Transcript Diuretics in Eng

Diuretic drugs
Assoc. Prof. Ivan Lambev ([email protected])
Diuretics exert their effect directly on the
kidneys. Most of them lead to electrolyte
excretion and
Hydrochlorothiazide
consequently to
Chlorthalidone
Indapamide
osmotic excretion
of water, which
increases the
24-hr
Mannitol
urine volume.
Amiloride
Triamterene
Spironolactone
Acetazolamide
Furosemide
Furosemide
Torsemide
Torsemide
1. Salidiuretics
(thiazides and their analogues)
They increase equivalently Na+ and Clexcretion (1:1) in distal renal tubules and
this increases diuresis. They lead to
excretion of 5 to 10% from filtrated Na+ ions
and have moderate diuretic action. They
can be classified as sulfonamides with free
–NH2 group, without antimicrobial activity.
Salidiuretics (saluretics)
Thiazides
Thiazide analogues
•Hydrochlorothiazide
•Cyclopenthiazide
•Clopamide
•Chlorthalidone
Vasodilators with antihypertensive effect
•Indapamide (stimulates synthesis of renal PGs
with vasodilating action)
Indapamide SR
(does not have
metabolic effects)
•cardioprotector
•nephroprotector
Hydrochlorothiazide
Chlorthalidone
Indapamide
5–10%
Thiazides have a weak antihypertensive
effect because they reduce arterial wall sensitivity
to NA (noradrenaline) and AT (Angiotensin).
They potentiate significantly the effect
of other antihypertensive drugs.
Thiazides increase plasma renin levels.
Reduction of plasma Sodium and
osmolarity leads to “paradoxal”
antidiuretic effect in diabetes insipidus.
Adverse reactions (ARs) of saluretics:
Hypokalemia and enhancing therapeutic and
toxic effects of CGs, hypochloremic alkalosis,
GI disorders, skin rashes and photosensibilization, muscle weakness and fatigue, hyponatremia, hypoglycemia, increased plasma level
of uric acids, hypercholesterolemia, impotence.
Thiazides decrease GF (glomerul filtration).
They reduce plasma volume in pregnant
women and decrease fetal oxygenation (PRC: D).
2. Loop Diuretics
Furosemide has p.o. bioavailability 65%
and t1/2 30–60 min. It acts on the ascending
limb of Henley's loop by increasing
urine excretion of Na+, Cl, Mg2+ and
Ca2+. Its diuretic effect is achieved in
20–30 min after p.o. administration
and lasts 4–6 h. Its effect after i.v.
administration begins in 3–5 min and
lasts 2 h. In low doses (5 to 10 mg p.o.)
furosemide has antihypertensive effect.
It does not disrupt GF.
Furosemide – indications:
Oedemas of different origin, acute ischemic
renal failure (in high DD, together
with mannitol), anuria and eclampsia, forced
diuresis in acute intoxications, hypertension,
resistant cardiac failure.
Furosemide enhances the action
of antihypertensive drugs and
non-depolarazing neuromuscular blockers.
Furosemide – ARs:
Hypokaliemia, skin rashes, hyperglycemia,
increased plasma levels of uric acid.
In fast i.v. administration – transient
hearing disturbances with temporary
deafness and orthostatic collapse.
Ototoxic risk is increased in co-medicaton
with aminoglycosides, cephalosporines,
polymyxins, sulfonamides or quinolones.
3. Carbonic anhydrase inhibitors
Acetazolamide inhibits carbonic
anhydrase (CA) mainly in proximal tubules.
H2O + CO2
CA
H2CO3
H2CO3– + H+
Acetazolamide has weak diuretic action.
It significantly enhances urine K+ excretion.
The loss of HCO3– anions decreases blood
alkaline reserve (for 48–72 h) and causes
metabolic acidosis. In this state the drug
becomes ineffective.
Acetazolamide blocks not only renal CA, but
also CA in the ciliary body in the eye
(reducing production of eye liquid) and in the
brain (facilitates GABA synthesis).
4. Potassiumsparing diuretics
Amiloride
Triamterene
Spironolactone
3%
They have weak
diuretic action
and save K+.
Often they are used
in combination with
diuretics, causing
hypokalemia.
Potassium-sparing diuretics
Competitive
aldosterone
antagonists:
Blockers of the
amiloride-sensitive
Na+ channels:
•Spironolactone
•Amiloride
•Triamterene
Spironolactone is a steroid compound,
which is a competitive aldosterone antagonist.
It increases Na+ excretion and decreases K+
and urea excretion. Its diuretic action is
weak and is achieved slowly.
Spironolactone is effective in oedemas,
caused by increased production of
aldosterone ascites in liver cirrhosis and
oedemas in congestive heart failure.
Spironolactone in low doses (25 mg/24 h)
potentiates the effect of ACE inhibitors. It
saves K+ and Mg2+ ions and has antiarrhythmic effect. It also prevents the development of
myocardial fibrosis, caused by aldosterone
and in this way contributes to enhancing
myocardial contractility.
Diuretidin®
(triamterene/hydrochlorothiazide)
is indicated in oedemas cardiac, renal,
liver or other origin and for the
treatment of hypertension with
other antihypertensive drugs.
®
Moduretic
(amiloride/hydrochlorothiazide)
has the same indications too.
5. Osmotic diuretics
60–80%
After oral administration Mannitol is not
absorbed and has laxative effect. After i.v.
administration it is not metabolized, it
filtrates in the glomerulus and not reabsorbed
in renal tubules, causing increased osmotic
pressure and excretion of isoosmotic equivalent
of water. It increases blood flow in 30%.
Мannitol does not influence renin synthesis.
It does not cross tissue barriers (BBB neither),
does not penetrate to the eye and brain and
in osmotic way reduces intraocular and intracranial pressure.
It is included in the treatment of brain oedema,
initial stages of acute renal failure, chronic
renal failure, glaucoma, intoxications with
drugs, excreted in the urine.
6. Phytodiuretics
Rhizoma Graminis
(Couch-grass)
Stipites Cerasorum
(Cherry)
Fructus Faseoli sine semine
(Haricot)
Fructus Petroselini
(Parsley)
Stigmata Maydis
(Maize, corn)
Rubia tinctorum L. (madder). Radix Rubiae
contains 2–3% di- or trioxyanthraquinones
glycosides, flavonoids and other bioactive
substances with diuretic, urolitholytic and
spasmolytic effects.
Infusions (1:10) made from madder facilitate dilution
of calculi, containing calcium and magnesium sulfate
in the renal pelvis and bladder.
It is an important ingredient of many phytoproducts
(Cystenal©, Rowatinex©), indicated in urolithiasis.