Diuretics Flashcards
What are diuretics?
Drugs inducing a state of increased urine flow and output
What are the main functions of the nephron?
Filtration, reabsorption, secretion and excretion
Reabsorption of salt is under control of?
aldosterone
Water is under control of?
vasopressin
How do diuretics work?
- diuretics are ion transport inhibitors that decrease the reabsorption of Na+ at different sites in the nephron
- Other electrolytes involved are Cl-, HCO3-, K+ - To maintain an osmotic balance the increased excretion of electrolytes is accompanied by increase in water excretion
What physiological changes do diuretics do to the body?
- increase the volume of the urine
- often change pH of urine
- change the ionic composition of the urine and blood
- change the levels of Na+, Cl-, HCO3-, K+
- cause side effects related to changes of
above electrolytes and others
- cause side effects related to changes of
How much fluid is filtered everyday?
180L of fluid
Where does filtration take place?
glomerulus
- plasma proteins and lipids are not filtered
Urine formation starts from?
glomerular filtration
- More than 99% of the glomerular filtrate is
reabsorbed in the tubules
How much urine is produced in 24 hours?
1.5L
Describe the normal amount of urine produced by a person?
1–2 litres per 24 hours
- highly variable depending on fluid intake and water loss through the skin and GI tract
What is the colour of normal urine?
- Straw or amber
- darker means more concentrated
- should be clear
- not cloudy
Describe the specific gravity of normal urine?
- 01–1.025
- a measure of the dissolved material in urine
- the lower the value, the more dilute the urine
Describe the pH of normal urine?
Average 6
- range 4.6–8.0
- diet has the greatest effect on urine pH
Describe the composition of normal urine?
95% water; 5% salts and waste products
Describe the nitrogenous waste present in normal urine?
- Urea—from amino acid metabolism
- Creatinine—from muscle metabolism
- Uric acid—from nucleic acid metabolism
Tubular reabsorption can be divided into 4 sites?
Site I: Proximal tubule
Site II: Ascending limb of loop of Henle
Site III: Cortical diluting segment of loop of Henle (descending)
Site IV: Distal tubule (DT) and collecting duct (CD)
What are the main kidney functions?
- Cleansing of extracellular fluid (ECF) and maintenance of ECF volume and composition
- affected by diuretics the most
- Maintenance of acid-base balance
- Excretion of metabolic wastes and foreign substances (eg, drugs, toxins)
Describe the application of diuretics?
- treatment of hypertension
- mobilization of oedematous/interstitial fluid associated with heart failure, cirrhosis, or kidney disease
- prevent renal failure
The relative magnitudes of Na+ reabsorption at different tubular sites are?
- PT 65–70%;
- Asc LH 20–25%;
- DT 8–9%;
- CD 1–2%.
Describe the diuretics that act on the proximal tubule?
these agents are either too weak or cause distortion of acid-base balance
Diuretic agents may include?
- carbonic acid anhydrase inhibitors
- loop diuretics
- thiazides
- K+ sparing diuretics
- osmotic diuretics
- Anti-diuretic hormone antagonists
- These agents work on different sections of the nephron
- It depends on processes affected and the types of electrolytes involved
What is the mechanism of action of diuretics?
Increases renal excretion of Na+ & H20
- Cellular action of diuretics is to reduce the reabsorption of Na+ with increased H2O loss occurring as a consequence
- causing Na+ retention (in lumen): ↓H2O reabsorption (↑urine volume)
What is the mechanism of action of carbonic anhydrase inhibitors?
inhibit the enzyme carbonic anhydrase in the proximal tubular epithelial cells
What is the function of carbonic anyhdrase?
is an enzyme which catalyses the reversible reaction H2O + CO2 -> H2CO3
- which spontaneously ionizes into H+ + HCO3
- only mild diuresis action
Where is carbonic acid anhydrase found?
- renal tubular cell (especially PT)
- gastric mucosa
- exocrine pancreas
- ciliary body of eye
- brain
- RBC
What are the therapeutic uses of carbonic acid anhydrase inhibitors?
