DIABETES Symptoms

LABETALOL

Labetalol  is a mixed alpha/beta adrenergic antagonist, which is used to treat high blood pressure.

(RS)-2-hydroxy-5-{1-hydroxy-2-[(1-methyl-3-phenylpropyl)amino]ethyl}benzamide

Brands - Normodyne, Trandate
Ab-Lol - from Steadfast ,  Cebalol - from Health Biotech, Evabet - from Celon,  Gravidol - from Mercury Labs,  Labesol- from SG Pharma, Labeta - from Geo Pharma,  Labil - from Celon (Revilon),
Lobet - from Samarth, Normadate - from GSK ,
Pih - from Dewcare, Talobet - from Celon , Tiplab-  from United Biotech ,

Indications
It has a particular indication in the treatment of pregnancy-induced hypertension which is commonly associated with pre-eclampsia.
It is also used to treat chronic and acute hypertension of pheochromocytoma and hypertensive crisis.


Administration
Labetalol is available in 100, 200, and 400 mg tablets and intravenously (available as Trandate) in 5 mg/ml solution. Adults taking tablets usually start with 100 mg twice daily, with a maximum of 2.4 g/day. In cases of emergency, dosage might be higher. Intravenous (IV) doses are usually started at 20 mg over two minutes. Additional doses of 40 mg, then 80 mg may be administered every ten minutes as needed. Additional 80 mg doses can be given to a total maximum dose of 300 mg. Additionally, labetalol can be administered by IV infusion at a rate of 2 mg/minute, with a maximum dose of 300 mg.

Side effects
Side effects may include:
Drowsiness
Fatigue
Weakness
Difficulty sleeping
Diminished sexual function
Orthostatic hypotension (due to alpha receptor blockade)
Scalp tingling
Drug eruption similar to lichen planus
A rare but potentially lethal side effect is respiratory distress.

Contra indications
Labetalol has relative contraindications for use in patients with asthma, congestive heart failure, any degree of heart block, bradycardia, or those in cardiogenic shock.

Chemistry
For adrenergic agents, when the substituent on the amine nitrogen is greater in size than a t-butyl group, then the molecule typically is found to have receptor affinity without intrinsic activity, and is therefore an antagonist. Labetalol has two chiral carbons and consequently exists as four stereoisomers. Two of these isomers, the (S,S)- and (R,S)- forms are inactive. The third, the (S,R)-isomer, is a powerful α1 blocker. The fourth isomer, the (R,R)-isomer, is a mixed nonselective β blocker and selective α1 blocker.
Labetalol acts by blocking alpha and beta adrenergic receptors, resulting in decreased peripheral vascular resistance without significant alteration of heart rate or cardiac output. The β:α antagonism of labetalol is approximately 3:1.

Mechanism of action
Labetalol combines both selective, competitive, alpha-1-adrenergic blocking and nonselective, competitive, beta-adrenergic blocking activity in a single substance. In man, the ratios of alpha- to beta- blockade have been estimated to be approximately 1:3 and 1:7 following oral and intravenous (IV) administration, respectively. The principal physiologic action of labetalol is to competitively block adrenergic stimulation of β-receptors within the myocardium (β1-receptors) and within bronchial and vascular smooth muscle (β2-receptors), and α1-receptors within vascular smooth muscle. This causes a decrease in systemic arterial blood pressure and systemic vascular resistance without a substantial reduction in resting heart rate, cardiac output, or stroke volume, apparently because of its combined α- and β-adrenergic blocking activity.

Absorption
Completely absorbed (100%) from the gastrointestinal tract with peak plasma levels occurring 1 to 2 hours after oral administration. The absolute bioavailability of labetalol is increased when administered with food.

Toxicity
LD50 = 66 mg/kg (Rat, IV). Side effects or adverse reactions include dizziness when standing up, very low blood pressure, severely slow heartbeat, weakness, diminished sexual function, fatigue


Drug Interactions

In one survey, 2.3% of patients taking labetalol HCl in combination with tricyclic antidepressants experienced tremor, as compared to 0.7% reported to occur with labetalol HCl alone. The contribution of each of the treatments to this adverse reaction is unknown but the possibility of a drug interaction cannot be excluded.

Drugs possessing beta-blocking properties can blunt the bronchodilator effect of beta-receptor agonist drugs in patients with bronchospasm; therefore, doses greater than the normal antiasthmatic dose of beta-agonist bronchodilator drugs may be required.

Cimetidine has been shown to increase the bioavailability of labetalol HCl. Since this could be explained either by enhanced absorption or by an alteration of hepatic metabolism of labetalol HCl, special care should be used in establishing the dose required for blood pressure control in such patients.

Synergism has been shown between halothane anesthesia and intravenously administered labetalol HCl. During controlled hypotensive anesthesia using labetalol HCl in association with halothane, high concentrations (3% or above) of halothane should not be used because the degree of hypotension will be increased and because of the possibility of a large reduction in cardiac output and an increase in central venous pressure. The anesthesiologist should be informed when a patient is receiving labetalol HCl.

Labetalol HCl blunts the reflex tachycardia produced by nitroglycerin without preventing its hypotensive effect. If labetalol HCl is used with nitroglycerin in patients with angina pectoris, additional antihypertensive effects may occur.

Care should be taken if labetalol is used concomitantly with calcium antagonists of the verapamil type.

