About Noonan Syndrome

What is Noonan Syndrome?

Noonan syndrome is a disorder that involves unusual facial characteristics, short stature, heart defects present at birth, bleeding problems, developmental delays, and malformations of the bones of the rib cage.

Noonan syndrome is caused by changes in one of several autosomal dominant genes. A person who has Noonan syndrome may have inherited an altered (mutated) gene from one of his or her parents, or the gene change may be a new change due to an error carried by the egg or sperm or occurring at conception. Alterations in four genes - PTPN11, SOS1, RAF1 and KRAS - have been identified to date.

Noonan syndrome is present in about 1 in 1,000 to 1 in 2,500 people.

What are the symptoms of Noonan Syndrome?

Symptoms of Noonan syndrome may include the following:

• A characteristic facial appearance.
• Short stature.
• Heart defect present at birth (congenital heart defect).
• A broad or webbed neck.
• Minor eye problems such as strabismus in up to 95 percent of individuals.
• Bleeding problems such as a history of abnormal bleeding or bruising.
• An unusual chest shape with widely-spaced and low set nipples.
• Developmental delay of varying degrees, but usually mild.
• In males, undescended testes (cryptorchidism).

How is Noonan syndrome diagnosed?

The diagnosis of Noonan syndrome is based on the person's clinical symptoms and signs. The specialist examines the person looking for the specific features of Noonan syndrome.

Individuals who have Noonan syndrome have normal chromosome studies. Four genes - PTPN11, SOS1, RADF1and KRAS - are the only genes that are known to be associated with Noonan syndrome. Approximately 50 percent of individuals with Noonan syndrome have mutations in the PTPN11 gene. Twenty percent of those with Noonan Syndrome have mutations in the SOS1. Mutations in the RAF1 gene account for between 10 and 15 percent of Noonan syndrome cases. About 5 percent of people with Noonan syndrome have mutations in the KRAS gene and usually have a more severe or atypical form of the disorder. The cause of Noonan syndrome in the remaining 10 to 15 percent of people with this disorder is not yet known. .

Symptoms of Noonan syndrome may include the following:

• A characteristic facial appearance.
• Short stature.
• Heart defect present at birth (congenital heart defect).
• A broad or webbed neck.
• Minor eye problems such as strabismus in up to 95 percent of individuals.
• Bleeding problems such as a history of abnormal bleeding or bruising.
• An unusual chest shape with widely-spaced and low set nipples.
• Developmental delay of varying degrees, but usually mild.
• In males, undescended testes (cryptorchidism).

What is the treatment for Noonan syndrome?

Treatment for individuals who have Noonan syndrome is based on their particular symptoms. Heart problems are treated in the same way as they are for individuals in the general population. Early intervention programs are used to help with developmental disabilities, when present. Bleeding problems that can be present in Noonan syndrome may have a variety of causes and are treated according to their cause. Growth problems may be caused by lack of growth hormone and may be treated with growth hormone treatment. Symptoms such as heart problems are followed on a regular basis.

Is Noonan syndrome inherited?

Noonan syndrome is inherited in families in an autosomal dominant pattern. This means that a person who has Noonan syndrome has one copy of an altered gene that causes the disorder. In about one-third to two-thirds of families one of the parents also has Noonan syndrome. The parent who has Noonan syndrome has a 1 in 2 (50 percent) chance to pass on the altered gene to a child who will be affected; and a 1 in 2 (50 percent) chance to pass on the normal version of the gene to a child who will not have Noonan syndrome. In many individuals who have Noonan syndrome, the altered gene happens for the first time in them, and neither of the parents has Noonan syndrome. This is called a de novo mutation. The chance for these parents to have another child with Noonan syndrome is very small (less than 1 percent).

FDA Approves PI3K Inhibitors for Breast Cancer

The impact of PI3K inhibitors on breast cancer cell and its tumor microenvironment

The FDA has approved Piqray (alpelisib, Novartis) tablets, to be used in combination with FDA-approved endocrine therapy fulvestrant, to treat postmenopausal women and men with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, PIK3CA-mutated, advanced or metastatic breast cancer.

The FDA also approved a companion diagnostic test, therascreenPIK3CA RWG PCR kit, to detect the PIK3CA mutation in a tissue or liquid biopsy. If a patient’s samples return a negative result from the test, they should also undergo a tumor biopsy for PIK3CA mutation testing.


