diuretics

Diuretic Drugs

1-Overview

2-Classification

3-Indiviual drugs
Lecture 1

1-Indications of Diuretics.

2-Adverse effects.

3-Mannitol and Carbonic Anhydrase inhibitors.

Lecture 2

The kidneys

Comprise 0.5% of body weight
But
They receive 25% the cardiac output
Overview

Each day the body produce 180 liter of glomerular filtrate

1.5 liters of urine
Overview

If only 1 % of re-absorption is affected ?

Vast increase in urine output
“Doubled”

Overview

A diuretic:
Is any drug which causes increase in water and solute excretion in the urine.

Sodium is the most important solute.

Definition:

According to the Site of action.

(understanding)

According to the Efficacy.

(clinical use)

Classification

The kidney contains

1,000,000 unite

(Nephron)

(Basic unite)

Classification according to the site of action

65 % of filtered sodium is reabsorbed in:

PCT
Na-K ATPase

Cl also re-absorbed

1-Proximal convoluted tubule(PCT)

1-Osmotic diuretic.

2- Carbonic Anhydrase Inhibitors.

Proximal convoluted tubule(PCT)

25 % of filtered sodium is re-absorbed

Ascending (Thick )

Na and Cl
“Interstitial concentration”

Hypertonic Medullary Concentration

2-Loop of Henle

Descending loop is permeable to water

Loop of Henle is the site of action of

“Loop diuretics”

Loop of Henle

Is the site of Thiazide diuretics

3-Distal convoluted tubule(DCT)

Na
Is exchanged for
K and H

Mineralocorticosteroid

“Aldosterone”
4-Collecting duct

Final concentration step is under ADH control

Ethanol decrease ADH hormone
Collecting duct

Is the site of action of Aldosterone antagonists

Spironolactone


“K-sparing Diuretics”
Collecting ducts

1- High efficacy

2-Intermediat efficacy

3-Low efficacy

Classification acoording to the efficacy

Furosemide

Frusemide

Decrease the urine concentration mechanism at loop of Henle

Affecting the medullary concentration mechanism

25% of filtered sodium excreted

1-High efficacy diuretics

Furosemide

Frusemide


Increasing the dose will increase the effect

“No Ceiling”

High efficacy diuretics

Furosemide

Frusemide

Overtreatment can induce dehydration

It is active even if the GFR is < 10 ml/min

Normal GFR = 120 ml/ min

High efficacy diuretics

Thiazide family drugs

Bendrofluazide
Chlorthalidone
Indapamide


2-Moderate efficacy

Thiazide family drugs

Increasing the dose will NOT increase the effect

“Low ceiling”

Ineffective when GFR < 20 ml/ min
Moderate efficacy

Potassium sparing diuretics

Osmotic diuretic

Spironolactone (Aldosterone antagonist)

Amiloride
Triamterene

3-Law efficacy

Potassium sparing diuretics


2-3 % of filtered sodium is excreted by k sparing diuretics

Law efficacy

Furosemide (Lasix)

Thiazides
Amiloride
3-Individual Drugs

Acts on the thick portion of loop of Henle (ascending)

K loss and hypokalemia

Mg and calcium loss also occur

Furosemide (Lasix)

Well absorbed

Half Life = 2 hours

10 hours in renal failure

20- 120 mg / day

20 mg amp

Pharmacokinetics of Furosemide

Adverse effects

Uncommon

electrolyte disturbance

Hypotension, nausea rarely deafness which is transient
Furosemide (Lasix)


Other Loop Diuretics:

Bumetanide 0.5-2 mg/day

Ethacrynic acid 50 mg/day

Furosemide (Lasix)

DCT increasing k exertion
Reduce the blood pressure

1- reduction of intravascular volume.

2-reduction in peripheral vascular resistance.

Direct effect on vascular smooth muscle.

Thiazides

Used in:

1-Cardiac failure in combination with other drugs.


2-Hypertension.

Thiazides

Well absorbed acting within an hour of administration.

Half life less than 4 hours.

Thiazides

Adverse Effects

Rashes and photosensitivity.
Thrombocytopenia.

Increase total plasma cholesterol

Thiazides





Photosensitivity

Bendroflumethiazide 5- 10 mg orally at the morning.

1.25-2.25 mg as anti hypertensive.

Hydrochlorthazide 25-100 mg/day

Thiazides

Spironolactone

(Aldactone)

Structurally related to Aldosterone

“Competitive inhibitor of Aldosterone”







Aldosterone
Spironolactone

Spironolactone (Aldactone)

1-Hepatic cirrhosis and Nehrotic Syndrome.

2-Congestive heart failure.

Low efficacy diuretics

Spironolactone (Aldactone)

Short half life = 1.6 hours

Ineffective alone but more effective when given with other drugs

Spironolactone can be used with loop diuretics

Impaired renal function may increase the potassium

Contra indicated

Spironolactone dose is 100- 200 mg

Per day.

Spironolactone

Adverse reactions

1-Estrogenic effect which is dose dependent.
Breast tenderness and enlargement.
10 % of male patients breast discomfort.
Menstrual irregularity.

2-Carcinogenic in rodents.

Mechanism of action:

Directly blocking the epithelial sodium channel (ENaC) in the DCT.

Inhibiting sodium re-absorption in the distal convoluted tubule.
Amiloride

Dosage: 5- 10 mg/ day

Amiloride

Amiloride + Hydrochlorothiazide

2.5-5 mg Amiloride
25-50 mg Hydrochlorothiazide

(Moduretic)

Hypertension and edema


Combination Formulae

High efficacy diuretics acts on:

A-Proximal con. Tubule
B-Loop of Henle.
C-Distal Con. Tubule.
D-Collecting Ducts.


MCQs

All the following drugs are potassium sparing diuretics except:

A-Amiloride.
B-Spironolactone.
C-Triamterene.
D-Furosemide.

MCQs

Which one of the following diuretics has estrogenic effect?

A-Amiloride.

B-Spironolactone.
C-Frusemide.
D-Hydrochlorothiazide.

MCQs

The main solute excreted by diuretics is;


A-Potassium.
B-Sodium.
C-Chloride.
D-Calcium.

MCQs

Dehydration due to overtreatment is most common with:

A-Spironolactone.

B-Amiloride
C-Furosemide.
D-Hydrochlorothiazide.

MCQs

It is best to take Furosemide:

A-At the morning.

B-At the afternoon.
C-Before dinner.
D-At Bedtime.


MCQs

All the following diuretic combinations are wrong except:

A- Furosemide + Ethacrynic acid.
B-Hydrochlorothiazide + Amiloride.
C-Amiloride + Spironolactone.
D-Chlorthalidone + Indapamide.
MCQs

Which one of the following diuretics has a significant effect on plasma cholesterol?

A-Furosemide.
B-Thiazides
C- Ethacrynic acid.
D-Spironolactone.
MCQs

Which diuretic is structurally similar to Aldosterone?

A-Furosemide.
B-Thiazides
C-Spironolactone.
D-Amiloride.
MCQs


Combination in diuretics are used to:

A-Increase efficacy.

B- Minimize the adverse reactions.
C-Improve the patient compliance.
D- All of the above.
MCQs