The document provides information about renal pharmacology. It discusses the anatomy and physiology of the renal system and its purpose in eliminating waste and regulating fluids and electrolytes. It then summarizes different types of diuretic drugs, including loop diuretics like furosemide, thiazide diuretics like hydrochlorothiazide, and potassium-sparing diuretics like spironolactone. It describes the mechanisms of action, therapeutic uses, adverse effects, and interactions of these important classes of renal drugs.
Diuretics - Diuretics are chemical agents which increase the excretion of urine by kidneys. They lead to the secretion of excess water and that accumulate in tissues and urine, results in decrease in body fluids especially the extracellular fluid. The increased excretion of water and electrolytes by the kidneys is dependent in three different processes viz., glomerular filtration, tubular reabsorption active and passive and tubular secretion. Diuretics are classified in mainly three types: 1.High ceiling diuretics -Loop diuretics acts mainly at thick ascending limb of the loop of Henle. These diuretics produce peak diuresis which is much greater than other diuretics. Loop diuretics inhibit reabsorption of Na+, Cl- and K+ ions by inhibiting Na+/K+/2Cl- symport of the thick ascending limb of loop of Henle. By inhibiting Na+/K+/2Cl- symport, these agents also inhibit reabsorption of Ca++ and Mg++.
E.g. Furosemide , bumetanide, torasemide.
2. Medium efficacy diuretics-(a)Thiazide -Thiazide diuretics act on the early distal convoluted tubule and inhibit the sodium-chloride symporter leading to a retention of water in the urine, as water normally follows penetrating solutes. The short-term anti-hypertensive action is based on the fact that thiazides decrease preload, decreasing blood pressure. E.g. Chlorothiazide, Hydrochlorothiazide, Benzothiazide
(b)Thiazide like diuretics- These diuretics are behave like thiazide diuretics. E.g. Chlorthialidone, Indapamide, Xipamide, Metolazone ).
3. Weak diuretics-
(a)Carbonic anhydrase inhibitor- Carbonic anhydrase inhibitor acts on proximal convoluted tubule.
Carbonic anhydrase inhibitors are a medication used in the management and treatment of glaucoma, idiopathic intracranial hypertension, altitude sickness, congestive heart failure, and epilepsy, among other diseases.
E.g. acetazolamide
(b) Potassium sparing - These are diuretics which do not promote the secretion of potassium into the urine; thus, potassium is retained and not lost as much as with other diuretics. Potassium sparing diuretics act on cortical collecting tubule. These type of diuretics inhibit sodium reabsorption in late distal tubule and indirectly spare potassium excretion. E.g. Spironolactone, Eplerenone, Triamterene, Amiloride, (c)Osmotic -Osmotic diuretic is a type of diuretic that inhibits reabsorption of water and sodium (Na). They are pharmacologically inert substances that are given intravenously. They increase the osmolarity of blood and renal filtrate. In the nephron, osmotic diuretics act at the portions of the nephron that are water-permeable like proximal convoluted tubule, descending limb of loop of Henle, collecting tubuel.
E.g. Mannitol, Glycerol, Isosorbide).
Uses of diuretics - Acute pulmonary oedema,
Congestive cardiac failure,
Forced diuresis in barbiturate poisoning, Hypertension and CCF, Idiopathic hypercalciuria,
Nephrogenic diabetes incipidus, Certain kidney disorders, acute kidney failure.
Any substance that promotes the production of urine
All diuretics increase the excretion of water from bodies
Alternatively, an antidiuretic such as vasopressin, or antidiuretic hormone.
Diuretics are used to treat heart failure, liver cirrhosis, hypertension, water poisoning, and certain kidney diseases
Diuretic and Urinary alkalizes-Dr.Jibachha Sah,M.V.ScDr. Jibachha Sah
Dr.Jibachha Sah,M.V.Sc (Veterinary pharmacology),Lecture,College of Veterinary science,NPI,Bhojard,Chitwan,Nepal.This is part of lecture note on veterinary pharmacologyAUTONOMIC AND SYSTEMIC PHARMACOLOGY, Sixth Semester, B.V.Sc & A.H 6th semester.
Dr.Jibachha sah,Email: jibachhashah@gmail.com,Mobile:00977-9845024121
Diuretics | Definition | Mechanism of Action | Classes of DrugsChetan Prakash
This presentation provides knowledge about Diuretics,Role of sodium, types of urine output, General mechanism of action, Normal Physiolofy of urine formation, GFR Formation, Classes of Diuretics, diuretics abuse and recent discovery. An assignment for the subject, Advanced Pharmacology-I, 1st year M.Pharm, 1st semester.
Diuretics - Diuretics are chemical agents which increase the excretion of urine by kidneys. They lead to the secretion of excess water and that accumulate in tissues and urine, results in decrease in body fluids especially the extracellular fluid. The increased excretion of water and electrolytes by the kidneys is dependent in three different processes viz., glomerular filtration, tubular reabsorption active and passive and tubular secretion. Diuretics are classified in mainly three types: 1.High ceiling diuretics -Loop diuretics acts mainly at thick ascending limb of the loop of Henle. These diuretics produce peak diuresis which is much greater than other diuretics. Loop diuretics inhibit reabsorption of Na+, Cl- and K+ ions by inhibiting Na+/K+/2Cl- symport of the thick ascending limb of loop of Henle. By inhibiting Na+/K+/2Cl- symport, these agents also inhibit reabsorption of Ca++ and Mg++.
E.g. Furosemide , bumetanide, torasemide.
2. Medium efficacy diuretics-(a)Thiazide -Thiazide diuretics act on the early distal convoluted tubule and inhibit the sodium-chloride symporter leading to a retention of water in the urine, as water normally follows penetrating solutes. The short-term anti-hypertensive action is based on the fact that thiazides decrease preload, decreasing blood pressure. E.g. Chlorothiazide, Hydrochlorothiazide, Benzothiazide
(b)Thiazide like diuretics- These diuretics are behave like thiazide diuretics. E.g. Chlorthialidone, Indapamide, Xipamide, Metolazone ).
3. Weak diuretics-
(a)Carbonic anhydrase inhibitor- Carbonic anhydrase inhibitor acts on proximal convoluted tubule.
