Lecture 2 Stuff Flashcards
What is the cause and effect of glaucoma?
Cause - damage to the optic nerve due to intraocular pressure
Effect - loss of vision
What are the causes of an increase of intraocular pressure?
Increase of production of aqueous humor
decrease of outflow of aqueous humor
Which beta blockers are non-selective?
timolol, carteolol(ISA), metipranolol, levobunolol (these seem to work better but have more side effects)
Which beta blockers are beta 1 selective?
betaxolol
Where is the main outflow for AH normally?
Trabecular meshwork
What are the Sympathomimetic (Mydriatics)?
alpha 2 agonists
Apraclonidine - Iopidine (don’t use because of hypertension side effect)
Brimonidine - Alphagan P (primarily used)
alpha and beta agonists
Epinephrine - Epifrin (used for surgical means and metabolized by people with brown eyes)
Dipivefrin - Propine (lipophilic derivatives allowing it to get to site of action)
What are the direct acting products of the Parasympapthomimetics (Miotics)?
Carbachol (Miostat and Isopto Carbachol)
Pilocarpine (Carpine, Pilocar, Piloptic, and Pilopine HS)
What are the indirect acting products of the Parasympapthomimetics (Miotics)?
Reversible:
Physostigmine (IsoptoEserine)
Irreversible:
Echothiophate (Phospholidine Iodine)
What does Mydriasis, miosis, and meiosis mean?
mydriasis - big pupil
miosis - little pupil
meiosis - cell division (watch for this trickery)
What are the carbonic anhydrase inhibitors?
Oral, Works good but has nasty side effects:
Acetazolamide (Diamox sequels) - antiepileptic
Methazolamide (Nepatazane)
Ophthalmic:
Dorzoloamide (Trusopt)
Brinzolamide (Azopt)
What are the prostaglandin agonists?
Bimatoprost (Lumigan and Latisse) Lantoprost (Xalatan) Travaprost (Travatan) Tafluprost (Zioptan) Unoprostone (Rescula not in US)
How long does it take for prostaglandins to take effect according to Dr. Maize?
3-5 weeks
What are the shelf life’s and expiration dates for the prostaglandins?
Bimatoprost - 2y shelf life, 4 weeks open
Latanoprost - 2y shelf life in fridge, 6 weeks open
Travoprost - 3y shelf life, 4 weeks open
What cannabinoids are good for glaucoma?
Marijuana (must be smoked ever 3 to 4 hours) Unknown mechanism of action….
What are the side effects of cannabinoids?
Ocular - conjunctival hyperemia, reduced tear production and miosis.
Short term - Reduction of systemic blood pressure and tachycardia, psychotropic effects of euphoria or dysphoria, disruption of short term memory, cognitive impairment, sense of time distortion, reduced coordination and sleepiness.
Long term - emphysema - lung cancer
What are the mast cell stabilizers?
Cromoyln Sodium (Optichrom) Nedocromil (Alocril)
What drugs affect open angle glaucoma?
Systemic and ophthalmic steroids
Docetaxel and paclitaxel
What drugs affect narrow angle glaucoma?
Adrenergic and anticholinergic drugs (epinephrine, amphetamine, antipsychotics, antihistamines) Sulfa drugs (Trimethoprim/Sulfamethoxazole, hydrochlorothiazide, acetazolamide)
Why won’t epinephrine (Epifrin) cross the cornea?
It is to polar, causes irritability, short acting.
What is Dipivefrine HCL?
Propine a dipivaloy ester prodrug. Has better absorption. than epinephrine.
What are the functional groups in alpha/beta agonists agents?
They are alpha beta agonists.
Phenethylamine core
beta-OH affects activity.
alpha-CH3 decreases activity but may increase DOA
As you increase size on the alpha 1 amine you decrease alpha and beta activity
What is the metabolism of the alpha/beta agonists agents?
Dipivefrin into Epi into Norepi into vanilylmadelic acid (VMA) via COMT
What are the alpha 2 agonists and what do they do??
Apraclonidine HCl (Lopidine) - does not cross BBB (adds an amine group to clonidine) Brimonidine tartrate (Alphagan) -1000 x more alpha 2 selective than clonidine (adds an pyrazine to clonidine) lower intraocular fluid production and increase outflow
What are the functional groups in alpha 2 agonists that affect SAR?
