Sofosbuvir

Sofosbuvir (brand names Sovaldi and Virunon) is a drug used for hepatitis C, with a high cure rate.

It inhibits the RNA polymerase that the hepatitis C virus uses to replicate its RNA.
It was discovered at Pharmasset and then acquired for development by Gilead Sciences.

On 6^th December 2013, the U.S. Food and Drug Administration approved Sovaldi for the treatment of chronic hepatitis C.

Sofosbuvir will cost $84,000 for 12 weeks of treatment used for genotype 1 and 2, and $168,000 for the 24 weeks used for genotype 3.

Mechanism of Action
Sofosbuvir is a prodrug that is metabolized to the active antiviral agent 2'-deoxy-2'-α-fluoro-β-C-methyluridine-5'-monophosphate. Sofosbuvir is a nucleotide analogue inhibitor of the hepatitis C virus (HCV) polymerase. The HCV polymerase or NS5B protein is a RNA-dependent RNA polymerase critical for the viral cycle.

Clinical studies
Sofosbuvir is being studied in combination with pegylated interferon and ribavirin, with ribavirin alone, and with other direct-acting antiviral agents. It has shown excellent clinical efficacy when used either with pegylated interferon/ribavirin or in interferon-free combinations. In particular, combinations of sofosbuvir with NS5A inhibitors, such as daclatasvir or GS-5885, have shown sustained virological response rates of up to 100% in people infected with HCV.

Data from the ELECTRON trial showed that a dual interferon-free regimen of sofosbuvir plus ribavirin produced a 24-week post-treatment sustained virological response (SVR24) rate of 100% for previously untreated patients with HCV genotypes 2 or 3.

Data presented at the 20th Conference on Retroviruses and Opportunistic Infections in March 2013 showed that a triple regimen of sofosbuvir, ledipasvir, and ribavirin produced a 12-week post-treatment sustained virological response (SVR12) rate of 100% for both treatment-naive patients and prior non-responders with HCV genotype 1. Gilead has developed a sofosbuvir + ledipasvir coformulation that is being tested with and without ribavirin.

Sofosbuvir - wikipedia
Sovaldi - Drugs.com

ACC/AHA Publish New Guideline for Management of Blood Cholesterol

(Nov. 12, 2013) —  The American College of Cardiology and the American Heart Association today released a new clinical practice guideline for the treatment of blood cholesterol in people at high risk for cardiovascular diseases caused by atherosclerosis, or hardening and narrowing of the arteries, that can lead to heart attack, stroke or death.

The guideline identifies four major groups of patients for whom cholesterol-lowering HMG-CoA reductase inhibitors, or statins, have the greatest chance of preventing stroke and heart attacks. The guideline also emphasizes the importance of adopting a heart-healthy lifestyle to prevent and control high blood cholesterol.

“The new guideline uses the highest quality scientific evidence to focus treatment of blood cholesterol on those likely to benefit most,” said Neil J. Stone, MD, Bonow professor of medicine at Northwestern University Feinberg School of Medicine and chair of the expert panel that wrote the new guideline. “This guideline represents a departure from previous guidelines because it doesn’t focus on specific target levels of low-density lipoprotein cholesterol, commonly known as LDL, or ‘bad cholesterol,’ although the definition of optimal LDL cholesterol has not changed. Instead, it focuses on defining groups for whom LDL lowering is proven to be most beneficial.”

The new guideline recommends moderate- or high-intensity statin therapy for these four groups:

• Patients who have cardiovascular disease;

• Patients with an LDL, or “bad” cholesterol level of 190 mg/dL or higher;

• Patients with Type 2 diabetes who are between 40 and 75 years of age; and

• Patients with an estimated 10-year risk of cardiovascular disease of 7.5 percent or higher who are between 40 and 75 years of age (the report provides formulas for calculating 10-year risk).

In terms of clinical practice, physicians can use risk assessment tools in some cases to determine which patients would most likely benefit from statin therapy, rather than focusing only on blood cholesterol to determine which patients would benefit.

“The likely impact of the recommendations is that more people who would benefit from statins are going to be on them, while fewer people who wouldn’t benefit from statins are going to be on them,” Dr. Stone said. Doctors may also consider switching some patients to a higher dose of statins to derive greater benefit as a result of the new guidelines.

The guideline was prepared by a panel of experts based on an analysis of the results of randomized controlled trials. The panel was charged with guiding the optimal treatment of blood cholesterol to address the rising rate of cardiovascular disease, currently the leading cause of death and disability in the U.S.

The panel chose to focus on the use of statins after a detailed review of other cholesterol-lowering drugs. “Statins were chosen because their use has resulted in the greatest benefit and the lowest rates of safety issues. No other cholesterol-lowering drug is as effective as statins,” said Dr. Stone. He added that there is a role for other cholesterol-lowering drugs, for example, in patients who suffer side effects from statins.

The report also stresses the importance of lifestyle in managing cholesterol and preventing heart disease. “The cornerstone of all guidelines dealing with cholesterol is a healthy lifestyle,” said Dr. Stone. “That is particularly important in the young, because preventing high cholesterol later in life is the first and best thing someone can do to remain heart-healthy. On the other hand, if someone already has atherosclerosis, lifestyle changes alone are not likely to be enough to prevent heart attack, stroke, and death, and statin therapy will be necessary.”

In addition to identifying patients most likely to benefit from statins, the guideline outlines the recommended intensity of statin therapy for different patient groups. Rather than use a “lowest is best” approach that combines a low dose of a statin drug along with several other cholesterol-lowering drugs, the panel found that it can be preferable to focus instead on a healthy lifestyle along with a higher dose of statins, eliminating the need for additional medications.

“The focus for years has been on getting the LDL low,” said Dr. Stone. “Our guidelines are not against that. We’re simply saying how you get the LDL low is important. Considering all the possible treatments, we recommend a heart-healthy lifestyle and statin therapy for the best chance of reducing your risk of stroke or heart attack in the next 10 years.”

