Diuretics Guide

Diuretics 2011/2012
1 Dr.Ahmed Abdel Rahman www.medadteam.org
DIURETICS
Definition:
drugs that increase urine volume.
Classification:
a) Pre-renal (Extra-renal) diuretics:
They increase urine output without acting on the nephrons, examples include:
1. Methylxanthines (theobromine, theophylline, caffeine), dopamine, dobutamine, and
cardiac glycosides (digitalis) increase renal blood flow and glomerular filtration rate
(GFR) by increasing COP and/or causing renal vasodilatation.
(Methylxanthines have also renal action- Cardiac glycosides have diuretic action in
patients with heart failure only).
2. Water and ethyl alcohol inhibit A.D.H.
3. Plasma expanders as dextran.
b) Renal diuretics: they act on the nephrons and may be classified into:
1. Thiazide diuretics: they are moderate efficacy- they inhibit Na+
transport in proximal
segment of distal convoluted tubules (DCT).
2. Loop diuretics: they are high efficacy diuretics- they inhibit Na+
transport in the loop of
Henle.
3. K+
-sparing (retaining=conserving) diuretics: they are low efficacy diuretics- they are
either aldosterone antagonists as spironolactone, or non-aldosterone antagonists as
amiloride and triamterene.
4. Carbonic anhydrase inhibitor(CAIs): they inhibit Na+
/H+
exchange in proximal
convoluted tubules (PCT) mainly. They are low efficacy and are self-limiting because
they cause acidosis (see later).
5. Acidifying diuretics: as NH4Cl, they are also self-limiting diuretics due to acidosis.
6. Osmotic diuretics: as Mannitol.
N.B.:
Thiazide diuretics, loop diuretics, K+
-sparing diuretics, and CAIs are known as "Natriuretics"
or "Saluretics" because they increase urinary excretion of Na+
with its iso-osmotic water.

Diuretics 2011/2012
Thiazide Diuretics
Source: Synthetic.
Chemistry: Related to sulphonamides.
Pharmacokinetics:
1. Well absorbed orally.
2. Pass placental barrier and may cause teratogenicity.
3. Excreted in PCT to (act from the inner side of the nephron) by active secretion thus
reducing secretion of uric acid leading to hyperuricemia. Probenicid reduces active
transport of thiazides and reduces their diuretic action.
Pharmacodynamics:
1. Diuretic action: characterized by:
a) Onset: delayed onset (thiazides are given only orally so they are not useful in
emergencies).
b) Duration: some thiazides are short acting as hydrochlorothiazide and others are long
acting as metolazone.
c) Efficacy: moderate efficacy.
d) Site of action: act on the proximal segment of DCT inhibiting Na+
, Cl-
and water
reabsorption which will be excreted in urine. The sulphonamide structure inhibits
carbonic anhydrase enzyme which causes very mild additional diuretic action.
e) Part of Na+
reaching DCT is reabsorbed in exchange for K+
(mainly) and H+
(to a less
extent).
f) Urine will also contain excess Mg2+
and lesser amounts of Ca2+
.
g) In conclusion, thiazides will produce the following changes in urine and in blood:
BLOODURINE
1. Hyponatremia.
2. Hypovolemia (moderate).
3. Hypochloremia.
4. HYPOKALEMIA.
5. Alkalosis.
6. Hypomagnesemia.
7. Hypercalcemia.
8. Hyperuricemia.
1. Excess Na+
(natriuresis).
2. Excess water (diuresis).
3. Excess Cl-
(chloruresis).
4. Excess K+
(kaluresis).
5. Excess H+
(acidic urine).
6. Excess Mg2+
.
7. Less Ca2+.
8. Less uric acid.

