Question

Identify two classes of diuretics with regard to mechanism of action, indications, dosage, routes of administration, adverse effects, toxicity, cautions, contraindications, and drug interactions. Using a minimum of two scholarly article to support it, describe how these diuretics work in the kidney and how they lower blood pressure in individuals. Please answer with a minimum of 250 words and in APA essay format, not a list. Do not forget to add two citations in APA.

Answer 1

The different classes of diuretics have different mechanisms of action but the overall aim of diuretic therapy is to increase the amount of water excreted in the urine. Some of the mechanisms of the different diuretics are described below,

Loop diuretics
These drugs act by inhibiting the Na+/K+/2Cl- transporter protein, present in the walls of the ascending loop of Henle. These agents cause a reduction in the reabsorption of NaCl or salt, which significantly increases diuresis. Patients taking a loop diuretic may also lose too much potassium and a doctor may prescribe a potassium supplement to take alongside the therapy. One example of a loop diuretic is furosemide.Loop diuretics are the most potent diuretics that reduce ECF, cardiac output, and blood pressure. The mechanism of action for loop diuretics like furosemide is by inhibiting the apical sodium/potassium/chloride transporter in the thick ascending limb of the loop of Henle.

Furosemide (Lasix) is a potent diuretic (water pill) that is used to eliminate water and salt from the body. In the kidneys, salt (composed of sodium and chloride), water, and other small molecules normally are filtered out of the blood and into the tubules of the kidney. The filtered fluid ultimately becomes urine. Most of the sodium, chloride and water that is filtered out of the blood is reabsorbed into the blood before the filtered fluid becomes urine and is eliminated from the body.Furosemide works by blocking the absorption of sodium, chloride, and water from the filtered fluid in the kidney tubules, causing a profound increase in the output of urine (diuresis). The onset of action after oral administration is within one hour, and the diuresis lasts about 6-8 hours. The onset of action after injection is five minutes and the duration of diuresis is two hours. The diuretic effect of furosemide can cause depletion of sodium, chloride, body water and other minerals. Therefore, careful medical supervision is necessary during treatment.

Common side effects of furosemide are:

• low blood pressure,
• dehydration and
• electrolyte depletion (for example, sodium, potassium).

Other important side effects include:

• jaundice,
• ringing in the ears (tinnitus),
• sensitivity to light (photophobia),
• rash,
• pancreatitis,
• nausea,
• diarrhea,
• abdominal pain, and
• dizziness.
• Increased blood sugar and uric acid levels also may occur.

Adverse effects

1. Gut (gastrointestinal or GI) reactions like pancreatitis, jaundice, anorexia, cramping, diarrhea, constipation, nausea, and vomiting
2. Systemic hypersensitivity reactions like severe anaphylactic shock, necrotizing angiitis, and interstitial nephritis
3. Central nervous system (CNS) reactions like vertigo, headaches, blurred vision, tinnitus, and hearing loss
4. Blood reactions like anemia, leukopenia, thrombocytopenia, and eosinophilia
5. Hypersensitive skin reactions like rash, itching, hives, photosensitivity, exfoliative dermatitis, and Steven-Johnson syndrome
6. Heart reactions like orthostatic hypotension (fainting or dizziness when standing up) and an increase in triglyceride and cholesterol levels

Other reactions include:

• weakness,
• muscle spasms,
• thrombophlebitis,
• fever, and
• hyperglycemia (high blood sugar).

The usual starting oral dose for treatment of edema in adults is 20-80 mg as a single dose. The same dose or an increased dose may be administered 6-8 hours later. Doses may be increased 20-40 mg every 6-8 hours until the desired effect occurs. The effective dose may be administered once or twice daily. Some patients may require 600 mg daily.

Administration of furosemide with aminoglycoside antibiotics (for example, gentamicin) or ethacrynic acid (Edecrin, another diuretic) may cause hearing damage.Furosemide competes with aspirin for elimination in the urine by the kidneys. Concomitant use of furosemide and aspirin may, therefore, lead to high blood levels of aspirin and aspirin toxicity.Furosemide also may reduce excretion of lithium (Eskalith, Lithobid) by the kidneys, causing increased blood levels of lithium and possible side effects from lithium.Sucralfate (Carafate) reduces the action of furosemide by binding furosemide in the intestine and preventing its absorption into the body. Ingestion of furosemide and sucralfate should be separated by two hours.

When combined with other antihypertensive drugs there is an increased risk of low blood pressure or reduced kidney function.

Nonsteroidal anti-inflammatory drugs (for example., ibuprofen, indomethacin [Indocin, Indocin-SR]) may interfere with the blood pressure reducing effect of furosemide.