8 WEEKS OF PREGNANCY

• From crown to rump your baby measures at 1.4-2cm or ½-¾ inch, the size of a pinto bean.
• From week 8 your baby graduates from being an embryo to being a fetus literally meaning the ‘little one’.
• The rudiments of all the vital body parts are in place now - all the main internal organs are already present.
• Baby now has the beginnings of a recognizably human face with nostrils, lips and a mouth with a tongue.
• Your baby is now covered with a thin layer of skin cells but is still translucent.
• Baby has already started moving around inside the uterus although you are not able to feel a thing.
• Toes and fingers begin to form although they are webbed; paddle shaped foot and hand areas are clearly present.
• Initially the arms develop faster than the legs - similarly after birth baby will develop hand and arm control faster than leg control.
• Baby's eyelids are beginning to form and until that completes, the eyes will appear open.
• The digestive tract especially the intestines are continuing to grow.
• Ten dental buds have formed in each jaw - these will become baby teeth.
• Heart function is now more fully developed with the heart pumping about 150 beats a minute (twice the adult rate).
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FOSINOPRIL

Fosinopril is an angiotensin converting enzyme (ACE) inhibitor used for the treatment of hypertension and some types of chronic heart failure. Fosinopril is the only phosphinate-containing ACE inhibitor marketed.

(2S,4S)-4-cyclohexyl-1-(2-{[2-methyl-1-(propanoyloxy)propoxy](4-phenylbutyl)phosphoryl}acetyl)pyrrolidine-2-carboxylic acid


Fosinoprilat and Fosinopril
Fosinoprilat proved to have the same problem as enalaprilat and the other carboxylate-containing ACE inhibitors (namely poor oral bioavailability). Addition of a hydrophobic side-chain modulated the ionisation characteristics of the molecule making it more bioavailable. Fosinopril is administered as a prodrug and is converted in vivo to the active form fosinoprilat.

Congestive heart failure and angiotensin II 
In congestive heart failure, the ability of the heart to pump enough blood to satisfy the physiological needs of the body is reduced.This condition has a variety of causes, including damaged heart valves, myocardial infarction, hypertension, vitamin B1 deficiency, and genetic mutations. When subsequent blood flow to the kidneys is reduced, the kidneys respond by increasing the secretion of renin from the juxtaglomerular apparatus. Renin converts the inactive angiotensinogen into angiotensin I, which is converted to angiotensin II (AII) by angiotensin converting enzyme (ACE). AII can have negative effects on the cardiovascular system after events such as heart failure and myocardial infarction. AII causes arterial vasoconstriction and hypertension resulting in an increase in afterload, increasing the resistance against which the heart works. Additionally, chronic increase in production of AII is associated with structural changes to the myocardium which reduces the functionality of the heart.

Effects of Fosinopril on treating heart failure
Fosinopril is de-esterified by the liver or gastrointestinal mucosa and is converted to its active form, fosinoprilat. Fosinoprilat competitively binds to ACE, preventing ACE from binding to and converting angiotensin I to angiotensin II. Inhibiting the production of AII lowers peripheral vascular resistance, decreases afterload and decreases blood pressure, thus helping to alleviate the negative effects of AII on cardiac performance. In heart failure patients, fosinopril increases exercise tolerance and lowers the frequency of events associated with worsening heart failure, such as dyspnea, the need for supplemental diuretics, fatigue, and hospitalizations. In a study examining the effects of fosinopril on insulin-like growth factor 1 (IGF-1) and IGF binding protein serum concentrations in high cardiovascular risk patients, a six-month treatment of fosinopril was associated with an elevation in IGF-1. Since a decline in IGF-1 is associated with an increased risk of ischemic heart disease, fosinopril may reduce ischemic risk.

Benefits of Fosinopril
Unlike other ACE inhibitors that are primarily excreted by the kidneys, fosinopril is eliminated from the body via both renal and hepatic pathways. This characteristic of fosinopril makes the drug a safer choice than other ACE inhibitors for heart failure patients with impaired kidney function resulting from poor perfusion as fosinopril can still be eliminated by the liver, preventing accumulation of the drug in the body.

Brands
fovas10 mg,20mg
fosinase 10,20

ENALAPRIL

Enalapril (Envas)  is an angiotensin converting enzyme (ACE) inhibitor used in the treatment of hypertension and some types of chronic heart failure. ACE converts the peptide hormone angiotensin I to angiotensin II. One of the actions of angiotensin II is the vasoconstriction of blood vessels resulting in an increase in blood pressure. ACE inhibitors such as enalapril prevent this effect. Enalapril has been shown to lower the death rate in systolic heart failure. Enalapril was the first member of the group known as the dicarboxylate-containing ACE inhibitors.

Enalapril is an ACE inhibitor. ACE stands for angiotensin converting enzyme.

Enalapril is used to treat high blood pressure (hypertension) and congestive heart failure.

Enalapril is also used to treat a disorder of the ventricles (the lower chambers of the heart that allow blood to flow out of the heart). This disorder can decrease the heart's ability to pump blood to the bod

chemically described as (S)-1-[N-[1-(ethoxycarbonyl)-3-phenylpropyl]-L-alanyl]-L-proline, (Z)-2-butenedioate salt (1:1). Its empirical formula is C20H28N2O5•C4H4O4, and its structural formula is:

Enalapril Dosing Information

Usual Adult Dose for Diabetic Nephropathy:
Initial dose (oral): 5 mg orally once a day.
Maintenance dose (oral): 10 to 40 mg orally per day in 1 to 2 divided doses.
Intravenous: 1.25 to 5 mg every 6 hours.

Usual Adult Dose for Hypertension:
Initial dose (oral): 5 mg orally once a day.
Maintenance dose (oral): 10 to 40 mg orally per day in 1 to 2 divided doses.
Intravenous: 1.25 to 5 mg every 6 hours.

Usual Adult Dose for Hypertensive Emergency:
Initial dose (oral): 5 mg orally once a day.
Maintenance dose (oral): 10 to 40 mg orally per day in 1 to 2 divided doses.
Intravenous: 1.25 to 5 mg every 6 hours.

Usual Adult Dose for Congestive Heart Failure:
Initial dose (oral): 2.5 mg orally once a day.
Maintenance dose (oral): 2.5 to 20 mg orally twice a day.
Doses should be titrated upward, as tolerated, over a period of a few days or weeks.
The maximum daily dose is 40 mg in divided doses.
Intravenous: 1.25 to 5 mg every 6 hours.