Carbonic anhydrase inhibitors are a medication used in the management and treatment of glaucoma, idiopathic intracranial hypertension, altitude sickness, congestive heart failure, and epilepsy, among other diseases.
E.g. acetazolamide
(b) Potassium sparing - These are diuretics which do not promote the secretion of potassium into the urine; thus, potassium is retained and not lost as much as with other diuretics. Potassium sparing diuretics act on cortical collecting tubule. These type of diuretics inhibit sodium reabsorption in late distal tubule and indirectly spare potassium excretion. E.g. Spironolactone, Eplerenone, Triamterene, Amiloride, (c)Osmotic -Osmotic diuretic is a type of diuretic that inhibits reabsorption of water and sodium (Na). They are pharmacologically inert substances that are given intravenously. They increase the osmolarity of blood and renal filtrate. In the nephron, osmotic diuretics act at the portions of the nephron that are water-permeable like proximal convoluted tubule, descending limb of loop of Henle, collecting tubuel.
E.g. Mannitol, Glycerol, Isosorbide).
Uses of diuretics - Acute pulmonary oedema,
Congestive cardiac failure,
Forced diuresis in barbiturate poisoning, Hypertension and CCF, Idiopathic hypercalciuria,
Nephrogenic diabetes incipidus, Certain kidney disorders, acute kidney failure.
Any substance that promotes the production of urine
All diuretics increase the excretion of water from bodies
Alternatively, an antidiuretic such as vasopressin, or antidiuretic hormone.
Diuretics are used to treat heart failure, liver cirrhosis, hypertension, water poisoning, and certain kidney diseases
Diuretic and Urinary alkalizes-Dr.Jibachha Sah,M.V.ScDr. Jibachha Sah
Dr.Jibachha Sah,M.V.Sc (Veterinary pharmacology),Lecture,College of Veterinary science,NPI,Bhojard,Chitwan,Nepal.This is part of lecture note on veterinary pharmacologyAUTONOMIC AND SYSTEMIC PHARMACOLOGY, Sixth Semester, B.V.Sc & A.H 6th semester.
Dr.Jibachha sah,Email: jibachhashah@gmail.com,Mobile:00977-9845024121
Diuretics | Definition | Mechanism of Action | Classes of DrugsChetan Prakash
This presentation provides knowledge about Diuretics,Role of sodium, types of urine output, General mechanism of action, Normal Physiolofy of urine formation, GFR Formation, Classes of Diuretics, diuretics abuse and recent discovery. An assignment for the subject, Advanced Pharmacology-I, 1st year M.Pharm, 1st semester.
This presentation is for the diploma students and it covers the topic diuretics. This course is designed to introduce to the students the concept of diuretics, summation of such search and writing a brief report based on collected information in student’s own words.
Completion of graduation project in the form of a report / essay is an essential requirement for obtaining the degree of D.Pharm.
The urinary system, also known as the renal system or urinary tract, consists of the kidneys, ureters, bladder, and the urethra. The purpose of the urinary system is to eliminate waste from the body, regulate blood volume and blood pressure, control levels of electrolytes and metabolites, and regulate blood pH.
Diuretics are medicines that help reduce fluid buildup in the body. They are sometimes called water pills. Most diuretics help the kidneys remove salt and water through the urine. This lowers the amount of fluid flowing through the veins and arteries. As a result, blood pressure goes down.
Diuretics are drugs that increase the flow of urine. They are commonly used to treat edema, hypertension, and heart failure. Typically, the pharmacological group consists of five classes: thiazide diuretics, loop diuretics, potassium-sparing diuretics, osmotic diuretics, and carbonic anhydrase inhibitors.
There are three main types of diuretic: loop diuretics, thiazide diuretics and potassium-sparing diuretics.
A detailed information about the diuretics - classification of drugs, mechanism of action, side effects, dosage and indications.
Classification based on the efficacy of the diuretics.
1. High
2. Moderate
3. Weak
A brief introduction given about the nephron structure and its indications.
Struggling with intense fears that disrupt your life? At Renew Life Hypnosis, we offer specialized hypnosis to overcome fear. Phobias are exaggerated fears, often stemming from past traumas or learned behaviors. Hypnotherapy addresses these deep-seated fears by accessing the subconscious mind, helping you change your reactions to phobic triggers. Our expert therapists guide you into a state of deep relaxation, allowing you to transform your responses and reduce anxiety. Experience increased confidence and freedom from phobias with our personalized approach. Ready to live a fear-free life? Visit us at Renew Life Hypnosis..
This presentation is for the diploma students and it covers the topic diuretics. This course is designed to introduce to the students the concept of diuretics, summation of such search and writing a brief report based on collected information in student’s own words.
Completion of graduation project in the form of a report / essay is an essential requirement for obtaining the degree of D.Pharm.
The urinary system, also known as the renal system or urinary tract, consists of the kidneys, ureters, bladder, and the urethra. The purpose of the urinary system is to eliminate waste from the body, regulate blood volume and blood pressure, control levels of electrolytes and metabolites, and regulate blood pH.
Diuretics are medicines that help reduce fluid buildup in the body. They are sometimes called water pills. Most diuretics help the kidneys remove salt and water through the urine. This lowers the amount of fluid flowing through the veins and arteries. As a result, blood pressure goes down.
Diuretics are drugs that increase the flow of urine. They are commonly used to treat edema, hypertension, and heart failure. Typically, the pharmacological group consists of five classes: thiazide diuretics, loop diuretics, potassium-sparing diuretics, osmotic diuretics, and carbonic anhydrase inhibitors.
There are three main types of diuretic: loop diuretics, thiazide diuretics and potassium-sparing diuretics.
A detailed information about the diuretics - classification of drugs, mechanism of action, side effects, dosage and indications.
Classification based on the efficacy of the diuretics.
1. High
2. Moderate
3. Weak
A brief introduction given about the nephron structure and its indications.
Struggling with intense fears that disrupt your life? At Renew Life Hypnosis, we offer specialized hypnosis to overcome fear. Phobias are exaggerated fears, often stemming from past traumas or learned behaviors. Hypnotherapy addresses these deep-seated fears by accessing the subconscious mind, helping you change your reactions to phobic triggers. Our expert therapists guide you into a state of deep relaxation, allowing you to transform your responses and reduce anxiety. Experience increased confidence and freedom from phobias with our personalized approach. Ready to live a fear-free life? Visit us at Renew Life Hypnosis..
