Ear Injection of AM-101 May Stop Tinnitus

Phantom ringing of the ears also known as tinnitus is an extremely frustrating condition that afflicts many people. Often triggered by hearing nerve damage, there's no good treatment to fix this condition once it sets in.

Until possibly now... 

AM-101 made by Auris Medical is an experimental drug containing esketamine hydrochloride embedded within a hyaluronic acid gel formulation. It works by blocking the NMDA receptors of the cochlear inner hair cell.

Normally, when there is trauma sustained by the cochlea whether it be loud noise or viral infection, excess amount of a neurotransmitter called glutamate gets release. The problem is that too much glutamate also triggers hearing nerve death due to over-excitation via the NMDA receptor. When these hearing nerves die, it leaves the brain cells responsible for hearing in a permanently switch-on state leading to tinnitus, even if there's no sound present.

AM-101 is hypothesized to block the NMDA receptor from being over-stimulated by the glutamate neurotransmitter thereby preventing hearing nerve death.

But, does it work?

According to one small prospective, double-blind, randomized, placebo-controlled study involving 248 patients, it DOES work to a significant degree.  42% reported their tinnitus was half as quiet as before compared with 14% in the placebo group. After 90 days, 57% of those taking the active gel said their tinnitus was 'much improved' or 'very much improved'.

Of course, the trick is to administer the drug before nerve death has set in after which it would be too late. In the study, only patients with onset of ringing within 3 months were eligible to participate.

Patient also need to realize that the drug is administered by injection through the eardrum and into the middle ear space. This injection technique is commonly used in the treatment of sudden nerve hearing loss where steroids are injected. Watch video of this injection method below.

Unfortunately, AM-101 is not available except under research protocols currently and is undergoing FDA clinical trials. The preliminary results are very promising however.

Reference:
Efficacy and Safety of AM-101 in the Treatment of Acute Inner Ear Tinnitus—A Double-Blind, Randomized, Placebo-Controlled Phase II Study. Otology & Neurotology: April 2014 - Volume 35 - Issue 4 - p 589-597

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Botox Injection Severe Side Effects Treatment

Side effects from botox injections are not uncommon and even expected to some degree in the region where the injection was performed. For example, when botox is injected into the voicebox for spasmodic dysphonia, normal and expected side effects include hoarseness and dysphagia.

However, in very rare instances, more severe side effects may occur that may even appear to be life-threathening including stridor, shortness of breath, profound difficulty swallowing, etc.

In such situations, beyond supportive care and ruling out more serious conditions like a heart attack, treatment with pyridostigmine can be quite effective in alleviating if not outright reversing the severe botox side effects.

Pyridostigmine is a drug that prevents the body from breaking down the chemical mediator (acetylcholine) that causes muscle contraction. Given botox works by preventing the release of acetylcholine, it makes sense that by preventing the body from breaking this hormone down, more of it is around to activate the muscle.

Put simply, pyridostigmine increases acetylcholine levels to counteract the botox effect of decreasing acetylcholine leading to a net zero effect theoretically. But does it work that way? According to one research paper, it certainly appears to do so!

In cases of stridor due to bilateral vocal cord paralysis or other severe side effect, an initial treatment of 300 mg of pyridostigmine x 2 doses separated by 6 hours followed by 30 mg 3x per day is recommended. Symptom improvement occurs fairly rapidly.

In less dire situations, simply starting a patient on pyridostigmine 30 mg 3x per day without an initial loading dose is sufficient.

Otherwise, behavioral support alone is recommended for less severe botox side effects.

Reference:

Pyridostigmine for Reversal of Severe Sequelae From Botulinum Toxin Injection. Journal of Voice. 2014 Jul 5. pii: S0892-1997(14)00091-5. doi: 10.1016/j.jvoice.2014.04.010. [Epub ahead of print]

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Cure for Noise-Induced Hearing Loss?