Usual Adult Dose for Left Ventricular Dysfunction:
Initial dose (oral): 2.5 mg orally twice a day.
Maintenance dose (oral): 20 mg orally in divided doses.
If possible, the dose of any concomitant diuretic should be reduced which may diminish the likelihood of hypotension.
Intravenous: 1.25 to 5 mg every 6 hours.

Usual Pediatric Dose for Hypertension:
Hypertension:
Oral:
Children 1 month to 17 years: Initial: 0.08 mg/kg/day (up to 5 mg) in 1 to 2 divided doses. Adjust dosage based on patient response.
Doses greater than 0.58 mg/kg (40 mg) have not been evaluated in pediatric patients



IMPORTANT INFORMATION 

Do not use enalapril if you are pregnant. Stop using and tell your doctor right away if you become pregnant.

You should not use enalapril if you have ever had angioedema.

If you have diabetes or kidney disease, you may not be able to take enalapril if you are taking medication that contains aliskiren. Tell your doctor about all medicines you use.

Enalapril can cause kidney problems. Call your doctor at once if you have swelling, rapid weight gain, little or no urinating, or if you feel short of breath.

Enalapril can affect your heart or your electrolyte levels. Call your doctor if you have chest pain, pounding heartbeats or fluttering in your chest, a slow heart rate or weak pulse, a tingly feeling, muscle weakness, or muscle tightness or contraction.



Before taking enalapril

You should not use enalapril if you have ever had angioedema, or if you are allergic to enalapril or to any other ACE inhibitor (benazepril, captopril, fosinopril, lisinopril, moexipril, perindopril, quinapril, ramipril, trandolapril).

To make sure enalapril is safe for you, tell your doctor if you have:

kidney disease (or if you are on dialysis);
liver disease;
heart disease or congestive heart failure (unless you are taking enalapril for this condition);
diabetes; or
a history of blood clot or stroke (including "mini-stroke").
FDA pregnancy category D. Do not use enalapril if you are pregnant. Stop using this medication and tell your doctor right away if you become pregnant. Enalapril can cause injury or death to the unborn baby if you take the medicine during your second or third trimester. Use effective birth control while taking this medication.

Home Remedy for Hair Fall

EATING DISORDERS

Eating disorders affect millions of teens and young adults around the world. They're most common in cultures that focus on weight and body image and can affect people of all races and ethnic backgrounds. Extreme focus on appearance often leads to poor body image and unhealthy eating behaviors, which can turn into eating disorders such as anorexia nervosa, bulimia, binge eating disorder, or a category called eating disorders not otherwise specified (ED-NOS). Eating disorders have serious health consequences and require treatment. Recovery is likely with the help of specially trained health care providers and a supportive family. We hope this guide will help you understand eating disorders, the different kinds of treatment, and the recovery process.

What are eating disorders?
Eating disorders are complicated medical and psychological conditions that affect a person's physical and emotional health and involve intense emotions and behaviors around food. Eating disorders are very dangerous illnesses and can lead to permanent consequences if left untreated.

The four types of eating disorders are anorexia nervosa, bulimia nervosa, binge eating disorder, and eating disorder not otherwise specified (EDNOS).
Anorexia (pronounced: an-or -rex-e-ah) involves food restriction (limiting or not having certain foods or food groups). People with anorexia drastically limit their food intake and have an intense fear of gaining weight, even though they may be underweight or they are losing a lot of weight
Bulimia (pronounced: bull-e-me-ah) involves cycles of binge eating followed by a purging behavior. People with bulimia will eat an unusually large amount of food in a short period of time and then purge by vomiting, using laxatives, enemas, diuretics, or by exercising excessively as a way to avoid gaining weight.
Binge eating disorder involves eating an unusually large amount of food in a short period of time and feeling a loss of control during this episode. Binge eaters do not purge afterwards, but often feel a lot of shame or guilt about their binge eating.
Eating disorder not otherwise specified (EDNOS) involves some combination of symptoms of the other eating disorders such as an intense fear of weight gain and a preoccupation with food (thinking about food or having food related thoughts most of the day). Many people with EDNOS have symptoms of the other eating disorders, but may not meet the exact criteria, and therefore are diagnosed with EDNOS.
Disordered eating is a term used to describe when someone doesn't have all the symptoms of an eating disorder, but their eating patterns and behaviors put them at risk for developing an eating disorder. For example, anorexia can start when dieting becomes too extreme; binge eating disorder or bulimia can start because dieting often restricts the amount and types of food, so when a diet is broken, it can lead to uncontrollable eating and loss of control around food.

Prevalence rates, or how often eating disorders occur varies with each disorder. While anorexia nervosa and bulimia nervosa are fairly rare, binge eating disorder and EDNOS are slightly more common. A study done in 2011 estimated that 0.3% of Americans between the ages of 13-18 suffer from anorexia, 0.9% from bulimia, and 1.6% from binge eating disorder (Swanson et al. 2011). Estimates of EDNOS differ from study to study, but may be as high as 15%.

HEALTH PYRAMID 3

HEALTH PYRAMID 2

FRESH VEGITABLE SANDWICH

DOXAZOSIN

Doxazosin mesylate, a quinazoline compound sold by Pfizer under the brand names Cardura and Carduran, is an α1-selective alpha blocker used to treat high blood pressure and urinary retention associated with benign prostatic hyperplasia (BPH).
On February 22, 2005, the US FDA approved a sustained release form of doxazosin, to be marketed as Cardura XL.
It is an alpha-1 adrenergic receptor blocker that inhibits the binding of norepinephrine (released from sympathetic nerve terminals) to the alpha-1 receptors on the membrane of vascular smooth muscle cells. The primary effect of this inhibition is relaxed vascular smooth muscle tone (vasodilation), which decreases peripheral vascular resistance, leading to decreased blood pressure.
Doxazosin and similar medications like prazosin have been found to help reduce the intensity of and/or stop posttraumatic stress disorder night terrors and nightmares. The full reasoning of this effect is not understood.
In Egypt, tablet formulation sold as Duracin produced by Biopharm group for research and the drug industry, Dosin by Eipico and Doxazocine by Multi-Apex.

