diuretics

Diuretic Drugs

1-Overview

2-Classification

3-Indiviual drugs
Lecture 1

1-Indications of Diuretics.

2-Adverse effects.

3-Manitol and Carbonic Anhydrase inhibitors.

Lecture 2

1- Oedema States

Sodium overload
“Cardiac, Renal, Hepatic”

“Acute pulmonary edema”

Indications of Diuretics

Oedema

2-Hypertension

Reduction of:

Intravascular volume and peripheral vascular resistance.
Indications of Diuretics

3-Hypercalcaemia

Furosemide reduces calcium
re-absorption in ascending limb of loop of Henle.
Indications of Diuretics

4-Idiopathic Hypercalciuria.

A cause of renal stone disease, treated by Thiazide
Indications of Diuretics

5- The syndrome of inappropriate secretion of anti-diuretic hormone

(SIADH)

May be treated with Furosemide.

Indications of Diuretics

6-Nephrogenic Diabetes Insipidus.

My be paradoxically treated with diuretics by contracting vascular volume, increase salt and water reabsorption in proximal tubule.
Indications of Diuretics

7-Congestive cardiac failure.

Reduction of oedema ,relief of dyspnea

Should avoid overtreatment !

Dizziness tiredness, postural hypotension
Monitor body weight !
Indications of Diuretics

Acute Pulmonary Oedema

Potent Loop Diuretic ex Furosemide (Lasix)

Used intravenously with combination of other drugs and oxygen

8-Hepatic ascites

Portal hypertension

Decrease in colloid pressure and hyperaldosteronism.

“Spironolactone”

Indications of Diuretics


Vigorous diuresis can cause encephalopathy!

Paracentesis

Indications of Diuretics

In secondary hyperaldosteronism of Nehrotic syndrome

Spironolactone (Aldactone) is preferred.

Indications of Diuretics

1-Potassium depletion:

Increasing the sodium which reaches the exchange at the DCT and collecting duct.

“Na exchanged for K”
Adverse effects

This can lead to Arrhythmia especially in patient receiving Digoxin

Safe lower limit of K = 3.5 mmol/L
Adverse effects

Loop diuretics cause smaller loss in K than Thiazides:

“For the same amount of diuresis”

But as loop is more potent

They cause more diuresis they cause more hypokalemia !
Adverse effects

Hypokalemia is more prone to occur in hyperaldosteronism whether primary or:

More commonly Secondary to liver disease congestive cardiac failure or nephrotic syndrome.
Adverse effects


Prevention of K depletion:

1-Good dietary intake.

Vegetables and fruits
2-K depleting drug with sparing diuretic.
3-Intermittent diuretics.
“Drug holidays”
Adverse effects

4-Potassium supplementation

KCL
because Cl is the principle ion excreted

All K preparations are irritant to GIT and esophageal ulceration can result.

Cupful of liquid preferably upright

Adverse effects

2-Hyperkalemia in potassium sparing diuretics

ACE Inhibitors
And can cause dangerous hyperkalemia if combined with K sparing diuretic
Adverse effects

Treatment of hyperkalemia:

1-Stop any K sparing diuretic.

2-Meassures to move K rapidly into the cells including:

Adverse effects

A-Sodium bicarbonate 50 ml of 8.4% solution.

B- Glucose 50 ml 50 % solution +10 units of soluble insulin.
C- Nebulised salbutamol (Beta 2 Agonist) 5-10 mg.
Adverse effects

Calcium Gluconate 10 ml of 10 % solution. IV

oppose the myocardial effects of raised serum K
Adverse effects


3-Hypovolaemia in overtreatment:

Postural hypotension

Dizziness
Lethargy
Somnolence
“Usually Insidious”

Adverse effects

4-Urinary retention:

Sudden vigorous dieresis especially in elderly

Adverse effects

5-Hyponatremia

especially in patient who drinks a lot of water.
Large quantities of water.


*Increase in ADH could be a mechanism.

Adverse effects

In Hyponatremia

Discontinue diuretic and water restriction.

Elderly are more predisposed

Adverse effects

6-Urate retention
Hyperuricaemia
Increase in uric acid

Thiazide and loop diuretics

NOT
Amiloride or Spironolactone

Adverse effects

Mechanism of Hyperuricaemia could be:
1-Volume depletion and decrease in GFR.

2-Diuretics are organic acids that competes with the site of transport

Adverse effects

7-Magnesium deficiency in loop and Thiazides

Loss of magnesium

K sparing diuretics leads to Magnesium retention

Cardiac arrhythmia

Adverse effects

8-Carbohydrate intolerance:

Intracellular potassium is necessary in the formation of insulin

Can change latent diabetes into overt diabetes.


