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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 19 of 19. This is the beginning of the thread.
Posted by medievil on December 23, 2006, at 12:14:36
i'm very interested in pindolol as an augmentation agent for parnate wich i'm going to take soon
because
- it potentiates the antidepressant effect
- it prevent any hypertensive crisisbut on wikipedia i've read beta blockers could cause diabetis, is this also the case for pindolol?
Posted by sdb on December 23, 2006, at 14:15:09
In reply to pindolol, does it increase the risk of diabetis?, posted by medievil on December 23, 2006, at 12:14:36
> i'm very interested in pindolol as an augmentation agent for parnate wich i'm going to take soon
> because
> - it potentiates the antidepressant effect
> - it prevent any hypertensive crisis
>
> but on wikipedia i've read beta blockers could cause diabetis, is this also the case for pindolol?pindolol does not change HDL/LDL ratio significantly. It tends to lower the "bad" LDL cholesterol slightly.
Some betablockers could progress diabetes if there was a diabetes before. But that a betablocker is a trigger to cause diabetes is very unlikely. It could may be more difficult to handle hypoglycemia.
It's very risky to say pindolol can prevent you from a hypertensive crisis. If you take pindolol for the first time there will be an increase in heart rate because of ISA and a vasoconstriction due to strong beta2-blocking properties thus elevating total peripheral resistance. In other words it could make the hypertensive crisis even worse. If you would first take pindolol and wait some time until pindolol has lowered blood pressure and has increased diameter of blood vessels pindolol could prevent you from a hypertensive crisis. MAO's can lower blood-pressure itself and pindolol would lower blood-pressure more by time. If you have a low blood-pressure that could make the pressure too low. A betablocker is not only a med that lowers blood-pressure its an antiarrhythmic. I can only suggest to do experiments with very low dosages of pindolol first. At best discuss that with your doctor.
sdb
Posted by Quintal on December 23, 2006, at 14:42:26
In reply to Re: pindolol, does it increase the risk of diabeti, posted by sdb on December 23, 2006, at 14:15:09
I don't think pindolol would prevent a hypertensive crisis with Parnate but it may cause hypotension, or worse, potentate any hypotensive action of Parnate may have on you. Pindolol is a non-selective beta-blocker and may increase your risk of diabetes like other drugs of its class by causing hyperglycemia.
--------------------------------------------------
Beta-blockers Raise Diabetes RiskMarch 30, 2000 - Beta-blockers may increase risk for diabetes. Dr. Frederick Brancati studied data on 12,550 non-diabetic patients from 45 to 64 years of age. At 3 and 6 years, patients were screened for diabetes.
Overall, patients with high blood pressure were 2-1/2 times more likely than others to develop type 2 diabetes. After adjusting for other factors, patients taking a thiazide diuretic, an ACE inhibitor, or calcium channel blocker did not have higher risk for diabetes. However, the risk for diabetes was 1-1/4 times higher for beta-blocker patients.
The authors note that "this adverse effect must be weighed against the proven benefits of beta-blockers in reducing risk of cardiovascular events."Source: N Engl J Med 2000;342:905-912,969-970
http://www.chfpatients.com/coreg.htm#beta-blockers_diabetes
--------------------------------------------------Pindolol:
"It acts on serotonin (5-HT1A) receptors in the brain resulting in increased postsynaptic serotonin concentrations."
http://en.wikipedia.org/wiki/PindololDoes this pose an increased risk of serotonin syndrome?
According to that article the combination of fluoxetine and 5-HT1A antagonist 'is reported to enhance extracellular levels of serotonin greater than fluoxetine alone'. It doesn't cause serotonin syndrome with fluoxetine, so the same may be true with Parnate, but with MAOIs I'd like to tread carefully where serotonin is concerned - it could creep up on you suddenly as you increase the dose. Does your pdoc say it's safe?
Q
Posted by linkadge on December 23, 2006, at 15:29:58
In reply to Re: pindolol, does it increase the risk of diabeti » sdb, posted by Quintal on December 23, 2006, at 14:42:26
I've read followup studies saying that pindolol does not enhance serotonin release and does not poses significant activity on 5-ht1a autoreceptors.
