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Diuretics Flashcards

1
Q

What are the functions of the kidneys?

A
  • Maintain correct ionic balance of blood

- Remove waste products

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2
Q

How much blood passes through kidney in 24 hours?

A

120L

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3
Q

How much urine is produced in healthy individuals?

A

1.5L

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4
Q

What is one functional kidney unit called?

A

Nephron

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5
Q

What is the glomerulus?

A

dense capillary network

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6
Q

How does blood enter the glomerulus?

A

Through Afferent arteriole

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7
Q

How is fluid filtered out of the glomerulus and what is the process called?

A

Due to high hydrostatic pressure fluid and dissolved solutes are pushed out into capsular space
filtration

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8
Q

Where does blood go after it is filtered out of glomerulus?

A

Proximal convoluted tubule

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9
Q

From PCT where does filtrate go next?

A

Descending loop of henle then ascending loop of henle then the DCT

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10
Q

How does blood leave the glomerulus?

A

Through efferent arteriole

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11
Q

When filtrate is traveling along loop of henle and DCT what is it called?

A

tubular fluid

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12
Q

How does the tubular fluid get back into the cortex of the kidney?

A

Through DCT out of collecting duct

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13
Q

In what form does tubular fluid leave the collecting ducts?

A

Urine

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14
Q

What is the structure, function and role of the PCT?

A

 Has Leaky tight junctions between epithelial cells=Na+ diffuse down electrical conc gradient into epithelial cell this transport coupled with glucose, phosphate, AA’s, lactate, Cl-, K+ and proton extrusion
 60-70% Na+ reabsorption
 Actively secretes organic acids and bases via OAT transporter- creatinine, NSAID, penicillin , diuretics actively secreted into filtrate by OAT
 Ammonia- diffuses into filtrate down conc grad

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15
Q

What is the structure, function and role of the descending loop of henle?

A

 Surrounded by interstitial fluid= hypertonic to the filtrate
 Conc/tonicity increases as loop of henle descends
 Cells permeable to H20
 Water diffuses out of lumen down conc grad
 Countercurrent multiplier= concentrates interstitial fluid in renal medulla

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16
Q

What is the structure, function and role of the ascending loop of henle?

A

thick
 Low permeability cells to H2O
 20-30% active Na+ reabsorption
 Cortical end= top part= Na out via basolateral memb Na/K pump
 Creates gradient for Na to cross apical memb from lumen via Na/K/Cl transporter
 K= some absorbed from filtrate= most diffuses back out through apical memb K channels

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17
Q

What is the structure, function and role of the DCT?

A

 Impermeable to H2O
 7% Na+ reabsorbed down conc gradient
 Sodium actively reabsorbed via conc gradient set up by Na-K pump

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18
Q

What is the structure, function and role of the collecting tubule?

A

 Up to 15% Water reabsorbed from filtrate by aquaporin channels which are ADH mediated
 ADH binds to vasopressin releases aquaporin channels from vesicles they are stored in and they insert into apical memb
 Removal of filtered water= urine production

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19
Q

What are the functions of diuretics?

A
  • Increase Na+ and water secretion= produce natriuresis
  • Increased Na+ of filtrate= H2O follows
  • Directly acts on nephron cells or change filtrate composition
  • Small decrease in reabsorption= large increase in Na+ excretion
  • Diuretics apart from spironolactone actively secreted by PCT cells into lumen
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20
Q

What are the uses of diuretics?

A
  • Increase urine output
  • Reduces plasma volume and plasma concentrates so interstitial fluid drawn into blood = reduced oedema= no cardiac failure, no liver failure, no acute renal failure
  • Hyperaldosteronism= increases Na+ retention= increases plasma vol= stopped by diuretics
  • Reverses hypertension by reducing plasma volume
  • Acute renal failure= low blood flow to kidneys= small vol of dilute urine produced= diuretics increase excretion and aid urine production and kidneys concentrating powers
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21
Q

What are the examples of loop diuretics?

A
  • Furosemide, bumetanide, torasemide
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22
Q

List some advantages of bumetanide?

A

more lipid sol
higher bioavailability
diffuses passively into filtrate

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23
Q

What is the MOA of loop diuretics?

A
  • Inhibit Na+/K+/2Cl- carrier in the thick ascending limb
     Act on Cl- binding site of Na/K/Cl carrier
     Blocks K+/Cl- uptake= lost in urine
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24
Q

What are the outcomes of the MOA of loop diuretics?

