Lecture 5.2: Diuretics Flashcards
What is Diuresis?
Increased formation of urine by the kidney
What are Diuretics?
Substances/Drugs that promote Diuresis
What is a Mechanistic Overview of how Diuretics work?
• Increased renal excretion of water AND sodium
• Leads to a reduction of ECF volume
Why are Diuretics used in Clinical Practice?
In conditions where Na⁺ and water retention cause expansion of ECF volume e.g. Heart Failure
How to calculate Total Body Water (TBW)?
0.6 x body weight
What makes up TBW? (2)
• Intracellular Fluid
• Extracellular Fluid
How to calculate Intracellular Fluid (ICF)?
0.4 x bodyweight
How to calculate Extracellular Fluid (ECF)?
0.2 x bodyweight
What makes up the ECF? What percentages of the ECF do they make up? (2)
• Interstitial Fluid (ISF): 75%
• Plasma: 25%
What is Natriuresis?
Increased sodium excretion
What is Kaliuresis?
Increased potassium excretion
What are Aquaretics? Example?
• A substance that causes net excretion of water
• Tolvaptan
What Types of Diuretics affect the PCT and Proximal Straight Tubule? Examples?
• Carbonic Anhydrase Inhibitors
• Acetazolamide
• Cetazolamide
• Methazolamide
What Types of Diuretics affect the Thin Descending & Ascending Loop of Henle? Examples?
• Osmotic Diuretics
• Mannitol
What Types of Diuretics affect the Thick Ascending Limb of the Loop of Henle? Examples?
• Loop Diuretics
• Furosemide
• Bumetanide
What Types of Diuretics affect the Distal Convoluted Tubule? Examples?
• Thiazide Diuretics
• Metolazone
• Indapamide
• Hydrochlorothiazide (HCTZ)
What Types of Diuretics affect the Cortical Collecting Tubule? Examples?
• K+-sparing Diuretics/ Inhibitors of Renal Na+ Channels
• Amiloride
• Triamterene
What Types of Diuretics affect the Collecting Tubule? Examples? (2)
• Na⁺ Channel Blockers: Amiloride
• Aldosterone Antagonists: Spironolactone
Mechanism of Action: Carbonic Anhydrase Inhibitors (Acetazolamide)
• Inhibits action of carbonicanhydrase in brush border &PCT cell
• Can cause metabolic acidosis due to loss of HCO3 in urine
What else are Carbonic Anhydrase Inhibitors used to treat?
• Useful in the treatment of Glaucoma
• Reduces formation of aqueous humour in the eye by about 50%
Mechanism of Action: Osmotic Diuretics (Mannitol)
• Small inert molecules
• Increases plasma osmolarity thus drawing out fluid from tissues & cells (IV
mannitol used to treat cerebral oedema)
• Freely filtered at the glomerulus, but not reabsorbed
• Increases the osmolarity of the filtrate
• Acts by altering the driving force for renal water absorption, which is osmolarity
• Not inhibitors of enzymes or transport proteins
• Causes loss of water, Na⁺ and K⁺ in the urine
Mechanism of Action: Loop Diuretics
• 30% of filtered Na⁺ absorbed via Na-K-2Cl transporter in LoH
• The K⁺ carried across apical membrane drifts back into lumen via K⁺ channels• • Creates a lumen positive potential
• Which helps to also to drive absorption of the positively charged ions Ca2+ and
Mg2+
• Loop diuretics block Na-K-2 Cl transporter
Mechanism of Action: Thiazide Diuretics
• Block Na - Cl transporter in DCT
• Increases Na⁺ (and H2O) loss
• Reduces Ca loss in urine
• Less potent diuretics than loop diuretics
• Only 5% of sodium reabsorption inhibited
• Sodium reabsorbed via NaCl transporter
What types of diuretics can produce life threatening Hyperkalaemia?
• K-Sparing Diuretics
• Aldosterone Antagonists
Mechanism of Action: Aldosterone Antagonists (e.g.spironolactone)
• Antagonise the action of Aldosterone
• Aldosterone acts on Principal cells of Late DT & CD
• ↑ Na reabsorption via ENaC
• Competitive inhibition of aldosterone receptor cause ↓ Na reabsorption
What are ‘Starling’s Forces’?