These study authors theorized that augmentation must have been through an alternative mechanism.
http://jpet.aspetjournals.org/cgi/content/full/291/1/229
Linkadge
Posted by sdb on December 23, 2006, at 15:31:15
In reply to Re: pindolol, does it increase the risk of diabeti » sdb, posted by Quintal on December 23, 2006, at 14:42:26
"Beta-blockers may increase risk for diabetes."
Almost every betablocker has a similar molecular structure but not all. And even if the structure is similar the effects are different and vary. Betablockers have different actions concerning endocrinology. Which one may increase? - imprecise. Furthermore the study seems to be pretty old. If you're doing meta-analysis there are other studies bring more clarity what is meant with "increase risk for diabetes".
kind regards
sdb
> I don't think pindolol would prevent a hypertensive crisis with Parnate but it may cause hypotension, or worse, potentate any hypotensive action of Parnate may have on you. Pindolol is a non-selective beta-blocker and may increase your risk of diabetes like other drugs of its class by causing hyperglycemia.
>
> --------------------------------------------------
> Beta-blockers Raise Diabetes Risk
>
> March 30, 2000 - Beta-blockers may increase risk for diabetes. Dr. Frederick Brancati studied data on 12,550 non-diabetic patients from 45 to 64 years of age. At 3 and 6 years, patients were screened for diabetes.
> Overall, patients with high blood pressure were 2-1/2 times more likely than others to develop type 2 diabetes. After adjusting for other factors, patients taking a thiazide diuretic, an ACE inhibitor, or calcium channel blocker did not have higher risk for diabetes. However, the risk for diabetes was 1-1/4 times higher for beta-blocker patients.
> The authors note that "this adverse effect must be weighed against the proven benefits of beta-blockers in reducing risk of cardiovascular events."
>
> Source: N Engl J Med 2000;342:905-912,969-970
> http://www.chfpatients.com/coreg.htm#beta-blockers_diabetes
> --------------------------------------------------
>
> Pindolol:
> "It acts on serotonin (5-HT1A) receptors in the brain resulting in increased postsynaptic serotonin concentrations."
> http://en.wikipedia.org/wiki/Pindolol
>
> Does this pose an increased risk of serotonin syndrome?
>
> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9507085&dopt=Abstract#
>
> According to that article the combination of fluoxetine and 5-HT1A antagonist 'is reported to enhance extracellular levels of serotonin greater than fluoxetine alone'. It doesn't cause serotonin syndrome with fluoxetine, so the same may be true with Parnate, but with MAOIs I'd like to tread carefully where serotonin is concerned - it could creep up on you suddenly as you increase the dose. Does your pdoc say it's safe?
>
> Q
Posted by jimmygold70 on December 23, 2006, at 15:45:20
In reply to pindolol, does it increase the risk of diabetis?, posted by medievil on December 23, 2006, at 12:14:36
I wouldn't take pindolol if you havce DM type II or the metabolic synrome. In case you have intact glucose tolerance test, pindolol might be worth a try.
> i'm very interested in pindolol as an augmentation agent for parnate wich i'm going to take soon
> because
> - it potentiates the antidepressant effect
> - it prevent any hypertensive crisis
>
> but on wikipedia i've read beta blockers could cause diabetis, is this also the case for pindolol?
Posted by Quintal on December 23, 2006, at 16:13:19
In reply to Re: pindolol, does it increase the risk of diabeti, posted by sdb on December 23, 2006, at 15:31:15
>Almost every betablocker has a similar molecular structure but not all. And even if the structure is similar the effects are different and vary. Betablockers have different actions concerning endocrinology.
I imagine so. I also presume you have evidence - studies of some kind to prove each beta blocker has different actions concerning endocrinology? We can't leave anything to chance afterall, or heaven forbid, be seen to make a generalization.
>Furthermore the study seems to be pretty old.
That study seems to have been conducted in 2000 - old by research standards maybe, but still relevant considering the length of time beta-blockers have been in use. I imagine the drugs have similar effects on human beings regardless of when the study was conducted.
>If you're doing meta-analysis there are other studies bring more clarity what is meant with "increase risk for diabetes".