(RS)-2-{4-[(2,3-Dihydro-1,4-benzodioxin-2-yl)carbonyl]piperazin-1-yl}-6,7-dimethoxyquinazolin-4-amine


EFFICACY
In March 2000, the ALLHAT study stopped its arm of the trial looking at alpha blockers, because doxazosin was less effective than a simple diuretic, and because patients on doxazosin had a 25% higher rate of cardiovascular disease and twice the rate of congestive heart failure as patients on diuretics. Pfizer, aware of the results before publication, launched a marketing campaign in early 2000, and sales were largely unaffected, despite the dangers highlighted by the study. Doxazosin shows potential for treatment of benign prostatic hyperplasia and erectile dysfunction.
Doxazosin has also shown some efficacy in treating chronic epididymitis.



INDICATION AND DOSAGE
Hypertension
Adult: As mesilate: Initially, 1 mg at bedtime increased after 1-2 wk according to response. Maintenance: 4 mg once daily. Max: 16 mg daily.

Benign prostatic hyperplasia
Adult: As mesilate: Initially, 1 mg once daily at bedtime increased after 1-2 wk; monitor BP after 2-6 hr. Maintenance: 2-4 mg daily. Max: 8 mg daily



Contraindications Known hypersensitivity to quinazolines.

Special Precautions Renal or hepatic impairment. Prostatic carcinoma should be ruled out before starting therapy. Orthostatic hypotension may occur at the initiation of therapy or when there is dose increase. Avoid driving or performing hazardous tasks for 24 hr after starting therapy or dose changes. Pregnancy and lactation.

Adverse Drug Reactions Chest pain, fatigue, headache, influenza-like symptoms, pain, hypotension, palpitation, abdominal pain, diarrhoea, nausea, oedema, dizziness, dry mouth, somnolence, dyspnoea, respiratory disorders, vision abnormalities, impotence, urinary tract infection, increased sweating, anxiety, insomnia. Vertigo, orthostatic hypotension, arrhythmia, hypotension, arthralgia/arthritis, muscle weakness, myalgia, kinetic disorders, ataxia, hypertonia, muscle cramps, flushing, tinnitus, sexual dysfunction, rhinitis, epistaxis, polyuria, urinary incontinence, fatigue/malaise, face oedema.



BRAND - DOXACARD

CLONIDINE

 Clonidine is a sympatholytic medication used to treat high blood pressure, ADHD, anxiety/panic disorder, and certain pain conditions. It is classified as a centrally acting α2 adrenergic agonist. An alternative hypothesis that has been proposed is that clonidine acts centrally as an imidazoline receptor agonist.

N-(2,6-dichlorophenyl)-4,5-dihydro-1H-imidazol-2-amine

USE

Clonidine has been investigated and prescribed first as an antihypertensive drug in the 1950s. It has found new uses later, including treatment of some types of neuropathic pain, opioid detoxification, sleep hyperhidrosis, and as veterinary anaesthetic drug. Clonidine is used to treat anxiety and panic disorder. It is also FDA approved to treat ADHD in an extended release form. It is becoming a more accepted treatment for insomnia, as well as for relief of menopausal symptoms.

Clonidine is increasingly used in conjunction with stimulants to treat attention-deficit hyperactivity disorder (ADHD), for which it is administered in late afternoon or evening for sleep, and because it sometimes helps moderate ADHD-associated impulsive and oppositional behavior, and may reduce tics, a problem in which a part of the body moves repeatedly and suddenly. Clonidine can be used in the treatment of Tourette syndrome (specifically for tics). Clonidine along with methylphenidate has been studied for treatment of ADHD. In 2010, the Food and Drug Administration approved the use of clonidine either as an adjunct to traditional stimulant therapy or as a monotherapy in the treatment of attention deficit hyperactivity disorder (ADHD).

Clonidine may be used to ease withdrawal symptoms associated with the long-term use of narcotics, alcohol and nicotine (smoking). It can alleviate opioid withdrawal symptoms by reducing the sympathetic nervous system response such as tachycardia and hypertension, as well as reducing sweating, hot and cold flushes, and general restlessness.The sedation effect is also useful although its side effects can include insomnia, thus exacerbating an already common feature of opioid withdrawal.
For some of the above reasons, clonidine is also used in some cases as an active placebo for narcotic analgesics in clinical trials and other lab experiments on morphine and its derivatives and mimics.

Clonidine can be used for migraine headaches and hot flushes associated with menopause.

Clonidine also has several off-label uses, and has been prescribed to treat psychiatric disorders including stress, sleep disorders, and hyperarousal caused by post-traumatic stress disorder, borderline personality disorder, and other anxiety disorders. Clonidine is also a mild sedative, and can be used as premedication before surgery or procedures. Its epidural use for pain during heart attack, postoperative and intractable pain has also been studied extensively.Clonidine has also been suggested as a treatment for rare instances of dexmedetomidine withdrawal.
Clonidine has also been found to prolong the effects of analgesia when used together with a local anesthetic such as ropivacaine or levobupivacaine.



MECHANISM OF ACTION
Clonidine treats high blood pressure by stimulating α2 receptors in the brain, which decreases cardiac output and peripheral vascular resistance, lowering blood pressure. It has specificity towards the presynaptic α2 receptors in the vasomotor center in the brainstem. This binding decreases presynaptic calcium levels, and inhibits the release of norepinephrine (NE). The net effect is a decrease in sympathetic tone.
It has also been proposed that the antihypertensive effect of clonidine is due to agonism on the I1-receptor (imidazoline receptor), which mediates the sympatho-inhibitory actions of imidazolines to lower blood pressure.

