Visine Long Lasting Uses, Side Effects & Warnings

Generic Name: oxymetazoline ophthalmic (OX i me TAZ oh leen off THAL mik)
Brand Name: Upneeq, Visine Long Lasting

Medically reviewed by Drugs.com on Oct 7, 2020. Written by Cerner Multum.

What is Visine Long Lasting?

Visine Long Lasting (for the eyes) is for temporary relief of minor eye redness or discomfort caused by minor irritants.

Upneeq is a prescription version of oxymetazoline ophthalmic that is used to treat blepharoptosis, a condition that causes a droopy eyelid over one or both eyes. Upneeq is for use in adults and children at least 13 years old.

Visine Long Lasting may also be used for purposes not listed in this medication guide.

Warnings

Follow all directions on your medicine label and package. Tell each of your healthcare providers about all your medical conditions, allergies, and all medicines you use.

Before taking this medicine

You should not use Visine Long Lasting if you are allergic to it.

Tell your doctor if you have ever had:

• high or low blood pressure;

• heart problems;

• Sjögren’s syndrome;

• blood circulation problems;

• glaucoma; or

• an eye injury or infection.

If you have any of the conditions above, ask a doctor or pharmacist before using the nonprescription (over-the-counter) version of oxymetazoline ophthalmic.

Ask a doctor before using Visine Long Lasting if you are pregnant or breastfeeding.

Always follow directions on the medicine label about giving this medicine to a child. Do not give this medicine to a child younger than 6 years old without medical advice.

How should I use Visine Long Lasting?

Use exactly as directed on the label, or as prescribed by your doctor. Using this medicine too long or too often may worsen your symptoms and cause damage to the blood vessels in your eyes.

Do not use while wearing soft contact lenses. A preservative in this medicine could permanently stain the lenses. Use the medicine at least 15 minutes before inserting your contact lenses.

Wash your hands before using eye medication.

Shake the eye drops well just before each use.

To apply the eye drops: Tilt your head back slightly and pull down your lower eyelid to create a small pocket. Hold the dropper above the eye and squeeze a drop into this pocket. Close your eyes for 1 or 2 minutes.

Use only the number of drops recommended.

Do not touch the tip of the eye dropper or place it directly on your eye. A contaminated dropper can infect your eye, which could lead to serious vision problems.

Call your doctor if your symptoms do not improve after 3 days of treatment.

Store this medicine in an upright position at room temperature. Do not freeze.

Keep this medicine out of the reach of children. Certain eye medications can cause serious medical problems in a young child who accidentally sucks on or swallows medicine from the eye dropper.

Each single-use container is for one use only. Throw it away after one use, even if there is still medicine left inside.

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What happens if I miss a dose?

Since Visine Long Lasting is sometimes used when needed, you may not be on a dosing schedule. Skip any missed dose if it’s almost time for your next dose. Do not use two doses at one time.

What happens if I overdose?

An overdose of Visine Long Lasting is not expected to be dangerous. Seek emergency medical attention or call the Poison Help line at 1-800-222-1222 if anyone has accidentally swallowed the medicine.

What should I avoid while using oxymetazoline ophthalmic?

Do not use other eye medications unless your doctor tells you to.

Visine Long Lasting side effects

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Stop using Visine Long Lasting and call your doctor at once if you have:

• a light-headed feeling, like you might pass out;

• ongoing or worsening eye redness;

• eye pain; or

• changes in your vision.

Common side effects may include:

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect Visine Long Lasting?

Ask a doctor or pharmacist before using oxymetazoline with any other medications, especially:

• heart or blood pressure medicine;

• a beta blocker–atenolol, carvedilol, labetalol, metoprolol, nadolol, nebivolol, propranolol, sotalol, and others; or

• an MAO inhibitor–isocarboxazid, linezolid, methylene blue injection, phenelzine, rasagiline, selegiline, tranylcypromine, and others.

This list is not complete. Other drugs may affect oxymetazoline, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible drug interactions are listed here.

More about Visine L.R. Long Lasting Redness Relief (oxymetazoline ophthalmic)

Consumer resources

Other brands

Upneeq, OcuClear

Professional resources

Related treatment guides

Further information

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Medical Disclaimer

Copyright 1996-2021 Cerner Multum, Inc. Version: 8.01.

Is Visine Bad For Your Eyes? Why You Should NEVER Use Visine Eye Drops

What Is Visine? How Does Visine Work?

It’s a seemingly simple solution to a simple problem: your eyes are red, itchy, and irritated, and Visine promises to fix that problem for you. It’s even in their slogan, which claims Visine “gets the red out”.

And it does, at least for a while. However, if you don’t understand what Visine is and how it works, you may be unaware that it could actually be causing more harm than good to your eyes and their symptoms. In fact, many eye doctors recommend that their patients forego this sort of harmful eye drop altogether.

Why Visine Is Bad For Your Eyes | Visine Side Effects

Visine is, fundamentally, a decongestant. Redness in your eyes can be caused by swollen and congested blood vessels; these blood vessels, when irritated, become filled with blood and get backed up. Visine solves the problem by causing the affected blood vessels to artificially constrict.

The active ingredients in Visine cause retinal blood vessels to physically shrink. This accomplishes the immediate goal of lessening the eye’s redness, however, as the medication eventually wears off, a phenomenon known to eye doctors as “rebound redness” may occur, which makes the initial problem that much worse.

In fact, over a prolonged period of continuous Visine usage, the rebound redness may actually become the default condition of the patient’s eyes. It’s true: Visine can permanently imprint on your eyes the very condition that it was originally intended to improve.

This is because Visine makes a basic mistake: it temporarily addresses the patient’s symptom (redness) without adequately solving the underlying cause (which may vary). And it can be even worse for contact lens wearers, because Visine can also dilate a patient’s pupils when used too much, too often. Contact lens wearers may become increasingly sensitive to light and experience blurry vision. For more information on Visine, check out the 5 Best & 5 Worst Eye Drops for Red Eyes.

What Happens If You Drink Visine? What Happens When You Put One Drop of Visine in Someone’s Drink?  

Although an interesting question, and one that we’ve never really contemplated before, it’s worth noting a few of the side effects that can occur if you ingest Visine. The active ingredient in Visine is Tetrahydrozoline HCl 0.05%. If swallowed, this substance can cause any or all of the following:

• Nausea and vomiting
• Breathing difficulty
• Blurred vision
• Lowered body temperature
• Seizures or tremors
• Fluctuations in blood pressure
• Shutdown of the central nervous system

As you can see, these are not small symptoms and Visine is nothing to play around with. Tetrahydrozoline HCl 0.05% works as a decongestant in the eyes, but can have drastic consequences if ingested. Especially prone to the above side effects are small children who may inadvertently swallow the solution.

If you are using Visine, make sure to keep it far out of reach of those tiny little hands, and think twice before pranking your best friend with a few drops in their drink.

Can You Use Visine With Contacts?

Now, let’s switch back to the eyes. Visine should not be used with contact lenses because it contains preservatives that could stick to the contact lenses, bathing your eyes in preservatives (and the medication) all day long.

Using Visine with contact lenses could greatly increase your risk of side effects such as red eyes, irritation, and overall discomfort of the eyes.

What About Visine Allergy Eyes Drops?

Visine-A® is Visine’s allergy eye drop, and the drops contain active ingredients of Naphazoline HCL 0.025% (which acts similar to Tetrahydrozoline as the redness reliever) and Pheniramine maleate 0.3% (which acts as the antihistamine to get rid of the itch). The company states that their product can help relieve itching and redness of the eyes due to pollen, ragweed, grass, and animal dander.

While this is not entirely untrue, it’s our opinion that this drop is not the best choice for those with allergies because it still contains that redness reliever that can lead to rebound redness. There are other options for allergies on the market, and these include over-the-counter eye drops such as Alaway and Zaditor. These two do not contain a redness reliever but will still give you nearly instant relief of those itchy, irritated eyes.

If Visine Is Bad, How Do I Fix My Red, Bloodshot Eyes? Visine Alternative

Maintain Proper Eyelid Hygiene

Even lubricant eye drops are not fixing the underlying problem of dry, red, irritated eyes.  We always recommend cleaning up your diet, drinking more water, and making sure to keep your eyelids clean with a hypochlorous acid eyelid cleanser, like Heyedrate Lid and Lash Cleanser (click here to check the price on Amazon). Hypochlorous acid is made naturally by the body to fight microorganisms and inflammation, and this spray formulation is no different.

To use, simply spray the solution onto your closed eyelids, rub it in, and let it dry. If you prefer, you can spray it onto a cotton ball or round before applying in the same way, or you can even just spray it on and go. There’s no need to ever rinse it off! This routine should be performed twice per day, every single day (remember to do it at the same time you brush your teeth, and it will quickly become a routine). 

Switch to an Anti-Inflammatory Diet

Diet, hydration, and cleaner eyelids allow for the body to work to heal itself without creating the problems associated with rebound redness from these astringent eye drops. Click here to read more about how the food you eat can affect your eyes.

We suggest incorporating diet changes slowly. Begin by adding more filtered water into your day. You should be drinking at least half your body weight in ounces of water per day (so, if you weigh 150 pounds, that’s 75 ounces per day). Do yourself a favor and get a reusable water bottle. Then, start to decrease or cut out the processed, fried, and sugary foods in your diet and replace them with fresh fruits, vegetables, and healthy fats. You can download a handy food chart here to get you started on your way to healthy eating.