Then please provide them. I posted what I thought was likely to be one of the studies that the person writing the wikipedia article used as his/her sources. I'd never heard of beta-blockers causing diabetes before and I wrote to that effect in my post before deciding to do a quick Google and check. When I found evidence to the contrary I was forced to re-write my original message. That study was the first I found and it seemed like a good idea to post it for medievil's perusal because this is afterall a public message board designed for mutual support not a peer reviewed research committee.
I happen to be in the final stages of roasting my turkey. Had I not been rushing backwards and forwards to grease it I would have spent more time examining the evidence. If those are the standards that are expected of me around here then I'll make a note to be more careful in future.
Kind regards
Q
Posted by sdb on December 23, 2006, at 17:04:05
In reply to Re: pindolol, does it increase the risk of diabeti » sdb, posted by Quintal on December 23, 2006, at 16:13:19
Hi Quintal,
You are welcome. Thanks for your help and your input. I think you're absolutely right that some betablockers should be carefully used for people with diabetes risk such as positive family anamnesis, pathological glucose tolerance and steroid medication. You know, in Great Britain it is discussed to avoid betablockers in first line treatment in essential hypertension. There are many new meds for hypertension available such as ACE-inhibitors, AT1-antagonists, vasodilators...
But a definitive fact is that betablockers are still widely and effectively used since many years for hypertension but many other cardiovascular disorders too.>If you're doing meta-analysis there are other >studies bring more clarity what is meant with >"increase risk for diabetes".
>>Then please provide them
Of course I would like to do but there are tons of studies so I can't give a clear picture here.
But back to the topic I can't predict the clinical effect without data for an individual of a combination parnate and pindolol. I would like to refer at the subject-title.
Kind regards
sdb
> >Almost every betablocker has a similar molecular structure but not all. And even if the structure is similar the effects are different and vary. Betablockers have different actions concerning endocrinology.
>
> I imagine so. I also presume you have evidence - studies of some kind to prove each beta blocker has different actions concerning endocrinology? We can't leave anything to chance afterall, or heaven forbid, be seen to make a generalization.
>
> >Furthermore the study seems to be pretty old.
>
> That study seems to have been conducted in 2000 - old by research standards maybe, but still relevant considering the length of time beta-blockers have been in use. I imagine the drugs have similar effects on human beings regardless of when the study was conducted.
>
> >If you're doing meta-analysis there are other studies bring more clarity what is meant with "increase risk for diabetes".
>
> Then please provide them. I posted what I thought was likely to be one of the studies that the person writing the wikipedia article used as his/her sources. I'd never heard of beta-blockers causing diabetes before and I wrote to that effect in my post before deciding to do a quick Google and check. When I found evidence to the contrary I was forced to re-write my original message. That study was the first I found and it seemed like a good idea to post it for medievil's perusal because this is afterall a public message board designed for mutual support not a peer reviewed research committee.
>
> I happen to be in the final stages of roasting my turkey. Had I not been rushing backwards and forwards to grease it I would have spent more time examining the evidence. If those are the standards that are expected of me around here then I'll make a note to be more careful in future.
>
> Kind regards
>
> Q
Posted by saturn on December 23, 2006, at 20:12:42
In reply to Re: pindolol, does it increase the risk of diabeti, posted by sdb on December 23, 2006, at 14:15:09
>>> MAO's can lower blood-pressure itself...
Can MAO's lower heart rate? Or do anticholinergic and adrenergic effects increase heart rate? ...Saturn.
Posted by Quintal on December 23, 2006, at 21:34:56
In reply to Re: pindolol, does it increase the risk of diabeti » sdb, posted by saturn on December 23, 2006, at 20:12:42
>Can MAO's lower heart rate? Or do anticholinergic and adrenergic effects increase heart rate? ...Saturn.
Parnate is more likely to increase heart rate after each dose since it usually has a stimulant effect and this often raises blood pressure. I noticed that my heart rate and blood pressure dropped after each dose wore off (this was my experience of it anyway and I've heard the same from others). Not sure about Nardil though from what I remember it often lowers blood pressure and heart rate. I didn't notice much change in heartbeat with Marplan except when my blood pressure was low and I had palpitations. This seemed to correct itself after a few weeks.
