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Vasodilators

Category: Medicines

Type

Involuntary and voluntary

Introduction and description

for credits see below

As the Wikipedia description of this class of drugs was very good, we have used their description. We acknowledge their 'help'.

Vasodilation (or vasodilatation) refers to the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. In essence, the process is the opposite of vasoconstriction, which is the narrowing of blood vessels.

When blood vessels dilate, the flow of blood is increased due to a decrease in vascular resistance. Therefore, dilation of arterial blood vessels (mainly the arterioles) decreases blood pressure. The response may be:

intrinsic - due to local processes in the surrounding tissue or
extrinsic - due to hormones or the nervous system

In addition, the response may be localized to a specific organ (depending on the metabolic needs of a particular tissue, as during strenuous exercise), or it may be systemic (seen throughout the entire systemic circulation).

Drugs that cause vasodilation are termed vasodilators.

Vasodilators are used to treat conditions such as hypertension, wherein the patient has an abnormally high blood pressure, as well as angina, congestive heart failure, and erectile dysfunction. The last class of drugs have been grouped under erectile dysfunction drugs. Thus what we are dealing with here is a class of drugs that are intended to treat various forms of heart failure or blood circulatory disease.

The purpose of vasodilation

The primary function of vasodilation is to increase blood flow in the body to tissues that need it most.

This is often in response to a localized need of oxygen, but can occur when the tissue in question is not receiving enough glucose or lipids or other nutrients.

The body uses many ways to increase blood flow to a specific site including releasing endogenous vasodilators, primarily adenosine, into the local interstitial fluid, which diffuses to capillary beds, provoking local vasodilation.

Some physiologists have suggested that it is the lack of oxygen itself that causes capillary beds to vasodilate by the smooth muscle hypoxia of the vessels in the region. This latter hypothesis is posited due to the presence of precapillary sphincters in capillary beds. Neither of these approaches to the mechanism of vasodilation is mutually exclusive of the other.

Vasodilation and 'arterial resistance'

Vasodilation directly affects the relationship between mean arterial pressure, cardiac output, and total peripheral resistance (TPR). In effect, it affects your blood pressure and your heart.

In theory, narrowed arteries send your blood pressure up and put a strain on the heart. Practically speaking, however, this is not true.

It is somewhat similar to a garden hose, if the hose is narrower, there is simply less water going through, it doesn't make much difference to the tap. The main problems with narrowing blood vessels is simply that you won't get enough oxygen, and by not getting enough oxygen or glucose to the tissues you will feel tired and lacking in get up and go.

If your blood vessels are very narrow or there are blockages, your get up and go will have gone.

The body thus compensates for narrowed arteries. After a large meal, when blood, oxygen and glucose are needed to digest it, an overwhelming feeling of tiredness may result. This is the time to rest or sleep - a hammock in the sun perhaps, or a cosy armchair by the fire - and let the stomach work away taking all the energy it needs. If you don't do this, it will put a strain on the heart, because you are pushing the heart by simulating 'fight or flight' to provide more oxygen and blood to more parts of the body.

In effect, it is only when you push yourself to do things you can in reality no longer do that the heart is put under strain, the blood pressure goes up, and the plaque is released and we get strokes.

To put this another way, vasoconstriction or narrowing of the arteries - whatever its cause - is not a problem unless there is a blockage, or we try to push ourselves to do things when our body is telling us to lie down and rest, and we fight against our body and what it is telling us to do.

The fallacy of blood pressure monitoring

Cardiac output (blood flow measured in volume per unit time) is computed by multiplying the heart rate (in beats per minute) and the stroke volume (the volume of blood ejected during ventricular systole).

TPR (total peripheral resistance) depends on several factors, including the length of the vessel, the viscosity of blood (determined by hematocrit) and the diameter of the blood vessel.

The latter is the most important variable in determining resistance, with the TPR changing by the fourth power of the radius. An increase in either of these physiological components (cardiac output or TPR) causes a rise in the mean arterial pressure.

This is an important factor to bear in mind if you have 'high blood pressure'. It is not only the narrowing of the blood vessels that may be causing this, but the viscosity of the blood - or as one of my pals put it 'thick blood'.

It may only be temporarily 'thick'.

All disease and illness - ALL - is caused by external pathogens or things like radiation or 'bad air'. If we are being attacked by viruses, parasites or bacteria, or we have damaged ourselves or have a wound or damage to our organs that needs repairing, or we have temporarily managed to get toxins of some sort in our blood, the blood consistency will change. There will be more immune system related cells at work and a lot of cholesterol, because the immune system uses cholesterol to repair cells and engulf toxins - entombing them.