Cool or Warm Compresses (Your Preference!)

If your symptoms just won’t go away, it may be worth your while to give a cold or warm compress a try before proceeding to the medication route. A cool compress will generally be helpful for those suffering from allergies, while a warm compress is great for dry, irritated eyes dealing with MGD and dry eye disease. To use a cool compress, place a mask in the freezer for at least 2 hours and then lie it over your closed eyes for 10 minutes. If using a warm compress, place it in the microwave for 20 seconds before testing the temperature on the inside of your wrist. Once it feels warm (but not too hot!) place it over your closed eyes for 10 minutes. Doing either of these once or twice per day may mean the difference between red, irritated eyes and those that appear healthy and vibrant.

And, obviously, you should absolutely visit an eye care professional if you’re experiencing any of the symptoms described above, prior to attempting to medicate your own eyes.

Visine Ingredients

Visine Active Ingredients

• Tetrahydrozoline HCI 0.05% – redness reliever

Visine Inactive Ingredients

• Benzalkonium chloride
• Boric acid
• Edetate disodium
• Purified water
• Sodium borate
• Sodium chloride 

So let us know…are you an avid Visine user? Do you have another great eye drop you enjoy using?

One Love,

Dr. Travis Zigler, SeeEO of Eye Love

Can Visine Kill You?

What Is Visine? How Does Visine Work?

It sounds like a simple solution to a simple problem: your eyes are red, itchy, and irritated, and Visine promises to fix that problem. It’s even in their slogan, which claims Visine “gets the red out”. And there is a Visine for everything – Dry eye, Original (whatever that is!), Allergy, Contacts, Irritation relief and even one called Totality!

And it does, at least for a while. However, if you don’t understand what Visine is and how it works, you may be unaware that it coul d actually be causing more harm than good to your eyes and their symptoms. In fact, many eye doctors recommend that their patients forego this sort of harmful eye drop altogether.

Why Visine Is Bad For Your Eyes | Visine Side Effects

Visine is, fundamentally, a decongestant
. Redness in your eyes can be caused by swollen and congested blood vessels; these blood vessels, when irritated, become filled with blood and get backed up. Visine solves the problem by causing the affected blood vessels to artificially constrict.

The active ingredients in Visine cause retinal blood vessels to physically shrink. This accomplishes the immediate goal of lessening the eye’s redness, however, as the medication eventually wears off, a phenomenon known to eye doctors as “rebound redness”
may occur, which makes the initial problem that much worse.

In fact, over a prolonged period of continuous Visine usage, the rebound redness may actually become the default condition of the patient’s eyes. It’s true: Visine can permanently imprint on your eyes the very condition that it was originally intended to improve.

This is because Visine makes a basic mistake: it temporarily addresses the patient’s symptom (redness) without adequately solving the underlying cause (which may vary).
And it can be even worse for contact lens wearers, because Visine can also dilate a patient’s pupils when used too much. Contact wearers may become increasingly sensitive to light and experience blurry vision.

A recent Story in the WaPoeven listed this as a potential source to kill someone! Don’t believe me? Follow the link..

So I urge you, to safely dispose of this drug from your cabinets. If you bring them to our office, we will help in safely disposing with the help of local pharmacies.

We always recommend cleaning up your diet, drinking more water, and making sure to keep your eyelids clean. To learn more, come see our friendly team or call us at 704-821-5009

Are You Overusing Eye Drops?

If you find yourself constantly reaching for your eye drops, it may be time to start looking into the bigger problem: Why do you need them so often? They’re a quick and gratifying fix to itchy or irritated eyes, but they don’t address what might be causing the irritation to begin with.

Signs You’re Overusing Eye Drops

The American College of Allergies, Asthma and Immunology says not to use eye drops regularly beyond a couple of weeks, unless instructed to do so by your eye doctor.

Dr. David McGarey of Barnet Dulaney Perkins Flagstaff says that usage depends on the type of eye drop, but regular use of eye drops is a concern. “Unless you’ve been directed to use over-the-counter eye drops by your doctor, you shouldn’t be using them on a daily basis. They aren’t meant for long-term eye care, but they can certainly provide relief while you’re searching for the reason for your condition,” he explains.

Three signs you’re overusing eye drops:

1. You’re consistently exceeding the daily use recommendations
2. You view eye drops as the cure rather a temporary treatment
3. You’ve got an auto Amazon subscription set up

A Primer on Over-the-Counter Eye Drops

Not all OTC eye drops are the same. What type of drops do you use?  

Types of Eye Drops	Description
Artificial Tears	Artificial tears are used to maintain moisture. They often contain electrolytes or thickening agents. Artificial tears are available with and without preservatives. If you’re using frequently, single-dose preservative-free eyedrops are recommended.
Medicated Eye Drops	• Medicated eye drops: These contain sympathomimetics, an ingredient that works by vasoconstriction. Blood vessels dilate from irritation and the drops help “clamp down” the superficial blood vessels. While this takes care of irritation or redness, it’s the opposite way the body would naturally repair the problem. • Allergy eye drops: A subset of medicated eye drops, these drops contain antihistamines. Using these for a long time can actually increase dryness and irritation.

Neither artificial tears nor medicated eye drops require a prescription. These are different than antibiotic or steroid drops you may get from your doctor for other conditions.

Risks of Overusing Eye Drops

1. They can cause “rebounding. ” That “clamping down” on blood vessels that eye drops do to stop itchiness means your sclera isn’t getting the oxygen and nutrients needed. When you stop using the drops, or their effects wear off, your eyes may work in overdrive to deliver oxygen to those vessels (which makes the problem come back)… which makes you want to reach for those eye drops all over again.
2. They can wash away your natural tears. Artificial tears feel great as they lubricate your eyes and help those with insufficient tear production. But overuse can literally wash away your natural tears and the natural moisturizers that protect your eye.
3. They can mask more serious problems. Just like a skin rash could just be an allergy to grass, it could also be flesh-eating bacteria. Addressing the symptom of itchy, red eyes, rather than the cause, which could be more serious, is risky.

Conditions that Eye Drops Could Be Masking

Here are some of the conditions that have itchy, red eyes as a symptom:

• Pink eye: A viral or bacterial eye infection, also called conjunctivitis, causing itchy, burning and swelling of one or both eyes. Some cases take care of themselves; others require a prescription antibiotic.
• Eye trauma: Rubbing or scratching your eye can cause a blood vessel break, making the eye red and itchy. Some more serious traumas will require surgery or prescription eye drops.
• Blepharitis: Inflamed and red eyelids, caused by bacterial or fungal infection, dry eye, gland dysfunction or parasites, all of which require further treatment than eye drops.
• Eye strain: Up all night focusing on work can make for tired, strained and irritated eyes, but if the strain is normal, you may need glasses to keep up.
• More serious allergy: Allergies to pets or the environment can manifest with dry, itchy eyes. Figure out specific allergens by visiting an allergist or removing specific things from your home one at a time to eliminate possibilities.
• Foreign objects: You might have something in your eye — dust, an eyelash, or something worse. If you’re having long-term issues with dry or itchy eyes, make sure a foreign body isn’t the culprit.

It’s Time To Schedule an Eye Exam

While you might be tempted to just keep using eye drops the way you have been, an eye exam could reveal deeper-seated issues and catch vision problems before they get too far to correct. Don’t cover the symptoms and neglect the cause. Eye drops are a convenient but temporary solution, not a long-term fix.

If you’re suffering from dry eyes or an irritation that hasn’t resolved on its own, it might be time to get your eyes examined. Call 602-603-4247 to schedule an appointment or visit a Barnet Dulaney Perkins office in your neighbourhood.

Tetrahydrozoline – an overview | ScienceDirect Topics

D Action of Dopamine on Peripheral Systems

Dopamine has been found to increase Aplysia gill contractions induced by siphon stimulation or by depolarization of gill motoneuron L7 (Ruben and Lukowiak, 1984). Dopamine also prevented habituation caused by repetitive stimulation of the siphon reflex (Carew et al. , 1972). The effect of dopamine was blocked following section of the ctenidial nerve or when L7 was hyperpolarized. It is suggested that dopamine can modulate the efficacy of the neuromuscular transmission of L7 or the interaction of L7 with parts of the gill peripheral nerve plexus. It was not possible to determine from these experiments whether dopamine was acting pre- or postsynaptically.

The opaline gland of Aplysia is a large multivesicular structure which when it contracts releases opaline into the surrounding medium (Tritt and Byrne, 1982). At least three motoneurons located in the right pleural ganglion innervate this gland. Dopamine, threshold 1−10 nM, when applied to the gland induces a contraction similar to those obtained following activation of the motoneurons. This dopamine effect persists when synaptic transmission is blocked, indicating that it is a direct postsynaptic action on the gland musculature. Dopamine also enhances the amplitude of the ejps recorded from the gland muscles. Fluphenazine, 100 μM, and haloperidol both block the direct action of dopamine and gland contractions following activation of the motoneurons. These compounds also block the ejps. This work presents evidence for dopamine as the excitatory transmitter onto the opaline muscles. Serotonin was found to enhance both the dopamine effect and the ejps in this preparation.

