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Drug interactions between nitric oxide and Viagra

Drug Interaction Classification

The classifications below are a guideline only. The relevance of a particular drug interaction to a specific patient is difficult to determine using this tool alone given the large number of variables that may apply.

Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.

Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.

Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.

Do not stop taking any medications without consulting your healthcare provider.

Disclaimer: Every effort has been made to ensure that the information provided by Multum is accurate, up-to-date and complete, but no guarantee is made to that effect. In addition, the drug information contained herein may be time sensitive and should not be utilized as a reference resource beyond the date hereof. This material does not endorse drugs, diagnose patients, or recommend therapy. Multum's information is a reference resource designed as supplement to, and not a substitute for, the expertise, skill, knowledge, and judgement of healthcare practitioners in patient care. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective, or appropriate for any given patient. Multum Information Services, Inc. does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. Copyright 2000-2016 Multum Information Services, Inc. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse, or pharmacist.

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Complications of Arginine & Cialis

Last Updated: Aug 16, 2013 | By Melissa Sandoval

Melissa Sandoval began writing professionally in 1996, dabbling in fiction and writing for new media and magazines. She has published work in "mental_floss magazine" and on websites such as TLC Family and TLC Style. Sandoval has work published in English and Spanish, including online topics guides en EspaГ±ol. Sandoval has a Bachelor of Arts in psychology from Wittenberg University.

Arginine is a popular supplement that people take for such conditions as congestive heart failure, chest pain, bladder inflammation and erectile dysfunction. Arginine can cause blood vessels to relax and increase blood flow. Cialis or tadalafil is a medication that doctors prescribe to treat erectile dysfunction or pulmonary arterial hypertension. Since both arginine and Cialis relax your blood vessels, taking them together can cause your blood pressure to drop too low. If your doctor has prescribed Cialis, you should not take arginine.

Nitric Oxide and Blood Pressure

Nitric oxide circulates in your blood and affects the smooth muscles that expand and constrict your arteries and arterioles. When nitric oxide comes into contact with the smooth muscles in your blood vessels, it causes them to relax and open up the vessels, which lowers your blood pressure. Taking Cialis and arginine together can cause the levels of nitric oxide in your blood to become too high and your blood pressure to drop too much. Your body depends on your blood pressure to squeeze oxygen into your cells, so if your blood pressure drops too low, your brain will become starved of oxygen and cause you to become lightheaded or pass out.

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Arginine and Nitric Oxide

Arginine, also called "L-arginine," is a naturally-occurring amino acid. It is called a "conditional" amino acid because you can live without it for a period of time, but your body needs it in times of stress. Arginine plays an important role in your body's urea cycle, which helps your body rid itself of excess nitrogen. Arginine is also a precursor of nitric oxide. Nitric oxide is the result of a chemical reaction between arginine and the enzyme nitric oxide synthase. Therefore, if you increase the amount of arginine in your body, you will also increase the amount of nitric oxide.

Cialis and Nitric Oxide

Cialis is one of a class of drugs called phosphodiesterase or PDE inhibitors. PDE is an enzyme that breaks down cyclic adenosine monophosphate or cAMP throughout the body and cyclic guanosine monophosphate, cGMP, in the penis. Both cAMP and cGMP are nucleotides that are important for cell function. Your body produces cGMP within the blood vessels in the penis as a response to increased nitric oxide in your blood. Cialis decreases the activity of cGMP, which allows more nitric oxide to stay in the blood vessels of the penis. The nitric oxide relaxes those blood vessels, allowing them to expand and cause an erection. Since Cialis also inhibits cAMP, it relaxes blood vessels in other parts of your body as well.

Precautions

Do not take arginine or Cialis if you are taking nitrates or blood pressure medications. You should reconsider taking arginine if you are taking medications that are similar to Cialis, such as Viagra. Do not take arginine if you have the herpes virus, because arginine can trigger herpes outbreaks. Avoid arginine if you are diabetic, since it can alter blood sugar levels. Tell your doctor about any other medications or herbal supplements you are taking before you start taking Cialis or arginine. Common side effects of arginine include bloating, diarrhea and nausea. Some common side effects of Cialis are nausea, diarrhea, flushing, heartburn and headache.