A

no effect on Na+/H+ exchanger= Na+ in and H+ out
no effect on HCO3= continuously reabsorbed from filtrate= conc increased due to plasma vol reduction= alkalosis
increases Ca2+ and Mg2+ secretion= harmful die effect
reduced uric acid secretion= gout precipitation
Blocks Na+ reabsorption= more Na+ in distal part of nephron= reduced H2O absorption further

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25
What other property or mechanism do loop diuretics exhibit?
Vasodilator mechanism
26
What are the different ways the vasodilator mechanism of loop diuretics could be caused?
reduced response to Ang II Increased production of vasodilating PG’s Reduced production of endogenous Na+/K+/ATP inhibitor= reduces vasoconstrictor properties Exert K+ channel opening effect in resistance arteries
27
What are the examples of loop diuretics?
- Furosemide, bumetanide, torasemide
28
What are the consequences if NSAIDs and loop diuretics are taken together?
Reduces diuretic action NSAID block PGE2 production by competing for OAT reduced Na+ and Cl- reabsorption in thick ascending loop Reduce delivery of diuretics into renal tubule
29
What does the renal tubule consist of?
Loop of henle, DCT, collecting tubule
30
What are the outcomes of the MOA of loop diuretics?
no effect on Na+/H+ exchanger= Na+ in and H+ out no effect on HCO3= continuously reabsorbed from filtrate= conc increased due to plasma vol reduction= alkalosis increases Ca2+ and Mg2+ secretion= harmful die effect reduced uric acid secretion= gout precipitation Blocks Na+ reabsorption= more Na+ in distal part of nephron= reduced H2O absorption further
31
What other property or mechanism do loop diuretics exhibit?
Vasodilator mechanism
32
What are the different ways the vasodilator mechanism of loop diuretics could be caused?
reduced response to Ang II Increased production of vasodilating PG’s Reduced production of endogenous Na+/K+/ATP inhibitor= reduces vasoconstrictor properties Exert K+ channel opening effect in resistance arteries
33
What type of drug class to loop diuretics interact with?
NSAIDs
34
What are the consequences if NSAIDs and loop diuretics are taken together?
NSAID block PGE2 production by competing for OAT reduced Na+ and Cl- reabsorption in thick ascending loop Reduce delivery of diuretics into renal tubule
35
What are the indications for loop diuretics?
```  Acute pul oedema  Chronic HF  Liver cirrhosis and ascites  Nephrotic syndrome  Renal failure  Hypertension  Reduced renal function  Hypercalcaemia ```
36
What are the common side effects of loop diuretics?
```  Hypotension  Hypokalemia  Metabolic alkalosis  Gout  Hearing loss due to CN VII damage  Exacerbate diabetes  Increase effects and toxicity of digoxin and type 3 antidysrhythmic ```
37
What effect do loop diuretics have on potassium?
Loss of potassium higher conc of Na+ in filtrate as reabsorption inhibited by diuretic more Na+ crossing apical memb increases Na/K exchanger activity more K into cell and diffuses out through apical K channels
38
Describe the pharmacokinetics of loop diuretics?
 GIT absorption  IV/oral  Peak effect in less than 1 hr for IV= 30 min  Strong binding to albumin= reaches site of action by PCT excretion  Excreted in urine  T1/2= 90 mins
39
What are the indications of Thiazide + thiazide like diuretics?
 Hypertension  Mild-mod CHF  Oedema  Nephrogenic diabetes insipidus
40
What us the MOA of Thiazide + thiazide like diuretics?
Inhibit Na/Cl cotransporter K+/cl- blocked lost in urine
41
What are the outcomes of the MOA of Thiazide + thiazide like diuretics?
no effect on Na+/H+ exchanger= Na+ in and H+ out no effect on HCO3= continuously reabsorbed from filtrate= conc increased due to plasma vol reduction= alkalosis increases Mg2+ secretion decreases Ca2+ secretion reduced uric acid secretion= gout precipitation
42
What other effect do Thiazide + thiazide like diuretics exhibit?
vasodilator effects
43
Describe the steps of the homeostatic mechanism used to limit hypotensive effects of diuretics during chronic dosing?
 Reduction in blood vol  Increases renin release  Ang I produced then to Ang II by ACE  Ang II= vasoconstriction and aldosterone secretion  Vasoconstriction= increased BP  Aldosterone secretion= increased Na+ reabsorption = increased BP
