DIURETICS PNA---PDF

DIURETICS

PRESENTED BY:-

PRASHANT N. AMALE

M.PHARM- (PHARMACOLOGY)

DEPARTMENT OF PHARMACEUTICAL SCIENCES RTMNU.

KIDNEY

• Kidney

– Excretion of wastes

– Acid-base homeostasis

– Osmolality regulation

– Blood pressure regulation

– Hormone secretion

• Functional Unit

– Nephron

RENAL PHYSIOLOGY

• Renal processes

– Filtration

• At glomerulus (GFR)

– Reabsorption

• Water, electrolytes

– Active tubular secretion

• Organic acids

and bases

3/5/2016 Free Template from www.brainybetty.com 5

= GLOMERULAR HYDROSTATIC PRESSURE (60 mmHg)

= BLOOD COLLOIDOSMOTIC PRESSURE(32 mmHg)

=CAPSULAR HYDROSTATICPRESSURE (18 mmHg)

NET OUTWARD = 60-18-32PRESSURE = +10 mmHg

FLOW OF GLOMERULAR FILTRATE

GLOMERULUS BOWMAN’S SPACE IN BOWMAN’S CAPSULE

PROXIMAL CONVOLUTED TUBULE (PCT)

DISCENDING LIMB OF LOOP OF HENLE (DCT)

ASCENDING LIMB OF HENLE’S LOOP (AscLH)

. DISTAL CONVOLUTED TUBULE

RENAL PELVIS COLLECTING DUCT

TUBULAR REABSORPTION & SITE OF DRUG ACTION

From Knauf & Mutschler Klin. Wochenschr. 1991 69:239-250

70%

20%

5%

4.5%

0.5%Volume 1.5 L/dayUrine Na 100 mEq/LNa Excretion 155 mEq/day

100%GFR 180 L/day Plasma Na 145 mEq/LFiltered Load 26,100 mEq/day

CA InhibitorsProximal tubule

Loop DiureticsLoop of Henle

ThiazidesDistal tubule

Antikaliuretics

Collecting duct

Thick Ascending Limb

Diuretics

Classification of Diuretics

Site 1 Proximal Convoluted Tubule (PCT)-Carbonic Anhydrase Inhibitors

Site 2 Loop of Henle (LH )- Loop diuretics

Site 3 Distal convoluted tubule (DCT)- Thiazide

Site 4 Collecting Duct (CD)- Potassium sparing diuretics

CARBONIC ANHYDRASE INHIBITORS (Acetazolamide(Oral) ; Dorzolamide (Ocular) ; Brinzolamide (Ocular)

Mechanism of action :-Simply inhibit reabsorption of sodium and bicarbonate.

It prevents the reabsorption of HCO3 and Na

•Inhibition of HCO3 reabsorption metabolic acidosis.•HCO3 depletion enhance reabsorption of Na and Cl hyperchloremia.•Reabsorption of Na ↑ negative charge inside the lumen ↑K secretion

SIDE EFFECTS OF ACETAZOLAMIDE:

Sedation and drowsiness; Hypersensitivity reaction (because it contains sulfur)Acidosis (because of decreased absorption of HCO3)

Renal stone (because of alkaline urine); Hyperchloremia, hyponatremia and

hypokalemia

1. OSMOTIC DIURETICS (E.G.: MANNITOL)

Mechanism of action: They are hydrophilic, that are easily filtered through the glomerulus with little re-absorption and thus increase urinary output via osmosis.PK: Given parentrally. If given orally it will cause osmotic diarrhea.

Adverse Reactions:- Extracellular water expansion may complicate heart

failure & produce pulmonary edema.- Dehydration

- Hypernatremia due to loss more water than sodium

B. Loop Diuretics :- Furosemide,Torsemide,Bumetanide

Dosage of loop diuretics:Furosemide 20-80 mgTorsemide 2.5-20 mgBumetanide 0.5-2.0 mg

Loop diuretics

Furosemide:

Taken orally or i.v

If taken orally only 50 % is absorbed

Torsemide:

Taken orally.

Better absorption

Fast onset of action

2/1t↑

Bumetanide (Bumex®)

Taken orally

40 times potent than furosemide.

Fast onset

Short duration of action

Hypokalemia, metabolic alkalosis, hypercholesterolemia, hyperuricemia, hyperglycemia, hyponatremiaDehydration and postural hypotensionHypocalcemia (in contrast to thiazides)HypersensitivityOTOTOXICITY (especially if given by rapid IV bolus)

ADVERSE EFFECTS OF LOOP DIURETICS

C. THIAZIDES :- Hydrochlorthiazide

THIAZIDES - PHARMACOKINETICS

• Rapid GI absorption

• Distribution in extracellular space

• Elimination unchanged in kidney

• Variable elimination kinetics and therefore variable half-lives of elimination ranging from hours to days.

SIDE EFFECTS OF THIAZIDES

• HYPERLIPIDEMIA; mechanism unknown but cholesterol increases usually 1% increase

• IMPOTENCE

• HYPONATREMIA due to thirst, sodium loss, inappropriate ADH secretion (can cause confusion in the elderly),

• HYPERSENSITIVITY

D. DIURETICS THAT INHIBIT TRANSPORT IN THE

CORTICAL COLLECTING TUBULE (e.g. potassium sparing diuretics).

Classification of Potassium Sparing Diuretics:

A) Direct antagonist of mineralocorticoid receptors (Aldosterone Antagonists e.g spironolactone

(AldactoneR) or

B) Indirect via inhibition of Na+ influx in the luminal membrane (e.g. Amiloride, Triametrene)

Spironolactone (AldactoneR)►Synthetic steroid acts as a competitive antagonist of

aldosterone with a slow onset of action.

► Mechanism of action:►Aldosterone cause ↑K and H+ secretion and ↑Na

reabsorption.

►The action of spironolactone is the opposite

SIDE EFFECTS ►Hyperkalemia (some times it’s useful other wise it’s

a side effect).► Hyperchloremic (it has nothing to do with Cl)

metabolic acidosis►Antiandrognic effects (e.g. gynecomastia: breast

enlargement in males, impotence) by spironolactone.

►Triametrene causes kidney stones.

Clinical Uses of K+ sparing Diuretics:-In states of primary aldosteronism (e.g. Conn’s syndrome, ectopic ACTH production) of secondary aldosteronism (e.g. heart failure, hepatic cirrhosis, nephrotic syndrome)– To overcome the hypokalemic action of diuretics– Hirsutism (the condensation and elongation of female

facial hair) because it is an antiandrogenic drug