The role for dopamine-containing neurons in the cilioinhibitory mechanism of Mytilus has also been investigated by Catapane et al. (1979). They correlated branchial nerve activity and ciliary activity following application of dopamine, 100 μM to the visceral ganglion. Following addition of dopamine, nerve activity increased while ciliary activity declined to zero. Pretreatment of the visceral ganglion with either ergometrine, 0.1−10 μM or methysergide, 1−10 μM, both antagonized cilioinhibition and increased nerve activity induced following application of dopamine. Pretreatment of animals on alternate days for 6 days with 6-hydroxydopamine, 100 μ g in 100 μ l injected into the posterior adductor muscle, greatly reduced the ability of dopamine to depress ciliary rates and enhance branchial nerve activity. These results provide further data for a role for dopamine in the control of ciliary activity in Mytilus gill.

There is evidence for dopamine and octopamine receptors on the heart and gut muscle of the lamellibranch Tapes, and these receptors appear to be separate (Wade and Dougan, 1978; Dougan and Wade, 1978a,b). Usingthe gut preparation as a model, structure activity studies indicated the presence of a specific dopamine receptor which, when activated, inhibited the electrically induced contractions of the gut (Table XX). On this tissue dopamine acts in the range of 5−50 nM. Adrenaline and noradrenaline were far less active than dopamine at this site. Apomorphine was a dopamine agonist on this receptor but was considerably less potent. A number of compounds antagonized the dopamine effect, including phentolamine, droperidol, pa-parverine, metoclopramide, and tetrahydropapaveroline. A number of other compounds when applied in seawater at pH 7.5−8 had direct inhibitory effects on the preparation. However, when the pH of the bathing medium was reduced to pH 6, these compounds behaved as dopamine antagonists, for example, napazoline, xylometazoline, tetrahydrozoline, haloperidol, spiroperidol, benperidol, trifluperidol, fluphenazine, and chlorpromazine. It would appear that dopamine receptors similar to the apomorphine-sensitive mammalian receptors occur in the Tapes gut.

TABLE XX. Relative Potencies of Dopamine Analogues on the Stimulated Tapes Intestine^a

Using the Tapes heart there is evidence for two distince dopamine receptors (Dougan et al. , 1975). For example, dopamine, 5−20 nM, may decrease, increase, or induce a complex biphasic response on the ventricle. This inhibitory effect of dopamine can be antagonized by phentolamine, which has no effect on acetylcholine inhibition on this preparation. Structure activity studies indicate differences between this inhibitory receptor and that on the Tapes gut. For example, d-amphetamine is only 10 times less potent than dopamine on the heart but is 2000 times less active on the gut, and 2-amino-1,2,3,4-tetrahydronaphthylene is also 10 times less active than dopamine on the heart but is more than 2000 times less active on the gut. Apomorphine only excited the heart, while 3-methoxydopamine, which had no inhibitory action on either the gut or the heart, was a potent excitant on the heart, being only five times less potent than dopamine. Interestingly, at lower concentrations apomorphine blocked the inhibitory effect of dopamine. Metoclopramide could differentiate between the two effects of dopamine on the heart; for example, it blocked the inhibitory action but had no effect on dopamine excitation. In some preparations the block of dopamine inhibition revealed the excitatory component. Bromocriptine blocked the inhibitory effect of dopamine on the heart, while lergotrile had both agonist and antagonist effects on the ventricle. At low concentrations it antagonized the inhibitory effect of dopamine, while at higher concentrations lergotrile increased the heart beat. Interestingly, pretreatment with metoclopramide potentiated the excitatory effect of lergotrile. The dopamine antagonist droperidol attenuated the excitatory effect of both dopamine and lergotrile. The effects of a range of antagonists on the three responses are summarized in Table XXI. No potent and specific antagonist of dopamine excitation was found on the heart. Dopamine is present in the heart and ganglia of Tapes and so may have a physiological role at this site.

TABLE XXI. Specificity of Some Dopaminergic Antagonists for Subspecies of Dopamine Receptors in Tapes watlingi^a

The dopamine receptors on the heart of the bivalve mollusc Tapes watlingi have been investigated, using both pharmacological and ligand binding studies (de Rome et al. , 1980). Dopamine, 1−10 μM, can both excite and inhibit the heart of Tapes, while octopamine only excites the heart. iV-Methyldopamine was of similar potency to dopamine and was a full agonist, while adrenaline, noradrenaline, and apomorphine gave a slight negative inotropic effect followed by excitation but required doses one to two orders of magnitude higher than required for dopamine. These authors demonstrated high-affinity binding of labeled dopamine to the heart membranes and displacement of 10 nM labeled dopamine by unlabeled dopamine in the range of 5−2000 nM which resulted in complex displacement curves which suggested the presence of at least two dopamine receptor populations. The IC₅₀ values for displacing labeled dopamine for dopamine, N-methyldopamine, and apomorphine were 7.5,17, and 51 nM, respectively. Octopamine, in the 0.1−100 nM range, was also able to displace labeled dopamine. IC₅₀ values for haloperidol, metoclopramide, and chlorpromazine were greater than 500 nM. The inhibitory action of dopamine on the heart could be blocked by d-LSD; the L-isomer was inactive. Phentolamine, 160 μM antagonized dopamine inhibition and octopamine excitation but had no effect on dopamine or serotonin excitation. Methysergide, 2−10 μM had no effect on dopamine or octopamine excitation but antagonized serotonin excitation. Haloperidol and metoclopramide blocked the inhibitory effect of dopamine, and in fact metoclopramide converted dopamine inhibition to excitation. This compound also blocks octopamine excitation.

Interestingly, labeled spiroperidol binding failed to detect any evidence for dopamine receptors in the nervous system of the cephalopods Sepia and Octopus (Covelli et al., 1981). The authors suggest that their inability to detect dopamine receptors may be due to their low receptor density since they were able to identify them in a wide range of vertebrates by using the same technique. Further studies using this and other ligands are required to resolve the position since it is very probable that there are dopamine receptors present in these animals.

Dopamine has been implicated as a neurotransmitter in the cephalopod retina (Silver et al., 1983). Previous studies have shown that dopamine and also acetylcholine are synthesized in retinal tissue from Octopus and Loligo (Lam et al., 1974). Very small amounts of noradrenaline, adrenaline, and serotonin were also found. Using the modified glyoxylic acid method, Silver et al. (1983) observed punctate fluorescence distributed evenly through the synaptic plexus in Octopus, while in Sepia and Alloteuthis dense fluorescence bands occurred at the vitreal and sclerad boundaries of the plexus. This fluorescence was green, since from biochemical studies dopamine is the major catecholamine, it is likely that this fluorescence is associated with dopamine. It is suggested that these dopamine neurons are centrifugal. Earlier studies by Tansey (1979, 1980) found fluorescence bands in the optic lobe corresponding to the layers containing the central dendrites of centrifugal cells. There is no evidence that the photoreceptors contain fluorescence material, and these may well contain acetylcholine.

In addition to serotonin and acetylcholine, there is evidence for a role for dopamine in the control of the anterior byssus retractor muscle (ABRM) of Mytilus (Hidaka et al., 1977). Dopamine, 0.1−1 μM relaxes catch, hyperpolarizes the membrane potential, and reduces membrane resistance. This hyperpolarization is blocked in zero-potassium and in low-sodium Ringer’s solution but is unaffected by changes in chloride ion concentration. Ouabain, 10 μM, blocks the hyperpolarization but not the relaxation. Low temperature, −1.0−1.5 °C, blocked both the hyperpolarization and relaxation. These authors conclude that these two actions of dopamine were probably mediated through separate dopamine receptors. Beside dopamine, its N-methyl, N-ethyl, and N-propyl derivatives all relax catch tension in Mytilus ABRM, dopamine being the most potent (Takayanagi et al. , 1981). This effect of dopamine and its analogues was antagonized by haloperidol. When the nerve to the ABRM is stimulated dopamine can be detected in the perfusate (Satchell and Twarog, 1979). As the stimulation of the pedal ganglion is increased, so more dopamine can be detected in the perfusate. The role of catecholamines and related compounds has been further studied by Muneoka and Kamura (1982). They found that in addition to dopamine, octopamine, noradrenaline, tyramine, phenylethanolamine, and serotonin, all potentiate contraction of the ABRM while histamine had no effect. In this respect, octopamine was the most potent of the compounds examined. Phentolamine, 10 μM blocked the potentiating action of octopamine and noradrenaline and partially blocked dopamine but had no effect against serotonin. Dopamine, noradrenaline, and octopamine also induced overall darkening of the chromatophores of Octopus when injected into the cephalic aorta (Andrews et al., 1983).

Red-Eye Drops: Poisonous to Drink, Safe If Used Correctly

Eye drops designed to treat redness are not intended to be consumed orally.  If swallowed, the medication can cause illness and even death. The poisonous effect made headlines when Lana Clayton, 52, was charged for murdering her husband by adding redness-relieving eye drops to his drinking water for three days. 

While eye drops can be dangerous if swallowed, experts say the chemical used to get the red out of your eyes is safe when used correctly. 

What is in redness-relieving eye drops?

Commonly used drops marketed to reduce redness in the eyes typically contain tetrahydrozoline, which was approved by the U.S. Food and Drug Administration (FDA) in 1954 and belongs to a family of drugs called imidazoles. The chemical is found in Visine, Murine Plus, Altazine, Clarine and some other over-the-counter eye drops, according to Drugs.com. Constricting blood vessels in your eyes is how they “get the red out.” 

The FDA considers the risk for these products to be low as they are labeled for external use only and are clearly marked “keep out of reach of children. ” 

What happens if you drink eye drops?