How many patients does case series should have In comparison to case reports.pdfpubrica101
Pubrica’s team of researchers and writers create scientific and medical research articles, which may be important resources for authors and practitioners. Pubrica medical writers assist you in creating and revising the introduction by alerting the reader to gaps in the chosen study subject. Our professionals understand the order in which the hypothesis topic is followed by the broad subject, the issue, and the backdrop.
https://pubrica.com/academy/case-study-or-series/how-many-patients-does-case-series-should-have-in-comparison-to-case-reports/
Defecation
Normal defecation begins with movement in the left colon, moving stool toward the anus. When stool reaches the rectum, the distention causes relaxation of the internal sphincter and an awareness of the need to defecate. At the time of defecation, the external sphincter relaxes, and abdominal muscles contract, increasing intrarectal pressure and forcing the stool out
The Valsalva maneuver exerts pressure to expel faeces through a voluntary contraction of the abdominal muscles while maintaining forced expiration against a closed airway. Patients with cardiovascular disease, glaucoma, increased intracranial pressure, or a new surgical wound are at greater risk for cardiac dysrhythmias and elevated blood pressure with the Valsalva maneuver and need to avoid straining to pass the stool.
Normal defecation is painless, resulting in passage of soft, formed stool
CONSTIPATION
Constipation is a symptom, not a disease. Improper diet, reduced fluid intake, lack of exercise, and certain medications can cause constipation. For example, patients receiving opiates for pain after surgery often require a stool softener or laxative to prevent constipation. The signs of constipation include infrequent bowel movements (less than every 3 days), difficulty passing stools, excessive straining, inability to defecate at will, and hard feaces
IMPACTION
Fecal impaction results from unrelieved constipation. It is a collection of hardened feces wedged in the rectum that a person cannot expel. In cases of severe impaction the mass extends up into the sigmoid colon.
DIARRHEA
Diarrhea is an increase in the number of stools and the passage of liquid, unformed feces. It is associated with disorders affecting digestion, absorption, and secretion in the GI tract. Intestinal contents pass through the small and large intestine too quickly to allow for the usual absorption of fluid and nutrients. Irritation within the colon results in increased mucus secretion. As a result, feces become watery, and the patient is unable to control the urge to defecate. Normally an anal bag is safe and effective in long-term treatment of patients with fecal incontinence at home, in hospice, or in the hospital. Fecal incontinence is expensive and a potentially dangerous condition in terms of contamination and risk of skin ulceration
HEMORRHOIDS
Hemorrhoids are dilated, engorged veins in the lining of the rectum. They are either external or internal.
FLATULENCE
As gas accumulates in the lumen of the intestines, the bowel wall stretches and distends (flatulence). It is a common cause of abdominal fullness, pain, and cramping. Normally intestinal gas escapes through the mouth (belching) or the anus (passing of flatus)
FECAL INCONTINENCE
Fecal incontinence is the inability to control passage of feces and gas from the anus. Incontinence harms a patient’s body image
PREPARATION AND GIVING OF LAXATIVESACCORDING TO POTTER AND PERRY,
An enema is the instillation of a solution into the rectum and sig
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Unveiling CRISPR: This naturally occurring bacterial defense system (crRNA & Cas9 protein) fights viruses. Scientists repurposed it for precise gene editing (correction, deletion, insertion) by targeting specific DNA sequences.
The Promise: CRISPR offers exciting possibilities:
Gene Therapy: Correcting genetic diseases like cystic fibrosis.
Agriculture: Engineering crops resistant to pests and harsh environments.
Research: Studying gene function to unlock new knowledge.
The Peril: Ethical concerns demand attention:
Off-target Effects: Unintended DNA edits can have unforeseen consequences.
Eugenics: Misusing CRISPR for designer babies raises social and ethical questions.
Equity: High costs could limit access to this potentially life-saving technology.
The Path Forward: Responsible development is crucial:
International Collaboration: Clear guidelines are needed for research and human trials.
Public Education: Open discussions ensure informed decisions about CRISPR.
Prioritize Safety and Ethics: Safety and ethical principles must be paramount.
CRISPR offers a powerful tool for a better future, but responsible development and addressing ethical concerns are essential. By prioritizing safety, fostering open dialogue, and ensuring equitable access, we can harness CRISPR's power for the benefit of all. (2998 characters)
Global launch of the Healthy Ageing and Prevention Index 2nd wave – alongside...ILC- UK
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Alongside the 77th World Health Assembly in Geneva on 28 May 2024, we launched the second version of our Index, allowing us to track progress and give new insights into what needs to be done to keep populations healthier for longer.
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Professor Orazio Schillaci, Minister of Health, Italy
Dr Hans Groth, Chairman of the Board, World Demographic & Ageing Forum
Professor Ilona Kickbusch, Founder and Chair, Global Health Centre, Geneva Graduate Institute and co-chair, World Health Summit Council
Dr Natasha Azzopardi Muscat, Director, Country Health Policies and Systems Division, World Health Organisation EURO
Dr Marta Lomazzi, Executive Manager, World Federation of Public Health Associations
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One of the most developed cities of India, the city of Chennai is the capital of Tamilnadu and many people from different parts of India come here to earn their bread and butter. Being a metropolitan, the city is filled with towering building and beaches but the sad part as with almost every Indian city
3. 01
Better understanding about
the anatomy and
physiology of the renal
system.
02
Better understanding about
the mechanism of action of
different types of drugs.
03
Better understanding
about the adverse effect of
the different types of
drugs.
4. RENAL SYSTEM
The renal system is a group of organs that work together to produce, store, and
release urine. Urine is the liquid waste material excreted from the body. The
organs that work together in this system include the kidneys, bladder, ureters,
and urethra. It is also known as the urinary or the excretory system.
