RENAL - Clinical Pharmacology of Diuretics Flashcards
SEE DRUGS TABLE
SEE DRUGS TABLE
RECAP - Describe some functions of the kidneys.
- Regulation of plasma fluid volume, electrolyte concentrations and osmolarity
- Regulation of acid base balance
- Elimination of waste products (mainly nitrogen containing compounds)
- Conservation of essential nutrients, such as glucose, amino acids and water soluble vitamins
- Production and secretion of hormones
Describe sodium transport in the renal tubular lumen i.e at the early PCT.
- Na+ is being actively pumped from the
ICF across the membrane to the ECF - This creates a decreased Na+
concentration inside the cell activating the
Na+ pumps on the apical membrane - The Na+/ H+ transporter and Na+/ glucose
co-transporter on the apical membrane
move Na+ from the nephron lumen to the
ICF
What is the general way that diuretics work?
- Diuretics increase Na+ (and thus water) excretion via a direct action on the kidney. They work by mainly reducing the re-absorption of salt from the ultrafiltrate.
- Because the salt remains in the ultrafiltrate the solute concentration in the ultrafiltrate is higher than the ICF thus the water remains in the ultrafiltrate and is excreted.
Na+ reabsorption from the renal tubular lumen occurs
via what mechanism?
Active transport via an ion channels
What are the main effects of loop diuretics?
SODIUM RETENTION
- K+ and H+ loss
- Decreased excretion of uric acid
- Increased excretion of Ca2+ and Mg2+
- Moderate vasodilatory effect via prostaglandin release
Post-removal, rebound effect on Na+
uptake from the tubular fluid
List some unwanted effects of loop diuretics
Metabolic alkalosis due to H+ loss
* Depletion of Ca2+ and Mg2+
* Depletion of ECF volume resulting in hypotension
* HIGH IV doses can cause deafness. Nausea and hypersensitivity reactions can occur
Why do thiazide diuretics have less side effects than loop diuretics?
More conservative in ion excretion
- Less side effects
RECAP - What changes to the heart are caused by heart failure?
- Decreased stroke volume and cardiac output
- Increased end-diastolic pressure
- Increased systemic resistance, venous pressure and blood volume
- Decreased arterial pressure and venous compliance
How do diuretics work in heart failure? PART 1
- Mild oedema can be controlled with a thiazide diuretic
- More serious oedema might need a loop diuretic
- Modest doses of loop diuretic are usually enough (if kidney function is ok)
- Where kidney function is compromised large doses might be required
- V. important: Electrolytes must be monitored during treatment
How do diuretics work in heart failure? PART 2
- Diuretics reduce pulmonary oedema caused by left sided heart failure
- When the heart is not able to pump efficiently, blood can back up into the veins that take blood through the lungs.
- As the pressure in these blood vessels increases, fluid is pushed into the air spaces (alveoli) in the lungs.
- Diuretics reduce the peripheral oedema caused by right sided heart failure
How do NSAIDs interact with diuretic use?
May decrease diuretic efficacy
How does thiazid diuretics cause hypocalcaemia?
Thiazide diuretics increase calcium reabsorption in the distal tubule. This increases the activity of the basolateral sodium-calcium antiporter, resulting in sodium ions entering the cell, to then be excreted into the urine.
