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Diuretics

Category: Medicines

Type

Involuntary

Introduction and description

 

Diuretics are a class of drug used to treat fluid retention - oedema

They, like many pharmaceuticals, have a record for producing hallucinations and other 'spiritual experiences', one of which is death, as such an examination is due.

Oedema and its causes

Odema can be caused by  lymph system disease.  The lymph system is a closed system.  Fluid enters through the walls of lymphatic vessels, which can stretch to hold more fluid as necessary.  The lymphatic system has no heart to pump lymph round the body.  Lymphatic vessels can contract, but the circulation of lymph depends mainly on external pressure, lymph is squeezed along vessels by the pressure associated with breathing, intestinal movements and the movements of skeletal muscles.  Thus any form of blockage or damage may cause oedema and inadequate pressure [poor breathing practises, lack of exercise etc] may also be the cause.

The lymph system should be the first system examined by doctors, but it rarely is, most doctors only examine the secondary causes - which are the renal or cardiovascular system.  In effect

In each case alternative treatments already exist with which to treat the oedema resulting from these conditions.  Follow the links to find out more.

 

One might expect that if you have fluid retention and an excess of water in your body as a result of heart disease, kidney failure, lymph system disease or liver disease, that the principle line of attack would be first of all to treat the root cause – the heart problems, the liver problems, the lymph system problems or the kidney problems.

And this is often the course of action taken.  But there also appears to be a medical school of thought that – being symptom based and not root cause based – treats each symptom in an isolated way and in this respect diuretics have emerged to treat water retention – too much fluid in the body.  Diuretics are also often abused by sufferers of eating disorders, especially bulimics, in the mistaken belief that loss of water = loss of weight, which it is in a sense, but hardly the sort that matters.

A diuretic thus provides a means of forced diuresis which elevates the rate of urination.

Types of diuretic

Interestingly diuretics are not based on vasopressin/ADH.  There are several categories of diuretics and whilst all diuretics increase the excretion of water from bodies, each class does so in a distinct way.  In general they achieve their effects through manipulation of the minerals in the body – the sodium balance in particular – at various stages of processing in the kidneys.  This is shown in the diagram below [from Wikipedia] that shows the classes and the area of activity

 

There are four main types of diuretic.  The detailed description for each of these can be found in the science section of the website.

  • Loop diuretics  - are primarily used to treat hypertension and oedema due to congestive heart failure or renal insufficiency.  Like many diuretics, this class of drugs can thus cause electrolyte imbalance, including loss of potassium, calcium, sodium, and magnesium. This loss of minerals affects the nervous system and can also result in reduced bone density – osteoporosis.   Another rare side effect is hearing loss.  Loop diuretics may also precipitate renal failure in patients concomitantly taking an NSAID and an ACE inhibitor
  • Thiazide diuretics  - are also used to treat hypertension (high blood pressure) and oedema (such as that caused by heart, liver, or kidney disease).  The members of this class of diuretics are derived from benzothiadiazine. This class of drugs can also cause electrolyte imbalance, including loss of potassium, calcium, sodium, and magnesium.  It can produce gout.  Other side effects include weight gain, headaches, impotence and high blood sugar leading to diabetes
  • Carbonic anhydrase inhibitors  - inhibit the enzyme carbonic anhydrase which is found in the proximal convoluted tubule. This results in several effects including bicarbonate retention in the urine, potassium retention in urine and decreased sodium absorption.  There is only one drug in this class.  Common side effects of using this drug include numbness and tingling in the fingers and toes, taste alterations, blurred vision, and kidney stones
  • Potassium-sparing diuretics  - are diuretic drugs that do not promote the secretion of potassium into the urine.  They are used as adjunctive therapy, together with other drugs, in the treatment of hypertension and management of congestive heart failure.  On their own this group of drugs may raise potassium levels beyond the normal range, termed hyperkalemia, which risks potentially fatal arrhythmias.  The risk is high in concurrent use of ACE inhibitors.  Although potassium  may be spared, calcium isn’t and this class of drug tends to increase the calcium lost in urine.

Side effects in more detail

 

Using the information from the Adverse Drug Reports submitted by doctors to the FDA and SEDA and summarised on the eHealthme website, we can now look in more detail at the figures and side effects for actual drugs as opposed to classes of drugs.