PREPERATION
Clonidine is typically available as tablets (Catapres, Dixarit), extended-release tablets (Kapvay), as a transdermal patch (Catapres-TTS), or as an injectable form to be given i.m., i.v. or epidurally - directly to the central nervous system.


BRAND -  CATAPRESS

CHLORTHALIDONE

Chlortalidone  or chlorthalidone (USAN) is a diuretic drug used to treat hypertension, originally marketed as Hygroton in the USA. It is described as a thiazide diuretic (or, rather, a thiazide-like diuretic because it acts similarly to the thiazides but does not contain the benzothiadiazine molecular structure). Compared with other medications of the thiazide class, chlortalidone has the longest duration of action but a similar diuretic effect at maximal therapeutic doses. It is often used in the management of hypertension and edema.
Unlike loop diuretics, chlortalidone efficacy is diminished in patients with certain renal diseases (e.g. chronic renal disease). A clinical trial  in 2002 compared chlortalidone to doxazosin in the treatment of high-risk hypertensive patients. In this study, only chlortalidone significantly reduced the risk of combined cardiovascular disease events, especially heart failure, when compared with drugs such as doxazosin. Chlortalidone was approved by the FDA in 1960. The ALLHAT study conclusions showed that there was no significant difference in all-cause mortality, fatal heart disease, or non-fatal myocardial infarction when chlortalidone was compared with lisinopril or amlodipine but did show decrease rates of heart failure after 6 years when compared with amlodipine and decreased rates of cerebrovascular disease after 6 years when compared with lisinopril leading the study conclusions to say that thiazide-type diuretics are preferred first-step in antihypertensive therapy.

(RS)-2-chloro-5-(1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl)benzene-1-sulfonamide

Mechanism of action

Chlortalidone increases the excretion of sodium, chloride, and water into the renal lumen by inhibiting sodium ion transport across the renal tubular epithelium. Its primary site of action is in the cortical diluting segment of the ascending limb of the loop of Henle. Thiazides and related compounds also decrease the glomerular filtration rate, which further reduces the drug's efficacy in patients with renal impairment (e.g. renal insufficiency). By increasing the delivery of sodium to the distal renal tubule, chlortalidone indirectly increases potassium excretion via the sodium-potassium exchange mechanism (i.e. apical ROMK/Na channels coupled with basolateral NKATPases). This can result in hypokalemia and hypochloremia as well as a mild metabolic alkalosis; however, the diuretic efficacy of chlortalidone is not affected by the acid-base balance of the patient being treated.
Initially, diuretics lower blood pressure by decreasing cardiac output and reducing plasma and extracellular fluid volume. Eventually, cardiac output returns to normal, and plasma and extracellular fluid volume return to slightly less than normal, but a reduction in peripheral vascular resistance is maintained, thus resulting in an overall lower blood pressure. The reduction in intravascular volume induces an elevation in plasma renin activity and aldosterone secretion, further contributing to the potassium loss associated with thiazide diuretic therapy.

Other use
Chlorthalidone may also be used to treat patients with diabetes insipidus and certain electrolyte disturbances and to prevent kidney stones in patients with high levels of calcium in their blood. Talk to your doctor about the possible risks of using this medicine for your condition.


Before taking chlorthalidone,
tell your doctor and pharmacist if you are allergic to chlorthalidone, sulfa drugs, or any other drugs.
tell your doctor and pharmacist what prescription and nonprescription medications you are taking, especially other medicines for high blood pressure, anti-inflammatory medications such as ibuprofen (Motrin, Nuprin) or naproxen (Aleve), corticosteroids (e.g., prednisone), lithium (Eskalith, Lithobid), medications for diabetes, probenecid (Benemid), and vitamins. If you also are taking cholestyramine or colestipol, take it at least 1 hour after chlorthalidone.
tell your doctor if you have or have ever had diabetes, gout, or kidney, liver, thyroid, or parathyroid disease.
tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking chlorthalidone, call your doctor immediately.
if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking chlorthalidone.
you should know that this drug may make you drowsy. Do not drive a car or operate machinery until you know how this drug affects you.
remember that alcohol can add to the drowsiness caused by this drug.
plan to avoid unnecessary or prolonged exposure to sunlight and to wear protective clothing, sunglasses, and sunscreen. Chlorthalidone may make your skin sensitive to sunlight.


Usual Adult Dose for Edema
Initial dose: 50-100 mg orally once a day.
Maintenance dose: 25-100 mg once a day or
50-200 mg every other day.

Usual Adult Dose for Hypertension
Initial dose: 25 mg orally once a day (15 mg for Thalitone).
Maintenance dose: 25-100 mg once a day (15-50 mg for Thalitone).

Renal Dose Adjustments
Chlorthalidone is not expected to be filtered into the renal tubule (its site of action) when the glomerular filtration rate is less than 10 mL/min.

Dose Adjustments
Dosage adjustments are recommended to be made no more frequently than weekly. Patients with liver disease or renal dysfunction should have dosage adjustments made cautiously.

Celiprolol

Celiprolol  is a medication in the class of beta blockers, used in the treatment of high blood pressure. It has a unique pharmacology: it is a selective β1 receptor antagonist, but a β2 receptor partial agonist. It is also a weak α2 receptor antagonist.
A recent clinical trial has suggested a use for this medication in the prevention of vascular complications of a rare inherited disease called vascular Ehlers–Danlos syndrome. This study demonstrated decreased incidence of arterial rupture or dissection (a specific type of arterial rupture in which the layers of the vessel separate prior to complete failure of the artery wall)

Brand names -  Cardem, Selectol, Celipres, Celipro, Celol, Cordiax, Dilanorm

(RS)-N'-{3-acetyl-4-[3-(tert-butylamino)-2-hydroxypropoxy]phenyl}-N,N-diethylurea

Before taking celiprolol

Some medicines are not suitable for people with certain conditions, and sometimes a medicine may only be used if extra care is taken. For these reasons, before you start taking celiprolol it is important that your doctor or pharmacist knows:

If you are pregnant, trying for a baby or breast-feeding.
If you have liver or kidney problems.
If you have low blood pressure or poor circulation.
If you have asthma or breathing difficulties.
If you have sugar diabetes.
If you have psoriasis (a skin problem).
If you have myasthenia gravis (a condition causing muscle weakness).
If you have been told you have a slow heartbeat or heart block (a slow and irregular heartbeat).
If you have been told you have Prinzmetal's angina (chest pain caused by spasms of the heart's blood vessels).
If you have phaeochromocytoma (a tumour on your adrenal gland).
If you are taking other medicines, including those available to buy without a prescription, herbal and complementary medicines.
If you have ever had an allergic reaction to a medicine, or if you have ever had any other severe allergic reaction.



