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ACE inhibitors

Category: Medicines

Type

Involuntary

Introduction and description

hugely simplistic diagram showing process

One mechanism in the body for maintaining the blood pressure is the release of a protein called renin from cells in the kidney. This produces another protein called angiotensin, which affects the adrenal gland.

When blood pressure falls or the salt water balance of the body is disturbed,  the kidneys release renin. 

A fairly complex process then follows where angiotensin is worked on by an Angiotensin Converting Enzyme (ACE)  and then goes on to stimulate the adrenal glands  to increase blood pressure by increasing the amount of salt and water the body retains.  Angiotensin is also very good at causing the blood vessels to tighten (a potent vasoconstrictor).

ACE inhibitors or angiotensin-converting enzyme inhibitors act clinically via your kidneys and they block or ‘inhibit’ the Angiotensin Converting Enzymes (ACEs).  By doing this they aim to lower blood pressure, which is why they are "used in the treatment of hypertension and congestive heart failure". 

In detail what ACE inhibitors aim to do is lower arteriolar [artery] resistance and increase venous [vein] capacity; increase cardiac output, cardiac index, stroke work, and volume; lower renovascular resistance; and help with excretion of sodium in the urine.

That is the theory.

Some more detail

The body is a hugely intricate system with a far more complex series of interactions than is implied in the rather naive description given above and used as the rationale for prescribing ACE inhibitors.

source Wikipedia

 

The entire system looks much more like the diagram shown to the left and even this is simplified.

There are far more control loops in place than just the one specified as can be seen, the lungs, the liver and even the brain is involved and the hormone corticotropin, so to a large extent, the side effects of ACE inhibition could have [and do have] some very far reaching effects.

And these consequences have never been properly explored.

Let me follow up an example.   Adrenocorticotropic hormone (ACTH), also known as corticotropin, is a polypeptide tropic hormone produced and secreted by the anterior pituitary gland. It is an important component of the hypothalamic-pituitary-adrenal axis and is often produced in response to biological stress (along with its precursor corticotropin-releasing hormone from the hypothalamus). Its principal effects are increased production and release of corticosteroids.

Corticosteroids are involved in a wide range of physiological processes, including stress response, immune response, and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte levels, and behavior.

ACE-Inhibitors and angioedema.  20/08/2012 by Carlo D'Apuzzo.
"A quite big tongue in an usual Ace-inhibitor user"

Thus if we interfere with the cycle we could get inflammation, psoriasis, rheumatism, increased weight as a consequence of poor carbohydrate usage, and aching muscles because of poor protein catabolism. And indeed, in some people, these effects are exactly what does result from taking ACE inhibitors.

There is a condition called angiodema, which is an inflammatory response to toxins and this response has been recorded in ACE inhibitor users.  The picture shows a man with a swollen tongue  from taking ACE inhibitors.

fromeHealthme case reports  Asked by DBL on Jul, 1, 2014 at 9:27 pm:  Age: 60   Gender: male; Conditions: Diabetic, Bullous Pemphigoid ; Medications: Lisinopril, Metformin, Victoza
Details:
I have not developed blisters, just hives. I have been tested for most common allergies and appear not to have allergies. I have seen some descriptions on line and with drugs that seem to indicate a relation between these drugs and Bullous pemphigoid, but I have not been able to find more than a line or so about this. Does anyone have more info??

Efficacy

suspected drug reaction

It is not possible to claim that ACE inhibitors 'work', as one cannot compare the effects of having or not having the drug with the same patient. Thus any study which claims efficacy is flawed.

Given that heart problems and atherosclerosis are caused by:

  • viruses,
  • toxins - including heavy metals
  • parasites,
  • fungi,
  • bacteria [such as that in the mouth when you have tooth decay or gingivitis],
  • radiation
  • nutritional deprivation

any improvement in a patient is more likely to be caused by the body having eradicated the cause by itself via the immune system.

case report from eHealthme Posted by sharonafix on Jul, 29, 2014 at 4:05 pm:   Age: 67   Gender: female; Conditions: Eyelid Swelling & Reddish; Medications: Lisinopril     Details: I have been taking Lisinopril for over 1 year. My eyelids started swelling and became very red, itching and swollen. I tried home remedies for allergies but nothing helped. My physician thinks I was having a reaction from Lisinopril.