Normally, when mammals (including humans) are exposed to very loud sounds, permanent hearing loss may result due to cochlear hair cell injury. However, an experimental drug code-named LY411575 was found to regenerate new hair cells by suppressing a protein called Notch.

In essence, this drug restored hearing to mice deafened by loud noise.

Listen to an explanation by Harvard researcher Dr. Edge in this video.

However, human trials are a very long way off… so prevention is still the best way to avoid permanent noise-induced hearing loss. Wear hearing protection whenever loud sounds may be present!

Reference:
Notch Inhibition Induces Cochlear Hair Cell Regeneration and Recovery of Hearing after Acoustic Trauma. Neuron Volume 77, Issue 1, 58-69, 9 January 2013

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Medications that (Might) Help Tinnitus?

The blunt answer is that there is no drug or supplement that has been consistently found to help with tinnitus (ringing of the ears).

Here's a partial table showing all the research that has been done either proving or disproving effectiveness to treat tinnitus (info collected from this review paper).

For a more comprehensive list going over 17 drugs, click here.

Drug	Research That Supports	Research That Disputes	Conclusion
Benzodiazepines (alprazolam, diazepam, clonazepam)	#1, #2, #3, #4	#1, #2, #3	Caution due to addiction and may worsen tinnitus if stopped.
Antidepressants (nortriptyline, amitriptyline, trimipramine, sertraline, paroxetine)	#1, #2, #3, #4, #5	#1, #2, #3, #4, #5, #6	TCA may benefit only in patients with depression symptoms
Anticonvulsants (carbamazepine, gabapentin, vigabatrin, tiagabine)	#1, #2, #3, #4, #5, #6, #7, #8, #9	#1, #2, #3, #4, #5, #6, #7	Mixed results
Antiglutamatergics (caroverine, memantine, acamprosate)	#1, #2, #3, #4	#1, #2, #3, #4	No conclusion.
(Anti)Dopaminergics (sulpiride, piribedil)	#1, #2, #3	#1	Studies are weak.
Ginkgo Biloba	#1, #2	#1, #2, #3	Not effective.
Melatonin	#1, #2, #3	#1	Potentially helpful.

For more meds, click here.

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Men's Ability to Taste Linked to Fertility?

Image by צביה from Wikipedia

Researchers found that two proteins that govern the ability to taste sweet and savory profoundly influenced sperm development.

This surprising connection between taste and male fertility occurred when the gene encoding the taste receptor proteins TAS1R3 (part of savory taste receptor) and GNAT3 (converts oral taste signal to a nerve signal) were modified in mice allowing for selective knockout with the drug clofibrate.

When these genetically modified mice were given clofibrate leaving the mice without any functional TAS1R3 and GNAT3, the males became sterile due to profoundly reduced sperm counts and malformations.

When clofibrate administration was stopped in these mice, fertility immediately came back.

Of note, clofibrate is a common drug prescribed to treat high cholesterol.

And it does potentially suggest that such cholesterol drugs may adversely influence human male fertility... as well as potentially lead to a safe and effective non-hormonal male contraceptive.

Reference:
Genetic loss or pharmacological blockade of testes-expressed taste genes causes male sterility. Published online before print July 1, 2013, doi: 10.1073/pnas.1302827110 PNAS July 1, 2013

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What are the Most Common Severe Drug-Induced Anaphylaxis?

Image by James Heilman, MD from Wikipedia

Interesting paper came out listing the most common severe drug-induced anaphylaxis. From a database of 333 patients who suffered from anaphylaxis,

• Anaphylactic shock (76.6%)
• Severe systemic reactions (10.5%)
• Acute laryngeal edema (9%)
• Severe bronchospasm (2.1%)
• Fatal in 6 cases (1.8%)

There were 270 cases (81.1%) of ambulatory anaphylaxis. Sixty-three cases (18.9%) occurred during anesthesia.

84 drugs were identified as being responsible for these cases of anaphylaxis.