Cholesterol is a sterol and an essential structural component of all animal cell membranes. It is required to maintain both membrane structural integrity and fluidity. In addition to its importance within cells, cholesterol also serves as a precursor for the biosynthesis of steroid hormones, bile acids, and vitamin D. Thus you should expect and even be happy that the viscosity of your blood has changed and the cholesterol levels are high if, for example:

You are old and ageing or physically damaged - if you do not have enough cholesterol to do the repairs, there will be cell death and decline - gradual degeneration of your cells, rapid ageing, and organ death, as there is nothing with which to repair cells. Someone with a damaged heart for example needs cholesterol for it to be repaired
You are sexually active - if you do not have enough cholesterol you will get inadequate and disrupted hormone levels. Steroid hormones help control the development of sexual characteristics. Without them one gets infertility, and impotence.
You are fighting cancer - cholesterol is needed to process vitamin D. Vitamin D deficiency has found to be associated with the advancement of cancers, for example; breast, colon, ovarian, and prostate.
You are a young growing child or have osteoporosis - cholesterol is needed to process vitamin D. Vitamin D deficiency impairs bone mineralization, leading to rickets in children and osteomalacia and osteoporosis in adults
You are depressed or very sad - cholesterol is needed to process vitamin D. Vitamin D deficiency is a risk factor for depression
You are mentally a bit unstable or unusual, for example sensitive, bipolar or even schizophrenic - cholesterol is needed to process vitamin D. One study found low serum vitamin D concentrations in patients with schizophrenia and it has been implicated in several mental health disorders
You have liver disease - cholesterol is needed to process vitamin D. Vitamin D deficiency plays a role in the pathogenesis of non-alcoholic fatty liver disease
You are diabetic, obese or have a metabolic disorder - Bile acids are a family of steroid molecules generated in the liver by cholesterol oxidation. They are signaling molecules that affect blood glucose levels promoting intracellular thyroid hormone activation
You have any bacterial infection - so called 'bad cholesterol' is actually key in fighting bacterial infection.
You have any form of disease relating to inflammation - cholesterol has an anti-inflammatory role in the body too
You wish to benefit from the food you are eating -Bile acids are a family of steroid molecules generated in the liver by cholesterol oxidation. They have a key role in nutrient absorption

You need cholesterol.

In effect, if you measure blood pressure and it is high, all it is telling you is that at one time your blood was so full of pathogens that the cholesterol used to engulf them all has created a lining on the walls of your blood vessels; and that you are possibly still full of the same pathogens and despite the valiant efforts of your immune system, the body is only just holding its own against them.

The solution?

HUNT THE PATHOGEN, SUPPORT THE IMMUNE SYSTEM.

As a somewhat apocryphal aside, it is noticeable that even the sort of measuring sleeve they put on your arm can have its effects - a chubby arm and the wrong sleeve can send the blood pressure way up high.

The most effective vasodilators

Even if there is a reason why our blood pressure and cholesterol are high, there is every reason to help ourselves by dilating the blood vessels to enable the cholesterol to get where it needs to go and let the oxygen and glucose get to our cells to give us more energy. So, what are the most effective vasodilators?

Heat – a person who has heart problems and anyone facing illness or the sort of problems faced above must keep warm, preferably be very warm. When the body is warm, the blood vessels automatically dilate to enable our body temperature to remain constant. By raising the body temperature to above that of the body normally, our metabolic systems will dilate the blood vessels to help us to remain stable. There are a number of ways in which to ensure we are warm

Warmth

Hot baths

Being in the sun

Saunas

Gentle exercise – NOT frenetic exercise, the sort of exercise that keeps the circulation going and the metabolism active

