Can sildenafil be given to women’s for cardiovascular disorders, if yes what is the dose for the same?

Sildenafil treats pulmonary arterial hypertension (high blood pressure in the lungs) in both men and women.  Sildenafil is indicated for the treatment of pulmonary arterial hypertension to improve exercise ability and delay clinical worsening.  A Sildenafil 20 milligram (mg) orally 3 times daily is indicated for the treatment of pulmonary arterial hypertension  to improve exercise ability. Administer doses approximately 4 to 6 hours apart, with or without food. Doses above 20 mg 3 times daily have not been shown to be more effective.

Reference:

MICROMEDEX(R) Healthcare Series Vol. 147

Nimesulide, a non-steroidal anti-inflammatory drug (NSAID) with ant inflammatory, analgesic and antipyretic effects, was first launched in Italy in 1985.

Similar to other Nonsteroidal anti-inflammatory agents, nimesulide has shown efficacy in a variety of conditions associated with inflammation, pain, and/or fever. However, although there are several studies comparing nimesulide with other Nonsteroidal anti-inflammatory agents, these are limited for any one particular indication

Now, nimesulide is banned in India .

Reference:

MICROMEDEX(R) Healthcare Series Vol. 147

Nimesulide: the current controversy, Indian Journal of Pharmacology 2003;  35:   121-122

Chronicle pharmabiz, Jan 2011

http://drugscontrol.org/news.asp?id=6112

Fenofibrate is approved by CDSCO for marketing in India in Dec. 1999 as lipid lowering agent.

Administration

Take 1 hour before or 4 to 6 hours after a bile acid binding resin

Take tablet or capsule with food or meal.

USFDA labeled indications

Hypercholesterolemia, primary hypercholesterolemia or mixed dyslipidemia (Frederickson Type 2a, 2b)

Hypertriglyceridemia, Frederickson types 4 and 5 hyperlipidemia, adjunct to diet

Contraindications:

gallbladder disease

history of hypersensitivity to fenofibrate, including severe skin rashes (eg, Stevens-Johnson syndrome, toxic epidermal necrolysis)

hypersensitivity to fenofibric acid, the active metabolite of fenofibrate

liver disease, active, including primary biliary cirrhosis and unexplained persistent liver function abnormality

nursing mothers

severe renal dysfunction, including patients receiving dialysis

Adverse effects:

COMMON

Abdominal pain, nausea, AST/SGOT level raised, liver function tests abnormal, backache, rhinitis

SERIOUS

Pancreatitis, cholestatic hepatitis, rhabdomyolysis

Avoid use of fenofibrate with following drugs unless told by doctor:

Use in pregnancy:

Drugs should be given only if the potential benefit justifies the potential risk to the fetus.

In breast feeding Infant risk cannot be ruled out.

Precautions:

Refer the prescription back to the doctor in case of history of cholelithasis, diabetes, hypothyroidism, pancreatitis, renal dysfunction, and myopathy.

Do not eat grapefruit or drink grapefruit juice & alcohol
while you are using this medicine.

Ask patient to avoid being near people who are sick or have infections.

Wash your hands often. Brush and floss your teeth gently.

Stay away from rough sports or other situations where you could be bruised, cut, or injured.

Be careful when using sharp objects, including razors and fingernail clippers.

Reference:

http://www.cdsco.nic.in/html/DRUGSAPRVD.htm

MICROMEDEX(R) Healthcare Series Vol. 147

Several forms of vitamin D exist. There are five forms of vitamin D. The two major forms are vitamin D2, and vitamin D3, these are known collectively as calciferol. Following table shows the difference between vitamin D3 & vitamin D4.

Reference:

MICROMEDEX(R) Healthcare Series Vol. 147

www.druglib.com

Following table provides information about Major & contraindicated interactions in severity of phenytoin.

Reference:

MICROMEDEX(R) Healthcare Series Vol. 147

Flunitrazepam is a benzodiazepine with hypnotic and amnesic effects. The drug has been used successfully for induction of general anesthesia, as a surgical premedicant, and for the management of insomnia. As an induction agent, flunitrazepam cannot be routinely recommended due to its variable effects, slow onset, and prolonged postoperative sedation.