"Piqray is the first PI3K inhibitor to demonstrate a clinically meaningful benefit in treating patients with this type of breast cancer. The ability to target treatment to a patient's specific genetic mutation or biomarker is becoming increasingly common in cancer treatment, and companion diagnostic tests assist oncologists in selecting patients who may benefit from these targeted treatments," said Richard Pazdur, M.D., director of the FDA's Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research.

Piqray’s efficacy was studied in a SOLAR-1 trial, randomized with 572 postmenopausal women and men with HR-positive, HER2-negative advanced or metastatic breast cancer whose cancer had progressed while taking, or after taking, an aromatase inhibitor. According to a press release, the results showed that the addition of Piqray to fulvestrant significantly prolonged the progression-free survival of patients whose tumors had a PIK3CA mutation.

Common side effects of PIqray include high blood sugar levels, an increase in creatinine, diarrhea, rash, a decrease in lymphocyte count, elevated liver enzymes, nausea, fatigue, an increase in lipase, decreased appetite, stomatitis, vomiting, weight loss, low calcium levels, prolonged aPTT, and hair loss.

Healthcare professionals should monitor patients for hypersensitivity reactions and are advised to not initiate treatment in patients with a history of severe skin reactions such as Stevens-Johnson syndrome, erythema multiforme, or toxic epidermal necrolysis. The safety of Piqray in patients with Type 1 or uncontrolled Type 2 diabetes has not been established at the time of this announcement.

Prior to treatment initialization, healthcare professionals should check fasting glucose and HbA1c, and to optimize glycemic control. Throughout treatment, patients should be monitored for the development of pneumonitis/interstitial lung disease and diarrhea

Novartis' breast cancer treatment wins FDA approval

(Reuters) - The U.S. Food and Drug Administration (FDA) said on Friday that it had approved Novartis AG’s treatment in combination with a hormone therapy for postmenopausal women, as well as for men, with a form of advanced breast cancer.

The drug, alpelisib, to be marketed under the brand name Piqray, belongs to a class of drugs known as PI3K inhibitors and is the first of its kind to be approved, the FDA said in a statement.
“Piqray is the first PI3K inhibitor to demonstrate a clinically meaningful benefit in treating patients with this type of breast cancer,” the FDA said.

The combination therapy has been approved to treat hormone receptor positive, HER2-negative breast cancer with mutations of the PIK3CA gene and was fast-tracked under a type of FDA’s pilot program.

Although PIK3CA mutations are the most common genetic change in hormone-receptor positive breast cancer, trials of agents seeking to put a brake on this pathway to tumor growth have largely disappointed so far.

Roche Holding AG, one of the world’s biggest producer of cancer drugs, scrapped its experimental PI3K inhibitor, taselisib, last year, citing limited benefits and serious side effects with the drug.

Nonsteroidal anti-inflammatory drugs safe for acute myopericarditis

Use of high-dose ibuprofen and aspirin is safe for acute myopericarditis patients with normal left ventricular ejection fraction (LVEF), a study has found.

Researchers examined the medical records of 60 patients with myopericarditis who received standard heart failure therapy if indicated. There were 29 patients (62 percent; mean age, 34 years; 13 percent female; mean LVEF, 56 percent) who received NSAIDs—acetylsalicylic acid at an average daily dose of 1,300 mg or ibuprofen at an average daily dose of 1,500 mg for an mean duration of 4 weeks.

Compared with patients treated with NSAIDs, those who were not treated were older and had lower LVEF. Late gadolinium enhancement at 3 months decreased in 82 percent of the patients (14 of 17) treated with NSAIDs and in 58 percent (7 of 12) of those without NSAIDs (p=0.15).

One adverse event (3 percent) occurred in the NSAID group. The patient had an asymptomatic episode of nonsustained ventricular tachycardia on 48-hour Holter at 3-month follow-up, which lasted for 9 beats. In this case, the initial LVEF was 56 percent and follow-up MRI showed a decrease in late gadolinium enhancement.

The findings indicate that NSAIDs are a valid and safe treatment option in the setting of acute myopericarditis, researchers said.

The study is said to be the first to assess the effect of NSAIDs in myocarditis on top of standard heart failure therapy in humans. However, it is limited by the small sample size, researchers said. Large randomized clinical trials are needed to test NSAIDs prospectively for efficacy.