The guidelines are intended to serve as a starting point for clinicians. Some patients who do not fall into the four major categories may also benefit from statin therapy, a decision that will need to be made on a case-by-case basis.

The expert panel that wrote the report was convened by the National Heart, Lung, and Blood Institute of the National Institutes of Health. At the invitation of the NHLBI, the American Heart Association and American College of Cardiology assumed the joint governance, management and publication of this guideline, along with four other prevention guidelines, in June. Committee members volunteered their time and were required to disclose all healthcare-related relationships, including those existing one year before the initiation of the writing project.

The full text of the report, “2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults,” will be published in future print issues of the of the Journal of the American College of Cardiology and the American Heart Association’s journal Circulation. It will also be accessible on the ACC (http://content.onlinejacc.org/article.aspx?doi=10.1016/j.jacc.2013.11.002) website and AHA (http://circ.ahajournals.org/lookup/doi/10.1161/01.cir.0000437738.63853.7a).

For more information, visit www.cardiosource.org.

Why are Generic Drugs so Cheap ?

Generic Substitution of Drugs

Gout Diet

Gout, a painful form of arthritis, has long been associated with diet, particularly overindulgence in meat, seafood and alcohol. As a result, gout treatment used to include severe dietary restrictions, which made the gout diet hard to stick to. Fortunately, newer medications to treat gout have reduced the need for such a strict diet.

Newer diet recommendations resemble a healthy-eating plan recommended for most people. Besides helping you maintain a healthy weight and avoid several chronic diseases, this diet may contribute to better overall management of your gout.

Purpose

Gout occurs when high levels of uric acid in your blood cause crystals to form and accumulate around a joint. Your body produces uric acid when it breaks down purines. Purines occur naturally in your body, but you also get them from eating certain foods, such as organ meats, anchovies, herring, asparagus and mushrooms.

A gout diet helps to control the production and elimination of uric acid, which may help prevent gout attacks or reduce their severity. The diet isn't a treatment for gout, but may help you control your attacks. Obesity also is a risk factor for gout, so losing weight can help you lower your risk of attacks.

Diet details

A gout diet reduces your intake of foods that are high in purines, such as animal products, which helps control your body's production of uric acid. The diet also limits alcohol, particularly beer, which has been linked to gout attacks. If you're overweight or obese, lose weight. However, avoid fasting and rapid weight loss because these can promote a gout attack. Drink plenty of fluids to help flush uric acid from your body. Also avoid high-protein weight-loss diets, which can cause you to produce too much uric acid (hyperuricemia).

To follow the diet:

• Limit meat, poultry and fish. Animal proteins are high in purine. Avoid or severely limit high-purine foods, such as organ meats, herring, anchovies and mackerel. Red meat (beef, pork and lamb), fatty fish and seafood (tuna, shrimp, lobster and scallops) are associated with increased risk of gout. Because all meat, poultry and fish contain purines, limit your intake to 4 to 6 ounces (113 to 170 grams) daily.
• Cut back on fat. Saturated fat lowers the body's ability to eliminate uric acid. Choosing plant-based protein, such as beans and legumes, and low-fat or fat-free dairy products will help you cut down the amount of saturated fat in your diet. High-fat meals also contribute to obesity, which is linked to gout.
• Limit or avoid alcohol. Alcohol interferes with the elimination of uric acid from your body. Drinking beer, in particular, has been linked to gout attacks. If you're having an attack, avoid all alcohol. However, when you're not having an attack, drinking one or two 5-ounce (148-milliliter) servings a day of wine is not likely to increase your risk.
• Limit or avoid foods sweetened with high-fructose corn syrup. Fructose is the only carbohydrate known to increase uric acid. It is best to avoid beverages sweetened with high-fructose corn syrup, such as soft drinks or juice drinks. Juices that are 100 percent fruit juice do not seem to stimulate uric acid production as much.
• Choose complex carbohydrates. Eat more whole grains and fruits and vegetables and fewer refined carbohydrates, such as white bread, cakes and candy.
• Choose low-fat or fat-free dairy products. Some studies have shown that low-fat dairy products can help reduce the risk of gout.
• Drink plenty of fluids, particularly water. Fluids can help remove uric acid from your body. Aim for 8 to 16 glasses a day. A glass is 8 ounces (237 milliliter). There's also some evidence that drinking four to six cups of coffee a day lowers gout risk in men.

A sample menu
Here's a look at what you might eat during a typical day on a gout diet:

Breakfast

• Whole-grain, unsweetened cereal with skim or low-fat milk, topped with fresh fruit
• Whole-wheat toast with trans-free margarine
• 100 percent fruit juice
• Coffee

Lunch

• Lean meat, poultry or fish (2 to 3 ounces) sandwich on whole-wheat bread, with lettuce, tomato and low-fat spread
• Carrot and celery sticks, side salad or vegetable soup
• Fresh fruit, such as apple, orange or pear
• Skim or low-fat milk

Dinner

• Baked or roasted chicken (2 to 3 ounces)
• Steamed vegetables
• Baked potato with low-fat sour cream
• Green salad with tomatoes and low-fat dressing
• Fresh fruit, such as berries or melon
• Nonalcoholic beverage, such as water or tea

Snacks can be added to this menu as long as you make healthy choices — such as fruits, vegetables and whole grains, and occasional nuts — and you are at a healthy weight or stay within your calorie limit. 

Results

Following a gout diet can help you limit your body's uric acid production and increase its elimination. It's not likely to lower the uric acid concentration in your blood enough to treat your gout without medication, but it may help decrease the number of attacks and limit their severity.

Following the gout diet and limiting your calories — particularly if you also add in moderate daily exercise, such as brisk walking — can also improve your overall health by helping you achieve and maintain a healthy weight. 

Risks

The gout diet isn't that different from the healthy-eating patterns recommended by the Dietary Guidelines for Americans. Thus, the risks of following the diet are few, if any. 

Read more:

Gout diet: What's allowed, what's not | MayoClinic  

Gout | NHS Choices
Got Gout but Love Meat? » Diagnosis: Diet

Attention Deficit Hyperactivity Disorder (ADHD)

What is attention deficit hyperactivity disorder?

