Volume Regulation

1. Pathophys

1.1. ec volume expansion- renal sodium retention, HF- perceieved vol depletion- activated RAAS and increased act of SNS and increased venous p--> oedema Hepatic Cirrhosis- disrupted hepatic venous outflowk portal hypertension, activation of RAAS Renal Impairment- decreased GFR- hypoalbuminemia-low plasma oncotic P- fluid into interstitium- decreased vasc vol- sodium retention

2. Renin Inhibitors

2.1. Aliskerin-effective antihypertensive, casues hypoT and reversible renal impariment and reduces GFR, contraindicated in pregnancy, low oral bioavailability

3. Ace Inhibitors

3.1. Captopril, enalopril and ramipril (prodrugs) and Lisinopril

3.2. Reduced vasoconstriction and increased natriuresis, HT HF and MI, bradykinin dry cough, HypoT initially, reversible renal impairment hyperkalemia (reduced aldosterone), can reduce GFR

4. Ang II receptor Antagonists

4.1. Losartan, Candesartan and Valsartan-oral, 6-8-10 t1/2s, like ACE-Is without dry cough,

5. Diuretics

5.1. Increase urine flow, decrease sodium absorption at different sites in the nephron, na and cl in urine more and water

6. Thiazides- DCT

6.1. MOA- inhibit Na/Cl tporter in apical memb of DCT HYDROCHLOROTHIAZISE< BENDROFLUMETHIAZIDE< CHLORTALIDONE increased excretion of Na and Cl, loss of K and decreased Ca excretion (reabsorp unlike loop), also VasoD properties, first line hyperT, oedema S/Es- K depletion (arrhythmias), Vol depletion, HyperCa, Hyperglyc, Hypersens

7. Volume reg vs Free water reg

7.1. Volume reg: effectors- SNS, ADH and RAAS; Affected- Na reabsorption, VasoC and H2O retention

7.2. Free water reg: effectors- thirst and ADH, Affected- free water intake via thirst and adh-dependent free water retention by kidney

8. Increased EC vol- oedema accum of fluid in interstitial space

9. Carbonic Anhydrase Is- PCT

9.1. ACETAZOLAMIDE, reversible inhibits type 2 and 4 increased delivery of Na and HCO3 to distal nephron, intially decrease plasma vol, weak effect on Na retention, us limited due to metabolic acidosis

10. Loop Diuretics

10.1. MOA- reversibly inhibit NA/K/2CL cotransporter in luminal memb of LOOP OF HENLE FUROSEMIDE, BUMETANIDE reduction in NA and CL absorp and paracellular reduction in Ca and Mg reduce tonicity of medullary interstitium and inhib reabsorp of water in collecting duct Uses-reduced acute pulm oedema of CHF, acute renal f, hypoalbum oedema, hypercalcemia S/Es- HypoK, HypoCa, acute Hypovolemia,

11. Potassium Sparing- Cortical Collecting Duct

11.1. enhanced aldosterone here, MOA- increase NA excretion in principal cells 1) NA channel blockers- Amiloride and Triamterene (A- blocks luminal Na channels, inhibits Na reabsorp, reduced K secretion and reduced H secretion- HyperK, Metab Acidosis, GI upset) 2)Aldosterone Antagonists- Spironolactone and Eplerenone (competes with aldosterone for IC receptors, preventing txn of new Na channels) (S/Es- binds to other steroid Rs in Spiro and causes gynaecomastia, ED, menstrual disorders and hirsutism)

12. Osmotic Diuretics

12.1. Pharm Inert, indirect act- modify content of filtrate by increased osm eg Mannitol- used for treatment of cerebral oedema as dont enter cells or BBB- when admin conc slution water leaves cells down osmotic gradient