Cefixime

Cefixime is a beta-lactamase stable third generation cephalosporin, which is a semi synthetic compound and was the first orally active and effective antibiotic with longest half life. It is used to treat the bacterial infection of the lungs, urinary tract and ear and it is stops the growth of bacteria in the body. It was the first antibiotic manufactured synthetically on a large scale. The original indication of Cefixime was in the treatment of typhoid.

Current use of Cefixime:

_________________________________________

Cefixime is given by oral route in the treatment of susceptible infections which contains gonorrhea, urinary tract, pharynsitis and otitis mediainfection.

Cefixime Dosage:

Take cefixime exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.The cefixime dose your doctor recommends will be based on (use any or all that apply):
• the condition being treated
• other medical conditions you have
• other medications you are taking
• how you respond to this medication
• your kidney function
• your weight

The recommended dose for cefixime in adults is 400 mg once a day or divided into two doses (200 mg each dose).
The recommended dose range for cefixime in children (weighing 44 kg or less or are 12 years of age or less) is 8 mg/kg once a day or 4 mg/kg twice a day.

Side Effects of Cefixime:

___________________________________

Common side effects of cefixime includes:
• Rrash,
• Diarrhea,
• Nausea,
• Loose stools,
• Upset stomach.
This is not a complete list of cefixime side effects. Ask your doctor or pharmacist for more information.

Important information about Carvedilol

• Carvedilol belongs to a class of medications called beta-blockers
• It is used to treat heart failure (condition in which the heart can not pump enough blood to all parts of the body) and high blood pressure used.
• It is also used to treat people who have had a heart attack. Carvedilol is often used in combination with other medications.

Mechanism of action

Carvedilol is a racemic mixture, in the nonselective activity of beta-adrenoceptor blocking of the S (-) – enantiomer is present and the alpha-adrenergic blocking activity in both R (+) -, as well as S (-) – enantiomer with the same activity is present. Blocking the capacity of beta-carvedilol adrenergic receptors reduces heart rate, myocardial contractility and myocardial oxygen demand. It also reduces systemic vascular resistance through its blocking properties of the alpha adrenergic receptor. It has been shown that carvedilol and its BM-910228 metabolite restore (less strong beta blockers, but a stronger antioxidant) inotropic reactivity to Ca2 + in the radical myocardium treated with free OH. Carvedilol and its metabolites also prevent the reduction induced by OH radicals in the sarcoplasmic reticulum Ca2 + ATPase activity. Therefore, carvedilol and its metabolites may be beneficial in chronic heart failure by preventing free radical damage.

side effects

The most common side effects  include:

• Dizziness
• Unusual tiredness
• Low blood pressure
• Diarrhea
• High blood sugar
• Lack of energy or weakness
• Slower heart rate
• increase in weight
• Changes in sexual desire or performance
• Dry eyes
• Dry and itchy skin
• Headaches
• Nausea

Serious side effects may include:

• Allergic reactions
• Changes in your heart rate
• The problems of the heart.
• Liver problems
• Problems in the eyes
• Urinary problems

Dosage for carvedilol

• Carvedilol tablets are usually given twice a day. If the blood pressure is high, the dose is 6.25 mg twice a day up to a maximum of 25 mg twice a day.
• In congestive heart failure, the dose is 3.25 mg twice a day up to a maximum of 25 mg twice a day. A maximum dose of 50 mg twice daily was used in subjects weighing more than 85 kg.
• It should be taken with food in order to slow down absorption and to reduce the occurrence of low blood pressure when standing up from a sitting position or (orthostatic hypotension) to sleep. Stopping and changing the dose of carvedilol should be done under the supervision of a doctor so sudden changes in dosage can cause arrhythmias, such as serious cardiac complications.
• The dose range for the treatment of heart failure or hypertension in prolonged-release capsules is 10 to 80 mg once a day.

Bupropion: Uses, Side effects, Dosage

Bupropion is a prescription medicine for the treatment of depression. It can improve mood and well-being. It can work by restoring the balance between certain natural chemicals in the brain.

It belongs to the class of antidepressants amino-ketone, which are no longer chemically related to the selective inhibitors of serotonin reuptake (SSRI).

This prescription medicine can also be used to treat attention deficit hyperactivity disorder (ADHD). It can also be used as a prescription treatment to help stop smoking by reducing the craving for nicotine and nicotine exposure. It can be used to prevent seasonal depression in autumn and winter. This medicine can also be used with other medicines to treat bipolar disorder. It can also be used to treat anxiety in people with depression.

