Pharmacology 9: Diuretics and drugs in kidney failure Flashcards
You are looking to treat a patient with severe pulmonary and peripheral oedema with a diuretic in hospital, which diuretic might you choose and by which route, and why.
Loop diuretic- potency- inhibit Na+/K+/2Cl- cotransporter in ATL of LOH, so about 5% of Na+ reabsorption inhibited. Bumetanide may be given as has 90% uptake, and with severe oedema, gut wall oedema will compromise furosemide uptake, and give IV as want to have effect quickly.
diuretics used in heart failure?
loop diuretic e.g. furosemide, and bumetanide- better absorption (90%) so may be better if gut wall oedema
thiazide diuretic. High Na+ reabsorption capacity of ATL makes them 1st line for acute relief of pulmonary and peripheral oedema in HF. Reduce pre-load, hence filling pressure on heart, reduce pulmonary oedema.
aldosterone antagonist= K+ sparing= combat ADR of hypokalaemia assoc with loop and thiazide, e.g. spironolactone or eplerenone
diuretics used in hypertension?
thiazide and aldosterone antagonist e.g. spironolactone, possible loop
diuretics used in liver failure?
aldosterone antagonist and loop
diuretic used in Conn’s syndrome?
aldosterone antagonist e.g. spironolactone
why might combination diuretic therapy e.g. loop and thiazide, be used?
patients have oedema which is resitant to tment with 1 diuretic, but vigorous tment, espec with loop, may cause acute hypotension.
why is spironolactone chosen to treat oedema arising from liver cirrhosis?
K+ sparing and hypokalaemia can precipitate encephalopathy that is associated with liver cirrhosis
Other than encephalopathy, what else can diuretics increase the risk of in a patient with alcoholic liver cirrhosis?
arrythmias as increased risk of hypomagnesaemia
why are thiazides usually given at start of day?
so diuresis induced doesn’t interfere with sleep
mechanism of action of thiazide diuretics?
inhibit Na+/Cl- co-transporter at beginning of DCT, so more Na+ and H20 excreted from body. This lowers circulating blood volume, hence preload of heart, force of myocardial contraction and SV, so CO reduced and aBP reduced.
so at low doses used in hypertension.
can be used in chronic heart failure to reduce oedema if mild HF and renal function intact.
ADRs of thiazides?
postural hypotension
hypokalaemia *increased tubular flow rate, increased K+ secretion by principal cells as more Na+ to move through ENaC, creating +ve luminal potential for K+ movement out into filtrate.
hypercalcaemia
hyponatraemia
gout- hyperuricaemia
hyperglycaemia- possibly due to drug-induced impairment of insulin secretion and/or reduced insulin sensitivity
erectile dysfunction
example of a thiazide diuretic used in mild to moderate heart failure
bendroflumethiazide
when might a thiazide diuretic be used in heart failure?
if mild to moderate HF and good renal function, but ineffective in patients with eGFR of < 30ml/min
why is the natriuresis produced by thiazides less than that produced by loop diuretics?
thiazides act downstream to loop, where 90% of Na+ reabsorption has occurred upstream of their site of action
how might thiazides decrease BP, other than inhibiting Na+/Cl- reabsorption at the DCT?
direct vasodilatory effect
The DCT is a site of PTH regulated reabsorption of Ca2+, how do thiazides promote increased transcellular Ca2+ reabsorption?
By inhibiting Na+ reabsoprtion, there is increased activity of NCX on BL membrane as more Na+ moved into cell from ECF down conc gradient as less Na+ in cell from movement across apical membrane, so more Ca2+ moved into ECF.
Also, reduced Na+ reabsoprtion creates -ve luminal potential promoting Ca2+ movement across apical membrane into cell, and then across BL membrane into ECF.
why should thiazides not be administered alongside anti-arrhythmic agents that prolong the QT interval e.g. amiodarone?
as predispose to torsades de pointes, possible due to thiazide induced hypokalaemia which increases risk of cardiac arrhythmias.
key kidney functions in terms of REEM?
regulatory- fluid balance, electrolyte balance, acid-base
excretory- waste products and drugs- glom filtration and tubular secretion
endocrine- erythropoietin, RAAS and PGs
metabolic- Vit D and polypeptides- insulin and PTH
5 actions of Ang II?
activate SNS stimulate aldosterone release increase Na/CL reabsorption by PCT of kidney increase ADH release arteriolar vasoconstriction
3 factors that stimulate renin release?
reduced perfusion pressure to kidney
SNS activation
reduced NaCl delivery to DCT