How to take celiprolol


Before you start this treatment, read the manufacturer's printed information leaflet from inside the pack. The leaflet will give you more information about celiprolol and a full list of side-effects which you may experience from taking it.
Take celiprolol exactly as your doctor has told you. There are two strengths of tablet - 200 mg and 400 mg. It is usual to start by taking one 200 mg tablet daily, although your doctor may later increase this to the 400 mg strength tablet. You should take the tablet first thing in the morning, preferably 'on an empty stomach'. This means that you should take it at least 30 minutes before breakfast or wait until two hours afterwards. Swallow the tablet with a drink of water.
If you forget to take a dose, take it when you remember. (If possible, remember to take it half an hour before a meal, or two hours after a meal). If you do not remember until the following day, skip the missed dose. Do not take two doses together to make up for a forgotten dose.

Getting the most from your treatment

Try to keep your regular appointments with your doctor. This is so your doctor can check on your progress.
It is very important to follow any dietary and lifestyle advice that you may have been given by your doctor, such as eating a healthy diet, not smoking, and taking regular exercise.
If you drink alcohol, ask your doctor for advice about taking celiprolol and alcohol. Alcohol will add to the blood pressure lowering effect of celiprolol and so may not be recommended for you.
If you have diabetes, celiprolol may block the symptoms of low blood sugar. Your doctor will be able to advise you about this.
If you are having an operation or dental treatment, tell the person carrying out the treatment that you are taking a beta-blocker.
Treatment with celiprolol is usually long-term so continue to take these tablets unless your doctor tells you to stop. Stopping treatment suddenly can cause problems in some people, so your doctor will probably want you to reduce your dose gradually if this is necessary.
If you buy any medicines, check with a pharmacist that they are suitable for someone with high blood pressure to take. Some medicines (including some cough, cold and flu remedies) may not be.


How to store celiprolol

Keep all medicines out of the reach and sight of children.
Store in a cool, dry place, away from direct heat and light


Taking other medicines

If you are taking more than one medicine they may interact with each other. At times your prescriber may decide to use medicines that interact, in other cases this may not be appropriate.
The decision to use medicines that interact depends on your specific circumstances. Your prescriber may decide to use medicines that interact, if it is believed that the benefits of taking the medicines together outweigh the risks. In such cases, it may be necessary to alter your dose or monitor you more closely.
Tell your prescriber the names of all the medicines that you are taking so that they can consider all possible interactions. This includes all the medicines which have been prescribed by your GP, hospital doctor, dentist, nurse, health visitor, midwife or pharmacist. You must also tell your prescriber about medicines which you have bought over the counter without prescriptions.
The following medicines may interact with Celiprolol hydrochloride:
adrenaline
amiodarone
chlortalidone
clonidine
cyclopropane
diltiazem
disopyramide
ether
floctafenine
hydrochlorothiazide
ibuprofen
indometacin
insulin
mefloquine
nifedipine
quinidine
theophylline
trichloroethylene
verapamil
The following types of medicine may interact with Celiprolol hydrochloride:
anaesthetics
antiarrhythmics
antihypertensives
barbiturates
calcium channel blockers
digitalis glycosides
dihydropyridine derivatives
monoamine oxidase inhibitors
oral antidiabetics
phenothiazines
prostaglandin synthetase inhibitors
sympathomimetics
tricyclic antidepressants

BISOPROLOL

Bisoprolol is a drug belonging to the group of beta blockers, a class of drugs used primarily in cardiovascular diseases. More specifically, it is a selective type β1 adrenergic receptor blocker. The FDA approved Duramed Pharmaceutical's application for Zebeta Oral Tablets as a new molecular entity on July 31, 1992. It has since been approved by the FDA for manufacture by Teva, Mylan, Sandoz, and Mutual Pharmaceutical Company.

Bisoprolol is used to treat high blood pressure, reduced blood flow to the heart (cardiac ischemia); congestive heart failure, preventative treatment before and primary treatment after heart attacks decreasing the chances of recurrence. During hypertension there is an elevated blood pressure, which is what bisoprolol targets. While in cardiac ischemia the drug is used to reduce the activity of the heart muscle and therefore reduce oxygen and nutrient demand, so reduced blood supply can still transport sufficient amounts of oxygen and nutrients.
Many beta-blockers are now available and in general they are all equally effective. There are, however, differences between them which may affect choice in treating particular diseases or individual patients.
Beta-blockers with a relatively short duration of action have to be given two or three times daily. Many of these are, however, available in modified-release formulations so that administration once daily is adequate for hypertension. For angina twice-daily treatment may sometimes be needed even with a modified-release formulation. Some beta-blockers such as atenolol, bisoprolol, carvedilol, celiprolol, and nadolol have an intrinsically longer duration of action and need to be given only once daily.

(RS)-1-{4-[(2-isopropoxyethoxy)methyl]phenoxy}-
3-(isopropylamino)propan-2-ol


SIDE EFECTS - Overdose of bisoprolol leads to fatigue, hypotension, low blood sugar, bronchospasms and bradycardia.[8] Bronchospasms and low blood sugar because at high doses drug can be an antagonist for β2 adrenergic receptors located in lung and in liver. Bronchspasm due to blockage in lungs of β2 receptor and low blood sugar because of decreased stimulation of glycogenolysis and gluconeogenesis in the liver via β2 receptor.