Bupropion Uses:-


Major depressive disorder
Depressed mood
Bipolar disorder
Persistent depressive disorder
Mild depression
Obesity
It may also be used to help quit smoking
Anoxious mood.

Bupropion mechanism

Bupropion selectively inhibits the neuronal uptake of dopamine, norepinephrine and serotonin; The increase in norepinephrine may reduce the symptoms of nicotine withdrawal, and the increase in dopamine in neural sites may reduce the desire for nicotine and the desire to smoke. Bupropion shows moderate anticholinergic effects.

Bupropion Side effects

The most common side effects of bupropion are:

• Dizziness
• Nervousness
• Constipation
• trouble sleeping
• dry mouth
• nausea
• vomiting
• Tremor
• headache
• Joint aches
• Ringing in your ears
• Urinating more than usual
• Flushing
• Appetite loss
• Gas
• Abdominal pain

Serious side effects

• Mental health effects
• Eye problems
• Seizures

If you have nausea, take your medicine with food.

Bupropion can cause serious side effects like it contain a “Black Box Warning”

Like other antidepressants, bupropion should carry a black box that indicates an increased risk of suicidal thoughts and behavior in children, adolescents, and adolescents aged 18 and 24 years.

The black box warning warns of the need to monitor patients taking antidepressants for signs of worsening depression and the onset of suicidal thoughts, especially during the first months of treatment or when the dose rises or falls.

Interactions

Antidepressants such as,

• Nortriptyline,
• Imipramine,
• Venlafaxin
• Desipramine,
• Paroxetine
• Fluoxetine or
• Sertraline.

High side effects may include seizures. If these medicines are needed, your doctor may start with a low dose and slowly increase it.

Antipsychotics such as

• Thioridazine
• Haloperidol,
• Risperidone.

Increased side effects may include seizures. If these medicines are needed, your doctor may start with a low dose and slowly increase it.

Monoamine oxidase inhibitors (MAOI) such as

• Phenelzine or
• Selegiline.

Using these medicines with bupropion can cause severe hypertension. There must be at least 14 days between the use of MAOIs and the use of bupropion.

Beta-blockers like

• Metoprolol.

Increased side effects may include low blood pressure. Your doctor may reduce the dose of these medications if you are taking bupropion.

Antiarrhythmia such as

• Propafenone or
• Flecainide.

Strong side effects include weakness and changes in the heartbeat (too fast or too slow). Your doctor may reduce the dose of these medications if you are taking bupropion.

Theophylline Increased side effects may include seizures. If you need this medicine, your doctor may start with a low dose and gradually increase it.

Corticosteroids are, for example,

• Prednisone or
• Methylprednisolone.

Using these medications with bupropion can cause seizures. If these medicines are needed, your doctor may start with a low dose and gradually increase it.

Using these drugs with bupropion will increase side effects

• Levodopa and
• Amantadine.

Increased side effects may include restlessness, agitation, shaking, loss of body movement, dizziness, balance disorders or difficulty walking.

Substances that dilute the blood, such as

• Ticlopidine or
• Clopidogrel.

If you are taking any of these medicines with bupropion, your doctor may adjust the dose of bupropion to keep bupropion levels in your body too high.

Dosage

• The usual starting dose for adults with depression is 100 mg twice daily, 3 to 100 mg twice daily. The maintenance dose is 100 mg three times a day.
• Bupropion immediate release tablets are usually given in one, two or three doses daily. For immediate release tablets, a single dose should not exceed 150 mg and each dose should be separated by 6 hours.
• For depression, the recommended dose of immediate release tablets is 100 mg (300 mg / day) three times daily. The maximum dose is 450 mg daily. The starting dose is 100 mg twice daily. The dose may be increased to 100 mg three times daily after three days and to 150 mg three times daily after several weeks if the initial response is insufficient.
• The initial dose of sustained release tablets is 150 mg per day; The target dose is 150 mg twice daily. The maximum dose is 200 mg twice daily.
• The starting dose of prolonged-release tablets is 150 mg per day; The target dose is 300 mg per day; The maximum dose is 450 mg daily. Prolonged tablets are given once daily.
• When used to quit smoking, bupropion usually starts at 150 mg once daily for three days, and then the dose is increased to 150 mg twice daily for 7 to 12 weeks if the patient tolerates the initial dose. Smoking is stopped two weeks after starting treatment with bupropion.
• The dose of seasonal affective disorder is 150 mg once daily up to 300 mg daily using bupropion hydrochloride prolonged release tablets.
• Alternatively, treatment with 174 mg bupropion hydrobromide can be started daily and increased to a target dose of 348 mg daily. Starting  treatment before the onset of seasonal depressive symptoms and continue the winter season.