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Nitric Oxide and Viagra

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In a random survey of males aged 40-70, more than 50 percent indicated that they had some form of erectile dysfunction (ED), i.e. the inability to achieve an erection. The development of the drug Viagra, an inhibitor of cyclic GMP-specific phosphodiesterase, has been of great importance to many males suffering from ED.

Achievement of a penile erection in males is largely an application of basic principles of hydraulics. Stimulation of the nerves innervating the penis causes the dilation of the deep arteries supplying blood to the penis. The large amount of blood entering the penis engorges the cavernous blood sinuses comprising much of the penis volume. This engorgement in turn acts to compress the veins draining blood from the penis. The increased inflow and decreased outflow of blood causes an erection. Cessation of nervous impulses to the penis acts to abolish the erection.

Nitric Oxide

Nitric oxide (NO) is of major importance in the signaling pathways leading to penile erections. NO is very unique for a biochemical signalling molecule because it is a gas. NO displays free radical behavior, and is formed from arginine by the enzyme nitric oxide synthase (NOS):

arginine + O2 citrulline + NO

As a gas, NO is able to pass through cell membranes without the aid of dedicated transporters and its free radical character makes it particularly reactive with iron-containing proteins.

Originally called UK-92,480, Viagra was initially developed for treatment of hypertension. In a subsequent human toleration study as a possible drug for angina, some very strange side-effects were noted.

NO acts as a vasodilator in the process of penile erection. NO is supplied from two sources. The first is as a neurotransmitter liberated by the cavernous nerve which innervates smooth muscle surrounding penile arteries. The second source is the endothelial cells lining the deep arteries of the penis. Endothelium-derived NO is formed in response to stimulation of the endothelial cells by cholinergic nerves. Acetylcholine causes the production of inositol triphosphate (IP3), an important second messenger in many hormone signal transduction pathways. IP3 opens calcium channels in the endoplasmic membrane of the endothelial cells; the liberated calcium then activates NO synthase and causes the production of NO.

Whatever the source, endothelial cells or cavernous nerve, NO diffuses across the muscle cell membrane and binds to guanylyl cyclase. Guanylyl cyclase catalyzes the synthesis of cyclic GMP from GTP. cGMP then activates a cGMP dependent protein kinase which in turn stimulates the uptake of calcium by the endoplasmic reticulum of the muscle cell. The reduced levels of cytoplasmic calcium cause the muscle cell to relax. As a consequence of muscle cell relaxation, vasodilation occurs.

Stimulation and inhibition of muscles by NO

As is true of any signaling pathway, there must be a way to terminate the action of the signal. cGMP is converted into GMP by a specific phosphodiesterase (PDE.) There are 10 families of PDEs: PDE1-10. The major PDE found in vascular smooth muscle is PDE5. Viagra (sildenafil) is a specific inhibitor of PDE5. By blocking the breakdown of cGMP, Viagra acts to prolong the effects of cGMP and, hence, the erection. The side effects of Viagra are relatively minor. Some minor vision problems have been reported; these are due to inhibition of PDE6, the phosphodiesterase used in signal transduction of light signals in the retina.

Other Biochemical Uses of NO

In addition to its role as a vasodilator and neurotransmitter, NO is produced by macrophages. These phagocytic cells of the immune system use NO to impair DNA synthesis and metabolism in microorganisms. NO can also react with other free radicals, in particular the superoxide radical, to form peroxynitrites that are effective against bacteria, fungi and other pathogens. Nitrites have been added as preservatives to meat for years; part of the effectiveness of added nitrites may be due to the antimicrobial action of generated NO.

Massive bacterial infections are known to cause septic shock, the hallmark characteristic of which is a dramatic lowering of blood pressure. This is due to the release of massive amounts of NO directed against the bacteria; the unfortunate side effect is the extreme vasodilation that occurs in response to NO.

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