The renal system, also known
as the urinary system, consists
of:
2 kidneys
2 ureters
The bladder
The prostate (in men)
And lastly, the urethra
5. PURPOSE OF THE URINARY SYSTEM
The purpose of the urinary system is to eliminate waste from the body, regulate
blood volume & blood pressure, control levels of electrolytes & metabolites, and
regulate blood pH
Each kidney consists of functional units called Nephrons which allows
filtration of the blood entering via the renal artery.
Following filtration, blood without waste exits via the renal vein.
The filtered waste substance, known as urine, exits the kidney via the ureters
which are tubes made of smooth muscle fibers that propel urine towards the
bladder.
Urine is stored in the bladder and subsequently expelled from the body by
urination.
6. Each kidney consists of 3 regions:
The renal cortex – this is the outer region
containing approximately 1.25 million
nephrons
The renal medulla – this is the middle region
containing 8-12 renal pyramids which functions
as a collecting chamber for urine
The renal pelvis – this is the inner region
which receives urine through the major calyces
to drain via the ureters.
7. ● Diuretics, or water pills, help your
kidneys put extra salt and water into your
urine or pee. This is how diuretics clear
extra fluid out and bring down your blood
pressure. Diuretics also help when you have
too much fluid collecting because of heart
failure or other medical problems.
DIURETICS
8. Mechanism of Action
Diuretic drugs increase urine output by the kidney. This is
accomplished by altering how the kidney handles sodium.
If the kidney excretes more sodium, then water excretion
will also increase. Most diuretics produce diuresis by
inhibiting the reabsorption of sodium at different segments
of the renal tubular system.
9. LOOP DIURETICS
The loop agents are the most effective diuretics available. These drugs
produce more loss of fluid and electrolytes than any other diuretics.
They are known as loop diuretics because their site of action is in the
loop of Henle.
Furosemide Furosemide [Lasix] is the most frequently prescribed
loop diuretic and will serve as our prototype for the group.
10. Mechanism of Action
Furosemide acts in the thick segment of the ascending
limb of Henle’s loop to block reabsorption of sodium
and chloride. By blocking solute reabsorption,
furosemide prevents passive reabsorption of water.
Since a substantial amount (20%) of filtered NaCl is
normally reabsorbed in the loop of Henle, interference
with reabsorption here can produce profound diuresis.
11. Pharmacokinetics
Furosemide can be administered orally, IV, and IM.
With oral administration, diuresis begins in 60
minutes and persists for 8 hours. Oral therapy is used
when rapid onset is not required. Effects of IV
furosemide begin within 5 minutes and last for 2
hours. Intravenous therapy is used in critical situations
(e.g., pulmonary edema) that demand immediate
mobilization of fluid. Furosemide undergoes hepatic
metabolism followed by renal excretion.
12. Therapeutic Uses
Furosemide is a powerful drug that is generally reserved for situations that require rapid or
massive mobilization of fluid. This drug should be avoided when less efficacious diuretics
(thiazides) will suffice.
Conditions that justify use of furosemide include:
● pulmonary edema associated with congestive heart failure (CHF);
● edema of hepatic, cardiac, or renal origin that has been unresponsive to less efficacious
diuretics; and
● hypertension that cannot be controlled with other diuretics.
Furosemide is especially useful in patients with severe renal impairment, since, unlike the
thiazides (see later in the chapter), the drug can promote diuresis even when renal blood
flow and glomerular filtration rate (GFR) are low. If treatment with furosemide alone is
insufficient, a thiazide diuretic may be added to the regimen. There is no benefit to
combining furosemide with another loop diuretic.
13. Adverse Effects
● Hyponatremia
● Hypochloremia, and
● Dehydration.
Furosemide can produce excessive loss of sodium, chloride, and water.
Severe dehydration can result. Signs of evolving dehydration include dry
mouth, unusual thirst, and oliguria (scanty urine output). Impending
dehydration can also be anticipated from excessive loss of weight. If
dehydration occurs, furosemide should be withheld.
14. Drug Interaction
● Digoxin is used for heart failure and cardiac dysrhythmias. In the
presence of low potassium, the risk of serious digoxin-induced toxicity
(ventricular dysrhythmias) is greatly increased. Because loop diuretics
promote potassium loss, the use of these drugs in combination with
digoxin can increase the risk of dysrhythmia. This interaction is
unfortunate in that most patients who take digoxin for heart failure must
also take a diuretic as well. To reduce the risk of toxicity, potassium
levels should be monitored routinely; when indicated, potassium
supplements or a potassium-sparing diuretic should be given.
15. Preparations, Dosage, and Administration
Oral
Furosemide [Lasix] is available in tablets (20, 40, and 80 mg) and in
solution (10 mg/mL, 40 mg/5 mL) for oral use. The initial dosage for
adults is 20 to 80 mg/day as a single dose. The maximum daily dosage is
600 mg. Twice-daily dosing (8:00 AM and 2:00 PM) is common. Dosing
late in the day produces nocturia and should be avoided.
Parenteral
Furosemide is available in solution (10 mg/mL) for IV and IM
administration. The usual dosage for adults is 20 to 40 mg, repeated in 1
or 2 hours if needed. Intravenous administration should be done slowly
(over 1 to 2 minutes). For high-dose therapy, furosemide can be
administered by continuous infusion at a rate of 4 mg/min or slower.
16. Other Loop Diuretics
● In addition to furosemide, three other loop diuretics are available: ethacrynic acid
[Edecrin], torsemide [Demadex], and bumetanide [Burinex , generic only in United States].
● All three are much like furosemide. They all promote diuresis by inhibiting sodium and
chloride reabsorption in the thick ascending limb of the loop of Henle.
● All are approved for edema caused by heart failure, chronic renal disease, and cirrhosis,
but only torsemide, like furosemide, is also approved for hypertension.
● All can cause ototoxicity, hypovolemia, hypotension, hypokalemia, hyperuricemia,
hyperglycemia, and disruption of lipid metabolism, specifically, reduction of HDL
cholesterol and elevation of LDL cholesterol and triglycerides.
● Lastly, they all share the same drug interactions: Their effects can be blunted by
NSAIDs, they can intensify ototoxicity caused by aminoglycosides, they can increase
cardiotoxicity caused by digoxin, and they can cause lithium to accumulate to toxic levels.
Routes, dosages, and time courses.