Attention deficit hyperactivity disorder (ADHD) is one of the most common childhood brain disorders and can continue through adolescence and adulthood. Symptoms include difficulty staying focused and paying attention, difficulty controlling behavior, and hyperactivity (over-activity). These symptoms can make it difficult for a child with ADHD to succeed in school, get along with other children or adults, or finish tasks at home.

What are the symptoms of ADHD in children?

Inattention, hyperactivity, and impulsivity are the key behaviors of ADHD. It is normal for all children to be inattentive, hyperactive, or impulsive sometimes, but for children with ADHD, these behaviors are more severe and occur more often. 

What causes ADHD?

Scientists are not sure what causes ADHD, although many studies suggest that genes play a large role. Like many other illnesses, ADHD probably results from a combination of factors. In addition to genetics, researchers are looking at possible environmental factors, and are studying how brain injuries, nutrition, and the social environment might contribute to ADHD. 

How is ADHD treated?

Currently available treatments aim at reducing the symptoms of ADHD and improving functioning. Treatments include medication, various types of psychotherapy, education and training, or a combination of treatments. 

Medications

Stimulants such as methylphenidate and amphetamines are the most common type of medication used for treating ADHD. Although it may seem counterintuitive to treat hyperactivity with a stimulant, these medications actually activate brain circuits that support attention and focused behavior, thus reducing hyperactivity. In addition, a few non-stimulant medications, such as atomoxetine, guanfacine, and clonidine, are also available. For many children, ADHD medications reduce hyperactivity and impulsivity and improve their ability to focus, work, and learn. Medications also may improve physical coordination.

http://www.empoweringparents.com/blog/adhd-add/disorder-or-difference-new-studys-says-adhd-kids-have-dimmer-prospects/

http://www.chadd.org/Understanding-ADHD.aspx 

http://en.wikipedia.org/wiki/Attention_deficit_hyperactivity_disorder

http://www.nimh.nih.gov/health/publications/attention-deficit-hyperactivity-disorder/index.shtml

Male Period (Irritable male syndrome)

The irritable male syndrome (IMS) is a behavioural state of nervousness, irritability, lethargy and depression that occurs in adult male mammals following withdrawal of testosterone (T). The negative mood state has been described in men following withdrawal of androgens and is a striking feature in male seasonally breeding mammals associated with the end of the mating season.

IMS in humans

In humans, irritable male syndrome is referred to as the andropause,
 

Andropause: The Male Menopause

Andropause, also known as the male menopause, is the result of a gradual drop in testosterone and DHEA which are androgens, giving the condition its name. When men get into their early 30s, they begin to gradually start decreasing testosterone levels at a rate of one to two percent a year. It is estimated approximately 4-5 million men have symptoms of low/low-normal testosterone levels and only 5-10% of these men will seek treatment.

Based on World Health Organization (WHO) data, it was found that the testosterone levels in most 70 year old men were 10 percent of the level in males in their early 20s. By early 40s, men can start experiencing symptoms of andropause.

 

The symptoms of andropause (Irritable Male Syndrome):

• • Weight gain
• • Sleep apnea
• • Memory loss
• • Diminished libido
• • Erectile dysfunction
• • Muscle loss
• • Depression
• • Fatigue

The risks and benefits of testosterone replacement need to be evaluated by a qualified medical provider. It is a very individualized treatment based on labs, signs and symptoms.  
 

Treatment Options

The following treatments have been found to be effective.

• Hormone replacement therapy
• Exercise, dietary changes, stress reduction
• Selective androgen receptor modulators. 

Avoiding Irritable Male Syndrome

In order to help balance hormone levels and avoid irritable male syndrome, men should try to eat a well-balanced diet. Men should try to breakdown their diet in the following manner to help balance their hormone cycle:

• 25 percent fat
• 35 percent low glycemic carbohydrates (carbohydrates that are digested slowly and that do not cause insulin levels to spike)
• 40 percent protein. 

In the future I will talk in details about food and diseases

Ref:

http://www.ncbi.nlm.nih.gov/pubmed/11999307 

http://www.desertsierramedical.com/services/bihr/hrt-for-men

http://web.archive.org/web/20100522141934/http://www.healthtree.com/articles/pms/basics/male-pms.php

http://en.wikipedia.org/wiki/Irritable_male_syndrome

Drug Substitutions, Definitions

 

Pharmaceutical equivalents:
are drug products that have identical:

• active drug ingredient (same salt, ester, or chemical form)
• strength or concentration
• dosage form
• route of administration

but may differ in: color, shape, packaging, excipents, preservatives, expiration time, and labeling

Bioequivalent drug products:
are pharmaceutical equivalents that have similar bioavilability when given in the same dose and studied under similar experimental conditions

some drugs may be considered bioequivalent that are equal  in the extent of absorption but not in the rate of absorption

this is possible if the difference in the rate of absorption is considered clinically insignificant, for example, for drugs for chronic use.

two products are considered bioequivalent if the 90% CI of the relative mean Cmax, AUC(0-t) and AUC(0-∞) of the test (e.g. generic formulation) to reference (e.g. innovator brand formulation) should be within 80.00% to 125.00%

 

Generic substitution:
the process of dispensing a different drug product in place of prescribed drug product
the substituted drug product contains the same active ingredient or therapeutic moiety as the same salt or ester in the same dosage form but is made by a different manufacturer

 

Automatic Generic Substitution:
means that the pharmacist may dispense either the prescribed product, or they may replace it with a generic or another brand without being required to inform the patient or healthcare professional.

this can not be applied to NTI-drugs "narrow therapeutic index drugs" as patients might receive a generic medicine with effectively 25% more active ingredient than the branded medicine on one occasion and one with effectively 20% less active ingredient on the next, with NTI-drugs this may be lethal

Pharmaceutical alternative:
are drug products that contain same therapeutic moiety but as different salts, esters, or complexes. e.g. tetracycline phosphate or tetracycline HCl equivalent to 250mg tetracycline base are considered Pharmaceutical alternatives

different dosage forms and strengths within a product line by a single manufacturer are also considered Pharmaceutical alternatives. 

e.g. an extended-release dosage form and a standard immediate release dosage form of the same active ingredient. 

e.g. ampicillin suspension and ampicillin capsule

 

Therapeutic alternatives:
are drug products containing different active ingredients that are indicated for the same therapeutic or clinical objectives

active ingredients in the therapeutic alternatives are from the same pharmacological class and are expected to have the same therapeutic effect when administered to patients for such condition of use
 

for example, ibuprofen is given instead of aspirin; cimetidine may be given instead of ranitidine
 

.............

