pool from fillin up) → β2-receptor most prominent (wanna open shit up); non-selective drugs, used in clinic
Why do we use Carbonic Anhydrase Inhibitors to Tx Glaucoma?Reduced formation of bicarb leads to a reduction in fluid transport (pumps not pumping to exchange fluid or something)
What are the local Carbonic Anhydrase inhibitors? What are the oral Carbonic Anhydrase Inhibitors?LOCAL = Dorsolamide & Brinzolamide. ORAL = Methazolamide, Dichlorophenamide, Acetazolamide (bicarb-lamide. except Dichlor) (MAD oral skills. local is BadDay when you gotta put crap in your eye)
What is the topical meiotic used? What does it do?Pilocarpine, ↑ aqueous outflow via trabecular outflow. (Muscarinic) (Carp swimming on the outflow of the river, avoiding the TReachery) (Alex TRABEC eating mushrooms & carp)
What are the 2 neuroprotection drugs used, & why are they used?Used to prevent excitotoxicity of the optic nerve in Glaucoma. (1) Amlodipine; calcium channel blocker
(2) Memantine; NMDA channel blocker (both end in ine, calcified pines & sniffing NMDA off fork tines)
What are the 4 groups of anti-inflammatories used on the eye?NSAIDs, Antihistamines & Mast-Cell Stabilizers, Glucocorticoids, Cyclosporin A (highly lipophilic immunosuppressant drug)
What is the absorption of NSAIDs like? How is it administered?Rapid absorption, can be admin topically or SC injxns - can consider systemic Tx
What are Antihistamines/Mast-Cell Stabilizers used for?Allergic conjunctivitis
How strong are Glucocorticoids as Anti-inflammatory agents? What SFx should you know? When should you not use?STRONG Anti-inflammatory effects, but they are IMMUNOSUPPRESSIVE & SHOULD NEVER BE USED ON DMGD CORNEA(impede healing i think)
Cyclosporin A - hydro or lipophilic? What SFx should you know? What is it used to Tx?Highly lipophilic. Can be immunosuppressive. Is used to Tx ERU- equine recurrent uveitis (trying to Tx a recurrently dzed horse is a vicious CYCLE)
Timolol Acetate is a _________ used to Tx ___, w/ ___ effect on the eye?Sympatholytic, used to Tx Glaucoma, cz constriction of the pupil (lol = β-blocker, so know it's Adrenergic. Think that Tim is under a lot of pressure & so he is constricting inwards in sympathy)
Parasympatholytic drugs → what pupillary response? What are the drugs? What is the dz this is used to Tx?Dilation (Mydriasis). The drugs are Atropine, Tropicamide, Scopolamine. Used to Tx uveitis in the horse & also used as a diagnostic agent (PS: Atropine makes you all dewey eyed)
Sympathomimetic drugs → what pupillary response? What are the drugs? What is the dz this is used to Tx?Dilation (Mydriasis). Phenylephrine, Epinephrine. Used to Tx anterior uveitis
What are the topical local anesthetics?Proparacaine & Tetracaine (TP just stays on the eye surface)
What are the infiltrative local anesthetics?Lidocaine & Bupivacaine (LB infiltrates!)
What is a disinfectant that can be used on the eye?Povidone Iodine (Iodine scrub on the eye)