17. THIAZIDES AND RELATED DIURETICS
● The thiazide diuretics also known as benzothiadiazides have effects
similar to those of the loop diuretics. Like the loop diuretics, thiazides
increase renal excretion of sodium, chloride, potassium, and water. In
addition, thiazides elevate plasma levels of uric acid and glucose. The
principal difference between the thiazides and loop diuretics is that the
maximum diuresis produced by the thiazides is considerably lower than
the maximum diuresis produced by the loop diuretics. In addition,
whereas loop diuretics can be effective even when urine flow is
decreased, thiazides cannot.
18. Thiazides and Related Diuretics: Dosages and Time Course of Effects
Generic Name – Brand Name
● Bendroflumethiazide – Naturetin
● Benzthiazide – Aquatag, Exna
● Hydroflumethiazide – Saluron, Diucardin
● Polythiazide – Renese
● Trichlormethiazide – Naqua, Metahydrin
● Quinethazone - Hydromox
Generic Name Brand Name Time Course Optimal Oral Adult
Dosage (mg/day)
Onset (hr) Duration (hr)
THIAZIDES
Chlorothiazide Diuril 1-2 6-12 500-1000
Hydrochlorothiazide Microzide 2 6-12 12.5-25
Methyclothiazide Enduron 2 24 2.5-5
RELATED DRUGS
Chlorthalidone Thalitone 2 24-72 50-100
Indapamide Lozide, generic only in
United States
1-2 Up to 36 2.5-5
Metolazone Generic only 1 12-24 2.5-20
19. Hydrochlorothiazide
● Hydrochlorothiazide is the most widely used thiazide diuretic and will
serve as our prototype for the group. Because of its use in hypertension, a
very common disorder, hydrochlorothiazide is one of our most widely
used drugs.
Mechanism of Action
Hydrochlorothiazide promotes urine production by blocking the reabsorption of sodium and
chloride in the early segment of the distal convoluted tubule. Retention of sodium and chloride in
the nephron causes water to be retained as well, thereby producing an increased flow of urine.
Because only 10% of filtered sodium and chloride is normally reabsorbed at the site where
thiazides act, the maximum urine flow these drugs can produce is lower than with the loop
diuretics. The ability of thiazides to promote diuresis is dependent on adequate kidney function.
These drugs are ineffective when GFR is low (less than 15 to 20 mL/min). Hence, in contrast to
the loop diuretics, thiazides cannot be used to promote fluid loss in patients with severe renal
impairment.
20. Pharmacokinetics
Diuresis begins about 2 hours after oral
administration. Effects peak within 4 to 6 hours and
may persist up to 12 hours. Most of the drug is
excreted unchanged in the urine.
22. Adverse Effects
● The adverse effects of thiazide diuretics are similar to those of the loop diuretics. In
fact, with the exception that thiazides are not ototoxic, the adverse effects of the
Hyponatremia, Hypochloremia, and Dehydration
● Hypokalemia
● Hyperglycemia
● Hyperuricemia
● Impact on Lipids and Magnesium
● Thiazides and loop diuretics are nearly identical.
Drug Interactions
The important drug interactions of the thiazides are nearly identical to those of the loop diuretics. By promoting potassium
loss, thiazides can increase the risk of toxicity from digoxin. By lowering blood pressure, thiazides can augment the
effects of other antihypertensive drugs. By promoting sodium loss, thiazides can reduce renal excretion of lithium, thereby
causing the drug to accumulate, possibly to toxic levels. NSAIDs may blunt the diuretic effects of thiazides. By
counterbalancing the potassium-wasting effects of the thiazides, the potassium sparing diuretics can help prevent
excessive potassium loss. In contrast to the loop diuretics, the thiazides can be combined with ototoxic agents without an
increased risk of hearing loss.
23. Preparations, Dosage, and Administration
● Hydrochlorothiazide is supplied in capsules (12.5 mg) and tablets
(12.5, 25, and 50 mg). Like most other thiazides, hydrochlorothiazide is
administered only by mouth. The usual adult dosage is 25 to 50 mg once
or twice daily. To minimize nocturia, the drug should not be administered
late in the day. To minimize electrolyte imbalance, the drug should be
administered on an intermittent basis (e.g., every other day). In addition to
being marketed alone, hydrochlorothiazide is available in fixed-dose
combinations with potassium sparing diuretics and a long list of other
drugs: beta blockers, angiotensin converting enzyme inhibitors,
angiotensin receptor blockers, calcium channel blockers, hydralazine,
clonidine, and methyldopa.
24. Other Thiazide-Type Diuretics
In addition to hydrochlorothiazide, five other thiazides and related drugs are
approved for use in the United States. All have pharmacologic properties similar
to those of hydrochlorothiazide. With the exception of chlorothiazide, these drugs
are administered only by mouth. Chlorothiazide can be administered IV as well as
PO. Although the thiazides differ from one another in milligram potency, at
therapeutically equivalent doses, all elicit the same degree of diuresis. Although
most have the same onset time (1 to 2 hours), these drugs differ significantly with
respect to duration of action. As with hydrochlorothiazide, disturbance of
electrolyte balance can be minimized through alternate-day dosing. Nocturia can
be minimized by avoiding dosing in the late afternoon. Lists three drugs—
chlorthalidone, indapamide, and metolazone—that are not true thiazides.
However, these agents are very similar to thiazides both in structure and function,
and hence are included in the group.
25. POTASSIUM-SPARING DIURETICS
● The potassium-sparing diuretics can elicit two potentially useful
responses. First, they produce a modest increase in urine production.
Second, they produce a substantial decrease in potassium excretion.
Because their diuretic effects are limited, the potassium-sparing drugs are
rarely employed alone to promote diuresis. However, because of their
marked ability to decrease potassium excretion, these drugs are often used
to counteract potassium loss caused by thiazide and loop diuretics. There
are two subcategories of potassium-sparing diuretics: aldosterone
antagonists and nonaldosterone antagonists. In the United States, only one
aldosterone antagonist, spironolactone is used for diuresis. Two
nonaldosterone antagonists, triamterene and amiloride are currently
employed.
