Flu medicine is found to be helpful in serious brain injury

Article first published as Severe Brain Injury Can Be Rapidly Treated With a Flu Medicine on Technorati.

Researchers have successfully confirmed that a flu medicine, amantadine, is efficient in treating the brain injury.

Their findings are consistent with observational reports suggesting the acceleration of recovery in patients who are receiving amantadine and the deceleration or loss of function after treatment is discontinued.

Researchers worked on 184 patients, who were in minimal conscious state for 4-16 weeks after severe brain injury. They divided the patients in two groups, one receiving the drug, amantadine, while the other received the dummy medicine i.e. placebo, for 4 weeks. Researchers have found that the group, which received the flu drug showed rapid improvement. They were better able to follow commands and reliably saying yes or no. They were also better able to use a spoon or hairbrush.

Researchers have discovered that very few, i.e. 17% of, patients of amantadine group remain in the “vegetative state” as compared to the other group, in which 32% remain in “vegetative state”.

Researchers have also given directions for future studies. Future research should focus on determining the pathophysiological characteristics of patients who have a response to amantadine, the most effective dosage and duration of treatment and timing of its initiation, and the effectiveness of amantadine in patients with nontraumatic brain injuries.

This research has been published online in The New England Journal of Medicine.

Antipsychotic drugs could be dangerous to dementia patients

Article first published as Some Antipsychotic Drugs are More Fatal for Patients with Dementia on Technorati.

Researchers including Krista Huybrechts, PhD, of Brigham and Women's Hospital in Boston, and colleagues have found that some antipsychotic drugs have more chances of death for the patients of dementia.

Researchers worked on more than 75000 patients of age 65 and older, who have just started any of the six antipsychotic drugs (haloperidol, aripiprazole, olanzapine, quetiapine, risperidone, ziprasidone), who were eligible for Medicaid and who were living in nursing homes in 2001-05, as approximately one-third of elderly people in nursing homes are treated with antipsychotics

Researchers compared the five drugs with risperidone, which is commonly used. They have found that the risk of death from haloperidol in dementia patients is very high and the drug’s usage "cannot be justified because of the excess harm." They have reported that quetiapine is safest among the six medications.

U.S. Food and Drug Administration (FDA) warned about the usage of antipsychotic drugs in dementia patients because of chances of death but this study is first of its kind to tell about the comparative efficacy of the drugs.

Researchers have not considered other antipsychotics as they form less than 1% of prescriptions.

This study has been published online in the British Medical Journal.

European regulators nod for Roche's Zelboraf

European Drug Regulators have approved the skin cancer drug, Zelboraf containing active ingredient Vemurafenib, for the treatment of BRAF V600 mutation-positive unresectable or metastatic melanoma, which is a fatal form of skin cancer.

Roche, manufacturer of Zelboraf, has announced this on Monday.

From SayPeople,

Zelboraf can be used as a monotherapy for the treatment of adult patients, whose late stage skin cancer have spread to other parts of the body and become inoperable. It can be given as a twice daily pill.

Further Reading:
SayPeople

Sinusitis can't be treated with amoxicillin

Researchers have recently published in The Journal of the American Medical Association that amoxicillin, an antibiotic, is not effective in treating the common type of sinusitis i.e. rhinosinusitis.

“We feel antibiotics are overused in the primary-care setting,” says Jane M. Garbutt, MD, research associate professor of medicine and the paper’s first author. “There is a movement afoot, led by the Centers for Disease Control and Prevention, to try to improve the judicious use of antibiotics. We hope this study provides scientific evidence that doctors can use with patients to explain that an antibiotic is not likely to help an acute sinus infection” as one in five antibiotics in the U.S. are prescribed for sinusitis.

“It’s a nasty disease,” Garbutt says. “People have significant symptoms. They feel miserable and miss time from work. If an antibiotic is not going to be of any benefit, then what is? That’s a question we haven’t answered yet. But we are working on it.”

Further Reading:
SayPeople

Orexigen and FDA has reached at an agreement about Contrave

Orexigen Therapeutics Inc., Biopharmaceutical Company, has developed a drug for diet and obesity i.e. Contrave.

The company reported on Monday that it has reached at an agreement with U.S. Food and Drug administration (FDA) over the details of design and analysis of the experimental drug.