These drugs certainly do not cure and they may actually slow the healing process down because of their side effects.

And there is sufficient anecdotal evidence to show they do not work, even at the rather naive level implied by the introductory section.  Even I have had some alarming effects - my blood pressure has  gone up to dangerous levels after taking these drugs and it was not high before.  And it appears I am not alone, the eHealthme site reports 1,174 people on Altace with the same problems - hypertension.

Side-effects

All the following side-effects have been obtained from the eHealthme web site, which is a composite record of the actual side effects reported to doctors and registered in the USA through FDA and SEDA.

Kidney disease - and in some cases failure.  Anyone who already has kidney problems should thus not use these products.  ACE inhibitors can induce or exacerbate renal [kidney] problems especially if the person is taking an NSAID or a diuretic.  This LINK takes you to the eHealthme list of drugs causing acute renal failure.  Lisinopril, for example, as of mid 2014 had caused  2,532 cases of acute renal failure.  Ramipril had caused 819, Quinapril had caused 107.  Unfortunately the eHealthme site separates all the different forms of kidney disease, so you never get a complete picture, but if we take kidney cysts, for example, Lisinopril has caused 403 cases and 416 cases of something they call loosely renal 'disorder'.   

Death - ACE inhibitors have caused deaths, in many cases the cause was kidney failure.  The following figures come from the eHealthme web site and show the number of deaths caused by each drug:

  • Ramipril - the number of deaths as of mid 2014 was 523
  • Lisinopril - the number of deaths as of mid 2014 was 1,837
  • Enalopril - the number of deaths as of mid 2014 was 486
  • Quinapril - the number of deaths as of mid 2014 was 101
  • Benazepril - the number of deaths as of mid 2014 was 55
  • Captopril - the number of deaths as of mid 2014 was 277

Potassium imbalance - You have to watch potassium levels in your body very very carefully if you use ACE inhibitors because suppression of angiotensin leads to a decrease in aldosterone levels. Since aldosterone is responsible for increasing the excretion of potassium, ACE inhibitors ultimately cause retention of potassium - hyperkaelemia.  Hyperkaelemia in its turn produces:

 

 

Zinc deficiency - According to at least one paper [see below] ACE inhibitors have caused zinc deficiency and zinc deficiency is associated with numerous diseases. Because it is so closely tied with the immune system, we can become more susceptible to just about every disease.  Zinc deficiency is extremely serious, please follow the link to get the full description.  For example, it can lead to

  • Taste, smell and sight deterioration. macular degeneration and blindness, hearing loss and loss of the sense of smell, simply because cells are not being replaced
  • Cognitive function deterioration – memory and reasoning can be impaired and lead to dementia, as dying cells are not replaced.
  • Psychological disorders - Plasma zinc level has been associated with many psychological disorders.

Antihypertensive medicines are to known to cause diverse disturbances to electrolyte homeostasis; however, their potential to affect zinc is less well known. The primary aim was to explore whether antihypertensive medicines have the potential to affect zinc status.
Studies reported increased urinary zinc losses for captopril (from 50 mg/day), enalapril (20 mg/day), ….. captopril (75 mg/day) …..Serum levels of zinc decreased with captopril (50-150 mg/day), …. The available evidence suggests that use of ACE inhibitors …. have the potential to reduce zinc levels in hypertensive patients. PMID: 23279674

Nausea and vomiting as well as diarrhoea – both these are indicators that the body regards them as toxic substances and is trying to get rid of them

 

 

Hypotension - assuming that potassium imbalance does not raise blood pressure, ironically the other common side effect is hypotension - low blood pressure with all that entails - dizziness, light headedness, weakness, faintness, hallucinations, and in the elderly the risk of falls.