Diuretics 2011/2012
2. Thiazides reduce Renal Blood Flow (RBF):
a) They are contraindicated in patients with renal impairment.
b) Reduction RBF leads to reduction of Glomerular Filtration Rate (GFR) and accordingly
thiazide act as Anti-diuretics only in patients with nephrogenic Diabetes Insipidus
(which may be induced by some drugs as Lithium, Methoxyflurane, and
Demeclocycline).
3. Antihypertensive action:
a) Arteriolar V.D.: this is the most important mechanism and can be explained by:
 Depletion of Na+
from the wall of arterioles thus reducing the vasoconstrictor
(pressor) response to noradrenaline and angiotensin.
 Increasing synthesis of vasodilator PGs (that is why NSAIDs may partially
antagonize the antihypertensive action of thiazides).
 Opening of K+
channels leading to hyperpolarization and V.D.
 Block of Ca2+
channels in arterioles causing V.D.
b) Diuretic action: this is of little importance in the antihypertensive action of thiazides.
4. Hyperuricemia: Thiazides reduce active tubular secretion of uric acid in PCT.
5. Hyperlipidemia: Thiazides increase LDL-cholesterol and triglycerides.
6. Hyperglycemia: Thiazides open K+
channels in B-cells of islets of Langerhans →
Hyperpolarization
Therapeutic uses:
1. Treatment of edema which is either: Cardiac (in mild and moderate congestive heart
failure), Renal, or Hepatic edema.
2. Treatment of mild and moderate hyperternsion: thiazides are preferred to loop diuretics
because they are arteriodilators Except in cases of emergency hypertension and in
patients with renal impairment where loop diuretics are preferred (loop diuretics can be
given I.V. and they increase renal blood flow).
3. Treatment of nephrogenic diabetes insipidus.
4. Treatment of idiopathic hypercalciurea and recurrent calcium stones.
5. Treatment of pre-menstrual tension syndrome.

Diuretics 2011/2012
Contraindications (precautions)Adverse Effects
1. With Digitalis (hypokalemia
induces digitalis toxicity).
2. Hypotension.
3. Allergy to thiazides and
sulphonamides.
4. Diabetes mellitus.
5. Gout.
6. Renal insufficiency
7. Pregnancy.
8. Hepatic insufficiency.
9. With steroids (as cortisol): see
later.
1. Hypokalemia (causes fatigue, headache,
and cardiac arrhythmias).
2. Hyponatremia (causes muscle cramps).
3. Hypovolemia.
4. Hypomagnesemia (may also precipitate
digitalis toxicity).
5. Hypochloremic alkalosis.
6. Hypotension.
7. Hypersensitivity (purpura, dermatitis,
photosensitivity, necrotizing vasculitis or
bone marrow depression) and cross allergy
with sulphonamides.
8. Hyperlipidemia.
9. Hyperglycemia.
10.Hyperuricemia and may precipitate acute
gouty attacks.
11.Decrease renal blood flow.
12.Teratogenicity.
13.May lead to hepatic coma in hepatic
insufficiency.
14.Gut upsets.

Diuretics 2011/2012
How to Avoid Hypokalemia?:
1. Addition of a K+
-sparing diuretic (amiloride-triamterene-spironolactone) or ACE
inhibitors.
2. Dietary potassium (in fruits and vegetables).
3. K+
supplements: K+
tablets (cause GIT irritation) or syrup (less irritant).
4. Intermittent use of diuretics.
Drug interactions:
1. With digitalis: Hypokalemia is the most important precipitating factor of digitalis toxicity.
2. With steroids: steroids cause Na+
and water retention thus antagonize the diuretic effect
of thiazides but more seriously they cause hypokalemia.
3. With sulphonamides: cross allergy.
4.
With K+
-sparing diuretics: synergism and correction of serum K+.
5. With ACE inhibitors and AT1 antagonists: synergism and correction of serum K+
.
6. With insulin and oral hypoglycemic drugs: thiazides antagonize the action of these drugs.
7. With uricosuric drugs (drugs that increase uric acid excretion in urine): thiazides
antagonize the action of these drugs.
8. With Probenicid: probenicid decreases active transport of thiazides and antagonizes their
diuretic action.
9. With NSAIDs: NSAIDs antagonize the antihypertensive action of thiazides because they
cause Na+
and water retention and inhibit the synthesis of vasodilator PGs.
Preparations:
1. Short acting thiazides:
Chlorthiazide and Hydrochlorothiazide (given/6-12 hours).
2. Long acting thiazides:
Chlorthalidone, Metolazone, and Polythiazide (given once daily).
3. Thiazide analogues: they are similar to thiazides in action but not in chemical structure.
Examples include:
a) Indapamide: weak diuretic but it causes arteriodilatation as thiazides (most probably
due to calcium channel block. Used in treatment of hypertension in sub-diuretic dose,
and is excreted in bile (long acting given once daily).
b) Diazoxide: it is a vasodilator drug (opens K+
channels) related to thiazides but is Not a
diuretic. It is given I.V. in emergency hypertension.
c) Metolazone.

