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DIEURETIC AGENTS
KEY TERMS:
1. Alkalosis – state of not having enough acid to
maintain normal homeostatic processes.
2. Edema – movement of fluid into the
interstitial spaces
3. Fluid rebound – reflex reaction of the body to
the loss of fluid or sodium.
4. High-ceiling diuretics – powerful diuretics that
work in the loop of Henle to inhibit the
reabsorption of sodium and chloride, leading to
a sodium-rich diuresis.
5. Hyperaldosteronism – excessive output of
aldosterone from the adrenal gland, leading to
increased sodium and water retention and loss of
potassium.
6. Hypokalemia – low potassium in the blood
(weakness, muscle cramps, weakening, nausea,
THIAZIDE AND THIAZIDE-LIKE DIURETICS
vomiting, diarrhea, and cardiac arrythmias).
7. Osmotic pull – drawing force of large molecules
of water.
DIURETICS
Diuretic agents – drugs that increase the amount
of urine produced by the kidneys and increase
sodium excretion.
- Indicated for the treatment of EDEMA
associated with heart failure, acute
pulmonary edema, liver disease, and
renal disease, and for treatment of
hypertension.
- Also used to decrease fluid pressure in
the eye.
- The type that decrease potassium levels:
treatment for conditions that cause
hyperkalemia.
HF – can cause edema because of failing heart
muscled does not pump sufficient blood to the
kidneys, causing activation of the renin-angiotensin-
aldosterone system and resulting in increase in blood
volume and sodium retention.
Pulmonary Edema / Left-sided HF - because of
increased volume of fluid backing up into the lungs.
Renal disease – edema because of loss of plasma
proteins into urine where there is damage to the
glomerular basement membrane.
Glaucoma – diuretics provide osmotic pull to
remove some fluid from the eye that decreases IOP.
FIVE CLASSES OF DIURETICS
Lymphatic Tissue – consists of many
1. Thiazide and thiazide-like diuretics
2. Loop diuretics
3. Carbonic anhydrase inhibitors
4. Potassium-sparing diuretics
5. Osmotic diuretics
CAUTION
COMMON ADVERSE EFFECTS
1. Gastrointestinal (GI) upset.
2. Fluid and electrolyte imbalances
3. Hypotension
4. Electrolyte disturbances
*DIURETIC DRUGS CAN BE FOUND IN THE
BOOK PAGE 2219.
 Belong to sulfonamides and the most
frequently used diurectics (mild diuretics)
 First-line drugs used to manage essential
hypertension
 Thiazide diuretics:
1. Chlorothiazide (Diuril)
2. Hydrochlorothiazide (generic) – frequently
used in this class
3. Methyclothiazide (generic)
 Thiazide-like diuretics:
1. Chlorthalidone (generic) – oldest in this
classs, can also be for IV infusion
2. Indapamide (generic)
3. Metolazone (zaroxolyn)
Therapeutic actions and indications:
- Act to block the chloride pump
- Blocking of the chloride pump keeps the
chloride and sodium in the tubule to be
excreted in the urine, thus preventing the
reabsorption of both chloride and sodium in
the vascular system.
PHARMACOKINETICS
- Well absorbed from the GI Tract after oral ,
onset is 1-3 hrs, peak effects within 406 hrs, and
duration of 6-12 hrs
- Metabolized in liver and excreted in urine
- Cross the placenta and enter breast milk
CONTRAINDICATIONS AND CAUTIONS
- Allergy to thiazide or sulfonamides to prevent
hypersensitivity reactions
- Fluid and electrolyte imbalances
- Severe renal disease
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- Systemic lupus erythematosus (SLE)
- Glucose tolerance abnormalities
- Diabetes mellitus
- Gout
- Liver disease
- Hyperparathyroidism
- Bipolar disorder
- Routine use during pregnancy is not appropriate.
- Potential for adverse effects on fluid and electrolyte changes in the fetus and baby.
ADVERSE EFFECTS
- Related to interference with normal regulatory mechanisms of the nephron
- Hypokalemia
- Decreased calcium excretion
- Decreased uric acid excretion
- Urine: highly alkalized during use because they block the reabsorption of bicarbonate
DRUG-DRUG INTERACTION
- Cholestyramine or colestipol – decreased absorption, should be taken separated by at least 2 hours
- Decreased digoxin toxicity
- Increase quinidine toxicity
- Decreased effectiveness of antidiabetic agents relating to changes in glocuse metabolism
- Risk of increase lithium toxicity
LOOP DIURETICS
- Work in the loop of Henle
- The high-ceiling diuretics: cause a greater diuresis
LOOP DIURETIC DRUGS
1. Ethacrynic acid (edecrin)
2. Bumetanide (generic) – 1st loop diuretic introduced
3. Furosemide (Lasix)
4. Torsemide (demadex)
THERAPUTIC ACTIONS AND INDICATIONS
- Block chloride pump in the ascending loop of Henle, where 30% of all filtered sodium is normally reabsorbed
- have a similar effect in the descending loop of Henle and in the distal convoluted tubule, resulting in the
production of a copious amount of sodium-rich urine
- choice when a rapid and extensive diuresis is needed
- SEVERE EDEMA OR ACUTE PULMONARY EDEMA: can work only on the blood that reaches the
nephrons.
- COMMONLY for the treatment of:
1. Acute HF
2. Acute pulmonary edema
3. Edema associated with HF or with renal or liver disease
4. Hypertension
PHARMACOKINETICS
- Available for oral or IV use
- Furosemide – can also be on IM
- Peak levels: 60 – 120 mins (orally), 30 mins (parenterally)
- Half-life: 30 – 60 mins, excreted primarily through urine.
CONTRAINDICATIONS AND CAUTIONS
- Allergy to loop diuretic
- Electrolyte depletion
- Anuria-severe renal failure
- Hepatic coma
ADVERSE EFFECTS
- Imbalance in electrolytes and fluid
- Hypokalemia
- Alkalosis (rise in serum pH to an alkaline state)
- Calcium is lost (hypocalcemia and tetany)
- Hypotension and dizziness
- Long term: hyperglycemia
- Ototoxicity and deafness reported
DRUG-DRUG INTERACTIONS
- Ototoxicity increases with aminoglycosides or cisplatin
- Anticoagulation effects with anticoagulants
- Decreased loss of sodium and decreased antihypertensive effects with indomethacin, ibuprofen, salicylates, or
other nonsteroidal inflammatory agents