- glaucoma
- epilepsy
- mountain sickness
- to alkalinise urine
- for urinary tract infection
- to promote excretion of certain acidic drugs
What are the side effects of carbonic anhydrase inhibitors?
- metabolic acidosis (mild)
- metabolic alkalosis
- hypokalemia
- renal stone formation
- drowsiness
- abnormal taste
- decreased libido
- lethargy
- paresthesia
What medications interact with carbonic anhydrase inhibitors?
- Aspirin/ salicylates
2. K+ depleting agents
What are the consequences of the interactions between CAAI and aspirin/salicylates?
acetazolamide induced acidosis:
- lethargy
- confusion
- coma
What is the consequence of the interaction between CAAI and K+ depleting agents?
induction of hypokalemia aggravated
Loop diuretics are also known as?
high ceiling diuretics
How much urine can be produced under loop diuretics?
up to 10L of urine in 24hrs
What is the mechanism of action of loop diuretics?
inhibits Na+- K+-2Cl¯ cotransport mainly on the Ascending Loop of Henry, therefore, reabsorption of Na+, K+, and CI- is decreased
Name the 4 loop diuretics?
- Furosemide
- Bumetanide
- Torsemide
- Sulphonamides
- Ethacrynic acid
- Not a sulphonamide derivative
- Derived from azo dyes
What are the therapeutic uses of loop diuretics?
- pulmonary edema - associated with CHF, 2. acute pulmonary edema (cardiac, hepatic or renal)
- hypertension
- Hypercalcaemia of malignancy
What are the side effects of loop diuretics?
1. Hypokalemic metabolic alkalosis
(concomitant use of K+ sparing diuretics/ or
K+ supplements)
2. Hyperuricemia
3. Ototoxicity
4. acute hypovolemia
5. hypokalemia (shock, hypotension,
arrhythmias)Describe the administration of Lasix?
Lasix is rapidly absorbed orally and could be administered both oral and parenteral
Describe the pharmacokinetics of loop diuretics?
- Duration of action is within 6 hrs, and has got rapid onset
- Oral route: Onset 60 min; peak 60–120 min + duration 6–8 h
- IV : Onset 5 min; peak 30 min + duration 2 h
- T½: 120 min - metabolized in the liver and excreted in urine
What drugs do loop diuretics interact with?
Aminoglycosides, cephalosporines, sulfonamides or quinolones; plasma protein binding displaced by warfarin
Describe the contraindications of loop diuretics?
Hypersensitivity to sulphonamides
Hepatic coma
Renal failure
Hypokalemia
What is the mechanism of action of Thiazides?
Inhibitors of Na+-Cl¯ symport
- moderately efficacious diuretics
- site of action mostly at segment III
- they also inhibit urinary calcium excretion
What are the therapeutic uses of Thiazides?
Hypertension; CHF; hypercalciuria; nephrogenic diabetes insipidus
What are the side effects of Thiazides related to diuretic effect?
Hypokalaemia Metabolic alkalosis Hyponatremia Hypovolemia & hypotension Hypomagnesemia Hypercalcemia
What are the side effects of Thiazides not related to diuretic effect?
Hyperuricemia
Hyperglycemia
↑LDL & cholesterol (hyperlipidaemia)
Impotence
What are the pharmacokinetics of Thiazides?
- Take time to produce stable reduction in BP
- 1 to 3 weeks
- prolonged t1/2 about 40 hrs
- exhibit poor absorption (hydrochlorothiazide)
- Oral route: Onset 2 h; peak 4–6 h; duration 6–12 hr
- T½: 5.6–14 h
- metabolized in the liver and excreted in urine
What drugs do Thiazides interact with?
Cardiac glycosides; Antidiabetic agents; Lithium; Uricosuric agents; NSAIDs; K+ depleting agents
What are the contraindications of Thiazides?
Severe renal/hepatic impairment
Hypokalemia
Pre-existing hypercalcemia
Hypersensitivity to thiazides /other sulphonamide derivatives
What is the mechanism of action for osmotic diuretics?
reduce water reabsorption resulting in a subsequent decrease of sodium reabsorption
e.g. mannitol
