HOSPITAL PHARMACY TRAINING

ASSIGNMENT WORK

By

P.SATHISH BABUB- PHARMACY- V SEMSRI RAMACHANDRA UNIVERSITY

INTRODUCTION Hospital pharmacy is a place where we have scope to learn a lots of things. It has helped us to train ourselves in lots of interdisciplinary phases of the pharmacy. We really found it very helpful. Importance of dispensing and things to be concentrated while we dispense in such a big well developed locality where thousands of people come every day. Though we felt that the training period was less we had scope to learn a lot things. We thank the staff in charge and the initiators for providing us such a good opportunity to explore. In this assignment I have compiled a list of drugs available at Sri Ramachandra hospital free pharmacy. These were the drugs what we dispensed during our posting period. The monograph of the drugs include the following categories:The name and structure of the drugIUPAC name and details about the moleculeThe pharmacological action of the drug, synthesis and usesBrand names of the particular drug available in the market These details helps us to know about the drugs and mode of action and their importance. These drugs are found to be economically and medicinally

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important. It is essential to know about all these as a pharmacist.

TABLE OF CONTENTS

DIAZEPAMDICLOFENACENALAPRILGLIBENCLAMIDE (GLYNASE)METFORMINPARACETAMOLAMITRIPTYLINELEVOTHYROXINEAMLODIPINECHLORTHALIDONE

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MONOGRAPH OF DIAZEPAM

IUPAC: 7-chloro-1-methyl-5-phenyl-3H-1,4-benzodiazepin-2-oneFORMULA: C16H13ClN2O ; MOLECULAR MASS: 284.7 g/mol.

Diazepam is a medication of the benzodiazepine type. It is commonly used to treat a range of conditions including anxiety, alcohol withdrawal syndrome, benzodiazepine withdrawal syndrome, muscle spasms, seizures, trouble sleeping, and restless legs syndrome. It may also be used to cause memory loss during certain medical procedures. It can be taken by mouth, inserted into the rectum, injected into muscle, or injected into a vein. When given into a vein effects begin in one to five minutes and last up to an hour. By mouth effects may take 40 minutes to begin.

Common side effects include sleepiness and trouble with coordination. Serious side effects are rare.  They include suicide, decreased breathing, and an increased risk of seizures if used too frequently in those with epilepsy. Occasionally excitement or agitation may occur. Long term use can result in tolerance, dependence, and withdrawal upon dose reduction. Abrupt stopping after long term use can be potentially dangerous. After stopping cognitive problems may persist for six months or longer. They are not recommended during pregnancy or breastfeeding. Its mechanism of action is by increasing the effect of the neurotransmitter gamma-Amino butyric acid (GABA).

PHARMACOLOGY: Diazepam is a long-acting "classical" benzodiazepine. Diazepam has anticonvulsant properties. Diazepam has no effect on GABA levels and no effect on glutamate decarboxylase activity, but has a slight effect on gamma-amino butyric acid transaminase activity. It differs from some other anticonvulsive drugs with which it was

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compared. Benzodiazepines act via micro molar benzodiazepine binding sites as Ca2+ channel blockers and significantly inhibit depolarization-sensitive Calcium uptake in rat nerve cell preparations.

Diazepam inhibits acetylcholine release in mouse hippocampal synaptosomes. This has been found by measuring sodium-dependent high-affinity choline uptake in mouse brain cells in vitro, after pretreatment of the mice with diazepam in vivo. This may play a role in explaining diazepam's anticonvulsant properties.

Diazepam binds with high affinity to glial cells in animal cell cultures. Diazepam at high doses has been found to decrease histamine turnover in mouse brain via diazepam's action at the benzodiazepine-GABA receptor complex. Diazepam also decreases prolactin release in rats.

SYNTHESIS:

MEDICINAL USES:

Treatment of anxiety, panic attacks, and states of agitation Treatment of neurovegetative symptoms associated with vertigo Treatment of the symptoms of alcohol, opiate, and benzodiazepine withdrawal Short-term treatment of insomnia Treatment of tetanus, together with other measures of intensive treatment Adjunctive treatment of spastic muscular paresis (paraplegia/tetraplegia) caused by cerebral

or spinal cord conditions such as stroke, multiple sclerosis, or spinal cord injury (long-term treatment is coupled with other rehabilitative measures)

Palliative treatment of stiff person syndrome Pre- or postoperative sedation, anxiolysis and/or amnesia (e.g., before endoscopic or surgical

procedures) Treatment of complications with a hallucinogen crisis and stimulant overdoses and psychosis,

such as LSD, cocaine, ormethamphetamine Preventative treatment of oxygen toxicity during hyperbaric oxygen therapy

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BRAND NAMES: Diastat, Valium.