Main Ref: Biopharmaceutics and pharmacokinetics, Dr.Hanan Refai, MUST, 2011  

The Inner Life Of Cell

Alice in Wonderland syndrome

In 1955, English psychiatrist John Todd (1914-1987) described Alice in Wonderland syndrome (AIWS) as self-experienced paroxysmal body image illusions involving distortions of the size, mass, or shape of the patient's own body or its position in space, often occurring with depersonalization and derealization.

Todd named AIWS for the perceptual disorder of altered body image experienced by the protagonist in the novel Alice's Adventures in Wonderland (1865), written by Lewis Carroll (the pseudonym of Reverend Charles Lutwidge Dodgson [1832-1898]), possibly based in part on Dodgson's own migrainous experiences. 

In the story, Alice followed a talking white rabbit down a rabbit hole and then experienced several dramatic changes in her own body size and shape (e.g., shrinking to 10 inches high, growing unnaturally large, and growing unnaturally tall but not any wider). 

Although Todd's report was the most influential, Lippman provided an earlier description in 1952. In Lippman's article, one of the patients reported feeling short and wide as she walked, and referenced Alice's Adventures in Wonderland in regard to her body image illusions, referring to them as a "Tweedledum" or "Tweedledee" feeling.

For the AIWS sufferer, the eye components are entirely physically normal. The AIWS involves a change in perception as opposed to a malfunction of the eyes themselves. The hallmark sign of AIWS is a migraine, and AIWS may in part be caused by the migraine. AIWS affects the sufferer's sense of vision, sensation, touch, and hearing, as well as one's own body image.

A prominent and often disturbing symptom is that of altered body image: the sufferer may find that he or she is confused as to the size and shape of parts of (or all of) his/her body. Alice in Wonderland syndrome involves perceptual distortions of the size or shape of objects. Other possible causes and/or signs of association with the syndrome are migraines, use of hallucinogenic drugs, and infectious mononucleosis. 

Also, patients with certain neurological diseases have experienced similar visual hallucinations.  These hallucinations are called "Lilliputian," which means that objects appear either smaller or larger than they actually are.

Patients may experience either micropsia or macropsia. Micropsia is an abnormal visual condition, usually occurring in the context of visual hallucination, in which affected persons see objects as being smaller than those objects actually are.  Macropsia is a condition where the individual sees everything larger than it actually is.

One theory is that patients with Alice in Wonderland syndrome were associated with infectious mononucleosis. Neuroimaging studies have not revealed any link, and the relationship (if any) between the syndrome and mononucleosis remains unknown. One 17-year-old male described his odd symptoms. He said, "quite suddenly objects appear small and distant (teliopsia) or large and close (peliopsia). I feel as I am getting shorter and smaller "shrinking" and also the size of persons are not longer than my index finger (a lilliputian proportion). Sometimes I see the blind in the window or the television getting up and down, or my leg or arm is swinging. I may hear the voices of people quite loud and close or faint and far. Occasionally, I experience attacks of migrainous headache associated with eye redness, flashes of lights and a feeling of giddiness. I am always conscious to the intangible changes in myself and my environment." 

The eyes themselves are normal, but the sufferer 'sees' objects with the wrong size or shape or finds that perspective is incorrect. This can mean that people, cars, buildings, etc., look smaller or larger than they should be, or that distances look incorrect; for example a corridor may appear to be very long, or the ground may appear too close.

The sufferer may also lose a sense of time, a problem similar to the lack of spatial perspective. That is, time seems to pass very slowly, akin to an LSD experience. The lack of time, and space, perspective leads to a distorted sense of velocity. For example, one could be inching along ever so slowly in reality, yet it would seem as if one were sprinting uncontrollably along a moving walkway, leading to severe, overwhelming disorientation. This can then cause the sufferer to feel as if movement, even within his or her own home, is futile.

In addition, some people may, in conjunction with a high fever, experience more intense and overt hallucinations, seeing things that are not there and misinterpreting events and situations.

Other minor or less common symptoms may include loss of limb control and general dis-coordination, memory loss, lingering touch and sound sensations, and emotional experiences.

Treatment is the same as that for other migraine prophylaxis: anticonvulsants, antidepressants, beta blockers, and calcium channel blockers. Chronic Alice In Wonderland Syndrome is untreatable and must wear itself out. Rest is the prime treatment, but another effective therapy is to join support groups to share experiences.

Read More:

Alice in Wonderland Syndrome: somesthetic vs visual perceptual disturbance | PubMed

Alice in Wonderland syndrome | Wikipedia

Pseudoephedrine

Pseudoephedrine ( Pseudo ephedrine ) (PSE) is a sympathomimetic drug of the phenethylamine and amphetamine chemical classes. It may be used as a nasal/sinus decongestant, as a stimulant, or as a wakefulness-promoting agent.

The salts pseudoephedrine hydrochloride and pseudoephedrine sulfate are found in many over-the-counter preparations, either as a single ingredient or (more commonly) in combination with antihistamines, guaifenesin, dextromethorphan, and/or paracetamol (acetaminophen) or another NSAID (such as aspirin or ibuprofen).

Pharmacokinetics.
Distribution: Distributes into breast milk.
Metabolism: Partially metabolized in the liver.
Elimination: Renal (55% to 75% as unchanged); acidic urine accelerates rate of excretion.
Onset: 15 to 30 min.
Peak: 30 to 60 min.
Duration: 3 to 4 h; 8 to 12 h (extended-release).