Mechanism of Action

Flunitrazepam is a 7-nitro-benzodiazepine agent used for treating insomnia and in anesthesia. Chemically, flunitrazepam is related closely to nitrazepam and clonazepam. This agent is an intermediate-to-long-acting benzodiazepine. Flunitrazepam produces a selective effect on the GABA-mediated receptor synapses in the brain. Flunitrazepam has a preference for the BZ2 receptor over the BZ1 receptor, both of which are closely associated with receptors for GABA, the major inhibitory neurotransmitter in the brain. The GABA receptor complex regulates the entrance of chloride into the postsynaptic neuron, and benzodiazepines are thought to increase GABA-mediated chloride conduction. Facilitation of GAMA- induced chloride conductance prolongs hyperpolarization of the cells, ultimately diminishing synaptic transmission.

Pharmacokinetics

Onset and Duration

A) Onset

1) Initial Response

a) Sedation, oral or intramuscular: 20 to 30 minutes.

b) Induction of anesthesia, intravenous: 1 to 3 minutes (unconsciousness occurs).

2) Peak Response

a) Sedation, oral or intramuscular: 1 to 2 hr.

B) Duration

1) Single Dose: Sedation, oral: 8 hours & psychomotor impairment may continue for up to 12 hr.

Drug Concentration Levels

A) Therapeutic Drug Concentration

1) Significant sedative and anxiolytic effects have been observed at plasma levels of 7 to 8 ng/mL

B) Time to Peak Concentration

For Oral is 1 to 2 hr, Intramuscular is 30 to 45 min, Intranasal is 41 to 185 min (increases with increasing doses).

Absorption

1) Well absorbed by intramuscular & Sublingual, conventional tablet.

2) In Oral & Rectal, suppository, 80% to 90% & 50% resp.

Effects of Food

1) Decreased rate and extent of absorption.

Distribution

Protein Binding: 78% to 80%.

Other distribution sites are Cerebrospinal fluid &Placenta.

The mean fetomaternal ratio was 0.7

The drug is eliminated slowly from tissues (50% of an intravenous dose after 24 hours).

Volume of Distribution is 3.3 to 5.5 L/kg.

Flunitrazepam is extensively metabolized in Liver via the mixed-function oxidase system.

The Metabolites are 7-amino metabolite, active, 3-hydroxy metabolite, Desmethyl derivatives  

The majority of a flunitrazepam dose is excreted via the urine as metabolites and around 10% in Feces.

Elimination Half-life is 16 to 35 hours

Reference: Micromedex healthcare series vol.147

Vitamin B12 deficiency is a lack of a sufficient amount of vitamin B12 in the body required for optimal health.  Vitamin B12 deficiency is caused by an inability of the body to absorb vitamin B12 or a lack of vitamin B12 in the diet. Vitamin B12 is essential for many aspects of health, including the production of red blood cells in the blood.

Vitamin B12 deficiency can be serious if untreated, because it can lead to decreased production of red blood cells in the blood. Healthy amounts of red blood cells are necessary for the proper delivery of necessary oxygen to the body's cells and tissues. A lack of sufficient amounts of red blood cells due to vitamin B12 deficiency results in a serious complication called vitamin B12 deficiency anemia or pernicious anemia.

SYMPTOMS OF VITAMIN B12 DEFICIENCY INCLUDE

• Very pale skin
• Shortness of breath
• Fatigue
• Dizziness
• Headache
• Cold hands and feets
• Chest pain
• Heart Palpitations

Natural sources of vitamin B12:

Ø      Emphasizes a variety of fruits, vegetables, whole grains, and fat-free or low-fat milk and milk products:

Ø      Milk and milk products are good sources of vitamin B12.

Ø      Include lean meats, poultry, fish, beans, eggs, and nuts in your diet.

Ø      Fish and red meat are excellent sources of vitamin B12.

Ø      Diet should be low in saturated fats, trans fats, cholesterol, salt (sodium), and added sugars.

REFERENCE:

1. http://www.wrongdiagnosis.com

2. U.S. Department of Agriculture, Agricultural Research Service. 2009. USDA National Nutrient Database for Standard Reference, Release 22. Nutrient Data Laboratory Home http://www.ars.usda.gov/ba/bhnrc/ndl

Vitamin D deficiency is a lack of a sufficient amount of vitamin D in the body needed for optimal health. Vitamin D deficiency can result in rickets, osteomalecia, and osteoporosis and increase risk for other potentially serious conditions.