I had no annoying problems with MAOIs myself - I'd rate them among the most tolerable of all meds I've taken besides benzos.
Q
Posted by Quintal on December 23, 2006, at 21:51:30
In reply to Re: pindolol, does it increase the risk of diabeti, posted by linkadge on December 23, 2006, at 15:29:58
>I've read followup studies saying that pindolol does not enhance serotonin release and does not poses significant activity on 5-ht1a autoreceptors.
>These study authors theorized that augmentation must have been through an alternative mechanism.
From what I gather they are suggesting that pindolol acts more as an agonist rather than an antagonist at 5-HT1A receptors.
"Overall, these results indicate that pindolol acts as an agonist rather than an antagonist at 5-HT1A autoreceptors in awake animals. "
I'm not sure how this translates into humans taking MAOIs - maybe there is no interaction between Parnate and pindolol but when I was faced with this dilemma myself I decided to err on the side of caution - I get the impression Parnate is not very forgiving of mistakes with serotegenic meds.
Q
Posted by Quintal on December 23, 2006, at 22:38:29
In reply to pindolol + MAO somebody ever taken this? } Q + all, posted by sdb on December 23, 2006, at 17:04:05
> Hi Quintal,
>
> You are welcome. Thanks for your help and your input. I think you're absolutely right that some betablockers should be carefully used for people with diabetes risk such as positive family anamnesis, pathological glucose tolerance and steroid medication. You know, in Great Britain it is discussed to avoid betablockers in first line treatment in essential hypertension. There are many new meds for hypertension available such as ACE-inhibitors, AT1-antagonists, vasodilators...
> But a definitive fact is that betablockers are still widely and effectively used since many years for hypertension but many other cardiovascular disorders too.
As I said, this is the first I've heard about beta blockers increasing the risk of diabetes and I did not raise the topic, but I find it interesting nevertheless.Here is a more detailed abstract from that beta blocker study:
__________________________________________________
Drug High Blood Pressure Treatment Increases Diabetes Risk
It was traditionally believed that some drugs used to treat high blood pressure might cause diabetes. Previous research has suggested that beta-blockers and other drugs called thiazide diuretics may lead to diabetes. However the results of a new study show that beta-blockers are the only blood pressure drugs linked to the disease.Potential mechanisms by which beta-blockers may contribute to the development of diabetes include weight gain, attenuation of the beta-receptor-mediated release of insulin from pancreatic beta cells, and decreased blood flow through the microcirculation in skeletal-muscle tissue, leading to decreased insulin sensitivity.
The results are based on a study of more than 12,000 people aged 45 to 64 who did not have diabetes. At the start of the study, participants underwent a physical examination, which included blood pressure measurements and an interview about the medications they were taking.
The study also found that just having high blood pressure more than doubles a person's risk of developing type 2 diabetes, which usually begins in adulthood. Interestingly, the data from both short-term and long-term studies indicate that ACE inhibitors may actually improve insulin sensitivity and decrease the risk of type 2 diabetes.
The New England Journal of Medicine 2000;342:905-912, 969-970
http://www.mercola.com/2000/apr/2/htn_drugs_cause_diabetes.htm
__________________________________________________"Monoamine oxidase (MAO) inhibitor activity (isocarboxazid [e.g., Marplan], isocarboxazid [e.g., Marplan], phenelzine [e.g., Nardil], procarbazine [e.g., Matulane], selegiline [e.g., Eldepryl], tranylcypromine [e.g., Parnate])—Taking beta-blockers while you are taking or within 2 weeks of taking monoamine oxidase (MAO) inhibitors may cause severe high blood pressure "
http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202087.html
Most sources say there is only a likelihood of increased hypotensive effect. I don't really know what to believe but with Parnate but I know I wouldn't want to take the chance unless I was under close medical supervision.
Q
Posted by yxibow on December 24, 2006, at 4:05:42
In reply to Re: pindolol + MAO somebody ever taken this? } Q + all » sdb, posted by Quintal on December 23, 2006, at 22:38:29
Just a word to the wise to discuss the risks of certain ACE inhibitors with your doctor. An early one gave my mother permanent angioedema.