26. Potassium-Sparing Diuretics: Dosages and Time Course of Effects
Generic Name – Brand Name
● Eplerenone - Inspra
Generic Name Brand Name Time Course Optimal Oral Adult
Dosage (mg/day)
Onset (hr) Duration (hr)
Spironolactone Aldactone 24-48 48-72 25-200
Triamterene Dyrenium 2-4 12-16 50-300
Amiloride Midamor 2 24 5-20
27. Spironolactone
Mechanism of Action
● Spironolactone (Aldactone) blocks the actions of aldosterone in the
distal nephron. Since aldosterone acts to promote sodium uptake in
exchange for potassium secretion, inhibition of aldosterone has the
opposite effect: retention of potassium and increased excretion of sodium.
The diuresis caused by spironolactone is scanty because most of the
filtered sodium load has already been reabsorbed by the time the filtrate
reaches the distal nephron.
28. Adverse Effects
• Hyperkalemia
• Endocrine Effects
• Benign and Malignant Tumors
Therapeutic Uses
• Hypertension and Edema
• Heart Failure
Other Uses. In addition to the applications already discussed, spironolactone can be used for
primary hyperaldosteronism, premenstrual syndrome, polycystic ovary syndrome, and acne
in young women.
Drug Interactions
• Thiazide and Loop Diuretics
• Agents That Raise Potassium Levels
29. Preparations, Dosage, and Administration
● Spironolactone (Aldactone) is dispensed in tablets (25, 50, and 100
mg) for oral dosing. The usual adult dosage is 25 to 100 mg/day.
Spironolactone is also marketed in a fixed-dose combination with
hydrochlorothiazide under the brand name Aldactazide.
30. Triamterene
Mechanism of Action
● Like spironolactone, triamterene (Dyrenium) disrupts sodium
potassium exchange in the distal nephron. However, in contrast to
spironolactone, which reduces ion transport indirectly through blockade
of aldosterone, triamterene is a direct inhibitor of the exchange
mechanism itself. The net effect of inhibition is a decrease in sodium
reabsorption and a reduction in potassium secretion. Hence, sodium
excretion is increased, while potassium is conserved. Because it inhibits
ion transport directly, triamterene acts much more quickly than
spironolactone. Initial responses develop in hours, compared with days
for spironolactone. As with spironolactone, diuresis with triamterene is
minimal.
31. ● Hyperkalemia
Other Adverse Effects. Relatively common side effects
include nausea, vomiting, leg cramps, and dizziness.
Blood dyscrasias occur rarely.
Preparations, Dosage, and Administration
Triamterene [Dyrenium] is available in 50- and
100-mg capsules for oral use. The usual initial dosage is 100
mg twice a day. The maximum dosage is 300 mg/day.
Triamterene is also marketed in fixed-dose combinations
with hydrochlorothiazide under the brand names Dyazide
and Maxzide.
Adverse Effects
32. Amiloride
Pharmacologic Properties
● Amiloride has actions similar to those of triamterene. Both drugs
inhibit potassium loss by direct blockade of sodium-potassium exchange
in the distal nephron. Also, both drugs produce only modest diuresis.
Although it can be employed alone as a diuretic, amiloride is used
primarily to counteract potassium loss caused by more powerful diuretics
(thiazides, loop diuretics). The major adverse effect is hyperkalemia.
Accordingly, concurrent use of other potassium sparing diuretics or
potassium supplements must be monitored closely. Caution is needed if
the drug is combined with an ACE inhibitor, angiotensin receptor blocker,
or direct renin inhibitor.
33. ● Amiloride is supplied in 5-mg tablets for oral use.
Dosing is begun at 5 mg/day and may be increased to
a maximum of 20 mg/day. Amiloride is available in a
fixed-dose combination with hydrochlorothiazide.
Preparations, Dosage, and Administration
34. MANNITOL: AN OSMOTIC DIURETIC
● Osmotic diuretics differ from other diuretics with regard to mechanism
and uses. At this time, mannitol is the only osmotic diuretic available in
the United States. Three related drugs—urea, glycerin, and isosorbide—
have been withdrawn.
35. Mechanism of Diuretic Action
● Mannitol (Osmitrol) is a simple six-carbon sugar that embodies the four properties of
an ideal osmotic diuretic. Specifically, the drug:
• Is freely filtered at the glomerulus.
• Undergoes minimal tubular reabsorption.
• Undergoes minimal metabolism.
• Is pharmacologically inert (i.e., it has no direct effects on the biochemistry or
physiology of cells).
● Following IV administration, mannitol is filtered by the glomerulus. However, unlike
other solutes, the drug undergoes minimal reabsorption. As a result, most of the filtered
drug remains in the nephron, creating an osmotic force that inhibits passive reabsorption of
water. Hence, urine flow increases. The degree of diuresis produced is directly related to
the concentration of mannitol in the filtrate: The more mannitol present, the greater the
diuresis. Mannitol has no significant effect on the excretion of potassium and other
electrolytes.
36. Pharmacokinetics
● Mannitol does not diffuse across the GI epithelium and cannot be transported
by the uptake systems that absorb dietary sugars. Accordingly, to reach the
circulation, the drug must be given parenterally. Following IV injection, mannitol
distributes freely to extracellular water. Diuresis begins in 30 to 60 minutes and
persists 6 to 8 hours. Most of the drug is excreted intact in the urine.
Therapeutic Uses
• Prophylaxis of Renal Failure
• Reduction of Intracranial Pressure
• Reduction of Intraocular Pressure
Adverse Effects
• Edema
Other Adverse Effects. Common responses include headache, nausea, and vomiting.
Fluid and electrolyte imbalance may also occur.
37. Mannitol (Osmitrol) is administered by IV infusion. Solutions for IV use range in
concentration from 5% to 25%. Dosing is complex and varies with the objective of
therapy (prevention of renal failure, lowering of ICP, lowering of IOP). The usual adult
dosage for preventing renal failure is 50 to 100 gm over 24 hours. The infusion rate
should be set to elicit a urine flow of at least 30 to 50 mL/hr. It should be noted that
mannitol may crystallize out of solution if exposed to low temperature. Accordingly,
preparations should be observed for crystals before use. Preparations that contain crystals
should be warmed (to redissolve the mannitol) and then cooled to body temperature for
administration. A filter needle is employed to withdraw mannitol from the vial, and an in-
line filter is used to prevent crystals from entering the circulation. If urine flow declines to
a very low rate or ceases entirely, the infusion should be stopped.