If we take an extract from the table for Hydrochlorothiazide (abbreviated HCTZ, HCT, or HZT), and chosen because in 2008 it was the second most commonly used blood pressure medication in the United States, we find the following:

Most common side effects over time  :

< 1 month

1 - 6 months

6 - 12 months

1 - 2 years

2 - 5 years

Renal Failure Acute

Dehydration

Dizziness

Dizziness

Anxiety

Hyponatraemia

Hyponatraemia

Dyspnoea

Hypotension

Fatigue

Dizziness

Renal Failure Acute

Hyponatraemia

Fatigue

Pulmonary Embolism

Dyspnoea

Dizziness

Renal Failure Acute

Dyspnoea

Dyspnoea

Hypokalaemia

Nausea

Dehydration

Pulmonary Embolism

Nausea

Vomiting

Diarrhoea

Hypertension

Syncope

Deep Vein Thrombosis

Dehydration

Hypokalaemia

Hypotension

Nausea

Dizziness

Asthenia

Asthenia

Death

Bradycardia

Pain

Hypotension

Fall

Syncope

Oedema Peripheral

Diarrhoea

Nausea

Hypotension

Back Pain

Pain

Chest Pain

 another example................

eHealthme case study  Louise (5 years ago):

Took this drug for approx. 3 months. Suffered the following:
- Extreme nausea/dizziness/fainting (at least 3 times a day)
- Constant menstruating (before the drug, my periods came regularly)
- Severe depression (no depression or down tendencies prior to taking the drug)
- Lack of sex drive
- Lack of drive to eat
- Extreme lethargy
- Itchy skin.
I wish records of side effects had been made more public prior to me taking this drug. Then I would have at least known what to look out for - the lack of information - leads to uncertainty, a general questioning of ones self and confusion. My advice is - if you notice differences - monitor them, ask friends if they've noticed changes in you at all. This drug majorly negatively affected my life. Be careful!

 Death

 

Again, using the ADRs summarised on the eHealthme site, the figures for deaths - the ultimate spiritual experience - are shown below:

Spironolactone and its trade names

  • On Aug, 24, 2015: 25,396 people reported to have side effects when taking Spironolactone. Among them, 753 people (2.97%) have Death
  • On Aug, 29, 2015: 76 people reported to have side effects when taking Spironolactone and hydrochlorothiazide. Among them, 3 people (3.95%) have Death
  • On Aug, 29, 2015: 113 people reported to have side effects when taking Spironolactone w/ hydrochlorothiazide. Among them, 1 people (0.88%) has Death
  • On Aug, 3, 2015: 19,966 people reported to have side effects when taking Aldactone. Among them, 594 people (2.98%) have Death

These two additional charts may also be of interest, it appears most people die within a year of taking these drugs - 75% of them- and 80% within two years.  There is also, given the age table, an indication that they are being mis-prescribed or mis-used.

Time on Aldactone when people have Death :

  < 1 month 1 - 6 months 6 - 12 months 1 - 2 years 2 - 5 years 5 - 10 years 10+ years
Death 29.63% 37.04% 14.81% 14.81% 1.85% 1.85% 0.00%

Age of people who have Death when taking Aldactone  :

  0-1 2-9 10-19 20-29 30-39 40-49 50-59 60+
Death 0.91% 1.36% 0.91% 0.91% 1.36% 7.95% 16.36% 70.23%

Triamterene and its trade names

  •  On Aug, 2, 2015: 4,166 people reported to have side effects when taking Triamterene and hydrochlorothiazide. Among them, 80 people (1.92%) have Death
  • On Aug, 8, 2015: 194 people reported to have side effects when taking Dyrenium. Among them, 3 people (1.55%) have Death
  • On Aug, 10, 2015: 6,165 people reported to have side effects when taking Maxzide. Among them, 129 people (2.09%) have Death
  • On Aug, 8, 2015: 8,191 people reported to have side effects when taking Dyazide. Among them, 104 people (1.27%) have Death
 

 Acetazolamide and trade names

  • On Aug, 29, 2015: 1,226 people reported to have side effects when taking Acetazolamide. Among them, 17 people (1.39%) have Death
  • On Aug, 17, 2015: 1,908 people reported to have side effects when taking Diamox. Among them, 39 people (2.04%) have Death

Clorthalidone and other trade names

  • On Aug, 26, 2015: 1,850 people reported to have side effects when taking Chlorthalidone. Among them, 33 people (1.78%) have Death
  • On Aug, 6, 2015: 575 people reported to have side effects when taking Hygroton. Among them, 6 people (1.04%) have Death

Hydrochlorothiazide and its trade names

  • On Aug, 1, 2015: 60,108 people reported to have side effects when taking Hydrochlorothiazide. Among them, 968 people (1.61%) have Death
  • On Aug, 29, 2015: 831 people reported to have side effects when taking Hctz. Among them, 5 people (0.60%) have Death
  • On Aug, 29, 2015: 354 people reported to have side effects when taking Microzide. Among them, 12 people (3.39%) have Death

Indapamide and its trade names

  • On Aug, 18, 2015: 6,377 people reported to have side effects when taking Indapamide. Among them, 86 people (1.35%) have Death
  • On Aug, 29, 2015: 1,440 people reported to have side effects when taking Lozol. Among them, 21 people (1.46%) have Death