MONOGRAPH OF DICLOFENAC

IUPAC:  2-(2,6-dichloranilino) phenylacetic acid.FORMULA: C14H11Cl2NO2 ; MOLECULAR MASS: 296.148g/mol.

Diclofenac is a non steroidal anti-inflammatory drug (NSAID) taken or applied to reduce inflammation and as an analgesic reducing pain in certain conditions. It is supplied as or contained in medications under a variety of trade names. In the United Kingdom, United States, India, and Brazil diclofenac may be supplied as either the sodium or potassium salt; in China, it is most often supplied as the sodium salt, while in some other countries it is only available as the potassium salt. Diclofenac is available as a generic drug in a number of formulations, including diclofenac diethylamine, which is applied topically. Over-the-counter (OTC) use is approved in some countries for minor aches and pains and fever associated with common infections.

PHARMACOLOGY: The primary mechanism responsible for its anti-inflammatory, antipyretic, and analgesic action is thought to be inhibition of prostaglandin synthesis by inhibition of cyclooxygenase (COX). It also appears to exhibit bacteriostatic activity by inhibiting bacterial DNA synthesis.

Inhibition of COX also decreases prostaglandins in the epithelium of the stomach, making it more sensitive to corrosion by gastric acid. This is also the main side effect of diclofenac. Diclofenac has a low to moderate preference to block the COX2-isoenzyme (approximately 10-fold) and is said to have, therefore, a somewhat lower incidence of gastrointestinal complaints than noted with indomethacin and aspirin.

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The action of one single dose is much longer (6 to 8 hour) than the very short half-life of the drug indicates. This could be partly because it persists for over 11 hours in synovial fluids.

Diclofenac may also be a unique member of the NSAIDs. Some evidence indicates it inhibits the lipoxygenase pathways, thus reducing formation of the leukotrienes (also pro-inflammatory autacoids). It also may inhibit phospholipase A2 as part of its mechanism of action. These additional actions may explain its high potency - it is the most potent NSAID on a broad basis.

Marked differences exist among NSAIDs in their selective inhibition of the two subtypes of cyclooxygenase, COX-1 and COX-2. Much pharmaceutical drug design has attempted to focus on selective COX-2 inhibition as a way to minimize the gastrointestinal side effects of NSAIDs such as aspirin. In practice, use of some COX-2 inhibitors with their adverse effects has led to massive numbers of patient family lawsuits alleging wrongful death by heart attack, yet other significantly COX-selective NSAIDs, such as diclofenac, have been well tolerated by most of the population.

SYNTHESIS:

MEDICINAL USES:

Diclofenac is used to treat pain, inflammatory disorders, and dysmenorrhea.[4] Inflammatory disorders may include musculoskeletal complaints, especially arthritis, rheumatoid arthritis,polymyositis, dermatomyositis, osteoarthritis, dental pain, TMJ pain, spondylarthritis, ankylosing spondylitis, gout attacks, and pain management in cases of kidney stones and gallstones. An additional indication is the treatment of acute migraines. Diclofenac is used commonly to treat mild to moderate postoperative or post-traumatic pain, in particular when inflammation is also present, and is effective against menstrual pain and endometriosis.

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BRAND NAMES: Aclonac, Cataflam, Voltaren.

MONOGRAPH OF ENALAPRIL

IUPAC:  (2S)-1-[(2S)-2-{[(2S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]amino}propanoyl]pyrrolidine-2-carboxylic acid

FORMULA: C20H28N2O5 ; MOLECULAR MASS: 376.447 g/mol.

Enalapril is an angiotensin-converting-enzyme (ACE) inhibitor used in the treatment of hypertension, diabetic nephropathy, 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.PHARMACOLOGY: Normally, angiotensin I is converted to angiotensin II by angiotensin-converting enzyme (ACE). Angiotensin II constricts blood vessels, increasing blood pressure. By inhibiting ACE, enalapril decreases levels of angiotensin II leading to less vasoconstriction and decreased blood pressure.SYNTHESIS:

MEDICINAL USES: Enalapril is used to treat hypertension, symptomatic heart failure, and asymptomatic left ventricular dysfunction. It has been proven to protect the function of the

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kidneys in hypertension, heart failure, and diabetes, and may be used in the absence of hypertension for its kidney protective effects. It is widely used in chronic kidney failure.