Hypotension represents an important side effect of ACE-inhibitors. It is predominantly due to either inhibition of systemic and/or local angiotensin II formation or to reduce degradation of bradykinin. If the activity of the renin-angiotensin system is stimulated, as in severe congestive heart failure and/or by diuretic pretreatment, the risk for the occurrence of hypotension is therefore increased. ...... The overall incidence of hypotension is about 2-4% in mild to moderate and about 5-8% in severe heart failure. Reduction of the dosage of the ACE-inhibitor ... usually results in normalization of blood pressure, .... PMID: 2024538

Depression, anxiety and suicide - a considerable number of reports have been received via SEDA and the FDA of both depression and anxiety resulting from ACE inhibitors.  This LINK takes you to the eHealthme general list of medications with a record of causing depression and you will see that ACE inhibitors figure quite prominently.  Ramipril, for example, had 435 case reports as at mid 2014. Lisinopril had an even greater number - 2,658.  This LINK shows the drugs causing anxiety and again ACE inhibitors feature strongly.  If we take Lisinopril, 4,135 case reports have been registered and Ramipril had 466.

Dermatitis, psoriasis, itching, rosacea and other skin problems - a whole range of skin problems appear to be caused by ACE inhibitors, or are side effects of the medication, for example:

Pityriasis rosea-like drug eruptions have been associated with numerous medications, including angiotensin-converting enzyme inhibitors, antirheumatic drugs, lithium, and, more recently, biologics such as imatinib, adalimumab, and etanercept. A literature review did not reveal an association between PR-like drug eruptions and tricyclic antidepressants such as nortriptyline. We report a case of PR-like drug reaction to nortriptyline for clinical interest. PMID: 23343697

Lisinopril, for example, had caused 332 cases of dermatitis and 338 cases of psoriasis by mid 2014, Ramipril had caused 91 cases of dermatitis and 79 cases of psoriasis. 

"ACE-inhibitor-induced angioedema
affecting the upper lip"

Pain - the pain is possibly a by product of any potassium imbalance created, as cramps and myalgia are a side effect of this.

Macular degeneration - blurred vision, and sight impairment is another side-effect, for example there are 144 case reports of macular degeneration on eHealthme for Lisinopril though only 18 for Ramipril. 

Pregnancy problems - ACE inhibitors should not be used if you are pregnant, they can cause all sorts of problems including still births – the following describes a controlled experiment to assess the effects:

An inhibitor of angiotensin-I-converting enzyme activity (D-3-mercapto-2-methylpropanoyl-L-proline, Captopril) was given to five ….pregnant ewes and eleven rabbits in late pregnancy. …. All ewes went into spontaneous labour at or near term. One lamb was live-born but very weak and failed to establish suckling. The remaining seven lambs were fresh still-births. ….. Gestation length was significantly prolonged in the treated rabbits by comparison with ten controls. The still-birth rate was 37% in the treated animals and 6% in the controls … The observations suggest that the drug rapidly crosses the placenta, and may cross the blood-brain barrier to exert a central effect. It may also interfere with the normal initiation of parturition.  PMID:  7047718

 and this is also of interest:

from Lawyersandsettlements.com
Waltham, MA: In the wake of a study published in June 2006, in The New England Journal of Medicine found a higher rate of birth defects in infants born to mothers who filled prescriptions for Angiotensin-Converting Enzyme Inhibitors (ACE inhibitors), during the first trimester of pregnancy.
The FDA advised women to reconsider the use of those drugs before becoming pregnant.....ACE Inhibitors cause birth defects

"I think what's most important about the study," Dr Kweder stated, "is that it just brings to light the importance of women carefully reviewing medication information with their health care providers before becoming pregnant or as soon as they become pregnant, and being aware of the potential risks of certain medicines."

Drugs used in the treatment of hypertension are real money makers for the pharmaceutical industry because they need to be taken for life, once a patient is diagnosed with the condition and ACE inhibitors are the most commonly prescribed.