"We are pleased to receive agreement on the SPA (Special Protocol Assessment) from the FDA after just one cycle of review," said Michael Narachi, President and CEO of Orexigen. "A few months ago, we received detailed written correspondence from the FDA's Director of the Office of New Drugs that identified a clear and feasible path forward for this important potential obesity therapy. We believe the rapid progress we have since made with the FDA's Division of Metabolic and Endocrinologic Products on the detailed protocol and plans for analysis is further indication of the alignment we have reached within the FDA on the requirements for resubmission of the Contrave NDA."

The company will work on 10,000 patients in a placebo-controlled trial to prove that there are very less chances of unacceptable increased adverse cardiovascular events.

Further Reading:
SayPeople

Loop Diuretics (Some Questions)

Q:1. Why loop diuretics are often called as high ceiling diuretics?

Ans: They are often called as high ceiling diuretics because they are highly effective in inhibition of coupled transport of Na+/K+/2Cl- through luminal membrane of thick ascending limb of Henle’s loop as ascending limb results in reabsorption of 20-30 percent of NaCl which has already been filtered.

Q:2. Compare loop diuretics and thiazide diuretics.
Ans:
Differences between loop diuretics and thiazide diuretics:
1. Loop diuretics are more effective than thiazide diuretics.
2. The onset of action and duration of action of loop diuretics is shorter than the thiazide diuretics.
3. Loop diuretics show efficacy even in the presence of electrolyte and acid base disturbance unlike thiazide siuretics.
4. Loop diuretics are not good than thiazide diuretics against uncomplicated mild to moderate hypertension.
5. Loop diuretics increase renal blood flow whereas thiazide diuretics have the ability of lessening renal flow of blood.
6. Loop diuretics tend to increase Ca2+ in urine whereas thiazide diuretics cause a decrease in Ca2+ in urine.

Similarities between loop diuretics and thiazide diuretics:
1. They have almost identical side effects.

Loop diuretics

These diuretics act on the medullary and cortical (thick) ascending limb of Henle’s loop, although to some extent they also act on the proximal and distal tubules. They are more effective than thiazide diuretics.


Mechanism of action:

They inhibit Na+/K+/2Cl- symport on luminal membrane of thick ascending limb of Henle’s loop causes
a. Decreased reabsorption of NaCl
b. Lessen the normal lumen positive potential that derives from K+ recycling resulting in increased excretion of Mg2+ and Ca2+

They tend to decrease renal vascular resistance and resulting in increased renal blood flow.

They also promote prostaglandin synthesis. Prostaglandins also have some role as diuretic.

Therapeutic uses:

They produce large amount of urine.
1. Acute pulmonary edema of heart failure
2. Acute pulmonary edema (When given IV)
3. Impaired renal function
4. Hypercalcemia
They causes an increased tub ular Ca2+ excretion.

5. Hyperkalemia
6. Increased intracranial pressure
7. Diabetic nephropathy
8. Hypertensive situations

Pharmacokinetics:
They have short duration of action of approximately 2-4.5 hours. They are eliminated by glomerular filtration and tubular secretion. Their half life depends on the renal function. They are excreted through urine.

Adverse effects:
They have almost similar adverse effects as those of thiazide diuretics. But they may cause severe electrolytic imbalances and water depletion.

• Hypersensitivity reactions:
Skin rash, interstitial nephritis

• Water, electrolytes and acid-base balance:
Voiding of extra water, Hypercalcemia, hyponatremia, Hypomagnesemia,

Hypokalemic metabolic alkalosis:
More Na+ at the collecting tubule results in more K+ exchange with Na+ in the tubule. This results in hypokalemia.

More K+ loss results in more H+, resulting in hypokalemic alkalosis.

This can be reduced by the use of potassium sparing diuretics or potassium rich foods.

• Blood:
Transient granulocytopenia and thrombocytopenia

• Muscles:
Severe pain and tenderness in patients with renal failure

• Miscellaneous:

Ototoxicity:
Affect on hearing.

Hyperuricemia:
Blocks secretion of uric acid by competitively working at renal and biliary secretary systems. This results in gouty attacks.

Acute hypovolemia:
They cause a reduction in blood volume. This results in hypotension, shock and cardiac arrhythmias.