Intentionally or accidentally drinking eye drops can lead to toxic blood levels. When used in the eyes as directed to reduce redness, these types of eye drops are not absorbed systemically in amounts that lead to toxicity.

When consumed orally, tetrahydrozoline passes quickly through the gastrointestinal tract, rapidly reaching the blood and the central nervous system.

Symptoms of an overdose of tetrahydrozoline include drowsiness, slow breathing or absence of breathing, slow heartbeat, hypothermia and possibly even coma.

Children are most at risk of Visine poisoning

Most cases of poisoning are not criminal, but accidental by children or pets who find the small bottles of odorless, clear solution. 

“Size of the individual and the total dose are the most critical issues for causing harm, and so children are most at risk,” said Wiley Chambers, MD, an ophthalmologist with the Center for Drug Evaluation and Research at the FDA. “In general, sleepiness or drowsiness are symptoms of concern if children — particularly those below the age of 6 — consume more than 1 milliliter in a day.” 

Clinical pharmacologist and president of PharmaLogic Development, Inc., Gary Novack, PhD, agrees. “Because of their small size, even a dose as low as 1 to 2 milliliters may be toxic to children, according to the FDA website.”

A typical bottle of eye drops contains anywhere from 15 to 30 milliliters of solution. Putting two drops in both eyes six times a day would only equal about one milliliter of fluid. 

What to do if someone drinks eye drops

According to the material safety data sheet you should NOT induce vomiting and you should do the following:

“Examine the lips and mouth to ascertain whether the tissues are damaged, a possible indication that the toxic material was ingested; the absence of such signs, however, is not conclusive. Loosen tight clothing such as a collar, tie, belt or waistband. If the victim is not breathing, perform mouth-to-mouth resuscitation. Seek immediate medical attention.”

Are Eye Drops Bad for You?

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90,000 Vaccine awakened side effects – Kommersant FM – Kommersant

Volunteers testing coronavirus vaccines talked about side effects. In June, the Gamaleya Center for Epidemiology and Microbiology began clinical trials on humans at the Burdenko Main Military Hospital and Sechenov University. The reaction to the drug in different groups of subjects turned out to be different: the volunteers from the Ministry of Defense did not feel any side effects, while at Sechenov University many had a fever, and they had to knock it down with paracetamol. Recently, the first results of clinical trials were presented in the United States. The main complaints include chills and muscle pain, but there are also more severe reactions.

According to Larisa Popovich, director of the Institute of Health Economics at the Higher School of Economics, it is too early to talk about the imminent release of the vaccine, even if there are no side effects from the drug at all: “The current stage is to assess the safety and toxicity. At the second stage, about 500 people are recruited, divided into groups, one is injected with a placebo, the other with a vaccine, and they look at the effectiveness.At the third stage, a huge number of people are taken, and doctors observe patients of different ages, statuses, with various concomitant diseases and determine what side effects, on what organs and tissues this vaccine can have.

9 thousand people were recruited to test two vaccines, which are now in the third stage, and in July 2021 they are only going to finish this study. At this stage, many were cut off. According to the first SARS, it was the most promising vaccine, but its trials were stopped because after some time hepatitis developed.Those reactions to the introduction, about which they spoke, if they did not lead to functional disorders of organs and tissues, can be considered a reaction of healthy people. Whether the rise in temperature will cause a cytokine storm in debilitated patients is unclear.

At the first stage, maybe you can skip this, but then you need to watch how everything will develop.

It is necessary to understand that muscle weakness is a rapidly passing functional slight malaise, or it is some kind of malfunction in the regulatory mechanisms.I am not sure that this story can be deeply studied at the first stage with 45 volunteers. ”

Amid news of a successful vaccine trial in the US, developer Moderna shares rose 17%. At the same time, it is possible that neither Russian nor American scientists will manage to reach the mass production of the drug, says Vitaly Zverev, scientific director of the Mechnikov Research Institute of Vaccines and Serums: “The presence of antibodies to the virus in everyone who has been ill is decreasing. And we still do not know what is the duration and intensity of immunity after an illness.Therefore, we, of course, can not even guess how long the immunity will be after the introduction of the vaccine.

And it seems that when creating an injection against this virus, you need to think about stimulating the so-called cellular immunity.

That is, memory cells, which then, when they encounter a pathogen, trigger an immune response, including the synthesis of antibodies, will recognize the virus.

This is a vector vaccine made with adenovirus and should not be given multiple times.That is, even in these clinical trials, which were, two different vectors are taken, because they also have an immune response, and the second time the body does not respond to what is injected. And I keep repeating that we are going to administer the vaccine to healthy people. This is not a medicine when we can take risks, when we save a person’s life. It was not possible to create a vaccine against SARS. It is unclear how the drugs that are being created now will work. In my opinion, no one needs all this haste, especially since it is now obvious that the virus is not as terrible as it seemed at first. “

Clinical trials of the Russian coronavirus vaccine are scheduled to be completed by the end of the month. According to the head of the Ministry of Health, Mikhail Murashko, the second phase of research is underway.

Lilia Galyavieva

YUMH.UZ

Mass vaccination will begin in Uzbekistan in April. In society, there are different opinions on this matter, sometimes disputes and discussions flare up about which vaccine to choose, whether it is worth getting vaccinated.
The issues of vaccination against COVID-19, increasing the adherence of the population to vaccinations are relevant for many countries of the world.

For example, in a number of European countries, vaccines are viewed with skepticism, including by medical personnel. So, according to a survey conducted in Germany in November 2020 within the framework of the COSMO project of the University of Erfurt, the Robert Koch Institute and the Federal Center for Health Education, the indicator of readiness to get vaccinated against coronavirus among health workers was 3.98 points – on a seven-point scale. On average, this indicator was higher among the population – 4.45 points.

The trend was confirmed by a survey among more than 2,300 medical workers in early December by two professional associations of intensive and emergency medicine – DGIIN and DIVI. He showed that 73 percent of German doctors are ready to be vaccinated against coronavirus, but only 50 percent of nurses and orderlies. Many nurses and orderlies are not convinced that new vaccines are sufficiently tested, and that new technologies will not lead to as yet unknown side effects in the long term, experts say.

This trend is also observed in Russia. Thus, 52 percent of 3,040 medical specialists – participants in the survey conducted on August 12-13, 2020 through the specialized application “Doctor’s Handbook” (Russia), said that they were not ready to receive the Sputnik V coronavirus vaccine created at the Gamalea Center. … 24.5 percent agree to be vaccinated.

When asked about the reasons for mistrust of the vaccine registered in August last year, 66 percent of those surveyed said that there was not enough data on its effectiveness.The fact that the tool was created in too short a time confused 48 percent of respondents. 20 percent of survey participants would recommend vaccination to patients, colleagues, or acquaintances.

In Uzbekistan, with the partnership of the Center for Advanced Technologies under the Ministry of Innovative Development of the Republic of Uzbekistan, the Research Institute of Virology of the Ministry of Health and the Chinese company Anhui Zhifei Loncom Biofharmaceutical, the third phase of clinical trials of the Uzbek-Chinese vaccine ZF-UZ-VAC2001 continues.

The study of the recombinant COVID-19 vaccine – ZF-UZ-VAC 2001 – began in the country on December 12, 2020, and the first volunteer was vaccinated on December 16, 2020. Since that day, 14,405 volunteers have been examined. Of these, 13,100 people were tested using an express test for COVID-19 and 9,970 people – using PCR analysis. Volunteers who were not diagnosed with COVID-19 infection underwent a medical examination.

As of March 24, 2021, 6,860 volunteers received the first dose, 6,630 people received a 2-dose, and 2,964 volunteers received a 3-dose of ZF-UZ-VAC2001 vaccine.However, in addition to statistics, there is no official information about the condition of the subjects, the results (at least intermediate) of the study. This, in turn, leads to the emergence of various rumors and speculation, an increase in mistrust of vaccination among the population.

In addition to the vaccine from the PRC, it is planned to use vaccines from other countries in Uzbekistan. To find out the mood and opinions of Internet users about the upcoming vaccination, the nationwide movement “Yuxalish” conducted an online survey in the Telegram messenger on March 29-31.In three days, it was possible to reach more than 19. 3 thousand people from different regions of the country (in particular, this online survey was published in more than 30 channels and groups in the messenger, including in the regions).

It is noteworthy that the option “I will not be vaccinated” was chosen by 44 percent of the respondents (8,599 messenger users). A third of the respondents – 34 percent (6 641) – voted for the Russian Sputnik V vaccine. Eight (1,516) and seven percent (1,351) users each choose ZF-UZ-VAC2001 (PRC-Uzbekistan) and Pfizer / BioNTech (USA-Germany), respectively.Five percent of survey participants (959) mentioned the AsrtaZeneca vaccine (UK), two percent (327) – Moderna (USA).

Of course, these data cannot be considered a full-fledged sociological cut; nevertheless, it can be argued that a certain percentage of Uzbeks will refuse to be vaccinated.

During the poll, individual users in the comments and via the Telegram bot sent a number of reasonable questions. In particular:

• Why is there no information about the health of the vaccinated?
• What are the side effects of different types of vaccines?
• How do I prepare for the vaccination process?
• Is it necessary to get vaccinated if a person has already been ill and has antibodies?
• Where can I get detailed information about the possible consequences and risks after vaccination?
• What dictated the choice of government authorities, including the Ministry of Health, in favor of a particular vaccine? Has there been preliminary research done?

