CIMDA

Unfortunately Elisabeth you have added implications with Stella being on high doses of preds at a young age.  Having said that I have known several puppies in Stella's situation and they have all gone on to be fit an active and regain their strength.

Jo

Quote from: Jo CIMDA on August 20, 2012, 11:23:28 AM

Hi
I have been looking into you using whole dried grapefruit juice instead of the real stuff.  I haven't had time to research properly but try this link.

http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2885.2009.01124.x/pdf

Hi

Below is the abstract of the above paper.  Adding grapefruit juice in order to successfully reduce cyclosporin dose  must be good not only for the dog but the owners 'pocket',  but any addition/alteration of dose should be under the supervision of your vet. There is no doubt that grapefruit juice has a remarkable effect on many drugs. Whole grapefruit power can be bought from the internet or, I believe, health food shops.

Jo


J Vet Pharmacol Ther. 2010 Apr;33(2):189-95.

Grapefruit juice, lyophilized grapefruit juice, and powdered whole grapefruit inhibit cytochrome P450-mediated triazolam hydroxylation by beagle dog liver microsomes.

Hanley MJ, Cerundolo R, Radwanski N, Court MH.


Source

Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA 02111, USA.


Abstract

Coadministration of grapefruit juice (GFJ) has been proposed to enhance the systemic availability and decrease the required dose of drugs such as cyclosporine that are extensively metabolized in the intestine and liver. Although GFJ inhibits human cytochrome P450 (CYP) 3A, effects on dog CYP have not yet been reported. Consequently, we determined whether GFJ inhibits triazolam hydroxylation by Beagle dog liver microsomes (DLM) using human liver microsomes (HLM) as positive control. Results were compared with the effects of lyophilized GFJ and commercially-available powdered grapefruit capsules, which may be more convenient dosage forms. GFJ inhibited alpha-hydroxytriazolam formation in both DLM and HLM with similar IC(50) (inhibitor concentration producing a 50% decrease in reaction velocity) values of 0.56% and 0.52% (v/v), respectively. Lyophilized GFJ and powdered grapefruit also inhibited DLM alpha-hydroxytriazolam formation with IC(50) values of 0.76 and 1.2 mg/mL, respectively. Consistent with mechanism-based enzyme inhibition, preincubation of DLM with any of the grapefruit products for 20 min resulted in significant enhancement of inhibition of triazolam alpha-hydroxylation by 8-20%. The results indicate that 16 g of lyophilized GFJ or 23 g of powdered grapefruit would be equivalent to dosing 100 mL of GFJ. In vivo pharmacokinetic interaction studies are needed to confirm these in vitro findings.

Aw Vicki, we all get neurotic but then you have to learn to 'pull back' otherwise you will be ill.

Pred can affect ligaments and this might be the clicking.  Is Soph a breed that suffers with slipping knee caps (patella luxation)?

All the side effects will gradually lessen as time goes on and the dose is lowered. I can remember feeling impatient and wanting all these effects to go away.  It will come.

Jo

Thank you Elisabeth - blunt isn't my usual approach.  You sound so confident now in the way you are managing Stella and it is lovely the way you have a feel for her condition.  It is something that so many of us can identify with.

Have a happy festive time.

Jo

Hi
I have been looking into you using whole dried grapefruit juice instead of the real stuff.  I haven't had time to research properly but try this link.

http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2885.2009.01124.x/pdf

If you can't get the article then I have (I hope) saved it to my computer and I can email it to you.

Jo

Quote from: Toggledog on August 17, 2012, 11:39:19 AM
I see that there is evidence that it is beneficial to give grapefruit juice with Atopica, but can't find how much? Also, if anyone has tried it, what is the best way -  Beano's a good lad, but I don't think he'll drink it neat!

Hi,  I have copied a couple of abstracts (below) for you to have a look at.  A friend of mine used to syringe the grapefruit juice into her dog's mouth.  The treatment and juice worked a treat.  Is Beano still on high doses of Atopica?