 
Dosage and Administration.

Pseudoephedrine Sulfate
Adults and Children older than 12 yr of age 

PO 120 mg sustained-release every 12 h.

Pseudoephedrine Hydrochloride
Adults 

PO 60 mg every 4 to 6 h or 120 mg sustained-release every 12 h. Not to exceed 240 mg/day.

Children. The BNFC states there is little evidence to support the use of systemic decongestants in children. However, the following oral doses of pseudoephedrine hydrochloride are suggested for children in the management of mucosal congestion of the upper respiratory tract:
• 2 to 6 years: 15 mg 3 or 4 times daily
• 6 to 12 years: 30 mg 3 or 4 times daily, Not to exceed 120 mg/day.
Over-the-counter cough and cold preparations containing sympathomimetic decongestants (including pseudoephedrine) should be used with caution in children and generally avoided in those under 2 years of age

Under 4 years of age.  Not approved by FDA because dosage not studied in this age range 

Avoid multi-ingredient products in children under 6 years of age (AAP recommendations 10/2008)

Indications.

• nasal congestion
• sinus congestion
• Eustachian tube congestion
• vasomotor rhinitis
• as an adjunct to other agents in the optimum treatment of allergic rhinitis, croup, sinusitis, otitis media, and tracheobronchitis.
• also used as a first-line prophylactic for recurrent priapism
• urinary incontinence (off-label use)

Adverse effects.

• Common adverse drug reactions (ADRs) associated with pseudoephedrine therapy include: CNS stimulation, insomnia, nervousness, excitability, dizziness and anxiety.
• Infrequent ADRs: tachycardia or palpitations. 
• Rarely, mydriasis (dilated pupils), hallucinations, arrhythmias, hypertension, seizures and ischemic colitis; as well as severe skin reactions known as recurrent pseudo-scarlatina, systemic contact dermatitis, and nonpigmenting fixed drug eruption. 
• Pseudoephedrine, particularly when combined with other drugs including narcotics, may also play a role in the precipitation of episodes of paranoid psychosis. It has also been reported that pseudoephedrine, amongst other sympathomimetic agents, may be associated with the occurrence of stroke.

  A child who suffered a generalised seizure after ingesting a large quantity of pseudoephedrine hydrochloride tablets was believed to be the first report of convulsions associated with overdose of a preparation containing the drug as a single ingredient.
Clark RF, Curry SC. Pseudoephedrine dangers. Pediatrics 1990; 85: 389–90.

Precautions and contraindications.
Not be used in patients with: 

• diabetes mellitus, 
• cardiovascular disease, 
• severe or uncontrolled hypertension, 
• severe coronary artery disease,  
• prostatic hypertrophy, 
• hyperthyroidism, 
• closed angle glaucoma, 
• pregnant women ( Category C ) .
• Do not give to breast-feeding mothers.
   A small, randomised, crossover study concluded that a single dose of 60 mg pseudoephedrine hydrochloride decreased 24-hour milk production by 24%. The authors of the study suggested that pseudoephedrine might be of benefit for suppressing excess milk production.3
  
  1. American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 2001; 108: 776–89. Correction. ibid.; 1029.
  2. Findlay JWA, et al. Pseudoephedrine and triprolidine in plasma and breast milk of nursing mothers. Br J Clin Pharmacol 1984; 18: 901–6.
  3. Aljazaf K, et al. Pseudoephedrine: effects on milk production in women and estimation of infant exposure via breastmilk. Br J Clin Pharmacol 2003; 56: 18–24.

Patients who are prone to anxiety or panic attacks should use pseudoephedrine with caution, as anxiety and restlessness are common side effects, mostly due to the drug's stimulant properties.

Since nasal congestion is considered to be a relatively minor illness, alternatives are preferred in patients with these conditions. Appropriate alternatives may include saline sprays/instillations, depending on the patient's condition. Topical decongestants should be used with caution and for no longer than three days to avoid rhinitis medicamentosa.

Under 4 years of age. Not approved by FDA because dosage not studied in this age range
Avoid multi-ingredient products in children under 6 years of age (AAP recommendations 10/2008)

Interactions.

• Concomitant or recent (previous fourteen days) monoamine oxidase inhibitor use can lead to hypertensive reactions, including hypertensive crises.
• The antihypertensive effects of methyldopa, mecamylamine, reserpine and veratrum alkaloids may be reduced by sympathomimetics (pseudoephedrine ). 
• Beta-adrenergic antagonists may also interact with sympathomimetics. 
• Increase of ectopic pacemaker activity can occur when pseudoephedrine is used concomitantly with digitalis. 
• Antacids increase the rate of pseudoephedrine absorption, while kaolin decreases it.

Abuse. 

Acute psychosis and visual and tactile hallucinations have been reported in an 18-year-old male after intravenous misuse of pseudoephedrine hydrochloride. Pseudoephedrine has also been used for the illicit manufacture of street stimulants such as metamfetamine 

Sullivan G. Acute psychosis following intravenous abuse of pseudoephedrine: a case report. J Psychopharmacol 1996; 10: 324–5.

 

Read More:

Martindale; The complete drug reference, 36th edition
Pseudoephedrine | MedlinePlus Drug Information
Pseudoephedrine | Wikipedia
Complete Pseudoephedrine (d-Isoephedrine) information from | Drugs.com
Pseudoephedrine for Stuffy Nose - Children's Hospital Colorado-Denver Area, Rocky Mountain Region

Immunology VIII. TRANSPLANTATION

Transplantation is complicated by the antigenic differences between donor and recipient, the most important of which are antigenic differences in the HLA class I and class II molecules (also known as transplantation antigens).

Autograft is transplantation of tissue from one site to another on the same person, as might be used for the treatment of severe burns, and does not require immunosuppressive therapy.   

Syngeneic transplant (or isograft) is a transplant between genetically identical individuals and also does not require immunosuppressive treatment. 