Metolazone and its trade names

  • On Aug, 29, 2015: 3,536 people reported to have side effects when taking Metolazone. Among them, 174 people (4.92%) have Death
  • On Aug, 8, 2015: 3,319 people reported to have side effects when taking Zaroxolyn. Among them, 143 people (4.31%) have Death
 

Trichlormethiazide and its trade names

  • On Aug, 29, 2015: 1,128 people reported to have side effects when taking Trichlormethiazide. Among them, 14 people (1.24%) have Death

Bumetanide and trade names

  • On Aug, 18, 2015: 4,500 people reported to have side effects when taking Bumetanide. Among them, 154 people (3.42%) have Death
  • On Aug, 29, 2015: 3,998 people reported to have side effects when taking Bumex. Among them, 205 people (5.13%) have Death

Furosemide and its trade names

  • On Aug, 15, 2015: 80,019 people reported to have side effects when taking Furosemide. Among them, 2,281 people (2.85%) have Death
  • On Aug, 29, 2015: 94,488 people reported to have side effects when taking Lasix. Among them, 3,501 people (3.71%) have Death

Over 80% of the people die within a year of taking this drug according to the chart below and 90% within 1-2 years.  The profile of the age of the people who have died indicates some form of mis-prescription.

Time on Furosemide when people have Death  :

  < 1 month 1 - 6 months 6 - 12 months 1 - 2 years 2 - 5 years 5 - 10 years 10+ years
Death 61.14% 14.29% 6.29% 8.00% 6.29% 2.86% 1.14%

Age of people who have Death when taking Furosemide  :

  0-1 2-9 10-19 20-29 30-39 40-49 50-59 60+
Death 1.17% 0.32% 0.53% 0.53% 1.71% 7.05% 11.21% 77.47%

 

Others

Diuril - On Aug, 11, 2015: 306 people reported to have side effects when taking Diuril. Among them, 20 people (6.54%) have Death

Chlorothiazide - On Aug, 26, 2015: 424 people reported to have side effects when taking Chlorothiazide. Among them, 7 people (1.65%) have Death

Torsemide - On Aug, 20, 2015: 8,603 people reported to have side effects when taking Torsemide. Among them, 297 people (3.45%) have Death

Edecrin- On Aug, 1, 2015: 174 people reported to have side effects when taking Edecrin. Among them, 12 people (6.90%) have Death

 

In summary

 

Using the eHealthme Adverse Drug reports submitted to the FDA and SEDA and adding the figure up for deaths - a figure which excludes the rest of the world, as these are US figures only, and also excluding all drugs for which figures are not available - we get a total as of August 2015 of

 

9,657 deaths

 

 

 

How it works

Why do people get hallucinations?  Superficially at least, the main cause of the hallucinations appears to be hypotension and its consequences, for example:

  • Loop diuretics cause an increase in the renal blood flow. This diuresis leaves less water to be reabsorbed into the blood, resulting in a decrease in blood volume.  The collective effects of decreased blood volume and vasodilation decrease blood pressure
  •  When administered acutely thiazides lower blood pressure by causing diuresis, a fall in plasma volume and a reduction in cardiac output. However, after chronic use thiazides cause a reduction in blood pressure by lowering peripheral resistance (i.e. vasodilation).

Diuretic therapy in heart failure: current controversies and new approaches for fluid removal. - Brandimarte F, et al Department of Cardiovascular, Respiratory and Morphological Sciences, Sapienza University, Rome, Italy.
Hospitalization for heart failure is a major health problem with high in-hospital and postdischarge mortality and morbidity.
Non-potassium-sparing diuretics (NPSDs) still remain the cornerstone of therapy for fluid management in heart failure despite the lack of large randomized trials evaluating their safety and optimal dosing regimens in both the acute and chronic setting. Recent retrospective data suggest increased mortality and re-hospitalization rates in a wide spectrum of heart failure patients receiving NPSDs, particularly at high doses.
Electrolyte abnormalities, hypotension, activation of neurohormones, and worsening renal function may all be responsible for the observed poor outcomes.


It is also clear from some of the scientific papers that diuretics are chronically misprescribed, being used for conditions such as obesity.  In other words not diuretic abuse by the anorexic, but mis-prescription to someone who is just morbidly obese…….

Management of diuretic treatment: a challenge in the obese patient - Lassen CK  Jespersen B ; Department of Nephrology, Aarhus University Hospital, Skejby, Aarhus N, Skejby, Denmark.
The obesity epidemic is a major health concern. The diagnosis of acute illness and fluid imbalance in the obese patient is complicated by a wide range of comorbidities such as cardiovascular disease, obesity hypoventilation syndrome, non-alcoholic steatohepatitis and lymphoedema..... Dosing of diuretics is difficult in these patients [sic]. The blood urea:creatinine ratio should be widely used to detect emerging cardiovascular and renal complications. This report presents an obese patient with congestive heart failure due to a myocardial infarction, who subsequently was overdosed with diuretics.