Diuretics 2011/2012
Loop Diuretics (High efficacy = High Ceiling Diuretics)
1. Source: synthetic.
2. Chemistry:
some are related to sulphonamides as frusemide (they inhibit carbonic anhydrase which
contributes very mildly to their diuretic action but may cause allergic reactions and cross
allergy with sulphonamides) but others are not sulphonamide derivatives as ethacrynic
acid.
3. Pharmacokinetics:
 Well absorbed orally, and can be given by I.V. and I.M. injection (useful in
emergencies).
 Highly bound to plasma proteins and can displace other drugs as warfarin leading to
toxicity (bleeding in case of warfarin).
 Pass placental barrier and may cause teratogenicity (fetotoxicity).
 Loop diuretics are actively secreted in PCT and-as thiazides- act from the inner side of
the nephron. They interfere with active tubular secretion of uric acid leading to
hyperuricemia, and probenicid reduces their diuretic effect.
 Partly metabolized by the liver.
4. Pharmacodynamics:
1. Diuretic action: characterized by:
a) Onset: rapid onset.
b) Duration: short duration.
c) Efficacy: high efficacy (the most potent available diuretics).
d) Site of action: loop diuretics inhibit reabsorption of Na+
, K+
, and 2Cl-
(co-transport)
from the thick segment of the ascending limb of loop of Henle leading to excess
excretion of these electrolytes in urine with iso-osmotic water. In addition; loop
diuretics decrease osmolarity of the medulla of the kidney and consequently
decrease water reabsorption from the collecting tubules causing potent diuresis.
e) Part of excess Na+
reaching DCT is reabsorbed in exchange for K+
(mainly) and H+
(to a less extent).
f) Urine will also contain excess Mg2+
and excess Ca2+
.
In conclusion loop diuretics will produce the following changes in urine and in blood

Diuretics 2011/2012
BloodUrine
1. Hyponatremia.
2. Hypovolemia (marked).
3. Hypochloremia.
4. HYPOKALEMIA.
5. Alkalosis.
6. Hypomagnesemia.
7. Hypocalcemia.
8. Hyperuricemia.
1. Excess Na+
(natriuresis).
2. Excess water (diuresis).
3. Excess Cl-
(chloruresis).
4. Excess K+
(kaluresis).
5. Excess H+
(acidic urine).
6. Excess Mg2+
.
7. Excess Ca2+
(calciurea).
8. Less uric acid.
2. Loop diuretics increase renal blood flow: they are the diuretics of choice in renal
insufficiency. This is because loop diuretics increase synthesis of vasodilator PGs (PGE
and PGI) in the kidney, this action is antagonized by NSAIDs. (Remember that
thiazides reduce RBF and GFR).
3. Antihypertensive action: this is due to their diuretic action and NOT due to
arteriodilatation.
(In contrast to thiazides; loop diuretics cause venodilatation but not arteriodilatation).
4. Hyperlipidemia: as thiazides; loop diuretics increase LDL-cholesterol and triglycerides.
5. Hyperglycemia: loop diuretics decrease insulin release from the pancreas less
markedly than thiazides.
5. Therapeutic uses:
a) Edema: loop diuretics are used in severe, acute, and refractory edema (combined
with K+
-sparing diuretics) which may be cardiac (due to congestive heart failure),
renal, or hepatic edema.
b) Loop diuretics are given I.V. in acute left ventricular failure (LVF) as they cause
diuresis and venodilatation which decreases pre-load). Also used in cerebral edema.
c) Hypertension: loop diuretics are preferred to thiazides in the following conditions:
 Hypertension in patients with renal insufficiency.
 Emergency hypertension.
 Resistant hypertension.
 Severe hypertension, especially with other antihypertensive drugs that may cause
Na+
and water retention as arteriodilators.
d) Acute renal failure.
e) Hypercalcemia.