BRAND NAMES: Vasotec

MONOGRAPH OF GLIBENCLAMIDE

IUPAC:  5-chloro-N-(4-[N-(cyclohexylcarbamoyl)sulfamoyl]phenethyl)-2-methoxybenzamideFORMULA: C23H28Cl N 3O5S ; MOLECULAR MASS: 494.004g/mol.

Glibenclamide (AAN, BAN, INN), also known as glyburide (USAN), is an antidiabetic drug in a class of medications known assulfonylureas, closely related to sulfa drugs. It was developed in 1966 in a cooperative study between Boehringer Mannheim and Hoechst.

It is sold in doses of 1.25, 2.5, and 5 mg, under the trade names Diabeta, Glynase, and Micronase in the United States and Daonil, Semi-Daonil, and Euglucon in the United Kingdom, and Delmide, Glybovin in India. It is also sold in combination with metformin under the trade names Glucovance, Benimet, and Glibomet, as well as Glucored and Glucored Forte (by Sun Pharmaceutical) in Russia, Belarus and other countries of the CIS.

PHARMACOLOGY: The drug works by binding to and activating the ATP-sensitive potassium channels (KATP) inhibitory regulatory subunit sulfonylurea receptor 1 (SUR1) in pancreatic beta cells. This inhibition causes cell membrane depolarization, opening voltage-dependent calcium channels. This results in an increase in intracellular calcium in the beta cell and subsequent stimulation of insulin release.

After a cerebral ischemic insult, the blood–brain barrier is broken and glibenclamide can reach the central nervous system. Glibenclamide has been shown to bind more efficiently to the ischemic hemisphere. Moreover, under ischemic conditions SUR1, the regulatory subunit of the KATP- and the NCCa-ATP-channels, is expressed in neurons, astrocytes, oligodendrocytes, endothelial cells and by reactive microglia.

MEDICINAL USES: It is used in the treatment of type 2 diabetes. As of 2011, it is one of only two oral antidiabetics in the World Health Organization Model List of Essential

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Medicines (the other being metformin). As of 2003, in the United States, it was the most popular sulfonylurea. It is not as good as either metformin or insulin in those who have gestational diabetes.

BRAND NAMES: Diabeta, Glynase, Micronase Daonil, Semi-Daonil, Euglucon, Delmide, Glybovin Gilema

SYNTHESIS:

RESEARCH:

Glibenclamide improves outcome in animal stroke models by preventing brain swelling and enhancing neuroprotection. A retrospective study showed, in type 2 diabetic patients already taking glyburide, NIH stroke scale scores on were improved on discharge compared to diabetic patients not taking glyburide.

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MONOGRAPH OF METFORMIN

IUPAC:  N,N-Dimethylimidodicarbonimidic diamideFORMULA: C4H11N5 ; MOLECULAR MASS: 129.16364g/mol.

Metformin is an oral antidiabetic drug in the biguanide class. It is the first-line drug of choice for the treatment of type 2 diabetes, in particular, in overweight and obese people and those with normal kidney function. Its use in gestational diabetes has been limited by safety concerns. It is also used in the treatment of polycystic ovary syndrome, and has been investigated for other diseases where insulin resistance may be an important factor. Metformin works by suppressing glucose production by the liver.

Limited evidence suggests metformin may prevent the cardiovascular and possibly the cancer complications of diabetes. It helps reduce LDL cholesterol and triglyceride levels and is not associated with weight gain; in some people, it promotes weight loss. Metformin is one of only two oral antidiabetics in the World Health Organization Model List of Essential Medicines (the other being glibenclamide).

PHARMACOLOGY: Metformin decreases hyperglycemia primarily by suppressing glucose production by the liver (hepatic gluconeogenesis). The "average" person with type 2 diabetes has three times the normal rate of gluconeogenesis; metformin treatment reduces this by over one-third. The molecular mechanism of metformin is incompletely understood: inhibition of the mitochondrial respiratory chain (complex I), activation of AMP-activated protein kinase (AMPK), inhibition of glucagon-induced elevation of cyclic adenosine monophosphate(cAMP), and consequent activation of protein kinase A (PKA), inhibition of

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mitochondrial glycerophosphate dehydrogenase, and an effect on gut microbiota have been proposed as potential mechanisms. Metformin and other biguanides may antagonize the action of glucagon, thus reducing fasting glucose levels. Metformin also induces a profound shift in the faecal microbial community profile in diabetic mice and this may contribute to its mode of action possibly through an effect onglucagon-like peptide-1 secretion.