Eating regularly – and eating well. By doing this we help our body to keep warm, give ourselves the energy to support gentle exercise and never eat so much at one meal [because we are ravenously hungry] that we put a strain on our system, forcing the body to divert blood and oxygen away from other organs and to the stomach. Little and regularly and well are the watch words
Laughing – watching funny movies or hearing silly jokes has a strange effect on the body. There is an initial tension as we wait for the punch line, then at the funny moment there is profound relaxation where the blood vessels dilate and we flush with pleasure
Making love – as long as there is no tension involved – time limits, guilt, the knowledge this has to be followed by loss or parting, ‘performance anxiety’, then making love is an exceptionally good vasodilator.
Food – many foods contain natural vasodilators. They have the advantage over any pharmaceuticals that it is almost impossible to overdose on a food, and that the natural products that are the most effective also have pathogen attacking abilities as well. As such one can heal and dilate at the same time. There are a number of key plants that combine both vasodilation and chelating ability – very important if the cause of your problem is a toxin or heavy metal. We have placed some observations in the healing section to show which foods have been researched - see the entries for Dr Duke.
Sleeping – as long as you are tucked up in a warm bed with a pair of thick winceyette pyjamas [I jest – or maybe I don’t] so you are cosy and warm, sleeping is a magnificent way to induce both vasodilation and healing combined. The more the better.
Peace and quiet – calm and lack of noise and in effect a lack of stress. Noise is stressful, it stimulates and grates. Note that music is not included here, by noise we mean noise – unwanted sound.
Low levels of lighting – not the glaring blaring light of neon, or large shops or arcades, not the cold light of offices, but the gentle peaceful warm light of a table lamp or the soft glow of a candle.
Nice smells – barely discernible wafts of perfume, natural smells of flowers and woodlands, the grass after fresh rain or it has just been mown, not the awful smells of fast food restaurants, or the reek of traffic and pollution, which has the opposite effect. Just the smell of ‘fresh’ air can do it.
Sacred geographies – particularly the inside of spiritual buildings or glorious mountain retreats.

In simplistic terms, safety, peace and security promote vasodilation, threats promote vasoconstriction.

If you glance through Dr Duke’s list of vasodilatory chemicals [see observation below] you will notice it includes Adenosine, Actein [in Black Cohosh], Acetylcholine [in Nettles and red peppers], ALA [omega-3 fatty acid] , Anthocyanins [found in lots of berries], Vitamin C, apigenin [found in celery and chamomile tea], apiole [found in parsley], arginine [an amino acid], baicalin [found in Scutellaria], Berbamine [found in berberis], Bulbocapnine [found in Fumewort], Caffeine [found in coffee], calcium [found in dairy products, seaweeds, many nuts and dandelions etc], capsaicin [Red peppers, chili peppers and ginger], chrysin [passionflowers, chamomile], theobromine [in chocolate] and vitamins like Niacin [vitamin B3].

The point to be made here is that via food or the plant medicines shown on this site, it is possible to get moderate doses of these on a regular basis without needing ‘drugs’. For reasons which are very difficult to understand, for example, the pharmaceutical industry have repackaged Niacin and given it a new name as a vasodilator. Niacin occurs naturally in a host of delicious fruit and vegetables.

Drugs are extremely poor substitutes for plants. Plants often combine symptom alleviation and pathogen attacking activities in the one plant, although the chemicals used to provide the symptom alleviation may be different to the ones that attack the pathogen - which is why you need the whole plant and nothing but the plant.

Drugs rarely address anything but symptom alleviation and their mechanism of action is often very crude, woking against the body and not with it.

As such, this rather begs the question, why are there so many drugs?

The Drugs

In preparing this entry, we initially split all the drugs into their categories. We had alpha blockers, Phenylethanolamine derivatives, Imidazoline derivatives, purine derivatives, ergot derivatives, nitrovasodilators, quinlone vasodilators, alpha2 adrenergic agonists, adrenergic release inhibitors, Ganglion-blocking/nicotinic antagonists, MAOIs, Adrenergic uptake inhibitors, non selective alpha blockers and alpha 1 blockers, Tyrosine hydroxylase inhibitors, and Endothelin antagonists. There were drugs that were once used as vasodilators but had been reclassified as treatment for benign prostatic hyperplasia. Many drugs had been withdrawn. The vast majority caused hallucinations [the remit of this site] and quite a significant number caused death [another remit of the site].

This split does not help to show the overall picture for the number of hallucinations caused, nor does it help to explain why they are happening - or the deaths for that matter, so although we have put the type in the observation descriptions, they are not used here.

Instead we have homed in on the pattern for the pharmaceuticals.

Cardiac crises

There are a number of drugs that are designed to deal with cardiac events. Although adverse events may be associated with them, the adverse event they are designed to help with has far worse consequences. In effect, these drugs are life savers and in a sense show what good medicine can be. One easily administered [usually] high dose of a compound that will easily get to the site and quickly open a blockage. Many people in the ambulance to the hospital have been saved by these medicines and before stents they were the only medicine that saved people’s lives.

