Adverse effects

My hospitalized patient has developed hyperkalemia while on heparin prophylaxis. Can heparin really cause hyperkalemia and what is its mechanism?

FA Manian MD, MPH, , , , , , , , Leave a comment

Heparin is one of the most overlooked causes of hyperkalemia in hospitalized patients, occurring in 5-8% of treated patients, including those on thromboprophylaxis1.

The mechanism of heparin-induced hyperkalemia appears to be through suppression of aldosterone synthesis by inhibiting the function of the glomerulosa zone of the adrenal medulla2,3.  Such inhibitory action is usually of no consequence when renal function is normal and potassium excretion is not otherwise impaired.

The risk of heparin-induced hyperkalemia is increased in the elderly, those with preexisting diabetes mellitus or renal insufficiency, as well patients on concomitant use of certain drugs such as spironolactone, ACE inhibitors, NSAIDs, and trimethoprim2. 

Hyperkalemia is usually detected after at least 3-4 days of treatment with subcutaneous heparin, and usually resolves within a few days of  discontinuation of therapy1,2.  Fractionated heparin products such as enoxaparin may also be associated with hyperkalemia2 but the risk appears to be lower1.

Fludrocortisone has been used to normalize serum potassium in patients who  remain on heparin.4

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References

  1. Potti A, Danielson B, Badreddine R, et al. Potassium homeostasis in patients receiving prophylactic enoxaparin therapy. J Thromb Haemost 2004;2:1208-9. http://onlinelibrary.wiley.com/doi/10.1111/j.1538-7836.2004.00791.x/pdf
  2. Thomas CM, Thomas J, Smeeton F, et al. Heparin-induced hyperkalemia. Diabetes Res Clin Pract 2008;80:e7-e8. https://www.ncbi.nlm.nih.gov/pubmed/18343525
  3.  Liu AA, Bui T, Nguyen HV, et al. Subcutaneous unfractionated heparin-induced hyperkalemia in an elderly patient. Australas J Ageing 2009;28:97. https://www.ncbi.nlm.nih.gov/pubmed/19566805
  4. Brown G. Fludrocortisone for heparin-induced hyperkalemia. CJHP 2011;64:463-4. https://www.cjhp-online.ca/index.php/cjhp/article/view/1091/1394

 

My hospitalized patient has developed hyperkalemia while on heparin prophylaxis. Can heparin really cause hyperkalemia and what is its mechanism?

My patient is being treated for a urinary tract infection with trimethoprim-sulfamethoxazole (TMP-SMX) and has developed hypoglycemia. Can it be related?

FA Manian MD, MPH1 Comment

Yes! The sulfamethoxazole component of TMP-SMX contains the identical sulfanilamide structural group as sulfonylureas used as oral hypoglycemics1.  It appears to act through mimicking the action of sulfonyureas on the pancreatic islet cells by acting as an insulin secretagogue leading to increased insulin secretion1.   Increased levels of plasma insulin dropping  following interruption of TMP-SMX has been reported,  and is thought to be dose and time dependent1,2.

A major risk factor for this complication is impaired renal function, but poor hepatic function, and concurrent use of drugs that decrease plasma glucose levels have also been implicated (1,2).  Occasionally there are no obvious risk factors.

sulfapiced

 Bonus Pearl: Did you know that sulfonamides were first noted to cause hypoglycemia in 1942, when they were used for treatment of typhoid, paving the way for the development of sulfonylureas as the original oral hypoglycemic agents . The Power of observation strikes again!

References

  1. Forde DG, Aberdein J, Tunbidge A, et al. Hypoglycemia associated with co-trimoxazole use in a 56-year-old caucasian woman with renal impairment. BMJ Case Reports 2012;doi:101136/bcr-2012-007215.
  2. Nunnai G, Celesia BM, Bellissimo F, et al. Trimethoprim-sulfamethoxazole-associated severe hypoglycemia: a sulfonylurea-like effect. Eur Rev Med Pharmacol Sci 2010;14:1015-18.
My patient is being treated for a urinary tract infection with trimethoprim-sulfamethoxazole (TMP-SMX) and has developed hypoglycemia. Can it be related?

Does marijuana use lead to any adverse cardiovascular effects?

FA Manian MD, MPH, , , , , Leave a comment

Although marijuana is often not considered to have serious cardiovascular effects, in animal studies THC, the active ingredient in cannabis, has been found to affect cardiovascular activity through a number of mechanisms, including inhibition of adrenal catecholamine secretion and modulation of cardiac vagal tone through inhibition of norepinephrine release from sympathetic neurons (1).

There have also been reports of temporal association between marijuana use and acute coronary syndrome, cardiac arrhythmias, cerebrovascular events, including TIA’s, strokes, and cerebral vasospasm, as well as peripheral vascular events, including arteritis, Raynaud’s phenomenon, and digital necrosis (2).

In a recent comprehensive case series, about 2.0 % of all cannabis-associated adverse events were reported cardiovascular in nature, with 25% resulting in death (2). However, it is often difficult to determine the relative contribution of marijuana and other concurrent conditions or substances (e.g. alcohol and tobacco) when cardiovascular complications occur. More research in this area is needed.

References

1. Szabo B, Nordheim U, Niederhoffer N. Effects of cannabinoids on sympathetic and parasympathetic neuroeffector transmission in the rabbit heart. J Pharmacol ExpTher 2001; 297:819-826. http://jpet.aspetjournals.org/content/297/2/819

2. Jouanjus E, Lapeyre-Mestre M, Micallef J, et al. Cannabis use: signal of increasing risk of serious cardiovascular disorders. J Am Heart Assoc 2014; 3:e000638.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4187498/

Contributed by Pierre Ankomah, MD, Boston, MA

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Does marijuana use lead to any adverse cardiovascular effects?

What is the mechanism of fluoroquinolone(FQ)-induced tendonopathy?

FA Manian MD, MPH, , , Leave a comment

An uncommon but serious side effect of FQs (e.g. ciprofloxacin, levofloxacin, and moxifloxacin) is Achilles tendon rupture.   A putative mechanism for this adverse effect is inhibition of host mitochondrial components (1).

Recall that mitochondria, the ATP-generating machine within our cells, are thought to be archaic bacterial ancestors that have co-evolved with us. Quinolones are inhibitors of bacterial gyrases and topoisomerases and also appear to be associated with DNA degradation of the mitochondria in some mammalian cells. In vitro, FQs appear to have a tropism for mitochondria in tenocytes, chondrocytes, and osteoblasts.  

Thus, it is possible that at least in some patients (e.g. those ≥60 years of age, on higher doses of corticosteroids, or with several renal disease or other idiosyncratic factors) the mitochondrial damage is sufficient to cause serious injury to the Achilles tendon (2).

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1. Barnhill AE, Brewer MT, Carlson SA. Adverse effects of antimicrobials via predictable or idiosyncratic inhibition of host mitochondrial components. Antimicrob Agents Chemother 2012;56:4046-4051.

2. Shakibaei M, Stahlmann R. Ultrastructure of Achilles tendon from rats after treatment with fleroxacin. Arch Toxicol 2001;75:97-102.

What is the mechanism of fluoroquinolone(FQ)-induced tendonopathy?