MEDICINAL USES: Metformin is primarily used for type 2 diabetes, but is increasingly being used in polycystic ovary syndrome, non-alcoholic fatty liver disease (NAFLD) and premature puberty, three other diseases that feature insulin resistance; these indications are still considered experimental. The benefit of metformin in NAFLD has not been extensively studied and may be only temporary; although some randomized controlled trials have found significant improvement with its use, the evidence is still insufficient.

BRAND NAMES: Glucophage

SYNTHESIS:

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MONOGRAPH OF PARACETAMOL

IUPAC:  N-(4-hydroxyphenyl)ethanamideN-(4-hydroxyphenyl)acetamide

FORMULA: C8H9NO2 ; MOLECULAR MASS: 151.163g/mol.

Paracetamol is classified as a mild analgesic. It is commonly used for the relief of headaches and other minor aches and pains and is a major ingredient in numerous cold and flu remedies. In combination with opioid analgesics, paracetamol can also be used in the management of more severe pain such as post-surgical and cancer pain.[13] Though paracetamol is used to treat inflammatory pain, it is not generally classified as an NSAID because it exhibits only weak anti-inflammatory activity.

While generally safe for use at recommended doses, even small overdoses can be fatal. Compared to other over-the-counter pain relievers, paracetamol is significantly more toxic in overdose but may be less toxic when used chronically at recommended doses. Paracetamol is the active metabolite of phenacetin and acetanilide, both once popular as analgesics and antipyretics in their own right. However, unlike phenacetin, acetanilide and their combinations, paracetamol is not considered carcinogenic at therapeutic doses.

PHARMACOLOGY:  The main mechanism proposed is the inhibition of cyclooxygenase (COX), and recent findings suggest that it is highly selective for COX-2.[84] Because of its selectivity for COX-2 it does not significantly inhibit the production of the

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pro-clotting thromboxanes.[84] While it has analgesic and antipyretic properties comparable to those of aspirin or other NSAIDs, its peripheral anti-inflammatory activity is usually limited by several factors, one of which is the high level of peroxides present in inflammatory lesions. However, in some circumstances, even peripheral anti-inflammatory activity comparable to NSAIDs can be observed. the active metabolite but that this reactive compound should react not only with the thiol in TRPA1 but also with any other suitably available nucleophile that it happens to encounter. It is suggested that thiol groups in cysteine proteases, e.g. the proteases that take part in the processing of procytokines, such as those generating IL-1β and IL-6, might be the targets giving rise to overall analgesic effects.

MEDICINAL USES: Paracetamol is used for reducing fever in people of all ages Paracetamol is used for the relief of pain, head ache, low back pain and post operative pain.

SYNTHESIS:

BRAND NAMES: Calpol, Dolo650, Palol, Ampar, Aldolol, etc.,

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MONOGRAPH OF AMITRIPTYLINE

IUPAC:  3-(10,11-Dihydro-5H-dibenzo[a,d]cycloheptene-5-ylidene)-N,N-dimethylpropan-1-amine

FORMULA: C20H23N ; MOLECULAR MASS: 277.403g/mol.

Amitriptyline is the most widely used tricyclic antidepressant (TCA). Amitriptyline is chemically basic and is in the form of hydrochloride salt (pKa 9.4) in the market. It is used to treat a number of mental disorders, including major depressive disorder and anxiety, and less commonly psychosis, attention deficit hyperactivity disorder, and bipolar disorder. Other uses include prevention of migraines, post herpetic neuralgia, neuropathic pain such as fibromyalgia, and less commonly insomnia.

Side effects may include seizures, an increased risk of suicide in those less than 25 years of age, urinary retention, and a number of heart issues. They should not be taken with MAO inhibitors or cisapride. In the United States and Australia, they are pregnancy category C which means that may cause problems during pregnancy. Use during breastfeeding does not appear to be a problem.

PHARMACOLOGY: Amitriptyline acts primarily as a serotonin-norepinephrine reuptake inhibitor, with strong actions on the serotonin transporter and moderate effects on the norepinephrine transporter. It has negligible influence on the dopamine transporter and therefore does not affect dopamine reuptake, being nearly 1,000 times weaker on it than

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on serotonin. It is metabolized to nortriptyline—a more potent and selective norepinephrine reuptake inhibitor—which may complement its effects on norepinephrine reuptake.