• Antibiotics (49.6%)
• Muscle relaxants, latex and anesthetics (15%)
• NSAIDS (10.2%)
• Tylenol (3.9%)
• Iodinated or magnetic resonance imaging contrast media (4.2%)
• Allergy shots and vaccines (3.9%)
• Other drugs (13%)

Among antibiotics, amoxicillin (97 cases), other penicillins (four cases), cephalosporins (41 cases), quinolones (15 cases), and pristinamycin (seven cases) were the most common.

Reference:
Severe drug-induced anaphylaxis: analysis of 333 cases recorded by the Allergy Vigilance Network from 2002 to 2010. Allergy. 2013 Jun 6. doi: 10.1111/all.12168. [Epub ahead of print]

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Chronic Cough Due to Statins

Statin drugs (simvastatin for example) are commonly used to treat high cholesterol and have many known side effects... but here's another. Statins are now believed to potentially cause a chronic dry cough according to a recent report!

This chronic cough side effect is common in other types of medications such as ACE-Inhibitors (lisinopril) and angiotensin receptor blockers (losartan) to treat high blood pressure.

Statins were not previously known to cause a chronic dry cough.

Reference:
Chronic cough as a complication of treatment with statins: a case report. Ther Adv Respir Dis. 2012 Jul 3. [Epub ahead of print]

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Azithromycin Increases Risk of Death Slightly... Well, So Does Tylenol and Ibuprofen

The media has made much fuss about a NEJM study suggesting a slight increased risk of death from taking azithromycin or z-pack. The more unhealthy you are, the higher the risk... no duh... (I would think the sicker you are, the greater the risk of death PERIOD... a sick person by definition is closer to death than a healthy person).

How slight? Compared to amoxicillin, about 47 additional cardiovascular deaths per one million courses of therapy.

Never mind the blatant biases found in the study nicely espoused on by cardiologist Dr. Wes in his blog. I should also point out that there's another study that did NOT find an increased risk of death with azithromycin.

Thinking you should never take a z-pack again due to this slight increased risk of death?

Well, good luck finding an alternative medication (of any kind) because they ALL have a potential risk of death.

Similar to z-pack, these other antibiotics also have an increased risk of sudden cardiac death:

• Avelox
• Bactrim
• Biaxin
• Cipro
• Diflucan
• Erythromycin
• Factive
• Floxin
• Foscavir
• Ketek
• Levaquin
• Sporanox
• Sulfa
• Tequin

It's not just antibiotics. These other common medications (not all-inclusive) also have an increased risk of sudden cardiac death:

• Benadryl (allergy)
• Pepcid (reflux)
• Albuterol (asthma)
• Prozac (depression)
• Serevent (asthma)
• Sudafed (decongestant)

The complete list can be found here.

Let's consider other popular drugs that also has an increased risk of death, though not necessarily from a cardiac trigger.

• ALL antibiotics due to a severe anaphylactic allergic reaction - Take Penicillin for example... about 300 die annually from penicillin allergic reaction in the US
• Tylenol causes liver failure - About 400 deaths per year in the US
• Ibuprofen causes internal bleeding - About 15,000 - 20,000 die per year in the US
• Alcohol related deaths - 75,000 deaths per year in the US
• Smoking related deaths - 443,000 deaths per year (one in five deaths) in the US

Never mind deaths from driving a car, accidental gunfire, drowning in a swimming pool, etc.

Life in general in the United States has a risk of death.

Source:
Azithromycin may up chance of sudden cardiac death. Heartwire 5/16/12
Popular Antibiotic May Raise Risk of Sudden Death. NYT 5/16/12
Azithromycin and the Risk of Cardiovascular Death. New England Journal of Medicine 2012; 366:1881-1890May 17, 2012
Use of Azithromycin and Death from Cardiovascular Causes. N Engl J Med 2013; 368:1704-1712May 2, 2013DOI: 10.1056/NEJMoa1300799

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