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QuoteWhat really happens when you mix medications? t.ted.com/1alDxbW @Rbaltman

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http://www.ted.com/talks/russ_altman_what_really_happens_when_you_mix_medications?utm_campaign=social&utm_medium=referral&utm_source=t.co&utm_content=talk&utm_term=science

QuoteIf you take two different medications for two different reasons, here's a sobering thought: your doctor may not fully understand what happens when they're combined, because drug interactions are incredibly hard to study. In this fascinating and accessible talk, Russ Altman shows how doctors are studying unexpected drug interactions using a surprising resource: search engine queries.

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"The Dangers of 'Polypharmacy,' the Ever-Mounting Pile of Pills"
http://www.nytimes.com/2016/04/26/health/the-dangers-of-polypharmacy-the-ever-mounting-pile-of-pills.html?smid=tw-nythealth&smtyp=cur

Quote
"We're not paying attention to the interactions and safety of multiple medications," said Dima Qato, the lead author of the JAMA Internal Medicine article (Dr. Alexander was a co-author) and a pharmacist and epidemiologist at the University of Illinois at Chicago. "This is a major public health problem."

I wish it had that effect on me, LOL.   

Bump.



Also going to add that another reason why beta-blockers (or those drugs that have beta blockade as a mechanism) are prescribed:


as anxiolytics.

Now why would this be a super-important thing to be aware of?

Well, because if you go to a psychiatrist that thinks that your anxiety (maybe even FA-related anxiety) needs medicating, you've got a significant chance of being prescribed a beta-blocking medication to treat that anxiety.


(I'll be back to add a few references later).

Zofran comes in a few forms.  At least one has lactose in it.  While I don't know how miniscule a risk that refined lactose may be finding out when poop has already hit the fan is not my place to find out.  So, the melty Zofran should be good.

Also, Benadryl has some barf calming effects but not nearly in the same level of Zofran.  It took the attending physician at ER and one well-connected resident with a pharm friend to find out which forms were free of any milk ingredient.

Going to bed.

-- or because there really isn't a better therapeutic option.  It's all a matter of risk-benefit, ultimately.

Some cardiac conditions just plain mandate beta-blockade.

Propranolol - epinephrine interactions are very well defined in the literature-- and have been quite well-elucidated since at least the early 1980's.

http://www.ncbi.nlm.nih.gov/pubmed/20831932

http://www.ncbi.nlm.nih.gov/pubmed/9230324

This first one is a REALLY important case study, because it demonstrates that this is not merely a theoretical risk;

http://www.ncbi.nlm.nih.gov/pubmed/23380109

http://www.ncbi.nlm.nih.gov/pubmed/8498731

http://www.ncbi.nlm.nih.gov/pubmed/17324313

All are examples of why it is so important to talk to prescribing physicians about every medication you are taking-- as well as the reasons for those prescriptions.  If you're on a beta blocker, the chances are good that stopping that beta blockade is not an option. 

Even more critical to note beta blockade with MedicAlert.

Elder DS and I both take Attenolol (actually he is off it now, his SVT is in remission), and neither allergists nor cardios have been concerned.  Maybe it's because we are on small doses?

Remember, until VERY recently most anaphylaxis happened in hospital settings-- by far.

(like, speculation is that this has only taken place within the last decade)

It has only been as atopy and food allergy have risen so dramatically that it has shifted.  This used to be a concern for maybe one patient in every few hundred, and relatively few surgical procedures were outpatient anyway.

Quote from: twinturbo on July 19, 2013, 09:34:26 AM
Full disclosure I'm limited to what I read on the internets... but in layperson terms what we're concerned with here is phenergan (or any promethazine family drug) preventing epinephrine's vasosuppressor effect. In terms someone like me, average allergy mom, would understand that means promethazine would block epinephrine's ability to contract blood vessels walls.

Anaphylaxis can include the symptom of blood vessel walls becoming flabby, less effectively able to circulate blood, resulting in an acute drop in pressure. No contraction of vessel walls to narrow, no hope of counteracting the drop in blood pressure, no way to fight shock should it occur. That particular combination of epinephrine and promethazine actually synergizers for a greater drop in pressure.

All other epinephrine effects are unaffected but for vasosuppression by promethazine? And no other drug's vasosuppressor effect can work against promethazine?

Right-- the problem is that under even partial beta-blockade (which is what this class of drugs does), epinephrine effect is unpredictable at best--  though the reason I posted this is that it is a secondary effect of the drug's MAJOR effect, which is H1-blockade... and THAT is the reason why most doctors (and even a few pharmacists) won't pick up on it as a red flag.  They think of promethazine as an anti-emetic because of it being a "first-gen antihistamine."  Sounds benign, right?    The side effects are almost all related to that H-1 blockade, and not to the other back-door mechanism that results in beta-blockade... it's neever USED as a beta-blocker, so that isn't how doctors and pharmacists encounter it.

Okay, as an aside, here, understand that one of the mental tricks that docs and pharmacists use to remember all of the stuff about therapeutic effects of drugs has them "categorizing" different drug classes into a sort of outline by effect/mechanism.  Which is fine until you get to a class which is 'dirty' in the pharmalogical sense, and has more than one mechanism of activity.  As long as that second mechanism/effect is mostly mild and benign, or impacts a receptor that isn't that important for the purposes of most patient care, it's not a big deal to not remember what that second thing is.  This is definitely a special case. 



Until pretty recently, the number of patients receiving vasopressors for "home" use (e.g. autoinjectors or anakits) was so small that this just didn't get much press...  and the effect has been recognized since at least the late 1940's, but it was the sort of thing that was a concern for HOSPITALISTS only.

