Big KNY3, did my research on Viagra side effects.Unlike you, " I don't wait until the data are out" to
Make my evaluations, because,
a)unlike you I can get an idea of a drug's toxicity
by looking at it's sibblings: When 2 aminoglycoside antibiotics are toxic ( Kanamycin and srteptomycin, you can suspect thsat ther new ones ( Gentamycin and Tobramycin ) also nephrotoxic; they were.
b) I have to make immediate investment decisions. You buy the stock as early as possible when it is cheap.
I contacted among the 4 MDs and one PhD in the research. They are among the top investigators. One of them was involved in making up the classification of phosphdiesterases in 6 types. He is a pharmacologist
( we'll call him Jim )He is also a pharmacologist.. The other one has been writing PDE articles for 20 years, over 20 on the retina. 2 of them head Retina Fellowship programs.They all publishe din top medical journals. I can't divulge anyone's names because I did not tell them I would publish this in the web. Also it was informal and not an in depth review. I asked them to comment om what is currently being alleged: a) penile PDE is PDEV and sildenafil ( Viagra ) is specific to it and does not affect any other part of the body including the retina. B) The retina's PDE is mostly PDE VI and therefore Sildenafil ( a PDE V inhibitor) will not inhibit it/affect it Results:
-Only one had heard of Sildenafil.
-Nobody has ( as yet ) looked at Viagra's retinal toxicity.One said that would be interesting to do based on the data we subsequently discussed.
-They all said THAT NOT ALL RETINA PDES' have been analyzed;ie there could be penile PDE V in the retina especially in the deeper ( cones ) levels which have not been studied too much.Most studies analyzed the surface of the retina ( the rods ) which is more accessible.
-There are many other PDEs in the retina such as calmodulin PDE which are not part of PDEVI
- Penile PDE V is found widely in other parrs of the body: it's in all the muscles; also in brain, heart.
-75% of retinal PDE V and penile PDE VI share the same structure so that it is possible for retinal PDE VI to be inhibited by penile PDE V.
-destruction of retinal PDE VI is a major cause of macular retinal degeneration one of the commonest causes of loss os vision in the elderly.
-retinal destruction can occur over a long time and one year of observation may not be enough to show it.
- I pointed out that sophisticated studies would have to be done on Viagra if one were to look for eye disturbances; that would include an exam by a retina specialist ; performance of an electroretinogram;possible fluorescein retinal angiography; the doctor agreed that it would be very unlikely that these tests would be done during Viagra's phase III study, on 4000 patients ( too expensive and time consuming ).
- The retina fellowship Director said that the fact that some Viagra patients ( we don't know the exact number ) have shown " visual abnormalities " and " blue halos " is of concern and needs to be evaluated.
- They all agreed that in the animal model of retina PDE gene destruction what happens is that there is a great increase of cyclic GMP ( since there is no lnger any PDE to destroy it ) and this cGMP overstimulates the retina and results in macular degeneration. So that if Viagra stimulates erection by increasing penile cyclic GMP ( which increases Nitric oxide production and causes penile vasodilatation ), any potential CONTEMPORANEOUS increase of RETINAL cGMP that it might cause could theoretically result in premature retinal degeneration.
This was the end of our discussion. One of them said he would research the matter further and get back to me.
Here is an abstract from a widely used 1997 textbook of ophthalmology on drug effects on the retina ( a 6 volume book !! ); ( things just aren't that simple in Medicine are they, GG ):
***
Clinical Ophthalmology
Volume 3
Editor
WILLIAM TASMAN MD
Ophthalmologist-in-Chief and Co-Director of the Retina
Service, Wills Eye Hospital; Professor and Chairman,
Department of Ophthalmology, Jefferson Medical College
of Thomas Jefferson University, Philadelphia
Associate Editor
EDWARD A. JAEGER, MD
Professor of Ophthalmology, Jefferson Medical College of
Thomas Jefferson University; Attending Surgeon, Wills
Eye Hospital, Philadelphia
Revised Edition-1997
Lippincott-Raven
Publishers
97
------
Chapter 37
------
OCULAR TOXICOLOGY
=================
By
F.T. FRAUNFELDER, and
S. M. MEYFR
Ocular toxicology, as all other areas of toxicology, is an ever expanding field but one filled with hard and soft data. Clinicians must base their decisions on available data, past experiences, and human variables. Often, the accumulated data are indecisive, and one is forced into conservative positions for medicolegal reasons. Topical or systemic sideffects from topical ocular medication are varied, as are adverse reactions from systemic medication, Ocular changes may be of minor importance, apparently neither harming the eye nor indicating more widespread systemic toxicity; miosis and occasional ptosis secondary to chloral hydrate are of this nature. In other instances, the toxic ocular reactions, such as the cataracts of corticosteroid therapy, the retinopathy of chloroquine therapy, or the optic neuropathy of ethambutol therapy, may threaten sight. Ocular toxicity may also be part of a more widespread toxic reaction; examples of this include the mucocutaneous syndrome caused by practolol and the fetal alcohol syndrome seen in offspring of alcoholic mothers. 'However, in certain cases it may be possible to make use of mild toxic ocular reactions as an indicator of more serious systemic toxicity, such as abnormal color vision seen with digitalis toxicity.
The period during which most patients are likely to suffer an adverse reaction is the first 7 to 10 of days of therapy. However, the advent of a toxic reaction may be delayed because it is dose dependent. This is the case with phenothiazine or chlo-
roquine retinopathy. Other reactions may be idiosyncratic, such as aplastic anemia secondary to topical ophthalmic chloramphenicol administration or optic neuritis due to ibuprofen.