Preparations, Dosage, and Administration
38. DISORDERS OF FLUID VOLUME AND OSMOLALITY
● Good health requires that both the volume and osmolality of extracellular and intracellular fluids
remain within a normal range. If a substantial alteration in either the volume or osmolality of these fluids
develops, significant harm can result. Maintenance of fluid volume and osmolality is primarily the job of
the kidneys, and, even under adverse conditions, renal mechanisms usually succeed in keeping the
volume and composition of body fluids within acceptable limits. However, circumstances can arise in
which the regulatory capacity of the kidneys is exceeded. When this occurs, disruption of fluid volume,
osmolality, or both can result.
● Abnormal states of hydration can be divided into two major categories: volume contraction and
volume expansion. Volume contraction is defined as a decrease in total body water; conversely, volume
expansion is defined as an increase in total body water. States of volume contraction and volume
expansion have three subclassifications based on alterations in extra cellular osmolality.
● In the clinical setting, changes in osmolality are described in terms of the sodium content of plasma.
Sodium is used as the reference for classification because this ion is the principal extracellular solute.
(Recall that plasma sodium content ranges from 135 to 145 mEq/L.) In most cases, the total osmolality of
plasma is about 2 times the osmolality of sodium. That is, total plasma osmolality usually ranges from
280 to 300 mOsm/kg water.
41. Isotonic Contraction
● Definition and Causes. Isotonic contraction is defined as volume contraction in which
sodium and water are lost in isotonic proportions. Hence, although there is a decrease in the
total volume of extracellular fluid, there is no change in osmolality. Causes of isotonic
contraction include vomiting, diarrhea, kidney disease, and misuse of diuretics. Isotonic
contraction is characteristic of cholera, an infection that produces vomiting and severe
diarrhea.
● Treatment. Lost volume should be replaced with fluids that are isotonic to plasma. This
can be accomplished by infusing isotonic (0.9%) sodium chloride in sterile water, a solution
in which both sodium and chloride are present at a concentration of 145 mEq/L. Volume
should be replenished slowly to avoid pulmonary edema.
42. Hypertonic Contraction
● Definition and Causes. Hypertonic contraction is defined as volume
contraction in which loss of water exceeds loss of sodium. Hence, there is a
reduction in extracellular fluid volume coupled with an increase in osmolality.
Because of extracellular hypertonicity, water is drawn out of cells, thereby
producing intracellular dehydration and partial compensation for lost extracellular
volume.
● Causes of hypertonic contraction include excessive sweating, osmotic diuresis,
and feeding excessively concentrated foods to infants. Hypertonic contraction
may also develop secondary to extensive burns or disorders of the central nervous
system (CNS) that render the patient unable to experience or report thirst.
● Treatment. Volume replacement in hypertonic contraction should be
accomplished with hypotonic fluids (e.g., 0.45% sodium chloride) or with fluids
that contain no solutes at all. Initial therapy may consist simply of drinking water.
43. Alternatively, 5% dextrose can be infused intravenously. (Since dextrose is rapidly
metabolized to carbon dioxide and water, dextrose solutions can be viewed as the
osmotic equivalent of water alone.) Volume replenishment should be done in stages.
About 50% of the estimated loss should be replaced during the first few hours of
treatment. The remainder should be replenished over 1 to 2 days.
44. Hypotonic Contraction
● Definition and Causes. Hypotonic contraction is defined as volume contraction in which loss of
sodium exceeds loss of water. Hence, both the volume and osmolality of extracellular fluid are reduced.
Because intracellular osmolality now exceeds extracellular osmolality, extracellular volume becomes
diminished further by movement of water into cells. The principal cause of hypotonic contraction is
excessive loss of sodium through the kidneys. This may occur because of diuretic therapy, chronic renal
insufficiency, or lack of aldosterone (the adrenocortical hormone that promotes renal retention of
sodium).
● Treatment. If hyponatremia is mild, and if renal function is adequate, hypotonic contraction can be
corrected by infusing isotonic sodium chloride solution for injection. When this is done, plasma tonicity
will be adjusted by the kidneys. However, if the sodium loss is severe, a hypertonic (e.g., 3%) solution
of sodium chloride should be infused. Administration should continue until plasma sodium
concentration has been raised to about 130 mEq/L. Patients should be monitored for signs of fluid
overload (distention of neck veins, peripheral or pulmonary edema). When hypotonic contraction is due
to aldosterone insufficiency, patients should receive hormone replacement therapy along with
intravenous infusion of isotonic sodium chloride.
45. Volume Expansion
● Volume expansion is defined as an increase in the total volume of
body fluid. As with volume contraction, volume expansion may be
isotonic, hypertonic, or hypotonic. Volume expansion may result from an
overdose with therapeutic fluids (e.g., sodium chloride infusion) or may
be associated with disease states, such as heart failure, nephrotic
syndrome, or cirrhosis of the liver with ascites. The principal drugs
employed to correct volume expansion are diuretics and the agents used
for heart failure. A specific form of volume expansion known as
hypervolemic hyponatremia can be treated with a vasopressin antagonist,
such as conivaptan or tolvaptan.
46. ACID-BASE DISTURBANCES
Systems that Maintain the Acid-Base Status:
● 1. Bicarbonate–Carbonic Acid Buffer System
● 2. Respiratory System
● 3. Kidneys
Four Principal Types of Acid-Base Imbalance:
1. RESPIRATORY ALKALOSIS
It is caused by hyperventilation
○ Treatment:
- The management depends on the severity of pH elevation.
Ex. holding a paper bag over the nose and mouth
47. 2. RESPIRATORY ACIDOSIS
This resulted from retention of CO2 secondary to hypoventilation
○ Primary causes of hypoventilation are:
■ depression of the medullary respiratory center
■ pathologic changes in the lungs (e.g., status asthmaticus, airway obstruction)
● Treatment:
- Oxygen and ventilator are given for assistance
- If severe, sodium bicarbonate may be infused.
3. METABOLIC ALKALOSIS
Characterized by increase in both the pH and bicarbonate content of plasma
The body’s compensation is through hypoventilation, increase renal secretion of bicarbonate and
accumulation of organic acids.
