Pharmacology Flashcards
four sites of diuretic action in the nephron
- PCT
- thick ascending loop of Henle
- early DCT
- collecting duct
transporters in the PCT
Na+ (passive Cl- absorption)
Na+/H+ exchange
what blocks Na+/H+ exchange in the PCT and early DCT?
carbonic anhydrase inhibitors
what transporter is present in the thick ascending loop of Henle?
Na+/K+/2Cl- co-transporter
what blocks the Na+/K+/2Cl- co-transporter in the thick ascending loop of Henle?
loop diuretics
transporters in the early DCT
Na+/H+ exchange
Na+/Cl- co-transport
what blocks Na+/Cl- co-transporter in the early DCT?
thiazides
transporter present in collecting ducts
Na+/K+ exchange
what blocks Na+/K+ exchange in the collecting duct?
potassium-sparing diuretics
two ways diuretics can enter the filtrate?
- glomerular filtration
2. secretion
which drugs can enter the filtrate by glomerular filtration?
drugs not bound to large plasma proteins
two transport processes that secrete components into the filtrate
- organic anion transporters (OATs)
2. organic cation transporters (OCTs)
which drugs can enter the filtrate via OATs?
acidic/negatively charged
PAH, thiazides and loop
which drugs can enter the filtrate by OCTs?
basic/ positively charged
triamterene and amiloride
examples of loop diuretics
furosemide
bumetanide
action of loop diuretics
inhibit Na+/K+/2Cl- in PCT by binding to the Cl- site
what do loop diuretics cause excretion of?
Na+
K+
Ca2+
Mg2+
when are loop diuretics contra-indicated?
severe hypovolvaemia
dehydration
adverse of loop diuretics
hypokalaemia (use potassium-sparing diuretics) metabolic alkalosis (Na+/H+ transporter) hypocalcaemia hypomagnesemia hypovolaemia hyperuricaemia dose-related hearing loss
example of a thiazide diuretic
bendroflumethiazide
action of thiazide diuretics
inhibit Na+/Cl- binding to Cl- site in early DCT
what do thiazides cause in the body?
increases Na+ in the collecting duct causing K+ loss and reabsorption of calcium
adverse of thiazides
hypokalaemia metabolic alkalosis hypovolaemia hypomagnesemia (not calcium so used in elderly with OP) hyperuricaemia ED impaired glucose tolerance in diabetes
what receptors does aldosterone act on?
cytoplasmic receptors
action of aldosterone
increases synthesis of a protein that activates ENaC and Na+/K+ATPase
examples of potassium-sparing diuretics
spironolactone and eplerenone
why do potassium-sparing diuretics have limited diuretic action?
modulated by aldosterone
action of potassium-sparing diuretics
antagonists of aldosterone receptor so increase excretion of Na+ while decreasing excretion of K+
action of amiloride and triamterene?
block luminal Na+ channels in collecting duct
when are potassium-sparing diuretics contraindicated?
severe renal impairment
hyperkalaemia
Addison’s
example of osmotic diuretic
mannitol
how do osmotic diuretics enter the filtrate?
glomerular filtration
where do osmotic diuretics act?
PCT
when are osmotic diuretics used?
acutely raised ICP and IOP
prevention of acute hypovolaemia in renal failure to maintain UO
adverse of osmotic diuretics
transient expansion of blood volume
hyponatraemia
examples of CA inhibitors
acetazolamide
action of CA inhibitors
increase excretion of HCO3-
when are CA inhibitors used?
glaucoma
following eye surgery
dysuria to prevent uric stones
example of a vaptan
tolvaptan
action of vaptans
competitive antagonists of ADH receptors which causes excretion of water without accompanying Na+ loss as it acts in the collecting duct
when are vaptans used?
SIADH to correct hyponatraemia
where is glucose reabsorbed in the nephron? and which transporter?
PCT by SGLT2
when does glucose appear in the urine?
concentration exceeds threshold
example of SGLT2i
empagliflozin
action of SLGT2i
excretion of glucose
weight loss
adverse of SGLT2i
genital bacterial and fungal infections
prostaglandins in the kidneys
PGE2
PGI2
what do prostaglandins cause in the kidney?
vasodilation
loss of Na+
allowing adaption to hypoperfusion and maintenance of UO
action of NSAIDs
inhibit COX and precipitate ARF in patients with low GFR
what is involved in the triple whammy effect?
ACEI/ARB (efferent vasodilation)
diuretics
NSAIDs (afferent vasoconstriction)
how is uric acid formed?
catabolism of purines
what predisposes to gout?
high urate in serum
action of probenecid and sulfinpyrazole
block reabsorption of urate in PCT
action of allopurinol
stops urate synthesis