44
What is the MOA of Potassium sparing diuretics?
- Block Na+ reabsorption - Block Na+/K+ exchange in collecting tubule= limited diuretic action  Act on nuclear R  Blocks synthesis of Na/K pump and ENaCs
45
What are the side effects of Thiazide + thiazide like diuretics?
 Increased urine frequency so take in morning  Erectile dysfunction  Hypokalaemia  Impaired glucose tolerance
46
Describe the pharmacokinetics of Thiazide + thiazide like diuretics?
 Oral only  Excreted in urine  Bendro= 2.5mg daily in hypertension= peak effect 4-6 hr lasts 8-12 hrs  Chlortalidone= 25mg OD= peak effect 2-6hrs lasts 72 hrs
47
How can K+ depletion be reduced?
```  More fruit juice  More instant coffee  More bananas  K+ supplements alone or combo with diuretic  Use K+ sparing diuretics ```
48
What class of drugs are Potassium sparing diuretics?
Aldosterone antagonists
49
What are examples of Potassium sparing diuretics?
Spironolactone, eplerenone
50
What is the MOA of spironolactone?
``` inhibits aldosterone no mineralocorticoid receptors activated no upregulation of the expression of the gene for Na/K pump and epithelial sodium channel called ENaC Directly blocks Na+ reabsorption Blocks K+ influx across basolateral memb reduced K+ in filtrate= less K+ lost ```
51
What are the indications of spironolactone?
o Primary hyperaldosteronism o Ascites caused by liver cirrhosis o Oedema o Mod-severe HF
52
What are the indications of eplerenone?
o Left ventricular failure after MI
53
What are the side effects of Potassium sparing diuretics?
 Hyperkalemia  GI upset  Gynaecomastia  Menstrual disorders/testicular atrophy
54
What class of drugs interact with Potassium sparing diuretics?
ACEI
55
What happens if ACEI and Potassium sparing diuretics interact?
```  Increases hypotensive effect  Excessive K retention  ACEI block Ang I to Ang II  Reduced aldosterone secretion and reduced vasodilation  Reduced vasodilation= reduced BP ```
56
Describe the pharmacokinetics of spironolactone?
o Good gut absorption o Metabolised to canrenone t1/2= 16 hrs o Slow onset of action
57
Describe the pharmacokinetics of eplerenone?
o Short elimination half life
58
Name 2 other diuretics?
Triamterene + amiloride
59
What is the MOA of Triamterene + amiloride?
- Inhibit Na+ reabsorption | - Block luminal Na channels in collecting tubules
60
What is a disadvantage of Triamterene + amiloride?
- Limited diuretic actions
61
What are the side effects of Triamterene + amiloride?
 Hyperkalaemia
62
What are the contraindications of Triamterene + amiloride?
renal impairment | drugs that increase K +
63
Describe the pharmacokinetics of Triamterene?
o Good oral absorption | o Partial liver metabolization
64
Describe the pharmacokinetics of amiloride?
o Less absorption o Slower onset o Excreted unchanged in urine
65
What are combined diuretic therapies?
``` Co-amiloride= amiloride + furosemide Co-amilozide= amiloride + hydrochlorothiazide ```
66
What are the indications for Co-amiloride?
oedema
67
What are the indications for Co-amilozide?
hypertension, CHF, oedema
68
Name an osmotic diuretic?
Mannitol
69
What is the MOA of osmotic diuretics?
- Filtered in glomerulus not reabsorbed - Increases filtrate osmolarity by drawing water from PCT, ascending LOH and CD epithelial cells into filtrate - Increase excretion of H2O and Na+
70
What are the indications for osmotic diuretics?
 Cerebral oedema  Raised intraocular pressure  Acute renal failure
71
What combination of diuretics maintains K balance?
osmotic + loop/thiazide
72
What are the side effects of osmotic diuretics?
 Hyponatremia  Headache  Nausea  Vomiting
73
Which class of diuretics are weak?
potassium sparing
74
What is the site of action of Loop diuretics?
Loop of henle
75
What is the site of action of thiazide diuretics?
DCT
76
What is the site of action of potassium sparing diuretics?
DCT and collecting tubule
77
What is the site of action of amiloride?
Collecting tubule
78
What is the site of action of mannitol?
PCT

THE PATIENT (8 decks)

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