How long does methadone stay in your system

How long does methadone stay in your system depends on many factors such as age, weight, metabolism, liver function and other diseases, as well as the duration of methadone use, frequency of use, dose level and concomitant use of other substances.

Methadone

Methadone belongs to a group of medications called opioids. It was created by German doctors during the Second World War. When he arrived in the United States, he used to treat extremely painful people. Today, the doctor can use it for the treatment of heroin addiction or narcotic analgesics.

It works a lot like morphine. You can take it as a tablet, powder or liquid. It must be prescribed by a doctor. People who take it illegally often inject it, exposing them to diseases such as HIV. Although safer than other narcotics, your doctor should monitor you while taking methadone. Consumption can be addictive or abusive.

Like other opioids, it works by changing how the brain and the rest of the nervous system respond to pain. Since methadone is a synthetic opioid, there is a risk of drug abuse in case of abuse. As the National Institute of Addiction explains, the regular use of an addictive substance causes physical dependence, a natural process of adaptation to the continued presence of the drug.

Methadone Uses

Your doctor may prescribe methadone for the following conditions

• Severe pain from chronic illness, an injury, or surgery, or .
• For the treatment of dry cough.
• Treatment for addiction to other opioids.

How long does methadone stay in your system?

How long does methadone stay in your system depends on its dose, and its metabolism.

Many factors influence how long methadone stays in your system. Individual health factors such as age, weight, metabolism, liver function and other conditions, as well as duration of methadone use, frequency of administration, dosage and use All other substances influence the rate of methadone treatment. The clinical duration of methadone in your system is between 2 and 13 days. Methadone is an effective drug that remains active long after the loss of its analgesic effects.

The US Food and Drug Administration has found that relieving methadone pain can take four to eight hours, but it may take 8 to 59 hours to completely cleanse the body.

The half-life of methadone was 24 to 36 hours. We measure the disappearance of a medicine in the blood with a concept of “half-life”.

Half Life

Half life is the time needed to reduce the amount of drugs in the blood by half. While methadone is typically processed out of your system within two weeks, The traces of the methadone may appear much longer depending on the type of test used. Employers, drug treatment programs, sports organizations and law enforcement agencies can request a methadone drug test.

While standard screening tests often detect the use of opioids such as heroin and morphine, they do not recognize the use of methadone. For this reason, if the screening test is to investigate the presence of methadone, specific and more expensive tests must be used. Urine, saliva, hair and blood tests have been developed to detect the presence of methadone in the system.

Here is How long does methadone stay in your system?

• Urine tests can detect methadone after 24 hours and up to 7 days.
• Saliva tests can detect methadone within 10 minutes of use and up to 10 days.
• Hair tests can detect methadone within 7 to 10 days after application and up to 90 days.
• Blood tests should be performed within 3 hours to reach the maximum dose, but can be detected as early as 3 hours after oral administration.  Blood tests can detect methadone for up to 2.5 days.

Methadone Overdose

Following are some of the symptoms of Overdose from this drug. These include

• Sleepiness;
• Slowed breathing;
• Slowed heart rate.
• Muscle weakness;
• Clammy skin;
• Cold,
• Changes in the size of pupils

If you think you or someone has overdosed on methadone, get emergency help right away.

Factors that Influence How long does methadone stay in your system?

These factors include

• Patient’s metabolic rate,
• Genetics of Patient.
• Level of liver functioning,
• Kidney functions
• Weight,
• Height, and
• Food intake over the relevant time period.

Summary

To understand How long does methadone stay in your system you must know the half-life of methadone. It varies a lot as follows: 24 to 36 hours, 13 to 47 hours, 15 to 40 hours and 8 to 59 hours. Since the widest window is between 8 and 59 hours and covers all other possibilities, it is certainly considered the most accurate window. In days, a half-life of 8 to 59 hours means 1 to 13 days. In other words, a person can keep methadone in the body for 1-13 days.