There is also evidence that diuretics are used by body builders in the mistaken belief that they reduce weight and increase muscle density.

A bodybuilder with diuretic abuse presenting with symptomatic hypotension and hyperkalemia; al-Zaki T, Taibot-Stern J.
 

So there appears to be quite a bit of evidence to suggest that the hallucinations are caused by misprescription, mis-use  and over use, causing hypotension. 

Even without these reasons, however, the side-effects listed above show that these drugs are treated as hostile agents by the body - the diarrhoea, nausea etc are all indications that in many cases the reason for hallucinations is through  poisoning.

In a small number of cases it may be interactions with food and herbal medicines 

Int J Cardiol. 2005 Jan;98(1):1-14. Cardiovascular pharmacotherapy and herbal medicines: the risk of drug interaction. Izzo AA, Di Carlo G, Borrelli F, Ernst E
Use of herbal medicines among patients under cardiovascular pharmacotherapy is widespread. In this paper, we have reviewed the literature to determine the possible interactions between herbal medicines and cardiovascular drugs. The Medline database was searched for clinical articles published between January 1996 and February 2003. Forty-three case reports and eight clinical trials were identified.

  • Warfarin - Warfarin was the most common cardiovascular drug involved. It was found to interact with boldo, curbicin, fenugreek, garlic, danshen, devil's claw, don quai, ginkgo, papaya, lycium, mango, PC-SPES (resulting in over-anticoagulation) and with ginseng, green tea, soy and St. John's wort (causing decreased anticoagulant effect).
  • Digoxin - Gum guar, St. John's wort, Siberian ginseng and wheat bran were found to decrease plasma digoxin concentration;
  • Aspirin - aspirin interactions include spontaneous hyphema when associated with ginkgo and increased bioavailability if combined with tamarind.
  • Statins - Decreased plasma concentration of simvastatin or lovastatin was observed after co-administration with St. John's wort and wheat bran, respectively.
  • Diuretics - Other adverse events include hypertension after co-administration of ginkgo and a diuretic thiazide
  • Antihypertensives - hypokalemia after liquorice and antihypertensives
  • Phenprocoumon - anticoagulation after phenprocoumon and St. John's wort.

Interaction between herbal medicine and cardiovascular drugs is a potentially important safety issue. Patients taking anticoagulants are at the highest risk.
PMID: 15676159

So the route by which the effects occur is different, but the effect is generally the same.

Observations

 

 

The following summary table provides a list of all the pharmaceuticals that appear to have produced hallucinations as listed on the eHealthme web site. 

Where more detail is provided in an observation the observation reference number is shown. 

The link takes you to the eHealthme website where an up-to-date list of all the side-effects can be found. 

Observation no

Drug Name

No of hallucinations

 

Amiloride

1

005057

Spironolactone  and Aldactone

132 + 103 = 235

005058

Triamterene [trade name Dyrenium, Maxzide and Dyazide]

50 + 47 + 94 = 191

005059

Acetazolamide [sold under the trade name Diamox]

2 + 12 = 14

 -

Chlortalidone [Chlorthalidone and Hygroton]

10 + 5 = 15

005060

Hydrochlorothiazide [abbreviated HCTZ, HCT, or HZT] plus the following trade names Microzide

380 + 3 = 383

 -

Indapamide /Lozol

49 + 3 = 52

 -

Metolazone [ brand names Zytanix,  Zydus Cadila, Zaroxolyn, and Mykrox]

16 + 15 = 31

 -

Trichlormethiazide [Achletin, Diu-Hydrin and Triflumen]

2

005061

Bumetanide (trade names Bumex or Burinex)

31 + 17 = 48

005062

Furosemide previously frusemide [Lasix, Fusid and Frumex etc etc]

574 + 742 = 1,316

 -

Torasemide [ torsemide]

51

-

Chlorothiazide sodium (Diuril)

2

 

Edecrin [Etacrynic acid]

-

 

 

2,341

Figures are not available for :

  • Etozoline (Diulozin, Elkapin, Etopinil) -  a loop diuretic used in Europe.
  • Muzolimine a loop diuretic, withdrawn worldwide because of severe neurological side effects.
  • Piretanide (Arelix, Eurelix, Tauliz) - a loop diuretic sold in Germany, France, and Italy
  • Tienilic acid [ticrynafen ] -  a loop diuretic approved by FDA on May 2, 1979, and withdrawn in 1982, after case reports indicated a link between the use of ticrynafen and hepatitis

 

Related observations