Jo

Lancet. 1995 Apr 15;345(8955):955-6.
Effect of grapefruit juice on blood cyclosporin concentration.
Yee GC, Stanley DL, Pessa LJ, Dalla Costa T, Beltz SE, Ruiz J, Lowenthal DT.
Department of Pharmacy Practice, College of Pharmacy, University of Florida Health Science Center, Gainesville 32610, USA.
Comment in:
•   Lancet. 1995 Jul 8;346(8967):122-3; author reply 123-4.
•   Lancet. 1995 Jul 8;346(8967):123; author reply 123-4.
Abstract
Grapefruit juice increases blood concentrations of some dihydropyridine calcium-channel blockers, which are metabolised by the P450 enzymes that also metabolise cyclosporin. We evaluated, in a randomised cross-over study, the effect of grapefruit juice on blood cyclosporin concentrations in 14 healthy adults. Each subject was given oral cyclosporin 300 mg with 250 mL grapefruit juice, orange juice, or water. Area-under-the-curve (AUC) was significantly higher with grapefruit juice than with water or orange juice (means 7057, 4871, and 4932 ng h/mL, respectively; p < 0.0001). Thus grapefruit juice may provide a non-toxic and inexpensive alternative to drugs that are used to reduce cyclosporin dose.
PMID: 7715295 [PubMed - indexed for MEDLINE]

******************
The effect of grapefruit juice on cyclosporine and prednisone metabolism in transplant patients
Auteur(s) / Author(s)
HOLLANDER A. A. M. J. (1) ; VAN ROOIJ J. ; LENTJES E. G. W. M. ; ARBOUW F. ; VAN BREE J. B. ; SCHOEMAKER R. C. ; VAN ES L. A. ; VAN DER WOUNDE F. J. ; COHEN A. F. ;
Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)
(1) Univ. hosp. Leiden, dep. nephrology, 2300 RC Leiden, PAYS-BAS
Univ. hosp. Leiden, cent. human drug res., dep. nephrology, Leiden, PAYS-BAS
Univ. hosp. Leiden, dep. clin. chemistry, Leiden, PAYS-BAS
Sandoz Pharma, dep. biopharmaceutics, Basel, SUISSE
Résumé / Abstract
Objective: To estimate the effect of grapefruit juice on cyclosporine and prednisone metabolism. Methods : This was an open, placebo-controlled, two-way crossover study performed in the academic departments of clinical pharmacology and nephrology. On two study occasions, 12 kidney transplant patients with stable cyclosporine trough levels received either grapefruit juice or water every 3 hours for a period of 30 hours. The main outcome measures were peak concentration and time to peak, area under the concentration-time curve, the ratio of the area under the curve of the metabolites/area under the curve of the parent drug, terminal half-life, and 24-hour trough levels of cyclosporine. Results: Grapefruit juice increased the peak concentration of cyclosporine by 185 ng/ml (95% confidence interval, 60 to 310; p=0.008). The ratio of the urea under the curve of the metabolites of cyclosporine to the area under the curve of cyclosporine was reduced by 0.137 on the grapefruit day (95% confidence interval, -0.221 to -0.054: p=0.004). After grapefruit juice, no signifiant changes were observed in the area under the curve and the time to peak of cyclosporine, prednisone, and prednisolone. Cyclosporine through levels were unchanged by grapefruit juice. Conclusions: Grapefruit juice inhibits the metabolism of cyclosporine for a brief period after administration, which may be explained by the inhibition of cytochrome P450 enzymes in the gut wall an to a lesser extent by inhibition of these enzymes in the liver. Grapefruit juice can be one of the factors leading to intraindividual variability in the pharmacokinetics of cyclosporine. Grapefruit juice had no significant effect on the metabolism of prednisone or prednisolone
Revue / Journal Title

That's very good news Vicki.  You don't want her platelets to rise too far so in 10 days if Soph were mine I would want the pred dose reduced again.  It is all very well using the preds to bring the disease into remission but these are very high doses (and they have to be) but there is no sense in keeping her on very high doses just because the vet is frightened she will relapse.  Prolonged and unnecessary use of preds is not good practice and what you have written illustrates the inexperience of the vet.  Good for you for challenging and doing the right thing. I wouldn't go back to that particular vet unless you have to because she is obviously one of those who won't acknowledge the harm that some vaccines and drugs can do and she doesn't like tjhe client thinking for themselves.  Go back to a vet you can work with.  Well done Vicki - and Soph!