Allograft (or allogeneic transplant) is a transplant between two genetically different individuals and often requires immunosuppressive therapy due to alloreactions (either graft rejection or graft versus host reaction, depending on the type of tissue transplanted).

Transfusion is a form of “living transplant” whereby blood is removed from one person for infusion into another. Human erythrocytes lack HLA classes I and II molecules. Major antigenic determinants of erythrocytes include the ABO glycolipids and the Rhesus (Rh) erythrocyte antigens. 

In routine ABO blood grouping, if antigens are absent from a person’s erythrocytes (A or B carbohydrates), then antibodies, usually IgM, that recognize those antigens naturally develop due to structural similarities between the A and B carbohydrates and the carbohydrates present in gut bacteria. As such, persons of blood type O would make anti-A and anti-B antibodies, whereas blood type AB would make neither set of antibodies. If the recipient of a blood transfusion is making antibodies that recognize antigens found on the transfused blood, then the newly transfused erythrocytes will be lysed by complement and phagocytes. Patients experience fever and chills associated with the hemolysis of the transfused blood. 

The Rh blood antigen (most typically, the D antigen) is a protein antigen; Rh positive individuals have the protein antigen, and Rh-negative individuals do not. The production of antibodies does not occur until the D antigen is introduced into the body and recognized as foreign by Rh-negative individuals (Rh immunization). Anti-Rh antibodies are the leading cause of HDN "hemolytic disease of the newborn" (discussed before).

Transplantation of solid organs. Common solid organ transplants are kidney, heart–lung (in combination or separately), pancreas, and liver (with or without intestine segment).

 Hyperacute rejection is the result of preformed antibodies against ABO blood group antigens or HLA antigens. These preformed antibodies act with complement, which leads to immediate destruction of the tissue and occlusion of the graft blood vessels, usually within minutes or hours of transplantation. Once established, no treatment is available to reverse the effects.
ABO incompatible kidney transplants have been successfully performed in investigational studies in Japan, Europe, and the United States by performing plasmaphoresis of the recipient before and after transplantation.
 Acute rejection is caused by effector T cells that are responding to HLA differences between donor and recipient. Acute rejection takes days to develop and can be reduced or prevented by the use of immunosuppressant drugs prior to and after transplantation.
 Chronic rejection occurs months or years after transplantation and is characterized by a gradual thickening of the vasculature of the transplanted tissue. As the lumen of the vessel walls narrow, the blood supply to the grafted tissue is eventually reduced, causing ischemia and tissue death.

Matching of donor and recipient HLA class I and class II allotypes improves the outcome of organ transplantation. The need for HLA matching and immunosuppressive therapy varies with the organ transplanted. The cornea of the eye can be transplanted without consideration of HLA type or immunosuppressive therapy because the cornea is not vascularized, and the immunological environment of the cornea suppresses inflammation. Liver cells express very low levels of HLA class I and class II antigens. Good HLA match between donor and recipient for liver transplantation can reduce the incidence of acute rejection; however, it does not appear to influence the overall graft outcome. Bone marrow transplantation is the most sensitive to HLA mismatches.

Hematopoietic stem cell transplantation (bone marrow transplantation). 
-Bone marrow transplantation is often used as a treatment for many genetic diseases that affect cells of the hematopoietic system, including many immunodeficiencies, and some cancer treatments, particularly those with immune system cancers.

-Hematopoietic stem cells are infused into the patient whose own bone marrow has been weakened or destroyed due to the immunodeficiency or cancer treatment. The grafted bone marrow cells repopulate the hematopoietic system of the recipient.

-Recipient rejection of the graft bone marrow is less of a concern because the recipient immune system is typically immunodeficient; however, the donor marrow is immunocompetent and can lead to graft versus host disease (GVHD).  In GVHD, mature T cells (TH or TC) that are present in the donor graft respond to the recipient HLA allotypes. The donor T-cell response can occur in any tissue, although the skin, intestines, and liver are principally involved.

-Almost all bone marrow transplant recipients experience some degree of GVHD, although the severity tends to correlate with the degree of HLA mismatch. In addition to reducing the incidence of GVHD, it is important that the donor and recipient match for at least one HLA class I and one HLA class II allotype in order to reconstitute the immune system.

Main Ref: Comprehensive Pharmacy Review 

Read More: WHO | Transplantation

 

Oxygen Injecting

Patients unable to breathe because of acute lung failure or an obstructed airway need another way to get oxygen to their blood -- and fast -- to avoid cardiac arrest and brain injury. A team led by researchers at Boston Children's Hospital has designed tiny, gas-filled microparticles that can be injected directly into the bloodstream to quickly oxygenate the blood.

The microparticles consist of a single layer of lipids (fatty molecules) that surround a tiny pocket of oxygen gas, and are delivered in a liquid solution.

In a cover article in the June 27 issue of Science Translational Medicine, John Kheir, MD, of the Department of Cardiology at Boston Children's Hospital, and colleagues report that an infusion of these microparticles into animals with low blood oxygen levels restored blood oxygen saturation to near-normal levels, within seconds.

When the trachea was completely blocked -- a more dangerous "real world" scenario -- the infusion kept the animals alive for 15 minutes without a single breath, and reduced the incidence of cardiac arrest and organ injury.

The microparticle solutions are portable and could stabilize patients in emergency situations, buying time for paramedics, emergency clinicians or intensive care clinicians to more safely place a breathing tube or perform other life-saving therapies, says Kheir.

"This is a short-term oxygen substitute -- a way to safely inject oxygen gas to support patients during a critical few minutes," he says. "Eventually, this could be stored in syringes on every code cart in a hospital, ambulance or transport helicopter to help stabilize patients who are having difficulty breathing."

  

The microparticles would likely only be administered for a short time, between 15 and 30 minutes, because they are carried in fluid that would overload the blood if used for longer periods, Kheir says.

Kheir also notes that the particles are different from blood substitutes, which carry oxygen but are not useful when the lungs are unable to oxygenate them. Instead, the microparticles are designed for situations in which the lungs are completely incapacitated.