Vitamin D is essential for many aspects of health, including the absorption of calcium and phosphorus from food, which is vital for healthy bones. Vitamin D deficiency can negatively affect the development and growth of cells, bones and teeth and hormone regulation. Vitamin D deficiency can also affect the nervous system and the immune system.

Vitamin D deficiency is caused by decreased exposure to the sun, an inability of the body to absorb vitamin D, or a lack of vitamin D in the diet. Vitamin D deficiency can also be due to a decreased ability of the body to absorb and use vitamin D, and other abnormal digestive and metabolic processes.

SYMPTOMS OF DEFICIENCY:

Many people have no symptoms of vitamin D deficiency until complications arise. Symptoms may also be mild. Symptoms of vitamin D deficiency include: 

1. Bone pain

2. Stopped posture

3. Muscle cramps

4. Weakness

5. Tingling

6. Loss of height

Having very pale skin may indicate that a person is at risk for vitamin D deficiency as well as for other disorders, diseases and conditions.

TREATMENT:

The treatment plan of vitamin D deficiency involves:

1. Sensible sun exposure:

Vitamin D is also known as the "sunshine vitamin" because the body manufactures the vitamin after being exposed to sunshine. 10 to 15 minutes of sunshine 3 times weekly is enough to produce the body's requirement of vitamin D. Despite the importance of the sun for vitamin D synthesis, it is prudent to limit exposure of skin to sunlight and UV radiation from tanning beds.

2. Diet rich in vitamin D -  

Very few foods in nature contain vitamin D. Vitamin D is found in the following foods:

Dairy products such as Cheese, Butter, Cream, Fortified milk

• Fish
• Oysters
• Beef liver
• Fortified cereals
• Margarine
• Egg yolks.

3. Vitamin D supplementation –

Cholecalciferols, Ergocalciferol are used as vitamin D supplements.

Reference:

1. Institute of Medicine , Food and Nutrition Board. Dietary Reference Intakes for Calcium and Vitamin D. Washington , DC: National Academy Press, 2010.

2. http://www.wrongdiagnosis.com/v/vitamin_d_deficiency/treatments.htm?ktrack=kcplink

3. http://ods.od.nih.gov/factsheets/vitamind

4. http://www.nlm.nih.gov

Lenalidomide is an Immune Modulator. Lenalidomide is an orally active agent used in the treatment of transfusion-dependent patients with 5q- myelodysplastic syndrome. Lenalidomide has also been studied in the treatment of relapse/refractory multiple myeloma.

On coadministartion of digoxin and lenalidomide, increased digoxin plasma concentrations found, so if these two agents are coadministered, digoxin plasma levels should be monitored periodically, based on clinical judgement and standard clinical practices.

Use of Lenalidomide is contraindicated in pregnancy.

Indications:

USFDA labeled indications

§        Multiple myeloma, in combination with dexamethasone, in patients who have received at least 1 prior therapy

§        Myelodysplastic syndrome

Non-USFDA labeled indications

§        Multiple myeloma, In combination with dexamethasone, first-line therapy

Precautions

¨    hematologic toxicity (grade 3 or 4 neutropenia and thrombocytopenia) has been frequently reported; CBC monitoring recommended; dose reduction or treatment interruption may be necessary

¨    males, sexually active; must comply with mandatory contraception requirements to prevent pregnancy

¨    Thromboembolism (deep vein thrombosis or pulmonary embolism) has been reported in patients with multiple myeloma treated with combination therapy; monitoring is recommended

¨    angioedema, some cases fatal, has been reported; discontinue therapy if angioedema occurs

¨    renal impairment (Creatinine Clearance less than 60 mL/min); dosage adjustment recommended

¨    serious skin dermatologic reactions (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis), some cases fatal, have occurred; use not recommended in patients with a history of grade 4, thalidomide-associated rash; consider therapy interruption or discontinuation if a grade 2 rash develops; discontinue therapy for serious dermatologic reactions including grade 4 rash or an exfoliative or bullous rash

¨    tumor lysis syndrome may occur; monitoring recommended

Adverse effects:

COMMON

Peripheral edema, Pruritus, Rash, Constipation, Diarrhea, Nausea, Anemia, , Neutropenia, , Thrombocytopenia, Arthralgia, Backache, Cramp, Dizziness, Headache, Insomnia, Dyspnea, Nasopharyngitis, Fatigue, Fever 

SERIOUS

Atrial fibrillation, Stevens-Johnson syndrome, Toxic epidermal necrolysis, Anemia, Deep venous thrombosis, Febrile neutropenia, Hematologic toxicity, Neutropenia, Thrombocytopenia, Thrombosis, Pneumonia, Pulmonary embolism

Reference: MICROMEDEX(R) [DRUGDEX® System] Healthcare Series Vol. 145

Quetiapine extended-release tablets should not be chewed, crushed or split and should be swallowed whole.