CARBONIC ANHYDRASE INHIBITORS

- Mild diuretics
- DRUGS:
1. Acetazolamide (Diamox)
2. Dichlorphenamide (Keveyis)
3. Methazolamide (generic)
THERAPEUTIC ACTIONS AND INDICATIONS
- Enzyme carbonic anhydrase: catalyst for the formation of sodium bicarbonate and for the excretion of
hydrogen
- Used to adjuncts other diuretics when an intense one is needed
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PHARMACOKINETICS
- Rapidly absorbed and widely distributed
- Acetazolamide: oral and IV use
- Peak: 2 – 4 hrs (15 mins in IV)
- Duration: 6 – 12 hours, excreted in urine
- Not be used in pregnancy
CONTRAINDICATIONS AND CAUTIONS
- Allergy to drug or to antibacterial sulfonamides or thiazides
- Patients with chronic noncongestive angle-closure glaucoma
- CAUTION: (found in the book)
ADVERSE EFFECTS
- Disturbances in acid-base and electrolyte balances
- Metabolic acidosis
- Hypokalemia
- Paresthesias (tingling) of the extremities
- Confusion and drowsiness
DRUG-DRUG INTERACTIONS
- Increased excretion of salicylates and lithium

POTASSIUM-SPARING DIURETICS
- Not as powerful as loop diuretics
- Retain potassium
- Used for patients at high risk for hypokalemia associated with diuretic use
- DRUGS:
1. Amiloride (midamor) – block potassium secretion
2. Eplerenone (inspra)
3. Spironolactone (Aldactone) – aldosterone antagonist (frequently prescribed – drug of choice for treating
hyperaldosteronism)
4. Triamterene (dyrenium) – block potassium secretion
THERAPEUTIC ACTIONS AND INDICATIONS
- Cause a loss of sodium while promoting the retention of potassium
- Diuretic effect: balance achieved in losing sodium to offset the potassium retained
- Often used as adjuncts with thiazide or loop or in patients risk if hypokalemia develops
PHARMACOKINETICS
- Well absorbed (oral)
- Protein bound, and widely distributed
- Metabolized in liver and excreted in urine
- Spironolactone – slow onset, 24 – 48 hours, peak at 48 – 72 hrs, duration at 72 hrs
- Amiloride and triamterene: peak at 6 – 10 hrs, duration of 16 – 24 hrs
- Eplerenone: peak concentration in 1.5 – 2 hrs, half-life: 3 – 6 hrs
CONTRAINDICATIONS AND CAUTIONS
- With allergy to drug
- Hyperkalemia
- Renal disease or anuria
ADVERSE EFFECTS
- Hyperkalemia most common which cause lethargy, confusion, ataxia, muscle cramps, and cardiac arrythmias
- Avoid foods rich in potassium
- Work much like aldosterone
- Androgen effects: hirsutism, gynecomastia, deepening of voice, and irregular menses
DRUG-DRUG INTERACTIONS
- Decreases if combined with salicylates