Jo

Hi Gail

I'm sorry for poor Lola and you!  Does the weather make a difference?  Is it very hot and stuffy where you live?

I do hope it is just a blip and not anthing worse.

Thinking of Lola and you.

Jo

Hi Cathy - Welcome

I'm sorry Lucy has DLE.  To be honest I doubt the dosing regime Lucy is on at the moment will actually bring the disease into remission.  As Penel says with AI  skin diseases, you do have options and steroids are not always needed, but given that Lucy is having steroids she will have to have  immunosuppressive doses  and not treated as if it is an allergic disease.  Please check out Michael J Day's drug protocol in the files.  He is a top sepcialist and his protocol can be used as a guide to treat AI disease.

There is also a lot of supplements you can give to Lucy that will assist the treatment, such as, Natural Vit E And evening Primrose oil etc., 

I hope the information you get from the files is helpful.

Jo

That is good news.  I'm so please you have someone who is competent looking after Rosie now.

Good luck
jo

Hi elisabeth

I'm glad to hear that you are back safe and sound and with Stella again.  I bet she made a big fuss of you.

I can't advise on all the supplements you are giving Stella because I haven't used all of them and maybe others will have more personal experience, but sometimes when the dog is stable and on low doses of prednisolone all the issues that are seen when a dog is on high doses don't apply anymore and one need to re-think the supplements based on the current siituation rather than what has been.  For example Stella's liver enzymes should be much lower now, if not back to normal, so does she need the same amount of milk thistle etc? I can quote the doses from the references that I have. Milk thistle 250 - 500 mg twice a day for dogs depending on size and the severity of the condition (The Veterinarians Guide to Natural Remedies for Dogs by Martin Zucker)  Kelp: small dogs: 1/8th - 1/4 teaspoon daily;  Medium dogs: 1/4 - 1/2 teaspoon daily;  Large dogs: 1/2 - 1 teaspoon daily.  Note: Caution;  the iodine content in kelp is very inconsistent and excessive supplementation is likely to lead to iodine toxicity (salivation, watery eyes and nose, irritation of the stomach and suppression of the thyroid gland leading to lethargy; Kronfeld 1983) Therefore it should be given in measured quantities rather than added freely. Note; Kelp may not be beneficial in thyroid disease of dogs or cats.  (The Pet Lovers Guide to Natural Healing for Cats and Dogs by Barbara Fougere BVSc) From the same book Dandelion dosing 0.25ml of tincture per 5kg bodyweight up to three times a day. It says it is very safe and can be used for long periods. I couldn't fine a reference to seaweed calcium but apparently the rule of thumb for adding calcium is to 'supplement if you are feeding homemade meals and not to add calcium if you are using strictly a commercial food'. Sorry but I don't have a reference for  shwagandha.  If you are in doubt you migh drop Jean Dodds a short email asking her for the doses etc.

I do love the confidence you have now when managing Stella.

Jo

That is very sweet of you Gail.  We are a group who help each other through our own experiences and that has proved to be such a good resource.

Thank you Gail - Penel and I really appreciate your contribution as we do everyone who takes time to help.  Having a network of international helpers means that the forum can be open 24hrs and I can go away on holiday, for example, confident that the forum is ongoing.

Another plus is we all get to know each other and our dogs too!

Jo

Hi

I'm sorry to read that Rosie is down to 15%.  I hope they can soon differentiate between iron deficiency anaemia and a relapse of AIHA.  I hope you get good news today.

Jo

That is such an upbeat post Harriet and so encouraging to others who are dealing with SLO.  Thank you for sharing your good news.  Well done Red!

Jo

Hi

In two months the preds should have been reduced at least 2-3 times.  When preds are given for a long time the PCV  can reach a plateau and this often occurs around the late 20% to early 30%.  31% may not show as pale gums.  Sometimes the gums will look pale in a healthy dog.  Anaemia of chronic disease is also a posibility and also iron deficiency anaemia caused by stomach ulcers that can be as a result of prednisolone.  I know she is having a gastroprotectant, which is good.  Personally, I think the history of treatment and the clinical signs she is showing all point to pred saturation. If there is no evidence of AIHA then why shouldn't the preds be reduced?

If the current problem is due to pred saturation, when the dose is lowered you should see an improvement within a few of days.

Good luck
Jo