● Treatment:
- Usually, it is corrected by infusing a solution of sodium chloride plus potassium chloride.
48. 4. METABOLIC ACIDOSIS
principal causes are:
1. chronic renal failure
2. loss of bicarbonate during severe diarrhea
3. metabolic disorders that leads in overproduction of lactic acid (lactic acidosis) or ketoacids
(ketoacidosis).
Treatment:
- This is treated by correcting underlying cause if the acidosis is severe administer an alkalinizing
salt (e.g., sodium bicarbonate, sodium carbonate)
- Usually, sodium bicarbonate is the preferred alkalinizing salt.
- It can either be administered through oral, especially on mild cases or intravenous for severe
reduction of pH.
49. POTASSIUM IMBALANCES
POTASSIUM
● most abundant intracellular cation, having 150 mEq/L. within the cell and extracellular
concentrations are about 4 to 5 mEq/L.
● plays a major role in conducting nerve impulses and maintaining the electrical
excitability of muscle
● it also helps in regulating acid-base balance.
● Regulation of Potassium Levels
● potassium is primarily regulated through kidneys
● potassium levels is also influenced by extracellular pH.
● insulin has also a profound effect on potassium:
50. HYPOKALEMIA
● deficiency of potassium in the blood.
● serum potassium levels below 3.5 mEq/L.
Causes:
- thiazide or loop diuretic treatment
- insufficient potassium intake
- alkalosis and excessive insulin
- increased renal excretion of potassium
- potassium loss associated with vomiting,
diarrhea, and abuse of laxatives
- sweating.
Adverse effects to skeletal muscle, smooth muscle,
blood pressure, and the heart has the following
Symptoms:
- weakness or paralysis of skeletal muscle
- a risk of fatal dysrhythmias
- intestinal dilation and ileus.
- digoxin toxicity for patients taking digoxin (a
cardiac drug)
- increases the risk of hypertension and stroke
Treatment and Prevention:
● Hypokalemia can be treated by the following
potassium salts:
○ potassium chloride
○ potassium phosphate
○ potassium bicarbonate.
51. POTASSIUM CHLORIDE
- used to treat mild or severe defeciencies
Types:
● Oral
Dosages for:
● prevention range from 16 to 24 mEq/ day.
● deficiency range from 40 to 100 mEq/day
Preparation:
● It is available in solution and in solid
formulations:
- immediate-release tablets
- sustained-release tablet
- effervescent tablets
- powders.
Adverse Effects:
● it irritates the GI tract (causes frequent
abdominal discomfort, nausea, vomiting, and
diarrhea)
Drug interaction:
- oral potassium chloride should be taken
with meals or a full glass of water to
prevent irritation
- Intravenous Potassium Chloride
52. Preparation:
● Intravenous solutions must be diluted (preferably to 40 mEq/L or less)
Nursing Consideration:
● it must be infused slowly (generally no faster than 10 mEq/hr in adults)
● must never be administered by IV push.
● assess serum potassium levels before infusion
● renal function assessed before and during treatment
Contraindications to Potassium Use
● avoid using under conditions that predispose to hyperkalemia (e.g., severe renal
impairment, use of potassium-sparing diuretics, hypoaldosteronism)
● it should not be used when hyperkalemia already exists
53. HYPERKALEMIA
● excessive elevation of serum potassium levels
Causes:
- severe tissue trauma
- untreated Addison’s disease
- acute acidosis (which draws potassium out of cells)
- acute renal failure
- misuse of potassium-sparing diuretics
- overdose with IV potassium.
Consequences:
- disruption of the electrical activity of the heart
- Confusion
- Anxiety
- Dyspnea
- weakness or heaviness of the legs
- numbness or tingling of the hands, feet, and lips
Treatment
● - do not consume any foods that contain potassium and
any medicines that promote potassium accumulation (e.g.,
potassium-sparing diuretics, potassium supplements).
Specific steps:
● infusion of a calcium salt (e.g., calcium gluconate)
● infusion of glucose and insulin
● infusion of sodium bicarbonate if acidosis is present
Steps to remove potassium:
● oral or rectal administration of sodium polystyrene
sulfonate [Kayexalate, Kionex]
● peritoneal or extracorporeal dialysis
54. MAGNESIUM IMBALANCES
MAGNESIUM
● it is important for the activity of many enzymes and for binding of
messenger RNA to ribosomes
● It helps in regulating neurochemical transmission and the excitability
of muscle.
● the normal concentration inside a cell is about 40 mEq/L which is
higher than the outside which is about 2 mEq/L
55. HYPOMAGNESEMIA
- low levels of magnesium in the body
Causes:
- diarrhea
- hemodialysis
- kidney disease
- prolonged IV feeding with magnesium-free
solutions
Symptoms:
- tetany
- disorientation, psychoses, and seizures
- nephrocalcinosis
Prevention and Treatment
- the treatment depends on the severity of
condition
- prophylaxis against magnesium deficiency -
magnesium oxide (orally)
- Frank hypomagnesemia - magnesium sulfate
(parenterally)
56. MAGNESIUM OXIDE
- the tablets form can be taken as supplements to dietary magnesium to help prevent
hypomagnesemia.
- excessive doses may cause diarrhea.
- adult dosage for prevention: 400 to 800 mg daily.
MAGNESIUM SULFATE
- preferred treatment for severe hypomagnesemia.
- IM dosage: 0.5 to 1 gm 4 times a day.
- IV therapy: 10% solution can be used, infused at a rate of 1.5 mL/ min or less
Adverse Effects:
● neuromuscular blockade that causes paralysis of the respiratory muscles
● suppress impulse conduction through the atrioventricular (AV) node
57. HYPERMAGNESEMIA
- toxic elevation of magnesium levels
- most common in patients with renal insufficiency, especially when magnesium-
containing antacids or cathartics are being used.
Symptoms:
- muscle weakness (resulting from inhibition of acetylcholine release)
- hypotension
- sedation
- ECG alterations.
- respiratory paralysis (when plasma levels reach 12 to 15 mEq/L.)
- cardiac arrest.
Management for weakened and paralyzed muscles can be through IV calcium.