OSMOTIC DIURETICS
- Pull water into the renal tubule without sodium loss
- DRUG: MANNITOL (osmitrol)
THERAPEUTIC ACTIONS AND INDICATIONS
- Mannitol: a sugar not well reabsorbed by the tubules
- Acts to pull large amounts of fluid into the urine due to osmotic pull
- Effects not limited to kidneys
- Used in acute situations when necessary to decrease IOP before eye surgery or during acute attacks of
glaucoma
PHARMACOKINETICS
- IV use, poorly reabsorbed by renal tubule, not secreted bu tubule and resistant to metabolism
- ACTION: depends on activity in the solution
CONTRAINDICATIONS AND CAUTIONS
- Patients with renal disease and anuria
- Pulmonary congestion
- Intracranial bleeding
- Dehydration
- HF
ADVERSE EFFECTS
- Sudden drop in fluid levels
- Nausea, vomiting, hypotension, light-headedness, confusion, and headache can be accompanied by cardiac
decompensation and even shock.
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DRUGS AFFECTING
GASTROINTESTINAL
SECRETIONS
KEY TERMS:
Acid rebound – reflex response of the stomach to lower-than-normal acid levels
Antacids – neutralize stomach acid
Digestive enzymes - break down foods into usable nutrients
Gastrointestinal protectant – drug that coats any injured area in the stomach to prevent further injury from acid
or pepsin
Histamine-2 (H2) Antagonist – drug that blocks the H2 receptor sites, used to decrease acid production in the
stomach
Peptic ulcer – erosion of the lining of the stomach or duodenum
Prostaglandin – any one of the numerous tissue hormones that have local effects on various systems and organs
of the body
Proton pump inhibitor – drug that blocks the H+, K+-ATPase enzyme system on the secretory surface of the
gastric parietal cells
*DRUG LISTS ARE ON THE BOOK PAGE 2463.

DIURETICS
Diuretic agents – drugs that increase the amount of urine produced

DRUGS USED TO TREAT GASTROESOPHAGEAL REFLEX DISEASE (GERD) AND ULCER DISEASE
Histamine-2 Antacids Proton pump inhibitors Gastrointestinal Prostaglandins
(H2) protectants
Antagonists
Block the Interact with acids at Suppress the secretion of Coat any injured area in Inhibit the secretion of
release of the chemical level to hydrochloric acid into the the stomach to prevent gastrin and increase the
hydrochloric neutralize them lumen of the stomach further injury from acid secretion of mucous
acid in lining of the stomach
response to providing a buffer.
gastrin
DRUGS:
1. Cimetidine
(Tagamet HB)
2. Ranitidine
(Zantac)
3. Famotidine
(Pepcid)
4. Nizatidine
(Axid)
(Other drugs
and their user
indications
are in the
book page
2473)
THERAPEU
TIC ACTION
&
INDICATIO
NS
- Block H2
receptors
located on the
parietal cells.
- Blocking
these receptors
prevents about
70% of the
hydrochloric
acid release
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from the
parietal cells
- Also
decrease
pepsin
production by
the chief cells
USED IN
THE
FOLLOWIN
G:
1. Short-term
treatment of
active
duodenal ulcer
or benign
gastric ulcer.
2. Treatment
of pathological
hypersecretory
conditions
such as
Zollinger
Ellison
Syndrome
3. Prophylaxis
of stress-
induced ulcers
and acute
upper GI
bleeding in
critical patients
4. Treatment
of erosive
gastroesophag
eal reflux
5. Relief of
symptoms of
heartburn, acid
indigestion,
and sour
stomach
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