Even the clonidine I take PRN for a rare very mild but distressing sialorrhea possibly caused by an antipsychotic (not clozaril and not for psychosis) -- not to mention it actually does have some anxiolytic potential in general -- can cause temporary angioedema.
I haven't heard of beta blockers being a major cause of lipid changes but I would imagine that anything that affects that system could possibly do so. Its certainly not something discussed much with propranolol that I've heard of.
I think first in mind for taking beta and alpha (and the more rare alpha-beta ones) blockers off label for anxiety is, is your pulse normally around 60 or so, and do you have concomitant high blood pressure, and if taken regularly cannot be discontinued suddenly, but must be tapered.
Posted by SLS on December 24, 2006, at 6:27:37
In reply to Re: pindolol, does it increase the risk of diabeti, posted by linkadge on December 23, 2006, at 15:29:58
> I've read followup studies saying that pindolol does not enhance serotonin release and does not poses significant activity on 5-ht1a autoreceptors.
>
> These study authors theorized that augmentation must have been through an alternative mechanism.
>
> http://jpet.aspetjournals.org/cgi/content/full/291/1/229
Interesting.What if pindolol were selective for postsynaptic receptors instead of somatodendritic autoreceptors? It might reduce the accomodation produced by fluoxetine during the first few weeks of treatment, apparantly accelerating the antidepressant response. However, it would not actually act to increase the ultimate response rate.
Just a way-out-there thought.
- Scott
Posted by medievil on December 24, 2006, at 9:43:14
In reply to Re: pindolol, does it increase the risk of diabeti » linkadge, posted by SLS on December 24, 2006, at 6:27:37
thx for your response guys
what about a ace inhibitor? will that one prevent hypertensive crisis? or is there no med that could prevent it?
Posted by linkadge on December 24, 2006, at 11:31:57
In reply to Re: pindolol, does it increase the risk of diabeti » linkadge, posted by Quintal on December 23, 2006, at 21:51:30
PArnate didn't agree with me. I did my best to follow the diet, but my heart rate doubled one day and BP through the roof. Sent me to the ER.
That was the end of that.
Linkadge
Posted by linkadge on December 24, 2006, at 11:38:54
In reply to Re: pindolol, does it increase the risk of diabeti » linkadge, posted by SLS on December 24, 2006, at 6:27:37
>What if pindolol were selective for postsynaptic >receptors instead of somatodendritic >autoreceptors? It might reduce the accomodation >produced by fluoxetine during the first few >weeks of treatment, apparantly accelerating the >antidepressant response. However, it would not >actually act to increase the ultimate response >rate.
Thats a possability. Apparently propranolol has a similar effect to pindolol. On paper it should be able to augment SSRI's like pindolol.
I still contend that a potent selective serotonin presynaptic autorecptor antagonist would be a fast acting cure for some people's depression.
Linkadge
Posted by willyee on December 26, 2006, at 3:52:08
In reply to pindolol + MAO somebody ever taken this? } Q + all, posted by sdb on December 23, 2006, at 17:04:05
Ive used the Beta Blocker LOPRESSOR MANY MANY times with parnate,both alone and with a BENZO,the only effect i got was one of relieaf or no appearent effect at all.
Posted by sdb on December 27, 2006, at 16:19:21
In reply to Re: pindolol, does it increase the risk of diabeti, posted by medievil on December 24, 2006, at 9:43:14
Dear medievil,
If you have a normal blood pressure for your age and you don't have a kidney disease producing to much renin it really does not make sense to take an ACE-inhibitor. An ACE-inhibitor blocks indirectly the effects of renin a protease released by the kidneys. If you're hypotensive because of an ACE-inhibitor it does not mean that you're totally secure from a hypertensive crisis caused by a MAO. Theoretically it would make more sense to take a selective betablocker or an alpha-receptor blocker because of tyramines indirect release of noradrenaline in peripheral vascular tissues such as the brain and the kidneys. IMO following the diet is the best strategy but if you're already hypertensive without meds I would ask your doc what's the best way to lower your blood pressure during a Parnate treatment.
sdb
> thx for your response guys
>
> what about a ace inhibitor? will that one prevent hypertensive crisis? or is there no med that could prevent it?
This is the end of the thread.
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