diuretics Flashcards

1
Q

what are diuretics

A

drugs which have direct actin on the kidney which increase the excretion of salt and water in urine

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2
Q

what are uses of diuretics

A

treatment of cardiac failure and other conditions that give rise to oedema and also treatment of hypertension

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3
Q

what are ways of reducing generalised oedema

A

remove of primary cause (e.g cardiac glycosides in treatment of heart failure)

reduce intake of salt

increase excretion of salt and water via kidney using a diuretic

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4
Q

what is the mechanism of action of diuretics

A

in principle there are 3 ways:
increase amount filtered into urine through nephrons

increase amount secreted into urine through nephrons

reduce reabsorption from filtrate

diuretics all work be reducing reabsorption of solutes and water from tubular lumen

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5
Q

normally how much is reabsorbed from urine in terms of solutes

A

normally a lot is reabsorbed: 99+% of sodium, chloride and water is reabsorbed

100% of HCO3 (bicarbonate) and 93+% of potassium

hence small impairments in reabsorption can lead to great increase in excretion

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6
Q

how does reabsorption occur from proximal convoluted tubule

A

proximal convoluted tubule:

NaCl is retrieved via:
passive entry of sodium from tubular fluid into tubular cells via their luminal membrane, excess sodium is expelled via active transport on the other face of the tubular cells

HCO3 is reabsorbed by a mechanism which involves exchange of sodium in the filtrate for H+ from the cell, supply of H+ is rate limited by carbonic anhydrase activity

carbonic anhydrase is blocked by acetazolamide which is a weak diuretic

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7
Q

how does reabsorption occur from thick part of ascending limb of loop of hence

A

NaCl is reabsorbed:

NaCl enter tubular cells via co-transport mechanism Na/K/2Cl in the luminal membrane

sodium is actively expelled via sodium pump in the basolateral membrane

the cotransporter which pumps sodium into tubular cells is blocked by loop diuretics such as furosemide

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8
Q

how does reabsorption in the distal convoluted tubule occur

A

further reabsorption of NaCl occurs here

NaCl enters tubular cells via Na/Cl transporter

thiazides block this transporter

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9
Q

how does reabsorption in the collecting ducts occur

A

these cells are impermeable to water in absence of vasopressin and to sodium in absence of aldosterone

chloride ions exit the tubule through the paracellular pathway

potassium and hydrogen ions are added to the filtrate here

a sodium pump in the basolateral membrane is the main source of energy for ion movements in collecting duct

aldosterone acts on nuclear receptor within tubule cell and on membrane receptors to increase the sodium pumps

aldosterone action is inhibited by spironolactone, a compeitive blocker, causing less sodium to be reabsorbed from urine, this is known as a ptoassium sparing diuretic

amiloride blocks the sodium channels and is another potassium sparing diuretic

vasopressin acts via V2 receptors which increase expression of aquaporins

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10
Q

when are thiazide diuretics used, where do they act

A

treatment of hypertension, use of high doses may be used to treat heart failure

sodium/chloride pump of distal convoluted tubule

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11
Q

what are physiological affects of thiazide diuretics

A

reduction in blood pressure partly due to direct consequence of diuretic action reducing plasma volume and partly due to vasodilator effects in vascular smooth muscle

relative importance of diuretic/vasodilator effect is difficult to establish

side effects:
hypokalaemia,more likely to be significant at higher doses for heart failure, a hazard since reduction in plasma potassium increases toxicity of cardiac glycosides which are sometimes used together in treatment of heart failure

may also increase plasma glucoses, uric acid and lipids though changes are usually small for hypertension doses, may cause diabetes to be made worse

plasma increase in uric acid may cause or intensify gout

adverse effects are relatively uncommon and are thiazides are usually well tolerated

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12
Q

what are physiological features of loop diuretics

A

e.g furosemide

features shared w thiazides:

orally active

lowers blood pressure (loop ones mechanism is unknown either by plasma volume reduction or vasodilation through potassium channels)

can cause potassium loss

can increase plasma uric acid and glucose

differences between loop diuretics and thiazides:

site of action: loop diuretics target thick part of ascending limb of loop of henle, thiazides target the distal convoluted tubule

maximum natriuresis (nutrients such as sodium in urine) attainable is much greater in loop diuretics than thiazides

loop diuretics increase excretion of calcium whereas thiazides reduce it (furosemide can be used in treatment of hypercalcaemia)

loop diuretics can cause deafness which is usually but not alway reversible, ototoxicity may be related to changes in electrolyte composition of endolymph