Hospitals have a lot more tools at their disposal for dealing with shock-- they can titrate to a dosage that can overcome blockade, and use continuous monitoring to make it safe, basically, in a way that in-office surgeons and patients in post-op recovery at home don't really have available.  They can also use volume rescusitation in a pinch... but again, not something that is a DIY project.  Also not something you're going to live to enjoy if you aren't IN the hospital already when you need that kind of intervention.


Most of us can't just start dopamine on a drip.  KWIM?

With my last cold, I went online to see if Nyquil could be taken together alongside my typical allergy meds.

Yep, it can.

What they apparently shouldn't be taken with is SSRI's. The concerning ingredient is Dextromethorphan. It's in a few varieties of Mucinex, Nyquil, and Robitussin. It's a cough surpressant and combined with the SSRI can cause serotonin syndrome. It's rare, and I believe (correct me if I'm wrong) that it's a cumulative effect, so you'd probably have to be on a strong SSRI or over-do the cough meds. This would've been good information to know, oh, maybe 5 colds ago since I routinely take mucinex with dex. A warning on the package would've been nice. But since I think it's cumulative and I'm careful with my dosing and I'm not dead yet, I think I personally can risk it. Others, beware.

Full disclosure I'm limited to what I read on the internets... but in layperson terms what we're concerned with here is phenergan (or any promethazine family drug) preventing epinephrine's vasosuppressor effect. In terms someone like me, average allergy mom, would understand that means promethazine would block epinephrine's ability to contract blood vessel walls.

Anaphylaxis can include the symptom of blood vessel walls becoming flabby, less effectively able to circulate blood, resulting in an acute drop in pressure. No contraction of vessel walls to narrow, no hope of counteracting the drop in blood pressure, no way to fight shock should it occur. That particular combination of epinephrine and promethazine actually synergizes for a greater drop in pressure.

All other epinephrine effects are unaffected but for vasosuppression by promethazine? And no other drug's vasosuppressor effect can work against promethazine?

Phenergan/promethazine.

Quote from: CMdeux on July 18, 2013, 09:16:52 PM
Well, most beta-agonists, it's a front-and-center kind of warning.  No pharmacy is going to miss it, and most docs know enough to be wary about that entire class.


Promethazine has a slighly different mechanism, though, and so it's a secondary mechanistic thing, and that is why our surgeon initially argued with me over it.  But I made him look it up, and sure enough-- it was there under the warnings at Epocrates, it was just about four pages of fine print down.

References:

http://onlinelibrary.wiley.com/doi/10.1111/j.1749-6632.1967.tb41232.x/abstract

http://onlinelibrary.wiley.com/doi/10.1111/j.1398-9995.2007.01435.x/full

Part of the risk is related to respiratory depression, which is DEFINITELY a feature of this class of H1 agonists.  There are also some indicators in older literature that they may may mask early CUTANEOUS symptoms of anaphylaxis-- but not the more serious respiratory or cardiac features.

http://link.springer.com/chapter/10.1007/978-0-387-09709-1_7/fulltext.html

This one is the money shot:


Skip Navigation LinksHome > May/June 1959 - Volume 20 - Issue 3 > Comparison of Vasopressor Responses in the Presence of Pheno...
< Previous Abstract | Next Abstract >
Anesthesiology:
May/June 1959 - Volume 20 - Issue 3 - ppg 261-267

A wee quote, I think, from that one:

QuoteHypotension is often seen when chlorpromazine is administered, and to a less degree with the other phenothiazines.  The appearance of hypotension is alarming, but more distressing is the inability to combat this hypotension with standard vasopressors.

(Gee, all that and respiratory impairment too??  No... no thank you.  )

More general info:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3265267/

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3522494/

(both include pretty technical details of pharmacology from a receptor standpoint)


Finally--

this one from Drugs.com's database:

Quote
Epinephrine - Because of the potential for Promethazine HCl Oral Solution to reverse epinephrine's vasopressor effect, epinephrine should NOT be used to treat hypotension associated with Promethazine HCl Oral Solution overdose.

and later;

Quote
The treatment of choice for resulting hypotension is administration of intravenous fluids, accompanied by repositioning if indicated. In the event that vasopressors are considered for the management of severe hypotension which does not respond to intravenous fluids and repositioning, the administration of norepinephrine or phenylephrine should be considered. EPINEPHRINE SHOULD NOT BE USED, since its use in patients with partial adrenergic blockade may further lower the blood pressure. Extrapyramidal reactions may be treated with anticholinergic antiparkinsonian agents, diphenhydramine, or barbiturates.Oxygen may also be administered.

The problem isn't-- exactly-- that it makes epinephrine less useful.  It's that as long as they're taking it, it makes epinephrine worse than useless in terms of combatting anaphylactic shock.  It's a paradoxical effect-- and one which mostly only pharmacology geeks like me know about.

BTW, no advice being offered here-- this is just something to DISCUSS with a physician.  There are alternatives to the phenothiazines, which are most often given as anti-emetics (that is, they are anti-nausea drugs).  Zofran is in an entirely different drug class, for example.

Beta blockade is NOT compatible with epinephrine-- this includes beta-blockers and those drugs which do so through a secondary mechanism (like the phenothiazines).  It means that epinephrine can't do what it is supposed to do-- this is why many allergist's offices won't do food challenges, immunotherapy, or even (in some cases) skin testing on patients under beta blockade.  If they anaphylax, there isn't much that can be done from a pharmacological standpoint.  Not good.