Contraindications:
It is contraindicated in patients with hepatic coma, hypokalemia, hypotension and hypersensitivity to sulfonamides.

Interaction:
Indomethacin interferes with the production of prostaglandin synthesis, so that is why causes some inhibitory effects on diuretic action of loop diuretics.

Chlorothiazides

Chlorothiazed is the prototype of thiazide diuretics. This is used widely, orally effective and well tolerated.

They are effective in edema of hepatic cirrhosis and heart failure.

Pharmacokinetics:
Onset of action is 2 hours after oral administration and 10-15 minutes after IV administration. Its duration of action is about 4-12 hours.

Diuretics

Introduction:

Diuretics are the drugs that cause the increased outflow of urine.

General action of diuretics:
Many types of diuretics
1. Decrease that amount of fluid which is reabsorbed by the renal tubules, from where the fluid returns to the blood
2. Increase glomerular filtration

General uses of diuretics:
They are used to remove excess water from the body which may contain some salts, toxins and other accumulated waste products such as urea.

They have the ability of getting rid of excess fluid from the body which may cause edema, which contains an abnormal accumulation of fluid from serum resulting in some of the disease.

Aprotinin

It is inhibitor of proteolytic enzymes.


It causes blockage of plasmin resulting in stoppage of bleeding.

It can cause inhibition of streptokinase.

It is used prophylactically for reducing blood loss around the time of operation. It is also used for hyperplasminaemia developed as a result of fibrinolytic drug overdosage.

It may start certain inflammatory conditions.

Vitamin K

It can be used for oral anti-coagulants.

Mechanism of action:
It causes post-translational modification of factors VII, IX and X.

Therapeutic uses:
It is usually administered to all newborn babies in order to prevent vitamin K deficiency leading to hemorrhagic diseases which is common in premature infants.

It is also used as an antidote of warfarin.

Adverse effects:
Rapid infusion of vitamin K may lead to chest pain, back pain and dyspnea.

Protamine sulfate

It is an antidote for heparin.

It is obtained from fish sperm.

It is strongly basic macromolecule due to the presence of more amount of arginine.

In this positive charge of protamine forms complex with negative charge of heparin (a polyanionic macromolecule) neutralizing its activity.

It is administered IV after proper dilution with physiological salt solution. Its duration of affect is 2 hours.

Hypersensitivity reactions may develop. On rapid injection, flushing, dyspnea, hypotension, and bradycardia may be caused.

Aminocaproic acid and Tranexamic acid

These are synthetic inhibitors of plasminogen activator with antiplasmin activity.

These are active orally and excreted in urine. Tranexamic acid can cross placenta.

Therapeutic uses:
Aminocaproic acid is effective in the treatment of complications caused by fibrinolysis such as in the treatment of cardiac bypass or major thoracic surgery. It is also found useful in the treatment of subarachnoid hemorrhage and angioedema.

The most important use of tranexamic acid is in the treatment of ovarian tumor which is malignant.

Adverse effects:
They may cause IV thrombosis.

Aminocaproic acid may cause rash, erythema, nausea, diarrhea and heartburn. It also some of the antiadrenergic effects leading to hypotension and nasal stuffiness.

Dosage:
Tranexamic acid is administered as 15mg/kg orallyas a loading dose then 30 mg/kg four times a day.

Classification of Coagulants

Introduction:

These are the substances which are helpful in the coagulation of the blood.

Bleeding can be caused by
1. Fibrinolytic states arising after prostatectomy or gastrointestinal surgery.
2. Hemophilia

In this case, hemophilia can be caused due to decrease of plasma coagulation factors such as factor VIII or IX.

Classification of Coagulants:
Protamine sulfate, Vitamin K, Aprotinin

Fibrinolytic inhibitors:
Aminocaproic acid, Tranexamic acid

Atorvastatin

Salt form of Atorvastatin is used i.e. atorvastatin calcium. It belongs to a drug calss of Statins.

Structure:

Credit: Drugbank.ca

Mechanism of Action:
It works by inhibiting the enzyme HMG-CoA (Hydroxymethyl glutaryl Coenzyme-A) reductase, which is present in the tissues of the liver and is responsible for the production of cholesterol in the body via mevalonate pathway.

Pharmacokinetics:
Maximum plasma concentrations is found within 1 to 2 hours. Absorption increases with increasing the dose of the drug. The absolute bioavailability is found to be 14%.

