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L21- drug effects on the kidney
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- 1Diuretics- diuretics are drugs that increase the excretion of salt (mainly Nacl) and water by the kidneys.
- they do this by reducing reabsorption of Na+ and Cl- back into the nephron
- this has an osmotic effect, meaning they also decrease reabsorption of water
- even a small decrease in the volume of water not being reabsorbed greatly increases urine volume. - 2Clinical use of diuretics- Oedematous conditions such as renal failiure, renal disease and hepatic disease are treated with loop diuretics.
- Hypertension is treated using thiazide-type diuretics, reducing blood volume and therefore cardiac output. May also dilate arteries. - 3Mechanisms of the clinical uses of diuretics- Oedematous conditions: loop diuretics, K+ sparing diuretics.
Jv= net flux of water across the vascular wall; increased flux causes oedema
- Hypertension: thiazide diuretics; reduce blood volume and cardiac output.
Many diuretics also dilate arteries. - 4Hydraulic and osmotic pressures in the microvasculature
- 5Normal mechanism in the kidney- blood is filtered in the glomerulus, from the blood into the nephron
- Na+ and H2O are reabsorbed back into the blood. Na+ reabsorption is regulated by aldosterone
- that which isn't reabsorbed ends up in the urine, dragging water with it. This is regulated by ADH. - 6Effects of drugs on mechanisms in the kidney.- Diuretics slightly inhibit the reabsorption of sodium, which can have a knock on effect to the amount of water reabsorbed into the blood, leading to a decrease in blood volume.
- 7Sodium reabsorption and how diuretics effect it- at the proximal tubule, 60-70% of Na+ is reabsorbed by H+ moving in
- at he loop of Henle 20-30% of Na+ is reabsorbed by sodium-potassium pumps (this is inhibited by loop diuretics)
- at the distal tubule, 5-7% of Na+ is reabsorbed via the sodium chloride cotransporter.
- at the collecting tubule, ENAC channel, Na+ is reabsorbed (inhibited by K+ sparing diuretics) - 83 types of diuretics and their mechanisms: 1. Loop diureticsLoop diuretics EG furosemide, torasemide, etacrynic acid
Mechanism:
- Block the Na+, K+ and 2Cl- co-transporters in the thick ascending loop of Henle. This causes a powerful diuresis because the kidneys lose their capacity to create a hypertonic medullary interstitium needed to drive ADH induced water reabsorption
Main use:
oedematous condition
Adverse effects:
Hypokalemia, metabolic alkalosis, depletion of plasma Ca2+ and Mg2+, hypovolaemia, ototoxicity (deafness,tinnatius dizzines); occurs if concurrent use w/ antibiotic aminoglycoside - 93 types of diuretics and their mechanism: 2. Thiazide-type diureticsThiazide-type diuretics eg Indapamine, bendroflumethazine, metolazone.
Mechanism:
Thiazide-type diuretics block Na+, Cl- co-transport in the distal convoluted tubule, reducing plasma volume, venous return and cardiac output. They also reduce total peripheral resistance (mechanism unknown).
Adverse effects:
Hypokalemia, hyperglycemia, hyperuricaemia - 103 types of diuretics and their mechanisms: 3. Potassium sparing diuretics- inhibit Na+ uptake and K+ secretion in the collecting tubule, reducing the loss of K+ from the body.
- can cause hyperkalemia if used alone, but using them in conjuction with other diuretics can help prevent this.
- 2 types of K+ sparing diuretics:
Aldosterone receptor antagonists and
Blockers of the epithelial Na+ channel (ENaC)
- main effect is via an active metabolite; 17a-thiomethyl-spironolactone - 11Why do loop diuretics and thiazide diuretics cause hypokalemia?- they inhibit Na+ absorption and K+ secretion at the collecting tubule:
^sodium moving into the cell causes it to become negatively charged, causing K+ to move into the cell, pushing others out via the ROMK channel - 12Effects of aldosterone- aldosterone is a 'mineralcorticoid' steroid hormone that increases Na+ reabsorption and K+ secretion in the collecting tubules.
- It is released from the adrenal cortex by angiotensin II.
- It acts on the cytoplasmic receptors in principle cells of the late distal tubule and collecting duct.
- increases production of aldosterone-induced proteins which act to increase the expression and effect of the Na+ pump and Na+ and K+ channels - 13—
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- L21 pharmacology drug effects on the kidney
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