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13
Q

what are general mechanisms of diuretics

A

all of them impaire reabsorptive activity of nephron

many diuretics (thiazides and loops) increase excretion of potassium thus causing hypokalaemia, this may be countered with a potassium sparing diuretic or potassium supplements

all effective diuretics sustain reduction in plasma volume, some may also cause vasodilation however these mechanisms are poorly understood

indomethacin and other NSAIDs attenuate and may even abolist the natriuretic and direct vascular effects of diuretics, mechanism is unclear

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14
Q

which sites do the different types of diuretics target

A

osmotic diuretics modify glomerular filtrate content at glomerulus

loop diuretics target thick part of ascending limb of loop of henle

acetazolamide: proximal convoluted tubule
thiazides: distal convoluted tubule

potassium sparing diuretics: collecting duct

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15
Q

give an example of a loop diuretic and a potassium sparing diuretic

A

loop: furosemide

potassium sparing: spironolactone and amiloride

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16
Q

what causes renin release

A

dropping of rate of glomerular filtration, fall in sodium content of fluid entering distal tubule, increased sympathetic activity

17
Q

where is renin secreted from

A

granular juxtaglomerular cells

18
Q

what is function of ACE

A

converts angiotensin 1 (inactive) to angiotensin 2 (causes vasoconstriction and aldosterone secretion)

also converts bradykinin (vasodilator, increased sensitivity of pain fibres) into inactive products

19
Q

what are physiological effects of aldosterone

A

potassium excretion increases because aldosterone promotes reabsorption of sodium from tubular fluid in exchange for potassium

causes release of vasopressin from posterior pituitary, this contributes to retention of water

increased sodium reabsorption

20
Q

how does renin-angiotensin-aldosterone system effect hypertension

A

overactivity of renin-angiotensin-aldosterone system may contribute to hypertension by:

promoting vasoconstriction (angiotensin 2)

sodium and water retention (aldosterone)

21
Q

give examples of ACE inhibitors, how do they affect people

A

captopril (first discovered)
enalapril (commonly used)

small drop in blood pressure in normals, much large reduction in hypertensives especially is plasma renin is high

administered alongside diuretics in heart failure, causes reduction in mean arterial pressure and vasodilation, meaning both pre and after load are reduced

if a thiazide is already being used ACE inhhibitors can cause large reductions in blood pressure to care is needed

22
Q

what are side affects of ACE inhibitors

A

cough due to increased bradykinin concentration, also causes activity of pain nerve endings in bronchial mucosa

23
Q

what are angiotensin 2 antagonists used for

A

treatment of hypertension

e.g losartan, orally active, causes less coughing cause bradykinin metabolism not affected

24
Q

where and when in vasopressin released

A

peptide hormone released from posterior pituitary

released in response to an increase in plasma osmolality and decrease in circulating blood volume

25
Q

what physiological effects does vasopressin have

A

makes collecting duct more water permeable, allowing for more reabsorption of water

at higher concentrations causes vasoconstriction

26
Q

what drugs affect vasopressin release

A

release is inhibited by alcohol

release is increased by angiotensin 2 and nioctine

27
Q

what is vasopressin used to treat

A

cranial diabetes insipidus (production of vassopressin is deficient)
since it is peptide hormone must be given via injection or nasal spray

desmopressin is more often used because it causes less vasoconstriction

28
Q

what is felypressin used for

A

analogue of vasopressin, more vasoconstrictor activity and antidiuretic

used as vasoconstrictor in conjunction with local anaesthetics in dentistry

29
Q

what vasopressin receptors are found where

A

V2 in renal tubules

V1 in blood vessels

30
Q

what are osmotic diuretics

A

high molecular weight compounds that are filtered but not reabsorbed

cause water retention within nephron by reducing osmotic gradient (lower water potential of urine) and hence diuresis e.g mannitol

only given by injection

used to reduce intracranial pressure and to increase rate of elimination of renal toxins

31
Q

how do thiazides and loop diuretics get to site of action

A

inside tubular lumen, via weak acid transport system;

proximal tubular cells secrete weak acids into lumen

32
Q

in what situations may change of urine ph be wanted

A

when some antibiotics are used to treat urinary tract infection (penicillin and tetracycline are more active in acid solution, sulphonamides are more active and soluble in alkaline solution)

in attempting increase of exretion of salicylate or phenobarbitone when taken in overdose

33
Q

what effect do carbonic anhydrase inhibitors have on urine ph

A

make urine more alkaline since they block bicarbonate reabsorption

34
Q

what is given to alkalinise urine

A

citrate