Diuretics 2011/2012
ContraindicationsAdverse effects
1. With Digitalis: hypokalemia
precipitates digitalis toxicity.
2. Hypotension.
3. Allergy to loop diuretics and
sulphonamides.
4. Diabetes mellitus.
5. Gout.
6. Pregnancy.
7. With other ototoxic drugs as
aminoglycosides.
8. Liver insufficiency: may precipitate
hepatic coma.
9. With steroids as Cortisol.
1. Hypokalemia.
2. Hypovolemia and dehydration.
3. Hyponatremia.
4. Hypomagnesemia.
5. Hypotension.
6. Hypochloremic alkalosis.
7. Hypocalcemia.
8. Hypersensitivity (and cross
allergy with sulphonamides with
some loop diuretics).
9. Hyperglycemia.
10.Hyperuricemia.
11.Hyperlipidemia.
12.Teratogenicity.
13.Ototoxicity: damage of the 8th
cranial nerve which may cause
deafness, especially if given
concomitantly with other
ototoxic drugs as
aminoglycosides (streptomycin)
or in renal impairment.
14.Gut upset.

Diuretics 2011/2012
6. Drug interactions:
1. With Digitalis: Hypokalemia and hypomagnesemia induce digitalis toxicity.
(How to avoid hypokalemia?).
2. With steroids: see thiazide diuretics.
3. With sulphonamides: see thiazide diuretics.
4. With K+
-sparing diuretics and ACE inhibitors (or AT1-antagonists): see thiazide
diuretics.
5. With NSAIDs: NSAIDs antagonize partially the diuretic action of loop diuretics because
they reduce vasodilator PGs which increase RBF, and they cause Na+
and water
retention.
6. With insulin and oral hypoglycemic drugs: see thiazide diuretics.
7. With probenicid: see thiazide diuretics.
8. With uricosuric drugs: see thiazide diuretics.
9. With Ototoxic drugs as Aminoglycosides: severe ototoxicity.
10.Reduce renal clearance of lithium (anti-manic and mood stabilizing agent) leading to
acute lithium toxicity (see CNS pharmacology).
Preparations:
1. Sulphonamide derivatives: Frusemide (Lasix®
)- Bumetanide- Torsemide.
2. Non-sulphonamide derivatives: Ethacrynic acid.
Very Important Note:
K+
-Losing (depleting) diuretics are commonly used in treatment of heart failure with digitalis
but never allow hypokalemia in these patients because it is the most important factor
precipitating digitalis toxicity.

Diuretics 2011/2012
Loop DiureticsThiazide Diuretics
Sulphonamide derivatives
and non-sulphonamides.
Oral and parenteral.
Rapid onset and short
duration.
High efficacy.
Thick segment of ascending
limb of loop of Henle.
Must be actively secreted
into PCT, inhibit Na+
, K+
,
and 2Cl-
reabsorption from
Loop of Henle leading
to:Natriuresis-diuresis-
chloruresis-kaluresis-acidic
urine-excess Mg2+
-excess
Ca2+
-less uric acid.
Increase RBF
(by increasing PG synthesis)
and GFR. They are the
diuretics of choice in renal
impairment.
 Only by diuresis and no
arteriodilatation.
1. Severe, refractory, and
acute edema (acute
LVF).
2. Emergency, severe, and
resistant hyperternsion.
3. Acute renal failure.
4. Hypercalcemia.
Sulphonamide derivatives.
Oral only.
Slow onset, may be short acting,
or long acting.
Moderate efficacy.
Proximal segment of DCT.
Must be actively secreted into
PCT, inhibit Na+
, Cl-
, and water
reabsorption from proximal
segment of DCT leading to:
Natriuresis- diuresis-chloruresis-
kaluresis-acidic urine-excess
Mg2+
-
less Ca2+
-less uric acid.
Decrease RBF and GFR:
 Contraindicated in renal
impairment.
 Useful in nephrogenic
diabetes insipidus.
 Mainly by arteriodilatation.
 Less importantly by diuresis.
1. Mild and moderate edema
(Cardiac edema due to heart
failure-Renal-Hepatic).
2. Mild and moderate
hypertension.
3. Nephrogenic diabetes
insipidus.
4. Idiopathic hypercalciurea.
5. Pre-menstrual tension.
1-Chemistry:
2-Route:
3-Onset and
duration:
4-Efficacy:
5-Site of action:
6-Diuretic action:
7-RBF and GFR:
8-Antihypertensive
action:
9-Therapeutic uses:

Diuretics 2011/2012
Hypokalemia-Hypovolemia
and Dehydration-
Hyponatremia-
Hypotension-
Hypomagnesemia-
Hypersensitivity-
Hyperlipidemia-
Hyperglycemia-
Hyperuricemia-
Teratogenic-Hypocalcemia-
Hepatic coma in liver
insufficiency-Ototoxicity.
Digitalis toxicity-
Hypotension-Allergy-
Diabetes mellitus-Gout-
Pregnancy-Liver
insufficiency-With steroids-
With other ototoxic drugs.
Sulphonamides:
Frusemide-Bumetanide-
Torsemide.
Non-sulphonamides:
Ethacrynic acid.
Hypokalemia-Hypovolemia-
Hyponatremia-Hypotension-
Hypomagnesemia-
Hypersensitivity-Hyperglycemia-
Hyperlipidemia-Hyperuricemia-
Teratogenic-Decrease RBF-
Hypercalcemia-
Hepatic coma in liver
insufficiency.
Digitalis toxicity-Hypotension-
Allergy-Diabetes mellitus-Gout-
Pregnancy-Renal impairment-
Liver insufficiency-With steroids.
Short acting:
Chlorothiazide-
Hydrochlorothiazide-
Long acting:
Chlorthalidone-Metolazone.
10-Adverse effects:
11Contraindications
(Precautions):
12-Preparations:
N.B: thiazides and loop diuretics are "K+
depleting diuretics".
Drugs causing Hypokalemia:
1. Thiazide diuretics (chlorothiazide-hydrochlorothiazide).
2. Loop diuretics (frusemide-bumetanide-ethacrynic acid).
3. Steroids: cortisol (glucocorticoid)-aldosterone (mineralocorticoid).
4. Adrenaline (by stimulation of renin release and β2-stimulation in skeletal muscles
increasing potassium uptake).

Diuretics 2011/2012
Drugs causing Hyperkalemia:
1. K+
-sparing diuretics: spironolactone (aldosterone antagonist)-amiloride and triamtertene
(non-aldosterone antagonists).
2. ACE inhibitors (captopril) and AT1-receptor antagonists (losartan).
3. β-blockers as propranolol (by inhibition of renin release and blocking β2-receptors).
4. Succinylcholine (depolarizing NMB) especially in renal impairment, burns, and severe
tissue damage.
5. Heparin (inhibits aldosterone synthesis).
Potassium Sparing Diuretics
Common Characteristics:
1. Route of administration: they are given orally only.
2. Onset of action: delayed, not useful in emergencies.
3. Efficacy: they have low efficacy (weak diuretic action).
4. Site of action: distal segment of DCT and cortical collecting tubules.
5. Diuretic action: inhibit Na+
/K+
exchange mainly and inhibit Na+
/H+
exchange to a lesser
extent. This causes excretion of Na+
, Cl-
, and water in urine and retention of K+
(hyperkalemia) and H+
(metabolic acidosis).
6. They are contraindicated in renal impairment to avoid severe hyperkalemia.
7. Unlike thiazides and loop diuretics: they do not cause hyperglycemia, hyperlipidemia, or
hyperuricemia (they have mild uricosuric action) and are not related to sulphonamides
(no cross allergy and no carbonic anhydrase inhibition).
8. Classification: they are classified according to their mechanism of action into 2 groups:
a) Aldosterone antagonists: e.g. Spironolactone- Canrenone (active metabolite of
spironolactone) –Eplerenone.
They are competitive antagonists with aldosterone for specific intraceullar
(cytoplasmic) mineralocorticoid receptors in cells of DCT and collecting tubules.
b) Non-Aldosterone antagonists: e.g. Amiloride and Triamterene: they inhibit Na+
influx
by blocking Na+
-channels in the luminal membrane of DCT and collecting tubular cells.