The absorption of extended-release quetiapine tablets is affected by food; give without food or with a light meal of approximately 300 calories. Regular-release tablets are only marginally affected by food, and may be given without regard to food

Indications

FDA labeled indications

Bipolar disorder, depressed phase

Bipolar disorder, maintenance

Major depressive disorder; Adjunct

Manic bipolar I disorder

Schizophrenia

Schizophrenia, maintenance

Adverse Effects

COMMON

Hypertension, Orthostatic hypotension, Tachycardia, Serum cholesterol raised), Serum triglycerides raised, Weight gain, Abdominal pain, Constipation, Increased appetite (, Indigestion, Vomiting, Xerostomia, Increased liver enzymes, Backache, Asthenia, Dizziness, Extrapyramidal disease, Headache, Insomnia, Lethargy, Somnolence, Tremor Agitation Nasal congestion , Pharyngitis, Fatigue, Pain

SERIOUS

Sudden cardiac death, Syncope , Diabetic ketoacidosis, Pancreatitis, Agranulocytosis, Leukopenia, Neutropenia, Anaphylaxis, Seizure, Tardive dyskinesia, Suicidal thoughts, Priapism, Neuroleptic malignant syndrome (rare )

Drug Interactions

Pregnancy Category

U.S. Food and Drug Administration's Pregnancy Category: C (Either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the fetus.)

Breast Feeding

Infant risk cannot be ruled out.

Reference:

MICROMEDEX(R) Healthcare Series Vol. 146

Following table includes the detail about interactions of vancomycin.

Reference:

MICROMEDEX(R) Healthcare Series Vol. 146

Upon binding, the virus docks with cell membrane when the haemagglutinin link to molecules on the cell surface. The cell surface folds inwards causing the virus particle to sink into the cell. The virus sinks deeper into the cell until it is completely wrapped up in cell membrane. The resulting membranous "bubble” breaks free from the surface of the cell and transports its contained virus into the cell. The engulfed virus then appears in an endosome . It is more acidic in the endosome and this modifies the haemagglutinin spikes. The altered haemagglutinin draws the membranes of the virus and endosome together and they merge, creating a hole through which the viral contents are poured into the cytoplasm. These contents include the viral matrix protein, M1, and the nucleocapsid. The nucleocapsid segments, which contain the viral genetic information, migrate to the nucleus. They move into the nucleus via nuclear pores and so deliver the viral genome to the nucleus. In the nucleus, the viral genetic material (-ve sense RNA) produces viral messenger RNAs of various kinds (vmRNA) which travel out through the nuclear pores. Some vmRNA directs the synthesis of nucleoprotein that travel back into the nucleus. Some matrix protein travels to the nucleus and some collects beneath the cell membrane. Other vmRNAs direct the production of external (transmembrane) viral proteins. The manufacture of such "external" proteins follows a different route. Production starts in the rough endoplasmic reticulum and progresses through the Golgi apparatus. In the nucleus, the viral -ve sense genome also produces full length +ve sense copies of itself. These are then used to create further copies of the viral genome. These new -ve sense viral genomic RNAs become associated with nucleoproteins and some matrix proteins that have migrated into the nucleus. Such newly formed nucleocapsids and their associated M proteins exit the nucleus via nuclear pores. With all these viral elements now in place, the newly forming virus particle can begin to take shape and to bud from the cell surface. The cell membrane that envelopes the emerging nucleocapsid and matrix protein becomes the viral envelope and the virus particle is released. The new virus particle is now ready to infect another cell.

Reference:

1. Tasleem Samji, “Influenza A: Understanding the Viral Life Cycle” Yale J Biol Med. 2009 December; 82(4): 153–159, Retrived from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2794490

2. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2794490/

3. http://www.who.int/csr/disease/swineflu/en/