MECHANISM OF ACTION

Bisoprolol is cardioprotective because it selectively and competitively blocks catecholamine (adrenalin) stimulation of β1 adrenergic receptors (adrenoreceptors), which are mainly found in the heart muscle cells and heart conduction tissue (cardio specific) but also found in juxtaglomerular cells in the kidney. Normally adrenalin and noradrenalin stimulation of the β1 adrenoreceptor activates a signalling cascade  which ultimately lead to increased contractility and increased heart rate of the heart muscle and heart pacemaker respectively. Bisoprolol competitively blocks the activation of this cascade and therefore decreases the adrenergic tone/stimulation of the heart muscle and pacemaker cells. Decreased adrenergic tone shows less contractility of heart muscle and lowered heart rate of heart pacemaker.
These are the favourable factors that are decreased and treat hypertension, heart attacks and ischemia. The decreases in contractility and heart rate are beneficial for hypertension because they reduce blood pressure but for preventive measures for heart attacks and cardiac ischemia these decreases in heart rate and contraction decrease the hearts demand for oxygen and nutrients; primary treatment post heart attacks is to prevent recurrence of the infarction.

DRUG INTERACTIONS
Major drug interation with - Theophylline, diltiazem, atazanavir, GUIFENESIN, EFEDRIN,


DISEASE INTERACTIONS

A. Beta-Blockers (including Bisoprolol) -  IN ASMA / COPD
In general, beta-adrenergic receptor blocking agents (i.e., beta-blockers) should not be used in patients with bronchospastic diseases. Beta blockade may adversely affect pulmonary function by counteracting the bronchodilation produced by catecholamine stimulation of beta-2 receptors. If beta-blocker therapy is necessary in these patients, an agent with beta-1 selectivity (e.g., atenolol, metoprolol, betaxolol) is considered safer, but should be used with caution nonetheless. Cardioselectivity is not absolute and can be lost with larger doses.

B. Beta-Blockers (including Bisoprolol) -  In Beta-Blockers (including Bisoprolol)  -    Bradyarrhythmia/Av Block
The use of beta-adrenergic receptor blocking agents (aka beta-blockers) is contraindicated in patients with sinus bradyarrhythmia or heart block greater than the first degree (unless a functioning pacemaker is present). Due to their negative inotropic and chronotropic effects on the heart, the use of beta-blockers is likely to exacerbate these conditions.

C. Beta-Blockers (including Bisoprolol) -  In Cardiogenic Shock/Hypotension :
The use of beta-adrenergic receptor blocking agents (aka beta-blockers) is contraindicated in patients with hypotension or cardiogenic shock. Due to their negative inotropic and chronotropic effects on the heart, the use of beta-blockers is likely to further depress cardiac output and blood pressure, which can be detrimental in these patients.

D. Beta-Blockers (including Bisoprolol) -  In Hemodialysis
Therapy with beta-adrenergic receptor blocking agents (aka beta-blockers) should be administered cautiously in patients requiring hemodialysis. When given after dialysis, hemodynamic stability should be established prior to drug administration to avoid marked falls in blood pressure. The hemodynamic status should be closely monitored before and after the dose.

E. Beta-Blockers (including Bisoprolol) -  In Hypersensitivity
The use of beta-adrenergic receptor blocking agents (aka beta-blockers) in patients with a history of allergic reactions or anaphylaxis may be associated with heightened reactivity to culprit allergens. The frequency and/or severity of attacks may be increased during beta-blocker therapy. In addition, these patients may be refractory to the usual doses of epinephrine used to treat acute hypersensitivity reactions and may require a beta-agonist such as isoproterenol.

F. Beta-Blockers (Includes Bisoprolol)  - Diabetes
Beta-adrenergic receptor blocking agents (aka beta-blockers) may mask symptoms of hypoglycemia such as tremors, tachycardia and blood pressure changes. In addition, the nonselective beta-blockers (e.g., propranolol, pindolol, timolol) may inhibit catecholamine-mediated glycogenolysis, thereby potentiating insulin-induced hypoglycemia and delaying the recovery of normal blood glucose levels. Since cardioselectivity is not absolute, larger doses of beta-1 selective agents may demonstrate these effects as well. Therapy with beta-blockers should be administered cautiously in patients with diabetes or predisposed to spontaneous hypoglycemia.


BRANDS - Available on the strength 5mg and 2.5mg

Bebedol
Bisbeta  - Shrristhi Health Care Products Pvt Ltd
 Biselect  Intas Laboratories Pvt Ltd
 Bisocar  Rusan Healthcare Pvt Ltd
 Bisod  Medreich Saimirra Ltd
 Concor  Merck (India) Ltd
 Zabesta  US Vitamins Limited

Fondaparinux

C₃₁H₄₃N₃Na₁₀O₄₉S₈ 

Fondaparinux (trade name Arixtra) is an anticoagulant medication chemically related to low molecular weight heparins. It is marketed by GlaxoSmithKline. A generic version developed by Alchemia is marketed within the US by Dr. Reddy's Laboratories.

STRUCTURE AND MECHANISM

Fondaparinux is a synthetic pentasaccharide Factor Xa inhibitor. Apart from the O-methyl group at the reducing end of the molecule, the identity and sequence of the five monomeric sugar units contained in fondaparinux is identical to a sequence of five monomeric sugar units that can be isolated after either chemical or enzymatic cleavage of the polymeric glycosaminoglycans heparin and heparan sulfate (HS). Within heparin and heparan sulfate this monomeric sequence is thought to form the high affinity binding site for the anti-coagulant factor antithrombin III (ATIII). Binding of heparin/HS to ATIII has been shown to increase the anti-coagulant activity of antithrombin III 1000 fold. In contrast to heparin, fondaparinux does not inhibit thrombin.