Uses:

It is used for the treatment of Cholesterol i.e. hyperlipidemia, dyslipidemia and hypercholesterolemia. It is used to reduce the risk of myocardial infarction, stroke and angina.

Side effects:
It may cause diarrhea, apin in extremeties and urinary tract infections.

Brand Names:

• Atogal (Ingers (Czech Republic))
• Atorpic
• Cardyl (Pfizer (Spain))
• Faboxim (Fabop (Argentina))
• Hipolixan (Pasteur (Chile))
• Lipitor (Pfizer, Elea (Argentina))
• Lipotropic (Drugtech (Chile))
• Lipovastatinklonal (Klonal (Argentina))
• Liprimar (Pfizer (Hungary, Ukraine), Goedecke (Russia))
• Lowden (Saval (Chile))
• Normalip (Quesada (Argentina))
• Sincol (Indeco (Argentina))
• Sortis (Pfizer (Austria, Czech Republic, Germany, Hungary, Poland, Portugal, Switzerland), Godecke (Germany), Parke, Davis (Germany))
• Sotis
• Torvacard (Zentiva (Czech Republic, Hungary, Poland, Russia, Ukraine))
• Torvast (Pfizer (Italy))
• Totalip (Guidotti (Italy))
• Tozalip
• Tulip (Lek (Czech Republic, Russia), Wermar (Mexico), Sandoz (Poland, Ukraine), Pharmacia (Spain))
• Vastina (Penn (Argentina))
• Xanator (Sieger (Greece))
• Xarator (Parke, Davis (Italy))
• Xavator
• Zurinel (Prater (Chile))

It is also available in the combination with amlodipine with the name of "Caduet".

Serotonin receptor blockers

5-HT3 serotonin receptor blockers include Ondansetron and granisetron.

Action:
It blocks 5-HT3 receptors in the periphery (visceral afferent fibers) and in the brain (chemorecptor trigger zone).

Pharmacokinetics:
• Orally or IV
• Prevents vomiting in 50 – 60% of patients treated with Cisplatin.

Clinical Uses:
It is used as prophylaxis of nausea and vomiting associated with cancer chemotherapy.

Side affects:
Headache.

5-HT1c and 5-HT2 receptor blockers include Ketanserin.

Action:

This drug potently blocks vascular α1-adrenoceptors resulting in hypotensive action. It antagonizes platelet aggregation caused by serotonin by blocking 5-HT2 receptors on platelets.

Uses:
It is used in hypertension and vasospastic conditions.

Serotonin

It is also known as 5-Hydroxy Tryptamine. It is an indole-ethylamine.
Synthesis:

Mechanism of action:
Seven families of 5-HT receptor sub-types (subscripts 1-7) are there. They act through a variety of cell membrane receptors that include:
1. Six involved G-protein coupled receptors.
2. One uses ligand gated ion channels.

Action:
It acts as a neurotransmitter causing strong inhibitory effect. It acts on chemosensitive endings causing bradycardia and hypotension. It can cause aggregation of platelets. It may cause hyperventilation due to chemoreceptor reflex.

Clinical uses of serotonin analogues:
1. Buspirone (a 5-HT1A agonist) is used as non-benzodiazepine anxiolytic.
2. Sumatriptan can be used in acute migraine and cluster headache.
3. Appetite suppression appears to be caused by the agonist action at 5-HT2C receptors in the central nervous system.
4. Cisapride (a 5-HT4 agonist) was used for gastroesophageal reflux disease and motility disorders.

Dihydroergotamine

Derivative of ergotamine, IV use, ≈ sumatriptan, nausea may occur.

Ergotamine

Same action as that of sumatriptan but has less specificity for 5-HT receptors and is weak α-adrenoceptor blocker. It can be given orally, sublingually, nasally or rectally. Side effects include diarrhea, nausea and vomiting.

Sumatriptan

Introduction:

It is 5-HT receptor agonist acting on 5-HT1D that innervates the intracranial vasculature.

Action:
It decreases the release of sensory neuropeptides, such as substance P.

Pharmacokinetics:
• Use orally or SC.
• Its onset of action is 20 minutes parenterally and 1-3 hours orally.
• T1/2 = 2 hrs.
It is effective in 80% of patients.