According to experts, refusal to vaccinate may not always be associated with fear or mistrust of vaccination.Among the main reasons is the fact that people have already been ill with COVID-19. One part of those who were not sick are expecting another vaccine, another part is worried about how they or their relatives will survive the vaccination. Some fear the side effects. Fear also breeds uncertainty about what doctors are administering as a vaccine.
Among the factors is the distrust of the population in the health care system as a whole. People are afraid that they will face excessive bureaucracy, queues, doubt that they will receive qualified medical care in a timely manner in case of complications from the vaccine, worry that an ineffectively organized vaccination process can lead to risks to their life and health.
To solve the problem, we need not situational measures, but work at a systemic level, first of all, overcoming the institutional distrust of citizens in medicine.

It is important to launch a massive and transparent information campaign among medical staff and ordinary citizens about vaccination. In this regard, the national movement “Yuxalish” proposes the following:

• Conduct a full-fledged sociological study to study the needs of the inhabitants of the republic in the vaccine and their preferences.Vaccination requires significant financial costs, including from the state budget, so the information obtained will need to be taken into account in the procurement process and the organization of the process. The head of state has repeatedly stressed that when solving complex issues, it is important to take into account the opinion and mood of the population.
• Organize training for vaccination professionals to work with a hostile or psychologically unprepared audience. This will allow health workers to develop the necessary communication skills in order to competently communicate with different categories of patients on vaccination against COVID-19.
• The approach to informing patients should be informal and the messages understandable. It is possible to attract volunteers from different age groups for these purposes. The use of modern multimedia technologies – infographics, videos, etc. will give its effect.
• Providing comprehensive and authoritative information (including on social media) by the Ministry of Health and other responsible authorities, for example, under the heading “The Truth About COVID-19 Vaccines”.So, you can show the process of moving an individual vaccine vial from production to a specific person. It is important to openly publish data on any post-vaccination complications – with facts, explanations and statistics, so as not to give grounds for speculation and manipulation of public opinion.
• Publicly destroy vaccine myths. It is important that credible scientific evidence, not conspiracy theories, appears at the top of the list when looking for information about vaccines.
• Show the process of vaccination of prominent statesmen and public figures, opinion leaders.Positive feedback from those who have already given the vaccine can free the population from fear. As an option – keeping “online diaries” by popular bloggers and influencers who were vaccinated against COVID-19.

In addition, the National Movement Yuxalish is ready:

• organize a public hearing with the involvement of national and foreign experts responsible for the implementation of vaccination structures;
• to assist in the training of volunteers (together with the Volunteer Association) in this direction;
• prepare a series of publications, in particular, expert opinions, infographics, on vaccination.

Press Service of the National Movement “Yuxalish”

90,000 Omega-3 fatty acids for depression in adults

Why is this review important?

Major depressive disorder (MDD) is characterized by depressed mood and / or a marked decrease in pleasure or interest in all activities. This has a negative impact on individuals and society, often in the long term. One possible treatment for MDD is n-3 polyunsaturated fatty acids (n-3 PUFAs), also known as omega-3 oils, which are found in oily fish, some other seafood, nuts, and seeds.Various evidence suggests that n-3 PUFAs may influence depression symptoms, but many studies have different results, making it difficult to draw conclusions.

Who will be interested in this review?

Health care workers, including general practitioners, mental health professionals and psychiatrists; people with MDD, milder or secondary depressive disorders; and their environment.

What questions does this review answer?

Do n-3 PUFAs affect depression symptoms, adverse side effects, recovery rates, quality of life, and dropout rates for people diagnosed with MDD compared with alternative agents?

What studies were included in this review?

We searched scientific databases to identify all randomized controlled trials in adults with a diagnosis of MDD in which people received n-3 PUFAs or an alternative that were conducted prior to May 2015.

We found 26 relevant studies: 25 studies involving 1438 people compared the effects of n-3 PUFAs with placebo, and one study involving 40 people compared the effects of n-3 PUFAs with antidepressants. All studies were directly relevant to our review, but we rated the quality of the evidence as low or very low.

What did the evidence from this review show us?

We currently do not have high-quality evidence to evaluate the effect of n-3 PUFAs on the treatment of MDD.We found small to moderate positive effects of n-3 PUFAs compared with placebo, but the magnitude of this effect is unlikely to be significant in people with depression, and we considered the quality of the evidence to be low or very low, with large differences between studies. The evidence for evaluating the side effects of n-3 PUFAs or the number of dropouts from trials prior to trial completion was also of insufficient quality.

What should be done next?

We need more evidence, in particular to explain differences between research results, such as studying people who will or will not benefit from n-3 PUFA supplementation.Future studies will also need to compare n-3 PUFAs with conventional antidepressant treatment and see what impact these treatments might have.

Biomarkers of cognitive impairment in cancer patients were identified

Oncology news

13.05.2019

Biomarkers of cognitive impairment in cancer patients have been identified

In a study published in Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, it was shown that patients with early breast cancer with higher levels of the sulfate form of dehydroepiandrosterone before chemotherapy have a lower risk of developing specific damage to the domains of the central nervous system that are responsible for clarity of thought. and fluency of speech.

The study involved 81 patients with early breast cancer. Patients had not previously received chemotherapy or radiation therapy and were prescribed curative chemotherapy. To assess cognitive impairment in patients, subjective and objective indicators of cognitive functions were assessed before, during and after chemotherapy. The questionnaires assessed clarity of thought, concentration, memory, fluency, functional interference, and multitasking. At the same time, a computerized neuropsychological test was used to assess the speed of information processing, reaction time, memory and attention of each patient.Patients also completed a series of questionnaires to assess fatigue symptoms, anxiety symptoms, and health-related quality of life. Researchers assessed serum levels of dehydroepiandrosterone (DHEA) and its sulfate form (DHEAS), neurosteroids that regulate brain tissue development. These indicators were assessed before starting chemotherapy.

Pre-chemotherapy DHEAS levels have been shown to be associated with impairments in the subjective cognitive domains of verbal function (fluency) (calculated hazard ratio 0.27) and clarity of thought (calculated RR 0.25) in a study.DHEA levels were not associated with impairment in any of the cognitive subdomains.

Toh Yi Long , lead author of the study, says: “ Our data suggest that patients who initially had higher DHEAS levels have a lower risk of developing subjective cognitive impairment. However, these data and the effect of DHEA and DHEAS on specific domains of cognitive function need to be verified and validated in independent cohorts . ”

Cognitive impairment in cancer patients, also commonly known as chemobrain, has been attributed to complications of the disease and its treatment. This is why the research team began looking for potential biomarkers to better understand the causes of this condition.

Chemical brain can be temporary or permanent, with some people reporting memory and concentration problems months after completing their cancer treatment.The researchers hoped to find ways to identify patients at increased risk of developing these symptoms based on a standardized quantitative biomarker. In the future, this will help to take appropriate preventive measures in order to mitigate side effects and help improve the quality of life of patients in the long term.

Sources:

1. Toh YL, Shariq Mujtaba J, Bansal S, Yeo A, Shwe M, Lau AJ, Chan A. Prechemotherapy Levels of Plasma Dehydroepiandrosterone and Its Sulfated Form as Predictors of Cancer-Related Cognitive Impairment in Patients with Breast Cancer Receiving Chemotherapy.Pharmacotherapy 2019,39: 553-563.
2. The ASCO Post. New Biomarkers Associated With Cancer-Related Cognitive Impairment Identified. Posted: April 29, 2019.

90,000 Immunologist called the danger of a hasty introduction of the coronavirus vaccine :: Society :: RBK

Photo: Sofia Sandurskaya / AGN “Moscow”

After the completion of the development of a vaccine against coronavirus infection, it is not worth rushing to introduce it because of the risk of side effects.This was stated by an Israeli immunologist, head of the department at the Hadassah Ar Ha-Tsofim hospital, Professor Yakov Berkun, reports RIA Novosti.

According to him, modern technologies can significantly reduce the time to develop a vaccine and test its effectiveness and safety. But despite this, it takes at least months to investigate all the possible consequences of vaccination.

As an example, Berkun cited the situation with the vaccination of the Israeli population against rotovirus about ten years ago.After the start of mass vaccinations, it turned out that they caused intestinal obstruction. “The studies have already ended, they have already begun to give to people, and then they had to take this vaccine out of production,” he said.

The head of the Gamaleya Center named the possible time frame for mass vaccination against COVID

The immunologist said that about ten laboratories around the world have already moved to the stage of clinical trials of a COVID-19 vaccine in humans, but the results of Chinese scientists are of the greatest interest.

Practical aspects of the use of mineralocorticoid receptor antagonists in the treatment of arterial hypertension | Plisyuk A.G., Orlova Ya.A.

The review discusses the practical issues of using mineralocorticoid receptor antagonists in the treatment of arterial hypertension. If the target blood pressure level is not achieved against the background of three-component therapy, mineralocorticoid receptor antagonists can be added to the treatment: spironolactone or eplerenone.

Diuretics were named the cornerstone in the treatment of arterial hypertension (AH) already in the first report of the Joint National Committee for the detection, diagnosis and treatment of hypertension in the United States (Joint National Committee – JNC), published in 1977.[1], and in the recommendations of the World Health Organization (WHO) 1978 [2]. In the VIII report of the Joint National Committee (JNC VIII) [3] and the joint recommendations of the WHO and the International Society for Hypertension 2003 [4], diuretics are recommended for the initial therapy of uncomplicated hypertension. Diuretics recommended for use as antihypertensive agents in JNC VIII are presented in Table. 13].