Administration

Fondaparinux is given subcutaneously daily. Clinically, it is used for the prevention of deep vein thrombosis in patients who have had orthopedic surgery as well as for the treatment of deep vein thrombosis and pulmonary embolism.

Comparison to other agents

One potential advantage of fondaparinux over LMWH or unfractionated heparin is that the risk for heparin-induced thrombocytopenia (HIT) is substantially lower. Furthermore, there have been case reports of fondaparinux being used to anticoagulate patients with established HIT as it has no affinity to PF-4. However, its renal excretion precludes its use in patients with renal dysfunction.

Unlike direct factor Xa inhibitors, it mediates its effects indirectly through antithrombin III, but unlike heparin, it is selective for factor Xa.

Uses

Fondaparinux is similar to enoxaparin in reducing the risk of ischemic events at nine days, but it substantially reduces major bleeding and improves long term mortality and morbidity.

It has been investigated for use in conjunction with streptokinase.

fondaparinux vs control

NCT00320398(ongoing)  NCT00320398

Fondaparinux  versus

patients undergoing either an elective primary total hip replacement (THR) surgery or a revision of a THR

Follow-up:  double-blind Japan

NCT00333021(ongoing)  NCT00333021

Fondaparinux  versus

Abdominal Surgery

Follow-up:  open  japan

fondaparinux vs no treatment

PROTECT (fundaparinux)(ongoing)  NCT00881088

fondaparinux 2,5 mg daily group during immobilization  versus no treatment

Patients with a nonsurgical fracture of the lower extremity immobilised in a below-knee plaster cast

Follow-up:  single blind

fondaparinux vs placebo

DRI4757(unpublished)

fondaparinux subcutaneously at 0.75, 1.5, 2.5, and 3.0 mg for at least 10 calendar days, (with a maximum of 14 days)  versus placebo

Japanese patients undergoing elective total knee replacement surgery

Follow-up: 14 days  double blind Japan

ARTEMIS (Cohen) ,2006

Fondaparinux 2.5 mg once daily for 6–14 days  versus placebo

High-risk medical patients

Follow-up: 6-15 days  double blind 8 countries

fondaparinux vs placebo (on top intermittent pneumatic comp.)

APOLLO (Turpie) ,2007

fondaparinux 2.5 mg s.c. for 5-9 days, starting 6-8 h postoperatively + intermittent pneumatic compression  versus placebo s.c. for 5-9 days, starting 6-8 h postoperatively + intermittent pneumatic compression

Patients aged at least 40 years undergoing abdominal surgery

Follow-up: 10 days  double blind US

fondaparinux vs control

Sasaki ,2010

fondaparinux 2.5mg daily for 14 days  versus usual care

patients undergoing hip fracture surgery

Follow-up: 14 days  open  Japan

fondaparinux vs enoxaparin

PENTAMAKS (Bauer) ,2001

fondaparinux 2.5-mg once-daily subcutaneous, starting 6 hours after surgery  versus enoxaparin 30mg twice daily (North america recommendation)

elective major knee surgery

Follow-up: 11 days  double blind North america

PENTHIFRA (Eriksson) ,2001

fondaparinux 2.5-mg once-daily subcutaneous, starting 6 hours after surgery  versus enoxaprin 40mg once daily

hip fracture surgery

Follow-up: 11 days  double blind 21 countries

PENTATHLON (Turpie) ,2002

fondaparinux 2.5-mg once-daily subcutaneous, starting 6 hours after surgery  versus enoxaparin 30mg twice daily (North america recommendation)

elective hip replacement surgery

Follow-up: 11 days  double blind USA, Canada, Australia

EPHESUS (Lassen) ,2002

fondaparinux 2.5-mg once-daily subcutaneous, starting 6 hours after surgery  versus enoxaprin 40mg once daily

elective hip replacement surgery

Follow-up: 11 days (6 weeks)  double blind 16 European countries

Turpie ,2001

pentasaccharide Org31540/SR90107A subcutaneous once daily at doses 0.75 mg, 1.5 mg, 3.0 mg, 6.0 mg, and 8.0 mg  versus enoxaparin 30mg once daily subcutaneous

patients undergoing total hip replacement

Follow-up: >15 days  double blind US, Canada, Autralia

L8541(unpublished)

fondaparinux 2.5mg subcutaneous once-daily for 7+/-2 days  versus enoxaparin 40mg s.c. once-daily

chinese patients undergoing major orthopaedic surgery of the lower limbs

Follow-up: 9 days (49d)  single-blind  China

L8635(unpublished)

Fondaparinux 2.5mg once daily subcutaneously for 7 days  versus enoxaparin 40mg once daily SC for 7 days

Taiwanese patients undergoing elective knee replacement

Follow-up: 10 days  open, blind assessment Taiwan

BRiEF  NCT00521885

fondaparinux 2.5mg qd  versus enoxaparin 40mg qd

acute medically ill, non-surgical patients

Follow-up:  Germany

PEGASUS ,2005

once-daily subcutaneous injections of fondaparinux 2·5 mg started 6 h after surgery for 5–9 days  versus once-daily subcutaneous injections of dalteparin 5000 units for 5–9 days (2500 units each, given 2 h before surgery and 12 h after the preoperative administration)

patients undergoing major abdominal surgery

Follow-up: 10 days (30 days)  double blind 22 countries

fondaparinux vs nadroparin

FONDACAST(ongoing)  NCT00843492

subcutaneously, once daily, fondaparinux 2.5 mg for at least 21 Days, up to complete mobilization, with a maximal duration of treatment of 45 days  versus daily nadroparin 2850 anti-Xa IU (0.3 mL) for at least 21 Days, up to complete mobilization

patients requiring rigid or semi-rigid immobilization for at least 21 days and up to 45 days because of isolated non-surgical below-knee injury

Follow-up: 5 weeks  open  Europe