MEDICINAL USES: Amitriptyline is used for a number of medical conditions including major depressive disorder (MDD) which is its only FDA-labeled indication. This is also a TGA- and MHRA-labelled indication. Some evidence suggests amitriptyline may have superior efficacy compared to other antidepressants, including the selective serotonin reuptake inhibitors (SSRIs), although it is rarely used as a first-line antidepressant nowadays due to its high degree of toxicity in overdose and generally poorer tolerability than the newer antidepressants such as the SSRIs and serotonin-norepinephrine reuptake inhibitors.

BRAND NAMES: Amitrip, Elevil, Endep, Levate

SYNTHESIS:

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MONOGRAPH OF LEVOTHYROXINE

IUPAC:  (S)-2-Amino-3-[4-(4-hydroxy-3,5-diiodophenoxy)-3,5-diiodophenyl]propanoic acidFORMULA: C15H11I4NO4 ; MOLECULAR MASS: 776.87g/mol.

Levothyroxine (INN, USAN) or L-thyroxine is a synthetic thyroid hormone that is chemically identical to thyroxine (T4), which is naturally secreted by the follicular cells of the thyroid gland. It is used to treat thyroid hormone deficiency, and occasionally to prevent the recurrence of thyroid cancer. Like its naturally secreted counterpart, levothyroxine is a chiral compound in the L-form. The related drug dextrothyroxine (D-thyroxine) was used in the past as a treatment for hypercholesterolemia (elevated cholesterol levels) but was withdrawn due to cardiac side effects.

PHARMACOLOGY: Levothyroxine is a synthetic form of thyroxine (T4), an endogenous hormone secreted by the thyroid gland, which is converted to its active metabolite, L-triiodothyronine (T3). T4 and T3 bind to thyroid receptor proteins in the cell nucleus and cause metabolic effects through the control of DNA transcription and protein synthesis.

MEDICINAL USES: Levothyroxine is typically used to treat hypothyroidism,[5] and is the treatment of choice for patients with hypothyroidism,[6] who often require lifelong thyroid hormone therapy.[7] It may also be used to treat goiter via its ability to lower thyroid-stimulating hormone(TSH), a hormone that is considered goiter-inducing.

BRAND NAMES: Thyronorm

SYNTHESIS:

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MONOGRAPH OF AMLODIPINE

IUPAC:  (RS)-3-ethyl 5-methyl 2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate

FORMULA: C20H25Cl N 2O5 ; MOLECULAR MASS: 408.879g/mol.

Amlodipine (as besylate, mesylate or maleate) is a medication used to lower blood pressure and prevent chest pain. It belongs to a group of medications known as dihydropyridine-type calcium channel blockers. Widening of these blood vessels lowers blood pressure. In angina, amlodipine increases blood flow to the heart muscle to relieve pain due to angina. It is on the World Health Organization's List of Essential Medicines, the most important medications needed in a basic health system.

PHARMACOLOGY: Amlodipine inhibits calcium ions into vascular smooth muscle cells and cardiac muscle cells. The contractile processes of cardiac muscle and vascular smooth

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muscle are dependent upon the movement of extracellular calcium ions into these cells through specific ion channels. Amlodipine inhibits calcium ion influx across cell membranes selectively, with a greater effect on vascular smooth muscle cells. Negative inotropic effects can be detected in vitro, but such effects have not been seen in intact animals at therapeutic doses. Serum calcium concentration is not affected by amlodipine. Amlodipine is a peripheral arterial vasodilator that acts directly on vascular smooth muscle to cause a reduction in peripheral vascular resistance and reduction in blood pressure. As a calcium channel blocker, amlodipine is expected to inhibit the currents of L-type Cav1.3 channels in the zona glomerulosa.

MEDICINAL USES: Amlodipine is used in the management of hypertension [4]  and coronary artery disease.

BRAND NAMES: Norvasc

SYNTHESIS:

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MONOGRAPH OF CHLORTHALIDONE

IUPAC:  (RS)-2-Chloro-5-(1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl)benzene-1-

sulfonamideFORMULA: C14H11ClN2O4S ; MOLECULAR MASS: 338.766g/mol.

Chlortalidone (INN/BAN) 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.

PHARMACOLOGICAL ACTION: Chlortalidone prevents reabsorption of sodium and chloride by inhibiting the Na+/Cl− symporter in the distal convoluted tubule. 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

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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.

MEDICINAL USES: Diuretic, used to treat hypertension

SYNTHESIS:

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BIBLIOGRAPHY

www.wikipedia.org

www.google.com/patents

www.drugs.com

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THANKYOU !!!

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