Read more:

Injecting life-saving oxygen into a vein | Boston Children's Hospital

Injecting Life-Saving Oxygen Into a Vein | ScienceDaily

Illusion of control

The illusion of control is the tendency for people to overestimate their ability to control events, for instance to feel that they control outcomes that they demonstrably have no influence over. The effect was named by psychologist Ellen Langer and has been replicated in many different contexts. It is thought to influence gambling behavior and belief in the paranormal.

Along with illusory superiority and optimism bias, the illusion of control is one of the positive illusions. Although, the idea of illusion of control has been studied prior to Langer. Psychological theorists have consistently emphasized the importance of perceptions of control over life events. One of the earliest instances of this is when Adler argued that people strive for proficiency in their lives. Heider later proposed that humans have a strong motive to control their environment and White hypothesized a basic competence motive that people satisfy by exerting control. Weiner, an attribution theorist, modified his original theory of achievement motivation to include a controllability dimension. Kelley then argued that people’s failure to detect noncontingencies may result in their attributing uncontrollable outcomes to personal causes. Later on, Lefcourt argued that the sense of control, the illusion that one can exercise personal choice, has a definite and a positive role in sustaining life. Nearer to the present, Taylor and Brown argued that positive illusions, including the illusion of control, foster mental health.

The illusion is more common in familiar situations, and in situations where the person knows the desired outcome. Feedback that emphasizes success rather than failure can increase the effect, while feedback that emphasizes failure can decrease or reverse the effect. The illusion is weaker for depressed individuals and is stronger when individuals have an emotional need to control the outcome. The illusion is strengthened by stressful and competitive situations, including financial trading. Though people are likely to overestimate their control when the situations are heavily chance-determined, they also tend to underestimate their control when they actually have it, which runs contrary to some theories of the illusion and its adaptiveness. People also showed a higher illusion of control when they were allowed to become familiar with a task through practice trials, make their choice before the event happens like with throwing dice, and when they can make their choice rather than have it made for them with the same odds. People even are more likely to show control when they have more answers right at the beginning than at the end even when the people had the same number of correct answers.

The illusion might arise because people lack direct introspective insight into whether they are in control of events. This has been called the introspection illusion. Instead they may judge their degree of control by a process that is often unreliable. As a result, they see themselves as responsible for events when there is little or no causal link. In one study, college students were in a virtual reality setting to treat a fear of heights using an elevator. Those who were told that they had control, yet had none felt as though they had as much control as those who actually did have control over the elevator. Those who were led to believe they did not have control said they felt as though they had little control.

Read More

ScienceDaily | Illusion of Control

Wikipedia | Illusion of Control

Facebook Profiles Raise Users' Self-Esteem and Affect Behavior

A Facebook profile is an ideal version of self, full of photos and posts curated for the eyes of family, friends and acquaintances. A new study shows that this version of self can provide beneficial psychological effects and influence behavior.

Catalina Toma, a UW-Madison assistant professor of communication arts, used the Implicit Association Test to measure Facebook users' self-esteem after they spent time looking at their profiles, the first time the social psychology research tool has been used to examine the effects of Facebook. The test showed that after participants spent just five minutes examining their own Facebook profiles, they experienced a significant boost in self-esteem. The test measures how quickly participants associate positive or negative adjectives with words such as me, my, I and myself.
"If you have high self-esteem, then you can very quickly associate words related to yourself with positive evaluations but have a difficult time associating words related to yourself with negative evaluations," Toma says. "But if you have low self-esteem, the opposite is true."
Toma opted to use the Implicit Association Test because it cannot be faked, unlike more traditional self-reporting tools.
"Our culture places great value on having high self-esteem. For this reason, people typically inflate their level of self-esteem in self-report questionnaires," she says. "The Implicit Association Test removes this bias."
Additionally, Toma investigated whether exposure to one's own Facebook profile affects behavior.
"We wanted to know if there are any additional psychological effects that stem from viewing your own self-enhancing profile," says Toma, whose work will be published in the June issue of Media Psychology. "Does engaging with your own Facebook profile affect behavior?"
The behavior examined in the study was performance in a serial subtraction task, assessing how quickly and accurately participants could count down from a large number by intervals of seven. Toma found that self-esteem boost that came from looking at their profiles ultimately diminished participants' performance in the follow-up task by decreasing their motivation to perform well.
After people spent time on their own profile they attempted fewer answers during the allotted time than people in a control group, but their error rate was not any worse. Toma says the results are consistent with self-affirmation theory, which claims that people constantly try to manage their feelings of self-worth.
"Performing well in a task can boost feelings of self-worth," Toma says. "However, if you already feel good about yourself because you looked at your Facebook profile, there is no psychological need to increase your self-worth by doing well in a laboratory task."
But Toma cautions against drawing broad conclusions about Facebook's impact on motivation and performance based on this particular study, as it examines just one facet of Facebook use.
"This study shows that exposure to your own Facebook profile reduces motivation to perform well in a simple, hypothetical task," she says. "It does not show that Facebook use negatively affects college students' grades, for example. Future work is necessary to investigate the psychological effects of other Facebook activities, such as examining others' profiles or reading the newsfeed."

 

Source: ScienceDaily

Immunology VII. TUMOR IMMUNOLOGY

 Tumor Immunology involves the antigenic properties of the transformed cell, the host immune response to the tumor cells, the effect of the growth of the tumor may have on the body, and the potential manipulation of the immune response to eradicate the tumor.

Cancer results from a single cell that has undergone multiple mutations that lead to uncontrolled cell growth. Tumors can be benign (encapsulated, local, and limited in size), malignant (continually increasing in size and encroaching on adjacent tissues), or metastatic (spreading out from the primary tumor to form secondary tumors often at distant sites). Exposure to chemicals, radiation, viruses, or accumulated errors during replication can facilitate the malignant transformation.