Movement of fluid across capillary walls is essential for maintaining a continuous exchange of oxygen and carbon dioxide between the body’s cells and the blood supply
Formation of Tissue Fluid: Movement between Intravascular and Interstitial Spaces
1) Capillary Hydrostatic Pressure: pressure due to force of gravity on fluid in the
capillary, pushing fluid out
2) Plasma Oncotic Pressure: osmotic pressure due to non-permeant molecules
such as proteins in the plasma, drawing fluid in
What is capillary hydrostatic pressure mainly influenced by?
Venous pressure in the systemic circulation
Does fluid move out at the arteriole or venous end?
• Fluid tends to move out at arterial end
• Moves in at the venous end
What are some Conditions that cause ECF Expansion and Oedema? (4)
• Congestive Heart Failure
• Nephrotic Syndrome
• Cirrhosis of the Liver
• Portal Hypertension
What is Congestive Heart Failure?
Heart failure is where the heart is unable to pump blood around the body properly and needs treatment to help it work
Why does Oedema build up in Congestive Heart Failure?
• ↑ systemic venous pressure → oedema
• Drop in CO → activation of Renin-Angiotensin System (RAAS) → Na+ & water
retention → expansion of ECF & oedema
How do you treat Oedema build up in Congestive Heart Failure?
• Loop diuretics – e.g. furosemide or bumetanide are 1st choice therapy
• Thiazide diuretics like metolazone are used as an adjunct
What is Nephrotic Syndrome?
Nephrotic syndrome is a condition that causes the kidneys to leak large amounts of protein into the urine
Why does Oedema build up in Nephrotic Syndrome?
Protein loss in urine → low plasma albumin → low oncotic pressure → oedema → reduced circulatory volume → RAS activated → Na & water retention → expansion of ECF & oedema
How do you treat Oedema build up in Nephrotic Syndrome?
• Loop diuretics like furosemide or bumetanide are used
• Thiazide diuretics like metolazone are used as an adjunct
What is Cirrhosis of the Liver?
Cirrhosis is a late-stage liver disease in which healthy liver tissue is replaced with scar tissue and the liver is permanently damaged
Why does Oedema build up in Cirrhosis of the Liver?
Cirrhosis of liver → less albumin production in liver → low plasma albumin → low oncotic pressure → oedema→ reduced circulatory volume → RAS activated → Na & water retention → expansion of ECF & worsening oedema
How do you treat Oedema build up in Cirrhosis of the Liver?
• Spironolactone
What is Portal Hypertension?
• Portal hypertension is elevated pressure in your portal venous system
• The portal vein is a major vein that leads to the liver
Why does Oedema build up in Portal Hypertension?
Portal hypertension → increased venous pressure in splanchnic circulation (high venous pressure + low oncotic pressure) → Ascites → reduced circulatory
volume → RAS activated → Na & water retention → expansion of ECF & worsening oedema
How do you treat Oedema build up in Portal Hypertension?
• Spironolactone
What are some Adverse Effects of Diuretics? (7)
• Primarily Electrolyte Imbalances
• Importantly Potassium Disturbances
• Hypovolaemia
• Hyponatraemia
• ↑ Uric acid levels in blood
• Metabolic Effects
• Erectile Dysfunction (Thiazides)
What Diuretics can cause Hypokalaemia?
• Loop and Thiazide Diuretics
• Increase the loss of potassium in the urine may cause Hypokalaemia
What Diuretics can cause Hyperkalaemia?
• K⁺ sparing Diuretics & Aldosterone Antagonists
• Reduce excretion of potassium in the urine may cause Hyperkalaemia
What are some substances with a diuretic effect?
• Alcohol – inhibits ADH release
• Coffee − ↑GFR and ↓ tubular Na⁺ reabsorption
• Other Drugs: Lithium, demeclocyline − inhibit ADH action on Collecting ducts
What are some Diseases that cause Diuresis? (4)
• Diabetes Mellitus – glucose in filtrate - osmotic diuresis
• Diabetes Insipidus (cranial) – ↓ADH release from post pituitary → diuresis
• Diabetes Insipidus (nephrogenic) – Poor response of Collecting ducts to ADH →
diuresis
• Psychogenic polydipsia (Increased intake of fluid)