Adverse effects

9-Calicium homeostasis

Loop diuretics Increases renal calcium loss.

Furosemide can be used to treat hypercalcaemia.

Adverse effects

Thiazides decrease renal excretion of calcium

Decreasing the risk of hip fracture in elderly!
Adverse effects

10-IV loop diuretics potentiate ototoxicity of aminoglycoside antibiotics

and nephrotoxicity of cephalosporins

Adverse effects

Small molecular weight substances
Filtered by glomerulus but:

NOT Reabsorbed


Increases osmolarity and prevent
re-absorption of water and sodium

“Proximal convoluted tubule”

Osmotic diuretics

Mannitol is a polyhydric alcohol

Given intravenously.

1-Reduction in intracranial pressure.

2-Maintain urine flow to prevent acute tubular necrosis and renal failure.

Increase urine volume

*Contraindicated in CHF and Pul Oedema

Osmotic diuretics

CO2 + H2O → H2CO3

(CA)
Carbonic Anhydrase enzyme


THEN BREAKDS DOWN TO
H ion + HCO3

Carbonic Anhydrase is present in:

“GIT, Eye, Pancreas, kidneys”
Carbonic Anhydrase Inhibitors

Carbonic Anhydrase

C. A.
Enzyme

Reduced hydrogen in PCT

Na loss and diuresis

Reduced HCO3 absorption

“Metabolic Acidosis”


*Not used as diuretic
Carbonic anhydrase inhibitors

Acetazolamide is the most commonly used.(Diamox)

*Reduction in intraocular pressure(IOP)
(Glaucoma)

Hypokalemia and Acidosis

Carbonic anhydrase inhibitors

Used also in treatment of mountain sickness

High altitude
Over 300 meters

Nausea
Lassitude
Headache
Pulmonary and cerebral edema
Carbonic Anhydrase inhibitors

High altitude

Mountain Sickness

Acetazolamide

*Hypoxia

*Hyperventilation

*Alkalosis

Carbonic anhydrase inhibitors

Acetazolamide


Acidosis
Increases respiratory drive

125-250 mg bid (Twice Daily)

Carbonic anhydrase inhibitors

Drowsiness

Fever
Rash
Paresthesia
Blood dyscrasia

Adverse effects

The Relation of serum creatinine with:

1-Renal function

2-GFR

***Final Remarks

A patient with ascites was receiving Thiazide & was stable until he developed hypersensitivity.
His treatment was changed to Furosemide 40 mg every other day and the dose was tittered to produce the same previous clinical efficacy.
By this the risk of K depletion and hypokalemia is:

A-Increased.

B- Decreased.
C- Remained the same.
D- Unpredictable.

MCQs

A patient with oedema was receiving hydrochlorothiazide but his oedema did not resolve & that is why the treatment was changed to Furosemide tab. 40 mg /day which caused dramatic improvement.
By this the risk of K depletion and hypokalemia is:

A-Increased.

B- Decreased.
C- Remained the same.
D- Unpredictable.


MCQs

60 years old lady with osteoporosis was in need for diuretic therapy and was prescribed Thiazide.
she was worried about the effect of the drug on her bone density and likelihood of fractures.
Your reply would be:

A-It has no effect.

B- It could be protective
C- It could be harmful.
D- Unknown effect.

MCQs

A patient with congestive heart failure was receiving Furosemide diuretic every other day.
His GP advised him that he could take the dose daily when he feels shortness of breath.
He consulted you complaining of severe fatigue, dizziness, dryness of the mouth, and somnolence.
The most likely cause of this could be:

A-Hypokalemia.

B-Hyperkalemia.
C-Hypocalcaemia
D- Dehydration and Overtreatment.
MCQs


A patient with gout was prescribed some form of diuretic therapy which cause elevation of his serum uric acid and caused acute attack of gouty arthritis.
This diuretic could be:

A- Amiloride.

B- Spironolactone.
C- Triamterene.
D- Bendrofluazide.

MCQs

A patient with hypovolaemic shock & severe hypotension has developed oliguria & was in need for drug to maintain adequate renal function and increase his urine output, the best choice for this would be:

A-Furosemide.

B- Mannitol.
C- Thiazide.
D- Acetazolamide.
MCQs

Which one of the following drugs increases the calcium loss in the urine?

A-Hydrochlorothiazide.
B- Amiloride.
C- Furosemide.
D- Triamterene.
MCQs

Acetazolamide is known to cause:

A- Metabolic Acidosis
B-Metabolic Alkalosis.
C- Hypokalemia & Metabolic Acidosis.
D- Hypoglycemia.
MCQs