The essence of the main approach to the treatment of hypertension, declared in the European guidelines for the management of patients with hypertension in 2013., lies in the fact that the main benefit of antihypertensive therapy is associated with a direct decrease in blood pressure (BP) and practically does not depend on which drug this effect was achieved [5]. This issue remains consistent with previous versions of the European Recommendations. In the Russian guidelines for the diagnosis and treatment of hypertension, the key provision is also the need to achieve the target blood pressure [6]. European experts did not consider it necessary to take into account the data of individual meta-analyzes [7-9], indicating the advantages of certain classes of drugs.The results of head-to-head studies and large meta-analyzes that did not show significant differences in clinical outcomes with the five main groups of antihypertensive drugs [10-13] were considered more convincing. In this regard, new European guidelines reaffirm that diuretics (including hydrochlorothiazide, chlorthalidone and indapamide), β-blockers, calcium antagonists, angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers should be used as first-line drugs for the treatment of hypertension. both in monotherapy and in combinations.
It is important that all recommendations have in common the definition of treatment-resistant hypertension. It is possible to speak of resistant hypertension if blood pressure does not reach target levels, despite the simultaneous use of three antihypertensive agents of different classes in optimal doses. It is impossible to make such a conclusion if there was no diuretic in the combination therapy prescribed to the patient [5, 6, 14-16].
Mineralocorticoid receptor antagonists (AMCR) are not first-line drugs for the treatment of hypertension.However, they are of particular importance in the development of resistant hypertension. This class of drugs is currently represented in the Russian Federation by spironolactone (SL) and eplerenone (EP). The diuretic effect of AMKR develops slowly – after 2–5 days and is rather weak. The inhibition of reabsorption of sodium filtered in the renal glomeruli is no more than 3%. The drugs have a long duration of action (up to several days). The antihypertensive effect does not depend on the level of renin in the blood plasma and does not manifest itself at normal blood pressure.EP differs from SL in relative selectivity for mineralocorticoid receptors.
AMKR have proven their positive effect on prognosis in patients with chronic heart failure [17–19]. In the treatment of high blood pressure, randomized clinical trials with firm endpoints for drugs in this group have not been conducted. Nevertheless, the European guidelines for the treatment of hypertension [5] suggest prescribing AMKR as the third or fourth drug to overcome refractoriness to antihypertensive therapy.These conclusions were drawn from the results of small trials (Table 2) and a secondary analysis of the ASCOT study [20]. Most of the studies presented in table. 2, SL and EP were used as part of a combination treatment.

It is well known that the antihypertensive effect of AMKR includes the renal and extrarenal pathways [32]. Treatment with AMCR has been shown to reduce target organ damage mainly by preventing the non-genomic effects of aldosterone, which lead to increased 90,024
arterial stiffness and the development of oxidative stress.For example, with 3- and 6-month treatment with spironolactone in patients with resistant hypertension, a decrease in the severity of left ventricular hypertrophy was observed [33]. The presence of AD-dependent and AD-independent effects make AMCR very attractive drugs for the treatment of such a complex and multifactorial condition as resistant hypertension.
All AMKR are applied 1-2 times / day in the morning. A limitation to their appointment is a serum potassium level of 5 mmol / l and higher. However, even with the appointment of these drugs, patients with normal potassium levels require more frequent monitoring of electrolytes because of the risk of developing hyperkalemia [34].This risk is increased in chronic kidney disease, especially when AMCR is used in combination with blockers of the renin-angiotensin-aldosterone system, and may be the reason for restrictions in their prescription [34].
In 2015, the results of a double-blind, placebo-controlled, cross-over design PATHWAY-2 were published, in which three drugs (AMCR, β-blocker and α-blocker) were tested as an adjunct for the treatment of hypertension resistant to triple antihypertensive therapy [ 35].The authors sought to test the hypothesis that true resistant hypertension is most often caused by sodium retention, and therefore SL will be superior to nondiuretic drugs in lowering blood pressure. The study included 436 patients from 14 centers in the UK aged 18–79 years with systolic blood pressure (SBP) above target, despite treatment for at least 3 months with the maximum allowable doses of three drugs. Patients consistently for 12 weeks. in addition to basic therapy, each of the 3 drugs received: spironolactone (25–50 mg), bisoprolol (5–10 mg), modified release doxazosin (4–8 mg), and placebo.The dose was doubled after 6 weeks. each cycle. The average decrease in home SBP SL exceeded that with placebo by an average of 8 mm Hg. Art. (p

Another indication for the appointment of AMCR is primary aldosteronism (PA), which developed against the background of aldosterone-producing adenoma or bilateral adrenal hyperplasia. The connection between AH and PA was revealed more than 50 years ago. The first reported case was a patient with severe hypertension and hypokalemia associated with increased secretion of aldosterone.In this patient, hypertension was cured by adrenalectomy [36]. At present, when PA is detected, the recommended starting dose of SL is 12.5–25 mg / day, reaching, if necessary, 100 mg / day or more. It is believed that EP has a lower antialdosterone activity and its starting dose should be 25 mg 2 r / day [5]. A multicenter, randomized, double-blind study studied the 16-week effect of SL (75-225 mg 1 r./day) and EP (100-300 mg 1 r./day) on blood pressure and the risk of side effects in patients with primary aldosteronism.Diastolic blood pressure decreased less with EP therapy (–5.6 ± 1.3 mm Hg) than with SL therapy (–12.5 ± 1.3 mm Hg). Differences in –6.9 mm Hg. Art. (-10.6, -3.3) were statistically significant (p

It should be noted that in the study by J.D. Spence et al., Published in 2017, EP at a dose of 25–50 mg 2 times / day significantly reduced resistance to concomitant antihypertensive therapy in both primary and secondary hyperaldosteronism [38].
The negative effect of SL on sexual function in men and the development of dysmenorrhea in women have long been known and are dose-dependent [39].These side effects often lead to low adherence to treatment with this drug, despite its proven positive effect on the prognosis of patients with cardiovascular disease [40]. Reducing the risk of developing cardiovascular complications with AMCR therapy in patients with hypertension has not been studied. All the more important is their influence on the quality of life of this category of patients. The new AMCR eplerenone has a selective effect on mineralocorticoid receptors, with minimal effects on progesterone, androgenic and glucocorticoid receptors.It is these properties that are associated with a decrease in its effect on sexual function and better tolerance [41]. In a study by G.H. Williams et al. EP did not differ from enalapril in the number of cancellations (7.9% versus 9.3% within 6 months, respectively) and side effects from the genital area [42].

Conclusion

If the target blood pressure level is not achieved against the background of 3-component therapy, including a diuretic (resistant hypertension), AMCR can be added to the treatment: spironolactone (starting dose 12.5-25 mg / day) or eplerenone (starting dose 25-50 mg / day ).The limitation to the appointment of these drugs is the serum potassium level of 5.0 mmol / L and higher. When AMKR is prescribed with a serum potassium level of more than 4.5 mmol / L, the level of creatinine and potassium should be measured after 2-4 weeks.
With long-term therapy of hypertension, control of the electrolyte composition of the blood should be carried out after 4–12 weeks. after prescribing or increasing the dose of the drug and then 1-2 times a year. In the appointment of AMKR with chronic kidney disease III degree (glomerular filtration rate – 30-59 ml / min / 1.73 m2), the level of creatinine and potassium should be measured after prescribing or increasing the dose after 2-4 weeks.and then 4-6 times a year.

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90,000 Prostate cancer – disease treatment in Germany. Euro-Hansa Deutschland

Local procedures
Topical treatments treat cancer from a specific, localized area of ​​the body.Such procedures include surgery and radiation therapy. For men who are diagnosed with early stage prostate cancer, topical treatment can completely get rid of the cancer. If the cancer has spread outside the prostate gland, other treatments, called systemic treatments, may be needed to kill cancer cells located elsewhere in the body.

Surgery
Surgery involves removing the prostate and some of the surrounding healthy tissue during surgery.An oncologist surgeon is a doctor who specializes in treating cancer with surgery. In prostate cancer, a urologist or urological oncologist is the surgical oncologist involved in the treatment. The type of surgery depends on the stage of the disease, the general health of the person, and other factors.

Surgical options include:
• Radical (open) prostatectomy.
A radical prostatectomy is the surgical removal of the entire prostate and seminal vesicles.Lymph nodes in the pelvic area can also be removed. This surgery can affect sexual function. Nerve-sparing surgery, when possible, increases the likelihood that a man will be able to maintain his sexual function after surgery by avoiding the surgical damage to the nerves that allows him to maintain an erection and orgasm. Orgasm can happen even if some of the nerves are cut, because they are 2 separate processes. Urinary incontinence is also a possible side effect of radical prostatectomy.To help restore normal sexual function, men may receive special medications, penile implants, or injections. Sometimes, another surgery can correct urinary incontinence.
• Robotic or laparoscopic prostatectomy. This type of surgery is arguably much less invasive than radical prostatectomy and may shorten recovery time. The camera and instruments are inserted through small incisions in the patient’s abdomen. The surgeon then directs robotic instruments to remove the prostate and some surrounding healthy tissue.In general, robotic prostatectomy causes less bleeding and less pain, but the side effects associated with sex and urinary incontinence may be similar to radical (open) prostatectomy. Details need to be discussed with your doctor at a preliminary stage. Talk to your doctor about whether he suggests this procedure and how it compares to the results of radical (open) prostatectomy.
• Bilateral orchiectomy. Bilateral orchiectomy is the surgical removal of both testicles.
Before surgery, consult your doctor about the possible side effects of your particular surgery. Generally, younger or healthier men can benefit more from a prostatectomy. Younger men are also less likely to develop permanent erectile dysfunction and urinary incontinence after prostatectomy than older men.