Nitroglycerin, for example, is used for the treatment of severe attacks of angina or acute myocardial infarction. Sodium nitroprusside abbreviated SNP, also belongs to this same class of nitric oxide releasing drugs and is used intravenously in cases of acute hypertensive crises. Again, if we take a very specialised drug like phentolamine [Regitine], it is used in hypertensive emergencies, and in the treatment of cocaine-induced cardiovascular complications.

Essential medicine, but only for one off use.

We have included the hallucinations, but with the intention of helping doctors reassure patients that it is one unfortunate side effect of opening the blocked dam of the blood supply, and as such should not reoccur once blood flow has stabilised.

Regular use drugs

Practically all adverse drug reports listed on the eHealthme site are for pharmaceutical drugs that people are told to take on a regular basis, for example, every day. Clearly any drug that has to be take regularly is not healing, it is at best alleviating and at worst masking symptoms.

The drugs are so varied that it is inappropriate to try to list typical symptoms.

Deaths

We have placed the eHealthme derived figures for deaths in the science section - see Vasodilator drug deaths.

It seemed inappropriate to list the figures for deaths associated with the medications used for one-off cardiac events. So these are the figures for the regular use drugs.

In total, as of mid September 2015, the total number of deaths caused by this class of drugs, excluding those used for cardiac events - thus only regular use drugs - derived from doctor only submited Adverse Drug Reports and submitted to the FDA and SEDA, and only for the US, and thus excluding the figures for the rest of the world was

13,585

How it works

Most common Edarbi side effects:

Hypotension (12 reports)
Dizziness (9 reports)
Renal Impairment (7 reports)
Diarrhea (6 reports)
Nausea (6 reports)
Fatigue (5 reports)
Oedema Peripheral (5 reports)
Muscle Spasms (5 reports)
Fainting (4 reports)
Loss Of Consciousness (4 reports)

Taking one not atypical drug in this class we can see that the majority of the symptoms - the nausea, diarrhoea, muscle spasms and renal impairment are symptoms of poisoning.

In looking at the rest of the symptoms, we believe that the hallucinations are all the result of hypoxia caused by sudden hypotension, in effect too strong a dose, or a combination of food that has strong vasodilatory properties with the drug.

If we take one example category to demonstrate. Angiotensin II receptor antagonists (more commonly called an "ARB", or angiotensin receptor blocker), have particularly high affinity for the type I (AT₁) angiotensin receptor. By blocking the action of angiotensin, they dilate blood vessels and reduce blood pressure. We can thus see that in overdose, over dilation of the coronery arteries will increase blood flow to the myocardium, but will lead to hypotension. This will lead to a decrease in oxygen supply and is likely to lead to the gradual shut down of non essential function and one non essential function in this case will be memory and reason. See how spiritual experience works.

It is worth adding that there is a debate in the medical community on whether angiotensin receptor blockers may or may not increase the risk of myocardial infarction (heart attack). This debate may shed some light on the deaths.

The CHARM-alternative trial, for example, showed a significant +52% (p=0.025) increase in myocardial infarction with Candesartan (versus placebo) despite an initial reduction in blood pressure. It is thought that as a consequence of AT1 blockade, ARBs increase Angiotensin II levels several-fold.

Increased levels of circulating Angiotensin II result in unopposed stimulation of the AT2 receptors, which may be harmful under certain circumstances through “mediation of growth promotion, fibrosis, and hypertrophy, as well as proatherogenic and proinflammatory effects”.

References and further reading

Papers

Psychosomatics 1987 Oct;28(10):555-6. Visual hallucinations and suicidal ideation attributed to isosorbide dinitrate. Rosenthal R PMID: 3432520

Paintings

The paintings are all by Frederick Carl Frieseke (April 7, 1874 – August 24, 1939) who was an American Impressionist painter who spent most of his life as an expatriate in France. His paintings often concentrated on various effects of dappled sunlight. He is especially known for painting female subjects, both indoors and out.

Observations

The figures below are from eHealthme, based on the Adverse Drug Reports submitted by doctors to the FDA and SEDA. Where the drug is to be found on eHealthme a link is provided so that you can look up the current figures and the side effects. The figures below were correct as at 2012, but we have also provided more up-to-date figure in the observations. Where the link to eHealthme does not take you to the drug, it may be because the drug has been recalled and discontinued; the drug figures and side effects are being updated; or the drug has been renamed. This latter situation is not unusual and makes it extremely difficult for any doctor to see the side effects and history of a drug in total.

A large number of drugs are only available outside the USA, as such no figures can be provided, as the eHealthme site is only for the USA. The symbol * has been used to indicate 'Not for sale in US' hence no figures.

