diuretics pna---pdf
TRANSCRIPT
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