Radiation therapy
Radiation therapy is the use of high-energy beams to kill cancer cells.A doctor who specializes in performing radiation therapy to treat cancer is called a radiation oncologist. A radiation therapy regimen or schedule usually consists of a specified number of treatments performed over a specified period of time.
Types of radiation therapy used to treat prostate cancer include:
• External beam therapy. External beam radiation therapy is the most common type of radiation therapy. A radiation oncologist uses a machine outside the body to focus an X-ray beam on an area with cancer.Some cancer centers use conformal radiation therapy (CRT), in which computers help pinpoint the location and shape of the cancer. CRT reduces radiation damage to healthy tissues and organs around the tumor by directing the beam of radiation therapy in different directions to focus the dose on the tumor.
One EBRT technique used to treat prostate cancer is called hypofractional radiation therapy. This is when a person receives a higher daily dose of radiation therapy for a shorter period, rather than lower doses for a longer period.
Hypofractional radiation therapy may be an option for the following people with early-stage prostate cancer that has not spread to other parts of the body:
– Men with low risk prostate cancer who need or prefer treatment instead of active supervision.
– Men with intermediate or high risk of prostate cancer receiving EBRT to the prostate gland, but not including the pelvic lymph nodes.
People who receive hypofractional radiation therapy may have a slightly higher risk of some short-term side effects after treatment compared to those who receive regular EBRT.This can include gastrointestinal side effects. Based on current research, people who receive hypofractionated radiation therapy do not have a higher risk of side effects in the long term.

Brachytherapy
Brachytherapy, or internal radiation therapy, is the injection of radioactive sources directly into the prostate. These sources, called seeds, emit radiation only around the area in which they are located and can remain for a short time (high dose) or for a longer time (low dose).Low-dose seeds remain in the prostate forever and work for up to 1 year after injection. However, how long they last depends on the source of the radiation. High dose rate brachytherapy usually remains in the body for less than 30 minutes, but may be required more than once. Brachytherapy can be used with other treatments such as external beam radiation therapy and / or ADT. Modern scientific medicine recommends the following options:
– Men with low-risk prostate cancer who need or choose active treatment may consider low-dose brachytherapy.Other options include external beam radiation therapy or radical prostatectomy.
– Men with intermediate-risk prostate cancer who choose external beam radiation therapy (with or without ADT) should be offered low- or high-dose brachytherapy. To enhance brachytherapy, a lower dose of radiation is given for a shorter period of time. Some men with intermediate-risk prostate cancer can only receive brachytherapy without radiation therapy or radiation therapy.
– Men with high-risk prostate cancer who are receiving external beam radiation therapy and ADT should be offered an increase in low- or high-dose brachytherapy.

Intensive – Modulated Radiation Therapy ( IMRT)
IMRT is a type of external beam radiation therapy that uses computed tomography to form a three-dimensional picture of the prostate gland prior to treatment.The computer uses this information about the size, shape, and location of the prostate cancer to determine how much radiation is needed to destroy it. With IMRT, large doses of radiation can be directed to the prostate without increasing the risk of damage to nearby organs.

Proton therapy
Proton therapy, also called proton beam therapy, is a type of external beam radiation therapy that uses protons rather than X-rays.At high energies, protons can destroy cancer cells. Current research has not shown that proton therapy provides more benefit to men with prostate cancer than traditional radiation therapy. It is also more expensive. Radiation therapy can cause side effects during treatment, including increased urination; problems with sexual function; problems with bowel function, including diarrhea, rectal discomfort, or rectal bleeding; and fatigue. Most of these side effects usually resolve with treatment.
Radiation therapy can cause side effects during treatment, including increased urination or frequency; problems with sexual function; problems with bowel function, including diarrhea, rectal discomfort, or rectal bleeding; and fatigue. Most of these side effects usually resolve with treatment.
Men may receive drugs, penile implants, or injections to help restore normal sexual function. Although some of the side effects of radiation therapy are rare, they may not appear until several years after treatment.

Focal treatments
Focal therapies are less invasive treatments that destroy small prostate tumors without treating the rest of the prostate. These treatments use heat, cold, and other cancer treatments, primarily for men with low to moderate risk prostate cancer. They are being studied, and most of them have not been approved as standard treatment options. Focal therapy is usually done as part of a clinical trial.

Cryosurgery , also called cryotherapy or cryoablation, is a type of focal therapy. This is the freezing of cancer cells using a metal probe inserted through a small incision in the area between the rectum and the scrotum, the skin sac that contains the testicles. It is not an established therapy or standard of care for men newly diagnosed with prostate cancer. Cryosurgery has not been compared to radical prostatectomy or radiation therapy, so doctors do not know if this is a comparable treatment option.Its effects on urination and sexual function are also not known.

High Intensity Focused Ultrasound ( HIFU) is a heat-based focal therapy. During HIFU treatment, an ultrasound probe is inserted into the rectum and then sound waves are directed to cancerous areas of the prostate gland. This treatment is designed to kill cancer cells while limiting damage to the rest of the prostate gland. The FDA approved HIFU for the treatment of prostate tissue in 2015.HIFU may be an attractive option for some patients, but the knowledge of who can benefit the most from this treatment is still unknown. Likewise, HIFU should only be performed by a highly experienced technician. You will need to discuss carefully with your doctor if HIFU is the best treatment for you.

Systemic Treatment
Doctors use therapies such as ADT, chemotherapy, and new drugs to reach cancer cells throughout the body.This is called systemic treatment.
Androgen deprivation therapy (ADT)
Since the growth of prostate cancer is driven by male sex hormones called androgens, lowering levels of these hormones can help slow cancer growth. The most common androgen is testosterone. Testosterone levels in the body can be lowered by surgically removing the testicles, known as surgical castration, or by taking medications that turn off testicular function, called medical castration.Which ADT method is used is less important than the primary goal of lowering testosterone levels.
ADT is used to treat prostate cancer in a variety of situations, including locally advanced, recurrent prostate cancer and metastatic prostate cancer. Some of the situations in which ADT can be used include:
• Men with NCCN-based intermediate risk and high-risk prostate cancer who have definitive radiation therapy are candidates for ADT.Definitive therapy is treatment that is given to treat cancer. Men with intermediate risk prostate cancer should receive ADT for at least 4 to 6 months. Those with high-risk prostate cancer should receive ADT for 24 to 36 months.
• ADT can also be given to men who have had surgery and microscopic cancer cells have been found in the removed lymph nodes. ADT is done to eliminate any remaining cancer cells and reduce the chances of cancer returning.This is known as adjuvant therapy. Although the use of adjuvant ADT is controversial, some specific patients benefit from this approach.
Specific types of ADT
• Bilateral orchiectomy. Bilateral orchiectomy is the surgical removal of both testicles. It was the first treatment for metastatic prostate cancer over 70 years ago. Although it is an operation, it is considered ADT because it removes the main source of testosterone production, the testes.The effects of this operation are permanent and cannot be reversed.
• LHRH agonists. LHRH stands for luteinizing hormone releasing hormone. Medicines known as LHRH agonists prevent the testes from receiving messages sent by the body to produce testosterone. By blocking these signals, LHRH agonists lower testosterone levels in a person in the same way they remove their testicles. Unlike surgical castration, the effects of LHRH agonists are often reversible, so testosterone production usually starts again as soon as the patient stops treatment.However, testosterone recovery can take any time from 6 to 24 months, and for a small proportion of patients, testosterone production does not return.
LHRH agonists are injected or placed as small implants under the skin. Depending on the drug used, they can be given once a month or once a year. When LHRH agonists are first used, testosterone levels rise briefly and then drop to very low levels. This effect is known as flash. Outbreaks occur because the testes temporarily release more testosterone in response to LHRH agonists in the body.This outbreak can increase the activity of prostate cancer cells and cause symptoms and side effects such as bone pain in men with cancer that has spread to the bones.
• LHRH antagonist. This class of drugs, also called a gonadotropin-releasing hormone (GnRH) antagonist, prevents the testes from producing testosterone similar to LHRH agonists, but they lower testosterone levels faster and do not cause flares. The FDA has approved degarelix (Firmagon), given monthly as an injection, for the treatment of advanced prostate cancer.One of the side effects of this drug is that it can cause a serious allergic reaction.
• Anti-androgens. While LHRH agonists and antagonists lower testosterone levels in the blood, antiandrogens block testosterone from binding to so-called “androgen receptors,” which are chemical structures in cancer cells that allow testosterone and other male hormones to enter cells. These drugs include bicalutamide (Casodex), flutamide (Eulexin), and nilutamide (Nilandron) and are taken as pills.Antiandrogens are usually given to men who have “hormone-sensitive” prostate cancer, which means that prostate cancer is still responding to testosterone suppression therapy. Antiandrogens are not usually used on their own to treat prostate cancer.