Imidazoline
Guanidine
What are the beta antagonists and what do they do?
betaxolol HCl (Betoptic) carteolol HCL (Ocupress) levobunolol HCl (Betagan) metipranolol HCl (Optipranolol) Timolol Maleate (Timoptic) decreases intraocular fluid production
What is the common core of the beta antagonists?
aryloxypropranolamine
Cartelol is the flipped structure of timolol, how does this affect the metabolism?
The half-life is longer.
Most p-aryloxpropanolamines are _________.
beta 1 antagonists.
Aryloxypropanolamines are more potent than _____________.
arylethanolamines
Carbonic anhydrase inhibitors have what in their active site?
Ziinc
What do CAI’s do?
decrease intraocular fluid production
What is the metabolism of CAI?
CA turns carbon dioxide and water into carbonic acid and then into bicarbonate ion which creates a hyperosmotic environment. The hyperosmotic environment then pulls in the water so when you use an inhibitor it stops the creation of bicarbonate ions which is an ingredient of AH. Therefore it stops the production of AH.
What are the CAI’s?
Topical: Brinzolamide (Azopt) Dorzolamide (Trusopt) Oral: Acetazolamide (Diamox) methazolamide (Neptazane)
What are the SAR of CAI?
Acidic aryl SO2NH2
What are the direct acting cholinergic agents?
affect Acetylcholine and increases fluid outflow
Carbachol Chloride (IsoptoCarbachol) - weak indirect as well
Pilocarpine (Isoptocarpine)
What are the indirect acting cholinergics
They inhibit acetylcholinesterase (AChe) Reversible: Physostigmine sulfate (IsoptoEserine) Irreversible: Echothiophate iodide (Phospholidine iodide)
What are the SAR of direct-acting cholinergics?
Ester groups and onium groups
all substitutions decrease activity
alpha substitutions decrease nicotinic activity
beta substitutions decrease muscarinic activity
What are the SAR of the indirect acting cholinergics?
acetyl, Carbamyl, and Phosphoryl interact with esteractic site in AchE
Duration of the AChE inhibition - depends upon FG present. The bigger the better at inhibited.
Prostaglandins are prodrugs. T/F
True
What are the SAR of prostaglandins?
Esters are the prodrugs.
Amide is ?
alkane/alkene/aromatic chains
What is allergic conjunctivitis and what are the treating agents?
Eye irritation with itching, redness and tearing
Antihistamines
Decongestants
Dual-acting (antihistamine and mast cell stabilizing)
Glucocorticoids (steroids)
Mast cell stabilizers Anti-infective
What are the 1st generation H1 antihistamines?
Ethylenediamines:
Antazoline (Vasocon-A)
Propylamines:
Pheniramine Maleate (Opcon-A)
What are the 2nd generation H1 antihistamines?
Olopatidine HCl (patanol) - tricyclic Levocabastine HCl (Livostin)
What are the decongestants?
Phenylethylamines Imidazolines: oxymetazoline (Afrin) naphazoline (Clear Eyes) tetrahydrozoline (Visine) xylometazoline (Otrivin)
What are the mast cell stabilizers?
Cromolyn (Opticrom)
Lodoxamide Tromethazmine (Alomide)
nedocromil (Alocril)
perimolast (Alamast)
What is the SAR of mast cell stabilizer?
not clearly established.
What are the dual acting agents for allergic conjunctivitis?
H1 antihistamines and mast cell stabilizers Emedastine (Emadine) azelastine (Astelin) ketotifen (Zaditor) epinastine (Elestat)
What SAR is found in H1 antihistamines?
diarylalkylamine pharmacophore
How do glucocorticoids work?
Agents bind to the GR and activate the GR complex to produce proteins which suppress pro-inflammatory proteins.
What are the glucocorticoids?
Dexamethasone Phosphate (Maxidex) Flurometholone (FML) Hydrocortisone (part of Cortisporin) Loteprednol (Lotemax) Prednisolone (Phosphate salt in Econopred) Rimexolone (Vexol)
What is the reference molecule for glucocorticoids?
Hydrocortisone
What is the SAR for glucocorticoid?
anti inflammatory activity is increased by:
double bond between C1 and C2
6 alpha-F
11 beta-OH