Most adverse drug reactions cease when the drug is discontinued. However, the toxic effect may persist and even progress after withdrawal of the drug, as in phenothiazine therapy, in which continued deterioration of vision may occur. Some reactions, such as the,corneal deposits following amiodarone administration, appear to reach a steady state with no progression even after discontinued drug use. Other adverse ocular reactions are irreversible; ethambutol-induced blindness is such an example. Fortunately, most ocular reactions are reversible, but some may take as long as a year or more to resolve.
In this chapter we briefly review some toxic implications of topical ocular therapy and deal mainly with the ocular toxicity of systemic drugs. Our intent is not to provide a comprehensive list but to emphasize the adverse drug effects of medications commonly used by ophthalmologists. Some of this information comes from the data collected by the National Registry of Drug-Induced Ocular Side Effects, a clearinghouse for drug information on adverse ocular effects. Physicians suspecting a possible drug-induced ocular change are encouraged to send their suspicions or a case report to the registry. Cases of greatest interest
are previously unsuspected, rare, severe, or unusual drug-related ocular side-effects. Please send your data to F. T. Fraunfelder, MD, Department of Ophthalmology, Oregon Health Sciences University, 3181 S. W. Sam Jackson Park Road, Portland, OR 97201.
In order that the data herein can best be used, it has been divided into four tables.
Table 1.
Adverse Ocular Reactions of Drugs.This table contains generic names of systemic and topical ophthalmic drugs. In this table it is possible to find a number of drugs that may induce a common side-effect simply because they are pharma-
cologically related. Only the more common ocular side-effects are recorded for those drugs listed.
Table 2.
Adverse Systemic Reactions of Drugs Commonly Used in Ophthalmology.This table contains generic names of drugs commonly used in ophthalmology and their adverse systemic effects. It also groups pharmacologically related drugs so that one can identify common systemic adverse effects. The route of administration is also given.
(text continues on p. 18)
22 Vol. 5 Chap 37 CLINICAL OPHTHALMOLOGY
TA-BLE 4. Visual Tests That Are Helpful in Monitoring for Ocular Toxicity (continued)
isoflurophate Sodium salicylate Procaine
Isotretinoin Thioridazine
Prochlorperazine
Mesotidazine Tranylcypromine Promethazine
Methylergonovine Trifluoperazine Propoxycaine
Methylprednisolone Trimethadione Protriptyline
Methysergide Reserpine
Naproxen
Dark Adaptation
----------------
Secobarbital
Paramethasone Alcohol Sodium salicylate
Perr)henazine Paramethadione Streptomycin
Phenacaine Quinidine Succinylcholine
Trimethadione
Piperocaine Talbutal
Polysaccharide-iron complex Thiopental
Extraocular Motility
------------------
Practolof
Thioridazine
Prednisolone Acetohexamide Timotol
Alcohol
Prednisone Tolazamide
Amitriptyline
Prochlorperazine Totbutamide
Amobarbital
Promethazine Trichlorethylene
Aspirin
Proparacaine
Trifluoperazine
Barbital
Quinacrine TubaHne
Betaxolol
Silver nitrate Valproate sodium
Bromide
Silver protein Valproic acid
Bupivacaine
Suramin Veratrum dnisone
Tamoxifen Carbamazepine Vinblastine
Chlordiazepoxide
Tetracaine Virrcristine
Chloroform
Thioridazine Vitamin A
Chloroprocaine
Thiothixene
Chlorpromazine
Fluorescein Angiography
-----------------------
Tolazamide
Tolbutamide Chlorpropamide Aluminum nicotinate
Urea
Diazepam
Triamcinolone Amyl nitrite @@atrum
Ethchlorvynol
Trifluoperazine Broxyquinoline
Floxuridine
Trifluridine Carbon dioxide
Fluorouracil
Vidarabine
Carmustine
Flurazepam
Vitamin D Diatrizoate megiumin@ /sodium
Guanethidine Epinephrine
Color Vision
---------
Imipramine Ergonovine
Amyl nitrite Isoniazid Ergotamine
Aspirin Ketamine Griseofulvin
proquine
Bromide Levobunolol lodochlorhydroxyquin
Chlorpromazine Lidocaine lodoquinol
Digitalis Lithium carbonate lothalamate meglumine/sodiufn
Digitoxin Mepivacaine
Methylergonovine
Digoxin Meprobamate
Methysergide
Ethambutol Mesoridazine Niacin
lbuprofen Methaqualone Niacinamide
Indomethacin Methylpentynol Nicotinyl alcohol
Isocarboxazid Metrizamide Nitroglycerin
9
Mesoridazine Metubine iodide Oral contraceptives
Methaqualone Nitrofurantoin
Oxygen
Nalidixic acid Nortriptyline
Phenylpropanolamine
Nialamide Oxyphenbutazone
Ouabain Pentobarbital Intraocular Pressure
Paramethadione Perphenazine Amitriptyline
Perphenazine Phenobarbital Amphetamine
Phenacetin Phencyclidine Atropine
Phenelzine Phenylbutazone Belladonna
Piperazine Phenytoin Betamethasone
Prochlorperazine Piperazine Carmustine
Promethazine Prilocaine Chlorphentermine
Quinidine Primidone Chymotrypsin
*********************************************
The above table discusssing drugs that can affect color vision ( in relation to Viagra patients having " blue halos "' does not show uo well but it is there.
Well Vivus thread and Big KNY3, this concludes todays lesson on ophthalmology. I will answer your other questions later.
TA
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