Immune recognition of cancers
1. Malignant tumors express molecules that may be recognized by the immune response. Tumor specific antigens are expressed on tumor cells, but not on normal cells (e.g., viral proteins). Tumor-associated antigens are expressed on tumor cells but can also be found on normal cells, although often in smaller amounts or on cells of a different developmental stage (e.g., p53 and CT antigens).
2. MHC class I chain-related (MIC) proteins are stress-induced proteins that are often expressed on the surface of transformed epithelial cells, which can then be recognized by NK cells and CTLs. Tumor cells that express tumor antigens via class I MHC are recognized and killed by CTLs. Tumor cells that alter gene expression to reduce class I MHC presentation are recognized and killed by NK cells.
3. Several types of cancers are associated with chronic viral infections. By preventing infection, vaccinations protect against cancers caused by those viruses (e.g., human papillomavirus vaccine and hepatitis B vaccine).

Monoclonal antibodies directed against tumor antigens can be used for diagnosis and therapy, either alone via typical antibody-mediated mechanisms or conjugated to cytotoxic drugs or radioactive isotopes.
Examples include rituximab (Rituxan), trastuzumab (Herceptin), and ibritumomab (Zevalin, conjugated to Indium-111). (Cancer Chemotherapy will be discussed later)

Ref: Comprehensive Pharmacy Review

Read More: Tumour immunology and immunotherapy | Nature Reviews

Sulfur Hexafluoride - Deep Voice Gas

Inception, Fact and Fiction

Inception is a 2010 science fiction film written, co-produced, and directed by Christopher Nolan. He explored "the idea of people sharing a dream space...That gives you the ability to access somebody's unconscious mind. What would that be used and abused for?"

So let's get some scientific principles first,

Lucid Dreaming is a dream in which one is aware that he is dreaming. often when one is asleep, there is something in consciousness which declares that what then presents itself is but a dream. 

In a lucid dream, the dreamer has greater chances to exert some degree of control over their participation within the dream or be able to manipulate their imaginary experiences in the dream environment.

Australian psychologist Milan Colic has explored the application of principles from narrative therapy (is a form of psychotherapy using narrative) with clients' lucid dreams, to reduce the impact not only of nightmares during sleep, but also depression, self-mutilation, and other problems in waking life. Colic found that clients preferred direction for their lives, as identified during therapeutic conversations, could lessen the distressing content of dreams, while understandings about life—and even characters—from lucid dreams could be invoked in "real" life with marked therapeutic benefits.

In 1985, Stephen LaBerge performed a pilot study which showed that time perception while counting during a lucid dream is about the same as during waking life. Lucid dreamers counted out ten seconds while dreaming, signaling the start and the end of the count with a pre-arranged eye signal measured with electrooculogram recording. A German study, by D. Erlacher and M. Schredl, also studied motor activity and found deep knee bends took 44% longer to perform while lucid dreaming. However, a 1995 study in Germany indicated that lucid dreams can have varied time spans, in which the dreamer can control the length. The study took place during sleep and upon awakening. They required the participants to record their dreams in a log and record how long the dreams lasted.

While dream control and dream awareness are correlated, neither requires the other—LaBerge has found dreams that exhibit one clearly without the capacity for the other; also, in some dreams where the dreamer is lucid and aware they could exercise control, they choose simply to observe. 

In 1992, a study by Deirdre Barrett examined whether lucid dreams contained four "corollaries" of lucidity:  

1. knowing that one dreams, 
2. that objects will disappear after waking, 
3. that physical laws need not apply, 
4. and having clear memory of the waking world, 

and found less than a quarter of lucidity accounts exhibited all four. 

A related and reciprocal category of dreams that are lucid in terms of some of these four corollaries, but miss the realization that "I'm dreaming," were also reported. 

Scores on these corollaries and correctly identifying the experience as a dream increased with lucidity experience. 

In a later study in Barrett's book, The Committee of Sleep, she describes how some experienced lucid dreamers have learned to remember specific practical goals such as artists looking for inspiration seeking a show of their own work once they become lucid or computer programmers looking for a screen with their desired code. However, most of these dreamers had many experiences of failing to recall waking objectives before gaining this level of control.

Now let's back to the movie,

In the not-too-distant future, technology has been developed that allows multiple individuals to experience the same dream. While the underlying structure of the dream is controlled by one person (the Architect), other people populate the dream with manifestations of their subconscious, or Projections. And Tom Cobb (the main character) knows exactly how to exploit this system. He is a mercenary thief of ideas, a corporate espionage agent who specializes in invading dreams and extracting vital information. However, his greatest challenge is to perform the opposite task. He must infiltrate another person’s mind and plant an idea there. Business tycoon Saito wants to break up an energy empire, in the interests of promoting competition. He hires Cobb to insert an idea (the concept of dissolving the conglomerate) into the mind of young Robert Fischer, the incoming owner. This, unfortunately, is more difficult than it would appear – in order for the idea to take hold, it must appear to have come via inspiration, not suggestion. Cobb and his team promptly set to work devising their reverse-heist operation, with some help from Ariadne a remarkably skilled dream Architect. Their plan – to lure Fischer further and further into a web of nested dreamscapes, while subtly planting the germ of an idea. But unfortunately, Cobb is struggling with his own inner demons. Torn by guilt over the loss of his wife Mal, he produces subconscious images of her in the dreamscape, leading to disastrous effects.

Deirdre Barrett, said that Nolan did not get every detail accurate regarding dreams, but their illogical, rambling, disjointed plots would not make for a great thriller anyway. However, "he did get many aspects right," she said, citing the scene in which a sleeping Cobb is shoved into a full bath, and in the dream world water gushes into the windows of the building, waking him up. "That's very much how real stimuli get incorporated, and you very often wake up right after that intrusion".

Nolan himself said, "I tried to work that idea of manipulation and management of a conscious dream being a skill that these people have. Really the script is based on those common, very basic experiences and concepts, and where can those take you? And the only outlandish idea that the film presents, really, is the existence of a technology that allows you to enter and share the same dream as someone else."

The idea of the movie is very genius and creative, but most of the story still just fiction.