Combined androgen blockade . Antiandrogens are sometimes combined with bilateral orchiectomy or LHRH agonist treatment to maximize male hormone blockade. This is because even after the testes stop producing hormones, the adrenal glands still produce small amounts of androgens.Many doctors also believe this combination approach is the safest way to start ADT, as it prevents a possible flare-up that sometimes occurs in response to LHRH agonist treatment. Some, but not all, studies have shown that combined androgen blockade can help patients live longer than treatment with ADT alone, surgery, or LHRH agonists or antagonists. Therefore, some doctors prefer to prescribe a combination drug treatment, while others may only prescribe a combination early in treatment to prevent an outbreak.
• Intermittent ADT. Traditionally, ADT was given throughout the patient’s life or until the cancer was no longer under control and then other treatment options were considered. Over the past two decades, researchers have studied the use of intermittent ADT, which is ADT that is given for a specific time (most often 6 months) and then temporarily stopped to allow testosterone levels to recover. For these patients, ADT restarts when PSA starts to rise again.When to resume therapy (i.e. at what PSA levels) remains controversial. Using ADT in this way can reduce the side effects associated with a lack of testosterone and improve the patient’s quality of life. This approach is most useful in patients who do not show signs of metastasis. Intermittent ADT has not been shown to be effective or better than lifelong ADT in men with metastatic disease.

Side effects ADT
ADT causes side effects that usually go away after treatment is completed, except in men who have had an orchiectomy.Common ADT side effects include:
• erectile dysfunction
• loss of sexual desire
• hot flashes with sweating
• Gynecomastia, which is growth of breast tissue that can sometimes lead to discomfort
• Depression
• Cognitive dysfunction and memory loss
• Weight gain
• loss of muscle mass 90,024
• Osteopenia or osteoporosis, which is thinning of the bones
Although testosterone levels may recover after discontinuation of ADT, some men who have had medical castration with LHRH agonists for many years may continue to have hormonal effects even if they no longer take these drugs.
Another serious side effect of ADT is the risk of metabolic syndrome. Metabolic syndrome is a collection of conditions such as obesity, high blood cholesterol, and high blood pressure that increase the risk of heart disease, stroke, and diabetes. It is currently not clear how often this happens or why exactly this happens, but it is clear that patients who receive surgical or medical castration with ADT have an increased risk of developing metabolic syndrome.The risk is increased even if the medical castration is temporary. Learn more about the symptoms of hormone deprivation and how to manage them.
The risks and benefits of castration should be carefully discussed with your doctor. For men with metastatic prostate cancer, especially if it progresses and causes symptoms, most doctors believe that the benefits of castration far outweigh the risk of side effects. Aggressive treatment of side effects is very important for patients receiving ADT.These include regular exercise, smoking cessation, a balanced diet, adequate amounts of vitamin D and calcium, and aggressive preventive cardiovascular care.

Chemotherapy
Chemotherapy is the use of drugs to kill cancer cells, usually by stopping their ability to grow and divide. Chemotherapy is usually done by a medical oncologist, a doctor who specializes in treating cancer with drugs.
Systemic chemotherapy enters the bloodstream to reach cancer cells throughout the body. Chemotherapy for prostate cancer is given through an intravenous (IV) tube placed into a vein with a needle. It can help patients with advanced or castration-resistant prostate cancer. A chemotherapy regimen or schedule usually consists of a specific number of cycles given over a period of time.
There are several standard drugs used for prostate cancer.Typically, standard chemotherapy starts with docetaxel (Docefrez, Taxotere) combined with a steroid called prednisone (several brands).
The FDA also approved another drug, cabazitaxel (Jevtana), based on studies that showed it improved survival compared to mitoxantrone for patients whose disease progressed after taking docetaxel. In clinical trials, cabazitaxel was compared with docetaxel in patients who did not receive chemotherapy.In these patients, treatment with cabazitaxel was no better than treatment with standard docetaxel. Another study compared a standard dose with a lower dose of cabazitaxel in people whose tumors grew after docetaxel treatment. In addition to having fewer side effects, this study also showed that a lower dose also helped patients live longer.
Recent research suggests that adding chemotherapy after 2 years of ADT for high-risk prostate cancer men undergoing radiation therapy is an effective approach to reduce relapse and improve survival.While these results are interesting, further research is needed to see if this treatment helps people with prostate cancer.
In general, side effects of chemotherapy depend on the individual, the type of chemotherapy received, the dose used, and the duration of treatment, but they can include fatigue, mouth and throat ulcers, diarrhea, nausea and vomiting, constipation, blood disorders, nervous system effects, changes in thinking and memory, sexual and reproductive problems, loss of appetite, pain and hair loss.The side effects of chemotherapy usually go away after treatment ends. However, some side effects may continue, come back, or develop later. Ask your doctor what side effects you may experience depending on your treatment plan. Your healthcare team will work with you to eliminate or prevent many of these side effects. Learn more about the basics of chemotherapy and preparation for treatment. Medicines used to treat cancer are continually being evaluated.Talking to your doctor is often the best way to find out about the medications you are prescribed, their prescriptions, and their potential side effects or interactions with other medications. Find out more about your prescriptions using searchable drug databases.

Urinary block
• Transurethral resection of the prostate (TURP). TURP is most commonly used to relieve symptoms of urinary blockage rather than to treat prostate cancer. In this procedure, while the patient is under complete anesthesia, which is medicine to block the sensation of pain, the surgeon inserts a narrow tube with a cutting device called a cystoscope into the urethra and then into the prostate to remove prostate tissue.
Bone pain and weakness
• Strontium and Samarium. These radioactive substances (beta emitters) are injected and absorbed near the bone pain area. The released radiation helps relieve pain, possibly causing a tumor in the bone to shrink. None of the substances help patients live longer.
• radium-223. This treatment is used to relieve bone pain in men with castration-resistant prostate cancer that has spread to the bones.Read more in the Treatment of Metastatic Castration-Resistant Prostate Cancer above.
• Bone-modifying drugs. Bone health is an important aspect of life for men with prostate cancer. Osteopenia and osteoporosis are bone conditions that can be caused by low testosterone levels. Therefore, preventing bone loss in men receiving ADT is important because it reduces the risk of bone loss. Bone-modifying drugs such as denosumab (Prolia, Xgeva) and zoledronic acid (Reclast, Zometa) can be given to prevent bone loss.Both of these drugs have unique side effects, so patients should discuss with their doctor when to take the drug and which drug is best, depending on the situation.
In metastatic castration-resistant prostate cancer, bone-modifying drugs have been shown to reduce the risk of skeletal-related events. Skeletal-related events are complications caused by prostate cancer that has spread to the bone, such as fractures and spinal cord compression.They are treated with orthopedic surgery and palliative radiation therapy to control pain.
Bone-modifying drugs have not been shown to help in the treatment of non-metastatic castration-resistant prostate cancer.
A possible condition associated with bone-modifying drugs is osteonecrosis of the jaw. This is an unusual but serious condition. Symptoms of osteonecrosis of the jaw include pain, swelling, and infection of the jaw; loose teeth; and open bone. It is important that all dental work is completed before taking these drugs.If a patient taking these drugs needs dental work, treatment should be stopped until the dental work is complete and the patient is healed.

Palliative care for metastatic cancer
As mentioned above and in the “Coping with Treatment” section, palliative care is important for relieving symptoms and side effects. This includes people with metastatic prostate cancer. Palliative care options include:
• TURP to treat symptoms such as bleeding or blockage of urine.
• Bone-modifying drugs such as denosumab or zoledronic acid can be used to strengthen bones and reduce the risk of skeletal-related events in men with prostate cancer that has spread to the bone.
• Intravenous radiation therapy with radium-223, strontium, and samarium can also help relieve bone pain.
• Palliative radiation therapy for specific areas of the bones can be used to relieve bone pain when medications are not helping.
Before starting treatment, talk to your healthcare team, including your dentist, about the possible side effects of your specific treatment plan and palliative care options. During and after treatment, be sure to tell your doctor or other doctor if you have a problem so that it can be resolved as quickly as possible.

On remission and relapses
Remission is when cancer is not found in the body and there are no symptoms. It can also be called no signs of illness or NED.
Remission can be temporary or permanent. This uncertainty makes many people worry that cancer will return. While there are treatments to help prevent recurrence, such as ADT and radiation therapy, which are described above, it is important to talk to your doctor about the possibility of cancer returning. There are tools your doctor can use, called nomograms, to assess your risk of recurrence. Understanding your risk of recurrence and treatment options can help you feel more prepared if your cancer comes back.Learn more about how to deal with your fear of recurrence.
Typically, after surgery or radiation therapy, the PSA level in the blood usually drops. If PSA levels start to rise again, it could be a sign that the cancer is back. If the cancer does return after initial treatment, it is called recurrent cancer.
When this happens, a new testing cycle will begin again to learn as much as possible about the repetition, including where the repetition is.Cancer can return to the prostate gland (called local recurrence), to tissues or lymph nodes near the prostate gland (regional recurrence), or to another part of the body such as the bones, lungs, or liver (distant or metastatic recurrence). Sometimes the doctor cannot find the tumor, although the PSA level has increased. This is known as PSA-only or biochemical relapse.
After this testing is done, you and your doctor will discuss your treatment options. The choice of treatment plan is based on the type of relapse and the treatment you have already received, and may include the procedures described above, such as radiation therapy, prostatectomy for men who received radiation therapy for the first time, or ADT.Your doctor may suggest clinical trials that investigate new treatments for this type of recurrent cancer.
Whichever treatment plan you choose, palliative care will be important to relieve symptoms and side effects. Palliative care usually includes pain medications, external beam radiation therapy, brachytherapy with radium-223, strontium or samarium, or other treatments for bone pain.