Diuretics 2011/2012
1) Aldosterone Antagonists:
a) Spironolactone (Aldactone):
1. Source: Synthetic.
2. Chemistry: Steroid.
 Absorbed orally.
 Converted in the liver into canrenone (active metabolite).
 Delayed onset and long duration.
 Passes B.B.B.
Mechanism of action:
Competitive antagonists with aldosterone for mineralocorticoid receptors in DCT and
cortical collecting tubules leading to inhibition of Na+
/K+
exchange (mainly) and
inhibition of Na+
/H+
exchange.
5. Pharmacological actions:
a) Low efficacy diuretic action by increasing Na+
,Cl-
, and water excretion in urine.
b) Retention of K+
in blood leading to "Hyperkalemia".
c) Retention of H+
in blood leading to "Metabolic acidosis" and decrease H+
excretion
in urine causing slight alkalinization of urine.
d) No hyperuricemia, hyperglycemia, or hyperlipidemia (unlike thiazides and loop
diuretics).
a) Being weak diuretics they are usually combined with thiazide diuretics or loop
diuretics in treatment of edema and hypertension; to achieve synergism and
maintain normal blood potassium.
b) Treatment of refractory edema and resistant hypertension due to
Hyperaldosteronism which is either primary (Conn's syndrome) or more commonly
secondary to liver cirrhosis, nephrotic syndrome, and congestive heart failure.
They are given alone or combined with thiazide or loop diuretics.
c) Alternative to thiazides and loop diuretics whenever they are contraindicated in
allergy to sulphonamides, D.M., and gout.

Diuretics 2011/2012
7. Adverse effects:
a) Hyperkalemia especially in: renal impairment-drugs that inhibit renin release as β-
blockers, NSAIDs (inhibit PGI2 which stimulates renin release)-ACE inhibitors and
AT antagonists.
b) Metabolic acidosis.
c) Hypersensitivity reactions as skin rash.
d) Gut upset: gastritis, diarrhea, gastric bleeding.
e) CNS disturbances: headache, drowsiness, confusion, and lethargy.
f) Feminization (Gynecomastia) and impotence in males, and irregular menstruation
and masculanization in females (deepening of voice and hirsutism) due to steroid
structure.
8. Drug interactions:
a) With thiazide and loop diuretics: synergism in diuretic action and maintain normal
blood K+
.
b) With ACE inhibitors, AT antagonists, β-blockers, and NSAIDS: severe hyperkalemia.
c) With Carbenoxolone( aldosterone-like drug derived from liquorice and acts as a
mucosal protective agent in treatment of peptic ulcer): spironolactone antagonizes
the action of liquorice on the stomach.
b) Eplerenone:
Similar to spironolactone but is non-steroid and accordingly no gynecomastia or
menstrual disturbances occur.
2) Non-Aldosterone Antagonists:
1. Source: Synthetic.
 Absorbed orally.
 Amiloride is excreted unchanged in urine. Triamterene is mainly metabolized in
the liver (shorter duration of action).
Mechanism of action: inhibit Na+
influx by blocking Na+
channels in DCT and cortical
collecting tubules (they do not compete with aldosterone) thus reducing Na+
/K+
exchange and to a lesser extent Na+
/H+
exchange.