Drug	No of hallucinations	Type
Isoxsuprine also called Vasodilan, Duvadilan	*	beta-adrenergic agonist
Buphenine also Nylidrin Arlidin and Opino	*	beta-adrenergic agonist
Bamethan	*	beta-adrenergic agonist
Nicotinyl alcohol - Pyridylcarbinol	*	Niacin derivative
Xanthinol Niacinate	*	Niacin with Purine derivative
Cyclandelate trade name Cyclospasmol	0	Discontinued
Phenoxybenzamine trade name Dibenzyline	0	Alpha blocker
Vincamine trade names Oxybral SR	*	Miscellaneous
Suloctidil	-	Withdrawn from market
Buflomedil trade name Loftyl	*	Possible withdrawal due to toxicity
Naftidrofuryl trade names Artocoron; Azunaftil; Di-Actane; Dusodril; Enelbin; Frilix; Gevatran; Iridus; Iridux; Luctor; Nafti; Naftoling; Naftodril; Nafoxal; Praxilene; Sodipryl retard; Vascuprax	*	Miscellaneous
Cinepazide or cinepazide maleate^, Kelinao or Anjieli	*	A2 adenoside agonist
Nitroglycerine	285	Nitrovasodilator ++
Isordil and Isosorbide	13 + 73 +59 = 145	Nitrovasodilator ++
Molsidomine	*	Nitrovasodilator ++
Nicorandil trade names Ikorel Angedil, Dancor, Nikoran,PCA, Aprior, Nitorubin, and Sigmart	*	Nitrovasodilator ++
PETN	*	&&
Flosequinan trade name Manoplax	-	Quinalone $$
Adenocard	2	Adenosine agonist
Alfuzosin	13	Alpha 1 adrenergic blocker
Dipyridamole trademarked as Persantine	16	Adenosine reuptake inhibitor
Doxazosin mesylate - sold under the brand names Cardura	42 + 53 = 95	Alpha-1 adrenergic receptor blocker
Losartan trade name Cozaar	80 + 77 + 8 + 169 = 334	Angiotensin II receptor antagonist
Terazosin - marketed as Hytrin or Zayasel	6 + 26 = 32	selective alpha 1 antagonist
Tracleer and Bosentan	40	dual endothelin receptor antagonist
Treprostinil, Remodulin, Tyvaso	6	synthetic analog of prostacyclin
Dilazep	*	Adenosine reuptake inhibitor
Gapicomine	*	Withdrawn from market
Prazosin, trade names Minipress, Vasoflex, Pressin and Hypovase	3 + 3 = 6	Alpha adrenergic blocker
Azilsartan trade name Edarbi	0	Angiotensin II receptor antagonist %
Candesartan trade names Blopress, Atacand	9 + 20 + 45 = 74	Angiotensin II receptor antagonist
Eprosartan marketed as Teveten and Eprozar	2	Angiotensin II receptor antagonist
Irbesartan trade names Aprovel, Karvea, and Avapro, Irda, CoIrda, CoAprovel, Karvezide, Avalide and Avapro HCT	46 + 14 + 68 = 128	Angiotensin II receptor antagonist
Olmesartan medoxomil - trade names: Benicar , Olmetec, WinBP, Golme, Erastapex	7 + 61 = 68	Angiotensin II receptor antagonist
Telmisartan trade name Micardis	8 + 66 + 1 = 75	Angiotensin II receptor antagonist
Valsartan - Diovan, Angiotan, Candesaran, Valtan and Valzaar	52 + 1 + 207 + 1 = 261	Angiotensin II receptor antagonist
TOTAL	1,582

++ A nitrovasodilator is a pharmaceutical agent that causes vasodilation (widening of blood vessels) by donation of nitric oxide (NO), and is mostly used for the one off treatment of angina pectoris and hypertensive crises. They can also be used in acute myocardial infarction, heart failure, and for lowering of blood pressure during surgery. Hallucinations are most often caused by resulting hypotension as the vessels very suddenly widen.

&& Pentaerythritol tetranitrate (PETN) is one of the most powerful explosive materials known, which when mixed with a plasticizer, forms a plastic explosive - Semtex. It is used as a vasodilator drug in the management of angina.

$$ Flosequinan was sold under the trade name Manoplax. It was withdrawn from the US market in October 1993 due to an increased risk of hospitalization or death

% Azilsartan marketed under the trade name Edarbi was only released in 2011

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