Diuretics and Bladder control Flashcards
how do loop diuretics work?
block the NaKCl symporter in the thick ascending limb of the LOH. this prevents the generation of a hyperosmotic medulla as it inhibits reabsorption of 25% filtered Na. (water would follow)
cause natriuresis so lose Na into lumen. because of the symporter disturbance, electrochemical gdnt altered so less able to reabsorb Mg and Ca by paracellular diffusion
give 2 examples of loop diuretics
frusemide and torasemide
what are the net effects of using loop diuretics?
loss of Na/ K/ Cl/ Ca/ Mg and H + water
causes hyponatraemia and ECF volume depletion (intravascular important), hypoK, hypoCl (alkalosis), hypoCa and hypoMg
what are the indications for loop diuretics?
CHF - IV emergency, orally once stable. (poor CO + low BP are detected and compensation is to increase circulating volume - pulmonary oedema (heart)). could use in hyperCa/ K, udder oedema, acute kidney injury etc
what are the pharmacological properties of frusemide?
actively secreted into the lumen. approx half excreted unchanged in urine. IV faster acting than oral. sigmoid response - threshold required but will reach a plateau response
what are the adverse effects of frusemide?
fluid and electrolyte balance. also GIT disturbances, ototoxicity in cats. reduction in volume will activate RAAS.
how can we overcome the adverse effects of frusemide?
monitor electrolytes and kidney function, use K sparing diuretics or use supplements. avoid nephrotoxic drugs
what is the cause of hypokalaemia?
loop diuretics and thiazide diuretics increase Na delivery to the DCT. this stimulates the aldosterone sensitive pump to compensate by exchanging Na for K (+H+). this is therefore lost in urine and could cause metabolic alkalosis.
where do thiazide diuretics work? and on what?
DCT on the Na/Cl symporter
how does the Na/Cl pump usually work?
by secondary active transport driven by ATPase
what is the net effect of thiazide diuretics?
moderate diuresis as most already absorbed, hypoK but Ca absorption enhanced
give an example of a thiazide
hydrochlorothiazide
what are the indications for use of thiazides?
CHF, sequential nephron blockade
also calcium oxalate urolithiasis as less Ca in filtrate because more absorbed.
describe the pharmacology of thiazides
excreted renally via secretion into tubular lumen, but reduced efficacy if renal blood flow compromised.
Given orally and formulated with a k sparing diuretic e.g. amiloride
what are the adverse effects of thiazides?
fluid and electrolyte disturbances - hypoNa + ECF depletion, hypoK, hypoCl alkalosis. CNS and GI signs uncommon
how can the adverse effects of thiazides be overcome?
monitor electrolytes and renal function, titrate upwards slowly to effect, consider use of K sparing diuretic/ supplement.
give 2 classes of K sparing drugs
Na channel blockers (different to Na/Cl symporter)
aldosterone antagonists
what are the effects of K sparing drugs?
retention of K and loss of Na/ Cl (water)
most modest diuretics. Combine with others for sequential nephron blockade)
give an example of a sodium channel blocker
amiloride
what are the indications for use of amiloride?
used in combo with loop or thiazide diuretics, CHF, K-sparing effect. works in DCT.
reaction of kidney in response to diuresis is to swap Na for K. blocks this mechanism
how is amiloride administered and what are the adverse effects
orally and in combo with thiazide.
adverse effects = hyperK, hypoNa and decreased ECF
give an example of an aldosterone antagonist
spironolactone
how does spironolactone work
binds to aldosterone receptor in cytoplasm. receptor-hormone complex moves to nucleus, targets DNA sequence to produce proteins that would upregulate Na reabsorption (channels). drug blocks receptor and is therefore K sparing. It also acts on the myocardium to inhibit aldosterone mediated fibrosis and remodelling.
what are the indications of spironolactone?
CHF, diuretic effect only when RAAS activated
what is the pharmacology of spironolactone?
no secretion into tubule required to have effect (intracellular)
orally administered alone or with benazepril (ACE inhibitor)
what are the adverse effects of spironolactone?
hyperK, hypoNa and reduced ECF, may bind to other steroid hormone receptors (sex) and poss facial dermatitis
how do carbonic anhydrase inhibitors work?
inhibit production of protons and carbonic acid. therefore less HCO3 for reabsorption and less H+ for exchange with Na. (Na/K) short acting. used for glaucoma
name an osmotic diuretic
mannitol
describe the properties of mannitol
hypertonic solution so diuresis due to osmotic effect; filtered at glomerulus and remains in tubule. pulls water in. given IV and has effects in all tissues - used in head trauma to reduce IC pressure and glaucoma
what is the pH of herbivorous/ carnivorous animals?
alkaline/ acid
why would urine pH be manipulated?
to reduce development of uroliths
what type of uroliths occur in alkaline urine? how would you acidify urine?
struvite uroliths form in alkaline pH, urine acidification dissolves and prevents formation.
diet/ NH4Cl
what type of uroliths form in acid urine? how does alkalinification occur?
oxalate, cysteine and urate uroliths form in acid urine.
diet/ K citrate
what types of muscle make up the urethral sphincter and urethra
smooth/ skeletal
what is the most common condition with insufficient urethral sphincter tone? and how is it treated
incontinent dogs (bitches) decreased urethral closure pressure. Give alpha-adrenergic agonists e.g. oestrogen/ testosterone. will increase density and sensitivity of receptors.
what is the most common condition with excessive urethral muscle tone? how is it treated?
urethral spasm in cats, must relax sm (prasozin, ACP) and skeletal (dazepam) adjunctive treatment would be analgesia, sufficient water intake and stress relief.
what type of muscle fibre make up the detrusor muscle?
smooth
what does activation of the parasymp NS cause in the detrusor muscle
contraction and therefore urine voiding
what would you use to treat bladder atony?
parasympathomimetic drugs. mimic function of Ach, SE = cholinergic (parasymp)
how would you treat detrusor instability (hyperexcitability)
parasympatholytics - block action of Ach and cause bladder relaxation.