This medication also interacts with certain drugs like:

• cisplatin (Platinol-AQ),
• cyclosporine,
• methotrexate (Rheumtrex, Trexall),
• phenytoin,
• antibiotics,
• heartmedications,
• laxatives,
• steroids.

Hydrochlorothiazide is a diuretic medication often used to treat high blood pressure and swelling due to fluid build up. Other uses include treating diabetes insipidus and renal tubular acidosis and to decrease the risk of kidney stones in those with a high calcium level in the urine.

This medication is used to treat high blood pressure. Lowering high blood pressure helps prevent strokes, heart attacks, and kidney problems. Hydrochlorothiazide belongs to a class of drugs known as diuretics/"water pills." It works by causing you to make more urine. This helps your body get rid of extra salt and water.

Mechanism of action
Hydrochlorothiazide is transported from the circulation into epithelial cells of the distal convoluted tubule by the organic anion transporters OAT1, OAT3, and OAT4.From these cells, hydrochlorothiazide is transported to the lumen of the tubule by multidrug resistance associated protein 4 (MRP4).

Normally, sodium is reabsorbed into epithelial cells of the distal convoluted tubule and pumped into the basolateral interstitium by a sodium-potassium ATPase, creating a concentration gradient between the epithelial cell and the distal convoluted tubule that promotes the reabsorption of water.Hydrochlorothiazide acts on the proximal region of the distal convoluted tubule, inhibiting reabsorption by the sodium-chloride symporter, also known as Solute Carrier Family 12 Member (SLC12A3).Inhibition of SLC12A3 reduces the magnitude of the concentration gradient between the epithelial cell and distal convoluted tubule, reducing the reabsorption of water.

Side effects include

Abdominal or stomach pain
back, leg, or stomach pains
black, tarry stools
bleeding gums
blistering, peeling, or loosening of the skin
bloating
blood in the urine or stools
bloody urine
blue lips and fingernails
blurred vision
burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
chest pain
chills
clay-colored stools
cloudy urine
cold sweats
confusion
constipation
cough or hoarseness
coughing that sometimes produces a pink frothy sputum
coughing up blood
cracks in the skin
darkened urine
decrease in urine output or decrease in urine-concentrating ability
decreased frequency or amount of urine
diarrhea
difficult, fast, or noisy breathing, sometimes with wheezing
difficulty with breathing
difficulty with swallowing
dizziness, faintness, or lightheadedness when getting up from a lying or sitting position
dry mouth
fast or irregular heartbeat
fever
flushed, dry skin
fruit-like breath odor
general body swelling
general feeling of discomfort or illness
general feeling of tiredness or weakness
greatly decreased frequency of urination or amount of urine
headache
hives
increased blood pressure
increased hunger
increased sweating
increased thirst
increased urination
indigestion
itching
joint pain, stiffness, or swelling
loss of appetite
loss of heat from the body
lower back or side pain
muscle cramps or pain
nausea or vomiting
nosebleeds
numbness, tingling, pain, or weakness in the hands or feet
pain in the joints or muscles
painful or difficult urination
pains in the stomach, side, or abdomen, possibly radiating to the back
pale skin
pinpoint red spots on the skin
puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
rash
red, irritated eyes
red skin lesions, often with a purple center
red, swollen skin
redness, soreness, or itching skin
scaly skin
seizures
shortness of breath
sore throat
sores, ulcers, or white spots on the lips or in the mouth
sores, welting, or blisters
sugar in the urine
swelling of the face, fingers, legs, ankles, feet, or lower legs
swollen or painful glands
tenderness of salivary glands
thickening of bronchial secretions
tightness in the chest
trembling
troubled breathing
unpleasant breath odor
unusual bleeding or bruising
unusual tiredness or weakness
unusual weight loss
vomiting of blood
weakness and heaviness of the legs
weight gain
wheezing
yellow eyes or skin

Dosage

Usual dose: 25 mg to 100 mg orally once or twice dail

-Some patients respond to intermittent therapy, (i.e., administration on alternate days or on 3 to 5 days each week). Excessive response and undesirable electrolyte imbalance are less likely to occur with intermittent dosing.

Usual Adult Dose for Hypertension
Initial dose: 25 mg orally once daily
Maintenance dose: May increase to 50 mg orally daily, as a single or 2 divided dose.

-Patients usually do not require doses in excess of 50 mg daily when used concomitantly with other antihypertensive agents.

Diuretics help rid your body of sodium and water. Most work by making your kidneys release more sodium into the urine. The sodium then takes water with it from your blood decreasing the amount of fluid flowing through your blood vessels hence lowering blood pressure.Diuretics, sometimes called water pills, help rid your body of salt (sodium) and water. Most of them help your kidneys release more sodium into your urine. The sodium takes with it water from your blood, decreasing the amount of fluid flowing through your veins and arteries. This reduces blood pressure.