Diuretics 2011/2012
4. Actions:
As Spironolactone:
Weak diuretic action- Hyperkalemia- Metabolic acidosis.
a) Amiloride and Triamterene are added to thiazides or loop diuretics in treatment of
edema (cardiac edema due to heart failure-renal edema - hepatic edema) to achieve
synergism and more importantly to correct hypokalemia induced by thiazides and
loop diuretics.
b) Amiloride can be used in lithium-induced nephrogenic diabetes insipidus.
6. Adverse effects:
a) Hyperkalemia especially in renal impairments and other drugs (see
Spironolactone).
b) Metabolic acidosis.
c) Hypersensitivity reactions: photosensitivity.
d) Gut upset.
e) Triamterene causes renal stones and may precipitate acute renal failure if given
with indomethacin (NSAID).
Carbonic Anhydrase Inhibitors
Therapeutic doses:
1. Glaucoma: in open angle glaucoma local CA inhibitors as dorzolamide and brinzolamide
are used, in narrow angle glaucoma acetazolamide is also given systemically.
2. Treatment of metabolic alkalosis.
3. Absence seizures (petit-mal epilepsy).
4. To alkalinize the urine, as in treatment of acute toxicity of acidic drugs as salicylates and
barbiturates.
5. Rarely used as diuretics (low efficacy and self-limiting).
Osmotic Diuretics:
 They are pharmacologically inert substances.
 They are freely filtered by the glomeruli but are not –or incompletely-reabsorbed, so
they are excreted in urine with iso-osmotic water and diuresis occurs. They increase
urinary Na+
, Cl-
, K+
, Mg2+
, HCO3
-
and Ca2+
.

Diuretics 2011/2012
 Examples:
a) Mannitol:
 Polysaccharide given by I.V.infusion.
 Uses:
1. Acute elevation of intra-cranial pressure (ICP).
2. Acute elevation of IOP (acute narrow angle glaucoma=acute congestive glaucoma).
3. Prevent Acute renal failure.
 Adverse effects:
Nausea and vomiting-Allergy-Transient expansion of extracellular fluid volume and
may aggravate acute heart failure.
 Contraindications:
Acute L.V.F. (acute pulmonary edema=cardiac asthma).
b) Glucose I.V.
c) Glycerin and isosorbide: given orally in acute narrow angle glaucoma.
Methylxanthines:
 Examples:
Caffeine,Theobromine, Theophylline, and Aminophylline.
 Diuretic action:
1. Pre-renal action by increasing COP and V.D. of renal blood vessels.
2. Renal action: inhibit Na+
reabsorption from PCT.
 Uses:
Aminophylline is given very slowly I.V. in acute L.V.F.
Cardiac glycosides:
Cardiac glycosides (digitalis) have diuretic action only in patients with congestive heart
failure by pre-renal action as they increase COP in these patients (see CVS pharmacology).
Dopamine:
Diuretic action occurs with moderate rate of infusion (stimulates D1-receptors causing renal
V.D. and increase renal blood flow) and with moderate rate of infusion (stimulate β1-
receptors causing increased COP).

Diuretics 2011/2012
Anti-Diuretics
1. ADH and drugs that increase release of ADH as morphine, nicotine, barbiturates, and
yohimbine.
2. Thiazide diuretics are anti-diuretics only in nephrogenic diabetes insipidus.
3. Amiloride is anti-diuretic in lithium-induced diabetes insipidus.
4. Chlorpropamide (anti-diabetic) is ADH like and is used in pituitary diabetes insipidus.
5. Vasoconstrictors as adrenaline and serotonin decrease renal blood flow and act as anti-
diuretics.
ADH Antagonists
1. Lithium carbonate: Antimanic and mood stabilizer. It induces nephrogenic diabetes
insipidus which is treated by amiloride.
2. Methoxyflurane: Inhalation halogenated general anaesthetic which may induce
nephrogenic diabetes insipidus.
3. Demeclocycline: Tetracycline antibiotic that may cause nephrogenic diabetes insipidus,
and is used to treat excess ADH secretion (Syndrome of Inappropriate ADH=SIADH).
Remember That:
 Diuretics causing Hypokalemia: Thiazides – Loop diuretics – CA inhibitors.
 Diuretics causing Hyperkalemia: Aldosterone antagonists (Spironolactone) and Non-
aldosterone antagonists (Amiloride and Triamterene).
 Diuretics causing Hypochloremic alkalosis: Thiazides and Loop diuretics.
 Diuretics causing Hyperchloremic Acidosis: CA inhibitors (Acetazolamide) and Acidifying
diuretics (NH4Cl).
 Self-Limiting diuretics: CA inhibitors and NH4Cl (due to acidosis).

Diuretics Guide

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Diuretics Guide