According to Web MD, there are currently 10 ACE inhibitors marketed in the US. In 2005, they collectively brought in $5 billion in sales, up 13% from 2004, according to the pharmaceutical market research firm IMS Health. They are the second most commonly prescribed class of drugs, and 149 million prescriptions for ACE inhibitors were written in 2005. The top three sellers are Lotrel, Altace, and Lisinopril

 

How it works

 

As you can see from the side effects, the mechanism by which spiritual experiences  - hallucinations in particular - are obtained can be varied.  It is clear one major cause is hypotension.

It is rare for doctors to work out the dose based on age or weight thus if one loses weight you could to all intents and purposes be upping the dose without realising it.  The table below shows the doses often recommended and there is no mention of weight or age.

ACE inhibitors dosages for hypertension

 

 

Dosage

Note: bid = 2 times a day, tid = 3 times a day, d = daily
Drug dosages from Drug Lookup, Epocrates Online.

Name

Equivalent daily dose

 

Start

Usual

Maximum

Benazepril

10 mg

 

10 mg

20–40 mg

80 mg

Captopril

50 mg (25 mg bid)

 

12.5–25 mg bid-tid

25–50 mg bid-tid

450 mg/d

Enalapril

5 mg

 

5 mg

10–40 mg

40 mg

Fosinopril

10 mg

 

10 mg

20–40 mg

80 mg

Lisinopril

10 mg

 

10 mg

10–40 mg

80 mg

Moexipril

7.5 mg

 

7.5 mg

7.5–30 mg

30 mg

Perindopril

4 mg

 

4 mg

4–8 mg

16 mg

Quinapril

10 mg

 

10 mg

20–80 mg

80 mg

Ramipril

2.5 mg

 

2.5 mg

2.5–20 mg

20 mg

Trandolapril

2 mg

 

1 mg

2–4 mg

8 mg

 

 

 

 

 

 

But this may only be one of several mechanisms and there is also a high likelihood that one of the knock-on effects of the Potassium imbalance is also a prime contributor, most of the illnesses resulting from Potassium imbalance can result in experiences.

And of course there is the ultimate spiritual experience - death

from http://www.peoplespharmacy.com/2013/06/06/lisinopril-side-effects-can-be-lethal/
"One night after taking lisinopril my lips began to swell as if I had a fever blister. Within two hours my face was extremely swollen and my throat began to feel like it was closing off my air passage. I went to the hospital and spent the night in the emergency room with an IV and other meds. "The doctors identified that I had a reaction from the lisinopril. I still had some swelling a full 24 hours after the incident. I was told that I was lucky and that they were close to doing a tracheotomy. .. I would strongly advise alternative medications other than lisinopril, and recommend anyone who has been taking this for any length of time have a discussion with their physician. "The final advice I have is that if you have a reaction seek medical attention immediately." Gary

Observations

The observations all come from eHealthme.  [correct as at 2010] Because they classify everything as an hallucination we have no information about whether the hundreds of experiences caused by these drugs were hallucinations or visions or out of body experiences!

I have provided a link to the eHealthme website for each drug so that you are able to see all the side-effects of each drug.

Observation identifiers

Observation name

Number of hallucinations

001112

Lisinopril

207

001113

Ramipril [Altace]

87

001114

Enalapril

46

001115

Quinapril

37

001116

Benazepril [Lotril]

17

 

Perindopril

17

 

Coversyl

13

001117

Captopril

87

 

Capoten

17

 

Fosinopril

19

 

Monopril

25

 

TOTAL

571

Other branded ACE inhibitors include the following although the eHealthme web site has no record of hallucinations with this product.  Note that this reflects the number of users rather than their effects as the products above are very extensively prescribed:

  • Zofenopril

The Lactotripeptides Val-Pro-Pro and Ile-Pro-Pro produced by the probiotic Lactobacillus helveticus or derived from casein have been shown to have ACE-inhibiting and antihypertensive functions.

Related observations